bromochloroacetic-acid and Carcinoma--Renal-Cell

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Proteins; Neoplasms, Second Primary; Neoplasms, Unknown Primary; Organ Specificity; Prostatic Neoplasms

To investigate the clinicopathological features, histogenesis and prognosis of mucinous tubular and spindle cell carcinoma (MTSCC).. Five MTSCCs were studied with histochemical, immunohistochemical staining, electron microscopy, and review of the related literatures.. Four cases of MTSCC were females and one was male. Three patients presented with flank discomfort and two were incidentally found with health examination. In gross examination, the tumors were circumscribed. The cut surface was solid, gray-white, yellow or red. Necrosis was present in one case of high-grade MTSCC. Microscopically, low-grade MTSCC was mainly consisted of tubular, spindle cell and mucinous stroma with relatively bland morphology, and mitoses were rare. While in the high-grade area of one case, the cells were spindle or polymorphic with severe atypia and high mitotic activity, without mucinous stroma and tubular structure. Mucin was positive for Alcian blue. The neoplastic cells were positive for vimentin (5/5), CKpan (5/5), CK7 (5/5), CK19 (5/5), 34betaE12 (1/5), EMA (5/5), E-cadherin (3/5), CD10 (1/5), P504S (5/5), and CAM5.2 (5/5). The Ki-67 index was low (< or = 5%) in the low-grade component, while it was high (15%) in the high-grade component. Ultrastructural study showed short microvilli along glandular lumens. The nuclear membrane was focally invaginated. Four cases were followed up for 3 to 52 months, and recurrence and metastasis were not found.. MTSCC occurs predominantly in females and it is a rare kidney neoplasm. Most of MTSCCs are low-grade and the prognosis is relatively good. However, the patients of high-grade MTSCC should be closely followed up.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Carcinoma; Carcinoma, Medullary; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Keratins; Kidney Neoplasms; Leiomyosarcoma; Male; Middle Aged; Mucin-1; Nephrectomy; Racemases and Epimerases; Vimentin

Clear cell carcinoma is the most common histotype among renal cell tumors. The prominent vascular network of sinusoidal vessels lined by delicate endothelial cells may often lead to hemorrhagic areas with secondary deposition of chunky birefringent hemosiderin granules. The finding of pigmentation other than iron, and in particular melanin deposits, in renal tumors is a rare occurrence that should lead to differential diagnosis with other primary and metastatic tumors of the kidney.

Topics: Biomarkers; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Male; Melanins; Middle Aged; Pigmentation

Topics: Adenoma, Oxyphilic; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Proto-Oncogene Proteins c-kit; Sensitivity and Specificity; Wilms Tumor; WT1 Proteins

Different types of multinucleated giant cells (MGC) have been documented in tumors with osteoclast-like appearance, with trophoblastic differentiation or as tumoral malignant giant cells. A new variety of MGC has been described in renal cell carcinoma. In order to study the frequency, nature and significance of this cellular type, we have reviewed our files. To assess the presence, nature and significance of these MGC in renal cell carcinomas and associated histologic subtype. To review all malignant renal tumors diagnosed in the last 5 years in our hospital and to carry out a morphologic and immunohistochemical study in renal cell carcinomas with syncytial type MGC. 55 renal cell carcinomas were reviewed. Clear cell (conventional) renal cell carcinoma was the most common type encountered (40 cases); two of these cases showed syncytial type MGC and low grade malignancy. Microscopically the MGC contained from 5 to 40 nuclei. Immunohistochemically, mononucleated and multinucleated cells were positive for cytokeratin CAM 5.2, cytokeratin AE1/AE3 and weakly positive for vimentin. Histiocytic, muscular, neural markers, beta-HCG and alpha-fetoprotein were negative. The presence of syncytial type MGC in renal cell carcinomas is an exceptional event. Among 55 renal cell carcinomas we found two cases, both of which were of clear cell subtype and low grade malignancy. The MGC proved positive for epithelial markers and probably are the result of mononucleated tumoral cell fusion. We are unaware of the impact of this MGC in the outcome of patients; such cells appear in low grade carcinomas and do not seem to be of dismal prognosis.

Topics: Biomarkers; Carcinoma, Renal Cell; Cell Division; Follow-Up Studies; Giant Cells; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Kidney Neoplasms; Neoplasm Staging; Vimentin

The gastrointestinal mesenchymal tumors from a heterogenous group that include several entities: leiomyomas, schwanomas and less differentiated tumors often referred as GIST. These neoplasm are uncommon and their clinical behaviour is most difficult to predict. We describe a malignant gastrointestinal stromal tumor of the ileum coexisting with renal cell carcinoma. The neoplasms were fixed in formaldehyde, embedded in paraffin and stained with hematoxylin-eosin. For immunohistochemical studies deparaffinized tissue sections were incubated with antibodies against vimentin, desmin, muscle specific actin, S100, CD34, GFAP, NSE and keratin. The epithelioid and spindle cells of ileal neoplasm were arranged in interlacing fascicle with occasional palisading and were positive for vimentin and CD34. Positivity for muscle specific actin was focally found. The renal neoplasm required differential diagnosis from metastatic GIST. The morphological and immunohistochemical investigations in our case were consistent with GIST coexisting with primitive renal cell carcinoma. One of the problems connected to the anatomo-clinical evaluation of GIST consist in the difficulty of making a prognosis. An almost complete review of the literature and view point on the topic has been performed. As a conclusion judging from papers regarding this argument, no clear parameters of biological behaviour exist excluding mitotic index.

Topics: Adenocarcinoma, Clear Cell; Aged; Antigens, CD34; Biomarkers, Tumor; Carcinoma, Renal Cell; Cytoskeletal Proteins; Female; Glial Fibrillary Acidic Protein; Humans; Ileal Neoplasms; Keratins; Kidney Neoplasms; Mitotic Index; Neoplasm Proteins; Neoplasms, Multiple Primary; Phosphopyruvate Hydratase; S100 Proteins

Herein is a review of clear cell neoplasms of selected sites in the urinary tract and male reproductive system, including the kidney, the urinary bladder, testis, epididymis, and prostate. Clear cell cytoplasmic alteration in neoplasms at these sites is a relatively common light microscopic finding. Examples of such neoplasms with clear cell change include the clear cell type of renal cell carcinoma, clear cell adenocarcinoma of urethra and bladder, the classic type of seminoma, papillary cystadenoma of the epididymis, and well-differentiated adenocarcinoma of the prostate. Of importance, numerous non-neoplastic benign entities may also manifest cleared cytoplasm and therefore are presented in the differential in this review. Indeed, knowledge of the neoplastic and non-neoplastic entities displaying clear cell change at each anatomic site should enable the surgical pathologist to approach the differential diagnosis of these conditions in a more logical and rigorous fashion.

Topics: Adenocarcinoma; Alkaline Phosphatase; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Genital Neoplasms, Male; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Mucin-1; Prostatic Neoplasms; Testicular Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms

Mass lesions of the central nervous system (CNS) that may assume a clear cell appearance are diverse in nature. Primary conditions in this category include oligodendroglioma, hemangioblastoma, germinoma (seminoma), clear cell and chordoid meningioma, pleomorphic xanthoastrocytoma, and lipid-rich glioblastoma. These proliferations usually can be identified by attention to clinical presentation, topographic location, radiographic details, and histological nuances. Occasionally, however, electron microscopy or immunohistological analysis may be necessary. A recommended panel of reagents for the evaluation of clear cell primary CNS lesions include antibodies to glial fibrillary acidic proteins, S-100 protein, epithelial membrane antigen, vimentin, keratins, placental-like alkaline phosphatase, and synaptophysin. This article reviews the salient clinicopathologic attributes of such proliferations, elaborates a practical approach to their diagnosis, and discusses important differential diagnostic considerations. The latter include malformative lesions, infarcts, inflammatory conditions, and secondary lymphomas, carcinomas, and melanomas.

Topics: Alkaline Phosphatase; Carcinoma, Renal Cell; Central Nervous System Neoplasms; Diagnosis, Differential; Germinoma; Glial Fibrillary Acidic Protein; Hemangioblastoma; Humans; Immunohistochemistry; Keratins; Meningioma; Mucin-1; Oligodendroglioma; S100 Proteins; Synaptophysin; Vimentin; Xanthomatosis

A case characterized by a rare synchronous occurrence of transitional cell carcinoma (TCC) of the renal pelvis and renal cell carcinoma (RCC) in the same kidney is presented. A retrospective analysis of 23 similar cases reported in the English literature over the last 71 years demonstrated a male-to-female ratio of 2:1, an average age of 64.5 years, and a left-to-right-side ratio of 3.2:1. The three most common findings at initial examination were hematuria (90%), flank pain (19%), and flank mass (14%). Moreover, 24% of patients had tumor metastases even at initial examination. Thirty-four percent of patients had bladder neoplasms, and 24% of them had a history of cigarette smoking. There is no tendency toward higher grade of malignancy or specific histologic pattern for TCC and RCC when they occur together in the same kidney. Immunohistochemical studies were used to examine TCC and RCC, with special attention paid to the site of their collision, which displayed multifocal lymphatic permeation. Both TCC and RCC were positive for epithelial membrane antigen (EMA) and cytokeratins identified by monoclonal antibodies CAM-5.2, AE1/AE3, and MAK-6. TCC was focally positive for keratin, detectable by antibody 34 beta E12, but RCC was not. The tumor tissue infiltrating the lymphatics, which seemed to be RCC, demonstrated positive staining for EMA and keratins CAM-5.2, AE1/AE3, and MAK-6 and negative staining for keratin 34 beta E12. Interestingly, the tumor in lymphatics displayed strong staining for carcinoembryonic antigen (CEA) but both TCC and RCC in the vicinity were negative. These findings suggest that keratin 34 beta E12 may play a role in the differential diagnosis between TCC and RCC and that tumor-invading lymphatics may change phenotype, including the neoexpression of CEA.

Topics: Aged; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Cell Nucleolus; Cell Nucleus; Female; Humans; Keratins; Kidney Neoplasms; Lymphatic System; Membrane Glycoproteins; Mucin-1; Neoplasm Invasiveness; Neoplasms, Multiple Primary

Chromophobe renal cell carcinoma is a relatively uncommon variant of renal carcinoma described in 1985. The main differential diagnosis is renal oncocytoma. Hale's colloidal iron staining is a powerful adjunct to morphological interpretation but it is not specific and is sometimes difficult to interpret. We studied the immunohistochemical expression of cytokeratin 7 to determine its value in distinguishing chromophobe renal cell carcinoma from renal oncocytoma.. Immunostaining was performed on paraffin-embedded tumor tissue of 6 chromophobe renal cell carcinomas and 11 oncocytomas with an antibody to cytokeratin 7 (clone OV-TL 12/30, Dako, France) using a streptavidin-biotin method.. All chromophobe renal cell carcinomas showed strong cytoplasmic staining with peripheral cell accentuation. In contrast, 8 of 11 oncocytomas were entirely negative and 3 showed only weak and focal staining in less than 5% of the tumor cells.. Immunohistochemical staining for cytokeratin 7 may be useful for the differential diagnosis of renal oncocytomas and chromophobe renal cell carcinomas when Hale's colloidal iron staining is uncertain.

Topics: Adenocarcinoma; Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Biopsy, Needle; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney Neoplasms; Male; Middle Aged; Sensitivity and Specificity

To evaluate the efficiency of pan-keratin immunostaining, tissue microarrays of 13,501 tumor samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. In normal tissues, strong pan-keratin immunostaining was seen in epithelial cells. Staining intensity was lower in hepatocytes, islets of Langerhans, and pneumocytes but markedly reduced in the adrenal cortex. Pan-keratin was positive in ≥98% of samples in 62 (83%) of 75 epithelial tumor entities, including almost all adenocarcinomas, squamous cell and urothelial carcinomas. Only 17 of 121 tumor entities (13%) had a pan-keratin positivity rate between 25% and 98%, including tumors with mixed differentiation, endocrine/neuroendocrine tumors, renal cell carcinomas, adrenocortical tumors, and particularly poorly differentiated carcinoma subtypes. The 15 entities with pan-keratin positivity in 0.9%-25% were mostly of mesenchymal origin. Reduced/absent pan-keratin immunostaining was associated with high UICC stage (p = 0.0001), high Thoenes grade (p = 0.0183), high Fuhrman grade (p = 0.0049), advanced tumor stage (p < 0.0001) and lymph node metastasis (p = 0.0114) in clear cell renal cell carcinoma, advanced pT stage (p = 0.0007) in papillary renal cell carcinoma, and with advanced stage (p = 0.0023), high grade (p = 0.0005) as well as loss of ER and PR expression (each p < 0.0001) in invasive breast carcinoma of no special type (NST). In summary, pan-keratin can consistently be detected in the vast majority of epithelial tumors, although pan-keratin can be negative a fraction of renal cell, adrenocortical and neuroendocrine neoplasms. The data also link reduced pan-keratin immunostaining to unfavorable tumor phenotype in in epithelial neoplasms.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma; Carcinoma, Renal Cell; Humans; Keratins; Kidney Neoplasms

Papillary renal neoplasm with reverse polarity is a form of recently described tumor. These tumors are defined by GATA3 positivity, negative vimentin staining, and the presence of both papillary structures and a layer of eosinophilic cells with apical nuclei and a granular cytoplasm. In the present report, we review 7 cases of papillary renal neoplasm with reverse polarity that were GATA3+ and vimentin-, consistent with past reports. In all 7 of these cases, we found that these tumors were additionally positive for 34βE12. All 7 of these tumors were categorized as stage pT1. On histological examination, these tumors exhibited branching papillae with apical nuclei. All 7 of these patients were alive on most recent follow-up, with 6 being disease free and one having developed prostate cancer. Together, this overview of 7 additional cases of papillary renal neoplasm with reverse polarity offers further insight into this rare and poorly understood disease.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Renal Cell; Female; GABA Plasma Membrane Transport Proteins; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged; Vimentin

There is growing evidence that alternative splicing (AS) plays an important role in cancer development. However, a comprehensive analysis of AS signatures in kidney renal clear cell carcinoma (KIRC) is lacking and urgently needed. It remains unclear whether AS acts as diagnostic biomarkers in predicting the prognosis of KIRC patients. In the work, gene expression and clinical data of KIRC were obtained from The Cancer Genome Atlas (TCGA), and profiles of AS events were downloaded from the SpliceSeq database. The RNA sequence/AS data and clinical information were integrated, and we conducted the Cox regression analysis to screen survival-related AS events and messenger RNAs (mRNAs). Correlation between prognostic AS events and gene expression were analyzed using the Pearson correlation coefficient. Protein-protein interaction analysis was conducted for the prognostic AS-related genes, and a potential regulatory network was built using Cytoscape (version 3.6.1). Meanwhile, functional enrichment analysis was conducted. A prognostic risk score model is then established based on seven hub genes (KRT222, LENG8, APOB, SLC3A1, SCD5, AQP1, and ADRA1A) that have high performance in the risk classification of KIRC patients. A total 46,415 AS events including 10,601 genes in 537 patients with KIRC were identified. In univariate Cox regression analysis, 13,362 survival associated AS events and 8,694 survival-specific mRNAs were detected. Common 3,105 genes were screen by overlapping 13,362 survival associated AS events and 8,694 survival-specific mRNAs. The Pearson correlation analysis suggested that 13 genes were significantly correlated with AS events (Pearson correlation coefficient >0.8 or <-0.8). Then, We conducted multivariate Cox regression analyses to select the potential prognostic AS genes. Seven genes were identified to be significantly related to OS. A prognostic model based on seven genes was constructed. The area under the ROC curve was 0.767. In the current study, a robust prognostic prediction model was constructed for KIRC patients, and the findings revealed that the AS events could act as potential prognostic biomarkers for KIRC.

Topics: Alternative Splicing; Amino Acid Transport Systems, Basic; Amino Acid Transport Systems, Neutral; Apolipoprotein B-100; Aquaporin 1; Biomarkers, Tumor; Carcinoma, Renal Cell; Computational Biology; Databases, Genetic; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genetic Predisposition to Disease; Humans; Keratins; Kidney Neoplasms; Prognosis; Protein Interaction Maps; Receptors, Adrenergic, alpha-1; Risk Assessment; Risk Factors; RNA-Seq; RNA, Messenger; Signal Transduction; Stearoyl-CoA Desaturase; Time Factors; Transcriptome

14-3-3σ is a protein expressed in many epithelial tissues associated with essential cell functions, including cell-cycle control, apoptosis, and cytoskeletal integrity. There is a paucity of knowledge of the tumorigenesis of canine renal cell carcinomas (RCCs), and the histological origin of this tumor has not been established. This study analyzed the expression of 14-3-3σ, Ki-67, cytokeratins, and vimentin in 40 canine RCCs. Aberrant expression of 14-3-3σ was demonstrated in 15 (38%) cases and was associated with a significantly shorter survival time ( P < .002). In contrast to canine RCC, normal kidney did not express 14-3-3σ. The Ki-67 proliferation index did not show utility as a prognostic factor. The distal convoluted tubular epithelium in normal kidneys coexpressed cytokeratins and vimentin, and thus maintenance of this coexpression pattern in canine RCC suggests that most tumors arise from the distal segment of the nephron. These results suggest that 14-3-3σ is a potential negative prognostic factor and a possible therapeutic target.

Topics: 14-3-3 Proteins; Animals; Carcinoma, Renal Cell; Dog Diseases; Dogs; Female; Keratins; Ki-67 Antigen; Kidney Neoplasms; Male; Retrospective Studies; Vimentin

Endolymphatic sac tumor (ELST) is a rare neoplasm arising in the temporal petrous region thought to originate from endolymphatic sac epithelium. It may arise sporadically or in association with Von-Hippel-Lindau syndrome (VHL). The ELST prevalence in VHL ranges from 3 to 16% and may be the initial presentation of the disease. Onset is usually in the 3rd to 5th decade with hearing loss and an indolent course. ELSTs present as locally destructive lesions with characteristic computed tomography imaging features. Histologically, they show papillary, cystic or glandular architectures. Immunohistochemically, they express keratin, EMA, and variably S100 and GFAP. Currently it is recommended that, given its rarity, ELST needs to be differentiated from other entities with similar morphologic patterns, particularly other VHL-associated neoplasms such as metastatic clear cell renal cell carcinoma (ccRCC). Nineteen ELST cases were studied. Immunohistochemistry (18/19) and single nucleotide polymorphism microarray testing was performed (12/19). Comparison with the immunophenotype and copy number profile in RCC is discussed. Patients presented with characteristic bone destructive lesions in the petrous temporal bones. Pathology of tumors showed characteristic ELST morphology with immunoexpression of CK7, GFAP, S100, PAX-8, PAX-2, CA-9 in the tumor cells. Immunostaines for RCC, CD10, CK20, chromogranin A, synaptophysin, TTF-1, thyroglobulin, and transthyretin were negative in the tumor cells. Molecular testing showed loss of 3p and 9q in 66% (8/12) and 58% (7/12) cases, respectively. Immunoreactivity for renal markers in ELST is an important diagnostic caveat and has not been previously reported. In fact, renal markers are currently recommended in order to rule out metastatic RCC although PAX gene complex and CA-9 have been implicated in the development of the inner ear. Importantly copy number assessment of ELST has not been previously reported. Loss of 3p (including the VHL locus) in ELST suggests similar mechanistic origins as ccRCC.

Topics: Adolescent; Adult; Carcinoma, Renal Cell; Cohort Studies; Computational Biology; Cytokines; Ear Neoplasms; Endolymphatic Sac; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Kidney Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Proteins; Nerve Tissue Proteins; PAX2 Transcription Factor; Young Adult

Clear cell renal cell carcinomas (CCRCCs) are the most common kidney tumors that despite current advances in diagnosis continue to have high rates of metastasis and mortality. In this study, we analyzed the cytokeratin (CK) AE1∕AE3 and vimentin immunoexpression in 26 CCRCCs in relation to histopathological prognostic parameters. Immunoreactions were positive and heterogeneous in all analyzed cases. CK AE1∕AE3 immunoexpression was associated with low grade and early stage lesions, while vimentin immunoexpression was associated with high grade and advanced lesions. The aspect may be used to determine the tumor heterogeneity and a better patients' stratification for therapy.

Topics: Carcinoma, Renal Cell; Epithelium; Female; Humans; Immunophenotyping; Keratins; Kidney Neoplasms; Male; Mesoderm; Middle Aged; Vimentin

A 36-year-old male was found to have a 7.0 cm left upper pole renal mass on renal ultrasound. Following nephrectomy, the mass was grossly ill-demarcated, friable and red-brown, invading renal parenchyma, hilar fat and the renal vein. Microscopically, the tumor had a nested and papillary architecture. The cells demonstrated abundant clear and eosinophilic cytoplasm and focal intracytoplasmic melanin pigment. Nucleoli were prominent. By immunohistochemistry, the tumor was positive for TFE3; HMB-45 stained approximately 5% of tumor cells corresponding to the histologic melanin pigment, which was confirmed with Fontana-Masson stain with bleach. Immunostains for PAX8, CD10, MiTF, and CAIX were negative; keratins Cam 5.2 and AE1/AE3 were focally positive. Targeted next-generation sequencing revealed an ARID1B-TFE3 gene fusion. Melanotic Xp11 renal cell carcinoma is a rare, pigment containing translocation variant demonstrating overlapping features with melanoma and is usually associated with an SFPQ-TFE3 gene fusion. The patient is alive and without evidence of disease 7 years after his diagnosis. The combination of high grade histopathology, the presence of melanin, absent PAX8, keratin positivity, and relatively indolent clinical behavior with a unique translocation may warrant recognition as a distinct renal cell carcinoma translocation subtype.

Topics: Adult; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biomarkers, Tumor; Biopsy; Carcinoma, Renal Cell; Chromosomes, Human, X; DNA-Binding Proteins; Gene Fusion; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Melanins; Neoplasm Grading; Nephrectomy; PAX8 Transcription Factor; Phenotype; Sequence Analysis, DNA; Transcription Factors; Translocation, Genetic

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a subtype of renal cell carcinoma (RCC) with unique morphologic features found exclusively in the background of end-stage renal disease. We analyzed the clinicopathologic features and immumoreactive profiles of 12 cases of ACD-RCC to further characterize this recently recognized entity. Review of histologic slides was performed in conjunction with immunohistochemical staining directed to the contemporary diagnostic antibodies and the putative target therapy-related markers. Histologically, the tumors showed characteristic inter-or intracellular microlumens and eosinophilic tumor cells. Intratumoral hemosiderin deposition and degenerating foamy tumor cells were consistent findings which were not previously described. Immunohistochemically, all the tumors were positive for alpha-methylacyl-CoA-racemase, CD10, pan-cytokeratin, PTEN (phosphatase and tensin homolog deleted on chromosome 10) and c-met, while negative for carbonic anhydrase-9, CD57, CD68, c-kit, pax-2, platelet-derived growth factor receptor (PDGFR)-α or vascular endothelial growth factor receptor (VEGFR)-2. Heterogenous staining was found for CK7 and kidney-specific cadherin. Positive reaction to c-met suggests its utility as a plausible therapeutic target in ACD-RCC. Thus, we present the unique morphologic and immunopathologic features of ACD-RCC, which may be helpful in both diagnostic and therapeutic aspects.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Renal Cell; Female; Humans; Keratins; Kidney Failure, Chronic; Kidney Neoplasms; Male; Middle Aged; Neprilysin; Proto-Oncogene Proteins c-met; Racemases and Epimerases

Although angiomyolipoma (AML) is a relatively rare entity, it is the most common benign mesenchymal neoplasm of the kidney.. To highlight the clinicopathological characteristics of AML and to assess the role of Human Melanoma Black-45 (HMB-45), Melan-A, smooth muscle actin (SMA), S-100 and cytokeratin in its diagnosis.. The study included 15 cases of AML. Clinical and radiological data were retrieved from the archival files and all cases were subjected to a histopathological evaluation as well as immunohistochemical staining for HMB-45, Melan-A, SMA, S-100, and cytokeratin.. AML was more common in females (female:male = 4:1), the mean age was 53.9 ± 6.45 years. 60% of patients were symptomatic while the remaining 40% were asymptomatic. A statistically significant relationship was found between size of the tumor and the presence of the symptoms (P = 0.02). Patients with tumor size less than 4 cm were asymptomatic, while those with tumor size larger than 4 cm had different symptoms. Thirteen cases were classic AML, while 2 cases were epithelioid AML. Classic AML demonstrated admixture of fatty tissue, thick-walled blood vessels, and smooth muscle, while epithelioid AML was composed mainly of epithelioid cells and contained no fat. HMB-45 was positive in all cases of AML (100%), Melan-A was positive in 13/15 (87%) while SMA was positive in 11/15 (73%) of AML with variable staining intensity. All cases of AML were negative for S-100 and cytokeratin.. AMLs have characteristic clinicopathological and immunohistochemical features and their recognition is crucial for proper diagnosis and treatment.

Topics: Adult; Angiomyolipoma; Carcinoma, Renal Cell; Cohort Studies; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Melanoma; Middle Aged; Retrospective Studies; S100 Proteins; Tomography, X-Ray Computed

Intramedullary spinal cord metastasis (ISCM) from renal cell carcinoma (RCC) is rare manifestation and most of them are treated by adjuvant treatment modalities like radiotherapy. Despite the radio-resistance of RCC itself, focal radiotherapy has been preferred as the first-line treatment modality of ISCM from RCC and only a few cases underwent surgical treatment. We describe a case of ISCM from RCC, which underwent surgical excision and pathologically confirmed. A 44-yr-old man was presented with rapid deterioration of motor weakness during focal radiotherapy for ISCM from RCC. After the surgery for removal of the tumor mass and spinal cord decompression, his motor power was dramatically improved to ambulate by himself. We report the first published Korean case of ISCM from RCC confirmed pathologically and describe our surgical experience and his clinical characteristics.

Topics: Adult; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Male; Motor Activity; Spinal Cord Neoplasms; Tomography, X-Ray Computed; Treatment Outcome; Vimentin

Clear cell renal cell carcinoma (CCRCC) has a rich, sinusoid-like vascularity frequently used as a diagnostic criterion. CCRCC with predominantly vascular architecture has not been described.. To describe 4 unusual CCRCC cases, primarily presenting with hemangioma-like morphologic pattern.. Clinicopathologic and selected immunohistochemical analysis of 4 cases of CCRCC mimicking hemangioma.. Cases were seen in 1 woman and 3 men (average age, 48.8 years; range, 40-66 years). Grossly, tumors were red-brown (3 of 4) with scant bright-yellow foci in 1. The average tumor size was 4 cm (range, 2.5-5.5 cm). Microscopically, all were composed of varying proportions of a rich, arborizing, sinusoid-like vasculature with focal hobnail appearance of endothelial cells. Entrapment of renal tubules between blood vessels was seen at the periphery of the tumors. This morphology was reminiscent of anastomosing hemangioma. Isolated tumor cells resembling lymphocytes with clear halos were sparsely interspersed between vessels. Cytokeratin immunostain confirmed the diagnosis of CCRCC.. Extensive sampling and immunohistochemical workup of what is deemed to be a benign vascular neoplasm of the kidney is needed to rule out the presence of individual carcinoma cells or small viable carcinoma cell clusters.

Topics: Adult; Aged; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Hemangioma; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged; Mucin-1

To explore the rationale for renal-sparing surgery as an alternative method to radical nephrectomy in the treatment of renal cell carcinoma (RCC), we analyzed clinical data from 94 patients diagnosed as having RCC. They were divided into 3 groups based on the maximum diameter of their tumor specimens. Group A had tumors size ranging from 0 to 4 cm, group B had tumors size ranging from 4 to 7 cm, and group C had tumors size greater than 7 cm. Tissue samples (5 cm) were taken from the upper pole side, lower pole side, and renal pelvic side of the tumor pseudocapsule; if the tumor was located on 1 pole of the kidney, samples were collected from 2 directions. The specimens were then embedded in paraffin and cut serially at segments 0 to 1, 1 to 3, and 3 to 5 cm. Staining with hematoxylin and eosin, anti-pancytokeratin, and vimentin was performed to determine tumor type and tumor infiltration. From the 94 patients analyzed, 2 patients in group A had RCC metastasis within 1 cm of tissue around the pseudocapsule, and 4 patients in groups B and C had lymph node metastasis without metastasis in the tissue 1 cm outside the pseudocapsule in all 3 directions described. There was no statistical significant difference found between the incidence of local metastasis of the various tumor sizes, suggesting that local metastasis of RCC is not associated with the size of the tumor. Based on the observation that incidences of local metastasis were low in early-stage RCC, we came to the conclusion that pseudocapsule of RCC tumor might have growth-limiting effect on the tumor enclosed. It is theoretically a safer and better surgical option for patients with RCC with a smaller size of tumor and indications for radical nephrectomy to undergo renal-sparing surgery with an excision margin of 1 cm of normal tissue around the pseudocapsule of the tumor.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Renal Cell; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged; Nephrectomy; Nephrons; Vimentin

To study the clinicopathologic features and histologic differential diagnosis of small cell neuroendocrine carcinoma (SmCC) of kidney.. The clinicopathologic features of 12 cases of SmCC of kidney encountered during the period from 1999 to 2010 were retrospectively reviewed.. Six cases of primary and 6 cases of metastatic SmCC involving kidney were identified. Amongst the primary renal SmCC, 2 were located in renal parenchyma and 4 in renal pelvis. Chest X-ray showed negative findings. Five of them underwent radical nephrectomy. On gross examination, the tumor was located centrally around the renal pelvis in 4 cases and peripherally in renal parenchyma in 1 case. On the other hand, 4 of the 6 cases of metastatic SmCC were discovered during therapy for pulmonary SmCC. Two of these patients presented with abdominal pain and gross hematuria, with lung and renal tumor masses identified simultaneously. The diagnosis of all the 6 cases of metastatic SmCC was confirmed by fine needle aspiration biopsy. Microscopically, pure SmCC was demonstrated in the 2 cases of primary renal parenchymal SmCC and 6 cases of metastatic SmCC. The 4 primary renal pelvic SmCC coexisted with urothelial carcinoma component. On immunohistochemical study, all cases were positive for cytokeratin, synaptophysin and CD56. All metastatic cases and 4 primary cases were also positive for TTF-1. Of six patients with primary SmCC two died 4 and 9 months after operation, and two were alive with a follow-up of 25 and 138 months, respectively. Five of six cases with metastatic SmCC died 3 - 8 months after diagnosis. The other 3 cases were failed to follow-up.. Both primary and metastatic SmCC can be found in the kidney. Although rare, primary SmCC is located either in renal parenchyma or in pelvis. The diagnosis of SmCC relies on morphologic examination and immunohistochemical study. TTF-1 immunostaining cannot reliably distinguish primary from metastatic SmCC in kidney. Correlation with clinicoradiologic findings and demonstration of coexisting urothelial carcinoma component (if any) is helpful in delineation of the tumor origin.

Topics: Adult; Aged; Carcinoma, Neuroendocrine; Carcinoma, Renal Cell; Carcinoma, Small Cell; CD56 Antigen; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratins; Kidney Neoplasms; Lung Neoplasms; Lymphoma; Male; Middle Aged; Nephrectomy; Nuclear Proteins; Retrospective Studies; Sarcoma, Ewing; Synaptophysin; Thyroid Nuclear Factor 1; Transcription Factors; Treatment Outcome; Wilms Tumor

A 92-year-old male presented for routine endoscopic surveillance of his gastrointestinal (GI) tract. He did not have any GI symptoms currently, and the patient had undergone a right nephrectomy for renal cell carcinoma 17 years previously. A lower GI endoscopy revealed polyps in the ascending colon, hepatic flexure, and sigmoid colon (2 polyps). All the polyps were snared and removed in toto. Histological evaluation of all 4 polyps showed similar features. There was expansion of the lamina propria by sheets of clear cells arranged in a nested pattern with a rich vascular network. Immunohistochemistry showed the tumor to be positive for low-molecular-weight cytokeratin, CD10, and vimentin. The features were morphologically and immunophenotypically that of clear cell renal cell carcinoma. This case highlights an extremely unusual presentation of recurrent renal cell carcinoma as multiple, separate colonic polyps 17 years after resection of the primary tumor.

Topics: Aged, 80 and over; Carcinoma, Renal Cell; Colonic Neoplasms; Colonic Polyps; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Male; Molecular Weight; Neoplasms, Multiple Primary; Neprilysin; Vimentin

To analyse the cytomorphologic spectrum of Wilms tumour (WT) on aspirates, the largest series reported to date.. Adequate aspirates from paediatric renal tumours over a period of 17 years were reviewed and selected if subsequent excision showed WT or aspirates were diagnostic for WT and clinical/radiological evidence consistent with that diagnosis. Smears were re-examined for the proportion of components, degree of pleomorphism and mitosis.. Of 110 aspirates, smears were triphasic in 44 (40.0%), biphasic (blastema and tubules) in 36 (32.7%) and monophasic (blastema alone) in 30 (27.3%). Stromal predominance was seen in 11 aspirates (10.0%) and five showed rhabdomyoblastic differentiation; all 11 were triphasic. Mean mitotic rate was 9.3/5000 cells (range 4-39/5000). Nuclear atypia not amounting to anaplasia and without atypical mitoses was seen in 15 (13.6%); these presented diagnostic problems. Two aspirates (1.8%) were considered anaplastic (unfavourable), both having atypical mitoses. Criteria similar to histology (i.e. 3-fold or more variation in nuclear size, marked hyperchromasia with bizarre nuclei and atypical mitoses in a biphasic or triphasic aspirate) helped in distinguishing anaplastic WT. Histopathological correlation in 67 cases showed good correlation of blastemal predominance, stromal predominance and anaplastic histology with the corresponding cytology. However, 9/27 (33.3%) triphasic tumours had only blastemal cells on corresponding aspiration because of sampling error. Cytokeratin was positive in 4 of 20 aspirates with blastema alone.. Aspirates from WT were triphasic or biphasic in the majority (72.7%), permitting cytological diagnosis, which was improved by cytokeratin immunocytochemistry. Blastemal and stromal predominance on histology correlated well with cytology, but many triphasic tumours showed only blastema on aspiration. Anaplastic WT can be detected on aspirates using criteria similar to histology.

Topics: 12E7 Antigen; Adolescent; Anaplasia; Antigens, CD; Biopsy, Fine-Needle; Carcinoma, Renal Cell; Cell Adhesion Molecules; Cell Differentiation; Child; Child, Preschool; Chromosomal Proteins, Non-Histone; Diagnosis, Differential; DNA-Binding Proteins; Female; Follow-Up Studies; Humans; Infant; Keratins; Kidney; Kidney Neoplasms; Male; Peptide Fragments; Rhabdoid Tumor; SMARCB1 Protein; Staining and Labeling; Synaptophysin; Transcription Factors; Wilms Tumor; WT1 Proteins

Topics: Adenoma, Oxyphilic; Cadherins; Carcinoma, Renal Cell; Catheter Ablation; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged; Neoplasms, Multiple Primary; Parvalbumins; S100 Proteins

Topics: Adenocarcinoma, Clear Cell; Adult; Carcinoma; Carcinoma, Mucoepidermoid; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Keratins; Male; Nasal Cavity; Nose Neoplasms; S100 Proteins

Topics: Adenocarcinoma, Follicular; Adenoma; Aged; Carcinoma, Renal Cell; Chromogranin A; Diagnosis, Differential; DNA-Binding Proteins; Female; Humans; Keratins; Kidney Neoplasms; Neprilysin; Thyroglobulin; Thyroid Neoplasms; Transcription Factors; Vimentin

Topics: Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Carcinosarcoma; Female; Follow-Up Studies; Humans; Keratins; Kidney Neoplasms; Lymphatic Metastasis; Male; Prostatic Neoplasms; Retrospective Studies; Survival Rate; Ureteral Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Vimentin

Tuberous sclerosis complex results from mutations in 1 of 2 interacting gene products, hamartin or tuberin. The syndrome is characterized by hamartomas and neoplastic lesions, including angiomyolipomas of the kidney and other organs. Renal cell carcinoma (RCC) in tuberous sclerosis remains relatively poorly characterized because historical studies were confounded by the inclusion of epithelioid angiomyolipomas. The authors present a patient with tuberous sclerosis and bilateral renal lesions, including multiple minute angiomyolipomas, cortical cysts, and 4 separate RCCs of unclassified type. The carcinomas shared distinctive morphological features, including sheet-like, glandular, trabecular, or cystic architecture and abundant granular eosinophilic cytoplasm. By definition, the carcinomas were keratin positive and negative for HMB-45 and Melan-A. Detailed immunohistochemical analysis revealed heterogeneity among the cortical cysts and carcinomas. The histopathological features of these carcinomas illustrate characteristics of renal carcinoma that are probably related to genetic alterations of tuberous sclerosis.

Topics: Adult; Angiolipoma; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Neoplasms, Multiple Primary; Treatment Outcome; Tuberous Sclerosis

Renal carcinomas are a heterogeneous group of tumors, difficult to classify and identify precisely. Since their prognosis depends very much upon their type, precise diagnosis might mean the difference between therapeutic success and patient death. Cytokeratins are particularly useful for the identification of the epithelial nature of the tumors, because their expression is maintained even in poorly differentiated tumors. Monoclonal cytokeratins such as CK7 and CK20 stain different components of the renal tubular system and are a useful duo for the identification of the origin of the different tumors that might arise in the kidney. Along with polyclonal cytokeratins such as AE1/AE3 and high molecular weight cytokeratin antibodies (34betaE12, Cam 5.2), epithelial membrane antigen (EMA) and vimentin, they are included in every diagnostic panel for renal tumors. We have selected 138 renal parenchyma tumor specimens, performed morphological diagnosis and then stained them with polyclonal cytokeratin antibody AE1/AE3, and monoclonal antibodies to CK7 and CK20. AE1/AE3 was expressed in 61.7% of the renal parenchyma tumors, with high intensity and percentage of positive cases in the papillary carcinomas (100%), and with rare and weakly positive cells in chromophobic cells carcinomas, clear cells carcinomas and sarcomatous carcinomas. CK7 was positive in 68% of the renal parenchyma tumors, with positive reaction in 100% of the cases of chromophobic cells and sarcomatous carcinomas. Clear cells carcinomas had the less percentage of positive cells, whereas papillary carcinomas were positive in seven out of eight cases. No difference in the staining pattern was noticed between type I and type II papillary carcinomas. CK20 was negative in all cases studied.

Topics: Antibodies; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Predictive Value of Tests; Prognosis

Metastatic clear cell renal cell carcinoma (CCRCC) should be considered in differential diagnosis of intraoral clear cell tumors, including mucoepidermoid carcinoma (MEC).. We compared the clinical, histologic, histochemical, and immunohistochemical characteristics of 9 oral metastatic CCRCCs and 8 intraoral clear cell MECs.. Oral metastatic CCRCC affected salivary-gland containing tissues in 7 cases (78%). Microscopically, oral metastasis revealed a proliferation of neoplastic clear cells arranged in an alveolar pattern with central blood vessels, features that were not seen in any intraoral clear cell MEC. Mucicarmine staining was positive only in clear cell MEC. Immunohistochemistry showed similarities in cytokeratin expression; vimentin and CD10 were expressed in all oral metastatic CCRCCs but in only 1 clear cell MEC each.. Besides clinical history, the alveolar pattern, vessel distribution, absence of mucicarmine staining, and vimentin and CD10 immunoexpression are useful in histologic differential diagnosis of CCRCC and clear cell MEC.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Aged, 80 and over; Carcinoma, Mucoepidermoid; Carcinoma, Renal Cell; Carmine; Cell Nucleus; Coloring Agents; Cytoplasm; Diagnosis, Differential; Female; Hemorrhage; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Male; Microvessels; Middle Aged; Mouth Neoplasms; Neprilysin; Salivary Gland Neoplasms; Vimentin

Topics: Antibodies, Monoclonal; Antibody Specificity; Biomarkers; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Keratin-18; Keratin-8; Keratins; Kidney Neoplasms

Topics: Carcinoma, Medullary; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasms, Squamous Cell; Nephrectomy; Radiotherapy, Adjuvant

Tumor-to-tumor metastasis in thyroid neoplasms is exceedingly uncommon. Two unusual cases of breast carcinoma and renal cell carcinoma metastatic to follicular variant papillary carcinoma are reported. On histologic sections, the donor tumor cells infiltrated the substance of the recipient tumor and the angiolymphatic channels, but the bulk of metastatic tumor was confined within the thyroid carcinoma. Immunohistochemical stains as well as molecular studies confirmed the origin of both donor tumors, as well as the diagnosis of follicular variant of papillary carcinoma in the recipient tumors. Distinguishing between two such tumor populations may be difficult when the donor tumor cells morphologically resemble primary neoplasms of the recipient organ. A history of previous malignancy and ancillary studies can be helpful in making this distinction and rendering the correct diagnosis. A brief review of literature and discussion of tumor-to-tumor metastasis in thyroid neoplasms is also presented.

Topics: Apoptosis Regulatory Proteins; Biomarkers; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Lobular; Carcinoma, Papillary, Follicular; Carcinoma, Renal Cell; DNA-Binding Proteins; Female; Galectin 3; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Loss of Heterozygosity; Male; Microsatellite Repeats; Middle Aged; Neoplasm Metastasis; Neoplasms, Second Primary; Neprilysin; Nuclear Proteins; Thyroglobulin; Thyroid Neoplasms; Trans-Activators; Transcription Factors; Vimentin

A germline insertion of a single nucleotide in the rat homologue of the human Birt-Hogg-Dubé (BHD) gene gives rise to dominantly inherited renal cell carcinoma (RCC) in the Nihon rat model. In this study, we established 7 lines (NR cell lines NR22, 24, 32, 45, 49, 54 and 64) from an RCC found in a Nihon rat. All cell lines consisted mainly of round or polygonal cells arranged in a cobblestone-like growth pattern. Cells of NR cell lines had abundant cytoplasm and tight junctions as well as microvilli on electron microscopy and were positive for cytokeratin on immunocytochemistry. Cell lines NR22, 24 and 32 showed rapid growth, whereas the growth of the remaining lines was very slow. While the modal chromosome number of lines NR24, 45 and 54 was 42, the remaining lines exhibited aberrant modal numbers ranging from 70 to 96. All NR cell lines formed tumors at subcutaneous inoculation sites in nude mice, and tumors from lines NR54 and 64 developed pulmonary metastases. All NR cell lines had a germline mutation in the rat Bhd gene in the gene analysis. NR cell lines would prove valuable experimental tools for studies on unique functions of the Bhd gene and renal carcinogenesis.

Topics: Animals; Base Sequence; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Proliferation; DNA Mutational Analysis; Female; Immunohistochemistry; Keratins; Liver Neoplasms; Loss of Heterozygosity; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron; Microvilli; Mutation; Neoplasms, Experimental; Proto-Oncogene Proteins; Rats; Rats, Mutant Strains; Tight Junctions; Transplantation, Heterologous; Tumor Suppressor Proteins; Vimentin

Collecting duct carcinoma is a highly aggressive renal epithelial malignancy, although it accounts for less than 1% of the incidence of renal epithelial neoplasms. Differential diagnoses between collecting duct carcinoma, pelvic urothelial carcinoma with marked invasion to the renal parenchyma (invasive urothelial carcinoma), and papillary renal cell carcinoma is often challenging. In our current study, we examined the utility of using commercially available antibodies, in conjunction with lectin histochemistry, for such differential diagnoses. We examined 17 cases of collecting duct carcinoma, 10 cases of invasive urothelial carcinoma and 15 cases of papillary renal cell carcinoma (type 1, 6 cases; type 2, 9 cases) in these evaluations. Our results indicated that Ulex europaeus agglutinin 1, E-cadherin, and c-KIT were frequently positive in collecting duct carcinoma and invasive urothelial carcinoma, in comparison with papillary renal cell carcinoma, which had negative results for CD10 and alpha-methylacyl CoA racemase. We found, however, that collecting duct carcinoma showed positivity for high-molecular-weight cytokeratin and low-molecular-weight cytokeratin at a low frequency compared with invasive urothelial carcinoma, and that these distinctions need further careful evaluation. In addition, high-molecular-weight cytokeratin positivity was not a reliable marker for collecting duct carcinoma. We conclude that Ulex europaeus agglutinin 1 reactivity and positivity for E-cadherin and c-KIT are effective in distinguishing collecting duct carcinoma from papillary renal cell carcinoma, and that negative results for alpha-methylacyl CoA racemase and CD10 are potentially useful hallmarks of this distinction also. In contrast, a differential diagnosis for collecting duct carcinoma and invasive urothelial carcinoma will require careful examination of multiple routinely stained specimens, particularly in cases of in situ neoplastic lesions in the pelvic mucosa.

Topics: Adult; Aged; Antigens, CD; Cadherins; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged; Mucin-1; Neprilysin; Peanut Agglutinin; Plant Lectins; Proto-Oncogene Proteins c-kit; Racemases and Epimerases; Urothelium

To assess the clinicopathological features and molecular genetic changes of multilocular cystic renal cell carcinoma (MCRCC).. All the data reviewed were from the files of pathology department of Changhai hospital collected from 1990 to 2006. In totally 706 cases of renal cell carcinoma studied, there were 21 MCRCC cases identified. The clinical and pathological features were assessed, immunohistochemical staining was performed, and loss of heterozygosity (LOH) and microsatellite instability (MSI) were assessed using four microsatellite markers on chromosomes 3, 9 and 14.. Of the 21 patients, the age ranged from 34 to 72 years (mean 50 years), 19 were male and two female. Tumors were found incidentally in 18 patients during physical examination, three patients had anemia or microhematuria. Among the 21 patients, 10 tumors were in the left kidney and 11 in the right. Eighteen patients were stage T1, two stage T2, and one stage T3 with perinephric tissue involvement. Follow up information was available in 20 patients, all showed no evidence of tumor recurrence or metastasis. Grossly, the tumor size ranged from 0.3 cm to 10.0 cm in the greatest dimension, consisting of multilocular cysts with variable sizes which contained light yellow, colloid or hemorrhagic fluid. The septae varied in thickness (ranged 0.1 cm to 0.5 cm, mean 0.2 cm). Microscopically the cysts were lined by single to multilayered epithelial cells with clear or lightly eosinophilic cytoplasm. There were clusters of clear cells seen in the septae stroma. Sixteen tumors were of Fuhrman grade 1, and five were of Fuhrman grade 2. Immunohistochemically, the clear cells were positive for vimentin, ABC, CAM5.2 and EMA. Six samples were positive for CD10, and 16 were positive for NSE. Among 21 patients, PCR amplification was successful in 11 patients. Microsatellite alterations were found in five patients. LOH was observed in 3 of 11 MCRCC (27%), two were at D3S1560 locus, and one at D14S617 locus. MSI frequency was identified in 2 of 11 MCRCC (18%), locating at D9S168 or D14S617 locus, respectively.. MCRCC is an uncommon tumor of kidney, constituting 2.9% of all RCC enrolled into the study. It has distinctive clinical and pathological characteristics with an excellent outcome. Results indicated that MCRCC is a rare entity with low malignant potential.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Biomarkers; Carcinoma, Renal Cell; Female; Humans; Keratins; Kidney; Kidney Diseases, Cystic; Kidney Neoplasms; Male; Middle Aged; Neoplasm Staging; World Health Organization

Tumor angiogenesis is a dynamic process that plays a major role in cancer progression. Vascular endothelial growth factor (VEGF) and its receptors play a pivotal role in angiogenesis. The expression of VEGF and its receptors VEGFR-1 and VEGFR-2 in renal cell carcinoma (RCC) was investigated in the perspective of anti-VEGF treatments.. Total VEGF protein levels were quantified by enzyme-linked immunosorbent assay (ELISA) in tumor tissue samples from surgical specimens of 65 patients with clear cell RCC. At the cellular level the VEGF isoforms VEGFR-1 and VEGFR-2 mRNA were quantified by real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in laser-microdissected tumoral epithelial as stromal cells and in corresponding normal tissue compartments. Colocalization of VEGF and VEGFR-1 proteins was studied by triple immunofluorescent labeling.. Protein VEGF in cytosolic extracts was significantly higher in tumoral than in nontumoral tissue (P< .0001). Event-free survival was significantly longer for patients with cytosolic VEGF lower than the cutoff (75th percentile of VEGF protein levels, P= .02). In laser-microdissected epithelial cells, VEGF(121) and VEGFR-1 mRNA expressions were higher in RCC than in corresponding nontumoral kidney (P= .007 and P= .002, respectively); they were also higher in stromal cells of RCC compared with nontumoral kidney (P= .02 and P= .003, respectively). There was no differential VEGFR-2 expression in epithelial or in stromal cells of tumoral or nontumoral kidney. By immunofluorescent labeling VEGF and VEGFR-1 colocalized on RCC tumor epithelial and stromal cells.. Combined laser microdissection and quantitative RT-PCR, as triple immunofluorescent labeling, underlined the preferential expression of the most soluble VEGF isoform, VEGF(121), and its receptor VEGFR-1, but not VEGFR-2, in epithelial and stromal cells of RCC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; Epithelial Cells; Female; Fluorescent Antibody Technique; Humans; Keratins; Kidney Neoplasms; Male; Microdissection; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stromal Cells; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2

Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Renal Cell; Female; Humans; Keratins; Kidney; Kidney Neoplasms; Mixed Tumor, Malignant; Tomography, X-Ray Computed; Treatment Outcome

Distinguishing hemangioblastomas from metastatic clear-cell renal cell carcinomas (CCRCCs) in the brain is a diagnostic challenge owing to similar clinical and morphologic presentations. Inhibin-alpha and aquaporin1 were shown as positive markers of hemangioblastoma, but are not totally reliable distinguishing hemangioblastoma from metastatic CCRCC. This study shows that the diagnosis can be achieved using a combination of markers. To identify the panel of markers useful for this differential, 67 hemangioblastomas and 34 metastatic CCRCCs were analyzed using a panel of antibodies including aquaporin1, inhibin-alpha, D2-40, cytokeratin AE1/AE3, epithelial membrane antigen, and CD10. The study confirms the usefulness of aquaporin1 (97% sensitivity, 83% specificity) and inhibin-alpha (88% sensitivity, 79% specificity) as positive markers of hemangioblastoma and shows that aquaporin1 is a superior positive marker versus inhibin-alpha for the differential. Positivity of tumor cells with cytokeratin AE1/AE3 is the signature of a metastatic CCRCC (100% specificity, 88% sensitivity) and CD10 expression as well (100% specificity, 79% sensitivity). The combined use of aquaporin1 and AE1/AE3 yields a high degree of sensitivity and specificity to differentiate between hemangioblastoma and metastatic CCRCC. All tumors but one aquaporin1 positive and cytokeratin AE1/AE3 negative (65/66) correspond to hemangioblastomas (97% sensitivity, 97% specificity, 98.5% diagnostic positive predictive value). Tumors with the opposite profile, aquaporin1 negative, and cytokeratin AE1/AE3 positive, (25/25), correspond to metastatic CCRCC (74% sensitivity, 100% specificity, 100% diagnostic positive predictive value). In summary, aquaporin1 is the most sensitive positive marker of hemangioblastoma. Despite its moderate specificity, when used in combination with epithelial marker AE1/AE3, it allowed to reliably distinguish hemangioblastoma from metastatic CCRCC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aquaporin 1; Biomarkers, Tumor; Brain Neoplasms; Carcinoma, Renal Cell; Child; Diagnosis, Differential; Female; Hemangioblastoma; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged

To study the clinicopathologic features and biologic behavior of renal cell carcinoma (RCC) with rhabdoid features.. Ten cases of RCC with rhabdoid features collected during the period from 1995 to 2005 were enrolled into the study. The clinical findings were analyzed and the hematoxylin and eosin-stained sections were reviewed. Immunohistochemistry and electron microscopy were also performed.. The age of patients ranged from 33 to 69 years (mean age = 52 years). Nine of the patients were males and 1 female. Five patients showed evidence of perinephric invasion. Two patients presented with regional lymph node metastases and 1 patient showed distant metastasis to the lung. Histologically, the rhabdoid foci were characterized by loosely cohesive trabeculae, acini, lobules and clusters of rhabdoid cells in otherwise clear cell RCC (9 cases) or papillary RCC (1 case). The rhabdoid cells were round to polygonal in shape and contained globular eosinophilic inclusion bodies in the cytoplasm, eccentric nuclei, vesicular chromatin pattern and prominent nucleoli. Coagulative tumor necrosis was commonly seen. Immunohistochemical study showed that the rhabdoid cells were diffusely positive for CD10 (10/10), cytokeratin AE1/AE3 (10/10), epithelial membrane antigen (10/10) and vimentin (10/10). Focal staining for neuron-specific enolase and S-100 protein was also noted. They were negative for CK7, CK20 and myogenic markers (including myogenin, smooth muscle actin and muscle-specific actin). The mean Ki-67 labeling index of the rhabdoid component was higher than that of the non-rhabdoid component (P < 0.05). Follow-up information was available in 8 patients. While 6 patients are still alive without recurrence, 2 patients died of the disease 6 and 29 months respectively after the operation.. RCC with rhabdoid elements are mainly observed in clear cell RCC and need to be distinguished from oncocytic renal tumors and malignant rhabdoid tumor of kidney. The higher proliferative activity in the rhabdoid areas may indicate more aggressive biologic behavior.

Topics: Adult; Aged; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Mucin-1; Nephrectomy; Neprilysin; Rhabdoid Tumor; Vimentin

Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged; Sarcoma

Mucinous tubular and spindle cell carcinoma of the kidney is a new diagnostic entity. We present the pathologic and genomic characteristics of three such low-malignant tumors. Two of the tumors were found in women aged 19 and 52 years, the third tumor was found in an 80-year-old man, and the tumor stages were pT2N0MX, pT2NXMX, and pT1NXMX, respectively. Findings by immunohistochemistry were similar but not identical for the three cases; markers for both proximal and distal parts of the nephron were expressed in each tumor, a finding that is in agreement with data from previous studies. The Ki-67-labeling index was below 5 in all three cases. Two of the tumors were predominantly hypodiploid (DNA-indexes 0.77 and 0.80), whereas the third tumor was hypertriploid (1.57) as measured by DNA-image cytometry. From the latter tumor live cells were available making it possible to establish its karyotype: 62-70,XXX,+del(X)(q11),-1,+2,+4,-5,-6,+7,-8,-9,-10,-11,+12,-13,-14,-15,+16,+17,+18,-19,+20,+21,-22[cp15]. Interphase fluorescence in situ hybridization analyses with centromere-specific probes for chromosomes 1, 3, 4, 6, 7, 9, 10, 17, 18, 20, and X showed that the two hypodiploid tumors had disomic and monosomic chromosome populations, whereas the karyotyped, near-triploid tumor was dominated by trisomic chromosome populations. Comparative genomic hybridization analysis was normal for the karyotyped tumor but abnormal for the two others. We conclude that multiple numerical chromosome aberrations may be a feature of mucinous tubular and spindle cell carcinomas of the kidney, but beyond that no clear-cut karyotypic aberration pattern is so far discernible.

Topics: Adenocarcinoma, Mucinous; Adult; Aged, 80 and over; Carcinoma; Carcinoma, Renal Cell; Chromosome Aberrations; DNA, Neoplasm; Female; Genome, Human; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Karyotyping; Keratin-7; Keratins; Kidney Neoplasms; Male; Middle Aged; Mucin-1; Nucleic Acid Hybridization; Vimentin

Metanephric adenoma (MA), a well-described renal neoplasm, usually behaves in a benign fashion. It may have areas that are morphologically similar to papillary renal cell carcinoma (RCC) type, or epithelial (tubular predominant) type Wilms' tumor. Prior immunohistochemical studies of MA have reported variable staining patterns. Alpha-methylacyl-CoA racemase (AMACR), a molecular marker for prostate carcinoma, has subsequently been found to be overexpressed in breast, colorectal and ovarian cancers, among others. Recent microarray analysis of renal tumors has shown an increase of AMACR mRNA levels in papillary RCC but not in other subtypes. We investigated the utility of immunohistochemical staining for AMACR, cytokeratin 7(CK7), CD57 and WT1 to differentiate between the above-mentioned three neoplasms. Immunohistochemical stains were performed on paraffin-embedded tissue sections from 25 papillary RCC, 10 MAs and eight Wilms' tumors. AMACR was positive in one (10%) of 10 MAs and 24 (96%) of 25 papillary RCC, while it was negative in all Wilms' tumors. CK7 was positive in 20 of 25 papillary RCCs, focally positive in one Wilms' tumor and was negative in all MAs. CD57 was positive in all six MAs that were stained, focally positive in one of 25 papillary RCC and one of eight Wilms' tumors. WT1 was positive in seven of 10 MAs, three of 25 papillary RCCs and all eight Wilms' tumors. In conclusion, diffuse and strong immunoreactivity for AMACR may be useful in differentiating papillary RCC from MA but a panel which includes AMACR, CK7 and CD57 is better in this differential diagnosis. AMACR is not helpful in differentiating MA from Wilms' tumor, but CD57 is helpful in this differential diagnosis. WT1 may be useful in separating Wilms' tumor from MA and papillary RCC but is not helpful in differentiating MA from papillary RCC.

Topics: Adenoma; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Renal Cell; CD57 Antigens; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney Neoplasms; Racemases and Epimerases; Wilms Tumor; WT1 Proteins

A clinicopathologic study of 108 cases of high-grade urothelial carcinomas of the renal pelvis is presented. Of the 108 tumors, 44 (40%) showed unusual morphologic features, including micropapillary areas (four cases), lymphoepithelioma-like carcinoma (two cases), sarcomatoid carcinoma (eight cases, including pseudoangiosarcomatous type), squamous differentiation and squamous cell carcinoma (15 cases), clear cells (two cases), glandular differentiation (two cases), rhabdoid, signet-ring or plasmacytoid cells (four cases), pseudosarcomatous stromal changes (four cases) and intratubular extension into the renal pelvis (three cases). Pathological staging was available in 62 patients; of these, 46 cases (74%) were in high stage (pT2-pT4) and 16 (26%) were in low stage (pTis, pTa, pT1). Clinical follow-up ranging from 1 to 256 months (median: 50 months) was available in 42 patients; of these, 26 (61%) died of tumor with a median survival of 31 months. The patients who did not die of their tumors showed only minimal or focal infiltration of the renal parenchyma by urothelial carcinoma, whereas those who died of their tumors showed massive infiltration of the kidney by the tumor. High-grade urothelial carcinomas of the renal pelvis can show a broad spectrum of histologic features similar to those seen in the urinary bladder. Our results support the finding that, unlike urothelial carcinomas of the bladder, the majority of primary urothelial carcinomas of the renal pelvis are of high histologic grade and present in advanced stages. Our study further highlights the fact that, in the renal pelvis, urothelial carcinomas show a tendency to frequently display unusual morphologic features and metaplastic phenomena. The importance of recognizing these morphologic variants of urothelial carcinoma in the renal pelvis is to avoid confusion with other conditions. The possibility of a high-grade urothelial carcinoma should always be considered in the evaluation of a tumor displaying unusual morphologic features in the renal pelvis, and attention to proper sampling as well as the use of immunohistochemical stains will be of importance to arrive at the correct diagnosis.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratin-7; Keratins; Kidney Neoplasms; Kidney Pelvis; Male; Middle Aged; RNA, Viral; Urinary Bladder Neoplasms

The prognostic relevance of disseminated cytokeratin-positive (CK+) tumor cells in the bone marrow of patients with different types of carcinoma has been demonstrated in several studies. In this prospective study, the frequency and prognostic value of CK+ tumor cells was investigated in the bone marrow of 55 consecutive patients with metastatic renal cell carcinoma (M1 RCC) in comparison with 256 M0 RCC patients from a previous study.. Aspiration of bone marrow from the anterior iliac crest was performed immediately before tumor resection in RCC patients. Cytospins were made and stained by immunocytochemistry using the APAAP (alkaline phosphatase-antialkaline phosphatase) protocol and monoclonal antibodies CK2 and A45-B/B3. Twenty-seven patients with no evidence of any malignant disease served as a control group.. CK+ tumor cells were detected in 42% (23 of 55 patients) of the M1 patients and 25% (63 of 256 patients) of the M0 patients (P <.01). No CK+ cells (0 of 27 patients) were detected in the control group. In the M1 group, CK- patients demonstrated a trend toward a better outcome compared with CK+ patients (log-rank test, P = .19). This difference was significant when applying a higher threshold (0-2 CK+ cells vs. > or = 3 CK+ cells; P <.05). On multivariate analysis, the detection of > or = 3 CK+ cells in the bone marrow was found to be an independent prognostic factor (P <.001).. The results of the current study indicate that disseminated CK+ cells play a role in the biology of tumor spread of RCC, and that their immunocytochemical detection can be useful in assessing the prognosis of patients with M1 disease.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Marrow Neoplasms; Carcinoma, Renal Cell; Case-Control Studies; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged; Neoplastic Cells, Circulating; Prognosis; Survival Analysis

Chromophobe renal cell carcinoma (ChRCC) and oncocytoma might mimic each other histologically. We studied the immunohistochemical staining pattern of caveolin-1 in 21 ChRCCs and 26 oncocytomas and compared it with cytokeratin (CK) 7 to evaluate its usefulness in differentiating these 2 neoplasms. All 21 ChRCCs (100%) were positive for caveolin-1, 20 of which were stained in 20% or more of the tumor cells. In contrast, only 3 (12%) of 26 oncocytomas showed positivity in fewer than 20% tumor cells and 23 (88%) of 26 were negative. In the nonneoplastic kidney, positive caveolin-1 staining was detected in the interstitial blood vessels and the parietal cells of the Bowman capsules but not in the tubular epithelium and glomerular and peritubular capillaries. All 21 ChRCCs (100%) were positive for CK7, with 18 (86%) stained in 20% or more of the tumor cells and 3 (14%) in fewer than 20%. Of 26 oncocytomas, 25 (96%) were positive for CK7, with 7 (27%) stained in 20% or more of the tumor cells and 18 (69%) in fewer than 20%. These results strongly suggest that caveolin-1 immunohistochemical analysis is useful for differentiating ChRCC from oncocytoma and is superior to CK7.

Topics: Adenoma, Oxyphilic; Biomarkers, Tumor; Carcinoma, Renal Cell; Caveolin 1; Cell Count; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney; Kidney Neoplasms

To investigate the diagnostic value of cytokeratin 7 (CK7) and parvalbumin at mRNA and protein levels.. CK7 and parvalbumin mRNA expression levels in 23 oncocytomas and 32 chromophobe renal cell carcinomas (RCCs) were examined using gene expression microarrays. Immunohistochemistry was performed using monoclonal antibodies specific for CK7 or parvalbumin in 41 chromophobe RCCs and 55 oncocytomas.. CK7 mRNA was overexpressed in 18 of 32 chromophobe RCCs but only 3 of 23 oncocytomas. Parvalbumin mRNA was overexpressed in 15 of 32 chromophobe RCCs and only 4 of 23 oncocytomas. In contrast, CK7 mRNA underexpression was noted in 13 of 23 oncocytomas and only 6 of 32 chromophobe RCCs, while parvalbumin underexpression was seen in 14 of 23 oncocytomas but only 6 of 32 chromophobe RCCs. By immunohistochemistry, 27 of 41 (66%) chromophobe RCCs expressed CK7 diffusely compared to only 3 of 55 (5%) oncocytomas. Diffuse parvalbumin expression was seen in all 41 of 41 (100%) chromophobe RCCs and only in 26 of 55 (47%) oncocytomas.. Both mRNA and protein expression levels of CK7 appear significantly higher in chromophobe RCC compared to oncocytoma (p < 0.001). Parvalbumin expression is less specific but often displays a patchy pattern in oncocytomas. Our study provides further evidence that CK7 and parvalbumin immunostains may be useful in differentiating oncocytoma from chromophobe RCC in problematic cases. Negative or patchy staining (< 50% cells) for CK7 and/or parvalbumin strongly favors the diagnosis of oncocytoma.

Topics: Adenoma, Oxyphilic; Antibodies, Monoclonal; Carcinoma, Renal Cell; Colloids; Diagnosis, Differential; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Iron; Keratin-7; Keratins; Kidney Neoplasms; Oligonucleotide Array Sequence Analysis; Parvalbumins; RNA, Messenger; Sensitivity and Specificity

Sarcomatoid renal cell carcinoma (SRCC) is an uncommon, aggressive renal cell carcinoma (RCC) accounting for 1.2% to 12.3% of renal cell carcinomas. SRCC may arise from any RCC subtype as it probably results from the de-differentiation of any renal epithelial malignancy. SRCC is characterised by a rapid progression and high metastatic rate. Currently there is no specific effective treatment for it. We report a new case of a 32-year-old man presented with two months backache. Ultrasound revealed a 7.5 cm heterogeneous mass at the inferior pole of the left kidney. A nephrectomy was performed. Histological study diagnosed a sarcomatoid renal cell carcinoma. The patient was doing well 6 months after initial surgery and then was lost to follow-up.

Topics: Actins; Adult; Biomarkers, Tumor; Carcinoma, Renal Cell; Cell Proliferation; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Vimentin

Renal cell carcinoma (RCC) is characterized by organ-specific metastases. The chemokine stromal derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 have been suggested to regulate organ-specific metastasis in various other cancers. On this basis, we hypothesized that the biological axis of CXCL12 via interaction with its receptor, CXCR4, is a major mechanism for RCC metastasis. We demonstrated that CXCR4 was significantly expressed on circulating cytokeratin+ RCC cells from patients with known metastatic RCC. We detected up-regulation of CXCR4 mRNA and protein levels on a human RCC cell line by either knockdown of the von Hippel-Lindau (VHL) tumor suppressor protein, or incubating the cells under hypoxic conditions. The enhanced CXCR4 expression was mediated through the interaction of the Hypoxia Inducible Factor-1alpha (HIF-1alpha) with the promoter region of the CXCR4 gene. Furthermore, the expression of CXCR4 on human RCC directly correlated with their metastatic ability in vivo in both heterotopic and orthotopic SCID mouse models of human RCC. Neutralization of CXCL12 in SCID mice abrogated metastasis of RCC to target organs expressing high levels of CXCL12; without altering tumor cell proliferation, apoptosis, or tumor-associated angiogenesis. Therefore, our data suggest that the CXCL12/CXCR4 biological axis plays an important role in regulating the organ-specific metastasis of RCC.

Topics: Animals; Biomarkers, Tumor; Carcinoma, Renal Cell; Cell Hypoxia; Cell Line, Tumor; Chemokine CXCL12; Chemokines, CXC; Chemotaxis; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Keratins; Kidney Neoplasms; Mice; Mice, SCID; Promoter Regions, Genetic; Receptors, CXCR4; RNA Interference; Transcriptional Activation; Von Hippel-Lindau Tumor Suppressor Protein

Diagnostic use of antibodies against aquaporin water channel proteins and PAX-2, a nuclear transcription factor in renal development, was tested in 202 renal neoplasms, using tissue microarray technique. Immunohistochemistry for aquaporin-1, aquaporin-2, PAX-2, CD10, and cytokeratin 7 was performed on 102 clear cell renal cell carcinomas, 44 papillary renal cell carcinomas (among them 34 type 1 and 10 type 2), 24 chromophobe renal cell carcinomas, three collecting duct carcinomas (carcinomas of the collecting ducts of Bellini), and 29 oncocytomas. Aquaporin-1 expression was found in clear cell renal cell carcinomas and papillary renal cell carcinomas of both types (78 and 73%, respectively), but not in chromophobe renal cell carcinomas, collecting duct carcinomas, and oncocytomas. Aquaporin-2 expression was not seen in any of the tested tumors. PAX-2 and CD10 was found in the majority of clear cell renal cell carcinomas (88 and 85%, respectively) but only in few papillary renal cell carcinomas, chromophobe renal cell carcinomas and oncocytomas. Decrease or loss of aquaporin-1 and PAX-2 was shown in higher grades compared to lower grades of clear cell renal cell carcinomas (P<0.0001 and <0.0245, respectively). Cytokeratin 7 was rarely seen in clear cell renal cell carcinomas, type 2 papillary renal cell carcinomas, and oncocytomas, but was found in the majority of type 1 papillary renal cell carcinomas (97.1%) and chromophobe renal cell carcinomas (88%). Aquaporin-1 and PAX-2 expression was found to correlate with nuclear grading for clear cell renal cell carcinomas but not for papillary renal cell carcinomas. No correlation of tumor stage and aquaporin-1 and PAX-2 expression was seen. Aquaporin-1 and PAX-2 are reliable markers for clear cell renal cell carcinomas of lower grades but not for higher grades. CD10 expression remains stable, independent of nuclear grading.

Topics: Adenocarcinoma, Clear Cell; Adenoma, Oxyphilic; Aquaporin 1; Aquaporin 2; Aquaporins; Biomarkers, Tumor; Blood Group Antigens; Carcinoma, Papillary; Carcinoma, Renal Cell; DNA-Binding Proteins; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney; Kidney Neoplasms; Neoplasm Staging; Neprilysin; PAX2 Transcription Factor; Tissue Array Analysis; Transcription Factors

Benign mixed epithelial and stromal tumor of the kidney (MEST) is a new, rare entity. These tumors are composed of two components: a stromal and an epithelial one. Clinical outcome is usually good, no specific cytogenetic alterations have been described up to now. We describe for the first time a case with translocation t (1; 19).

Topics: Actins; Adult; Biomarkers, Tumor; Carcinoma, Renal Cell; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Cysts; Desmin; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Male; Neoplasms, Complex and Mixed; Neoplasms, Glandular and Epithelial; Nephrectomy; Stromal Cells; Translocation, Genetic

The differential diagnosis of oncocytic neoplasms of salivary glands includes both primary and metastatic tumors, one of which is renal cell carcinoma. This study compared immunohistochemical staining characteristics of oncocytomas arising from salivary gland to metastatic renal cell carcinoma using a panel of markers.. Immunohistochemistry for cytokeratin 7 (CK7), cytokeratin 20 (CK20), epithelial membrane antigen (EMA), vimentin, CD10, and renal cell carcinoma marker (RCC) was performed on 10 oncocytomas and compared with ten metastatic renal cell carcinomas.. There were overlapping histologic findings in the oncocytomas and metastatic renal cell carcinomas, with oncocytomas displaying clear cell changes in 2 of 10 cases. CK7 was positive in 9 of 10 oncocytomas and CK20 in 8 of 10 (7/10 stained for both), and vimentin was only weakly positive in 4 of 10 oncocytomas. All oncocytomas were EMA positive, with membranous staining, and all were negative for CD10 and RCC. Metastatic renal cell carcinoma was strongly positive for vimentin, EMA, and CD10 in most cases. RCC and CK7 were variably positive in metastatic renal cell carcinomas (4/10), and only 1 of 10 showed weak staining with CK20.. Salivary gland oncocytomas and metastatic renal cell carcinomas share some similar histologic and immunohistochemical characteristics. CD10 and CK20 were the most useful markers to distinguish metastatic renal cell carcinoma from oncocytomas in the salivary gland, whereas RCC, EMA, CK7, and vimentin are not as useful.

Topics: Adenoma, Oxyphilic; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Male; Middle Aged; Mucin-1; Neprilysin; Salivary Gland Neoplasms; Vimentin

To investigate the morphologic features, differential diagnosis, prognosis and histogenesis of papillary renal cell carcinoma (PRCC).. Tumors composed of at least 50% papillae and > 1 cm in diameter were included in this study. Light microscopic observation, immunohistochemical assay of EMA, CK7, CD10, Vim, 34 beta E12 by tissue chip were performed.. Among 516 cases of renal epithelial tumors 33 cases of PRCC were detected. Grossly, hemorrhage, necrosis and multifocality were commonly seen. Besides typical papillae, inconspicuous papillary patterns, such as trabecular, tubular, micronodular and pseudostratified patterns could be seen. Foam cells and psammoma bodies in stroma, and hemosiderin in tumor cells were characteristic. Tumors were of two major types: basophilic type (n = 10), with small cuboid cell and pale cytoplasm (n = 10), 9 of them were low in Fuhrman grading; eosinophilic type (n = 22) with large columnar cells, rich in eosinophilic cytoplasm, 19 of them were high in Fuhrman grading. The remaining case was of clear cell type. The basophilic tumors were all positive for distal tubule marker EMA/CK7, none for proximal tubule marker CD10, 7 tumors positive for Vim. Eosinophilic tumors were positive for EMA/CK7 (9/22), CD10 (10/22) and Vim (6/22). All the tumors studied were negative for 34 beta E12. Follow-up data were available for 24 cases (mean 37 months) with 3-year survival rate of 64.3%, 5-year survival rate of 50%.. PRCC was a distinct malignant entity with unique pathological features. The prognosis of PRCC was worse than that of chromophobe renal cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Papillary; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratin-7; Keratins; Kidney Neoplasms; Kidney Tubules; Male; Middle Aged; Mucin-1; Neprilysin; Survival Rate; Vimentin

Topics: Adenocarcinoma, Mucinous; Carcinoma, Renal Cell; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney Neoplasms; Middle Aged; Mucin-1; Plant Lectins; Vimentin

Hybrid renal cell neoplasms (HRCNs) containing areas of tumor cells displaying cytological features of chromophobe renal cell carcinoma (CHRCC) and renal oncocytoma (RO) have been recently described in patients with renal oncocytosis and Birt-Hogg-Dube (BHD) syndrome (autosomal dominant genodermatosis). In this study, we identified cases of sporadic HRCN. We reviewed 425 consecutive renal cell carcinomas (RCC), 18 CHRCC, six HRCN, and 25 RO. Five HRCN were identified, including four from the group of RCC and two from RO. Patient age ranged from 40 to 68 years (mean age: 54 years), and the male:female ratio was 4:1. Tumors measured from 1.8 to 5 cm (mean diameter: 3.0 cm). Tumoral necrosis was not seen. Vascular invasion into medium-sized veins was identified in one HRCN. Chromophobe cells accounted for 20-80% of the tumors. Hale's colloidal stain showed weak to moderate diffuse cytoplasmic staining in scattered cells corresponding to those displaying routine staining features of chromophobe cells. Areas of oncocytic cells in studied tumors and control oncocytomas showed negative or focal cytoplasmic staining usually bordering extra- or intra-cytoplasmic lumina. Immunostaining for cytokeratin 7 and vimentin showed focal immunoreactivity in three cases and negative reactivity in all six cases, respectively. None of the study cases had microscopic RO, as commonly seen in renal oncocytosis, or were associated with BHD syndrome Sporadic HRCN accounted for 1% of RCC. They were of smaller size than RCC and were associated with a favorable prognosis.

Topics: Adenoma, Oxyphilic; Adult; Aged; Carcinoma, Renal Cell; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney Neoplasms; Male; Middle Aged; Vimentin

Among the epithelial renal tumours with eosinophilic cytoplasm, the main differential diagnostic problem arises between renal oncocytomas (ROs) and eosinophilic variants of chromophobe renal cell carcinomas (RCCs). We investigated the possible role of anti-mitochondrial (AMA), anti-caveolin 1 (CAV1), anti-CD63 (CD63) and anti-cytokeratin 14 (CK14) antibodies in the differential diagnosis of eosinophilic epithelial tumours and applied the Muller and Mowry modification of Hale's colloidal iron stain (HCI). Thirty-five ROs and 77 eosinophilic RCCs (27 chromophobe, 28 clear cell and 22 papillary RCCs) were included in this study. Apical and/or polar CD63 immunostaining (94%) and diffuse AMA (91%) and CAV1 (88%) immunostainings were the characteristics of ROs, whereas diffuse CD63 immunostaining (96%) and diffuse-peripheral AMA (96%) and CAV1 (92%) immunostainings were characteristic immunohistochemical features of eosinophilic chromophobe RCCs. We showed CK14 antibody not to be useful in the differential diagnosis of the eosinophilic epithelial renal tumours. The staining localisations with AMA, CAV1 and CD63 antibodies were significantly different between tumour groups. AMA had 96% sensitivity and 94% specificity, whereas CAV1 had 92% sensitivity and 97% specificity in diagnosing chromophobe RCCs. With HCI staining, ROs, showing apical and/or polar staining, could be differentiated from chromophobe RCCs, showing diffuse cytoplasmic staining. HCI had fairly low (69%) sensitivity and 100% specificity, whereas CD63 had 95% sensitivity and 100% specificity to diagnose ROs. We recommend using CD63 as the best marker of choice for distinguishing ROs from eosinophilic chromophobe RCCs when standard diagnostic criteria are not helpful.

Topics: Adenoma, Oxyphilic; Antigens, CD; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged; Mitochondria; Platelet Membrane Glycoproteins; Sensitivity and Specificity; Tetraspanin 30

Approximately 30-40% of primary and localized renal cell carcinoma (RCC) will eventually become metastatic disease. Therefore, the detection and molecular characterization of circulating tumor cells (CTC) in RCC may have important prognostic and therapeutic implications. Venous blood samples were obtained from a total of 214 RCC patients before and after nephrectomy or during adjuvant immune chemotherapy in two urological centers. After density gradient centrifugation, the CD45-negative cell population was isolated from peripheral blood samples (BS) by a semi-automated immunomagnetic depletion procedure using the MACS technology. Enriched cell populations potentially containing CTC were stained for cytokeratin and evaluated by a trained pathologist. CTC were found in 105 out of 363 BS (29%) originating from 80 out of 214 patients (37%). The median tumor cell number was five (range 1-51) per BS, i.e. approximately one CTC was detectable per 2-3 ml peripheral blood after tumor cell enrichment. For a subpopulation, follow-up data indicate that 62% of the patients with CTC detection in the blood developed progressive disease with single or multiple distant metastases or died because of RCC within two years. Here we show that the standardized immunomagnetic depletion protocol is a powerful tool for detecting and isolating intact RCC-derived CTC. The occurrence and the quantity of CTC in RCC patients is an early disease event. Furthermore, the occurrence of CTC is correlated with an advanced tumor stage and seems to be associated with a more aggressive tumor phenotype.

Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Cell Separation; Centrifugation, Density Gradient; Disease Progression; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Leukocyte Common Antigens; Magnetics; Male; Neoplasm Metastasis; Neoplastic Cells, Circulating; Phenotype; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; Time Factors

Electron microscopy and immunohistochemical techniques are powerful tools for the determination of tissue origin. Both techniques have been used in the current experiment for histogenesis of renal cell carcinoma. Fifty kidney tumors were subjected to immunohistochemical detection for intermediate filaments cytokeratin and vimentin, which are normally expressed in epithelial tissue and mesenchymal tissues, respectively. Twenty cases of the above were examined by electron microscopy for detection of ultrastructure features. From each kidney, two specimens were taken, one from the diseased area and another far from it to serve as a control. Immunohistochemical study revealed in cases of renal cell carcinoma, cytokeratin and vimentin were expressed alone in 44% of cases, and 40% of cases, respectively. Twelve percent of cases were coexpressed with both cytokeratin and vimentin. Electron microscopic study of diseased specimens revealed the expression of desmosomes which was observed in almost all tumor specimens. The expression of the vimentin in some cases either alone or with cytokeratin was interpreted as a change in the characters of some tumor cells which indicates the need for additional techniques in such cases to get the proper interpretation. The prevalence of the expression of cytokeratin and the persistence existence of desmosomes indicate the epithelial origin of the tumor. This data is very beneficial for determination of line of therapy and follow up of the patients. The results confirm the power of combined use of both immunohistochemistry and electron microscopy in the field of histogenesis.

Topics: Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Cortex; Kidney Neoplasms; Vimentin

Renal oncocytomas and chromophobe renal cell carcinomas (RCCs) share a common phenotype and both originate from the intercalated cells of the collecting duct. This makes it very difficult to differentiate between the two tumors immunohistochemically. Therefore, we studied the results of immunohistochemistry focusing on certain characteristic structures that are occasionally present in renal oncocytomas. We carried out Hale's colloidal iron staining and immunohistochemistry for various cytokeratins (cytokeratins 7, 8, 10, 10/13, 14, 18, 19 and 20, and AE1/AE3) in four oncocytomas and six chromophobe RCCs. In addition, one renal oncocytoma and one chromophobe RCC were studied using electron microscopy. Two renal oncocytomas and one chromophobe RCC were completely unstained by colloidal iron. There was no evident difference between the immunohistochemical characteristics of oncocytomas and those of chromophobe RCCs. However, in all four renal oncocytomas we identified intracytoplasmic ring-like positive reactions for some cytokeratins (at least 3 antigens of cytokeratins 7, 8 and 19, and AE1/AE3), which corresponded ultrastructurally to the intracytoplasmic lumens (ICLs). In contrast, no such structures were found in any of the chromophobe RCCs using the antibodies employed. Therefore, immunohistochemical identification of ICLs by cytokeratin typing may be useful for differentiating between renal oncocytomas and chromophobe RCCs and be more sensitive in this respect than colloidal iron staining.

Topics: Adenoma, Oxyphilic; Adult; Aged; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged; Retrospective Studies; Sensitivity and Specificity; Staining and Labeling

Keratin immunohistochemistry represents a widely applied differential diagnostic tool in surgical pathology. To investigate the value of keratin subtyping for the diagnosis among histological subtypes of renal cell carcinoma and oncocytomas, we performed a detailed immunohistochemical study, applying 22 different monoclonal keratin antibodies on a large series of 233 renal tumors [125 conventional, 22 chromophobe, and 20 papillary (12 type-1, 8 type-2 tumors) cancers and 66 oncocytomas] using a tissue microarray technique. Immunoreactivity for keratin 7, 8, 18, and 19 was present in all tumor entities, albeit in varying quantities. With antibodies directed against keratins 8 and 18, oncocytomas showed a distinct perinuclear and punctate dot-like pattern, which was not observed in renal cancer specimens. The only tumors showing immunoreactivity for keratin 20 were two type-2 papillary cancers. All other monospecific keratin antibodies yielded consistently negative results. Overall, in contrast to some recent publications, keratin subtyping generally appeared to be of additional value only for the differentiation of renal epithelial tumors. Hence, with respect to differential diagnostic value, Hale's colloidal iron stain and vimentin immunostaining are still the most useful tools in renal tumor pathology.

Topics: Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged

Topics: Adenocarcinoma, Clear Cell; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Humans; Keratins; Kidney Neoplasms; Kidney Tubules, Collecting; Neoplasms, Multiple Primary

We report 3 cases of a new renal cell tumor entity with a review of the literature. These 3 cases were retrieved from the files of this institution from 1991 to 2002. The clinical data and all histologic slides were reviewed and an immunohistochemical study was performed. Patients were all females. Tumors were almost similar with well-defined margins. Tumor architecture was tubular and focally fusiform with an abundant myxoid stroma. Tumor cells were low cuboidal, slightly eosinophilic with low nuclear grade. Immunohistochemistry was in favor of a distal nephron differentiation. All patients were healthy after surgery. We describe 3 cases of a new clinicopathological entity entitled low-grade tubular myxoid renal tumor with a benign clinical course.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Renal Cell; Female; Humans; Immunohistochemistry; Keratins; Kidney; Kidney Neoplasms; Magnetic Resonance Imaging; Nephrectomy; Treatment Outcome; Vimentin

In some cases distinction between chromophobe renal cell carcinoma (CRCC), oncocytoma and clear cell (conventional) renal cell carcinoma (eosinophilic variant) using routine light microscopy remains problematic. The present study investigates the level of agreement in the diagnosis of CRCC, as well as the histological features most frequently used for this diagnosis by two pathologists with a special interest in renal neoplasia. The sensitivity and specificity of immunohistochemical markers in cases with overlapping histological features in the diagnosis of CRCC were also studied. Electron microscopy was performed, as a diagnostic gold standard, on all of the cases.. Thirty-two renal tumours with predominantly eosinophilic cytoplasm were reviewed in a blinded fashion by two pathologists. The diagnosis and morphological features used to render each diagnosis were tabulated. Validation of the utility of keratin 7 and 20, epithelial membrane antigen (EMA), vimentin, CD10, parvalbumin, RCC antigen, antimitochondrial antibody and Hale's colloidal iron was performed by the construction of a tissue microarray (TMA) master block. Based on histological criteria alone, overall agreement on the diagnosis of these tumours was reached in 69% of the cases, while there was total disagreement in 12%. In 59% of the cases, total agreement was reached in classifying the case as a CRCC based on histology alone. Kappa statistics for interobserver variability were calculated as only slight agreement (kappa = 0.3). The histological features most frequently associated with a diagnosis of CRCC were accentuated cell borders (87%) and a combination of hyperchromatic wrinkled nuclei (79%) and perinuclear halos (74%). The most sensitive and specific marker for CRCC was parvalbumin (sensitivity 0.91; specificity 1.0). The immunohistochemical profile of EMA+/ vimentin- was useful but had low specificity (sensitivity 0.75; specificity 0.4). CD10 had the highest sensitivity (1.0) but worst specificity (0.25) for CRCC. Keratin 7 had high sensitivity (0.83) but fairly low specificity (0.37) for CRCC. Hale's colloidal iron and the RCC antigen marker were not contributory. Finally, the antimitochondrial antibody was found to be fairly sensitive (0.83) for excluding CRCC.. A small but significant proportion of renal tumours with cells having eosinophilic cytoplasm cannot be classified, even by experienced pathologists, based on histology alone. In these cases it is imperative to use markers with known sensitivity and specificity for the diagnosis of CRCC.

Topics: Adenoma, Oxyphilic; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Microscopy, Electron; Mucin-1; Neprilysin; Observer Variation; Parvalbumins; Pathology, Clinical; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; Single-Blind Method; Tissue Array Analysis; Vimentin

Diagnosis of renal epithelial tumours of adult is often easily made. Nevertheless, it can be difficult to distinguish clear cell carcinoma (CCC) and chromophobe carcinoma (CCHRO), or the eosinophilic variants of CCC and CCHRO with papillary carcinoma (CTP) and oncocytoma (ONCO). The objective is to study and validate immunohistochemical phenotypes of these tumours and to evaluate if they are helpful and to define a diagnostic strategy.. 310 tumours (75 CCC, 89 CTP, 50 CCHRO and 96 ONCO) were collected and put on 4 tissue-arrays blocks. Immunohistochemical stainings were performed with some usual antibodies: pancytokeratin AE1-AE3, EMA, vimentin, CD10, CK7, CK20 and RCC (Renal Cell Carcinoma).. Pancytokeratin AE1-AE3 is expressed mainly in CTP (82.5%). The cytoplasmic staining of EMA is seen in almost all CCHRO (98%) and more than half of CTP (57%). Vimentin is rather specific of CCC (54.5%) and CTP (85%) whereas it is negative in ONCO and CCHRO. CD10 is expressed in the majority of CCC (86.5%) and in some of CTP and CCHRO 65 and 39% respectively. CK7 is rather specific of CTP and CCHRO with 79 and 81.5% of positivity rate. Based on statistical analysis, we have built a diagnostical tree allowing to distinguish 79% of tumours using only three antibodies: CK7, vimentin and CD10.. CCC are CK7-/Vim-/CD10+ or CK7-/Vim+; CTP are CK7+/Vim+; CCHRO are CK7+/Vim-; and ONCO CK7-/Vim-/CD10-. In the oncocytoma/chromophobe group, ONCO are more often CK7-/EMA- and CCHRO CK7+/EMA+.

Topics: Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Papillary; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney Neoplasms; Male; Middle Aged; Neoplasms, Glandular and Epithelial; Neprilysin; Phenotype; Reproducibility of Results; Vimentin

A rare case of sarcomatoid renal cell carcinoma (RCC) with predominantly osteosarcomatous differentiation occurring in a 36-year-old male is reported. Immunohistochemistry excluded the possibility of primary osteosarcoma of the kidney.

Topics: Adult; Carcinoma, Renal Cell; Cell Differentiation; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Osteosarcoma; Vimentin

Renal cell carcinoma comprises several histological types with different clinical behavior. Accurate pathological characterization is important in the clinical management of these tumors. We describe gene expression profiles in 41 renal tumors determined by using DNA microarrays containing 22,648 unique cDNAs representing 17,083 different UniGene Clusters, including 7230 characterized human genes. Differences in the patterns of gene expression among the different tumor types were readily apparent; hierarchical cluster analysis of the tumor samples segregated histologically distinct tumor types solely based on their gene expression patterns. Conventional renal cell carcinomas with clear cells showed a highly distinctive pattern of gene expression. Papillary carcinomas formed a tightly clustered group, as did tumors arising from the distal nephron and the normal kidney samples. Surprisingly, conventional renal cell carcinomas with granular cytoplasm were heterogeneous, and did not resemble any of the conventional carcinomas with clear cytoplasm in their pattern of gene expression. Characterization of renal cell carcinomas based on gene expression patterns provides a revised classification of these tumors and has the potential to supply significant biological and clinical insights.

Topics: Adenocarcinoma, Clear Cell; Antigens, CD; Carcinoma, Papillary; Carcinoma, Renal Cell; Cytoplasmic Granules; DNA Fingerprinting; DNA, Complementary; Gene Expression Regulation, Neoplastic; Humans; Keratins; Kidney Neoplasms; Multigene Family; Nephrectomy; Nephrons; Neprilysin; Oligonucleotide Array Sequence Analysis; Vimentin

The diagnosis of primary clear cell carcinoma of the ovary or kidney is usually straightforward. However, problems in ascertaining the site of the primary tumor may arise when there is widespread metastatic disease or when clear cell carcinoma is present in both the ovary and kidney. In this study, the value of a panel of antibodies in distinguishing between an ovarian and renal clear cell carcinoma was evaluated. The panel comprised cytokeratin (CK)7 and 20, vimentin, estrogen receptor (ER), CD10, and renal cell carcinoma (RCC) marker. Ovarian clear cell carcinomas (n=14) were positive with CK7 (14/14), vimentin (6/14), ER (2/14), and RCC marker (2/14). All were negative with CD10 and CK20. Renal clear cell carcinomas (n=14) were positive with CD10 (14/14), RCC marker (14/14), vimentin (7/14), CK7 (2/14), and CK20 (1/14). All were negative with ER. This panel allows clear cell carcinomas of the ovary and kidney to be distinguished with a high degree of certainty and is a useful adjunct to histologic examination. Primary ovarian clear cell carcinomas are characterized by CK7 positivity, whereas primary renal neoplasms are characterized by positivity for CD10 and RCC marker and negative staining with CK7.

Topics: Antibodies; Biomarkers, Tumor; Carcinoma, Renal Cell; Coloring Agents; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Neprilysin; Ovarian Neoplasms; Receptors, Estrogen; Vimentin

Topics: Adenocarcinoma, Clear Cell; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Humans; Keratins; Kidney Neoplasms

Several investigations indicate the prognostic value of disseminated cytokeratin positive tumor cells in bone marrow of patients with carcinoma of different origin. In this study we evaluated the prognostic significance of epithelial cells in bone marrow of patients with renal cell carcinoma (RCC).. Aspiration of bone marrow was performed preoperatively in 335 patients with RCC between 1990 and 1998. A total of 287 patients fulfilled all study inclusion (eg M0 R0 tumor stage) and exclusion (eg second malignancy during followup) criteria for the final analysis. Cytospin preparations were made after density gradient centrifugation of bone marrow samples and incubated with monoclonal antibodies directed against cytokeratin 18 (CK2) and pan-cytokeratin. Staining was performed using the alkaline phosphatase-anti-alkaline phosphatase method and 256 samples were evaluated. RESULTS In 25% (63 of 256) of the patients cytokeratin positive (CK+) cells were detected in bone marrow. Tumor progression (defined as tumor associated death, local recurrence or new metastases) was present in 12% (31 of 256) during the followup period (median 40 months), and 14% (9 of 63) with CK+ cells and 11% (22 of 193) with negative bone marrow status exhibited tumor progression. Survival analysis (log-rank test) showed no significant difference between the CK+ and cytokeratin negative group. The detection of CK+ cells was not an independent prognostic parameter in multivariate analysis (Cox regression model).. These results indicate that the immunocytochemical detection of disseminated cytokeratin positive tumor cells in the bone marrow of patients with RCC has no prognostic significance.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Needle; Bone Marrow; Bone Marrow Neoplasms; Carcinoma, Renal Cell; Cell Count; Disease Progression; Epithelial Cells; Female; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Male; Middle Aged; Neoplasm Staging; Regression Analysis; Survival Analysis

Chromophobe renal cell carcinomas and renal oncocytomas share morphologic similarities and may present a diagnostic challenge on routine hematoxylin-eosin staining. Currently recommended additional studies of Hale's colloidal iron staining and electron microscopy are often difficult to interpret and technically challenging and may not be readily available. Previous studies have reported conflicting results with regard to the cytokeratin 7 staining pattern in chromophobe renal cell carcinomas and renal oncocytomas. Cytokeratin 20 expression in chromophobe renal cell carcinomas has not previously been studied. Formalin-fixed paraffin-embedded tissue of 11 chromophobe renal cell carcinomas and 21 renal oncocytomas were retrieved from the archived files (1984-2000) of four teaching hospitals. Of the 11 chromophobe renal cell carcinomas, eight stained positive (73%) for cytokeratin 7, one stained focally positive (9%), and two cases (18%) were completely negative. Cytokeratin 7 staining of the 21 oncocytomas revealed 4 positive (19%), 7 focally positive (33%), and 10 negative cases (48%). Cytokeratin 20 was uniformly negative on all 11 cases of chromophobe renal cell carcinomas and all 21 cases of oncocytomas. Cytokeratin 7 does not appear to show the consistent immunoreactivity in chromophobe renal cell carcinomas and renal oncocytomas, as has been previously suggested. Cytokeratin 20 immunostaining in chromophobe renal cell carcinomas and renal oncocytomas is uniformly negative. Despite the technical and interpretive challenges of Hale's colloidal iron, it is still the most useful stain in differentiating chromophobe renal cell carcinomas from renal oncocytomas.

Topics: Adenoma, Oxyphilic; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms

Our aim is to identify as many candidates as possible for tumor-associated T-cell epitopes in individual patients. First, we performed expression profiling of tumor and normal tissue to identify genes exclusively expressed or overexpressed in the tumor sample. Then, using mass spectrometry, we characterized up to 77 different MHC ligands from the same tumor sample. Several of the MHC ligands were derived from overexpressed gene products, one was derived from a proto-oncogene, and another was derived from a frameshift mutation. At least one was identified as an actual T-cell epitope. Thus, we could show that by combining these two analytic tools, it is possible to propose several candidates for peptide-based immunotherapy. We envision the use of this novel integrated functional genomics approach for the design of antitumor vaccines tailored to suit the needs of each patient.

Topics: Antigens, Neoplasm; Cancer Vaccines; Carcinoma, Renal Cell; CD8-Positive T-Lymphocytes; Epitopes, T-Lymphocyte; Frameshift Mutation; Gene Expression Profiling; HLA-A Antigens; HLA-B Antigens; Humans; Keratins; Kidney Neoplasms; Membrane Proteins; Oligonucleotide Array Sequence Analysis; Peptides; Perilipin-2; Proto-Oncogene Mas

The suitability of proteome-based strategies for the targeting of tumor-associated markers along with further analysis regarding their clinical significance were investigated in human renal cell carcinoma (RCC). The immunogenic protein expression profile of normal kidney and RCC cell lines was studied by proteome analysis combined with immunoblotting using sera from healthy donors and RCC patients, also termed PROTEOMEX. Employing this approach, a series of proteins reactive with either RCC patient sera and/or reactive with control sera were identified by microanalysis of tryptic peptides. Some of these candidate antigens represent members of the cytoskeletal family, such as cytokeratins, in particular cytokeratin 8, cytoskeletal tropomyosin, F-actin capping protein, gamma-actin, stathmin, tubulin-alpha, tubulin-beta and vimentin. The expression pattern and clinical significance of three of these antigens, namely cytokeratin 8, stathmin and vimentin, were further analyzed in a large series of surgically removed RCC lesions of distinct subtypes. A heterogeneous expression pattern of cytokeratin 8, stathmin and vimentin was demonstrated in the different RCC subtypes. All epithelial cells of the autologous normal kidney showed a strong cytokeratin 8 staining pattern, whereas they totally lack vimentin expression. Stathmin was expressed in 10% of tubule cells. In conclusion, PROTEOMEX could be employed for the identification of tumor-associated antigens of the cytoskeleton which are differentially expressed in RCC of distinct subtypes as well as in normal renal epithelium.

Topics: Antigens, Neoplasm; Carcinoma, Renal Cell; Cell Line; Electrophoresis, Gel, Two-Dimensional; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Microtubule Proteins; Phosphoproteins; Stathmin; Vimentin

To distinguish common epithelial tumors arising in the kidney may have significant implications, in terms of molecular ontogeny and prognosis. It is important to investigate the distribution of immunoexpression of commonly used markers among renal neoplasms and to develop a useful panel as an adjunct to histologic examination, which could lead to the accurate diagnosis of both primary and metastatic tumors. Immunohistochemical stains for CD10, vimentin (VIM), E-cadherin (E-CD), cytokeratins (CK) 7, 8, 19, and 20, high molecular weight keratin (HCK), and peanut lectin agglutinin (PL) (Arachis hypogaea) were performed on 45 (96 for CK7, CK20) conventional (CC), 20 papillary (PC), and 6 (24 for CK7, CK20) chromophobe renal carcinomas (CPC); 12 oncocytomas (OC); 5 collecting duct carcinomas (CDC), and 25 urothelial carcinomas of the renal pelvis (UC). Reactivity for CD10 was evaluated on the basis of the presence of cell surface staining; that for all CKs, cytoplasmic/membranous staining; and that for PL, luminal staining. Both CD10 and VIM were predominantly expressed in CC and PC; E-CD in CPC, OC, and UC; CK7 in PC, CPC, and UC; CK8 and CK19 in CDC and UC; CK20 in UC; HCK in CDC and UC; and PL in CDC. CC and OC were predominantly CK7-/CK20-; PC, CK7+/20-; CPC, CK7+/CK20- or CK7-/CK20-; and UC, CK7+/CK20- or CK7+/CK20+. CDC showed slight predominance of CK7-/20- over CK7+/CK20-. CC was most frequently CD10+/CK7-/HCK-/PL-; PC, CD10+/CK7+/HCK-/PL-; CPC, CD10-/CK7+/HCK-/PL-; OC, CD10-/CK7-/HCK-/ PL-; CDC, CD10-/CK7+/HCK-/PL+ or CD10-/CK7-/ HCK+/PL+; and UC, CD10-/CK7+/HCK+/PL-. Discriminant analysis suggested that CD10/CK7/HCK/PL may be a useful primary immunopanel for distinguishing among CC, PC, CDC, and UC.

Topics: Adenoma, Oxyphilic; Biomarkers, Tumor; Cadherins; Carcinoma, Papillary; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Neprilysin; Peanut Agglutinin; Prognosis; Vimentin

We report a case of chromophobe cell carcinoma in a 41-year-old woman who was admitted to our hospital because of right upper abdominal pain. We performed right radical nephrectomy under the diagnosis of renal cell carcinoma. The cut surface appearance of the tumor was homogeneous, grey beige and solid. This tumor was diagnosed as chromophobe cell renal carcinoma after microscopic and immunohistochemical studies. We report our case with reference to the relevant literature.

Topics: Adult; Carcinoma, Renal Cell; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Nephrectomy

The histopathological diagnosis of chromophobe renal cell carcinoma can present a diagnostic challenge, as these tumours can resemble either conventional renal cell carcinoma or oncocytoma. The aim of this study was to determine whether cytokeratin 7 expression is of practical use in the distinction of these three entities.. A total of 40 cases previously diagnosed as either chromophobe renal cell carcinoma, conventional renal cell carcinoma or oncocytoma were identified. A representative section of each was stained with H&E and cytokeratin 7. Following independent review of the cases by three pathologists, a consensus diagnosis for each case was reached and the pattern of cytokeratin 7 staining was assessed. There were 12 cases of chromophobe renal cell carcinoma in the study, all of which showed a characteristic peripheral membrane pattern of staining for cytokeratin 7. Seventeen of the 18 cases of conventional renal cell carcinoma studied were negative for cytokeratin 7, while one case showed weak focal staining of <5% of the cells. The 10 cases of oncocytoma showed patchy weak to moderate cytoplasmic expression of cytokeratin 7, without the characteristic peripheral membrane accentuation seen in the chromophobe carcinomas.. Immunohistochemical staining for cytokeratin 7 appears to be a useful adjunct in the diagnosis of chromophobe renal cell carcinoma, and in distinguishing this tumour from both oncocytoma and conventional renal cell carcinoma.

Topics: Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney Neoplasms

Renal clear cell carcinoma rarely metastasizes to the ovary potentially mimicking a primary ovarian clear cell carcinoma. The immunocytochemical profiles of the two tumors were compared. Control groups of ovarian endometrioid and serous adenocarcinomas were also examined using the same antibody panel. Paraffin sections were studied with the immunocytochemical technique using eight antibodies. Renal clear cell carcinomas were positive for vimentin (8/12 cases), CK5/6 (0/12), 34 beta E12 (1/12), Ber-Ep4 (5/12), CA125 (0/12), ER (1/12), and PGR (1/12). Ovarian clear cell carcinomas showed positivity with vimentin (1/10 cases), CK5/6 (2/10), 34 beta E12 (10/10), Ber-Ep4 (10/10), CA125 (8/10), ER (7/10), and PGR (6/10). Endometrioid adenocarcinomas were positive for vimentin (9/10 cases), CK5/6 (8/10), 34 beta E12 (10/10), Ber-Ep4 (9/10), CA125 (9/10), ER (9/10), and PGR (10/10). Eight serous adenocarcinomas were positive in all cases for all the antibodies except CK5/6 (7/8 cases) and 34 beta E12 (7/8 cases). All the tumors reacted for epithelial membrane antigen. This immunohistochemical panel allows clear cell carcinomas of kidney and ovary to be distinguished. The latter has a greater phenotypic similarity with serous and endometrioid adenocarcinomas than with renal clear cell carcinoma demonstrating yet again that these ovarian tumors share a common histogenetic origin.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Aged, 80 and over; Antigens, Surface; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Middle Aged; Mucin-1; Ovarian Neoplasms; Receptors, Estrogen; Receptors, Progesterone; Vimentin

Whereas papillary renal cell carcinoma is now established as a subtype of renal cell neoplasia, division of these tumors into 2 distinctive morphotypes has been proposed. Type 1 tumors have cells with scanty pale cytoplasm arranged in a single layer on the basement membrane of papillary cores. In these tumors, psammoma bodies and foamy macrophages are frequently seen, and the tumors frequently express cytokeratin 7. Type 2 tumor cells have pseudostratified nuclei and usually have voluminous eosinophilic cytoplasm. Recent studies have supported this subclassification of papillary renal cell carcinoma by demonstrating differing genotypes for type 1 and 2 tumors. To further study the subclassification of papillary renal carcinoma, we compared clinical features, nuclear grade, stage, tumor growth kinetics, and survival in a series of 50 type 1 and 16 type 2 papillary renal cell carcinomas. Comparison of patient age at presentation, sex, and primary tumor size shows no significant difference between the 2 tumor types. Type 1 tumors were of significantly lower Fuhrman grade (P =.0001) and higher Robson stage (P =.009) than type 2 tumors. There was no significant difference when tumors were staged according to the TNM classification. Assessment of tumor growth kinetics showed significantly different mean silver-staining nucleolar organizer region (AgNOR) scores and Ki-67 indices (AgNOR type 1, 3.83, type 2, 7.24, P =.0001; Ki-67 type 1, 3.17%, type 2, 6.01%, P =.0002). Multivariate analysis showed tumor type (P =.03), presence of metastases (P =.04), AgNOR score (P =.001), and Ki-67 index (P =.03) to be independently associated with survival. These results provide evidence of the clinical utility of dividing papillary renal cell carcinomas into 2 types according to histologic characteristics.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Papillary; Carcinoma, Renal Cell; Cell Division; Cell Nucleus; Cytoplasm; Female; Humans; Keratin-7; Keratins; Ki-67 Antigen; Kidney Neoplasms; Kinetics; Macrophages; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Nucleolus Organizer Region; Silver Staining; Survival Rate

This case report describes a 75 year old man who had a renal papillary carcinoma associated with a low grade tumour of the collecting ducts. These tumours showed different immunohistochemical patterns for epithelial membrane antigen, cytokeratin 19, and Ulex europaeus lectin expression. In addition, cytogenetic findings were 47, XY, +7 <7> and 45, XY, -8, add(12)(q-ter)<10> for the papillary renal carcinoma and the low grade tumour of the collecting ducts, respectively. This is the first report where these two types of tumour are associated and cytogenetically distinguished.

Topics: Aged; Biomarkers; Carcinoma, Papillary; Carcinoma, Renal Cell; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, Pair 12; Diagnosis, Differential; Humans; Immunohistochemistry; Karyotyping; Keratin-7; Keratins; Kidney Neoplasms; Kidney Tubules, Collecting; Lectins; Male; Mucin-1; Neoplasms, Multiple Primary; Plant Lectins

Clear cell (CRCC), papillary (PRCC) and chromophobe (CHRC) renal cell carcinoma (RCC) are the three most frequent subtypes of RCC. The rate and distribution of their metastatic lesions have not been well documented. We compared metastatic RCC according to subtype and primary tumor characteristics to better understand their behavior and to aid in the diagnosis of metastatic RCC. Pathology reports and clinical charts related to 283 CRCC, 48 PRCC and 13 CHRCC, including their respective sarcomatoid variants, were reviewed. A hundred and thirty-seven CRCC, 5 PRCC and 1 CHRCC with metastases were identified. CRCC and non-CRCC (PRCC and CHRCC) had different patterns of metastasis and primary tumor growth. CRCC metastases were predominantly distributed in lungs, bone, brain, lymph nodes, and adrenal glands. The associated primary CRCC measured 1.5 to 15 cm, were of all grades and stages, and were often associated with invasion of small or large veins. Three PRCC had regional lymph node metastases, 1 PRCC had both regional and mediastinal lymph node metastases. Bone metastasis was present in 1 case each of PRCC and CHRCC. One PRCC with metastasis solely to regional nodes measured 4 cm. The other 4 cases of PRCC with regional lymph node and/or distant metastases as well as the CHRCC with distant metastases were greater than 8 cm in diameter. In metastasizing and non-metastasizing non-CRCC, invasion of small veins was rare and invasion of renal veins was not seen. We cannot comment with any certainty on the metastatic behavior of CHRCC. In our experience, PRCC tend to loco-regional invasion with lymph node spread. They have a low potential for vascular invasion and distant metastases that likely occur only at late stages of the disease. CRCC has a propensity for vascular invasion and may be associated with distant metastasis at an early stage. Therefore, metastatic RCC at a distant location are most likely to be of CRCC origin than PRCC origin.

Topics: Adrenal Gland Neoplasms; Aged; Bone Neoplasms; Brain Neoplasms; Carcinoma, Renal Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Survival Rate; Vimentin

The cytokeratin 14 (CK14) expression in oncocytomas or oncocytic tumours of various tissue origins has not been established. We have studied CK14 expression in 30 cases of oncocytic tumours of various tissue origins and 33 cases of renal cell carcinoma with overlapping features (mimics) by immunohistochemistry.. Immunohistochemistry (ABC-HRP method) was performed for detection of CK14 in 30 cases of oncocytic tumour and 33 cases of renal mimics. To demonstrate CK14 specificity and sensitivity in oncocytic tumours, mES-13 (an anti-mitochondrial monoclonal antibody) immunohistochemistry was also performed in 20 of 30 cases on oncocytic tumour and all 33 cases of renal mimics. We found that all 30 cases of oncocytic tumour showed cytoplasmic CK14 positivity. All 20 cases of oncocytic tumour studied with mES-13 were positive. CK14 immunoreactivity was identified in only four cases of renal cell carcinoma (one conventional renal cell carcinoma with granular cytoplasm and three chromophobe renal cell carcinomas with eosinophilic cytoplasm). In contrast, all 33 cases of renal cell carcinoma were positive for mES-13 to varying degrees.. The homogeneous, cytoplasmic, and granular CK14 immunoreactivity is sensitive and specific for oncocytic tumours, whereas CK14 immunoreactivity in renal mimics is light and sporadic with peripheral accentuation.

Topics: Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-14; Keratins; Male; Middle Aged; Mitochondria

The reliability of using fine-needle aspiration (FNA) to distinguish renal oncocytoma (RO), a benign tumor, from renal cell carcinoma (RCC), which has eosinophilic granular cytoplasm, has been questionable. However, it is clinically significant, because radical nephrectomy may be avoided in patients with RO. The authors retrospectively studied the cytologic features and ancillary study findings of RO compared with findings in RCCs with eosinophilic granular cytoplasm to evaluate the reliability of FNA-based diagnosis of RO.. The authors reviewed 19 tumors, including 11 ROs, three chromophobe RCCs (CRCCs), three granular variant RCCs (GRCCs), and two eosinophilic variant papillary RCCs (EPRCCs). Smears and cell blocks were prepared using either computed tomography-guided or ultrasound-guided FNA material. Surgical specimens were available for all tumors. Cytokeratin, vimentin, and Hale colloidal iron (HCI) stains were performed on all 19 tumors. Electron microscopy (EM) was available for six tumors.. Although most tumors demonstrated their classic cytologic features, the specific diagnosis using conventional smears or even core biopsies was difficult in some tumors, especially ROs, due to the overlapping cytomorphology among these tumors. Cytologic material was obtained from 10 of 11 RO specimens. Of 10 ROs, 8 original FNA-based diagnoses were oncocytic neoplasm. Immunoperoxidase studies revealed that all tumors of each type were positive for cytokeratin, whereas only GRCCs and EPRCCs were positive for vimentin. The two vimentin negative neoplasms, RO and CRCC, could be distinguished by HCI stain, which showed diffuse or focal cytoplasmic positivity in CRCCs and apical/perinuclear staining (73%) or negative staining (27%) in ROs. Ultrastructurally, cytoplasm densely packed with mitochondria was characteristic for oncocytoma.. This study demonstrated that ROs can be distinguished reliably from RCCs on the basis of cytologic morphology combined with ancillary studies, including immunostaining with cytokeratin and vimentin antibodies and HCI stain. EM provides additional information to confirm the diagnoses.

Topics: Adenoma, Oxyphilic; Aged; Antibodies; Biopsy, Needle; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Keratins; Kidney Neoplasms; Male; Microscopy, Electron; Middle Aged; Retrospective Studies; Vimentin

Hemangioblastomas are intracranial and intraspinal tumors arising sporadically or in patients with von Hippel-Lindau disease. To date, hemangioblastomas have not been described in the skin. Proliferating clear cells with a variable vascular component are found histologically. These clear cells stain for neuron-specific enolase but not cytokeratin or epithelial membrane antigen, allowing them to be differentiated from metastatic renal cell carcinoma.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carcinoma, Renal Cell; Diagnosis, Differential; Hemangioblastoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Nose Neoplasms; Phosphopyruvate Hydratase; Skin Neoplasms

Here we report tumor-to-tumor metastases identified in two patients with von Hippel-Lindau (VHL) disease. The first patient had bilateral renal carcinomas and multiple cerebellar hemangioblastomas, and the second patient had a renal carcinoma and multiple hemangioblastomas in the retina, cerebellum and spinal cord. A cerebellar lesion from the first patient and a spinal lesion from the second patient contained two distinct components. The inner part of these tumors consisted of a nested mass of polygonal clear cells that expressed cytokeratin and epithelial membrane antigen, while the outer part of the tumors showed proliferation of capillaries and intervening foamy stromal cells that were negative for cytokeratin and epithelial membrane antigen. The tumors were thus considered to be hemangioblastomas complicated by metastatic lesions of renal cell carcinoma of clear cell type. These cases indicate that tumor-to-tumor metastasis should be considered when hemangioblastoma contains a clear cell carcinoma component in the setting of VHL disease, and that immunohistochemical staining for cytokeratin and epithelial membrane antigen is useful for the diagnosis.

Topics: Biomarkers, Tumor; Brain Neoplasms; Carcinoma, Renal Cell; Female; Hemangioblastoma; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Middle Aged; Mucin-1; Neoplasms, Second Primary; Stromal Cells; von Hippel-Lindau Disease

Hale's colloidal iron staining of 8 chromophobe cell carcinomas (CCC) was compared with that of non-chromophobe renal cell carcinomas (RCC), renal oncocytomas, and renal adenomas. Six non-chromophobe RCC showing diffuse and moderate cytoplasmic staining contained extensive areas with translucent cytoplasm as observed in CCC. Seventeen of 25 conventional RCC of the clear cell variant (randomly chosen from 130 cases), 21 of 26 RCC with areas of chromophilic cytoplasm, and 16 of 20 papillary RCC, 7 of 14 adenomas and 14 of 16 oncocytomas displayed focal areas with mild to moderate staining of the cytoplasm. Hale's colloidal iron staining was partially reduced by digestion with neuramidase but not with hyaluronidase. This positive staining demonstrated glycoproteins containing sialylated glycoconjugates, probably a type of acid epithelial mucin. We suggest that there is a spectrum of mucin-like changes in typical CCC representing RCC with extensive and marked "mucin-like changes". The eosinophilic variant of CCC and some RCC with extensive chromophobe cell features represent renal neoplasms with moderate changes. The other RCC, oncocytomas and papillary renal neoplasms with mild to moderate staining with Hale's colloidal iron represent renal neoplasms with focal mucin-like changes. RCC with extensive chromophobe cell features may pose a differential diagnostic problem with CCC.

Topics: Adenocarcinoma; Adenoma; Adenoma, Oxyphilic; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Iron; Keratins; Kidney Neoplasms; Mucin-1; Neoplasm Proteins; Neuraminidase; Vimentin

The expression of MUC1, MUC2, mucin-associated Thomsen-Friedenreich-related antigens (TF, sialosyl-TF, Tn, and sialosyl-Tn), and cytokeratin 19 (CK19) was systematically investigated in situ in 58 resected human kidney tumours, surrounding tissue of normal appearance, and two normal kidneys obtained at autopsy, using monoclonal antibodies. In kidney tissues of normal appearance, TF, s-TF, MUC1 and CK19 were positive in distal tubules and collecting ducts but negative in proximal tubules. In contrast, MUC2, Tn, and s-Tn were negative throughout the normal renal tubular system. Almost all renal cell carcinomas (RCCs) showed strong immunoreactivity for MUC1, but all were negative for MUC2. Some RCCs expressed TF, Tn, s-Tn, and CK19. In addition, the immunomorphological characteristics of the majority of clear-cell RCCs and clear/granular RCCs with anti-MUC1 and anti-CK 19 closely resembled those of the collecting duct and the distal tubule rather than the proximal tubule. In the renal tissue of otherwise normal appearance adjacent to clear-cell RCCs and clear/granular RCCs, clear cells with excessive storage of glycogen were often found in the collecting duct system, but only rarely in the proximal tubules. These results suggest that the majority of clear-cell RCCs and clear/granular RCCs may originate from the collecting duct system.

Topics: Adenoma, Oxyphilic; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Tubules, Collecting; Kidney Tubules, Distal; Mucin-1; Peptide Fragments

A 60-year-old Japanese male with a chromophobe cell carcinoma of his left kidney is reported. The tumor, 18 x 27 mm in size, was incidentally found by abdominal ultrasonography. Computed tomography and magnetic resonance imaging demonstrated a well-demarcated solid tumor arising from the lower pole of the left kidney. Histopathological examination of the surgically removed tumor revealed that it was composed of solid sheets of cancer cells having abundant and slightly eosinophilic reticular cytoplasm with accentuated cell membranes making up a plant cell-like appearance. Electron microscopic examination demonstrated numerous intracytoplasmic microvesicles. Although the tumor cells were positive for cytokeratin and epithelial membrane antigen, they did not show vimentin immunoreactivity. The unique histological finding of this tumor from other reported renal chromophobe carcinomas was that it had a peripheral fibrotic area with a focus of metaplastic ossification.

Topics: Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Microscopy, Electron; Middle Aged; Ossification, Heterotopic

Patients with metastatic renal and colon carcinoma have a very poor prognosis. In many cases, the tumor recurs after surgical excision and chemotherapy. Therefore, it might be beneficial for cancer patients to induce an immune attack against the tumor by inserting a cytokine gene into the tumor cells. Here, two different techniques for isolation of single tumor cells were compared. An enzymatic solution was superior to an EDTA/DTT isolation solution for establishing tumor primary cultures. In total, 18 primary cell cultures could be established from 68 patients with colon and renal cell carcinoma. Cells were further characterized concerning fibroblast contamination, cell proliferation and HLA-typing. These primary tumor cells might be of value for cytokine gene transfer and in vaccination protocols for cancer patients.

Topics: Adenocarcinoma; Antigens, Neoplasm; Carcinoma, Renal Cell; Cell Culture Techniques; Cell Division; Cell Separation; Clone Cells; Colonic Neoplasms; Cytokines; Electroporation; HLA Antigens; Humans; Keratins; Kidney Neoplasms; Neoplasm Metastasis; Recombinant Fusion Proteins; Transfection; Tumor Cells, Cultured

Genetic, immunohistochemical, and histologic data has led to the reclassification of renal cell carcinoma in the last decade. Recent studies suggest that renal cell carcinomas in children and young adults may represent a distinct group of tumors. These tumors have unique genetic findings (most commonly t(x;1)(p11:q21)), a predominantly papillary architecture, numerous calcifications, granular cytoplasm, and a possible relationship with neuroblastoma.

Topics: Adolescent; Adrenal Gland Neoplasms; Biomarkers; Carcinoma, Renal Cell; Child; Child, Preschool; Chromosome Aberrations; Female; Humans; Karyotyping; Keratins; Kidney Neoplasms; Mucin-1; Neuroblastoma; Vimentin

To undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms.. Thirty-one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Müllerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified.. Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.

Topics: Biomarkers, Tumor; Calbindin 2; Carcinoma; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lung Neoplasms; Mesothelioma; S100 Calcium Binding Protein G; Sarcoma; Thrombomodulin

Tumor-to-tumor metastasis is rare. We report a case of metastatic renal cell carcinoma in meningioma. A 67-year-old woman presented a two-week history of motor dysphagia and decreased short-term memory. She had undergone a left radical nephrectomy for a renal cell carcinoma 7 years ago, and had not received any adjuvant therapy. MRI disclosed a 3.0 x 3.0 x 3.0-cm sized round tentorial-based extraaxial mass with peritumoral edema in the left posterior temporal lobe. During operation, the tumor was found to be an encapsulated mass firmly attached to the tentorium. Histologically, the tumor was a meningotheliomatous meningioma extensively infiltrated by metastatic renal cell carcinoma, accompanying widespread coagulative necrosis. Immunohistochemical staining for cytokeratin revealed strong positivity only in the renal cell carcinoma component. The patient's postoperative course was uneventful. Post-operative radiation therapy was applied to the whole brain. Three months after operation, the patient developed right hemiparesis and dysphagia. Brain MRI at that time did not reveal recurrence or any other causative lesions, although the whole body scan disclosed uptake at the second lumbar vertebra and rib. The patient refused further treatment.

Topics: Aged; Carcinoma, Renal Cell; Female; Humans; Keratins; Kidney Neoplasms; Magnetic Resonance Imaging; Meningeal Neoplasms; Meningioma

The purpose of the present study was to investigate the possible histogenetic relationship of renal cell carcinoma (RCC) and angiomyolipoma (AMYL) occurring in the same renal nodule by examining two cases of composite RCC and AMYL in patients without stigmata of tuberous sclerosis and by reviewing the medical literature of similar cases. Case 1 represents an epithelioid variant of AMYL with multiple additional nodules of typical AMYL in a surgically removed kidney. The patient subsequently developed a lesion consisting of a mixture of epithelioid variant of AMYL and RCC 24 months later in the retroperitoneum and, an additional 4 months later, in the liver. The RCC cells resembled mononucleated epithelioid cells of the epithelioid AMYL except that they were focally reactive with epithelial membrane antigen (EMA) in the retroperitoneum and focally reactive with both EMA and cytokeratin (CK) in the liver. Case 2 consisted of a typical AMYL admixed with a chromophil cell RCC. A review of the medical literature revealed seven additional cases with histopathological findings similar to this case. All cases had multiple foci of typical AMYL. Immunostaining results are available in five tumors. Chromophil RCC showed variable reactivity with CK and EMA. In addition, RCC in the two cases in the present study also displayed a positive reaction with mucin staining and a positive reactivity with carcinoembryonic antigen. There appears to be a spectrum of histopathological and immunohistochemical changes from the epithelioid variant of AMYL through a mixed epithelioid AMYL/RCC to chromophil RCC in three successive specimens in case 1. Moreover, the intimate admixture of AMYL and RCC and the similar expression of epithelial markers of RCC in the two cases in the present study, as well as other cases in the literature, suggest that some RCC develop from the same precursor cell as AMYL or from a component of AMYL.

Topics: Adult; Angiomyolipoma; Carcinoembryonic Antigen; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Liver; Male; Middle Aged; Mucin-1

Although rare, renal cell carcinoma (RCC) can metastasize to the bladder. When this occurs, it might complicate diagnosis. Morphologically, RCC can be confused with transitional cell carcinomas (TCCs), especially those exhibiting clear cell features, and also with other bladder tumors, such as paragangliomas and metastatic melanomas. We report seven cases of RCC metastatic to the bladder that occurred in 6 men and 1 woman who were 35 to 69 years old. The most common presenting symptom was the reappearance of hematuria, which developed from 2 to 131 months (mean, 41.3 mo) after the removal of the primary RCC. In all of the patients, the metastatic RCC involved multiple organs; no case had an isolated metastasis to the bladder. The prognosis was poor, and five patients died of disease between 4 and 24 months (mean, 12.8 mo) after diagnosis of the metastasis to the bladder. The remaining two patients were lost to follow-up. All of the tumors were conventional clear or "granular" cell RCCs, with nuclear grades of 2 or 3. In five patients, metastases were confined to the lamina propria, but in two patients, tumors involved the muscularis propria as well. A comparative immunohistochemical study showed that metastatic RCCs were positive for CAM5.2, vimentin, and Leu-M1, and negative for cytokeratin 20, cytokeratin 7, 34betaE12, carcinoembryonic antigen, S-100 protein, HMB45, and chromogranin. Classic and clear cell TCCs were positive for all of the cytokeratins and carcinoembryonic antigen and negative for vimentin. Paragangliomas were positive for chromogranin and showed scattered positivity for the S-100 protein in the sustentacular cells. Metastatic melanomas were positive for S-100 protein and HMB45. The histologic appearance of RCC, particularly the delicate fibrovascular stroma with abundant sinusoidal vessels, is a feature that can be used to recognize the tumor. When there is difficulty diagnosing metastatic RCC, TCC, or other tumors in the bladder, the immunohistochemical findings can assist in the differential diagnosis.

Topics: Adult; Aged; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Chromogranins; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Lewis X Antigen; Male; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Paraganglioma; S100 Proteins; Urinary Bladder Neoplasms; Vimentin

Detection of circulating cancer cells in peripheral blood may improve cancer staging and monitoring. This study was undertaken to investigate the clinical implications of detection of circulating cancer cells in renal cancer patients. Cytokeratin-19 (CK19) mRNA was amplified by nested reverse transcription-polymerase chain reaction (RT-PCR) in the peripheral blood of 33 healthy volunteers and 19 patients with renal cell carcinoma. The detection limit of the method was 10 cancer cells in 10(7) peripheral blood mononuclear cells. The positive detection rate was 47% for renal cancer patients and 9% for healthy volunteers. The number of patients expressing CK19 mRNA in each clinical stage was 0 out of 3 patients in stage 1; 2 out of 8 (25%) in stage 2; 3 out of 4 (75%) in stage 3; 4 out 4 (100%) in stage 4. A significant correlation was seen between CK19 mRNA expression and clinical stage (p = 0.0023). This method may be useful for early detection of micrometastasis, and facilitate the design of better therapeutic strategies for the treatment of renal cancer patients.

Topics: Adult; Aged; Carcinoma, Renal Cell; Female; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged; Neoplastic Cells, Circulating; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Clear cell adenocarcinoma of salivary glands (CCASG) is a relatively rare tumor, composed entirely of clear cells of putative ductal origin. It bears striking morphologic similarities to renal cell carcinoma (RCC) of clear cell type on hematoxylin and eosin stains. Differentiation between CCASG and metastatic RCC to the salivary glands has been considered problematic or even impossible on morphologic grounds. We examined three cases of CCASG and 12 cases of RCC (6 primary and 6 metastatic) by hematoxylin and eosin staining, immunohistochemistry, and electron microscopy. Two distinctive immunohistochemical and ultrastructural patterns emerged from this analysis. CCASG showed positivity for high molecular weight cytokeratin and carcinoembryonic antigen and ultrastructurally showed prominent squamoid differentiation, glycogen pools, and absence of lipid. In contrast, RCC was characterized by positivity for vimentin and complete absence of staining for high molecular weight cytokeratin and carcinoembryonic antigen. On ultrastructural studies, RCC lacked any squamoid differentiation, and the tumor cells contained abundant cytoplasmic lipid in addition to glycogen. Thus, based on the consistent differences on the immunohistochemical staining patterns and their characteristic subcellular morphology, CCASG and RCC can be distinguished on pathologic evaluation. The different direction of differentiation of the cells in CCASG and RCC (i.e., ductal in the former and renal tubular and mesodermal in the latter) results in their distinctive immunophenotypical and ultrastructural features.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Carcinoembryonic Antigen; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Glycogen; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Lipids; Male; Middle Aged; Salivary Gland Neoplasms; Vimentin

The differentiation of epithelial tumors arising in the kidney (urothelial vs. renal cell carcinoma) sometimes can be difficult by clinical and radiologic studies. Because urothelial and renal epithelium express unique cytokeratin (CK) 7 and 20 profiles, the authors studied the utility of these markers to confirm the diagnosis of urothelial carcinomas that present clinically as kidney masses.. Using commercially available monoclonal antibodies, paraffin section immunohistochemistry was used to examine two recent cases of urothelial carcinomas presenting as renal tumors. Tissues were stained for CK7 and CK20 and the expression compared between the tumor and benign tissue.. Both cases showed solid renal masses that clinically and radiographically could have been of renal cell origin, but subsequently were confirmed histologically to be extensive renal involvement by urothelial carcinoma. The tumors coexpressed both CK7 and CK20, which is the expected profile for carcinomas of urothelial but not renal origin.. The results of the current study show that coexpression of CK7 and CK20 is a useful diagnostic aid in the differential diagnosis of epithelial kidney tumors of urothelial cell versus renal cell origin.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Middle Aged

Renal cell carcinoma (RCC) arising in acquired cystic kidney disease (ACKD) is considered to be a tumor of low malignant potential, compared with classic RCC. The aim of the present study was to identify any significant differences in the antigenic profiles or tumor cell proliferative activity of ACKD-associated RCC and classic RCC that might be responsible for differences in their biologic behavior. We studied the immunohistochemical profiles and proliferative activity of 12 classic RCCs and 5 ACKD-associated RCCs with markers of proximal tubules (Leu M1, alpha-1 antitrypsin, CAM 5.2), markers of distal tubules (Arachis hypogaea lectin, AE1/AE3, epithelial membrane antigen [EMAJ, CAM 5.2), vimentin, and proliferating cell nuclear antigen (PCNA). We performed proliferation analysis with the CAS 200 image analysis system. For each case, 8 to 20 fields of tumor tissue in the areas of maximal PCNA staining were quantitated, and the percentage of PCNA-positive nuclear area for each individual tumor was calculated. All of the five ACKD-associated RCCs expressed AE1/AE3, EMA, and CAM 5.2 in more than 50% of the tumor cells. Arachis hypogaea lectin was significantly expressed in three of the five ACKD-associated RCCs. Leu M1 and alpha-1 antitrypsin reacted with fewer than 10% of the tumor cells in all of the five ACKD-associated RCCs. In contrast, the 12 classic RCCs showed expression of CAM 5.2 in 11 cases, alpha-1 antitrypsin in 10 cases, Leu M1 in 9, EMA in 8, and AE1/AE3 in 3 cases in more than 50% of the tumor cells and a totally negative reaction with Arachis hypogaea lectin in 8 cases, EMA in 4, AE1/AE3 in 4, and vimentin in 5 cases. Although coexpression of proximal and distal tubule markers was seen in some cases of RCC in either category, there was uniform and strong staining for distal tubule markers in ACKD-associated RCC and for proximal tubule markers in classic RCC. The mean percentage of PCNA-positive nuclear area for the ACKD-associated RCCs (2.41%) was significantly (P < .05) less than that of the classic RCCs (21.42%). The differences in expression of proximal and distal tubule markers and proliferative activity might be responsible for the differences in the biologic behavior of ACKD-associated RCC and classic RCC.

Topics: Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Analysis of Variance; Biomarkers, Tumor; Carcinoma, Renal Cell; Cell Nucleus; Cell Transformation, Neoplastic; Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Kidney Diseases, Cystic; Kidney Neoplasms; Kidney Tubules; Lewis X Antigen; Male; Middle Aged; Mucin-1; Peanut Agglutinin; Proliferating Cell Nuclear Antigen; Vimentin

Eleven cases of sarcomatoid renal cell carcinoma were studied to determine the relative frequency of various subtypes of renal cell carcinoma that may be associated with sarcomatoid transformation. The epithelial components in these tumors were subcategorized according to established histologic criteria into chromophobe carcinoma (n = 6 cases), clear cell carcinoma (n = 3), papillary carcinoma (n = 1), and indeterminate (n = 1). In nine cases, material was available for immunohistochemical and DNA ploidy studies. The sarcomatoid component in all cases showed positivity for epithelial membrane antigen cytokeratin, indicating an epithelial derivation of these cells. Staining for mesenchymal markers was mostly negative, except for vimentin, which reacted strongly in all cases. DNA ploidy studies using flow cytometry and cell image analysis provided very similar results. Five of five chromophobe sarcomatoid carcinomas showed hypodiploid cell lines in the epithelial areas, whereas the sarcomatoid components mostly showed aneuploid peaks. In the remaining cases, DNA ploidy pattern was more variable. These findings indicate that chromophobe carcinoma may be the most frequent epithelial component associated with sarcomatoid renal cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; DNA; Female; Flow Cytometry; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged; Mucin-1; Ploidies; Retrospective Studies; Sarcoma; Vimentin

Papillary renal cell carcinomas (RCCs) traditionally have been defined histologically as tumors with at least 50% true papillae. However, these tumors also have characteristic immunohistochemical and genetic features that separate them from other RCCs. We identified six tumors composed of solid sheets of cells without true papillae but that otherwise resembled papillary RCCs, which we feel represent solid variants of papillary RCCs. All six tumors were primary lesions of the kidney, all were strongly reactive for epithelial membrane antigen, cytokeratin 7, and callus keratin, and all were negative for the high molecular weight keratin antibody 34BE12. Four of four tumors tested showed trisomies for chromosome 7, chromosome 17, or both by either cytogenetic analysis or fluorescence in situ hybridization. Four cases were composed of solid sheets of cells containing distinct micronodules that in some cases resembled abortive papillae. The cells composing the micronodules had abundant eosinophilic cytoplasm, open chromatin, and in some cases prominent nucleoli. The intervening cells had similar nuclei, but the amount of cytoplasm was variable. In three of these micronodular cases, multiple tumors diffusely replaced the kidney; in the fourth case two typical clear cell RCCs and a typical papillary RCC were also present in the same kidney, but the micronodular tumor was unifocal. The two remaining cases were solitary tumors consisting of solid sheets of cells forming ill-defined tubules. These cells had scant clear cytoplasm and small round to elongate nuclei with occasional nuclear grooves but only rare small nucleoli. Limited follow-up has shown no evidence of disease in any patient thus far. The differential diagnosis includes "renal adenoma," renal adenomatosis, metanephric adenoma, and clear/granular cell RCC. We conclude that solid variants of papillary RCCs lack true papillae but have characteristic histologic, immunohistochemical, and genetic features.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; Chromosomes, Human, Pair 17; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Kidney Neoplasms; Male; Middle Aged; Mucin-1

We describe an unusual case of a basaloid squamous-cell carcinoma (BSCC) of the tonsil in a 56-yr-old man that metastasized to a primary renal-cell carcinoma (RCC) and the lung. The diagnosis of the second primary, the RCC, was based on fine-needle aspiration (FNA) cytology. A subsequent nephrectomy specimen revealed BSCC metastatic to RCC, clear-cell type. Retrospective analysis of the FNA of the renal mass revealed classic RCC morphology and, in addition, another cytologically distinctive pattern characterized by occasional sheets of cohesive neoplastic cells with hyperchromatic nuclei and nuclear molding representative of BSCC. The cytologic features of a subsequent FNA of the lung were characteristic of metastatic BSCC. Our retrospective analysis of cytologic material from the renal mass underscores the importance of raising the possibility of tumor-to-tumor metastasis when distinctly different morphologic features are seen in an otherwise typical cytology of a neoplasm in patients with an already known or suspected second primary. To our knowledge, this case report is the first one documenting metastasis of BSCC to RCC.

Topics: Biopsy, Needle; Carcinoma, Basosquamous; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Second Primary; Tonsillar Neoplasms

Cytokine-supported ex vivo expansion of peripheral blood progenitor cells (PBPCs) offers new perspectives for autografting after high-dose chemotherapy. One of the potential advantages is the possibility to reduce the volume of blood processed from the patient, thus allowing reduction of the overall tumor cell number in the final autograft. However, ex vivo expansion will only be advantageous if contaminating tumor cells are not expanded concomitantly. This question has not previously been addressed. Therefore, we analyzed unseparated PBPC preparations, CD34(+)-selected cell fractions, and ex vivo-expanded cell preparations from stage IV (n = 16) and high-risk stage II/III (n = 8) breast cancer patients for the presence of human epithelial antigen- (HEA) or cytokeratin (CK)-positive tumor cells. We found that three of 16 (18.8%) of the unseparated PBPC products from stage IV patients were HEA- and/or CK-positive, whereas none of the stage II/III patients were found to be positive after two cycles of induction chemotherapy with etoposide (VP16), ifosfamide, cisplatin, and epirubicin (VIP-E). After CD34+ cell selection (Ceprate SC; CellPro, Bothell, WA) and stem-cell factor (SCF), interleukin (IL)-1, IL-3, IL-6, and erythropoietin (EPO)-mediated ex vivo expansion of the CD34+ cells for 14 to 21 days, no tumor cells could be detected in these primary breast cancer patients at a sensitivity of 1 tumor cell per 4 x 10(5) nucleated cells. Thus, to answer the question of whether tumor cells are expanded concomitantly on ex vivo expansion of normal CD34+ cells, we cocultured defined numbers of primary renal carcinoma cells (RS-85), xenograft-derived breast cancer cells, and small-cell lung cancer cells with CD34+ cells selected from normal donors or cancer patients, either in serum or serum-free culture media. We found that none of the three epithelial tumor cell types increased significantly in number during a 14-day coculture period when compared with normal CD34+ cells alone or tumor cells alone, which increased 110- +/- 77-fold and 45- +/- 26-fold, respectively. However, during coculture, the tumor cells did not undergo cell death and were able to regrow when maintained in serum for longer time periods. We conclude that cytokine-supported expansion cultures of positively selected CD34+ PBPCs from primary high-risk stage II/III or stage IV breast cancer patients do not contain detectable tumor cells, which suggests that there is no increased risk of concomitan

Topics: Animals; Antigens, CD34; Biomarkers, Tumor; Blood Cells; Blood Physiological Phenomena; Breast Neoplasms; Carcinoma, Renal Cell; Cattle; Cell Culture Techniques; Cell Separation; Cell Survival; Cells, Cultured; Coculture Techniques; Culture Media, Serum-Free; Female; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Keratins; Kidney Neoplasms; Mucin-1; Neoplasm Proteins; Neoplasm Staging; Neoplasm, Residual; Neoplastic Cells, Circulating; Risk; Sensitivity and Specificity; Time Factors; Transplantation, Heterologous; Tumor Cells, Cultured

The usefulness of serum tissue polypeptide-specific antigen (TPS), a cytokeratin 18-associated marker, in renal cell carcinoma (RCC) was assessed in vitro and in vivo.. Indirect immunoperoxidase staining for TPS expression was performed on frozen sections of normal renal tissue and RCC specimens. By using a monoclonal TPS immunoradiometric assay, serum TPS concentrations were analyzed in 82 healthy controls, in 20 patients with locoregional RCC before and after surgery and in 18 patients with advanced disease following surgery receiving immunotherapy with interferon-gamma.. Using immunohistochemistry, TPS was found to be expressed by both normal and cancerous renal epithelial cells. The mean TPS concentrations in 82 healthy controls was 56 +/- 49 U/1 with a 95% percentile of 78.5 U/1. Out of 20 patients with locoregional RCC, 8 presented with elevated values (mean 168 +/- 82 U/1) above the cut-off level (78.5 U/1, sensitivity 40%) which dropped to normal within 2 weeks after surgery. During a follow-up period of 1 year, none of the patients presented with tumor recurrence and TPS concentrations remained low (mean 52 +/- 36 U/1). In 18 patients receiving interferon-gamma therapy, serum TPS concentrations were monitored over a period of 12 months. In 5/18 patients, baseline levels were within the normal range (mean 37 +/- 21 U/1); interestingly, these at the same time were the only responders to immunotherapy (n = 2) or at least showed stable disease (n = 3). Response to therapy was reflected by low serum TPS levels (mean 28 +/- 23 U/1) over the entire observation period. Thirteen patients suffered progressive disease during therapy, all of them exhibiting significantly elevated (p < 0.005) pretherapeutic TPS concentrations (mean 186 +/- 124 U/1) that remained equally elevated throughout therapy (mean 192 +/- 102 U/1), reflecting tumor progression.. TPS might have some clinical value as prognostic marker in RCC, possibly by reflecting the proliferative tendency of the tumor.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Renal Cell; Disease Progression; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Immunoradiometric Assay; Interferon-gamma; Keratins; Kidney Neoplasms; Male; Middle Aged; Neoplasm Staging; Nephrectomy; Peptides

We developed a modified in vitro invasion assay system using monolayers of vascular endothelial cells. A type I collagen gel was formed in plastic dishes, and overlaid with type IV collagen. Calf pulmonary arterial endothelial (CPAE) cells were seeded onto these plates, and incubated until they reached confluence. Five human renal cell carcinoma cell lines with various metastatic potentials in vivo were then seeded on the monolayer CPAE cells, and their colony formation and invasion activities were examined for 9 days. At day 4, the highly metastatic cell lines increased the number of colony foci on monolayer CPAE cells several fold higher than their poorly metastatic counterpart. The horizontal spreading patterns were also different between poorly and highly metastatic cell lines. On day 9, the number of carcinoma foci that penetrated the monolayer of CPAE cells and type IV collagen sheets into type I collagen gels in highly metastatic cell lines greatly increased as compared with that of poorly metastatic cell lines. Our in vitro invasion assay using monolayer CPAE cells would be useful to evaluate protease activities and colony formation during invasion.

Topics: Animals; Carcinoma, Renal Cell; Cattle; Collagen; Endothelium, Vascular; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Models, Biological; Neoplasm Invasiveness; Pulmonary Artery; Time Factors; Tumor Cells, Cultured; von Willebrand Factor

Even when clinical data strongly suggest the presence of a metastatic neoplasm in the breast, this occurrence almost invariably raises great problems in diagnostic pathology. Both cases presented here had a well-recognized primitive neoplasm located elsewhere. Nonetheless, great importance was given to the application of ancillary techniques; the immunostains for "breast discriminants"--GCDFP15, HMFG1, and HMFG2--on tissue sections helped the recognition of a metastatic renal cell carcinoma; and the stains for S100 protein, smooth muscle actin, cytokeratins, and neurofilaments on cytologic material allowed the identification of a metastatic mediastinal leiomyosarcoma.

Topics: Actins; Adult; Biopsy, Needle; Breast Neoplasms; Carcinoma, Renal Cell; Fatal Outcome; Female; Humans; Keratins; Kidney Neoplasms; Leiomyosarcoma; Mediastinal Neoplasms; Middle Aged; S100 Proteins; Vimentin

Long-Evans (Eker) rats carry a mutation that predisposes them to develop spontaneous renal cell tumors of two morphologic patterns: solid chromophilic masses or cystic lesions lined by eosinophilic cells. Previous studies have suggested that these tumors arise from the proximal tubules. In the present study, lectin-binding characteristics and cytokeratin expression of various stages of hereditary rat renal epithelial neoplasia were examined to localize the portion of the nephron from which tumors arise. Lectin-binding histochemistry has been used as a marker of cell surface glycoprotein expression, thought to be important in the differentiation of benign from malignant epithelial lesions and in the determination of their cell of origin. The presence or absence of keratin intermediate filaments in the rat nephron has been used to identify nephron segments. The polyclonal antibody to high- and low-molecular-weight cytokeratin stained the cells of the collecting ducts but not the proximal or distal tubules. Binding to the proximal tubules by the lectins Conavalia ensiformis (Con A), Dolichas biflorus, Ricinus communis (RCA-1), and Triticum vulgare and to the distal tubules by Con A, RCA-1, Arachis hypogaea (PNA) with and without neuraminidase, and the antibody for cytokeratins was demonstrated. The lectin binding and cytokeratin staining patterns of rat hereditary renal cell carcinoma, adenoma and the preneoplastic lesions of atypical tubules and hyperplasias suggest that cystic adenomas arise from the distal nephron, principally the collecting duct, whereas the solid atypical tubules, hyperplasias, and adenomas arise from the proximal nephron, principally the proximal tubule.

Topics: Adenoma; Animals; Biomarkers, Tumor; Carcinoma, Renal Cell; Concanavalin A; Histocytochemistry; Hyperplasia; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Tubules, Distal; Kidney Tubules, Proximal; Lectins; Male; Plant Lectins; Precancerous Conditions; Rats; Rodent Diseases; Wheat Germ Agglutinins

We report the clinical, radiographic, pathologic, and immunohistochemical features of a patient with widespread meningeal carcinomatosis from renal cell carcinoma. Clear and spindle tumor cell subtypes infiltrated the meninges of the cauda equina, oculomotor nerve, spinal cord, and cerebral hemispheres, forming abortive glandular or tubular aggregates without evidence of parenchymal invasion. Cytokeratin epitopes were labeled immunohistochemically with Cam 5.2 antibodies, but epithelial membrane antigen and neuron-specific enolase were not present.

Topics: Carcinoma, Renal Cell; Cauda Equina; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Meningeal Neoplasms; Middle Aged; Nerve Fibers; Oculomotor Nerve; Spinal Cord; Spinal Nerve Roots; Tomography, X-Ray Computed

Papillary renal cell carcinoma (RCC) is an uncommon subtype of RCC that has distinctive gross, histologic, and cytogenetic features, but for which only limited immunohistochemistry data have been reported. We compared 36 papillary RCCs and five renal cell adenomas with 19 non-papillary (clear cell and granular) RCCs using a variety of antibodies to keratin and carcinoembryonic antigen (CEA). Papillary tumors were often multifocal and associated with coexistent adenomas, whereas nonpapillary tumors generally lacked these features. Low-grade papillary RCCs demonstrated three occasionally overlapping histologic patterns (typical, trabecular, and sclerotic), whereas high-grade tumors were characterized by an admixture of many patterns. Immunohistochemically, 100% (36 of 36 cases) of the papillary tumors were positive for AE1/AE3, and 92% (33 of 36 cases) were positive for callus keratins; only 3% (one of 36 cases) stained for 34BE12, and 11% (four of 36 cases) weakly stained for CEA. The five renal cell adenomas were likewise positive for AE1/AE3 (five of five cases) and callus (five of five cases) keratins. In contrast, 85% (16 of 19 cases) of the nonpapillary tumors stained for AE1/AE3, but only 5% (one of 19 cases) stained for callus; none (0/19) stained for 34BE12, and 10% (2/19) weakly stained for CEA. The consistent expression of callus keratins by papillary RCCs and renal cell adenomas underscores the close relation of these lesions, providing additional evidence for their oncological distinction from nonpapillary RCCs.

Topics: Adenoma; Adult; Aged; Carcinoembryonic Antigen; Carcinoma, Papillary; Carcinoma, Renal Cell; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged

Chromophobe renal cell carcinoma (RCC) is a recently established subtype of RCC, which has rarely been reported in Japan. In this communication, the authors report two Japanese cases of chromophobe RCC together with the immunohistochemical findings. The tumors were composed of sheets and cribriform glands formed by tumor cells with cloudy and reticular cytoplasm. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. The tumor cells were positive for cytokeratin, epithelial membrane antigen, and Tamm-Horsfall protein. Occasionally, LeuM1-positive cells were also noted. Vimentin was negative, unlike the usual RCC. Reactivity for peanut agglutinin was more frequent than that to Lotus tetragonolobus agglutinin. The results of this study suggest that the tumor cells possessed phenotypes similar to the distal nephron rather than to the proximal tubular cells.

Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carcinoma, Renal Cell; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lectins; Lewis X Antigen; Vimentin

To investigate the relationships among vimentin, keratin and cellular polarity, reorganized glands composed of renal cell carcinoma cells were investigated in vitro. We employed two different three-dimensional collagen gel culture methods, the "floating sandwich method (FSM)" and the "dispersed embedding method (DEM)." The cells composed of reorganized glands formed by FSM culture showed distinct polarity. In contrast, the cellular polarity of the cells formed by DEM culture was less distinct. Keratin was evenly distributed throughout the cytoplasm regardless of the culture method. In contrast, in reorganized glands obtained by FSM culture, vimentin was distinctly polarized at the basal pole while glands obtained by DEM culture showed random distribution of vimentin. These results suggest that there is a close relationship between cell polarity and intracellular localization of vimentin, and that there may be different mechanisms controlling the organization of the two intermediate filament (IF) networks.

Topics: Carcinoma, Renal Cell; Cell Polarity; Collagen; Culture Techniques; Gels; Humans; Intermediate Filaments; Keratins; Kidney Neoplasms; Microscopy, Electron; Neoplasm Proteins; Tumor Cells, Cultured; Vimentin

Renal cell carcinoma can have solitary adrenal metastasis years or even decades after resection of the primary tumor. The difficulty in distinguishing an adrenocortical adenoma from a solitary metastasis of a renal cell carcinoma prompted us to study 10 adrenal adenomas, 11 primary renal cell carcinomas, and three renal cell carcinomas metastatic to the adrenal gland by immunohistochemical stains and flow cytometry to determine if these techniques could help make the distinction. Immunohistochemical staining was performed for detection of cytokeratin, vimentin, and epithelial membrane antigen (EMA). Cytokeratin, vimentin, and EMA were detected in 10/11, 9/11, and 11/11 primary renal cell carcinomas, respectively, and 1/3, 2/3, and 3/3 metastatic renal cell carcinomas, respectively. All cases of adrenal adenoma were negative for the three antigens. DNA content analysis by flow cytometry showed no evidence of an abnormal DNA stemline in any of the cases except one renal cell carcinoma. We conclude that staining for EMA is consistently strongly positive in primary and metastatic renal cell carcinomas and consistently negative in adrenal adenomas, proving to be a useful distinguishing marker. Cytokeratin and vimentin, although uniformly absent in adrenal adenomas, are variably and often only weakly positive in renal cell carcinomas, and therefore of less help in making the distinction. Flow cytometry analysis has no discriminatory value in these cases.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Membrane Glycoproteins; Mucin-1; Ploidies; Vimentin

We investigated in vitro invasiveness and type IV collagenolytic activity of cells from a primary and a metastatic lesion of a patient with renal cell carcinoma. The temporarily cultured cells (SRCC-1P) derived from the primary lesion and those (SRCC-1M) from the metastatic lesion exhibited positive staining for both cytokeratin and vimentin, indicating that they were of renal cell carcinoma origin. An in vitro invasion assay revealed that the cells of SRCC-1M were significantly more invasive than those of SRCC-1P, which showed only marginal invasion. Type IV collagenolytic activity correlated with the in vitro invasiveness, in which SRCC-1M apparently had the higher activity. These results indicate that type IV collagenolytic activity contributes to the invasiveness of the cells in vitro.

Topics: Adrenal Gland Neoplasms; Carcinoma, Renal Cell; Collagen; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Tumor Cells, Cultured; Vimentin

Malignant spindle cell neoplasms are a diagnostic challenge regardless of their location. In the retroperitoneum a major consideration in the differential diagnosis is sarcomatoid renal cell carcinoma; if an epithelial component cannot be recognized histologically, special studies may be required to reach the correct diagnosis. In an attempt to better characterize this entity, 23 cases of sarcomatoid renal cell carcinoma (6.3%) were identified from a review of 363 renal cell carcinomas. Blocks were available for immunohistochemical analysis in 18 cases. The epithelial and sarcomatoid portions were studied with a panel of antibodies directed against cytokeratin (AE1/AE3, CAM 5.2, and 34 beta E12), epithelial membrane antigen, Leu-M1, muscle-specific actin, S100 protein, desmin, and vimentin. The epithelial nature of the spindle cell component was best demonstrated by positive reactivity with the anti-cytokeratin AE1/AE3 (in 17 [94%] of the 18 cases). The other epithelial markers stained the spindle cell component less frequently: cytokeratin CAM 5.2 in seven cases (39%); epithelial membrane antigen in nine cases (50%); and high-molecular-weight cytokeratin 34 beta E12 in no cases (0%). In 10 cases (56%) vimentin positivity and in six cases (33%) actin positivity was seen in the spindled areas. The spindle cell component stained for Leu-M1 in four cases (22%) and for S100 protein in one case (6%) and did not react for desmin in any case. From this study we conclude that in the majority of sarcomatoid renal cell carcinomas the epithelial nature of the spindle cells, as indicated by cytokeratin expression, can be documented using immunohistochemical methods.

Topics: Carcinoma, Renal Cell; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratins; Kidney Neoplasms; Sarcoma

Morphological analysis of the sclerotic changes in peripheral lung carcinoma (PLC) and nephrosclerosis in renal-cell carcinoma (RCC) established a promoting role of sclerosis in carcinoma development. The pneumosclerosis role as a background process in the PLC development is proved by the following facts: high proportion (83%) of the carcinoma in the scar among PLC; identity of the scar collagen composition in PLC and that in metatuberculosis and metapneumonic pneumosclerosis foci; detection of metatuberculosis foci in 75% of PLC; the presence of the precancerous changes in the epithelium entrapped in the pneumosclerotic foci, not only with signs of morphological atypia, but with the disturbance of nuclear DNA and cellular oncogene expression as well. The association of RCC with nephrosclerosis is shown by a high proportion (82.7%) of the RCC development against the background of nephrosclerosis; the dependence of the so-called cortical adenoma development on the degree of nephrosclerosis; epithelial proliferation in the nephrosclerotic foci with the appearance of undifferentiated cells with the altered DNA content and the expression of cytokeratins and vimentine. Carcinoma morphogenesis against the background of sclerosis may be described as follows: development of sclerosis (focal and/or diffuse), the appearance of the focal epithelial hyperplasia in the scar, dysplasia or adenoma and finally carcinoma.

Topics: Adenoma; Carcinoma, Renal Cell; Cell Differentiation; Cell Division; Collagen; DNA; Humans; Keratins; Kidney Neoplasms; Lung Neoplasms; Nephrosclerosis; Precancerous Conditions; Sclerosis; Vimentin

The immunostaining patterns of adrenocortical tumors are not clearly defined, primarily due to their inconsistent expression of cytokeratins (CK). To address this issue and to investigate whether adrenocortical tumors can be immunohistochemically differentiated from histologically similar tumors arising from the kidney and liver, we studied four normal adrenal glands, two adrenocortical adenomas (ACAs), 31 adrenocortical carcinomas (ACCs), 37 renal cell carcinomas (RCCs), and 33 hepatocellular carcinomas (HCCs) with anti-CK antibodies AE1, CAM 5.2, UCD/PR10.11, 35BH11, PKK1, and Ks19.1, as well as antibodies to vimentin (VIM), epithelial membrane antigen (EMA), and HMFG-2. Normal adrenal cortical cells showed variable staining with all anti-CK antibodies on fixed and frozen sections. In contrast, only one of two fixed ACAs stained with a single anti-CK, although both neoplasms reacted with multiple anti-CK antibodies on frozen sections. Similarly, 20 of 31 fixed ACCs contained VIM, but only one tumor stained for CK; frozen sections of this and another, previously negative tumor, however, stained with most of the anti-CK antibodies tested. One-dimensional Western immunoblot analysis confirmed the presence of CKs 18 and 19 in two examples of normal adrenal cortex, one ACA, and the ACC immunohistochemically positive on fixed and frozen sections, with CK 19 identified in the ACC that was positive on frozen section alone. All fixed HCCs and most RCCs stained with multiple anti-CK antibodies (33 and 34 cases, respectively), with a proportion of tumors positive for VIM (six and 22 cases, respectively), EMA (seven and 30 cases, respectively), and HMFG-2 (15 and 28 cases, respectively). The results suggest that CK expression is diminished in most adrenocortical tumors to levels too low to be recognized following the deleterious effects of fixation. While the immunohistochemical absence of CK, EMA, and HMFG-2 in fixed sections in the majority of ACCs is distinctive, sufficient phenotypic overlap exists such that differentiation between RCC and HCC may not be possible in an individual case.

Topics: Adrenal Cortex Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Diagnosis, Differential; Electrophoresis, Polyacrylamide Gel; Humans; Immunoblotting; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Liver Neoplasms

26 cases of renal cell carcinoma (RCC) were studied by both light microscopy and electron microscopy, accompanied with 9 cases of human embryo kidney as control. 20 cases of RCC in different degree of cell differentiation, 4 cases of human embryo kidney and 1 case of adult human kidney were studied with immunohistochemical methods. The results indicated that the histostructures and antigen expression of RCC were rather complicated and the ultrastructures and antigen expression changes of RCC seemed very similar to those of the developing embryonic kidneys. This indicated, that RCC might have originated from nephroblastoma cells.

Topics: Carcinoma, Renal Cell; Cell Differentiation; Embryo, Mammalian; Humans; Immunohistochemistry; Keratins; Kidney; Kidney Neoplasms; Microscopy, Electron; Vimentin

Forty-two renal cell carcinomas, one oncocytoma and normal renal tissue were studied for the presence of cytokeratins and vimentin. The investigations were performed by immunofluorescence microscopy applying a panel of mono- and polyclonal antibodies to intermediate filament proteins. In all tumours except chromophobic renal cell carcinoma (CRCC) and oncocytoma a co-expression of cytokeratins and vimentin could be shown. The intermediate filament expression was often, however, very heterogeneous particularly with respect to the distribution of cytokeratins and vimentin, to the clonality of the antibodies used and to the tumour areas studied. The latter could be impressively demonstrated by examining a whole tumour. In CRCC and oncocytoma all tumour cells expressed cytokeratins and, in addition, single tumour cells also expressed vimentin. In normal renal tissue we could show vimentin-positive epithelia of proximal and distal tubules, which is reported for the first time.

Topics: Adenoma; Carcinoma, Renal Cell; Cytoskeletal Proteins; Desmoplakins; Epithelium; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Kidney Neoplasms; Kidney Tubules, Distal; Kidney Tubules, Proximal; Vimentin

A 19-month-old black girl had a radical nephrectomy for a Wilms' tumor that contained areas of epithelium indistinguishable from renal cell carcinoma. She was treated with chemotherapy but subsequently had pulmonary metastases develop and massive abdominal recurrence. The recurrent tumor was histologically renal cell carcinoma with no identifiable Wilms' tumor elements. The child died with recurrent and metastatic tumor 13 months after nephrectomy. Pathologic, immunoperoxidase, and flow cytometric studies of this unusual case are presented.

Topics: Carcinoma, Renal Cell; Female; Humans; Immunoenzyme Techniques; Infant; Keratins; Kidney Neoplasms; Lung Neoplasms; Ploidies; Recurrence; Vimentin; Wilms Tumor

Ten renal cell carcinomas in children under 15 years were investigated. The average age was 122.5 months and the girls predominated in our cases (7 girls, 3 boys). By using the classification of Thoenes et al., Pathol Res Pract 181: 125-143, 1986 a predominance of clear cell-eosinophilic tumor cell type and of the tubulopapillary growth pattern was found. Immunohistochemistry revealed a heterogeneity of cytokeratin expression. By using the monoclonal antibodies Cam 5.2 and KL 1, cytokeratins were found in 7 cases each. The other 4 cytokeratin antibodies used were less sensitive. The expression of cytokeratin 13 in 3 cases suggested a more complex histogenesis than assumed. Vimentin was found in 3 tumors, but an association to a higher grade (G) of malignancy was not found in these cases. One tumor expressed the Tamm-Horsfall-protein, which is predominantly found in the distal tubule of the normal kidney. In summary the results of immunohistochemistry characterized the great heterogeneity of these tumors. Follow-up information was available in 9 cases. All patients with G I- and G II-tumors were free of disease after an average time of 39.6 months (mean 27 months). Two of the 3 cases with G III-tumors died after 9 and 15 months, despite additional chemo- or radiotherapy. Therefore tumors of grade I and II of the Thoenes classification seem to have a good prognosis.

Topics: Adenocarcinoma; Adolescent; Antibodies; Carcinoma, Renal Cell; Child; Child, Preschool; Eosine Yellowish-(YS); Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lectins; Male; Prognosis; Staining and Labeling; Wilms Tumor

Bellini duct carcinomas have recently been identified as a new entity in the spectrum of renal cell carcinomas and 10 cases have now been reported. The present paper adds detailed clinical and morphological data on six new cases. In addition, immunohistological and electronmicroscopical results support the origin of these tumours from the renal collecting ducts, especially the papillary ducts (Bellini ducts). A set of immunohistological reactions, including reactions to cytokeratins 13 and 19, vimentin and UEA-1 was found to facilitate the differential diagnosis of Bellini duct carcinomas from other renal cell carcinomas and infiltrating urothelial carcinomas of renal pelvis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Renal Cell; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Tubules, Collecting; Lectins; Male; Middle Aged; Plant Lectins; Vimentin

Sixty-six renal cortical epithelial tumors were classified by light and electron microscopy into 18 oncocytomas and 48 renal carcinomas, and their pattern of cytokeratin and vimentin reactivity was evaluated by immunoperoxidase using paraffin-embedded tissue. We found by electron microscopy that most oncocytomas (11 of 15) contain globular filamentous bodies that consist of a complex of intermediate filaments and organelles. These structures were found to correlate on immunohistochemistry with a discrete punctate cytoplasmic pattern of cytokeratin reactivity, provided the antibody preparation contained specificity for cytokeratins 8 and 18. A similar punctate finding was not observed in four oncocytomas nor in the 48 renal carcinomas. Although 11 oncocytomas failed to express vimentin, seven tumors showed focal reactivity restricted to rare individual cells in areas of sclerosis (five tumors) or in cell clusters bordering central scars (two tumors). We conclude that many oncocytomas contain a potentially diagnostically useful punctate pattern of cytokeratin reactivity and that focal vimentin reactively may be observed in otherwise typical oncocytomas, restricted to tumor cells appearing to be undergoing atrophy.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; Female; Humans; Immunoenzyme Techniques; Inclusion Bodies; Keratins; Kidney Neoplasms; Male; Microscopy, Electron; Middle Aged; Vimentin

We studied the distribution of intermediate-sized filaments in developing and adult kidneys and renal cell carcinoma (RCC) by indirect immunohistochemistry, using a pan-cytokeratin mouse monoclonal antibody (MAb), chain-specific anti-cytokeratin MAb, and anti-vimentin and anti-desmin MAb, to resolve controversy concerning intermediate-sized filament expression in the kidney. With the pan-cytokeratin MAb, cytokeratin expression was detectable in all stages of nephron development, starting with expression in the renal vesicles, the progenitors of the glomeruli, proximal tubules, Henle's loop, and part of the distal tubules. Using chain-specific anti-cytokeratin MAb, cytokeratin 8 and 18 expression was demonstrated in all developmental structures of the nephron, whereas cytokeratin 19 expression was more complex. None of the nephrogenic blastema cells from which the renal vesicles arise expressed cytokeratins. Transient expression of vimentin and cytokeratin 19 was observed in differentiating collecting ducts and proximal tubule cells at the S-shaped stage of nephron development, respectively. In RCC, cytokeratin expression closely resembled that of the mature proximal tubule, i.e., RCC cells expressed cytokeratins 8 and 18. However, in a subset of RCC additional cytokeratin 19 expression was noted. In addition, all except one RCC showed co-expression of cytokeratins and vimentin.

Topics: Adult; Antibodies, Monoclonal; Carcinoma, Renal Cell; Embryonic and Fetal Development; Epithelium; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Kidney; Kidney Neoplasms; Kidney Tubules; Staining and Labeling

We used a battery of antigens to determine whether immunohistochemistry can (a) contribute to resolving the histogenesis of the stromal component of the capillary hemangioblastoma, and (b) answer cases of difficult pathologic differential diagnosis with metastatic clear cell carcinoma. The stromal cells of the capillary hemangioblastoma are antigenically polymorphous and may express immunoreactive erythropoietin, renin, keratin, Leu M1, Leu 7, actin, neuron-specific enolase, S100 protein, and glial fibrillary acidic protein. However, the use of epithelial membrane antigen allows certain histopathologic distinction between capillary hemangioblastoma and metastatic clear cell carcinoma.

Topics: Adenocarcinoma; Aged; Antigens, Differentiation; Antigens, Neoplasm; Carcinoma, Renal Cell; Cerebellar Neoplasms; Diagnosis, Differential; Erythropoietin; Hemangiosarcoma; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Male; Membrane Glycoproteins; Mucin-1; Renin

Two cases of von Hippel-Lindau's disease with special reference to the occurrence of renal carcinoma are presented. The first case demonstrates the difficulty of differentiating cerebellar haemangioblastoma from metastatic renal carcinoma affecting the cerebellum. The valuable differentiating histological features were positive staining of metastatic renal carcinoma by antiepithelial membrane antigen (anti-EMA) and the demonstration of a distinct pattern of packeting of cells by staining reticulin fibres. Staining with periodic acid Schiff and cytokeratin antibody (anti-CK) were not found to be useful. The second case exhibits the wide variety of neoplasms which may be present in von Hippel-Lindau's disease. Special stains support the findings of the first case.

Topics: Adult; Angiomatosis; Biomarkers, Tumor; Carcinoma, Renal Cell; Cerebellar Neoplasms; Cerebellum; Cerebral Angiography; Diagnosis, Differential; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Magnetic Resonance Imaging; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Tomography, X-Ray Computed; von Hippel-Lindau Disease

42 renal cell carcinomas and 1 oncocytoma were investigated by means of immunofluorescence (including double immunofluorescence) using a panel of mono- and polyclonal antibodies to vimentin and cytokeratins. In all tumors except chromophobe cell renal carcinoma (CCRC) and oncocytoma generally a coexpression of vimentin and cytokeratins could be demonstrated; however, the intermediate filament expression was often very heterogeneous with regard to the distribution of vimentin and cytokeratins in general, depending on the mono- and polyclonality of the antibodies and on the areas of a tumor investigated. In CCRC and oncocytoma all tumor cells contained cytokeratin filaments. In addition, as revealed by double immunofluorescence, in only occasional tumor cells we could demonstrate vimentin.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma, Renal Cell; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Kidney Neoplasms; Vimentin

We applied a panel of antibodies to formalin-fixed, paraffin-embedded sections of 55 renal cell carcinomas using a three-stage immunoperoxidase technique. The antibody panel included two anti-keratins, AE1 and CAM5.2, anti-epithelial membrane antigen (EMA), anti-vimentin, anti-S100 protein, and the anti-leukocyte marker PD7/26. Forty-eight of 55 renal cell carcinomas expressed keratins. CAM5.2 stained 46 tumors (84%) and AE1 stained 37 neoplasms (67%). AE1 reacted with two CAM5.2-negative tumors. EMA was expressed by 35 carcinomas (64%), including three of the CAM5.2-negative neoplasms. Therefore, using all three antibodies, 50 neoplasms (91%) expressed antigens of epithelial differentiation. Anti-EMA and AE1 were complementary to each other; the combination stained 46 of the carcinomas, comparable with CAM5.2 alone. Vimentin was expressed by 26 tumors (47%), and S100 was expressed by one. PD7/26 did not stain any of the cases. Vimentin expression correlated with nuclear grade; low nuclear grade neoplasms infrequently expressed vimentin, while the converse was true for high nuclear grade tumors. Keratin expression was related to tumor cell type and histologic pattern, as fewer neoplasms of clear cell type and with a solid pattern expressed keratins. In contrast, all papillary and eight of nine (89%) spindled carcinomas expressed keratins.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma, Renal Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1

The histogenesis of renal cell carcinoma and oncocytoma is controversial. We compared immunohistochemical profiles of normal kidney, nine carcinomas, and six oncocytomas. Carcinomas and oncocytomas expressed the following antigens respectively: proximal tubule--Uro 3 (56 & 67%), alpha-1-antitrypsin (89 & 50%); proximal and distal tubule--Uro 10 (67 & 83%); distal tubule--B2-microglobulin (100 & 100%); distal/medullary tubule--epithelial membrane antigen (89 & 83%), neuron-specific enolase (78 & 100%), glandular cytokeratin (78 & 100%), epidermal keratin (67 & 67%); and medullary tubule--Uro 8 (89 & 83%). All tumors, except one oncocytoma, had at least one positive reaction for each antigen group. Oncocytomas predominantly stained for distal/medullary tubular antigens; none showed a predominance of proximal tubular antigens. Carcinomas also demonstrated largely distal/medullary tubule antigens; 44% showed prominence of proximal tubular antigens as well. Assignment of an exclusive proximal, distal or medullary tubule origin to renal neoplasms does not appear valid. Divergent histogenesis from a precursor stem cell is likely.

Topics: Adenoma; Antigens; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Tubules; Neoplastic Stem Cells; Vimentin

This paper reports on 32 chromophobe cell renal carcinomas observed in 697 renal cell cancers (RCC) of adults (peak in the sixth decade of life). The chromophobe cell-type differs from other types of RCC macroscopically, the cut-surface being predominantly of grey-beige colour. Histologically, there are two variants: one is the typical (light) variant (n = 22) and the other is eosinophilic (n = 10). Both variants have in common (a) reaction of the cytoplasm with Hale's acid iron colloid; (b) electron microscopic detection of cytoplasmic microvesicles (150-300 nm), frequently with 'inner vesicles', and (c) low glycogen content in comparison with the clear cell carcinoma. Immunocytochemical investigations on the intermediate filaments show a positive reaction for cytokeratins No. 18 (uniformly) and Nos. 7 and 19 (to varying extents) for both variants, whereas vimentin was not found in any of these carcinomas, in contrast to the clear-cell type. The cytomorphological grading revealed predominantly G II tumours. A lymph node metastasis was found in one patient. On the basis of the mortality curves determined, the prognosis for patients with chromophobe cell carcinomas is more favourable than that of the clear-cell type. In terms of differential diagnosis, on the one hand, the typical (light) variant of the chromophobe cell RCC must be delimited from the clear-cell RCC, and on the other hand, the eosinophilic variant must be distinguished from the chromophilic or 'granular' RCC. Microscopic, histological, histochemical, electron microscopic, and intermediate filament analysis results document that the chromophobe cell type of RCC is a distinct entity. The implications for the nomenclature of RCC, especially with regard to the 'granular' type, are discussed.

Topics: Adult; Aged; Carcinoma, Renal Cell; Eosine Yellowish-(YS); Female; Glycogen; Humans; Intermediate Filaments; Keratins; Kidney Neoplasms; Male; Microscopy, Electron; Middle Aged; Prognosis; Staining and Labeling; Vacuoles; Vimentin

Topics: Adult; Aged; Carcinoma, Renal Cell; Electrophoresis, Gel, Two-Dimensional; Female; Fluorescent Antibody Technique; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged; Vimentin

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Biopsy, Needle; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Kidney; Kidney Diseases, Cystic; Kidney Neoplasms; Male; Middle Aged

We examined the expression of the diverse cytokeratin (CK) polypeptides as well as vimentin in human renal cell carcinomas of various subtypes and in renal oncocytomas by applying both two-dimensional gel electrophoresis and immunocytochemistry by using polypeptide-specific monoclonal antibodies. The tumors were classified according to the guidelines of the World Health Organization, with some modifications based primarily on recently proposed cytomorphological criteria. All clear cell carcinomas (G I, G II; N = 20) co-expressed CKs nos. 8 and 18, and vimentin, with CK no. 19 being present in 13 of the 20 cases and exhibiting a heterogeneous distribution. Dedifferentiated carcinomas (G III; N = 8) also co-expressed CKs nos. 8 and 18 as well as vimentin, but in addition, exhibited CK no. 19 and, in many cases, CK no. 7; in 1 case, only vimentin was expressed. Both eosinophilic-granular (N = 3) and basophilic (small cell cuboidal; N = 6) carcinomas contained CKs nos. 8 and 18, and the co-expression of vimentin was a consistent feature of these tumors; CK no. 19 was found in all of these cases, while CK no. 7 was present in the majority. In chromophobe cell carcinomas (N = 8), in contrast to all of the other carcinoma types, no vimentin was detected in the tumor cells, with only CKs nos. 8, 18, and to a variable extent 7, being present. Similarly, oncocytomas (N = 8) lacked vimentin and exhibited only CKs nos. 8 and 18. Conspicuous scattered CK no. 19-positive cells were found in these two last tumor types. No CK polypeptides other than simple-epithelium-type CKs (nos. 7, 8, 18, and 19) were detected in any of the tumors studied. These results indicate that, in renal cell tumors, the expression of intermediate-filament proteins is strikingly correlated with the specific morphologic appearance. While the co-expression of CKs nos. 8 and 18 and vimentin was a surprisingly consistent feature of the most common subtypes of renal cell carcinomas, CK no. 19 exhibited remarkable heterogeneity of expression both within individual tumors and between different tumors, the expression patterns of this CK being correlated to the tumor subtypes. The consistent absence of vimentin in chromophobe cell carcinomas and oncocytomas makes it possible to define these as a separate class of renal cell tumors. This finding supports the view that chromophobe cell carcinomas represent a distinct tumor entity and points to their close phenotypic relationship to benign oncocytomas as we

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; Cell Differentiation; Female; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Kidney Neoplasms; Male; Middle Aged; Phenotype; Vimentin

Most renal cell carcinomas coexpress vimentin and keratin, while renal tubular epithelia express only keratin. Investigation of the intermediate filament composition of tubular epithelia in diseased rat and human kidneys now shows that altered tubular epithelia unequivocally coexpress keratin and vimentin. In rats, pronounced coexpression of vimentin and keratin was observed in chronic nephrosis induced by daunomycin, and the extent of coexpression seemed to increase with the incidence of altered collapsed and cystically dilated tubules and with the degree of tubular epithelial proliferation. It was also seen during tubular regeneration after acute tubulotoxic injury induced by mercury chloride poisoning, with vimentin expression being lost in fully regenerated tubular epithelium. In man, expression was seen in chronically and irreversibly damaged kidneys. Thus, vimentin can be expressed temporarily in acutely and reversibly damaged kidneys and chronically in irreversibly damaged kidneys. Vimentin could perhaps be regarded as an indicator of the regenerating and proliferating activity of tubular lesions.

Topics: Animals; Carcinoma, Renal Cell; Daunorubicin; Epithelium; Humans; Hypertension, Renovascular; Immunohistochemistry; Keratins; Kidney Diseases; Kidney Neoplasms; Kidney Tubular Necrosis, Acute; Kidney Tubules; Male; Rats; Rats, Inbred Strains; Regeneration; Vimentin

Topics: Adult; Aged; Carcinoma, Renal Cell; Electrophoresis, Polyacrylamide Gel; Female; Humans; Intermediate Filament Proteins; Isoelectric Focusing; Isoelectric Point; Keratins; Kidney Neoplasms; Male; Middle Aged; Molecular Weight; Vimentin

Nine primary human renal-cell tumors (RCT), one lymph-node metastasis, 4 human xenografts of a RCT in nude mice and a rat RCT line were analyzed by flow cytometry (FCM) using propidium iodide for DNA analysis and antibodies to cytokeratin and vimentin in the indirect immunofluorescence technique for labelling of specific tumor-cell populations. By means of 2-dimensional FCM analysis, vimentin- and cytokeratin-positive (tumor) cells were compared and their DNA content and proliferative fraction analyzed separately from those of cytokeratin-negative stromal and inflammatory cells. In primary human RCT, 2 subpopulations of cells were detected and analyzed separately. Small numbers of tumor cells with an abnormal DNA stemline were also detected. In addition, co-expression of intermediate filament proteins of both the cytokeratin and the vimentin types was detected in the aneuploid cell population. Comparison of 2 model systems of RCT with primary human RCT revealed a similar pattern of tumor-cell subfractions within these tumors. The 2-parameter FCM analysis permits the detection of subpopulations in complex cell suspensions and the quantification of these fractions, as well as analysis of their cellular DNA content.

Topics: Animals; Carcinoma, Renal Cell; Flow Cytometry; Fluorescent Antibody Technique; Humans; Keratins; Kidney Neoplasms; Lymphoma; Mice; Mice, Nude; Rats; Rats, Inbred Strains; Vimentin

The diagnosis of adrenocortical carcinoma (ACC) is often difficult, because this tumor may present with direct extension into adjacent renal parenchyma or with metastatic disease. Renal cell carcinoma and other histologically similar tumors are potentially confused with ACC by conventional light microscopy, and their separation from the latter is often impossible without the aid of additional studies. Furthermore, the distinction between adrenal cortical adenoma and ACC may also be problematic. Because of these factors, the authors studied 10 cases each of ACC, adrenocortical adenoma, and renal cell carcinoma (RCC) immunohistochemically, in an attempt to develop objective parameters which may aid in this differential diagnostic dilemma. Nontrypsinized, formalin-fixed, paraffin-embedded specimens were used in all cases, and tissue from the adrenocortical tumors was also studied for intermediate filament content after protease digestion. All 20 nontrypsinized adrenocortical neoplasms were positive for vimentin, but not for cytokeratin, epithelial membrane antigen, or blood group isoantigens. Conversely, each of 10 cases of RCC expressed epithelial membrane antigen, cytokeratin, and blood group isoantigens, but none was immunoreactive for vimentin. Two adrenocortical carcinomas and three adenomas manifested cytokeratin positivity after trypsin digestion. There were no significant differences between the immunostaining profiles of ACC and adrenocortical adenoma, which suggest that this distinction must still rely upon clinical and morphologic criteria.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adult; Aged; Antigens; Blood Group Antigens; Carcinoma; Carcinoma, Renal Cell; Cell Nucleolus; Cell Nucleus; Child, Preschool; Cytoplasm; Diagnosis, Differential; Epithelium; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Infant; Isoantigens; Keratins; Kidney Neoplasms; Male; Middle Aged; Vimentin

A fluorescence study was performed in 16 renal cell carcinomas using antibodies to renal tubular antigens (RTA), two intermediate filaments, cytokeratin and vimentin, and two lectins, soybean agglutinin (SBA) and peanut agglutinin (PNA). We observed the presence of RTA, cytokeratin, and vimentin in all of our specimens. The expression of vimentin, the cytoskeletal protein of mesenchymal cells, was considered to be very interesting feature of the tumor. Binding sites of SBA, normally present in glomeruli, proximal and distal tubules, were detectable in the neoplastic cells in only 37.5% of our specimens. PNA did not react with the tumor except for the small area of 2 specimens. Lectins may be useful for estimating the characteristics or renal cell carcinoma including its malignant potentials, and antibodies to RTA and intermediate filaments seem to be available for the diagnosis of the tumor in metastatic lesions.

Topics: Antibodies; Antibodies, Monoclonal; Antigens; Antigens, Neoplasm; Carcinoma, Renal Cell; Cytoskeleton; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Kidney Neoplasms; Kidney Tubules; Lectins; Peanut Agglutinin; Plant Lectins; Soybean Proteins; Vimentin

One hundred cutaneous tumors were investigated immunohistopathologically for the expression of intermediate filament (IF) proteins. Epithelial tumors, such as basocellular and squamous cell carcinomas, cutaneous adnexal tumors, and metastatic carcinomas showed keratin positivity in a varying number of tumor cells with two keratin antibodies with different specificities. Neoplastic cells of fibrohistiocytic tumors, pigmented nevi, melanomas, hemangiomas, glomus tumors, and lymphomas were positive for vimentin, but not for keratin or desmin. Cutaneous leiomyomas and leiomyosarcomas, on the other hand, were positive for desmin. The results show that the typing of IFs enables the differential diagnosis between carcinomas and sarcomas or melanomas, epidermal appendage tumors, and mesenchymal tumors, and between fibrohistiocytic and leiomyocytic tumors, and therefore are of diagnostic value in histopathologic problems of the skin.

Topics: Adenocarcinoma; Adenoma, Sweat Gland; Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Desmin; Diagnosis, Differential; Fluorescent Antibody Technique; Hemangioma; Histiocytoma, Benign Fibrous; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Leiomyoma; Melanoma; Neoplasm Metastasis; Nevus, Pigmented; Skin Neoplasms; Vimentin

The expression of intermediate-sized filaments (IF) was examined by immunocytochemical methods in 40 primary renal cell carcinomas and compared with the IF distribution in the normal adult human kidney. All tumours stained positively with cytokeratin IF antibodies. Co-expression of cytokeratins and vimentin was observed in 21/40 (52,5%) renal carcinomas. Double immunofluorescence labelling demonstrated that in most of these cases tumour cells contained both cytokeratin and vimentin type IF. In normal human kidneys, cells of the various tubular segments disclosed a positive reaction with cytokeratin antibodies in a different intensity and intracellular localization. Co-expression of cytokeratin and vimentin IF in normal adult human kidneys has never been observed. From a histogenetic point of view, co-expression of cytokeratins and vimentin in renal cell carcinoma obviously represents an atavistic phenomenon since vimentin is re-expressed by these tumour cells during neoplastic transformation. This finding indicates the metanephric origin of the renal parenchyma. In surgical pathology the possibility of very rare co-expression of cytokeratin and vimentin IF within tumour cells should be considered, particularly in the differential diagnosis of clear cell carcinomas.

Topics: Carcinoma, Renal Cell; Cytoskeleton; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Kidney; Kidney Glomerulus; Kidney Neoplasms; Kidney Tubules; Vimentin