mart-1-antigen and Kidney-Neoplasms

Extrarenal retroperitoneal angiomyolipomas are rare.. To review the literature.. Angiomyolipomas, previously classified as hamartomas, are now classified as benign tumours. Thirty cases of primary retroperitoneal angiomyolipomas have been reported. Diagnosis of the disease upon is based radiological and pathological findings of triphasic features of (a) fat and (b) blood vessels and myoid tissue. Immunohistochemistry tends to be positive for HMB45, MART1, HHF35, calponin, NKI-C3, and CD117. The lesion is common in women. Treatment options have included the following: (a) radical surgical excision of the lesion with renal sparing surgery or radical nephrectomy in cases where malignant tumours could not be excluded and (b) selective embolization of the lesion alone or prior to surgical excision. One case of retroperitoneal angiomyolipoma was reported in a patient 15 years after undergoing radical nephrectomy for angiomyolipoma of kidney and two cases of distant metastases of angiomyolipoma have been reported following radical resection of the tumour.. With the report of two cases of metastases ensuing surgical resection of the primary lesions there is need for academic pathologists to debate and review angiomyolipomas to decide whether to reclassify angiomyolipomas as slow-growing malignant tumours or whether the reported cases of metastases were de novo tumours or metastatic lesions.

Topics: Actins; Adult; Aged; Aged, 80 and over; Angiomyolipoma; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Diagnosis, Differential; Embolization, Therapeutic; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Microfilament Proteins; Middle Aged; Nephrectomy; Rare Diseases; Retroperitoneal Neoplasms; Sex Factors; Treatment Outcome

Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with CP-675,206, a fully human anti-CTLA4 monoclonal antibody, may break peripheral immunologic tolerance leading to effective immune responses to cancer in humans. A phase I trial was conducted to test the safety of CP-675,206.. Thirty-nine patients with solid malignancies (melanoma, n = 34; renal cell, n = 4; colon, n = 1) received an intravenous (IV) infusion of CP-675,206 at seven dose levels. The primary objective was to determine the maximum-tolerated dose and the recommended phase II dose.. Dose-limiting toxicities and autoimmune phenomena included diarrhea, dermatitis, vitiligo, panhypopituitarism and hyperthyroidism. Two patients experienced complete responses (maintained for 34+ and 25+ months), and there were two partial responses (26+ and 25+ months) among 29 patients with measurable melanoma. There have been no relapses thus far after objective response to therapy. Four other patients had stable disease at end of study evaluation (16, 7, 7, and 4 months). Additionally, five patients had extended periods without disease progression (36+, 35+, 26+, 24+, and 23+ months) after local treatment of progressive metastases. Longer systemic exposure to CP-675,206 achieved in higher dose cohorts predicted for a higher probability of response.. CP-675,206 can be administered safely to humans as a single IV dose up to 15 mg/kg, resulting in breaking of peripheral immune tolerance to self-tissues and antitumor activity in melanoma.

Topics: Adult; Aged; Antibodies, Blocking; Antibodies, Monoclonal; Antibodies, Neoplasm; Antigens, CD; Antigens, Differentiation; Antigens, Neoplasm; Autoimmune Diseases; Cancer Vaccines; Colonic Neoplasms; CTLA-4 Antigen; Female; Humans; Immune Tolerance; Immunotherapy; Infusions, Intravenous; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma; Middle Aged; Neoplasm Proteins; Neoplasms; Regression Analysis; T-Lymphocyte Subsets; Treatment Outcome

Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a recently described renal tumour entity with frequent cytokeratin (CK)20 positivity, commonly harbouring TSC mutations. In contrast, frequency of CK20 expression and presence of TSC mutations are unclear in TFEB-amplified RCC and TFEB-translocated RCC, which frequently express Melan A. Herein, we provide a comparative analysis of six ESC RCC with four TFEB-amplified/translocated RCC.. We assessed the frequency of CK20 and Melan A expression by immunohistochemistry and of TSC mutations by next-generation sequencing. TFEB alterations were confirmed by fluorescence in-situ hybridisation (FISH). All tumours showed voluminous eosinophilic cells with granular cytoplasm, prominent nucleoli, and most showed admixture of solid and cystic areas. CK20 expression was found in all six ESC RCC and in all RCCs with TFEB alterations. Melan A positivity was identified in five of six ESC RCC and four of four RCC with TFEB alterations. We found TSC mutations in two ESC RCCs, including in one case also harbouring a CIC fusion, and identified a TSC mutation in one TFEB-amplified RCC.. ESC RCC represents an emerging renal tumour entity with some histological, immunohistochemical and molecular overlap to TFEB-amplified/translocated RCC. FISH for TFEB aids in this differential diagnosis in challenging cases.

Topics: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Kidney Neoplasms; MART-1 Antigen

The renal angiomyolipoma (AML) is a benign tumor characteristically composed of fat, smooth muscle tissue, and vessels. We collected AMLs from our nephrectomy database, reclassified them according to their histological appearance, recorded the demographic, clinical, and pathological parameters, and compared them with oncocytoma (RO) and renal cell carcinoma (RCC). Immunohistochemistry was ordered in 41 cases. In 2224 nephrectomies, we found 52 AMLs with a 53 mm median size. The mean age was 52.76. Forty-eight tumors were sporadic, while four were hereditary. The revision resulted in 31 classic, 13 leiomyoma-like, five lipoma-like, two epithelioid, and one AML with epithelial cysts. SMA was diffusely positive, except for the epithelioid type, while MelanA harbored stronger expression than HMB45. AML was more frequent in females and appeared ten and 7 years earlier than RO and RCC, respectively. The follow-up time was 7.42 years, and neither tumor-related death nor relapse occurred. AML is rare in nephrectomies and develops primarily in females in their 50s with an average size of 50-60 mm at the surgery. The histological appearance in order of frequency is classic, leiomyoma-like, lipoma-like, epithelioid, and cystic. The MelanA, HMB45, and SMA immunohistochemistry can support the light-microscopic findings.

Topics: Angiomyolipoma; Antibodies, Monoclonal; Carcinoma, Renal Cell; Female; Hamartoma; Humans; Kidney; Kidney Neoplasms; Leiomyoma; Lipoma; MART-1 Antigen; Middle Aged

BACKGROUND Microscopic tumor foci have been detected incidentally on renal biopsy, including renal cell carcinoma and renomedullary interstitial cell tumor (medullary fibroma). A report is presented of a case of an incidental finding of microscopic renal angiomyolipoma that was diagnosed and completely excised on core needle biopsy. CASE REPORT A 44-year-old woman was referred to our hospital for evaluation of persistent mild proteinuria. Three years previously, she was diagnosed with Cushing's syndrome associated with a right adrenal cortical adenoma, which was successfully treated with unilateral adrenalectomy. At the time of surgery, abdominal computed tomography (CT) showed no renal lesions. During the present admission, a renal biopsy was performed that showed minimal changes in the renal glomeruli and interstitium. Immunofluorescence showed weakly positive staining for IgM in the glomeruli and no dense deposits. A microscopic focus of a predominantly spindle-cell tumor was found in the corticomedullary region. Immunohistochemistry showed positive immunostaining for HMB-45, Melan-A, and alpha-smooth muscle actin (ASMA), which supported a diagnosis of angiomyolipoma. Abdominal ultrasound at one-year follow-up showed no evidence of residual renal tumor. CONCLUSIONS To our knowledge, this is the first reported case of a completely excised incidental microscopic renal angiomyolipoma. This case demonstrated that even when imaging findings are normal, renal biopsy may detect microscopic foci of primary renal tumors.

Topics: Actins; Adult; Angiomyolipoma; Biomarkers, Tumor; Biopsy, Large-Core Needle; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Incidental Findings; Kidney Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens

Angiomyolipoma with epithelial cysts (AMLEC) is a distinctive variant of angiomyolipoma characterized by grossly apparent epithelial cysts and a cellular, müllerian-like subepithelial stroma. Some authors suspect that the epithelial cysts mainly represent dilated entrapped native renal collecting duct epithelium, while other authors think that they represented true epithelial differentiation of the AML. Recently, it has been reported that obvious immunolabeling of melanocytic markers such as Melan A and HMB45, which are often immunolabeled in classical angiomyolipoma, are present in epithelial cysts in cases of AMLEC. Here, we report the case of a 43-year-old Japanese woman with AMLEC, and attempt to elucidate the significance of melanocytic marker immunolabeling in the cyst's epithelium. In the present case, Melan A was labeled in the cyst's epithelium, and was thought to reflect its labeling in renal tubules existing in the renal parenchyma outside the tumor. This finding may indicate that the cyst epithelium is derived from entrapped renal tubules inside the AML. Non-immunolabeling of the estrogen and progesterone receptors in the cyst epithelium may also suggest that the cyst epithelium is not neoplastic, in contrast to their labeling in neoplastic cells existing in cyst wall. Further examination, such as molecular analysis, is needed to determine whether these epithelial cysts is neoplastic or non-neoplastic.

Topics: Adult; Angiomyolipoma; Biomarkers, Tumor; Cysts; Epithelium; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Kidney Tubules; MART-1 Antigen

Topics: Adult; Angiomyolipoma; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Humans; Kidney Neoplasms; Liver Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasms, Multiple Primary; Tomography, X-Ray Computed; Tuberous Sclerosis; Young Adult

To study the clinicopathologic features, immunophenotype and genetic changes of perivascular epithelioid cell neoplasms (PEComa).. A total of 25 cases of PEComa located in various anatomic sites were selected for immunohistochemical staining (SP or EnVision method). TFE3 fluorescence in-situ hybridization was also performed to determine the TFE3 gene status.. The age of patient ranged from 21 to 61 years (mean = 43 years). The male-to-female ratio was 1: 1.3. Histologically, 22 cases represented conventional angiomyolipomas, composed of a mixture of adipose tissue, spindle element, epithelioid smooth muscle cells and abnormal thick-walled blood vessels in various proportions. Three cases involving lung, soft tissue and broad ligament had subtle but distinctive morphologic features. Nested or sheet-like architecture with epithelioid or spindle cells was observed. Immunohistochemical study showed that HMB 45, melan A, smooth muscle actin and cathepsin K were expressed in 80% (20/25), 88% (22/25), 88% (22/25) and 100% (25/25) of PEComa, respectively. Within positive cases, the average proportion of positive tumor cells was 36%, 41%, 35% and 90% respectively for HMB 45, melan A, smooth muscle actin and cathepsin K. TFE3 was negative in all of the 22 renal and hepatic PEComa studied, while it was positive in the 3 cases of extra-hepatorenal PEComa. None of the 25 cases exhibited evidence of TFE3 gene fusion or amplification.. Extra-hepatorenal PEComa have distinctive morphologic features and are associated with TFE3 overexpression. Cathepsin K immunostaining demonstrates high sensitivity and specificity in PEComa, better than other commonly employed immunomarkers. This marker is thus useful in diagnosis of PEComa and distinction with other neoplasms.

Topics: Actins; Adult; Angiomyolipoma; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cathepsin K; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Kidney Neoplasms; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Perivascular Epithelioid Cell Neoplasms; Young Adult

Two cases of epithelioid angiomyolipoma of the kidney are reported. A 62-year-old female with incidental left renal tumor underwent laparoscopic leftpartial nephrectomy under a diagnosis of renal cell carcinoma. A pathological examination revealed epithelioid angiomyolipoma. The second case was that of a 35-year-old female with back pain. A laparoscopic right nephrectomy revealed epithelioid angiomyolipoma. This recently identified variant of angiomyolipoma is sometimes associated with aggressive clinical behavior including local recurrence and metastasis.

Topics: Adult; Angiomyolipoma; Biomarkers, Tumor; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Humans; Kidney Neoplasms; Laparoscopy; Magnetic Resonance Imaging; MART-1 Antigen; Melanoma-Specific Antigens; Nephrectomy; Tomography, X-Ray Computed; Treatment Outcome

Renal angiomyolipoma (AML) may present as rare variants such as epithelioid and AML with epithelial cysts posing difficulties for the diagnosis to the surgical pathologist. We report a case of a 46-year-old male patient presenting a 5-cm solid tumor in the lower pole of the left kidney, with cystic changes at cut surface. The tumor exhibited 95% of epithelioid cells with atypical nuclei. A small focus of typical AML was observed. The immunoprofile of tumor cells was classical of AML including expression of melanocytic markers such as HMB45 and Melan A. We report the immunohistochemical study of the cystic component in an epithelioid AML. In contrast to the immunoreactivity reported in typical AML, the present case shows obvious expression of melanocytic markers in the cystic epithelial lining. This is strong evidence that these cysts are neoplastic and derived from AML, rather than entrapped native collecting duct epithelium.

Topics: Angiomyolipoma; Biomarkers, Tumor; Cysts; Epithelial Cells; Epithelioid Cells; gp100 Melanoma Antigen; Humans; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Treatment Outcome

To study the clinicopathologic features and differential diagnosis of perivascular epithelioid cell tumors (PEComas) occurring in the urinary system.. The clinicopathologic features of 21 cases of PEComa from September 2002 to September 2010 occurring in the urinary system were retrospectively reviewed. Immunohistochemical study for HMB 45, S-100 protein, smooth muscle actin, desmin, Melan A and Ki-67 was carried out.. Amongst the 21 cases studied, there were 5 males and 16 females. The age of patients ranged from 16 to 76 years (median = 51.3 years). Twenty cases occurred in the kidney and 1 in the bladder. The predominant histopathologic subtype of renal PEComas was classic type (10/20), followed by epithelioid type (5/20), smooth muscle type (3/20), inflammatory type (1/20) and sclerosing type (1/20). Immunohistochemical study showed that HMB 45 and smooth muscle actin were positive in 95.2% (20/21) and 80.9% (17/21) cases, respectively. Melan A, desmin and S-100 protein were expressed in 71.4% (15/21), 61.9% (13/21) and 33.3% (7/21) cases, respectively. The mean proliferative index was 1.29% (range = 0 to 5%). HMB 45 and Melan A were expressed in all of the 5 cases of epithelioid PEComas, whereas smooth muscle actin and desmin were only expressed in one of them. There was no significant difference between epithelioid PEComas and non-epithelioid PEComas in the expression of HMB 45, Melan A, smooth muscle actin and desmin. Positive staining for HMB 45 and smooth muscle actin was demonstrated in the case of bladder PEComa.. PEComas of the urinary system predominantly affect the kidney. Epithelioid renal PEComas and bladder PEComa are relatively rare and have unique pathologic features. It is necessary to distinguish PEComas from other malignant tumors. Immunohistochemical study for HMB 45, Melan A and smooth muscle actin is helpful for confirmation of diagnosis.

Topics: Actins; Adolescent; Adult; Aged; Carcinoma, Renal Cell; Desmin; Diagnosis, Differential; Female; Gastrointestinal Stromal Tumors; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Kidney Neoplasms; Leiomyosarcoma; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Perivascular Epithelioid Cell Neoplasms; S100 Proteins; Urinary Bladder Neoplasms; Young Adult

Translocation-type renal carcinoma has been recently discovered, and it is possible that this tumor may have been previously diagnosed as other types of renal tumor. We have subjected 41 renal tumors, including VHL gene mutation-negative clear cell renal cell carcinoma (RCC), papillary RCC, and chromophobe RCC, to immunohistochemistry of transcription factor E3 (TFE3) and TFEB. All tumors were histologically evaluated by additional immunohistochemical study. As a result, 5 tumors showed a positive reaction for TFE3 with a range from 1+ to 2+ in intensity. No tumors were positive for TFEB. In 5 tumors immunohistochemically positive for TFE3, chimeric transcripts including ASPL-TFE3, PRCC-TFE3, CLTCTFE3, PSF-TFE3, or Nono-TFE3 were not detected. The diagnosis of 6 tumors was changed by reevaluation through retrospective histological and immunohistochemical study. In 4 of 6 tumors, the diagnosis of clear cell RCC was changed to chromophobe RCC. In 1 tumor, oncocytoma was detectable, and RCC with rhabdoid features and sarcomatoid changes was detected in 1 tumor. Finally, the cutoff value of TFE3 immunohistochemistry should be more than 2+ with a wide range. The translocation-type renal carcinoma seems to be quite rare.

Topics: Adenoma, Oxyphilic; Adult; Aged; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cadherins; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Male; MART-1 Antigen; Melanosomes; Middle Aged; Mutation; Proto-Oncogene Proteins c-kit; S100 Proteins; Transcription, Genetic; Von Hippel-Lindau Tumor Suppressor Protein

Topics: Adult; Angiomyolipoma; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Tumor Suppressor Protein p53

To study the pathologic features and immunophenotype of 3 cases of melanotic epithelioid clear cell tumor of kidney.. More than 2000 cases of renal tumors were retrospectively reviewed. Three cases of melanotic epithelioid clear cell tumor were identified. Immunohistochemical study was carried out using the paraffin-embedded tissue samples. Electron microscopy was also performed in 1 case.. Amongst the 3 cases studied, the male-to-female ratio is 1:2. Histologically, 2 cases showed a clear cell carcinoma-like pattern. Papillary structures covered by clear cells and eosinophilic cells were observed in 1 case. Immunohistochemical study showed that the tumor cells in all cases expressed HMB 45. Two of them were also positive for Melan A. The staining for epithelial markers and S-100 protein was negative. Melanosomes were not identified by ultrastructural examination.. Melanotic epithelioid clear cell tumor is a rarely seen neoplasm of kidney. There are some histologic overlaps with renal cell carcinoma, epithelioid angiomyolipoma and melanoma. Immunohistochemical study is useful in confirming the diagnosis. The tumor represents a morphologic variant of epithelioid angiomyolipoma.

Topics: Adolescent; Adult; Angiomyolipoma; Carcinoma, Renal Cell; Diagnosis, Differential; Epithelioid Cells; Female; Follow-Up Studies; Humans; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Retrospective Studies

Diagnosis of low-grade clear cell lesions in kidney can be challenging to the pathologist in practice. There is limited information in the literature addressing the practical issues that may be encountered in this regard. Herein is presented two cases: one was an adrenal cortical nodule; the second, an intrarenal adrenal heterotopia that was assumed to be renal cell carcinoma initially. Certain red flags should prompt pathologists to investigate further; close morphological examination including immunohistochemistry may be warranted in these lesions.

Topics: Adrenal Cortex; Antigens, Neoplasm; Biomarkers; Carcinoma, Renal Cell; Choristoma; Diagnosis, Differential; Female; Humans; Kidney Diseases; Kidney Neoplasms; MART-1 Antigen; Middle Aged; Mucin-1; Neoplasm Proteins

A unique case of a mixed epithelial stromal tumor (MEST) that was predominantly composed of adipose tissue is reported here. Radiographically and grossly, the lesion was thought to be an angiomyolipoma, based upon its fatty appearance. Microscopically, the lesion was predominantly composed of mature adipose tissue but also contained clusters of bland tubules surrounded by smooth muscle bundles and collagen. By immunohistochemistry, the stroma labeled diffusely for estrogen and progesterone receptors, while the muscle bundles labeled for desmin. Melanocytic markers HMB45 and Melan A, typically positive in angiomyolipoma, were nonreactive. This case expands the morphologic spectrum of MEST to include mimics of angiomyolipoma.

Topics: Adipose Tissue; Aged; Angiomyolipoma; Antigens, Neoplasm; Desmin; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Kidney Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasm Proteins; Neoplasms, Complex and Mixed; Nephrectomy; Receptors, Estrogen; Receptors, Progesterone

Presented herein are two unusual epithelioid angiomyolipomas (AML) displaying prominent stromal sclerosis. Both patients were middle-aged women without a clinical history of tuberous sclerosis. One patient (case 1) had a 2 cm lesion arising in the renal cortex, and another (case 2) had a pararenal retroperitoneal tumor measuring 13 cm. Both tumors were composed of sheets or nests of polygonal epithelioid or short spindle cells having uniform round to oval nuclei and eosinophilic cytoplasm with cords of hyalinized sclerotic stroma between them. The tumor in case 2 had small areas of mature-looking fat cells. Immunohistochemically, epithelioid tumor cells were diffusely positive for actins and desmin in both cases, and melanoma antigen recognized by T cells (MART)-1 was positive in patient 2. Scattered HMB-45-immunoreactive cells were identified in the sclerotic cords of both tumors, but epithelioid tumor cells were essentially negative for HMB-45. The characteristic clinicopathological and immunohistochemical features of the present cases are analogous to a subset of epithelioid AML or sclerosing perivascular epithelioid cell tumors previously reported.

Topics: Angiomyolipoma; Antigens, Neoplasm; Biomarkers, Tumor; Epithelioid Cells; Female; Humans; Immunoenzyme Techniques; Kidney Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Retroperitoneal Neoplasms; Sclerosis

Renal angiomyolipoma is a tumor composed of varying amounts of fat, smooth muscle, and blood vessels. Characteristically, tumor cells express melanocytic markers such as HMB-45 and Melan-A. Recently, several other markers have been described as having excellent diagnostic sensitivity in cutaneous melanocytic lesions.. To compare the sensitivities of 5 melanocytic markers in renal angiomyolipoma and to study the expression patterns of these markers in the 3 different components of angiomyolipoma.. A tissue microarray of 20 renal angiomyolipomas was constructed. For each case, 3 cores containing fat, blood vessels, and smooth muscle were taken. The tissue microarray was then stained for HMB-45, Melan-A, tyrosinase, NK1-C3, and CD117.. HMB-45 was positive in 95%, Melan-A in 85%, NK1-C3 in 70%, tyrosinase in 50%, and CD117 in 40% of the cases. All (20/20) were positive for HMB-45 and Melan-A combined. These 5 markers had different sensitivities in the 3 components. HMB-45 was positive in 90%, 85%, and 80% of fat, smooth muscle, and blood vessel components, respectively; Melan-A in 70%, 60%, and 40%; NK1-C3 in 55%, 55%, and 45%; tyrosinase in 30%, 40%, and 10%; and CD117 in 20%, 40%, and 10%, respectively, of these 3 components.. HMB-45 and Melan-A combined were positive in 100% of the renal angiomyolipomas. We recommend the use of these 2 markers in the workup of this entity, including those with predominantly 1 component. Other melanocytic markers are of limited use. A tissue block comprising predominantly fat or smooth muscle components should be used when performing melanocytic marker immunostain.

Topics: Adipose Tissue; Adult; Aged; Angiomyolipoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Blood Vessels; Female; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Male; MART-1 Antigen; Melanocytes; Melanoma-Specific Antigens; Middle Aged; Monophenol Monooxygenase; Muscle, Smooth; Neoplasm Proteins; Proto-Oncogene Proteins c-kit; Sensitivity and Specificity

This report deals with 11 examples of renal angiomyolipomas (AML) which appear to include an epithelial element as a part of the neoplasm in the form of gross or microscopic cysts-usually both. There were seven females and four males between the ages of 20 and 70 years with mean age of 45 years. Three of these were known to be symptomatic: intermittent flank pain and gross hematuria for 2 months; recurrent hematuria both before and after flank trauma and a third patient with acute abdomen due to a ruptured tumor blood vessel. Cysts were described in three of the six cases where radiographic data were available. Seven tumors were in the right kidney and four in the left. In gross descriptions, cysts were mentioned in seven and they ranged from 6.0 to 2.0 cm with a median and mean maximal diameter of 5.0 and 4.0 cm, respectively. Microscopically, virtually all of the tumors included multiple smaller cysts and these were lined by flat, cuboidal or columnar epithelium and occasionally hobnail epithelium. There was usually a subepithelial collar of poorly differentiated cells, but the solid element of all tumors was myomatous angiomyolipoma; only one case had any adipose tissue. A dominant histological feature was the prominent lymphatic channels-identical to those of lymphangiomyomas and myomatous or triphasic AMLs. They are much more conspicuous in these cystic cases. Immunohistochemically, all tumors tested were reactive with actin, desmin and HMB-45, with the latter being more intensely positive in the subepithelial collars. Estrogen and progesterone receptors were usually positive, also. The behavior of these lesions appears to be no different from that of other AMLs.

Topics: Actins; Adult; Aged; Angiomyolipoma; Antigens, Neoplasm; Cysts; Desmin; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Muscle, Smooth; Neoplasm Proteins; Receptors, Estrogen; Receptors, Progesterone

The epithelioid variant of angiomyolipoma (EAML) is a rare tumor of unpredictable behavior that is composed of epithelioid, spindle, and giant cells and contains no or only a minimal amount of lipomatous tissue. The picture can lead to an erroneous diagnosis of renal cell carcinoma or sarcoma. We report on a case of EAML in the kidney of a 47-year-old female without any signs of tuberous sclerosis and review the literature. Grossly, a well-demarcated, spheroid, largely hemorrhagic tumor measuring 4.2 cm in diameter occupied the central third of the kidney. Histologically, it was solid, highly cellular, with occasional microcysts, composed of medium to large epithelioid cells with clear or oxyphilic cytoplasm, short spindle cells, and numerous giant multinucleated cells. After extensive sampling, adult-appearing fat tissue was found to present as rare foci of microscopic dimensions. Immunohistochemically, the tumor cells showed positive reactions with antibodies against HMB-45, melan A, CD-68, muscle-specific actin, and, rarely, smooth muscle actin. Cytokeratins and epithelial membrane antigen were negative. The EAML is a variant growing in a carcinoma-like pattern that can lead to an erroneous diagnosis of renal cell carcinoma. An extensive sampling and HMB-45 and CD-68 positivity combined with cytokeratin negativity are of paramount importance for the correct diagnosis. As a sporadic renal tumor it followed a benign course in most of the reported cases.

Topics: Actins; Angiomyolipoma; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Epithelioid Cells; Female; Giant Cells; Humans; Kidney Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Treatment Outcome

We report 3 recent cases of angiomyolipoma of the kidney. Although generally regarded as a benign neoplasm, angiomyolipoma rarely behaves in an aggressive manner, producing complicated clinical courses leading to metastasis and death. The presence of epithelioid elements within the tumor can result in difficulty differentiating benign from malignant angiomyolipoma and differentiating this tumor from renal adenocarcinoma. The presence of lymph node involvement can cause difficulty in differentiating multicentric disease in lymph nodes from metastasis to lymph nodes. The presence of cytologic abnormalities in the primary tumor can result in difficulty in differentiating atypia in benign angiomyolipoma from malignant sarcomatous transformation of a benign lesion. The 3 cases reported show many of these problems. Criteria for predicting malignancy in epithelioid tumors and sarcomatous transformation are not well recognized because of the rarity of this entity. The typical immunophenotype of all types of angiomyolipoma (cytokeratin-negative and melanomarkers-positive) is very useful in diagnosis but does not help in the differentiation from renal adenocarcinoma at frozen section. We report the empiric use of Ki67 and p53 in these cases as adjuncts to clinical and histologic assessment in predicting behavior. High Ki67 expression was a feature of malignant epithelioid angiomyolipoma. Low levels of p53 expression were seen in the angiomyolipoma with sarcomatous transformation. Benign angiomyolipomas were consistently negative for both Ki67 and p53.

Topics: Adult; Angiomyolipoma; Antigens, Neoplasm; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Kidney Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Tumor Suppressor Protein p53; Vimentin

Melanoma markers, especially the new microphthalmia transcription factor (mitf), have not been previously compared in hepatic and renal angiomyolipomas.. To evaluate expression of the novel melanocytic markers mitf and tyrosinase in angiomyolipomas, and to compare these markers with the established markers HMB-45 and melan-A in both hepatic and renal tumors.. Clinical, histopathologic, and immunohistochemical features of 15 hepatic angiomyolipomas were compared with those of 10 renal angiomyolipomas.. No significant differences between patients with hepatic angiomyolipomas and renal angiomyolipomas were found with respect to age, gender, race, and tumor size. Hepatic angiomyolipomas exhibited a predominance of the epithelioid smooth muscle cell component, in contrast to their renal counterparts, which were predominantly spindled. The smooth muscle cells expressed HMB-45 in 100% of cases in both groups, melan-A in 14 of 15 hepatic angiomyolipomas and 8 of 9 renal angiomyolipomas, mitf in 5 of 12 hepatic angiomyolipomas versus 6 of 10 renal angiomyolipomas, and tyrosinase in 3 of 12 and 2 of 10 hepatic angiomyolipomas and renal angiomyolipomas, respectively. The extent and intensity of immunostaining with HMB-45 and melan-A were dependent on whether spindled or epithelioid cells predominated; the epithelioid cells showed stronger and more widespread reactivity than the spindled cells.. We believe that the best immunohistochemical marker for confirming the diagnosis of angiomyolipoma is HMB-45, followed by melan-A. Routine use of mitf and/or tyrosinase is not indicated.

Topics: Adult; Aged; Angiomyolipoma; Antigens, Neoplasm; Biomarkers, Tumor; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Microphthalmia-Associated Transcription Factor; Middle Aged; Monophenol Monooxygenase; Neoplasm Proteins; Transcription Factors

By stimulating human lymphocytes with an autologous renal carcinoma, we obtained CTL recognizing an antigen derived from a novel, ubiquitous protein. The CTL failed to lyse autologous EBV-transformed B cells, even though the latter express the protein. This is due to the presence in these cells of immunoproteasomes, which, unlike standard proteasomes, cannot produce the antigenic peptide. We show that dendritic cells also carry immunoproteasomes and fail to present this antigen. This may explain why the relevant CTL escape thymic deletion and are not regularly activated in the periphery. Lack of cleavage by the immunoproteasome was also observed for melanoma differentiation antigen Melan-A26-35/HLA-A2, currently used for antitumoral vaccination. For immunization with such antigens, proteins should be less suitable than peptides, which do not require proteasome digestion in dendritic cells.

Topics: Antigen Presentation; Antigens, Neoplasm; B-Lymphocytes; Base Sequence; Cell Line, Transformed; Cysteine Endopeptidases; Dendritic Cells; DNA, Complementary; Herpesvirus 4, Human; Humans; Kidney Neoplasms; MART-1 Antigen; Melanoma; Molecular Sequence Data; Multienzyme Complexes; Neoplasm Proteins; Peptides; Proteasome Endopeptidase Complex; Proteins; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured

We tested 505 cases of nonhematopoietic neoplasms by immunohistochemistry using a newly characterized monoclonal antibody (clone 56C6) against the CD10 antigen. CD10 was expressed widely in neoplasms of the genitourinary tract, including 41 (89%) of 46 cases of renal cell carcinoma, 13 (54%) of 24 cases of transitional cell carcinoma, and 11 (61%) of 18 cases of prostatic adenocarcinoma. In addition, 5 (100%) of 5 endometrial stromal sarcomas, 3 (60%) of 5 rhabdomyosarcomas, 7 (50%) of 14 pancreatic adenocarcinomas, 5 (45%) of 11 cases of schwannoma, and 12 (40%) of 30 cases of malignant melanoma also were positive for CD10. Similar to normal tissue, CD10 positivity was restricted to the apical surface of malignant glandular cells of well-differentiated colonic, pancreatic, and prostatic adenocarcinoma, whereas in poorly differentiated adenocarcinoma and other tumors, such as melanoma, transitional cell carcinoma, renal cell carcinoma, and endometrial stromal sarcoma, the CD10 positivity showed diffuse cytoplasmic or membranous/Golgi patterns. The monoclonal antibody clone 56C6 is a reliable marker for CD10 in paraffin immunohistochemistry after heat-induced epitope retrieval. CD10 expression in renal cell carcinoma and endometrial stromal sarcoma may be a useful marker in the differential diagnoses of these tumors because both tumors otherwise lack specific markers.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Renal Cell; Diagnosis, Differential; Endometrial Neoplasms; Female; Hematologic Neoplasms; Humans; Immunoenzyme Techniques; Kidney Neoplasms; Male; MART-1 Antigen; Neoplasm Proteins; Neprilysin; Paraffin Embedding; Sarcoma, Endometrial Stromal

Angiomyolipomas are tumours of uncertain histogenesis, most often occurring in association with the kidney. A characteristic finding is their reactivity with HMB-45, a monoclonal antibody to the melanocyte-associated antigen gp-100. We tested 18 angiomyolipomas for their reactivity with A103, a monoclonal antibody to Melan-A (MART-1), another melanocyte-associated marker, and compared it with HMB-45. All cases were positive with both antibodies, yet most cases showed a more homogeneous staining pattern with A103. Normal kidney was immunohistochemically negative for both antibodies. We also performed RT-PCR assays for gp-100 and Melan-A in 4 of the 18 angiomyolipoma samples and in three normal kidney samples. All 4 angiomyolipoma specimens revealed mRNA for both melanocyte differentiation markers. gp-100 mRNA was found in the samples of normal kidney, but Melan-A mRNA was not. Our study shows that angiomyolipomas express the melanocyte-associated antigens Melan-A and gp-100 at the protein and at the mRNA level, suggesting a true expression of these antigens rather than cross-reacting epitopes. Based on the mRNA expression pattern, immunohistochemical analysis is the preferred method for the detection of gp-100, while Melan-A can be used at the protein and mRNA levels. Our study demonstrates that A103 is a useful marker for the diagnosis of angiomyolipomas.

Topics: Angiomyolipoma; Antigens, Neoplasm; Biomarkers, Tumor; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Kidney Neoplasms; Liver Neoplasms; MART-1 Antigen; Melanocytes; Membrane Glycoproteins; Neoplasm Proteins; Reverse Transcriptase Polymerase Chain Reaction; Staining and Labeling

Distinguishing adrenal cortical neoplasms from either hepatocellular carcinomas or renal tumors can be difficult. Two recently described antibodies, A103 and inhibin A, are most often reported to be reactive with adrenal cortical neoplasms but with neither hepatocellular carcinoma nor renal cell carcinoma. To compare the sensitivity and specificity of these two antibodies in the diagnosis of adrenal cortical tumors, we stained 22 adrenal cortical adenomas, 4 adrenal cortical carcinomas, 25 hepatocellular carcinomas, and 43 renal tumors, including 33 renal cell carcinomas and 8 oncocytomas, with the A103 and inhibin A using an avidin-biotin complex technique. Fifteen (68%) of 22 adrenal adenomas and 2 (50%) of 4 adrenal cortical carcinomas were reactive with A103. Nineteen (86%) of 22 adrenal adenomas and 3 (75%) of 4 adrenal cortical carcinomas were reactive for inhibin A. None of the renal tumors or hepatocellular carcinomas reacted with A103, but 1 (4%) of 25 hepatocellular carcinomas (a high-grade pleomorphic tumor) and 1 (2%) of 43 renal tumors (a clear-cell renal cell carcinoma) were reactive with inhibin A. The cytoplasmic reactivity for A103 in adrenal tumors was coarsely granular and most common in clear-cell areas. Reactivity for inhibin was either cytoplasmic or membranous and stained both clear-cell and granular areas. We conclude that both antibodies are useful in the immunohistochemical diagnosis of adrenal cortical neoplasms and that A103 is slightly more specific and inhibin slightly more sensitive.

Topics: Adenoma; Adenoma, Oxyphilic; Adrenal Cortex Neoplasms; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Inhibins; Kidney Neoplasms; Liver Neoplasms; Male; MART-1 Antigen; Neoplasm Proteins; Sensitivity and Specificity