glycogen and Adenocarcinoma--Clear-Cell

Clear-cell tumor of the lung is a rare entity of unknown etiology and histogenesis. This neoplasm typically presents as an asymptomatic, peripheral, sharply rounded mass in the lung, and histologically composed of large cells with a clear cytoplasm rich in glycogen, blended with an abundant network of sinusoid-type vessels. Immunohistochemical and ultrastructural procedures lead to diagnosis. We describe a primary pulmonary clear cell "sugar" tumor observed in a 28-year-old woman, and give a review of the literature. Clinical aspects, differential diagnosis, therapy and histogenetic aspects are discussed.

Topics: Adenocarcinoma, Clear Cell; Adult; Antigens, Neoplasm; Biomarkers, Tumor; Cytoplasm; Diagnosis, Differential; Female; Glycogen; Humans; Immunohistochemistry; Lung Neoplasms; Melanoma-Specific Antigens; Neoplasm Proteins; Pneumonectomy; Radiography; Treatment Outcome

Glycogen rich clear cell carcinoma of the breast is a rare neoplasm with different morphological characteristics to ordinary breast carcinomas. However, it has some common features with clear cell carcinomas of other organs. This report describes a case of clear cell carcinoma of the breast with a solid papillary pattern centrally localised in the left breast of a 45 year old woman. Antibodies directed against cytokeratin 7 (CK7), CK10, CK14, CK17, CK18, CK19, CK20, CK5/6/18, CK8/18, high molecular weight cytokeratin AE3, high molecular weight cytokeratin 34betaE12, the oestrogen receptor, the progesterone receptor, chromogranin, S-100 protein, smooth muscle actin, vimentin, and carcinoembryogenic antigen were applied to analyse the immunophenotypical profile of this rare neoplasm.

Topics: Adenocarcinoma, Clear Cell; Antigens, CD; Breast Neoplasms; Cytoplasm; Female; Glycogen; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Middle Aged; Vimentin

A group of lesions show morphologic and immunophenotypic evidence of differentiation toward a putative perivascular epithelioid cell. These so-called PEComas include angiomyolipoma, lymphangiomyoma, lymphangioleiomyomatosis, renal capsuloma, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and clear cell "sugar" tumor. PEComas are characterized by strong immunoreactivity with the HMB45 antibody and variable expression of muscle markers. This family of lesions may be composed of a spectrum of cells from epithelioid to spindle cells with clear to granular eosinophilic cytoplasm. One member of this family, composed of epithelioid cells with glycogen-rich clear cytoplasm, is descriptively called a clear cell "sugar" tumor. This tumor, originally described in the lung, is being recognized increasingly in extrapulmonary sites. We report a case of a primary extrapulmonary clear cell "sugar" tumor occurring in the right breast of a 16-year-old girl. The tumor was composed of clear epithelioid cells with abundant glycogen and distinct cell borders. The tumor showed strong immunoreactivity with HMB45 antibody and Melan-A. There was focal vimentin staining. In addition, there was diffuse and strong nuclear staining for progesterone receptor. Antibodies to actins, S-100 protein, cytokeratins (AE1/AE3 and CAM5.2), desmin, and estrogen receptor were negative. The tumor was completely excised, and the patient is well without evidence of disease 9 months postexcision.

Topics: Adenocarcinoma, Clear Cell; Adolescent; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Cytoplasm; Female; Glycogen; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasm Proteins

Clear cell ("sugar") tumour of the lung is a rare neoplasm, generally presenting as a discrete nodule on the chest X-ray. We report a case of clear cell tumour of the lung in a 64-year-old woman. The tumour at presentation was 1 mm in diameter.

Topics: Adenocarcinoma; Adenocarcinoma, Clear Cell; Antigens, Neoplasm; Biomarkers, Tumor; Diabetes Mellitus, Type 2; Fatal Outcome; Female; Glycogen; Hemoptysis; Humans; Lung Neoplasms; Melanoma-Specific Antigens; Middle Aged; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms, Multiple Primary; Smoking; Solitary Pulmonary Nodule

Clear cell tumors of the lower respiratory tract comprise a diverse group of lesions. The prototypical lesion is the benign clear cell tumor or "sugar tumor," a tumor of enigmatic histogenesis, whose name derives from the high glycogen content of the cells. Analogous to the salivary gland lesion of the same name, acinic cell tumors may also occur in the tracheobroncheal tree. The topic of "clear cell carcinoma" is discussed, which in the opinion of the authors does not constitute a distinct tumor entity. A discussion of potential lesion metastatic to the lung with clear cell histology is also presented. Histological details of the various entities are discussed, as well as the significant histochemical, immunohistological, and electron microscopic features; in particular, such findings that are relevant to differential diagnosis are stressed, including the distinction of primary and metastatic lesions.

Topics: Adenocarcinoma, Clear Cell; Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma, Acinar Cell; Carcinoma, Renal Cell; Child; Diagnosis, Differential; Female; Glycogen; Humans; Immunohistochemistry; Lung Neoplasms; Male; Middle Aged

Glycogen-rich clear cell carcinoma (GRCC) is a very rare form of primary breast cancer (<0.1% of all breast cancers). It is characterized by the presence of neoplastic cells with a glycogen-abundant clear cytoplasm (the Periodic Acid Schiff-positive, diastase-sensitive). The expression of steroid receptors (estrogen and progesterone receptors) has been variably reported (35% to 100% of the cases), whereas most studies reported low human epidermal growth factor receptor 2 positivity in GRCC. High androgen receptor positivity without androgen receptor splice variant-7 was reported in one recent study. Although sparse, the preliminary theranostic data on GRCC indicate the potential of targeted treatments in selected cases (antiandrogen, PIK3CA, and immune checkpoint inhibitors). Because of its rarity, the prognosis for GRCC patients remains controversial. Herein, we comprehensively appraise the epidemiological, morphologic, molecular, and clinical characteristics of this rare mammary malignancy.

Topics: Adenocarcinoma, Clear Cell; Biomarkers, Tumor; Breast Neoplasms; Female; Glycogen; Humans; Incidence; Molecular Targeted Therapy; Prognosis; Receptor, ErbB-2

A 48-year-old woman had a left breast mass identified during routine breast cancer screening. The mammogram showed pleomorphic-segmental microcalcifications in the mediolateral-oblique view of the left breast. Ultrasonography showed a hypoechoic mass approximately 3.7 cm in diameter with multiple calcifications. Contrast-enhanced magnetic resonance imaging of the breast showed non-mass like enhancement of approximately 4 cm in diameter in the C area of the left breast. She was diagnosed with glycogen-rich clear cell carcinoma (GRCC) by ultrasound-guided vacuum-assisted biopsy. Nipplesparing mastectomy was performed along with sentinel lymph node biopsy. The intraoperative consultation suggested sentinel lymph node metastasis and we therefore performed axillary lymph node dissection. Pathological examination reported microinvasive carcinomas, 0.4 cm in maximum diameter, and extensive intraductal components, 5 cm in size. The tumor cells were stained on PAS staining, but the stains were digested with diastase. The cells were negative for adipophilin. GRCC was first reported by Hull et al. This is a rare type of breast carcinoma. There is no standard therapy for this disease or any data on the prognosis of breast cancer patients with GRCC.

Topics: Adenocarcinoma, Clear Cell; Axilla; Breast Neoplasms; Female; Glycogen; Humans; Lymph Nodes; Mastectomy; Middle Aged; Neoplasm Micrometastasis; Prognosis; Sentinel Lymph Node Biopsy

Topics: Adenocarcinoma, Clear Cell; Aged; Biopsy; Cell Differentiation; Gastrectomy; Glycogen; Humans; Male; Staining and Labeling; Stomach Neoplasms

Epithelial ovarian carcinoma (EOC), the major cause of gynaecological cancer death, is a heterogeneous disease classified into five subtypes. Each subtype has distinct clinical characteristics and is associated with different genetic risk factors and molecular events, but all are treated with surgery and platinum/taxane regimes. Tumour progression and chemoresistance is generally associated with major metabolic alterations, notably altered mitochondrial function(s). Here, we report for the first time that the expression of the mitochondrial regulators PGC1α and TFAM varies between EOC subtypes; furthermore, we have identified a profile in clear-cell carcinoma consisting of undetectability of PGC1α/TFAM, and low ERα/Ki-67. By contrast, high-grade serous carcinomas were characterised by a converse state of PGC1α/TFAM, ERα positivity and a high Ki-67 index. Interestingly, loss of PGC1α/TFAM and ERα was found also in a non-clear cell EOC cell line made highly resistant to platinum in vitro. Similar to clear-cell carcinomas, these resistant cells also showed accumulation of glycogen. Altogether, our data provide mechanistic insights into the chemoresistant nature of ovarian clear-cell carcinomas. Furthermore, these findings corroborate the need to take into account the diversity of EOC and to develop subtype specific treatment strategies.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Line, Tumor; Cystadenocarcinoma, Serous; Disease Progression; DNA-Binding Proteins; Drug Resistance, Neoplasm; Female; Glycogen; Humans; Middle Aged; Mitochondrial Proteins; Ovarian Neoplasms; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Prognosis; Transcription Factors

Clear cell carcinoma (CCC) is a histologically distinct carcinoma subtype that arises in several organ systems and is marked by cytoplasmic clearing, attributed to abundant intracellular glycogen. Previously, transcription factor hepatocyte nuclear factor 1-beta (HNF1B) was identified as a biomarker of ovarian CCC. Here, we set out to explore more broadly the relation between HNF1B and carcinomas with clear cell histology. HNF1B expression, evaluated by immunohistochemistry, was significantly associated with clear cell histology across diverse gynecologic and renal carcinomas (P<0.001), as was hypomethylation of the HNF1B promoter (P<0.001). From microarray analysis, an empirically-derived HNF1B signature was significantly enriched for computationally-predicted targets (with HNF1 binding sites) (P<0.03), as well as genes associated with glycogen metabolism, including glucose-6-phophatase, and strikingly the blood clotting cascade, including fibrinogen, prothrombin and factor XIII. Enrichment of the clotting cascade was also evident in microarray data from ovarian CCC versus other histotypes (P<0.01), and HNF1B-associated prothrombin expression was verified by immunohistochemistry (P = 0.015). Finally, among gynecologic carcinomas with cytoplasmic clearing, HNF1B immunostaining was linked to a 3.0-fold increased risk of clinically-significant venous thrombosis (P = 0.043), and with a 2.3-fold increased risk (P = 0.011) in a combined gynecologic and renal carcinoma cohort. Our results define HNF1B as a broad marker of clear cell phenotype, and support a mechanistic link to glycogen accumulation and thrombosis, possibly reflecting (for gynecologic CCC) derivation from secretory endometrium. Our findings also implicate a novel mechanism of tumor-associated thrombosis (a major cause of cancer mortality), based on the direct production of clotting factors by cancer cells.

Topics: Adenocarcinoma, Clear Cell; Blood Coagulation; Blood Coagulation Factors; Carcinoma, Renal Cell; Computational Biology; DNA Methylation; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Glucose-6-Phosphatase; Glycogen; Hepatocyte Nuclear Factor 1-beta; Humans; Immunohistochemistry; Kidney Neoplasms; Oligonucleotide Array Sequence Analysis; Ovarian Neoplasms; Risk; Venous Thrombosis

Glycogen rich clear cell carcinoma (GRCC) of the breast is a rare subtype of invasive ductal carcinoma and involves a poor prognosis. In the literature, less than 150 cases have been reported. Many researchers have attempted to characterize GRCC according to electron microscope, flow cytometry, or clinical data. However, an organized study of the immunophenotype of GRCC has yet to be reported.. Here, we present three cases of GRCC and their immunohistochemical profiles.. Histologically, all three cases contained periodic acid stain (PAS) positive and d-PAS labile granules in their clear cytoplasm. Case I showed positivity for only estrogen receptor (ER) and c-erbB2. Case II exhibited positivity for progesterone receptor and negativity for ER and c-erbB2. Case III presented with triple negative invasive carcinoma. The expression pattern of E-cadherin was concordant with epidermal growth factor receptor and c-kit, but discordant with ki-67. Among these three cases, p53-positive cases exhibited a low proliferative index (ki-67: 15%), while p53-negative cases showed a high proliferative index (ki-67: 50-60%).. In conclusion, the immunophenotype of GRCC is not uniform, but is similar to that of conventional ductal carcinoma.

Topics: Adenocarcinoma, Clear Cell; Breast Neoplasms; ErbB Receptors; Female; Glycogen; Humans; Immunohistochemistry; Immunophenotyping; Ki-67 Antigen; Proto-Oncogene Proteins c-kit; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone

Glycogen-rich carcinoma of the breast is a rare histological subtype of breast cancer, usually reported to have poor prognosis.. We present the case of a 59-year-old woman who underwent a mastectomy for a 3.5 cm clinically palpable left breast carcinoma, originally diagnosed as fibroadenoma on a screening mammogram four years before presentation. Diagnosis of clear cell carcinoma was based on certain histological characteristics of the tumour and immunohistochemical analysis (PAS staining, keratins AE1/AE3, EMA, cytokeratin 7, cytokeratin 20, melanosomes, vimentin, Chromogranin, Synaptophysin, S-100, SMA). No lymph node metastasis was found and as the tumour was ER positive and PgR negative, patient was treated only with an aromatase inhibitor upfront and remains free of disease 48 months now since operation.. Glycogen-rich clear cell carcinoma of the breast is a rare tumor, its clinical behavior reported to be rather aggressive so far, might varies depending on special characteristics such as low grade and strongly positive ER expression.

Topics: Adenocarcinoma, Clear Cell; Breast Neoplasms; Female; Glycogen; Humans; Lymphatic Metastasis; Middle Aged

Clear cell (CRCC) and papillary (PRCC) renal cell carcinomas (RCC) are the two most frequent subtypes of RCC. In this study, we studied RCC which displayed a hybrid morphology with areas of PRCC and CRCC or which contained papillary structures with clear cell changes (CCC). Consecutive cases of RCC collected over a 12-year period were reviewed to identify RCC with papillary structures and a possible admixture between CRCC and non-oncocytic PRCC. Special stains for glycogen and immunostaining for cytokeratin 7 were applied to sections containing both areas of classical PRCC and PRCC with CCC. Of the total of 541 RCC retrieved, there were 68 non-oncocytic RCC having papillary structures that could be grouped into: (a) group 1 (15 cases), CRCC with areas of papillary formation; (b) group 2a (9 cases), PRCC with extensive CCC with areas of foamy epithelial cells or macrophages; (c) group 2b (18 cases), RCC with areas of classical PRCC with focal CCC; and (d) group 3 (26 cases), RCC with features of groups 2a and 2b and containing areas of classical CRCC. There was a high rate (12/68) of sarcomatous transformation in the study cases. Groups 2 and 3 were associated with a higher rate of vascular invasion, distant metastasis, and mortality than classical PRCC and a higher rate of lymph node metastasis than CRCC. Our study identifies two groups of RCC (referred to as groups 2 and 3) that exhibit characteristic cytohistopathologic hybrid features that set them apart from classical RCC. This type of hybrid tumor seems to be associated with a more aggressive biologic behavior, and its recognition may facilitate the classification of RCC with ambiguous morphology.

Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Papillary; Biomarkers, Tumor; Canada; Carcinoma, Renal Cell; Glycogen; Humans; Immunoenzyme Techniques; Keratin-7; Kidney Neoplasms; Survival Rate

We report a case of clear cell "sugar" tumour of the lung (CCTL) occurring in a 26-year-old lady. The patient was asymptomatic and the lesion was picked up in the course of a pre-employment medical examination. A well-defined 5 cm nodule in the right lower lobe was detected on routine chest X-Ray. Microscopical examination of the coin lesion showed clear cells containing abundant diastase-sensitive intracytoplasmic glycogen, as demohstrated with periodic acid-Schiff stains. Tumour immunoreactivity for HMB-45 and non-reactivity for cytokeratin support the histological diagnosis. To our knowledge, this is the first reported case of CCTL in Malaysia.

Topics: Adenocarcinoma, Clear Cell; Adult; Antigens, Neoplasm; Biomarkers, Tumor; Female; Glycogen; Humans; Lung Neoplasms; Melanoma-Specific Antigens; Neoplasm Proteins; Periodic Acid-Schiff Reaction; Radiography, Thoracic; Treatment Outcome

Twenty cases of invasive ductal carcinoma of the breast with a pure or partial glycogen-rich clear cell carcinoma(GRCC)component are reported. GRCC of the breast is composed almost entirely of polygonal cells with clear cytoplasm. These contain large amounts of partly water-soluble glycogen.. The cases were analyzed using various parameters, including age at presentation, tumor size, tumor grade, axillary lymph node and Her2/neu status.. Between 1990 and 2004, 723 patients with primary breast carcinomas were treated and clinicopathologic analysis was performed. 20 cases were identified as GRCC among the 723 cases. The patients' age at presentation ranged from 33 to 68 years (mean, 52 years). Tumor size ranged from 1 to 6.5 cm (mean, 2.6 cm); 35% (7 of 20) of cases that underwent axillary dissection had positive lymph nodes. Among 15 of 20 cases who were followed for 1-72 months, 5 cases died from their breast carcinoma within 5 years following the diagnosis.. Our series included more small size carcinomas than did previous series. Lymph node status does not appear to be markedly different from that of the usual invasive ductal carcinomas. Her2/neu expression was similar to that found in common breast carcinomas.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Genes, erbB-2; Glycogen; Humans; Lymphatic Metastasis; Middle Aged; Prognosis

Clear cells have been described in many tumors of varying differentiation. Although clear cell carcinoma is well-recognized in the lower urinary and female genital tracts, its occurrence in the gastrointestinal tract and related structures is uncommon. There have been only a few case reports and small series reporting this morphologic phenomenon in the stomach, colon, and biliary tract. Clear cell carcinoma of the endometrium has been associated with poor prognosis, but the prognostic significance of clear cells in gastric adenocarcinoma is unknown. Herein we describe three cases of clear cell, glycogen-rich, gastric adenocarcinoma and evaluate the frequently used classification systems for gastric cancer. Two tumors showed a tubulopapillary pattern and one showed a predominantly diffuse sheet-like growth. The proliferation (MIB) index in all cases was approximately 20%. Only case 1 showed focal staining for alpha-fetoprotein and both cases 1 and 2 showed focal carcinoembryonic antigen reactivity. In conclusion, we describe three cases of clear cell gastric carcinoma that presented as high-stage disease.

Topics: Adenocarcinoma, Clear Cell; alpha-Fetoproteins; Carcinoembryonic Antigen; Cell Division; Female; Gastrectomy; Glycogen; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Staining and Labeling; Stomach Neoplasms

Clear cell tumors of the lung are commonly primary, clear-cell, bronchial carcinomas or metastasis of a renal cell carcinoma. Compared to this, pulmonary sugar tumor is a rare entity. A large intracellular content of glycogen and immunohistochemical procedures lead to diagnosis. The demonstration of the premelanosomal protein HMB-45 is considered as proof, but this is not airtight. We present a case of metachronic, benign, and HMB-45-negative sugar tumor of the lung after hypernephroma and give a review of the literature.

Topics: Adenocarcinoma, Clear Cell; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Glycogen; Humans; Kidney Neoplasms; Lung; Lung Neoplasms; Male; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Neoplasms, Multiple Primary; Nephrectomy; Pneumonectomy; Postoperative Complications; Thoracoscopy; Tomography, X-Ray Computed

Primary clear cell carcinoma of the breast is a rare tumor. The clear cell morphology of the neoplastic population in these tumors has been ascribed to the presence of intracellular lipid, mucin or glycogen, or to myoepithelial, apocrine, or neuroendocrine differentiation. However, a clear cell neoplasm exhibiting evidence of a range of differentiation has not been previously reported. We describe a case of a glycogen-rich primary clear cell breast carcinoma occurring in a 59-year-old woman that showed positivity for apocrine and neuroendocrine markers, as well as possible myoepithelial differentiation. The tumor was a 4-cm mass composed predominantly of periodic acid-Schiff-positive clear cells arranged in a solid, infiltrative pattern. Immunohistochemical staining of the tumor cells was variably positive for cytokeratin, progesterone receptors, gross cystic disease fluid protein-15, neuron specific enolase, chromogranin, and S-100 protein and negative for estrogen receptors, smooth muscle actin, CD31, and CD34. The patient refused any form of further investigation or treatment, but shows no evidence of recurrence or metastatic disease after 18 months of follow-up.

Topics: Adenocarcinoma, Clear Cell; Biomarkers, Tumor; Breast Neoplasms; Cytoplasmic Granules; Female; Follow-Up Studies; Glycogen; Humans; Immunohistochemistry; Middle Aged; Treatment Refusal

Glycogen-rich, clear cell carcinoma of the breast (GCC) is a rare type of breast cancer. Histological features are usually those of ductal carcinoma, but cases featuring lobular, tubular, and mixed ductal-tubular carcinoma have been reported. The presence of "numerous cells with clear cytoplasm" has been reported in some cases of primary neuro-endocrine tumors of the breast. Moreover, no case of GCC of the breast with neuro-endocrine features has been described. We report a case of 33-year-old woman with a palpable lump of the right breast. Fresh tissue obtained from the operating theatre was fixed in 10% formalin and routinely processed to paraffin. Serial sections were stained with haematoxylin and eosin (H&E), periodic acid Schiff (PAS) and PAS following diastase digestion (PASd); other sections were processed for immunohistological detection of chromogranin, synaptophysin, vimentin and smooth muscle actin. For electron microscopy, the tissue was fixed in 2.5% glutaraldehyde in cacodylate buffer. The samples were post-fixed in osmium, dehydrated in ethanol and embedded in araldite. Thin sections, counterstained in uranyl acetate and lead citrate, were studied under a Philips 400T electron microscope. The lump at histological examination was entirely composed of optically clear, neoplastic cells. The cytoplasm was filled with numerous PAS-positive granules which did not stain after the diastase digestion, leading to a diagnosis of GCC of the breast. Some histological (i.e. pattern of growth, blunt edges of neoplastic glands and numerous vessels) and cytological features (i.e. nuclear monomorphism and fine chromatin) prompted us to investigate the possible neuro-endocrine differentiation of the lesion. Immunohistochemical and ultrastructural studies strongly support such hypothesis. To the best of our knowledge, we report the first case of GCC of the breast with neuro-endocrine features.

Topics: Actins; Adenocarcinoma, Clear Cell; Adult; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Neuroendocrine; Cell Differentiation; Cell Nucleus; Chromatin; Chromogranins; Cytoplasmic Granules; Female; Glycogen; Humans; Mastectomy, Radical; Microscopy, Electron; Neoplasm Proteins; Periodic Acid-Schiff Reaction; Protein Isoforms; Staining and Labeling; Synaptophysin; Vimentin

Clear cell tumour or "sugar tumour" of the lung is a rare primary neoplasm with unique histologic and electron microscopic features that may resemble those of metastatic renal cell carcinoma. An immunohistochemical studies are useful in a differential diagnosis these tumours: HMB45 in combination with a panel of various antibodies. The authors present a benign clear cell tumour of the lung, diagnosed on the base of its morphological, immunohistochemical and ultrastructural features.

Topics: Adenocarcinoma, Clear Cell; Adult; Antigens, Neoplasm; Carcinoma, Renal Cell; Cytoplasm; Diagnosis, Differential; Glycogen; Humans; Immunohistochemistry; Lung Neoplasms; Male; Melanoma-Specific Antigens; Neoplasm Proteins

We describe two cases of primary intraosseous hyalinizing clear cell carcinomas of the jaws. One tumor arose in the mandible, the other in the maxilla. Both patients were adult women. Histologically, both tumors were characterized by a population of clear, glycogen-rich cells arranged in solid nests, trabeculae, and occasional single files, surrounded by a markedly hyalinized fibrous stroma. In close admixture with the clear cells, a second component of smaller cells having eosinophilic cytoplasms was also noted. Focal areas of squamous metaplasia were seen in one of the tumors. Neither nuclear pleomorphism nor mitotic activity were conspicuous features. Mucicarmine stains were negative in both tumors. Immunohistochemically, the tumor cells expressed cytokeratins and epithelial membrane antigen. Stains for S100 protein, smooth muscle specific actin, and carcinoembryonic antigen were all negative. Both patients are alive and well 14 and 17 months respectively after the diagnosis without evidence of metastasis or recurrence. The major importance of recognizing the existence of this rare form of salivary gland-type adenocarcinoma arising as a primary lesion in the mandible or the maxilla lies in avoiding misdiagnosing it as other primary or metastatic clear cell neoplasms, including various odontogenic clear cell tumors, other primary intraosseous salivary gland tumors, and metastatic clear cell adenocarcinomas from other organs, particularly the kidney.

Topics: Adenocarcinoma, Clear Cell; Aged; Diagnosis, Differential; Female; Glycogen; Humans; Hyalin; Mandibular Neoplasms; Maxillary Neoplasms; Middle Aged; Odontogenic Tumors; Salivary Gland Neoplasms

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

We determined the proliferation rate and apoptotic activity of glycogen-rich carcinomas of the breast as opposed to non-clear cell tumors by means of MIB-1 immunohistochemistry and in situ detection of oligonucleosomal fragments (TUNEL reaction). The retrospective biopsy series included six invasive clear cell carcinomas of the glycogen-rich type as well as 15 randomly selected cases of invasive ductal carcinoma without evidence of glycogen storage. Three patients in the clear cell group and seven patients in the control cohort developed lymph-node metastasis. The MIB-1 labeling index of glycogen-rich carcinomas averaged 9.05%, while that of the controls was 30.03%. Apoptotic nuclei were present in a mean of 1.26% of glycogen-rich carcinoma cells. The control tumors exhibited an average apoptotic frequency of 5.85%. Tumor size, hormone receptor status, and presence or absence of lymph node involvement were found not to correlate with either proliferation or apoptosis. We conclude that glycogen-rich breast carcinomas are characterized by a peculiar 'low proliferation-low apoptosis' cell kinetic profile. The aggressive clinical behavior of these neoplasms may possibly be accounted for by an ineffective apoptotic elimination of otherwise slowly proliferating tumor cells.

Topics: Adenocarcinoma, Clear Cell; Aged; Aged, 80 and over; Apoptosis; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Case-Control Studies; Cohort Studies; DNA Fragmentation; Female; Gene Expression Regulation, Neoplastic; Glycogen; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Lymphatic Metastasis; Middle Aged; Oligonucleotides; Random Allocation; Retrospective Studies

Twenty-one glycogen-rich clear cell carcinomas of the breast were studied. There were 13 invasive carcinomas and 8 intraductal carcinomas. Ten of the invasive carcinomas contained an intraductal component. Three intraductal carcinomas were papillary carcinomas ("intracystic" papillary carcinoma), and the others showed a mixture of solid, micropapillary, and cribriform patterns of growth. Most of the invasive carcinomas had nested, corded, or sheet-like growth patterns, and all were grade 2 or 3 neoplasms. Among patients with invasive carcinoma, two had metastases to axillary lymph nodes and three died of tumor. One patient with intraductal papillary carcinoma experienced two local recurrences, with invasion in the second recurrence. Thirteen cases (62%) exhibited focal apocrine features. Based on this small series, the clear cell morphology did not appear to influence the clinical outcome once stage and grade were taken into account. Glycogen-rich clear cell carcinoma of the breast may be a variant of apocrine carcinoma.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Female; Glycogen; Humans; Middle Aged

Fine-needle aspiration cytology, immunocytochemistry, and electron microscopic findings are described in a case of glycogen-rich clear cell carcinoma of the breast. The aspirate contained many small and large papillary cell groups and numerous single tall columnar cells with apical cytoplasmic projections and mild to moderate degree of nuclear pleomorphism. Cytochemical localisation of glycogen and immunostaining on air-dried smears with CEA and actin monoclonal antibodies permitted the correct identification and differential diagnosis of the tumor. Electron microscopic examination of the resected specimen confirmed the diagnosis of glycogen-rich clear cell carcinoma. The differential diagnosis and potential diagnostic pitfalls are discussed, and recommendation are offered to prevent misdiagnosis.

Topics: Adenocarcinoma, Clear Cell; Biopsy, Needle; Breast; Breast Neoplasms; Female; Glycogen; Humans; Immunohistochemistry; Microscopy, Electron; Middle Aged

Four new permanent cell lines (RCC-A, -B, -C, and -D) derived from different human renal cell carcinomas of the clear cell type were established in tissue culture. The cell lines displayed characteristic differences in cell size and shape, which allowed individual identification by phase contrast microscopy. Ultrastructurally, the cell lines exhibited varying amounts of cytoplasmatic glycogen and lipid. Immunohistochemistry revealed co-expression of vimentin and cytokeratin in all cell lines. The mean population doubling time ranged from 27 h (RCC-A) to 104 h (RCC-D). RCC-B and -C cells produced slowly growing tumours after heterotransplantation into nude mice, whereas RCC-A and RCC-D cells were non-tumorigenic. The modal chromosome number was either near-diploid (RCC-A, -B, and -C) or near triploid (RCC-D). Clonal abnormalities affecting the short arm of chromosome 3 were seen in all cell lines. Northern blot analysis revealed no expression of the proto-oncogenes c-fos, c-ros, and c-mos, whereas c-Ki-ras expression was observed in all cell lines. Expression of c-myc was observed in RCC-A, RCC-B, and RCC-D cells, whereas c-raf expression could be detected in RCC-B and RCC-D. Tumour suppressor gene p53 mRNA was observed in the cell line RCC-D.

Topics: Adenocarcinoma, Clear Cell; Animals; Cell Line; Chromosome Aberrations; Chromosomes, Human, Pair 3; Genes, myc; Genes, p53; Genes, ras; Glycogen; Humans; Keratins; Kidney Neoplasms; Mice; Mice, Nude; Microscopy, Phase-Contrast; Neoplasm Transplantation; Ploidies; Vimentin

The case of a minor salivary gland tumour, arising from the tongue, with nodal metastasis is presented. Biopsy of the tumour and fine-needle aspiration cytology of the neck swelling showed the presence of a clear cell carcinoma with evidence of nodal metastases. A commando operation was performed and the defect was reconstructed using a local tongue flap. The literature review indicated that the neoplasm was rare and its site of occurrence rather unusual.

Topics: Adenocarcinoma, Clear Cell; Adult; Female; Glycogen; Humans; Lymphatic Metastasis; Neck; Salivary Glands, Minor; Tongue Neoplasms