Micropapillary Carcinoma of the Breast with Necrosis-like Cell Death: A Case Report

A primary invasive micropapillary carcinoma of the breast in a 46-year-old woman is reported. Histologically, it was composed predominantly of papillary tumor cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells were positive for cytokeratin (CK) 7, estrogen receptor (ER), and progesterone receptor (PR), but negative for p53, CK 20, CD34, c-Erb-B2, CK5, epidermal growth factor receptor (EGFR), vimentin, and c-kit. MUC1 expression was found at the reversed apical membrane of neoplastic cell clusters. Accordingly, electron microscopy showed the lack of basement membrane and presence of microvilli at the basal surface of the tumor cells. Moreover, ultrastructural examination revealed single tumor cell death characterized by patchy condensations of chromatin throughout the nucleus. These nuclear alterations were associated with the occurrence of empty cytoplasmic vacuoles, conferring a necrosis-like phenotype to this cell death. Alternative programmed cell deaths are reviewed and their morphologic distinction is discussed.     

Immunohistochemical demonstration of H antigen, peanut agglutinin receptor, and Saphora japonica receptor expression in infant thymuses and thymic neoplasias.

Ten infant thymuses and 13 primary thymic tumors obtained from archived paraffin-embedded tissue were examined for the presence of tissue blood group O antigen (H), peanut agglutinin receptor antigen (PNA-r), Saphora japonica agglutinin receptor antigen (SJA-r), carcinoembryonic antigen (CEA), cytokeratin (CK), and epithelial membrane antigen (EMA). In the thymuses studied, Hassall's corpuscles contained abundant immunoreactive CK, PNA-r, and H antigens, whereas CEA, SJA-r, and EMA were present focally in Hassall's corpuscles. Immunoreactive CK, PNA-r, and CEA were demonstrated focally in the subcapsular region, cortical nurse cells, and subcapsular-perivascular monocytic cells, respectively. PNA-r was present in all 12 epithelial type tumors, including all eight thymomas. CEA was present in nine tumors, including six thymomas. Six thymomas contained H antigen and SJA-r; five continued CK and EMA. SJA-r and EMA were also present in one carcinoid tumor of thymic origin. In epithelial thymomas, the antigens stained nests of epithelial cells resembling the pattern of staining in Hassall's corpuscles. Membrane staining of spindle cells of both spindle cell and epithelial thymomas was less intense than staining of epithelial type cells.     

Cytopathologic findings and differential diagnostic considerations of primary clear cell carcinoma of the lung

Primary clear cell carcinoma (CLCC) of the lung is an extremely rare disease and is a subtype of large cell carcinoma, according to the World Health Organization (WHO) classification. A case is presented here in which intraoperative squash smears in a 53‐year‐old man revealed sheet and small clusters or tumor cells with prominent nucleoli and fine granular chromatin. Abundant translucent cytoplasm with occasional cytoplasmic vacuoles and intracytoplasmic eosinophilic inclusions was also identified. A cytopathologic diagnosis of a CLCC was suggested. Further evaluation and immunohistochemical studies were conducted on formalin‐fixed, paraffin‐embedded material. Nests of slightly acidophilic clear tumor cells with a prominent cellular membrane and an alveolar growth pattern were identified on H&E sections. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for CK(AE1/AE3), CK7, and CA19‐9 but were negative for Napsin A, CK20, CDX2, TTF‐1, alpha‐fetoprotein, chromogranin A, synaptophysin, CD10, and CD56. The diagnosis of primary CLCC of the lung was confirmed based on cytopathologic, histopathologic, immunohistochemical results, and a detailed systemic examination to exclude a possible extrapulmonary origin. We report here the cytopathological features of CLCC of the lung with an emphasis on differential diagnostic considerations. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Histiocytoid carcinoma of the male breast

Histiocytoid carcinoma of the breast is a rare tumor with approximately 30 cases reported, all occurring in female patients. We report the first case of histiocytoid breast carcinoma in a male patient. A 68-year-old man presented with a 2.5-cm breast mass. Microscopic examination of the needle core biopsy revealed a diffuse (lobular type) infiltration of tumor cells as angulated clusters, linear arrangements, small nests, and individual cells; there was no duct formation. The nuclei were round-oval and hyperchromatic with inconspicuous nucleoli and finely dispersed chromatin. The cytoplasm was abundant, was amphophilic, and ranged from granular to vacuolated. A subset of tumor cells contained periodic acid Schiff-positive cytoplasmic material, which was largely but incompletely removed by diastase treatment. There was minimal nuclear pleomorphism, and mitotic figures were inconspicuous. The intervening stroma was densely fibrotic, and the tumor infiltrated among tightly packed collagen bundles. Immunohistochemistry was positive for estrogen receptor, progesterone receptor, androgen receptor, vimentin, epithelial membrane antigen, and pan-cytokeratin. The tumor was negative for CK7, CAM5.2, 34BE12, AE1/AE3, GCDFP-15 (BRST-2), E-cadherin, and CD68. The mastectomy resection demonstrated similar histologic findings. Sentinel lymph node biopsy was negative. The morphology of this tumor is similar to that described for histiocytoid carcinoma of the female breast, a rare entity. Such tumors are felt to be variants of lobular carcinomas, which is supported by diffuse infiltrative growth, loss of E-cadherin expression, and strong ER positivity. We believe our case to be the first reported example of histiocytoid carcinoma in a male breast.     

Mucinous tubular and spindle cell carcinoma of the kidney with neuroendocrine differentiation: report of two cases

We encountered 2 cases of mucinous tubular and spindle cell carcinoma (MTSCC) during a short time. In a 61-year-old man who had macroscopic hematuria for 1 month, the 14.5 x 14.0 x 12.0-cm resected tumor involved the right middle aspect of the renal parenchyma and compressed the renal pelvis. In an asymptomatic 47-year-old man, a renal tumor was found during an annual physical examination. The 3.5 x 3.0 x 2.0-cm tumor was located at the upper pole of the right kidney. The histologic findings in both cases were similar Tumors consisted of tightly packed, small, elongated tubules separated by pale mucinous stroma. The tumor cells were cuboidal to spindled with eosinophilic cytoplasm and low nuclear grade. Mitoses were few or nonexistent and without abnormal figures. Both tumors were immunoreactive for cytokeratin (CK) cocktail (AE1/AE3), high-molecular-weight CK (34betaE12), low-molecular-weight CK (35betaH11), CK7, epithelial membrane antigen, E-cadherin, and vimentin. The tumor cells also were reactive for neuron-specific enolase, chromogranin, and synaptophysin. The ultrastructure of the tumor cells contained abundant mitochondria, junctional complex, and dense-core neurosecretory granules. We present 2 additional cases of MTSCC showing typical morphologic features with neuroendocrine differentiation.     

BCL-2、CK20、CD10、AR表达在基底细胞癌和毛母细胞瘤鉴别诊断中的意义

目的 观察BCL-2、CK20、CD10、AR在基底细胞癌(basal cell carcinoma,BCC)和毛母细胞瘤(trichoblastoma,TB)中表达的不同,以提高它们在两者诊断和鉴别诊断中的作用.方法 对确诊的32例BCC和8例TB石蜡包埋标本行BCL-2、CK20、CD10、AR免疫组化染色,观察它们在肿瘤细胞及其周围间质中的表达.结果 32例BCC中BCL-2肿瘤上皮弥漫阳性表达30例,阴性2例;CK20均为阴性;CD10肿瘤上皮部分表达23例,阴性9例,肿瘤间质阳性4例,阴性28例;AR阳性表达7例.8例TB中BCL-2上皮部分均阳性表达,CK20散在阳性6例,阴性2例,CD10部分上皮阳性4例,阴性4例,间质阳性3例,阴性5例;AR均为阴性.统计结果,BCL-2、CK20表达差异有显著性意义(P＜0.01),AR、CD10差异无显著性意义.结论 BCL-2弥漫强阳性、CK20阴性支持诊断BCC,反之支持诊断TB.     

Small cell carcinoma of the urinary bladder

Primary small cell carcinoma of the urinary bladder is very rare; only several studies have been reported in the English literature. A 62-year-old woman was admitted to our hospital because of hematuria and dysuria. Bladder endoscopy revealed a large polypoid tumor at the bladder base. Transurethral bladder tumorectomy (TUR-BT) was performed. Many TUR-BT specimens were obtained. Histologically, the bladder tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK8, CK18, neurone-specific enolase, chromogranin, NCAM (CD56), synaptophysin, Ki-67 (labeling=100%), p53, KIT (CD117), and platelet-derived growth factor receptor-α (PDGFRA). The tumor cells were negative for CK5/6, CK 34BE12, CK7, CK14, CK19, CK20, p63, CD45, and TTF-1. A molecular genetic analysis using PCR-direct sequencing showed no mutations of KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. No metastases were found by various imaging techniques. The patient is now treated by cisplatin-based chemotherapy.     

Fine‐needle aspiration cytology in a rare case of recurrent mucinous carcinoma of skin,displaying psammoma bodies on smears

Primary mucinous carcinoma of skin is an uncommonly documented tumor, especially on fine‐needle aspiration cytology (FNAC) smears. A 58‐year‐old gentleman presented with a recurrent swelling over his right zygoma. Earlier, he had undergone surgical resection at the same site, on two occasions, 4 years back. FNAC smears from the recurrent nodule displayed clusters and singly scattered relatively monomorphic, polygonal to plasmacytoid cells with mild nuclear atypia and moderate to abundant cytoplasm, including focal intracytoplasmic vacuoles. At places, tumor cells were arranged around psammoma bodies against a background of mucinous material. Histopathological sections from the subsequent tumor resection revealed tumor cells arranged in the form of islands, nests, cribriform, and papillary arrangements amidst mucinous stroma, along with focal psammomatous calcification, consistent with a recurrent mucinous adenocarcinoma. On immunohistochemistry, tumor cells were diffusely positive for CK 7, estrogen receptor (ER), and progesterone receptor (PR), while negative for CDX2, CK20, and TTF1. Diagnosis of a recurrent mucinous carcinoma of skin was offered. Patient underwent adjuvant radiotherapy for achieving better loco regional clearance and is disease‐free, 4 months after. FNAC is a useful diagnostic tool for timely identification of mucinous carcinoma of skin, including recurrent lesions. Psammomatous calcification can be identified within this uncommon tumor, in recurrent lesions. While surgical resection remains the treatment mainstay, immunohistochemical expression of ER and PR in this tumor perhaps could have therapeutic impact, especially in recurrent cases. Diagn. Cytopathol. 2015;43:937–940. © 2015 Wiley Periodicals, Inc.     

A subset of prostate basal cells lacks the expression of corresponding phenotypic markers

Immunohistochemical staining for cytokeratin (CK) 34ssE12 has been routinely used to elucidate prostate basal cells for differentiation between non-invasive and invasive lesions. Our previous studies, however, revealed that some morphologically distinct basal cells observed on H&E-stained sections completely lacked CK34ssE12 expression. Our current study attempted to assess whether these basal cells would also lack the expression of other phenotypic markers, and whether basal cell alterations would affect the proliferation status of the associated tumor cells. Consecutive sections from prostate tumors with large basal cell clusters that were morphologically distinct in H&E sections but were completely negative for CK 34ssE12 were morphologically and immunohistochemically assessed with a panel of basal cell phenotypic and other markers. In addition to CK 34ssE12, these basal cells also completely lacked the expression of other phenotypic markers, including CK5, CK14, p63, and maspin, in contrast to adjacent basal cells, which were strongly positive for these markers. Tumors surrounded by basal cell layers that lack the expression of basal cell phenotypic markers showed a significantly higher rate of cell proliferation and mast cell infiltration than their counterparts. These findings suggest that basal cells might be targets of a variety of pathological alterations, which could significantly impact biological presentations of associated tumor cells.     

Cytokeratin 20-positive large cell neuroendocrine carcinoma of the colon

Herein is presented a case of cytokeratin (CK) 20-positive large cell neuroendocrine carcinoma of the colon, in which the tumor was clinically at stage IV and located in the ascending colon. Pathological examination of the resected tumor revealed nested and solid proliferation of large undifferentiated cells with vesicular nucleus and prominent nucleoli. No areas showed differentiation toward adenocarcinoma or squamous cell carcinoma. Tumor cells were immunohistochemically positive for chromogranin A, synaptophysin, CD 56 (focal), and bore electron-dense granules. With these features, the tumor was diagnosed as a large cell neuroendocrine carcinoma of the colon. Liver metastasis and local recurrence progressed, and the patient died of the primary disease 7 months after operation. The autopsy confirmed this diagnosis without detectable tumors in the lungs. Interestingly, more than half of the tumor cells were positive for CK 20, while CK 7 was not expressed. Most neuroendocrine carcinomas do not express CK 20, with the exception of Merkel cell carcinomas, and most colorectal adenocarcinomas express CK 20. To the best of the authors' knowledge, the present case is the first CK 20-positive, CK 7-negative colorectal neuroendocrine carcinoma to be described, suggesting a link between colorectal neuroendocrine carcinoma and conventional adenocarcinoma.     

Cell death in MMTV-c-myc transgenic mouse mammary tumors may not be typical apoptosis

Enforced expression of c-myc has been shown to serve as an apoptotic stimulus in cultured cells. Prior studies have also demonstrated that several tissues expressing c-myc transgene display a large number of dead cells, although a morphologic or biochemical verification of apoptosis in these tissues has actually not been presented. In the present study, we examined the morphologic properties of cell death in the mammary tumors developed from MMTV-c-myc transgenic mice. We found that c-myc-expressing mammary tumor cells exhibited malformation of mitochondria, characterized by an amorphous matrix with very few cristae. The mitochondria were also frequently degenerated by lysis of the matrix and cristae. The protein level of cytochrome c was much lower in the areas of c-myc-expressing tumor cells compared with the adjacent tumor foci, which was previously shown to have decreased expression of c-myc, reduced frequencies of cell death, and increased frequencies of proliferating cells. In the c-myc-expressing tumor areas, there were many dying or dead cells organized in clusters, termed "dead cell islands." These cells exhibited shrinkage, DNA breakage as indicated by a positive TUNEL staining, and nuclear localization of apoptosis-inducing factor, but a lack of typical apoptotic morphology, such as nuclear condensation and formation of cell membrane blebs and apoptotic bodies. Many macrophages infiltrated into these dead cell islands, engulfing the dying or dead tumor cells. In the total tumor tissue, the protein level of caspase-3 was very low, and the poly(ADP)-ribose polymerase was present mainly as the unprocessed, inactive form. Collectively, these results suggest that programmed cell death in the c-myc transgenic mammary tumor tissue may not be typical apoptosis and may involve a caspase-independent mechanism.     

Malignant myoepithelioma of the breast

Malignant myoepithelioma of the breast is rare. A 50-year-old Japanese woman was admitted to our hospital because of a right breast tumor (11 × 10 × 5.5 cm). Core needle biopsy revealed malignant spindle cells. A mastectomy was performed. The tumor consisted of malignant spindle, round, pleomorphic and giant cells with many mitotic figures and necrotic areas. Tumor and osteoclast-like giant cells were scattered. Much lymphovascular permeation was seen. In a few areas, particularly on the tumor periphery, there were merges between the tumor cells and myoepithelial cells of the non-tumorous ducts, as if the tumor emanated from the duct myoepithelium. The tumor was invasive into the skin and pectoral muscle. Immunohistochemically, the tumor cells were diffusely positive for vimentin, CD10, α-smooth muscle antigen, and Ki-67 (labeling = 95%). The significant areas of the tumor were positive for S100 protein, p63, p53, CD68, caldesmon, desmin and TGFβ1. A few areas were positive for pancytokeratin (AE1/3), cytokeratin (CK) 5/6, and CK 34βE12. In contrast, the tumor cells were negative for pancytokeratins (WSS, CAM5.2), CK7, CK8, CK14, CK18, CK19, CK20, EMA, CEA, bcl-2, myoglobin, CD34, CD56, CD45, HMB45, GFAP, α-1-antitrypsin, synaptophysin, estrogen receptor, progesterone receptor, HER2/neu, MUC1, MUC2, MUC5AC and MUC6. The author diagnosed the tumor as malignant myoepithelioma, as myoepithelial markers (C10, p63, S100 protein, α-smooth muscle actin, caldesmon) were positive, and also because there was a transition between the tumor cells and myoepithelium of non-tumorous ducts. The grade of the tumor was high. The patient was treated with chemoradiation and was free of disease 5 months after the operation.     

Biphasic alveolosquamoid renal carcinoma: a histomorphological,immunohistochemical, molecular genetic,and ultrastructural study of a distinctive morphologic variant of renal cell carcinoma

Only a few cases of sarcomatoid renal cell carcinomas (RCCs) with squamous differentiation have been published. We present 2 RCCs exhibiting a hitherto not reported biphasic neoplastic cell population exhibiting a predominantly alveolar architecture where squamoid differentiation was identified in one of the neoplastic cell populations. None of the tumors showed chromophobe features or any evidence of sarcomatoid transformation. The tumors arose in 2 adult patients and were characterized by routine histology, immunohistochemistry, ultrastructure, array comparative genomic hybridization, confirmatory fluorescent in situ hybridization, and loss of heterozygosity analysis. Tumors measured 3 and 4 cm and were located within the renal parenchyma and had no pelvicalyceal connection. Both tumors were composed of a distinctly dual-cell population. The larger tumor cells displayed squamoid features and formed round well-demarcated solid alveolated islands that, in large parts, were surrounded by a smaller neoplastic cell component. The squamoid cells were immunoreactive for cytokeratins (CKs) (AE1-AE3, Cam 5.2, CK5/6, CK7, and CK20), epithelial membrane antigen, racemase/AMACR, and carboanhydrase IX (in 1 case focally). The small cell population was positive for CK7, epithelial membrane antigen, and racemase/AMACR, whereas CK20, AE1-3, and carboanhydrase IX were negative. CD10 was focally positive in the large squamoid cells in 1 case. Cathepsin K, E-cadherin, and CD117 displayed focal positivity in 1 case. Vimentin, RCC marker, parvalbumin, S100 protein, S100 A1, p63, p53, CDX2, uroplakin III, HMB45, TFE3, WT1, synaptophysin, chromogranin A, thyroglobulin, and TTF1 were negative. The proliferative activity (Ki-67) was low (1%) in the small cell component in both cases, whereas the large neoplastic tumor cells displayed a significantly higher proliferation (20%-35%). Ultrastructurally, desmosomes and tonofilaments were identified in the large tumor cells, confirming squamoid differentiation in a subset of tumor cells. Array comparative genomic hybridization of 1 analyzable case (confirmed with fluorescent in situ hybridization and loss of heterozygosity analysis) revealed partial or complete losses of chromosomes 2, 5, 6, 9, 12, 15, 16, 17, 18 and 22, (including biallelic loss of CDKN2A locus) and partial gains of chromosomes 1, 5, 11, 12 and 13. Follow-up at 6 years showed no recurrence or metastasis in 1 patient. The other (male) patients had a subcutaneous metastasis at presentation, but during a 1-year follow-up no evidence of recurrence or further metastatic events have been documented. Our data indicate that biphasic alveolosquamoid renal carcinoma is a unique and distinctive tumor. The large squamoid and small tumor cells have overlapping but still distinctive immunohistochemical patterns of protein expression. Multiple chromosomal aberrations were identified, some of them located in regions with known tumor suppressor genes and oncogenes.     

Renal mucinous tubular and spindle cell carcinoma: report of four cases and literature review

Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) is an unusual renal tumor. It is important to increase the recognition of the clinicopathological features of MTSCC-K and improve its clinical and differential diagnosis. This report described four cases of MTSCC-K with clinical, imaging, and pathological examination and showed that the tumor boundaries of MTSCC-K were clear, and tumor cells arranged into tubules and cord-like beams, between which was lightly stained myxoid stroma. The tumor cells were smaller and cube- or oval-shaped, with single small eosinophilic nucleoli, low-grade nuclei, and little nuclear fission. The myxoid stroma was scattered around lymphocytes and plasma cells. Immunohistochemical markers including CK7, CD117, EMA (epithelial membrane antigen), vimentin, and CK8/18, showed positive expression in tumor cells, but the tumor cells were negative for CD10 and villin. The proliferation index of Ki-67 was 5-10%. Since MTSCC-K is a rare low-grade malignancy, with unique histological and immunohistochemical characteristics, it is important for clinicians and pathologists to have a defined awareness of this tumor type in order to decrease the rate of misdiagnosis.     

Differential effects of PPARgamma agonists on the metabolic properties of gliomas and astrocytes

Recent studies show that thiazolinediones (TZDs), agonists of the peroxisome proliferator-activated receptor gamma (PPARgamma), induce apoptosis in glioma and glioblastoma cells. Here we compared the effects of troglitazone (Trog), a TZD with low affinity for binding to PPARgamma but with potent metabolic effects, on survival and metabolism in GL261 glioma cells versus primary astrocytes. Trog dose-dependently induced cell death in GL261 cells (with over 90% death at 30 microM) but did not cause any toxicity in astrocytes at the same doses. Measurements of glucose and lactate levels after incubation with Trog (30 microM) indicated an overall increase of glucose consumption and lactate production in both cell types. In astrocytes the ratio of lactate produced to glucose utilized was not significantly altered by Trog, while in glioma cells this ratio was decreased by about 40%. Trog dose-dependently reduced mitochondrial membrane potential (DeltaPsi(m)) in both cell types; and the loss of DeltaPsi(m) was greater in the tumor cells (90% loss at 20 microM) than in astrocytes (70% loss at 20 microM). These results suggest that differences in metabolic responses could contribute to the selective resistance of astrocytes to cytotoxic effects of Trog. TZDs such as Trog should therefore be considered for testing in treatment of gliomas.     

Inhibition of casein kinase 2 enhances the death ligand- and natural kiler cell-induced hepatocellular carcinoma cell death

Recent studies have shown that the inhibition of casein kinase 2 (CK2) sensitizes many cancer cells to Fas ligand- and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. However, it has not been demonstrated directly whether CK2 inhibition can also enhance the cytotoxicity of natural killer (NK) cells, which actually use the death ligands to kill cancer cells in vivo. To address whether NK cell-mediated cancer cell death is affected by the inhibition of CK2, we first checked whether the death ligand-induced apoptosis of hepatocellular carcinoma cells (HCCs) and HeLa were affected by CK2 inhibition. We then investigated the effect of CK2 inhibition on NK cytotoxicity against HCCs and HeLa cells and its mechanistic features. Inhibition of CK2 by emodin increased the apoptotic cell death of HepG2, Hep3B and HeLa when the cancer cell lines were treated with a soluble form of recombinant TRAIL or an agonistic antibody of Fas. This phenomenon appeared to be correlated with the expression level of death receptors on the cancer cell surface. More interestingly, the inhibition of CK2 also greatly increased the NK cell-mediated cancer cell killing. The NK cytotoxicity against the cancer cells increased about twofold when the target cells were pretreated with a specific CK2 inhibitor, emodin or 4,5,6,7-tetrabromobenzotriazole. Furthermore, the increase of the NK cytotoxicity against cancer cells by CK2 inhibition was granule-independent and mediated possibly by the death ligands on the NK cell surface. This suggests that CK2 inhibitors could be used to enhance the cytotoxicity of NK cells and consequently increase host tumour immunity.     

Wolffian adnexal tumor, so-called female adnexal tumor of probable Wolffian origin (FATWO): immunohistochemical evidence in support of a Wolffian origin.

Wolffian adnexal tumor (WAT) is a rare neoplasm believed to originate from wolffian remnants on the basis of its location in areas where these remnants are abundant. To study its histogenesis, the immunoprofile of 25 WATs was compared with that of 10 cervical and vaginal mesonephric remnants and 12 rete ovarii. WATs were unilaterally located in the broad ligament (n = 10), mesosalpinx (n = 9), ovarian hilus (n = 5), and pelvis, not otherwise specified (n = 1). They showed varying morphologies with solid (spindle cells), tubular (lined by columnar cells), retiform and multicystic (spaces lined by cuboidal and attenuated cells) patterns. WATs were immunoreactive for pan-cytokeratin (AE1/3, CK1) (100%), CAM 5.2 (100%), cytokeratin 7 (CK7) (88%, focal staining), keratin 903 (17%), epithelial membrane antigen (EMA) (12%), estrogen receptor (28%), progesterone receptor (24%), androgen receptor (78%), inhibin (68%), calretinin (91%), and vimentin (100%). No immunostaining was detected with monoclonal carcinoembryonic antigen and cytokeratin 20. The pattern of staining was nearly identical to that of the rete ovarii and differed somewhat from mesonephric remnants, which were diffusely immunoreactive for CK7, immunopositive for EMA (apical staining), and nonreactive for inhibin. Our findings provide immunohistochemical support for the derivation of WATs from wolffian remnants, in particular from the rete ovarii. Because of immunoreactivity for inhibin and calretinin in a significant number of WATs, our results further show that these immunostains alone do not allow absolute distinction of WATs from sex cord-stromal tumors and adenomatoid tumors, respectively, with which they may be confused.     

Ultrastructure and immunohistochemistry of a fetal-type Leydig cell tumor.

A symptomless scrotal mass was removed from a 34-year-old man. The lesion was 7 cm in diameter and it was grossly a hemorrhagic cyst with indurated walls. By light microscopy tumor cell clusters and cords were seen infiltrating the testicle, tunica albuginea, and paratesticular tissue. In the immunohistochemical analysis the tumor cells were immunoreactive with anti-S-100 protein and anticarcinoembryonic antigen, but they did not express cytokeratin or alpha-fetoprotein as tested with paraffin sections. Tumor cell clusters were enveloped by a laminin-positive basement membrane. Electron microscopy revealed abundant smooth endoplasmic reticulum, lipid droplets, and membranous whorls in the cytoplasm. Lamellar whorled bodies were also seen in mitochondria, which contained tubulovesicular cristae. The presence of a well-developed, often multilayered basement membrane was confirmed at ultrastructural level. The activity of 3-beta-hydroxysteroid dehydrogenase suggested that the tumor cells were capable of androgen synthesis. The morphological features are reminiscent of fetal-type Leydig cells and are distinctly different from the Leydig cell tumors described so far.