Malignant small-cell epithelial tumor of the peritoneum coexpressing mesenchymal-type intermediate filaments

A 28-year-old man with a large abdominal mass was found to have a tumor involving the peritoneum that had no other apparent primary origin. By light microscopy, the histologic pattern of the tumor was that of a small-cell epithelial neoplasm. Electron-microscopic examination demonstrated desmosomes and paranuclear aggregates of intermediate filaments. Immunohistochemical studies revealed reactivity for keratin, desmin, and vimentin. The globoid staining observed for the last two markers correlated with the paranuclear concentration of intermediate filaments observed by electron microscopy. We believe this case represents an unusual small-cell epithelial tumor, expressing mesenchymal-type intermediate filaments, that should be distinguished from other small-cell neoplasms.     

Spindle-cell carcinoma of the upper aerodigestive tract mucosa. An immunohistologic and ultrastructural study of 18 biphasic tumors and comparison with seven monophasic spindle-cell tumors

The histogenetic origin of the spindle-cell component of spindle-cell carcinoma of the head and neck mucosa remains controversial. The spindle cells have been considered a variant growth pattern of squamous-cell carcinoma, a non-neoplastic mesenchymal reaction, and a malignant admixture of epithelial and mesenchymal neoplasm. To evaluate the spindle-cell component, we studied 25 tumors (18 biphasic and seven monophasic) by utilizing the following: an avidin-biotin complex immunoperoxidase technique with a variety of antikeratin antibodies (AE1, AE3, CAM 5.2, 35BH11, and polyclonal Dako) and a monoclonal antivimentin antibody, and an avidin-biotin alkaline phosphatase double-labeling technique to detect coexpression of keratin and vimentin. The immunohistologic staining pattern was compared with electron-microscopic studies. Eight of 18 biphasic neoplasms contained immunoreactive keratin in the spindle-cell component that was distributed focally in a minority of cells in 3 tumors and diffusely throughout five of the neoplasms. Four of seven ulcerated monophasic spindle-cell tumors devoid of histologic squamous-cell carcinoma also were keratin positive, confirming epithelial differentiation. The majority of the spindle cells in all the tumors contained vimentin intermediate filaments. In three immunoperoxidase keratin positive biphasic tumors examined with alkaline phosphatase double labeling, occasional spindle cells were found that coexpressed keratin and vimentin and were interspersed with cells expressing either intermediate filament. Electron microscopy was performed on the spindle-cell component of 13 tumors, nine biphasic and four monophasic. Of the biphasic tumors, four were immunoperoxidase keratin positive; three of these showed epithelial differentiation by electron microscopy. Five biphasic tumors were keratin negative, and three tumors had epithelial differentiation by electron microscopy. Four monophasic spindle-cell tumors were immunoperoxidase keratin positive, and one of these had epithelial features by electron microscopy. Two monophasic tumors were keratin negative and without ultrastructural evidence of epithelial features. By using a combination of immunohistochemical and electron-microscopic observations, we identified evidence for epithelial differentiation in the spindled cells in 11 of 18 biphasic tumors and four of seven monophasic spindle-cell tumors.     

Sarcomatoid carcinoma of urinary bladder: immunohistochemical study of an uncommon case

A case of sarcomatoid carcinoma of the bladder is reported herein. Immunohistochemical staining with human pancytokeratin antibody was negative, while vimentin staining was strongly positive, suggesting a diagnosis of sarcoma of the bladder. Further immunohistochemical analysis revealed positivity for AE1/AE3 cytokeratins, permitting a correct diagnosis of sarcomatoid carcinoma of the bladder. It can be difficult to distinguish between sarcomatoid carcinoma, undifferentiated carcinoma and sarcoma, particularly if the biopsy specimens are of small size. In rare cases, sarcomatoid tumors may express epithelial markers different from those revealed by human pancytokeratin staining.     

An immunohistochemical study of normal endometrial stroma and endometrial stromal neoplasms. Evidence for smooth muscle differentiation.

To determine the immunohistochemical staining profile of endometrial stromal cells, we analyzed a series of formalin-fixed, paraffin-embedded normal endometrial tissues, stromal nodules, and stromal sarcomas for immunoreactivity with a panel of eight antibodies. Normal proliferative-phase (five cases) and secretory-phase (five cases) endometrial stromal cells showed the following immunopositivity: vimentin 10 of 10, muscle-specific actin (MSA) 10 of 10, alpha-smooth muscle actin (alpha sm) 10 of 10, desmin nine of 10, cytokeratin (AE1/AE3 and CAM 5.2) zero of 10, epithelial membrane antigen (EMA) zero of 10, and S-100 protein zero of 10. Antibodies to vimentin, MSA, and alpha sm stained a greater number of proliferative-phase stromal cells as compared with secretory-phase cells. Only rare stromal cells were immunoreactive for desmin, except for one case in which predecidual cells were diffusely positive. Both endometrial stromal nodules reacted with antibodies to MSA, alpha sm, and desmin, and one was vimentin positive. Each was unreactive for epithelial markers and S-100 protein. The 12 endometrial stromal sarcomas had the following immunopositivity: vimentin 11 of 12, MSA 10 of 12, alpha sm 10 of 12, desmin seven of 12, AE1/AE3 one of 12, CAM 5.2 two of 12, EMA zero of 12, and S-100 protein zero of 12. The antibodies to MSA and alpha sm usually stained a greater number of cells than did the desmin antibody. Three stromal sarcomas had sex cord-like areas, one of which exhibited focal CAM 5.2 positivity. These immunohistochemical findings for normal and neoplastic endometrial stromal cells indicate smooth muscle differentiation and are similar to those of smooth muscle neoplasms and myofibroblastic cells.     

Histogenesis of benign pleomorphic adenoma (mixed tumor) of the major salivary glands. An ultrastructural and immunohistochemical study

Twenty-two benign pleomorphic adenomas of the major salivary glands were studied by transmission electron microscopy and immunohistochemical techniques (three cases) in order to characterize the cell types comprising the epithelial and so-called mesenchymal regions of the tumors. Light- and electron-microscopic studies showed the tumors to consist of variable mixtures of neoplastic ductular epithelial cells, rare acinar cells, and metaplastic myoepithelial cells. Many of the loosely organized "stromal cells" contained structures indicative of their myoepithelial origin, e.g., perinuclear tonofilaments, ectoplasmic actin microfilaments, and remnants of basement membrane. Polyclonal antikeratin antisera strongly stained ductular epithelial and myoepithelial cells, squamoid cell nests, and periductular myoepithelial cells, whereas myxoid and chondroid cells were less intensely stained. Monoclonal cytokeratin antibody AE1 stained only the ductular epithelial cells in both the normal glands and tumors. In contrast, S-100 protein, which is present only in scattered acinar cells and myoepithelial cells in the normal parotid gland, was found in the ductular and periductular myoepithelial cells, isolated myxoid cells, and chondroid and cartilagenous cells in the tumors. Actin was found in all the cell types of the tumor but staining was strongest in the ducts. Double immunofluorescence staining for cytokeratin and vimentin revealed coexpression of both types of intermediate filaments in occasional normal acinar and intercalated duct myoepithelial cells, and in some cells in the myxoid and chondroid regions of the tumors. In the tumors, vimentin was present in occasional periductular myoepithelial cells, stellate myxoid cells, and especially in chondroid cells and chondrocytes. Our findings indicate that benign pleomorphic adenomas of the major salivary glands are pure epithelial cell tumors. The histologic complexity of these neoplasms is due to the ability of the neoplastic ductular myoepithelial cell to modulate its morphologic appearance and intermediate filament composition, and to produce large amounts of matrix substances. We further postulate that these tumors arise from neoplastically transformed intercalated ducts.     

Calretinin,a more sensitive but less specific marker than alpha-inhibin for ovarian sex cord-stromal neoplasms: an immunohistochemical study of 215 cases

Although inhibin has been shown to be a sensitive marker for ovarian sex cord-stromal and fibrous neoplasms, it may be negative in some cases. Calretinin, a mesothelial marker, has shown promise as a marker for sex cord-stromal neoplasms. The aim of this study was to evaluate and compare calretinin and inhibin as immunohistochemical markers for sex cord-stromal and fibrous neoplasms. A total of 215 ovarian neoplasms were immunostained with commercially available antibodies to calretinin and inhibin. These tumors included 87 sex cord-stromal (39 granulosa cell, 13 Sertoli-Leydig, 4 Sertoli, 9 thecomas, 14 fibrothecomas, and 8 other stromal tumors), 37 fibrous (20 fibromas, 9 adenofibromas, and 8 fibrosarcomas), 65 epithelial, 22 germ cell, and 4 miscellaneous neoplasms. The staining was evaluated on a 0-4 scale based on percentage of neoplastic cells labeling: 0 = none; 1+ = 1-25%; 2+ = 26-50%; 3+ = 51-75%; 4+ = 76-100%. Calretinin reactivity was detected in 100% of sex cord-stromal and 90% of fibrous neoplasms, including 32 that were inhibin negative (2 granulosa cell tumors, 1 Sertoli-Leydig cell tumor, 1 thecoma, 3 fibrothecomas, 16 fibromas, 6 adenofibromas, and 3 fibrosarcomas). All four calretinin-negative fibrous neoplasms were inhibin negative. Calretinin staining was also detected in 22% of epithelial neoplasms but none of the germ cell and miscellaneous neoplasms tested. Inhibin staining was detected in 92% of sex cord-stromal neoplasms, 22% of fibrous neoplasms, 2% of epithelial neoplasms, and none of the germ cell and miscellaneous neoplasms tested. Calretinin has a 97% sensitivity and 85% specificity for sex cord-stromal and fibrous neoplasms, whereas inhibin has a 71% sensitivity and 99% specificity. This study shows that both calretinin and inhibin are useful in the diagnosis of ovarian sex cord-stromal and fibrous neoplasms. Calretinin is a more sensitive but less specific immunohistochemical marker than inhibin. Calretinin is particularly useful in the diagnosis of sex cord-stromal and fibrous neoplasms that are inhibin negative. The high frequency of calretinin in fibrous neoplasms suggests that a subgroup of these neoplasms may be derived from specialized gonadal stromal cells, perhaps thecal cells.     

Bladder cancer discovered by ovarian metastasis: Cytokeratin expression is useful when making differential diagnosis

A 49-year-old woman underwent hysterectomy and bilateral adnexectomy after the diagnosis of a right ovarian tumor with paraaortic and pelvic lymph node metastases. The pathological diagnosis was undifferentiated carcinoma of the ovary. After the operation, a bladder tumor was discovered during the evaluation for microscopic hematuria. The bladder tumor was pathologically diagnosed as transitional cell carcinoma, pT1b, G3. Although the pathological findings of the bladder cancer and ovarian cancer were very similar, we could diagnose primary bladder cancer with ovary and lymph node metastases according to the immunohistochemical staining pattern of cytokeratins 7 and 20. Herein, the clinical usefulness of immunohistochemical staining using cytokeratins for making a differential diagnosis of the origin of a tumor in the pelvic cavity is demonstrated.     

Cellular differentiation in ovarian sex-cord-stromal and germ-cell tumors studied with antibodies to intermediate-filament proteins

Seventy ovarian sex-cord-stromal and germ-cell tumors were immunohistochemically studied for the presence of intermediate-filament proteins of different types used as markers for cellular differentiation. Cells of ovarian granulosa-cell tumors constantly expressed vimentin and appeared to lack cytokeratin. Two tumors previously classified as granulosa-cell tumors were reclassified as poorly differentiated "common" epithelial tumors based on their cytokeratin positivity, vimentin negativity, and morphologic features. Dysgerminomas and Leydig-cell tumors showed only vimentin positivity. Tubular structures in androblastomas, which are considered to represent Sertoli-cell differentiation, were cytokeratin positive, and thus differed from the majority of normal Sertoli cells that are known to express vimentin and not cytokeratin. Embryonal carcinomas, choriocarcinomas, and endodermal sinus tumors showed cytokeratin positivity in the neoplastic cells whereas vimentin was observed in the stromal cells. In immature teratomas, epithelial differentiation was demonstrated with cytokeratin antibodies, and neural and glial differentiation was also frequently demonstrated by immunostaining with antibodies to neurofilaments and glial fibrillary acidic protein. The results show that antibodies to intermediate filaments can be used in the differential diagnosis between ovarian epithelial and nonepithelial tumors, and they provide a very accurate additional method to characterize the cellular differentiation of ovarian neoplasms.     

Keratin in epithelioid sarcoma. An immunohistochemical study

Intermediate-sized filaments have been noted in epithelioid sarcoma by previous investigators, two of whom have reported that the filaments represent vimentin. We utilized polyclonal antibodies directed against keratin and immunoperoxidase techniques (PAP) to stain 32 of the more than 300 cases accumulated at the AFIP . All of our material was formalin-fixed, paraffin-embedded. Seventy-five percent of our cases (24/32) showed positive immunoreactivity, a feature that may be of diagnostic help in distinguishing epithelioid sarcoma from modular fasciitis, benign and malignant fibrous histiocytoma, malignant melanoma, and necrotizing granuloma. In these cases, the reaction was enhanced using predigestion with trypsin. The immunoreactivity varied from tumor to tumor, perhaps due to formalin fixation. Since synovial sarcoma and mesothelioma may also be cytokeratin-positive, our findings indicate that keratin immunoreactivity is not confined to epithelial tumors and may also occur in neoplasms traditionally regarded as mesenchymal.     

Sarcoma-like mural nodules in mucinous cystic tumors of the ovary revisited: a clinicopathologic analysis of 10 additional cases

Ten mucinous cystic ovarian tumors that contained sarcoma-like mural nodules are described. The nodules were studied by conventional and immunohistochemical methods. The sarcoma-like mural nodules occurred predominantly in middle-aged women, were multiple and sharply demarcated from the adjacent mucinous tumor, had small size, and exhibited a heterogeneous cell population. Distinction of these lesions from true sarcomatous nodules and foci of anaplastic carcinoma is important because of the worse prognosis of the two latter tumors compared with the favorable behavior of the sarcoma-like mural nodules. Six of the eight patients with follow-up information were alive and clinically free of recurrence at a mean follow-up interval of 12 years. Two patients died of other causes (thyroid and breast carcinomas). The nature of the nodules is not clear. Sarcoma-like mural nodules probably represent a reactive and self-limited phenomenon within a neoplasia. Their coexpression of vimentin and cytokeratins is consistent with an origin from submesothelial mesenchymal cells, which undergo partial transformation into epithelial cells.     

Classification and pathology of testicular germ cell and sex cord-stromal tumors.

Germ cell tumors of the testis are the most frequent testicular neoplasms, with seminoma predominating. The pathologist must be able to discriminate between seminoma and nonseminomatous germ cell tumors as well as sex cord-stromal tumors and metastatic lesions. Appropriate therapy and accurate prognostic information are dependent on the proper classification of testicular neoplasia. Characteristic histologic features, serum markers, and immunohistochemistry are helpful in this regard. Sex cord-stromal tumors comprise a small minority of testicular neoplasms. It remains critically important not to confuse these neoplasms with testicular germ cell or metastatic tumors, and, again, recognition of the characteristic histologic features, immunohistochemical findings, and clinical information is diagnostic. The urologist can provide the pathologist with key clinical information in the attempt to make a correct diagnosis.     

Clear cell tumor of the lung. A clinicopathologic, immunohistochemical, and ultrastructural study of eight cases.

We studied eight clear cell tumors of the lung (CCTL) to better define their clinical, immunohistochemical, and ultrastructural features, and to clarify their distinction from other neoplasms, particularly metastatic renal cell carcinoma. Patients ranged in age from 31 to 67 years (mean, 51 years). Seven patients had clinically benign, asymptomatic lesions measuring less than 2 cm in diameter that were devoid of necrosis. The eighth patient had a symptomatic, partially necrotic CCTL 4.5 cm in diameter that metastasized to the liver and peritoneum; the patient died of tumor 17 years after diagnosis. Ultrastructural study of seven CCTL showed interdigitating cell processes (all cases), primitive cell junctions (five of seven cases), intracytoplasmic glycogen (all cases), and rare dense core granules (two of seven cases). Immunohistochemically, paraffin-embedded sections from all eight CCTL were negative for cytokeratin (CK), epithelial membrane antigen (EMA), chromogranin, and vimentin. Focal staining was seen for S-100 protein (three of eight cases), neuron-specific enolase (three cases), synaptophysin (one case), and Leu 7 (one case). Although these findings suggest that at least some CCTL exhibit neuroendocrine differentiation, the tumor's histogenesis remains uncertain. Of more practical importance, the combined absence of CK, EMA, and vimentin in formalin-fixed, paraffin-embedded CCTL virtually precludes confusion with renal cell carcinoma. Although traditionally considered benign, CCTL larger than 2 cm that are symptomatic, and focally necrotic should be regarded as potentially malignant neoplasms.     

The significance of epithelial differentiation in mixed mesodermal tumors of the uterus. A clinicopathologic and immunohistochemical study

Mixed mesodermal tumors and carcinosarcomas of the uterus are classified as sarcomas. However, in other sites, malignant biphasic tumors may be classified as carcinomas, mesotheliomas, or sarcomas. In order to clarify their behavior and patterns of differentiation, we performed a clinicopathologic and immunohistochemical study of 22 cases aimed at analyzing the pattern of spread and histologic appearance of the metastasis, as well as the distribution of intermediate filaments in the primary tumor and the metastasis. Four monoclonal antibodies (Mabs) were used to detect epithelial lineage, three that recognize keratin (AE1/AE3, CAM5.2, MAK6) and one that recognizes epithelial membrane antigen (EMA). A Mab against vimentin was also used. Metastases involved the omentum, pelvic peritoneum, ovaries, fallopian tubes, pelvic or para-aortic lymph nodes, liver parenchyma, and tonsil. These metastases were composed of carcinoma only. Lymphatic/vascular invasion was identified in 11 cases; it consisted exclusively of carcinoma. In all 12 cases evaluated immunohistochemically, keratin and EMA were identified in the majority of the cells in the epithelial component and in a more focal distribution in the spindle cell component in 11 (92%). Vimentin was detected in the majority of spindle cells in nine cases (75%) and in a more focal distribution in the epithelial component in six cases (50%). In the spindle cell component, keratin and EMA were present in widely scattered individual spindle-shaped and rounded cells, within solid clusters of rounded cells, and in nests of cells with small lumens. The distribution of keratin, EMA, and vimentin in the metastases (carcinoma in all instances) was similar to the epithelial component in the primary tumor. Our findings indicate that the epithelial component of these tumors invades lymphatic/vascular spaces and metastasizes, whereas the spindle cell component has limited metastatic potential, if any. Since the behavior of these neoplasms is dictated by the epithelial element, we believe that mixed mesodermal tumors of the uterus should be classified as carcinomas rather than sarcomas.     

Rhabdoid papillary meningioma.

We have studied an uncommon case of rhabdoid papillary meningioma in a 15-year-old boy with a dura-based mass arising in the left posterior fossa. The patient exhibited prominent extracranial extension during the past 6 years, consisting of a mixture of both perivascular pseudopapillary growth and rhabdoid cytologic features of neoplastic meningothelial cells. The meningothelial features were evidenced by the focal whorl formation of tumor cells, coexpression of epithelial membrane antigen and vimentin, and ultrastructural findings of interdigitated cytoplasmic process and intercellular junction. However, the regional and histologic resemblances to ependymoma were further complicated by unexpected focal expression of glial fibrillary acidic protein, neurofilament, and alpha-smooth muscle actin of the tumor cells. The rhabdoid morphology was characterized by sheets of tumor cells with eccentric nuclei and abundant eosinophilic cytoplasm with often recognizable intracytoplasmic hyaline inclusions. These inclusions revealed ultrastructural paranuclear whorls of intermediate filaments, ruling out the other forms of intracytoplasmic eosinophilic inclusions resembling rhabdoid morphology. Diagnosis of an unusual rhabdoid papillary meningioma with aggressive behavior is resoluble by immunohistochemical and ultrastructural analyses.     

Histogenesis of Human Renal Cell Carcinoma by using Electron Microscopy and Immunohistochemical Techniques

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

Combined hepatocellular-cholangiocarcinoma: a histopathologic,immunohistochemical, and in situ hybridization study

Combined hepatocellular-cholangiocarcinoma (CHC) forms a small but significant proportion of primary liver carcinomas. However, its diagnostic features are not well established, and this has possibly contributed to the variability in its reported clinical outcome in the literature. Many such tumors with features intermediate between hepatocellular carcinoma and cholangiocarcinoma (CC) may have been considered CC in the past based on positivity for "biliary differentiation" cytokeratins and the lack of availability of highly sensitive and specific hepatocellular markers. The utility of in situ hybridization for albumin mRNA, a recently available sensitive and specific hepatocellular marker, has not been reported in CHC. We investigated 27 CHCs with regard to their histomorphologic spectrum and association of these morphologies with immunohistochemical staining for different cytokeratins (CK7, CK19, and CK20; AE1; Cam 5.2), epithelial membrane antigen, polyclonal carcinoembryonic antigen and alpha-fetoprotein, and in situ hybridization for albumin mRNA. All 27 tumors contained areas morphologically intermediate between hepatocellular carcinoma and CC (transitional-type tumors), and in each case such areas formed at least 25% of the tumor. Nine (33%) tumors showed areas with "antler-like" morphology, a feature not previously described in CHC. Twenty-two of 23 tumors (96%) showed positive signals on in situ hybridization for albumin mRNA. Positivity for both hepatocellular (albumin mRNA) and biliary (keratin immunohistochemical profile) markers confirmed the light microscopic impression of biphenotypic differentiation in these tumors. Immunohistochemical positivity for all cytokeratins (except CK7) and epithelial membrane antigen, as well as the expression of albumin mRNA by in situ hybridization, did not show significant differences between hepatocellular carcinoma and CC-like areas. Based on the cytokeratin profile and results on polyclonal carcinoembryonic antigen/alpha-fetoprotein alone, many such tumors would be classified as CC. However, the positivity for albumin mRNA by in situ hybridization proves that such an interpretation would not have been accurate. Clinically, CHCs showed many differences from pure hepatocellular carcinoma, including the absence of cirrhosis (0 of 27), rarity of serum hepatitis B or C marker positivity (4 of 27), and normal to only mildly elevated serum alpha-fetoprotein levels (median 187 ng/mL). The tumor followed an aggressive clinical course, with overall 3-and 5-year survival rates of 30% and 18%, and in the resected cases of 38% and 24%, respectively.     

β-catenin (CTNNB1) S33C mutation in ovarian microcystic stromal tumors

Microcystic stromal tumor (MCST) is a recently described subtype of ovarian tumor characterized by prominent microcystic histologic pattern and diffuse immunoreactivity for CD10 and vimentin. However, its pathobiology, particularly its histogenesis, remains largely unclear. Here, we report 2 cases of ovarian MCST, in which we have performed extensive histologic, immunohistochemical, and genetic investigations to determine its distinct nature among ovarian neoplasms. The patients were 32 and 41 years of age. Both tumors were solid and cystic masses involving the right ovary. Microscopically, tumor cells with generally bland, round-to-ovoid nuclei grew in microcystic, macrocystic, and solid patterns. Intervening thick fibrous stroma was observed. Immunohistochemically, tumor cells were diffusely and strongly positive for CD10, vimentin, and Wilms tumor 1. Furthermore, we detected aberrant nuclear expression of β-catenin protein in both cases. Of interest, mutation analyses revealed the presence of an identical point mutation, c.98C>G, in exon 3 of β-catenin (CTNNB1) in both tumors. This is an oncogenic mutation that causes replacement of serine with cysteine at codon 33, leading to the loss of a phosphorylation site in the β-catenin protein. The results of this study strongly suggest that dysregulation of the Wnt/β-catenin pathway plays a fundamental role in the pathogenesis of ovarian MCST. Finally, by comparing the immunophenotype of MCST with its histologic mimics and other ovarian sex cord-stromal tumors, we were able to identify unique features of MCST and a panel of markers useful in differential diagnosis.     

Immunoprofile of a carcinosarcoma of the submandibular gland.

Carcinosarcomas are a very rare group of true malignant tumors of the salivary gland. As the name indicates, the tumor is composed of an epithelial and a mesenchymal component, both malignant. We report a case of carcinosarcoma of the submandibular gland in an 86-year-old woman. The epithelial component showed a squamous carcinoma phenotype, whereas the mesenchymal component was morphologically similar to a fibrosarcoma. The epithelial component was strongly positive for CK13, CK14, and AE1/AE, and groups of positive cells were seen for CK19 and vimentin. The whole mesenchymal component was positive for vimentin, negative for cytokeratins, and focal cells were positive for smooth- muscle actin. Both components were strongly positive for P53 and Cyclin D1, and focally positive for MDM2. Rare multinucleated giant cells showed expression of CD68, and focal dendritical cells on carcinomatous nests were positive for S-100. The CK7, CK8, Factor XIIIa, c-erbB-2, P16, CDK-4, Rb1, and E2F-1 were not detected in these 2 groups of malignant cell populations.     

Hepatic progenitor cells in hepatocellular adenomas.

Hepatocellular adenoma is a benign tumor of the liver that has a small but not negligible risk of malignant transformation into hepatocellular carcinoma. In analogy with the established role of oval cells in hepatocarcinogenesis in rodent models, human hepatic progenitor cells may have a function in the development of liver tumors. To investigate this issue, we performed immunohistochemistry on biopsies of 10 consecutively resected hepatocellular adenomas using markers for hepatic progenitor cells. Sections of paraffin-embedded and frozen biopsies were stained using antibodies against cytokeratins 7, 8, 18, and 19, chromogranin-A, OV-6, and neural cell adhesion molecule. Hepatic progenitor cells were observed in five of 10 hepatocellular adenomas. These five tumors also contained cells with an immunohistochemical phenotype intermediate between hepatic progenitor cells and hepatocytes. Hepatic progenitor cells and intermediate hepatocyte-like cells were scattered throughout the tumors with a density that varied from area to area. Ultrastructural examination confirmed the presence of hepatic progenitor cells. Our study shows that hepatic progenitor cells are present in a considerable proportion of hepatocellular adenomas, supporting the hypothesis that human hepatic progenitor cells can play a role in the development of hepatocellular tumors.