Extremely well differentiated papillary adenocarcinoma of the lung with prominent cilia formation.

We describe a 54-year-old woman with primary pulmonary adenocarcinoma showing a characteristic papillary architecture and prominent cilia formation. Immunohistochemically, the tumor cells were positive for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and Leu-M1, and negative for lactoferrin and surfactant apoprotein. An ultrastructural study also indicated differentiation toward bronchial surface epithelial cells. To our knowledge, this type of neoplasm has not been reported as peripheral-type adenocarcinoma of the lung.     

Malignant mixed müllerian tumor of the ovary. Report of a case studied by immunohistochemistry.

A case of malignant mixed müllerian tumor of the ovary in a 57-year-old woman is reported along with the results of an immunohistochemical study. The tumor, measuring 16 x 10 x 9 cm, was composed predominantly of adenocarcinoma with a smaller amount of anaplastic carcinoma as an epithelial component and chondrosarcoma, liposarcoma, fibrosarcoma and rhabdomyoblasts as mesenchymal elements. Immunohistochemistry using paraffin sections demonstrated cytokeratin (CK) and epithelial membrane antigen (EMA), generally regarded as epithelial markers, not only in the epithelial component but also in chondrosarcoma cells. Vimentin and desmin, generally regarded as mesenchymal markers, were exhibited partly in carcinoma cells as well as in mesenchymal elements. Positive staining for S-100 protein was obtained not only in chondrosarcoma and liposarcoma cells, but also partly in adenocarcinoma cells. This intricate immunohistochemical picture reflected the histologic findings. It is noteworthy that both carcinoma cells and chondrosarcoma cells demonstrated simultaneous expression of CK, EMA, vimentin, desmin and S-100 protein. This somewhat unusual antigen expression by tumor cells may indicate a change in the nature of tumor cells due to microenvironmental factors.     

Malignant Mixed Mullerian Tumor of the Ovary

A case of malignant mixed mullerian tumor of the ovary in a 57 year old woman is reported along with the results of an immunohistochemical study. The tumor, measuring 16·10·9cm, was composed predominantly of adenocarcinoma with a smaller amount of anaplastic carcinoma as an epithelial component and chondrosarcoma, liposarcoma, fibrosarcoma and rhabdomyoblasts as mesenchymal elements. Immunohistochemistry using paraffin sections demonstrated cytokeratin (CK) and epithelial membrane antigen (EMA), generally regarded as epithelial markers, not only in the epithelial component but also in chondrosarcoma cells. Vimentin and desmin, generally regarded as mesenchymal markers, were exhibited partly in carcinoma cells as well as in mesenchymal elements. Positive staining for S 100 protein was obtained not only in chondrosarcoma and liposarcoma cells, but also partly in adenocarcinoma cells. This intricate immunohistochemical picture reflected the histologic findings. It is noteworthy that both carcinoma cells and chondrosarcoma cells demonstrated simultaneous expression of CK, EMA, vimentin, desmin and S 100 protein. This somewhat unusual antigen expression by tumor cells may indicate a change in the nature of tumor cells due to microenvironmental factors. Acta Pathol Jpn 40: 845 850, 1990.     

Cytology, immunopathology and flow cytometry in the diagnosis of pleural and peritoneal effusions

There were 106 pleural and peritoneal effusions studied in order to investigate the contribution of immunocytochemistry and flow cytometry to routine cytologic diagnosis. A panel of antibodies (to cytokeratin, vimentin, human milk fat globule, epithelial membrane antigen and carcinoembryonic antigen) was applied to aceton-fixed slides, using immunoperoxydase and immunofluorescence methods. Flow cytometry was performed using a double labeling method, i.e., propidium iodide for DNA staining and keratin for labeling of epithelial cells. In this way DNA aneuploidy was more evident in the histograms when the fluid contained many reactive nonepithelial cells (lymphocytes). A designation of marker profiles was made for the three most frequently occurring diagnoses, i.e., reactive mesothelial proliferation (I), adenocarcinoma (II), and malignant mesothelioma (III). For the differentiation between adenocarcinoma and malignant mesothelioma, carcinoembryonic antigen was the most useful marker as 75% of the adenocarcinomas was carcinoembryonic antigen-positive and the malignant mesotheliomas were consistently negative. Furthermore, evident DNA-aneuploidy strongly supported the diagnosis of adenocarcinoma, as most malignant mesotheliomas were DNA-euploid, even though occasional DNA-aneuploidy was found in malignant mesotheliomas when different effusions from the same patient were examined. For the differentiation between reactive mesothelial cells and malignant mesothelioma human milk fat globule and/or epithelial membrane antigen, in this study proved to be most reliable, their presence strongly indicating malignancy. It is stressed that the method used (fixation, antibodies, washing procedures) can influence these findings. In 16 patients (17%) performing immunopathology and/or flow cytometry meant an important contribution to diagnosis.     

A monoclonal antibody to cell surface antigen of human thymic epithelial cell.

The cell surface molecule identified by a monoclonal antibody(TE-1) to human thymic epithelial cell showed the specificity for thymic epithelial cells of both the cortex and medulla. TE-1 reacted with the epithelial cells of normal thymus and thymoma in fresh frozen tissues. The antigen recognized by TE-1 was mostly confined to the cell surface membrane and arranged in reticular network with long processes between thymocytes. On immunohistochemical analysis, TE-1 did not recognize normal epithelial cells of the uterine cervix, skin and stomach, and neoplastic cells of squamous cell carcinoma and gastric adenocarcinoma, all of which were stained with anti-cytokeratin monoclonal antibody. Among the tumor cell lines tested with flow cytometry, most of epithelial and all of hematopoietic cell origin were not labeled with TE-1. In summary, TE-1 appears to be a monoclonal antibody against a surface antigen of human thymic epithelial cell that is immunohistologically different from known epithelial cell surface antigens reported so far.     

Sarcomatoid carcinoma of the colon: a case report

Sarcomatoid carcinoma is a rare biphasic tumor characterized by a combination of malignant epithelial and mesenchymal cells. We report a rare case of sarcomatoid carcinoma of the colon. A 41-yr-old woman was hospitalized with a history of melena. Total colectomy was performed under the impression of colonic carcinoma. Histologically, the tumor was composed of differentiated adenocarcinoma in superficial portion and sarcomatoid spindle cells in deeper portion with a transitional area between the two portions. The sarcomatous areas revealed polygonal and spindle-shaped anaplastic malignant cells arranged in sheet, short fascicular or haphazard pattern. Immunohistochemically, tumor cells showed a positive immunoreaction for cytokeratin, epithelial membrane antigen, and vimentin. The histopathological and immunohistochemical transitions between the adenocarcinoma area and the spindle cell area suggested that the sarcomatous elements originated from the adenocarcinoma during tumor progression.     

Ductal adenocarcinoma of the pancreas with huge cystic degeneration: a lesion to be distinguished from pseudocyst and mucinous cystadenocarcinoma

Cystic neoplasms of the pancreas are rare and often mistaken for pseudocyst by imaging studies and macroscopic examination. We describe an unusual tumor of the pancreas composed of a mural nodule of anaplastic carcinoma arising from a huge ductal adenocarcinoma undergoing cystic degeneration. The cyst measured 27 x 13 x 4 cm. Light microscopy showed that the cyst was partly lined by a single layer of cuboidal to columnar tumor cells with focal mucin production and was surrounded by hyalinized connective tissue. Most lining epithelial cells were absent owing to extensive degenerative process. Immunohistochemical studies showed positive staining of cytokeratin and vimentin for pleomorphic giant tumor cells, which were negative for leukocyte common antigen (CD45), KP-1 (CD68), epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA). The ductal adenocarcinoma stained strongly positive for cytokeratin and EMA, and negative for vimentin, CD45, CD68, and CEA. The clinical course of the current case was extremely poor and the prognosis resembled that of an anaplastic carcinoma. Therefore, we like to emphasize the importance of complete excision and extensive sampling of any cystic neoplasms in the pancreas including those with large cystic component to avoid missing the malignant elements.     

Effusion cytology of epithelioid rhabdomyosarcoma

We report a case of epithelioid rhabdomyosarcoma in a pleural effusion. In contrast to most rhabdomyosarcomas in effusions, the cells presented as cohesive clusters of atypical cells with abundant eosinophilic cytoplasm which mimicked an adenocarcinoma. Immunohistochemistry was positive for epithelial membrane antigen and muscle markers and negative for keratins.     

Immunohistochemistry and K-ras sequence of pancreatic carcinosarcoma

Herein is presented a case of carcinosarcoma of the pancreas in an 82-year-old woman, analyzed on immunohistochemistry and K-ras sequence. The tumor, which arose in the pancreas head, was removed on pancreaticoduodenectomy. The patient died, however, of disseminated intravascular coagulation syndrome from postoperative sepsis 13 days later. Microscopically, the tumor consisted of malignant epithelial (well-differentiated adenocarcinoma cells) and mesenchymal (spindle-shaped tumor cells) components. The adenocarcinoma cells had positive immunostaining for cytokeratin AE1/AE3, cytokeratin 7, epithelial membrane antigen (EMA), CEA and carbohydrate antigen 19-9 (CA 19-9), while focal staining of these proteins was observed in the sarcomatous cells. In contrast, the sarcomatous cells had diffuse immunostaining for vimentin, CD10 and p53, while these proteins were not expressed in the ductal adenocarcinoma cells. These findings support the dual characteristics of a carcinosarcoma. DNA sequencing of the present case indicated point mutations of K-ras in both codons 12 and 34 on exon 2. The latter mutation is likely to correlate with the sarcomatous characteristics of this tumor. The tumor cells had specific and diffuse positive staining for CD10 and p53, with features characteristic of rapid growth.     

Osteoclast-like giant cell tumour of the gallbladder

Summary We describe a rare carcinoma of the gallbladder containing osteoclast-like giant cells. Well-differentiated adenocarcinoma was found in the mucosa of the fundus, and osteoclast-like giant cells were present mainly in a haemorrhagic mass protruding from the mucosal surface. The metastatic hepatic tumour was composed chiefly, if not exclusively, of osteoclastoma-like cells, but minute carcinomatous elements were also present. There was an apparent transition between the giant cells and tubular structures in both the gallbladder tumour and hepatic tumour. However, ultrastructural study did not reveal any evidence of epithelial differentiation in the giant cells. Immunohistochemical studies suggested that the mononuclear and giant cells were mesenchymal and histiocytic in nature (vimentin and factor XIII a positive). A few exceptional giant cells transforming from the fine tubular structure were positive for epithelial membrane antigen. In conclusion, the osteoclast-like giant cell tumour component was thought to represent mesenchymal metaplasia in pre-existent adenocarcinoma.     

Apocrine adenocarcinoma of the bilateral axillae.

A case of apocrine adenocarcinoma arising in the bilateral axillae is reported. The patient was an 88-year-old Japanese male who complained of a mass lesion and pus-like discharge in the right axilla. Another mass was also noticed in the left axilla. No other neoplastic lesion was found in other sites of the body. The histologic appearances of the bilateral axillary tumors were almost identical. Both were adenocarcinoma with varying degrees of differentiation, composed of glands and nests of atypical epithelial cells with abundant eosinophilic cytoplasm. Some neoplastic cells exhibited cytoplasmic projections on their apical surface. Foci of in situ carcinoma were observed within the neoplastic tissue in the bilateral axillae. The neoplastic cells were immunohistochemically positive for epithelial membrane antigen (EMA) and gross cystic disease fluid protein (GCDFP-15), but negative for carcinoembryonic antigen (CEA). On the basis of their histologic and immunohistochemical features and distinctive location, the tumors were diagnosed as apocrine adenocarcinoma.     

Biliary carcinosarcoma arising in nonparasitic simple cyst of the liver

We report a carcinosarcoma arising in a nonparasitic simple cyst of the liver. Sequential imaging findings revealed that the tumour originated in a hepatic cyst and was composed of well-differentiated tubular adenocarcinoma and high-grade spindle cell sarcoma without apparent transition between the two. At the margin of the tumour, a single layer of benign cuboidal epithelium and outer fibrous bands were present, suggesting that the tumour had arisen from a nonparasitic simple cyst of the liver. Immunohistochemically, carcinoma cells were positive for cytokeratins, epithelial membrane antigen and CA 19-9 and negative for vimentin, while sarcomatous cells were positive for vimentin and negative for cytokeratins, epithelial membrane antigen and CA 19-9. Sarcomatous cells did not show any immunophenotypic features of smooth muscle cells, striated muscle cells, histiocytes, lipocytes, nerve cells, Schwann cells or endothelial cells. Ultrastructurally, no specific differentiation was seen in the sarcomatous cells.     

Mixed mesodermal tumor of the ovary: Immunohistochemical study with histogenetic consideration

The clinical, histological and immunohistochemical features of three cases of ovarian mixed mesodermal tumor (MMT) were examined. The epithelial component was serous papillary cystadenocarclnoma in case 1 and 3, and endometrioid adenocarcinoma in case 2. In case 1, undifferentiated adenocarcinoma was also seen. The mesenchymal component was fibrosarcomatous and chondrosarcomatous in case 1 and 2. In case 3, only fibrosarcomatous area was seen. No endometriosis was observed. Immunohistochemically, the epithelial component showed positivity for epithelial membrane antigen in all three cases. S-100 protein was positive in two cases with chondrosarcomatous differentiation. The fibrosarcomatous area showed positivity for vimentin in all three cases. However desmin, myosin and myoglobin were negative. The antibodies thought to be epithelial or mesenchymal markers unexpectedly reacted positively in some cells; for example, EMA was positive in fibrosarcomatous and chondrosarcomatous cells. Therefore, it was speculated that because the undifferentiated tumor cells had a biphasic character, MMT might originate from immature multipotential cells of surface epithelium and subcapsular connective tissue of the ovary.     

Apocrine Adenocarcinoma of the Bilateral Axillae

A case of apocrine adenocarcinoma arising in the bilateral axillae is reported. The patient was an 88 year old Japanese male who complained of a mass lesion and puslike discharge in the right axilla. Another mass was also noticed in the left axilla. No other neoplastic lesion was found in other sites of the body. The histologic appearances of the bilateral axillary tumors were almost identical. Both were adenocarcinoma with varying degrees of differentiation, composed of glands and nests of atypical epithelial cells with abundant eosinophilic cytoplasm. Some neoplastic cells exhibited cytoplasmic projections on their apical surface. Foci of in situ carcinoma were observed within the neoplastic tissue in the bilateral axillae. The neoplastic cells were immunohistochemically positive for epithelial membrane antigen (EMA) and gross cystic disease fluid protein (GCDFP-15), but negative for carcinoembryonic antigen (CEA). On the basis of their histologic and immunohistochemical features and distinctive location, the tumors were diagnosed as apocrine adenocarcinoma. Acta Pathol Jpn 41: 927-932, 1991.     

Immunohistochemical studies on carcinoembryonic antigen in adenocarcinomas of the uterus

In order to distinguish endocervical adenocarcinoma from endometrial adenocarcinoma, an immunoperoxidase stain for carcinoembryonic antigen (CEA) was tried. All of 10 endocervical adenocarcinomas revealed CEA and an adenosquamous carcinoma in the uterine cervix also showed it, while a mesonephroid adenocarcinoma in the uterine cervix did not. The immunohistochemical reaction products for the antigen were not observed in the glandular structures of 20 endometrial adenocarcinomas, although CEA was detected in all foci of squamous epithelial metaplasia occurred within 7 endometrial adenocarcinomas. CEA was detected in the endocervical type of glandular epithelium within a special endometrial adenocarcinoma containing predominantly endocervical type glandular epithelium. The immunoperoxidase staining pattern for CEA in the endocervical adenocarcinoma was related to the degree of histological differentiation of tumors, as follows; in the well differentiated glandular structure CEA was located on the luminal surface, while it was detected in the whole cytoplasm of tumor cells within the moderately and poorly differentiated areas. In conclusion, the immunoperoxidase stain for CEA would be useful for estimating malignancy of glandular structures within the uterus, distinguishing endocervical adenocarcinoma from endometrial adenocarcinoma, and grading of histological differentiation of endocervical adenocarcinoma.     

Epithelial membrane antigen in the cytodiagnosis of effusions and aspirates: immunocytochemical and ultrastructural localization in benign and malignant cells

Immunoreactivity for epithelial membrane antigen (EMA) was evaluated in exfoliated benign and malignant cells using immunoperoxidase and immunogold techniques. In addition, protein A-colloidal gold was used for ultrastructural localization of EMA. Our results suggest that EMA is useful in distinguishing adenocarcinoma cells (strongly positive) from reactive mesothelial cells (negative or weakly positive), lymphoid cells (negative), and a variety of nonepithelial neoplasms (negative) with which they may be confused. Exfoliated cells from two mesotheliomas were also strongly positive for EMA. Ultrastructurally, EMA was distributed in a dense, even, linear pattern along the cell membrane and microvillous surface processes of adenocarcinoma cells. A similar but sparse distribution pattern was observed in reactive mesothelial cells. These observations reflect the increased sensitivity and higher resolution of the immunogold technique.     

IMMUNOHISTOCHEMICAL STUDIES ON CARCINOEMBRYONIC ANTIGEN IN ADENOCARCINOMAS OF THE UTERUS

In order to distinguish endocervical adenocarcinoma from endometrial adenocarcinoma, an immunoperoxidase stain for carcinoembryonic antigen (CEA) was tried. All of 10 endocervical adenocarcinomas revealed CEA and an adenosquamous carcinoma in the uterine cervix also showed it, while a mesonephroid adenocarcinoma in the uterine cervix did not. The immunohistochemical reaction products for the antigen were not observed in the glandular structures of 20 endometrial adenocarcinomas, although CEA was detected in all foci of squamous epithelial metaplasia occurred within 7 endometrial adenocarcinomas. CEA was detected in the endocervical type of glandular epithelium within a special endometrial adenocarcinoma containing predominantly endocervical type glandular epithelium. The immunoperoxidase staining pattern for CEA in the endocervical adenocarcinoma was related to the degree of histological differentiation of tumors, as follows; in the well differentiated glandular structure CEA was located on the luminal surface, while it was detected in the whole cytoplasm of tumor cells within the moderately and poorly differentiated areas. In conclusion, the immunoperoxidase stain for CEA would be useful for estimating malignancy of glandular structures within the uterus, distinguishing endocervical adenocarcinoma from endometrial adenocarcinoma, and grading of histological differentiation of endocervical adenocarcinoma.     

Comparative immunofluorescence study of carcinoembryonic antigen in pseudomucinous cystadenoma of the ovary and adenocarcinoma of the large intestine

The localization of carcinoembryonic antigen (CEA) in a pseudomucinous cystadenoma of the ovary and an adenocarcinoma of the large intestine was studied by the indirect immunofluorescence method. CEA was found to be concentrated in the membranes and basal part of the epithelial cells in both types of tumor.     

Pleomorphic giant cell carcinoma of the prostate

We report the clinical and pathologic features of 2 cases of pleomorphic giant cell carcinoma of the prostate. One case was found at autopsy in a 77-year-old man and was composed of high-grade prostatic adenocarcinoma with prominent anaplastic giant cells. The patient presented with metastases to multiple retroperitoneal lymph nodes, liver, and lumbar vertebrae. The second case occurred in a 45-year-old man who underwent transurethral resection of the prostate and was found to have high-grade prostatic adenocarcinoma with an extensive anaplastic giant cell component. The patient presented with distant metastases and died within 9 months. Both regular adenocarcinoma and anaplastic giant tumor cells displayed cytoplasmic immunoreactivity for prostate-specific antigen, prostatic acid phosphatase, and keratin AE1/AE3; in one case, scattered cells were also positive for chromogranin and epithelial membrane antigen. Pleomorphic giant cell carcinoma is a rare variant of prostatic adenocarcinoma with a poor prognosis that should be considered in the differential diagnosis of prostatic pleomorphic tumors.