Gastric carcinosarcoma with neuroendocrine differentiation as the carcinoma component and leiomyosarcomatous and myofibroblastic differentiation as the sarcomatous component

Gastric carcinosarcoma with neuroendocrine differentiation is a very rare neoplasm. In this article we present such a case. The gastroendoscopic examination of a 59-year-old Japanese man disclosed gastric cancer during follow-up after operation for rectal cancer. Subsequently, total gastrectomy was carried out because of gastric cancer. A large tumor measuring 9.2 x 8.4 cm was observed in the posterior wall of the upper portion of the stomach. The tumor was composed of carcinoma and sarcomatous cells, and the histological transition of both components was observed. Immunohistochemically, carcinoma and sarcomatous cells were positive for cytokeratin CAM5.2. The carcinoma contained adenocarcinoma and malignant cells with neuroendocrine differentiation. The sarcomatous component showed leiomyosarcomatous and myofibroblastic differentiation. The present tumor is the fifth case of gastric carcinosarcoma with neuroendocrine differentiation and the first case of gastric carcinosarcoma with myofibroblastic differentiation. Pathologists should bear in mind that gastric carcinosarcoma may show various types of differentiation.     

Adenocarcinoma with neuroendocrine differentiation of the urinary bladder. Clinicopathologic, immunohistochemical, and ultrastructural study

We describe a primary mixed adenocarcinoma-neuroendocrine carcinoma of the urinary bladder of probable urachal origin. Neuroendocrine differentiation was confirmed by ultrastructural (neurosecretory granules) and immunohistochemical studies (chromogranin and neuron-specific enolase). Two local recurrences and multiple metastases consisted exclusively of the neuroendocrine component. The patient died 30 months after diagnosis with widely metastatic neuroendocrine carcinoma.     

Low-grade tubular-mucinous renal neoplasm with neuroendocrine differentiation: a histological, immunohistochemical and ultrastructural study

Low-grade tubular-mucinous renal neoplasm (LGTMRN) was recently established as a distinct carcinoma classification. A 70-year-old, female traffic accident victim underwent a detailed examination that disclosed a huge mass in the lower pole of the left kidney. The patient underwent a nephrectomy based on a diagnosis of renal tumor. Macroscopically, the tumor was well demarcated and a whitish color with focal hemorrhage. Histological examination showed that tumor cells proliferated through tubular, trabecular, and solid growth patterns in the mucinous background. Focally, foci of clear cells or the proliferation of spindle cells was also observed. Nuclei were generally round and uniform in size. No abnormal mitotic figures were identified. Immunohistochemically, tumor cells were diffusely positive for AE1/AE3, vimentin and chromogranin A, and focally positive for cytokeratin (CK) 18, CK19, Ulex europaeus agglutinin-1, epithelial membrane antigen, neuron-specific enolase (NSE), CD9 and CD57. Ultrastructurally, tumor cells contained a moderate number of mitochondria, rough endoplasmic reticulum and dense-core granules. No renin granules or glycogen were observed. Microvilli were focally seen. Our results render further evidence that LGTMRN is a distinct entity from the hitherto established renal neoplasms. Foci of clear cells and neuroendocrine differentiation should be added to the histological spectrum of LGTMRN.     

Ciliated carcinoma of the endometrium associated with mucinous and neuroendocrine differentiation: A case report with immunohistochemical and ultrastructural study

A case of endometrial ciliated carcinoma mixed with foci of mucinous adenocarcinoma and argyrophil cells is described. The patient suffered from diabetes mellitus, hypertension and obesity, but had no history of estrogen use. Although the tumor presented well differentiated histologic features, it showed complete diffuse, endophytic extension. Approximately half of the cilia had abnormal inner structures, with 8 + 2 microtubular pattern. Some ciliated cells contained intracytoplasmic mucin, while others contained neurosecretory granules. These findings suggest that malignant ciliated cells have the capacity of further transformation into mucinous or endocrine cells.     

A unique early gastric tubular adenocarcinoma arising from a pre-existent carcinoid tumor in a patient with a more than 20-year history of type A gastritis: an immunohistochemical and ultrastructural study

A unique early gastric tubular adenocarcinoma developed from a pre-existent carcinoid tumor in a patient with a more than 20-year history of type A gastritis, multiple endocrine cell micronests, hypergastrinemia, and a high level of serum antiparietal cell autoantibody. The patient was a 60-year-old Japanese man. The background gastric mucosa around the tumor showed marked atrophy with intestinal metaplasia, in which endocrine cell micronests were frequently observed, and was consistent with type A gastritis. The mass was composed of both adenocarcinoma and carcinoid tumor. The adenocarcinoma was restricted to the lamina mucosa and submucosal area, and constituted a minor component of the tumor mass. The carcinoid tumor was the dominant constituent of the tumor, that invaded continuously the subserosa and muscularis propria. Based on this examination together with the detailed immunohistochemical and ultrastructural studies, the adenocarcinoma was presumed to have developed from the pre-existent carcinoid tumor. Ultrastructurally there were no amphicrine cells in the tumor, containing both endocrine granules and mucin droplets.     

Chromogranin A in gastric neuroendocrine tumours: an immunohistochemical and biochemical study with region-specific antibodies

The aim of the present study was to investigate ECLomas and enterochromaffin-like (ECL) cell hyperplasia in gastric human mucosa regarding the immunohistochemical expression of chromogranin A (CgA) epitopes and to measure the same CgA epitopes in plasma samples. Eight gastric biopsies from ECLomas, seven of type I and one of type III, and biopsies from one patient showing only ECL cell hyperplasia were included in the study. Our results revealed a varying expression of region-specific CgA epitopes in the ECLomas regarding both the frequency of immunoreactive cells and intensity of immunoreactivity. CgA284–301 (pancreastatin) was not revealed in any neoplasm, whereas CgA361–372 (catestatin) was expressed in all ECLomas. However, the number of immunoreactive cells to vesicular monoamino transporter 2 (VMAT 2) or the commercial monoclonal CgA (CgA250–284) antibodies were generally higher. The plasma concentrations of the region-specific CgA radioimmunoassays differed considerably, with highest concentrations of CgA1–17 and CgA116–130 epitopes and the lowest with the CgA17–37, CgA63–76, CgA238–247 and CgA441–424 epitopes. No relationship was found between tissue expression and plasma concentration of CgA epitopes. In conclusion, this study shows that VMAT 2 and the commercial CgA antibodies seem more useful for histopathological diagnosis of ECLomas than the antibodies to the other CgA regions.     

A case of small cell gastric carcinoma with an adenocarcinoma component operated curatively

We present a case of a primary advanced gastric tumor that was composed of 2 different pathological components: small cell carcinoma and moderately-differentiated adenocarcinoma. The patient was still alive four years after the surgery was performed, without recurrence. A large part of the tumor consisted of a diffuse sheet of small cell carcinoma, which transitioned into another small portion consisting of moderately-differentiated tubular adenocarcinoma components. Therefore, this case raised the possibility that small cell gastric carcinoma may originate from totipotential stem cells of the stomach. Although small cell carcinoma progresses aggressively, and patients with it have an extremely poor prognosis, this patient recovered uneventfully after the surgical resection, and has remained in good health, without any recurrences.     

Differential diagnosis between uterine carcinosarcoma versus carcinoma with sarcomatous metaplasia: an immunohistochemical and ultrastructural case study

Uterine carcinosarcomas are biphasic neoplasms with carcinomatous and sarcomatous elements. However, several elements suggest that carcinosarcomas may be more closely related to carcinoma of the endometrium and that they arise from an unique stem cell. Recently, the authors observed an uterine tumor that at histologic examination showed an apparently double population of cells: malignant epithelial element admixed with mesenchymal spindle-shaped cells. The immunohistochemical stainings instead showed cytokeratin positivity and negativity for stromal markers. Electron microscopy showed the neoplastic tissue to be made of a single population of poorly differentiated epithelial cells, thus confirming the immunohistochemical findings and leading to the diagnosis of uterine metaplastic carcinoma.     

Renin storage and cell differentiation in juxtaglomerular cell tumors: an immunohistochemical and ultrastructural study of three cases

Three renin-secreting juxtaglomerular cell tumors were studied by ultrastructural and immunocytochemical methods. Both active and inactive renins were identified in tumor extracts. By immunofluorescence and the peroxidase-antiperoxidase (PAP) method with antirenin antiserum, immunolabeling was intracytoplasmic and irregularly distributed throughout the tumor tissue. Electron microscopic examination revealed various types of secretory granules, including atypical giant crystalloid protogranules in one case, and the postembedding PAP procedure showed labeling of all types of granules. Acid phosphatase staining was observed within secretory granules and autophagic vacuoles. The process of renin storage and release is discussed. The presence in one case of a neural component and a distal tubular structure supports the view of a hamartomatous lesion.     

Non-small cell lung carcinomas with neuroendocrine features. A light microscopic, immunohistochemical and ultrastructural study of 11 cases

Eleven resected primary lung carcinomas classified as large cell carcinomas or squamous cell carcinomas, but showing some microscopic resemblances to bronchial carcinoid and small cell carcinoma, were studied. All cases were neurone-specific enolase and protein gene product 9.5 positive, indicating neuroendocrine differentiation. Staining for bombesin, C-terminal peptide of human pro-bombesin and chromogranin was positive in some cases. Electron microscopy showed dense-core granules in six of seven cases investigated, the remaining case showing small granules of uncertain nature. All but one patient died within 15 months after operation. These data indicate that neuroendocrine differentiation in non-small cell carcinomas of the lung may in some cases be suspected on routine histology. The follow-up data suggest that the identification of these cases might have implications for prognosis and therapy, and consequently for diagnostic lung tumour classification.     

Granulocytic sarcoma of the cervix: an immunohistochemical, histochemical, and ultrastructural study.

Light microscopical and routine immunohistochemical studies of a cervical neoplasm in a 32 year old woman initially suggested a histiocytic lymphoma, but histochemical staining for chloroacetate esterase established the correct diagnosis. This was supported by electron microscopic findings. Eight months later the patient developed a granulocytic sarcoma in her left breast and haemotological features of acute myeloid leukaemia. Accurate initial diagnosis of granulocytic sarcoma in a non-leukaemic patient may reduce the risk of subsequent acute myeloid leukaemia if appropriate chemotherapy is begun in time.     

Acinic cell carcinoma of the breast: an immunohistochemical and ultrastructural study

The clinicopathological features of six cases of breast carcinomas showing features of acinic cell differentiation, which are similar to those seen in homologous tumors of salivary glands, are presented. The patients, all women, were 35–80 years of age. One case recurred after 4 years, and in two cases axillary lymph-node metastases were found at the time of surgery. Histologically the tumors showed a microglandular pattern merging with solid areas. Cytologically, immunohistochemically, and ultrastructurally the tumors were very similar to cases of acinic cell carcinoma of the parotid gland.The differential diagnostic criteria with microglandular adenosis and carcinomas showing granular cytoplasm are discussed. It seems that acinic cell carcinomas of the breast have to be added to the long list of tumors that affect the salivary glands and can also arise in the breast. Received: 19 November 1999 / Accepted: 7 February 2000     

Hyalinizing spindle cell tumor with giant rosettes and low-grade fibromyxoid sarcoma: an immunohistochemical and ultrastructural comparative investigation

Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) and low-grade fibromyxoid sarcoma (LGFMS) are 2 variants of fibrosarcoma, which share several clinicopathologic features. This study compares the light microscopic, immunohistochemical, and ultrastructural features of 2 examples of HSCTGR and 3 of LGFMS to determine the degree of overlap of these 2 tumors. HSCTGR were composed of bland spindle cells within hyalinized to myxoid stroma. Scattered throughout the lesions were characteristic rosette-like structures, formed by a central collagenous core surrounded by spindled neoplastic cells. LGFMS consisted of a mixture of fibrous and myxoid areas, composed of fibroblast-like cells arranged in a swirling, whorled growth pattern. Immunohistochemical analysis showed diffuse positivity for vimentin in all cases, while few scattered tumor cells stained for CD57, CD34, factor XIIIA, and actin. The extracellular matrix showed intense positivity for type IV collagen, laminin, and fibronectin, with the exception of myxoid areas of LGFMS and the central core of the giant rosettes in HSCTGR. Ultrastructurally, both tumor types were composed of cells with the features of fibroblasts, embedded in a collagenous stroma with irregular deposits of amorphous basal lamina-like substance. In conclusion, HSCTGR and LGFMS share similar immunophenotypic and ultrastructural features, and together with other fibrosing fibrosarcomas, like sclerosing epithelioid fibrosarcoma, may constitute a subset of fibrosarcomas formed by fibroblasts capable of producing large amounts of basal lamina-like material.     

Large cell carcinoma of the lung with neuroendocrine differentiation. A comparison with large cell "undifferentiated" pulmonary tumors.

Twelve large cell carcinomas of the lung showing evidence of neuroendocrine differentiation (LCCND) were compared with 15 other large cell pulmonary tumors that lacked such features (NELCUC). All lesions were composed of partially necrotic, nested, or sheet-like arrays of mitotically active, nucleolated large cells that were at least twice the size of those seen in small cell carcinomas. Examples of LCCND were defined by immunoreactivity for neuron-specific enolase, Leu-7, synaptophysin, and chromogranin-A, and by their content of neurosecretory granules on electron microscopy. NELCUCs were devoid of these immunohistologic and ultrastructural features. There were six women and six men with LCCND, who ranged in age from 38 to 82 years. Of nine individuals in this group with Stage T1NOMO or T2NOMO disease at diagnosis, five (55%) died of their neoplasms within 3 years of diagnosis; three more (33%) have recurrent or persistent tumors and are likely to die as a result. On the other hand, 47% of patients with NELCUC of similar stages are free of disease after a similar follow-up period. LCCND is a distinctive clinicopathologic disease and should not be classified with unspecified large cell anaplastic carcinomas of the lung. Its behavior is potentially aggressive and may justify consideration of a specialized treatment protocol. Because electron microscopic evaluation of immunohistologic features must be done to recognize LCCND, it is probably underdiagnosed.     

Mesothelioma with clear cell features: an ultrastructural and immunohistochemical study of 20 cases

Mesotheliomas with clear cell morphology are rare and only a few individual case reports have been documented in the literature. The author reports a series of 20 epithelioid mesotheliomas with clear features, 17 of which originated in the pleura and 3 in the peritoneum. Eighteen of the patients were men and 2 were women. Twelve patients had a history of asbestos exposure. Electron microscopy and special histochemical stains demonstrated that the cytoplasmic clearing seen in hematoxylin and eosin-stained sections resulted from multiple factors that can occur either singly or in combination. The most frequent cause of the cytoplasmic clearing was the accumulation of large amounts of intracytoplasmic glycogen. Another but somewhat less common factor was the accumulation of large amounts of lipid, which occurred alone or with glycogen. Other less common causes were marked mitochondrial swelling, the presence of numerous intracytoplasmic vesicles, and a large number of intracytoplasmic lumens. The value of immunohistochemistry in helping to distinguish epithelioid mesotheliomas from some carcinomas with clear cell morphology is emphasized. In addition, it was determined that because electron microscopy was decisive in establishing the cause of the cytoplasmic clearing in most of the cases, tissue for electron microscopy should routinely be procured for ultrastructural studies.     

Balloon cell nevus of the soft palate: an immunohistochemical and ultrastructural study

An ultrastructural analysis of oral balloon cell nevus of intramucosal type complemented with an immunohistochemical study was performed for the first time. The lesion was composed of large balloon cells with an admixture of small nevus cells and melanophages at the periphery. Balloon cells showed cytoplasmic accumulation of vacuoles of varying sizes and the presence of microgranular and vacuolated melanosomes were found. Residual cytoplasm contained no identifiable organelles. A spectrum of transitional forms between balloon cells and conventional nevus cells with microvacuoles was readily observed. Both cells exhibited intense immunoreactivity to multiple melanocytic markers. Ballooning phenomenon was not evident in melanophages containing a large amount of melanosome complex. It can be inferred, from the present and previous observations, that progressive vacuolization of melanosomes in nevomelanocytes may be responsible for the formation of peculiar ballooning appearance, suggesting an aberrant melanogenesis.     

Osteoclast-like giant cell tumor of the pancreas: an immunohistochemical and ultrastructural study

We report a rare case of osteoclast-like giant cell tumor of the pancreas in a 70-year-old Japanese woman. The tumor was composed of a proliferation of ovoid to spindle-shaped mononuclear cells admixed with osteoclast-like giant cells. The tumor cells were immunore-active for vimentin, ±₁-antitrypsin, and CD68. In ultrastructural examination, the giant cells resembled osteoclasts, and the mononuclear stromal cells had fibroblastic and histiocytic features. No elements of epithelial differentiation were found in this tumor. These findings suggest that this tumor had a derivation similar to giant cell tumor of bone.This study was presented at the 28th Annual Meeting of the Clinical Electron Microscopy Society of Japan, Osaka, October 17–19, 1996.     

Small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features of the thoracic wall: A case report with histological,immunohistochemical and ultrastructural examinations

A case of small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features is presented. The tumor was encountered in a 32 year old Japanese woman with an initial presentation of palpable tumor in the left lateral region of the thorax. The resected tumor was a partially well encapsulated whitish medullary one and consisted of small round and spindle tumor cells, together with so-called rhabdoid cells in the small round cell area. Although pseudorosettes were often observed, true rosette formation could not be detected anywhere. Ultrastructurally, despite a histologic variety of tumor cells, most tumor cells possessed numerous mitochondria, some of which occasionally contained abnormal filamentous or crystalloid structures. Various amounts of microfilaments were present in most tumor cells and microtubules were present in a few. A minority of small round cells possessed a small number of neurosecretory granules, especially in short cytoplasmic processes. A positive immunoreaction for neuron specific enolase was found by immunohistochemical examination in several small round tumor cells and for neurofilaments in lesser numbers. Despite the lack of S-100 protein, MB2 was detected in both small round and spindle cells. On the basis of these findings, the tumor of the present case corresponds to malignant peripheral nerve sheath tumor with neuronal differentiation and oncocytic features.