Neuroendocrine liver metastasis in gastric mixed adenoneuroendocrine carcinoma with trilineage cell differentiation: a case report

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare disease, which mostly occurs in the gastroin testinal tract and pancreas. Here we report a case of gastric MANEC with tri-lineage differentiation in which only the neuroendocrine component had metastasized to the liver. Liver and gastric masses were detected by abdominal computed tomography, and the preoperative relationship between liver and gastric masses was unknown. The histopathological analysis after operation confirmed the gastric mass to be MANEC, whereas the liver mass was actually the metastatic neuroendocrine component of the gastric MANEC. In the pathologic diagnosis, tri-lineage differentiation, including tubular adenocarcinoma, neuroendocrine carcinoma and squamous cell carcinoma was observed in the gastric MANEC tissues. The mitotic and Ki-67 labeling indexes of the resected tumor tissue were high, and thus, the tumor was classified as a grade G3 neuroendocrine carcinoma, which has a poor prognosis. Multiple low-density masses were found in the right lobe of the liver 2.5 months after operation.     

Cytological features of mixed adenoneuroendocrine carcinoma of the ampulla: Two case reports with review of literature

Mixed adenoneuroendocrine carcinoma (MANEC) of ampulla is rare, with only 13 cases reported, and the diagnoses were all based on histology mostly after surgery. We describe two new cases with cytological features of signet ring‐cell carcinoma mixed with small‐cell carcinoma, and intestinal adenocarcinoma mixed with large‐cell neuroendocrine carcinoma. Our cases and literature review demonstrate the higher frequency of periampullary‐duodenum subtype in MANEC compared with non‐MANEC ampullary carcinomas. In accordance, of the 14 MANEC cases with detailed morphology available, the most common glandular components are intestinal‐type carcinoma (6/14), followed by goblet carcinoid tumor (3/14), signet ring‐cell carcinoma (2/14), pancreatobiliary‐type carcinoma (2/14), and pancreatic acinar cell carcinoma (1/14). The intestinal‐type carcinoma and goblet carcinoid in MANEC are favorable histological types showing no distant metastasis or mortality (0/9) during 6–36 months follow‐up. In contrast, the signet ring cell, pancreatobiliary‐type carcinoma, and acinar cell carcinoma are unfavorable with distant metastatic rate and mortality rate of 80% (4/5) during 3–16 months follow‐up. The combination of favorable glandular histological types with high‐grade neuroendocrine tumors (neuroendocrine carcinoma) has a mortality rate of 0% (0/3), whereas the combination of unfavorable glandular types with low‐grade neuroendocrine tumors (e.g., carcinoid, atypical carcinoid) has a mortality rate of 100% (3/3). In addition, younger age (<40 years) seems to be associated with high mortality rate of 100% (2/2). Overall, cytology preparations are able to make the diagnosis of MANEC and distinguish the subcomponents. Disease progression is apparently driven by the carcinomatous component of the tumor. Diagn. Cytopathol. 2014;42:1075–1084. © 2014 Wiley Periodicals, Inc.     

Metaplastic breast carcinoma: a retrospective study of 26 cases

Metaplastic breast carcinoma is a rare invasive breast cancer. Metaplastic breast carcinoma is mainly characterized by an epithelial or mesenchymal cell population mixed with adenocarcinoma. We collected 26 cases of metaplastic breast carcinoma in the First Affiliated Hospital of Bengbu Medical College from 2008 to 2014. Tumor size, tumor grade, vascular invasion, ER/PR status, histologic classification, and HER2/neu status were assessed for all cases and the literature was reviewed. Clinicopathologic characteristics of patients diagnosed with metaplastic breast carcinomas and its key points of differential diagnosis were discussed. All patients were female, with the median age of 50 years. The mean tumor size was 3.2 cm. 4 subtypes of metaplastic breast carcinomas were documented. Fibromatosis-like metaplastic carcinomas are typically characterized by wavy, intertwined, gentle spindle cells. When the tumor components are almost squamous cell carcinoma components and the primary squamous cell carcinoma of other organs and tissues are excluded, we can diagnose breast squamous cell carcinoma. In spindle cell carcinoma, atypical spindle cells are arranged in many ways and are usually accompanied by inflammatory cell infiltrate. Cancer with interstitial differentiation has mixed malignant epithelial and mesenchymal differentiation, and the mesenchymal components are diverse. Most tumors are triple negative. At present, surgical resection combined with chemotherapy or radiation therapy is the most effective and acceptable method for treating metaplastic breast carcinoma.     

Small-cell neuroendocrine carcinoma of the uterine cervix associated with micro-invasive squamous cell carcinoma and adenocarcinoma in situ

A case of small-cell neuroendocrine carcinoma of the uterine cervix associated with squamous cell carcinoma and adenocarcinoma In situ is reported. The tumor consisted mainly of uniform small cells with a population of intermediate cells that resembled carclnold tumor cells. Foci of micro-invasive squamous cell carcinoma and adenocarcinoma In situ were recognized separately, adjacent to the main tumor. Both Gri-mellus stain and Immunostalning of serotonin were positive for small-cell and Intermediate-cell carcinoma. Neurosecre-tory granules were demonstrated by electron microscopy. Mlcroaclnl with positive mucln staining and microvilli-like structures suggested glandular or exocrine differentiation of trie tumor. Three distinctive types of differentiation, neuroendocrine, exocrine and squamous characteristics, were expressed In the tumor.     

A case of mixed adenoneuroendocrine carcinoma of the gallbladder arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction

A 54‐year‐old Japanese woman was referred with a gallbladder tumor. Based on the results of the computed tomography scan, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiopancreatography, a mucin‐producing neoplasm of the gallbladder associated with pancreaticobiliary maljunction was diagnosed. Extended cholecystectomy, extrahepatic bile duct resection, and choledochojejunostomy were performed, and she remains free of recurrence 24 months after resection. Histopathological examination revealed that the papillary component of the lesion was an intracystic papillary neoplasm with diverse characteristics of pancreaticobiliary epithelium and intestinal epithelium including mucin. In this component, most of the papillary lesion was a high‐grade intraepithelial neoplasm, but also showed slight invasion into the muscular layer. The nodular component consisted of both poorly differentiated biliary type adenocarcinoma and large cell neuroendocrine carcinoma. We report a rare case of a mixed adenoneuroendocrine carcinoma arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction. As for the histogenesis of this tumor, based on the histopathologic appearance, transdifferentiation from poorly differentiated biliary type adenocarcinoma to large cell neuroendocrine carcinoma is considered the most possible histogenesis of this tumor.     

An extremely rare case of Epstein‐Barr virus‐associated gastric carcinoma with differentiation to neuroendocrine carcinoma

Epstein‐Barr virus (EBV)‐associated gastric carcinoma (EBVGC) is defined as a neoplasm comprising monoclonal proliferation of EBV‐infected gastric epithelial cells. Although the typical histology is gastric carcinoma with lymphoid stroma (GCLS), the histologic features of the tumor vary. We report herein the case of a 78‐year‐old man with multiple simultaneous EBVGCs revealing different histopathologic morphologies; one was mixed adenoneuroendocrine carcinoma (MANEC), and the other was GCLS. Both tumor types exhibited positive results for EBV in situ hybridization. To the best of our knowledge, this represents the first report of EBVGC showing neuroendocrine differentiation. Immunohistochemistry also revealed a loss of gastrointestinal features, including CDX2, MUC5AC, and MUC6 expression, among tumor cells from the neuroendocrine component of the MANEC. We describe the pathologic features of this rare neoplasm and discuss the mechanisms underlying the neuroendocrine differentiation of EBVGC cells, along with providing a brief review of the literature.     

Cytological features of mixed adenoneuroendocrine carcinoma of the ampulla of Vater: A case report with immunocytochemical analyses

Mixed adenoneuroendocrine carcinoma (MANEC) is defined as a tumor that has morphologically recognizable both adenocarcinoma and neuroendocrine carcinoma components comprising at least 30% of either components. MANEC occurring in the ampulla of Vater is extremely rare, and only 16 cases have been reported in the English language literature. In the present report, we describe the first case of MANEC of the ampulla of Vater with immunocytochemical analyses. An 82‐year‐old Japanese male was incidentally found to have a tumorous lesion in the ampulla of Vater. Endoscopic ultrasound‐fine needle aspiration (EUS‐FNA) of the tumor was performed. The Papanicolaou smear demonstrated the presence of different three components. The most dominant component was cohesive clusters of small round cells with round to oval nuclei with powdery chromatin and scant cytoplasm, which corresponded to small cell carcinoma. The second component was an adenocarcinoma, which was composed of irregularly overlapping clusters of tall columnar cells with large round to oval nuclei containing conspicuous nucleoli. The third component was an adenoma, which was comprised of flat cohesive clusters of columnar cells without atypia. Immunocytochemical analyses demonstrated that synaptophysin was expressed in the small round cells, and cdx‐2 was expressed in all three components. Accordingly, a cytodiagnosis of MANEC with adenoma component was made. Preoperative diagnosis of ampullary MANEC is difficult. However, this report clearly demonstrates three different components in the EUS‐FNA cytological specimen. Therefore, we suggest that cytological examination is a useful method for diagnosis of MANEC of the ampulla of Vater.     

Undifferentiated spindle cell carcinoma of the gallbladder: A clinicopathologic, immunohistochemical, and flow cytometric study of 11 cases

Eleven primary spindle cell carcinomas (SpCCs) of the gallbladder are reported. They occurred in eight women and three men ranging in age from 59 to 80 years (mean age, 66.5 years). Histologically, the tumors showed interlacing bundles of atypical spindle cells with eosinophilic cytoplasm, oval to elongated nuclei, and conspicuous nucleoli. Eight SpCCs contained tiny foci of neoplastic glands similar to those seen in adenocarcinoma, and two of these cases also had small foci of neoplastic squamous epithelium. A gradual transition between the squamous cell carcinoma and the spindle cell component was observed in one tumor. Immunohistochemically, all SpCCs were positive for at least one of the epithelial markers (epithelial membrane antigen, nine cases; , nine cases; carcinoembryonic antigen, three cases; and EAB 903, one case), and the tumor cells also were immunoreactive to mesenchymal marker (vimentin, eight cases), muscle markers (alpha-smooth muscle actin, one case; desmin, one case), and histiocytic marker (HAM 56, one case). Abnormalities in tumor suppressor gene p53 expression also were found in two of the 11 SpCC cases using monoclonal antibody PAb 1801. In six cases for which data were available flow cytometry revealed aneuploidy in three SpCCs (50%). The survival curve of the SpCC cases (mean survival, 9 months) was less favorable than that of 224 cases of adenocarcinoma of the gallbladder (mean survival, 81 months) (P = .0011). These results indicate that SpCC of the gallbladder is an epithelial tumor with sarcomatoid components and its prognosis is unfavorable.     

Gastrointestinale gemischte adenoneuroendokrine Karzinome

Mixed adenoneuroendocrine carcinomas (MANECs) are a challenge for the diagnostics and the concept of a histogenetic tumor typing. They are classified into three malignant subgroups: high grade malignant MANECs combine an adenoma or adenocarcinoma with a small cell or large cell neuroendocrine carcinoma, intermediate grade malignant MANECs consist of a neuroendocrine tumor (NET grade 1 or 2), often a globlet cell carcinoid and a poorly differentiated adenocarcinoma or diffuse carcinoma of signet ring cell type. The prototype of a low grade malignant MANEC is the globlet cell carcinoid. Molecular analysis indicates a common clonal origin of the different components in MANECs. The prognosis is determined by the most aggressive tumor component. The pathogenesis of MANECs is apparently a sequence of increasing malignant transformation which leads either from an adenoma/adenocarcinoma to a small or large cell neuroendocrine carcinoma or from a neuroendocrine tumor (NET), often a globlet cell carcinoid to a poorly differentiated adenocarcinoma or a diffuse carcinoma of signet ring cell type.     

Morule-like features and tumor-associated lymphoid proliferation in gallbladder carcinoma

A unique case of gallbladder carcinoma with morule-like features and tumor-associated lymphoid proliferation in a 53-year-old man is presented. The surgically resected gallbladder demonstrated a polypoid tumor with a thin stalk, measuring 1.3 x 0.5 cm. Histologically, a well-differentiated tubular adenocarcinoma was accompanied by multiple spindle cell nodules. The stroma of the tumor showed dense lymphocytic infiltrate. Immunohistochemically, the spindled cell nodules were diffusely positive for cytokeratin AE1/AE3 but negative for S-100, NSE, and chromogranin A. The immunohistochemical results considered to be spindle cell nodules were morule-like features. Intranuclear expression of beta-catenin was observed in morule-like features and carcinoma cells. Ki-67 labeling index was 16.7% of carcinoma cells, but Ki-67 immunoreactivity was negative in spindle cell nodules; therefore, morule-like features were considered to represent metaplastic foci of carcinoma cells and not nodular growth of carcinoma cells. Although the exact pathogenesis of marked lymphoid proliferation in the stroma remained unknown, tumor-produced substances may derive from lymphoid proliferation.     

Small Cell (Endocrine Cell) Carcinoma of the Gallbladder with Squamous and Adenocarcinomatous Components

Small cell (endocrine cell) carcinoma of the gallbladder in a 62-year-old woman is reported. The palliative cholecystectomy specimen revealed a submucosally invading tumor with extensive hemorrhagic necrosis. At autopsy, performed five months after surgery, a huge tumor measuring 14×12×8cm was located at the liver hilus. No signs or symptoms related to overproduction of hormones were recorded throughout her illness. Neither lung lesions nor gall stones were identified. Histologically, diffuse proliferation of small, spindle shaped atypical tumor cells with numerous mitoses was evident. Intraepithelial tumor cell proliferation in the gallbladder mucosa was seen focally. The neuroendocrine nature of the tumor cells was confirmed by the histologic pattern of growth with pseudo-rosette formation, positive reaction for Grimelius' argyro-philia, neuron-specific enolase and Leu 7, and ultra-structural demonstration of neuroendocrine-type granules. Immunostaining for a variety of hormones was all negative. Characteristically, foci with squamous and adenocarcinomatous differentiation were identified in the tumor tissue. The glandular components were immuno-reactive for carcinoembryonic antigen, secretory component, epithelial membrane antigen and CA19–9. The histogenesis and totipotentiality of the neoplasm were discussed.     

Gallbladder Adenocarcinoma with Florid Neuroendocrine Cell Nests and Extensive Paneth Cell Metaplasia

We report a unique case of gallbladder adenocarcinoma associated with florid neuroendocrine cell nests and extensive Paneth cell metaplasia that has not been described previously. The patient was a 79-yr-old woman with a pedunculated, polypoid mass in the gallbladder. Microscopically, the mass was composed of tumor cells showing tubular and papillary growth patterns, consistent with well-differentiated adenocarcinoma. One-third or more of the tumor cells showed Paneth cell appearance. Goblet cell-type tumor cells were also intermingled. In addition, neuroendocrine cell nests, that were connected to the neoplastic glands, were scattered throughout the stroma. Immunohistochemically, the labeling index of MIB-1 in adenocarcinoma cells including Paneth cell-type carcinoma cells was approx 40%. Neuron-specific enolase, chromogranin A, and synaptophysin were positive in the neuroendocrine cells forming solid nests and intermingled within neoplastic glands. They were immunopositive for serotonin but negative for insulin, glucagon, somatostatin, and pancreatic polypeptide (PP). Although MIB-1-positive neuroendocrine cell nests were very few with weak staining, we think that the neuroendocrine cell nests were neoplastic in nature. The formation of the multifocal neuroendocrine nests may be a consequence of the trophic effects of unknown substance(s), which can promote serotonin-producing neuroendocrine cells to proliferate. We postulate that Paneth cell-type carcinoma cells may be intimately related to such substance(s) in our case.     

Ductulo‐insular pancreatic endocrine tumor with amyloid deposition: Report of a case

We report a case of ductulo‐insular pancreatic endocrine tumor (DI‐PET) in a 50‐year‐old woman. The patient presented with symptoms and signs of hypoglycemia, and a small tumor in the uncus of the pancreas was extirpated. The tumor predominantly consisted of a neuroendocrine tumor (NET) of grade 2, which surrounded a minor component of ductular proliferation accompanied by a desmoplastic stroma. Both components were largely juxtaposed but admixed with each other in small areas. The NET component was immunoreactive for insulin and accompanied by the marked deposition of amyloid in the stroma. The ductular component consisted of a haphazard proliferation of ductules showing mildly atypical cytological features and immunoreactivities for cytokeratins 7 and 19. DI‐PET is a rare composite neoplasm that should be distinguished from mixed ductal‐neuroendocrine carcinoma because of the marked differences in treatment modalities and prognoses between the tumors. DI‐PET associated with stromal amyloid deposition has not been reported to date. The ‘transdifferentiation’ of NET cells into ductular cells is considered as the most plausible histogenetic mechanism of this tumor, although other possibilities, such as an origin from a primitive endodermal stem cell or the induction of ductular proliferation by stimulation with NET‐derived humoral factors, cannot be excluded.     

A resected case of neuroendocrine carcinoma of the stomach with unusual lymph node metastasis

Gastric endocrine cell carcinoma is a relatively rare tumor. We experienced a case of early gastric cancer in which an endocrine cell carcinoma was identified within a differentiated adenocarcinoma, and a component of this endocrine cell carcinoma had metastasized to lymph nodes of the stomach. In its 2010 revision regarding digestive system tumors, WHO classified cancer cells with characteristics of both glandular system cells and neuroendocrine cells as mixed adeno neuroendocrine carcinoma (MANEC) under the neuroendocrine carcinoma (NEC) category. In this case, we observed an endocrine cell carcinoma continuous with an intramucosal differentiated adenocarcinoma, and cancer cells with an irregular gland duct structure were observed in the proliferative portion of the submucosal tissue. In addition, there was a 35 mm size lymph node metastasis in the lesser curvature of the stomach consisting entirely of poorly differentiated cancer cells with polymorphic, highly atypical nuclei and scant cytoplasm. Immunohistological analysis showed that the endocrine carcinoma in the gastric mucosa was chromogranin A positive and the infiltrated area of the submucosal tissue was also chromogranin A positive. The lymph node metastasis was positive not only for chromogranin A, but also for Synaptophysin and CD56. Furthermore, the Ki67 labeling index was high at approximately 80 % for the gastric endocrine cell carcinoma and approximately 90 % for the lymph node metastases. Until now, there are no reports related to the patients with early gastric cancer accompanied with lymph node metastasis of MANEC. This case is very interested in considering the mechanism of lymph node metastasis of MANEC. The patient has shown no sign of recurrence for 1 year and 4 months after postoperative chemotherapy.     

Mixed adenoneuroendocrine carcinoma of the gallbladder,amphicrine type: Case report and review of literature

Amphicrine type mixed adenoneuroendocrine carcinoma (MANEC), also known as amphicrine carcinoma, is an exceedingly rare neoplasm comprising of tumor cells simultaneously demonstrating both neuroendocrine and exocrine differentiation. Majority of reported cases were found in tubular gastrointestinal tracts such as colon. Herein, we report the first case of amphicrine carcinoma in gallbladder in a 57-year-old female who presented with abdominal pain, vomiting, and gallbladder mass on imaging followed by radical cholecystectomy. Macroscopically, the tumor was a polypoid solid mass with a firm and tan-white cut surface located at the gallbladder fundus. Histologically, the tumor cells were composed of monotonous-appearing signet-ring cells with fine chromatin, variably conspicuous nucleoli, brisk mitotic figures, and spotty necrosis. They were loosely clustered, forming nests and cords but no glandular formation. Immunohistochemically, the entire tumor showed strong and diffuse immunoreactivity for CDX2, p53, and synaptophysin, with patchy positivity for CD56, chromogranin, and INSM1. Kreyberg stain highlighted both intracytoplasmic and extracellular mucin. Ki-67 proliferation index was approximately 70%. Next-generation sequencing performed on a 724 cancer-related gene panel identified TP53 mutation at c.844C>T (p.R282W). To our knowledge, this is the first case of amphicrine carcinoma in gallbladder. It highlights the complex dynamism and controversial pathogenesis of this unique entity, the exact mechanism and clinicopathologic behavior of which are not yet understood.     

Spindle cell carcinoma of the breast: A case report and an immunohistochemical study including p53 and Ki-67 expression

A rare case of spindle cell carcinoma (SpCC) of the breast occurring In a 51-yearold Japanese woman Is reported. A firm and well-circumscribed tumor, measuring 9times8.5times8.5 cm, was located on the upper lateral region of the right breast. Microscopically, the tumor consisted of sheets of both malignant spindle cells and poorly differentiated ductal carcinoma containing squamold islands with gradual transition to the spindle cell component. The Immunocyto chemical expression of epithelial markers was recognized in the spindle cells, as well as in the carcinomatous cells. Moreover, the spindle cell component expressed vimentin, α-smooth muscle actln and S-100 protein. Ultrastructurally, in addition to the features of adenocarcinoma, squamous or rnyoeptthelial differentiation was confirmed in the spindle cell component. These findings thus suggest an epithelial origin with squamous differentiations and myoepithellal participation In the genesis of SpCC. In a comparative study, the expression of p53 protein and KI-67 as a proliferation marker In each component of this tumor was also Investigated. The mean p53 labeling index (LI) in both the carcinomatous and spindle cell area was similar, however the mean MIB-1 LI in the spindle cell area was significantly higher than that in the carcinomatous area. The results indicate that p53 over-expression is Involved In the tumorigenesis of both components in the SpCC, and the spindle cell component shows a higher degree of proliferative activity than the carcinomatous component.     

Chromophobe renal cell carcinoma with neuroendocrine differentiation

Chromophobe renal cell carcinoma was described by Thoenes et al. in 1986, and associations with carcinoma of collecting ducts, conventional renal cell carcinoma and sarcomatoid renal cell carcinoma have been described. We report a case of chromophobe renal cell carcinoma which showed neuroendocrine differentiation. This is the first known case to be clearly identified as such. The patient was a 56‐year‐old man with constant right flank pain and hematuria; CT scan revealed an 8.5 cm non‐homogeneous mass involving the right kidney. Right radical nephrectomy was performed. The tumor showed a mixture of classical and eosinophilic patterns of chromophobe cell carcinoma. Additionally, it showed insular, glandular and rosetoid‐like formations embedded in a dense eosinophilic hyaline stroma. The cells were cuboid or cylindrical with well‐defined boundaries, finely stippled chromatin and a small nucleolus. The appearance of the cytoplasm varied from faintly eosinophilic to coarsely granular eosinophilic. Immunohistochemically, the neuroendocrine areas were reactive for C‐kit, epithelial membrane antigen, cytokeratin, cytokeratin 7, chromogranin A, neuron‐specific enolase, CD56 and S‐100 protein. Our case represents a typical chromophobe carcinoma with neuroendocrine differentiation. Additionally, the immunohistochemical profile in both types of lesion suggests a common origin from renal tubular cells.     

Colliding primary lung cancers of adenosquamous carcinoma and large cell neuroendocrine carcinoma

We report an extremely rare case of primary lung cancer showing various histological elements diagnosed as the collision of an adenosquamous carcinoma and a large cell neuroendocrine carcinoma by loss of heterozygosity (LOH) analysis of the human androgen receptor (AR) and phosphoglycerate kinase (PGK-1) genes. The tumor exhibited a tiny ground-glass opaque shadow suggesting atypical adenomatous hyperplasia 18 months prior to surgery. However, the tumor grew rapidly, and the resected tumor consisted of two closely located nodules. The larger nodule was composed of well-differentiated adenocarcinomatous and moderately to poorly differentiated squamous cell carcinomatous elements, while the smaller nodule consisted of a large cell neuroendocrine carcinomatous element with partial squamoid differentiation having focal continuity with the adenocarcinomatous element. Both the adenocarcinomatous and squamous cell carcinomatous elements revealed transitional features and LOH of AR and PGK-1 genes, while the large cell neuroendocrine carcinomatous element showed a monoclonal pattern but possessed both alleles of AR and PGK-1 genes. From these clinical and pathological results, the parental cell of the large cell neuroendocrine carcinomatous element was considered to be different from that of the adenosquamous carcinomatous element.     

A gastric carcinosarcoma with neuroendocrine cell differentiation and undifferentiated spindle-shaped sarcoma component possibly progressing from the conventional tubular adenocarcinoma; an immunohistochemical and ultrastructural study

A 56-year-old Japanese man underwent total gastrectomy with lymph-node dissection for a gastric tumor. In the oral rim of the excised large ulcerated tumor, a small nodular mass demonstrated a unique histology of a carcinosarcoma composed of more than three distinctive components. A major part of the large ulcerated tumor tissue consisted of conventional tubular adenocarcinoma, with the coincidental focal distribution of solid cell nests of poorly differentiated or neuroendocrine cell (small cell) carcinoma. Sarcoma cells were another of the constituents of the small nodular tumor with atypical spindle-shaped cells. All the excised lymph-node metastasis demonstrated the histology of tubular adenocarcinoma. In the sarcoma cells, many of the lineage-specific immunohistochemical markers were negative. Only vimentin was positive. Electron microscopy revealed that the neuroendocrine cell carcinoma contained cells with abundant small aggregations of neurosecretory-type granules in their cellular cytoplasm. Primitive cellular junctions and incomplete basal lamina were seen in the sarcoma cells. No transitional or hybrid-type cells were seen between carcinoma and sarcoma cells. The interfaces between the cancer cell nests and the proliferation of sarcoma cells are clearly discerned. It was speculated that the unique histology of carcinosarcoma might have progressed from the conventional type of pre-existing advanced tubular adenocarcinoma.     

Gastric small-cell undifferentiated carcinoma with adeno and squamous cell carcinoma components

A unique gastric tumor is reported. A large portion of the tumor consisted of a diffuse sheet of undifferentiated cells reminiscent of a small cell undifferentiated carcinoma. The tumor cells showed a few dense core granules and a poorly developed attachment apparatus by electron microscopy. In addition, small portions of the tumor showed adenocarcinoma and squamous cell carcinoma. Another noteworthy finding was that some of the metastatic hepatic nodules consisted of relatively monotonous polygonal cells with a distinct cord-like pattern showing argentaffinity and argyrophilia which were indicative of an atypical carcinoid. This case is a rare example of a gastric tumor with differentiation towards endocrine as well as adeno and squamous cell carcinoma.