Small Cell Carcinoma of the Gallbladder Combined with Adenocarcinoma

A rare case of small cell carcinoma (SCC) of the gallbladder combined with adenocarcinoma is reported. The patient was a 70-year-old Japanese man, who died of the disease shortly after the onset of symptoms. Autopsy disclosed a small tumor (1.0 cm in longest diameter) in the fundus of the gallbladder, with widespread metastasis. Histochemically, the tumor cells showed negative reactions for argyrophilic and argentaffin stainings, a weak immunohistochemical reaction only for neuron-specific enolase, and negative reactions for all of the other neurosecretory markers used, including neurofilament, chromogranin, somatostatin, gastrin and leu-7. However, electron microscopic examination revealed a few typical neurosecretory granules (NSG) in the cytoplasm of some tumor cells. We suggest that: 1. The presence of NSG in the cytoplasm of tumor cells is the most reliable diagnostic criterion for SCC. 2. SCC, at least the combined type, arises from a multipotential stem cell.     

Tubular Adenoma of the Gallbladder with Squamoid Spindle Cell Metaplasia:Report of Three Cases with Immunohistochemical Study

Three cases of tubular adenoma of the gallbladder with squamoid spindle cell metaplasia are reported. Two of the three patients, who were middle-aged Japanese, had a solitary polyp in the gallbladder, and the other had three polyps. All the lesions were detected incidentally by ultrasonography. The polyps were pedunculated with a fine or frail stalk, and ranged from 0.5 to 3.9 cm in diameter. Histologically, they were tubular adenomas accompanied by scattered foci composed of a compact collection of short-spindle or oval cells with mild atypia. These cells did not retain intercellular bridges, and lacked intracellular keratinization. Immunohistochemically, the spindle cells stained positively for high-molecular-weight cytokeratin (EAB 903, a marker of squamous cell differentiation), whereas adenoma cells lining the tubules were negative for this antigen. Therefore, the spindle cell component is considered to represent squamoid metaplasia of adenoma cells. Acta Pathol Jpn 41: 41–45, 1991.     

Paneth cell-rich papillary adenocarcinoma and a mucoid adenocarcinoma occurring synchronously in colon: a light and electron microscopic study

A 71-year-old man who presented with iron deficiency anaemia and weight loss was found to have two colonic tumours: a mucoid adenocarcinoma at the splenic flexure and a papillary adenocarcinoma rich in Paneth cells in the ascending colon. The light and ultrastructural features of the neoplastic cells are described, and the significant of the presence of neoplastic Paneth cells is discussed.     

Gallbladder neuroendocrine carcinoma: report of 10 cases and comparision of clinicopathologic features with gallbladder adenocarcinoma

Few cases of neuroendocrine carcinoma (NEC) of the gallbladder (GB-NEC) have been reported. Data obtained from the 10 patients with GB-NEC treated in our hospital between January 2008 and December 2012 were retrospectively analyzed and compared with those of 377 patients with gallbladder adenocarcinoma. GB-NEC accounted for 2.2% of all gallbladder cancers. The patients (8 females and 2 males) were 59.0 ± 10.0 years old. Four patients presented mixed adenocarcinoma, while six had pure NEC. Immunohistochemical examinations showed a positive rate of 100% for CgA, NSE, and CK; the positive rates for Syn, EMA, and CD56 were 88.9, 87.5, and 75%, respectively. TNM grades II, IVA, and IVB were found in 1, 2, and 7 patients, respectively. GB-NEC patients showed significantly higher N2 lymphatic metastasis rates than gallbladder adenocarcinoma patients (70.0 vs. 34.0%; P < 0.05). Two patients were treated with radical resection and the remaining 8 with palliative operation. The 1-, 2-, and 3-year survival rates were 20, 10, and 0%, respectively (median survival time, 3.0 m); the 1-, 2-, 3-, and 5-year survival rates for all gallbladder adenocarcinoma patients were 38.0, 31.0, 30.1, and 28.4%, respectively (median survival time, 6.0 m), the difference was statistically significant (P = 0.038). The results demonstrate that GB-NEC was mainly found in aged females and shows high malignancy. Its prognosis is poorer than that of gallbladder adenocarcinoma, and surgical resection combined with TACE, radiotherapy, and chemotherapy could increase patient survival.     

Adenomyoma with goblet and Paneth cells of the ileum

A case of ileal adenomyoma with goblet and Paneth cells is reported. A 75-year-old man died of ruptured hepatocellular carcinoma. As an incidental finding at autopsy, a 9 x 7 x 6 mm(3)-sized nodule was found in the ileal wall. Histologically, the lesion occupied the submucosa and muscularis propria, and consisted of glandular structures of various sizes and interlacing smooth muscle bundles surrounding the glandular elements. Goblet cells and Paneth cells were interspersed in the glandular element. Immunohistochemically, the glandular element was positive for cytokeratin (CK) 7 and negative for CK 20. This is the first reported case of adenomyoma of the gastrointestinal tract that contained Paneth cells. The result of the immunohistochemical staining favored the heterotopic pancreas theory concerning its pathogenesis. The appearance of goblet and Paneth cells might be the result of metaplasia.     

人胎肺神经内分泌细胞的发育及其作用

目的：探讨胎肺生长发育中神经内分泌细胞的表达及其功能意义。方法：检测３０例人胎肺组织,采用组织化学Ｇrimelius嗜银反应、免疫组织化学、透射电镜技术及显微图像分析。结果：神经内分泌细胞最早在胚胎第１２周胎肺出现,主要为分泌ＧＲＰ细胞,其分布与细支气管发育分化密切相关;ＣＴ阳性细胞在胚胎１６周胎肺出现;分泌ＣgＡ细胞在２０周 出现。随胎龄增长,神经内泌细胞数量递增,胚胎２４周达高峰。此后细胞数量递减,出生     

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.     

Primary Small Cell Neuroendocrine Carcinoma of the Kidney

The histological, immunohistochemical, and ultrastructural features of a primary small cell neuroendocrine carcinoma of the renal parenchyma are described. Tumor cells were positive for cytokeratin, neuron-specific enolase, and Leu 7, but Grimelius- and chromogranin-negative. They also exhibited positivity with anti-MIC2 antibody. By electron microscopy, tonofibrils, primitive desmosomes, and dense-core granules with a neuroendocrine appearance were present. This is only the 7th recorded example of such a tumor at this site, which showed an aggressive course characterized by widespread bony metastases.     

Neuroendocrine Carcinoma of the Stomach with Extensive Somatostatin Immunoreactivity

Upper gastrointestinal tract neuroendocrine tumors producing predominantly somatostatin have thus far been described only in the duodenum; their characteristic features include the frequent presence of psammoma bodies (psammomatous somatostinomas), and the association with von Recklinghausen's neurofibromatosis. Gastric neuroendocrine tumors, on the other hand, tend to display immunoreactivity to serotonin but may include small subpopulations producing gastrin, motilin, pancreatic polypeptide, and somatostatin. In this report we describe a neuroendocrine carcinoma of the stomach with rapidly fatal outcome, displaying neurosecretory granules by electron microscopy and immunoreactivity to pan-neuroendocrine markers, ie, chromogranin and neuron-specific enolase. The only neuroendocrine regulatory peptide detected in the tumor was somatostatin, identified by immunohistochemistry in the majority of neoplastic cells. In contrast with duodenal somatostinomas, there were no psammoma bodies and no demonstrable association with von Recklinghausen's neurofibromatosis. To our knowledge this appears to be the first report of a malignant neuroendocrine tumor with diffuse somatostatin immunoreactivity.     

Benign Signet Ring Cell Change with Multilayering in the Gallbladder Mucosa: A Case Report

We describe a case of benign signet ring cell change in the gallbladder mucosa. On histopathological examination of H&E-stained sections, the gallbladder epithelium showed multilayering. The epithelial cells were large, columnar to polygonal with a small round basal or eccentric nucleus and vacuolated cytoplasm, giving them a signet ring appearance. There was no nuclear atypia, hyperchromatism or mitotic activity. The cells showed uniform positivity with mucicarmine, PAS and Alcian blue stains. The cytoplasmic vacuolations were negative for fat stains (Oil red O and Sudan IV). On immunohistochemistry, the cells showed positivity with antibodies for pancytokeratin (PCK) and epithelial membrane antigen (EMA). A diagnosis of benign signet ring cell change with multilayering in the gall bladder mucosa was made. Thoroughly reviewing the literature, we found only one case of benign signet ring cell aggregates in the gallbladder mucosa documented earlier. The lesion is hereby reported because of the unique histomorphology and the diagnostic dilemma which can occur as a malignant change in situ has to be excluded.     

Ultrastructural and Histochemical Study on the Paneth Cells in the Rat Ascending Colon

Paneth cells (PCs) contribute to the host defense against indigenous bacteria in the small intestine. We found Paneth cell‐like cells (PLCs) in the rat ascending colon, but the nature of PLCs is never clarified. Therefore, the present study aimed to clarify the cytological characteristics of PLCs and discuss their cellular differentiation. PLCs were localized in the bases of intestinal crypts, especially follicle‐associated intestinal crypts in proximal colonic lymphoid tissue, but were very seldom found in the ordinary intestinal crypts of the ascending colon. PLCs possessed specific granules with highly electron‐dense cores and haloes, as well as PCs in the small intestine. The secretory granules of PLCs were positive for PAS reaction, lysozyme and soluble phospholipase A2, but negative for Alcian blue staining, β‐defensin‐1 and ‐2, as well as the ones of PCs. Furthermore, intermediate cells possessing both the PLC‐specific granules and the mucus granules similar to those of goblet cells (GCs) were occasionally found in the vicinity of PLCs. Intermediate cells ranged from goblet cell‐like cells rich in mucus granules to PLC‐like cells with few mucus granules. The cellular condensation and fragmentation were exclusively found in PLCs but never seen in intermediate cells or GCs. The PLCs, which were identified as PC, were suggested to be transformed from GCs through intermediate cells and finally to die by apoptosis in intestinal crypts of proximal colonic lymphoid tissue in the rat ascending colon. Anat Rec, 297:1462–1471, 2014. © 2014 Wiley Periodicals, Inc.     

Neuroendocrine cells are present in the domestic fowl ovary

Neuroendocrine cells are present in virtually all organs of the vertebrate body; however, it is yet uncertain whether they exist in the ovaries. Previous reports of ovarian neurons and neuron‐like cells in mammals and birds might have resulted from misidentification. The aim of the present work was to determine the identity of neuron‐like cells in immature ovaries of the domestic fowl. Cells immunoreactive to neurofilaments, synaptophysin, and chromogranin‐A, with small, dense‐core secretory granules, were consistently observed throughout the sub‐cortical ovarian medulla and cortical interfollicular stroma. These cells also displayed immunoreactivity for tyrosine, tryptophan and dopamine β‐hydroxylases, as well as to aromatic L‐DOPA decarboxylase, implying their ability to synthesize both catecholamines and indolamines. Our results support the argument that the ovarian cells previously reported as neuron‐like in birds, are neuroendocrine cells.     

一株人胰腺癌细胞系的建立及其特性

人胰腺癌是很难建系的癌细胞之一,特别是从原发瘤建立的细胞系。我们成功地从一个胰腺癌组织建立了一株人胰腺癌细胞系,命名为PC-3。PC-3细胞呈上皮样,贴壁生长,经过四年连续培养,细胞系稳定。通过免疫组化、电镜观察、染色体及DNA含量分析,细胞集落形成及裸鼠移植,生长因子对瘤细胞生长的影响和癌基因的表达证实PC-3细胞系为人胰腺癌细胞系。PC-3细胞系的建立进一步丰富了人胰腺癌细胞库,对深入了解人胰腺癌细胞生物学及分子生物学特性提供了有力的物质基础。     

Clinicopathologic and Immunohistochemical Characteristics of Goblet Cell Type Adenocarcinoma of the Lung

Twenty-two resected goblet cell type adenocarcinomas of the lung were examined clinicopathologically and immunohistochemically. The stage and survival curve of goblet cell type adenocarcinomas were compared with those of 44 cases of pure or mixed Clara cell and bronchial surface epithelial cell (Clara and BSE) type adenocarcinomas. Each case of goblet cell type was matched with two cases of Clara and BSE type as to sex, age and date of surgery. In goblet cell type adenocarcinomas, lymph node metastasis was less frequently and intrapulmonary metastasis was more frequently detected than in other types of adenocarcinomas (p < 0.001 and p < 0.05, respectively). Goblet cell type adenocarcinomas showed better prognoses than Clara and BSE type adenocarcinomas. However, the estimated survival curves of those two groups become similar after adjustment of the TNM condition using Cox's proportional-hazard general linear model. This result indicated that the longer survival of goblet cell type adenocarcinoma was due to the characteristic distribution of TNM conditions, that is, unique local growth and low incidence of lymph node metastasis. When goblet cell type adenocarcinoma was macroscopically classified into two types, i.e. solitary peripheral nodule type (nodular type) and multifocal nodular type or consolidation of all or part of a lobe (diffuse type), the nodular type had better prognosis than the diffuse type (p < 0.05). Immunohistochemically, 83%, 11%, and 0% of goblet cell type adenocarcinomas were positive for NCC-CO-450, carcinoembryonic antigen (CEA), and surfactant apoprotein, respectively. Most Clara and BSE type adenocarcinomas were negative for NCC-CO-450, but positive for CEA and surfactant apoprotein. NCC-CO-450 was considered to be a good immunohistochemical marker of goblet cell type adenocarcinoma of the lung. These results indicated that goblet cell type tumors are different from most adenocarcinomas of other types both clinicopathologically and immunohistochemically. Acta Pathol Jpn 41: 737-743, 1991.     

Quantitative electron microscopic observations on Paneth cells of germfree and ex-germfree Wistar rats

Summary Ultrastructural changes of Paneth cells of germfree (Gf) rats which had been inoculated with bacteria-containing feces from conventionally-reared (SPF) rats were quantitatively examined. 12 and 24 h after inoculation, the Paneth cells showed a striking decrease in the number of secretory granules and the occurrence of large vacuoles. Phagosomes containing bacteria were not seen. After 4 days, the secretory granules reaccumulated and smooth-surfaced apical vesicles increased in number. It is discussed that the large vacuoles may be related to membrane-retrieval events following the massive extrusion of secretory granules whereas the apical vesicles appear to serve this function when exocytosis is not pronounced. In addition to the large secretory granules ca. 10% of Paneth cell profiles contained a few dense-cored vesicles measuring about 150 nm in diameter which resemble peptidergic neurosecretory granules.     

Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon

To develop stem cell therapy for small intestinal (SI) diseases, it is essential to determine whether SI stem cells in culture retain their tissue regeneration capabilities. By using a heterotopic transplantation approach, we show that cultured murine SI epithelial organoids are able to reconstitute self-renewing epithelia in the colon. When stably integrated, the SI-derived grafts show many features unique only to the SI but distinct from the colonic epithelium. Our study provides evidence that cultured adult SI stem cells could be a source for cell therapy of intestinal diseases, maintaining their identity along the gastrointestinal tract through an epithelium-intrinsic mechanism.     

Incidence of Paneth Cells in Minute Tubular Adenomas and Adenocarcinomas of the Large Bowel

This study attempted to demonstrate the incidence of Paneth cells within large bowel tubular adenoma and adenocarcinoma according to location and macroscopic appearance using minute tumors (up to 5 mm in size). We have shown that Paneth cells were sometimes seen in the early stage of the development of large bowel epithelial neoplasia. According to the macroscopic appearance (elevated or depressed type), in large bowel epithelial neoplasia, there was a statistical difference between the depressed type (32.5%, 14 of 40 cases) and the elevated type (16.6%, 24 of 145 cases) (Chi square analysis, p < 0.05) in the incidence of Paneth cells. Paneth cells were seen more frequently in adenocarcinoma (45.8%, 11 of 24 cases) than in tubular adenoma (16.8%, 27 of 161 cases), with a significant statistical difference (Chi square analysis, p < 0.01). According to location, in both tubular adenoma and adenocarcinoma, Paneth cells were more frequently observed in the proximal colon (tubular adenoma: p < 0.01, adenocarcinoma: p < 0.05, Chi square analysis). Acta Pathol Jpn 42: 579 584, 1992.     

Small Cell Neuroendocrine Carcinoma of the Urinary Bladder: Report of Three Cases with Ultrastructural Analysis

Three cases of small cell neuroendocrine carcinoma of the urinary bladder were studied by light and electron microscopic techniques. Dense-core, membrane-bound granules were identified in the cytoplasm of all 3 cases, substantiating the light microscopic impression of a morphologic similarity to other neuroendocrine carcinomas, such as small cell (oat cell) carcinoma of the lung. Two of the three cases showed clinical evidence of distant metastases, suggesting an aggressive biologic potential of this tumor similar to oat cell carcinoma of the lung. A partial remission was induced in these 2 cases using chemotherapy protocols similar to the drug regimens for small cell (oat cell) carcinomas of the lung. Recognition of this distinct entity has important clinical implications regarding therapeutic approach.