The prevalence, prognostic significance and hormonal content of endocrine cells in gastric cancer

Twenty-six of 100 cases of gastric adenocarcinoma contained argyrophil cells. All these tumours were carcino-embryonic antigen positive and 13 contained variable amounts of gastro-enteropancreatic peptides and amines. There was no significant difference in mucin type, extent or incidence of intestinal metaplasia between tumours with and those without endocrine cells. The prognosis for both groups was similarly poor, contrasting with that for carcinoid and atypical carcinoid. Endocrine cell hyperplasia was evident in the adjacent mucosa in some of the cases of endocrine positive tumours. There was no association between achlorhydria and the presence of endocrine cells in the tumours. The origin of the neoplastic endocrine cells remains speculative, occurring either as a mutation of a single stem cell or as a synchronous malignant transformation of two epithelial cell types exposed to a particular carcinogenic factor(s). Adenocarcinomas containing endocrine cells appear to be as biologically aggressive as the usual adenocarcinomas of the stomach and therefore should be treated in a like manner.     

Glandular duodenal carcinoid--a somatostatin rich tumour with neuroendocrine associations

The clinical and pathological features of four cases of duodenal carcinoid tumour are presented. All four tumours showed a glandular pattern, and in three cases this was associated with psammoma bodies. In three tumours somatostatin was identified by immunocytochemistry in most tumour cells. In two cases the duodenal tumours were associated with von Recklinghausen's disease and phaeochromocytoma. The importance of these unusual features is discussed, and it is suggested that these glandular carcinoids are a specific subgroup of endocrine cell tumours which appear to have potentially important clinical and pathological associations.     

Nuclear pleomorphism in typical carcinoid tumours of the lung: problems in frozen section interpretation

Pulmonary typical carcinoid tumours are generally easy to diagnose with their uniform cells, carcinoid growth pattern and lack of mitoses. However, nuclear pleomorphism, which is common in other neuroendocrine tumours, is not emphasized in pulmonary carcinoid tumours. Three cases of typical carcinoid tumours, because of marked nuclear pleomorphism on frozen section, were misdiagnosed as non-small cell carcinomas.     

A very rare case of synchronous primary lung cancer lymph node metastasis

A 76 year old patient presented with two synchronous primary lung tumours. One was identified as an adenocarcinoma and the second as an atypical carcinoid tumour. When reviewing the lymph node slides it was seen that one lymph node contained metastatic deposits from both primary tumours. Synchronous lung tumours are fairly rare occurrences, but even rarer is the finding of synchronous metastases to the same lymph node. The atypical carcinoid deposit was very subtle in appearance and could easily have been overlooked. This case demonstrates a useful learning point to not miss these rare and subtle findings as the resulting tumour staging was affected and may have implications for further patient management.     

Mixed carcinoid and adenocarcinoma of the appendix: report of 4 cases with immunohistochemical studies and a review of the literature.

Four cases of mixed carcinoid and adenocarcinoma of the appendix were reported. All cases presented with a dominant cecal-appendiceal tumor mass and local metastasis. Two patients had multiple peritoneal implants mimicking primary peritoneal serous adenocarcinoma or carcinomatosis. Histopathologic features of the tumors are similar, with infiltrating microglandular and cribriform patterns of tumor nests, and variable numbers of goblet cells. A literature review of "goblet cell carcinoid" that included nonlocalized cases revealed a significant percentage (>14%) of tumor-associated death, in contrast to the classic carcinoid tumor. Immunohistochemical stains were helpful to separate these tumors from carcinoid tumors and primary peritoneal serous adenocarcinoma. Mixed carcinoid and adenocarcinomas were cytokeratin (CK)-20 positive, and negative or weakly positive for chromogranin A and synaptophysin. Carcinoid tumors were CK20 negative and diffusely positive for chromogranin A and synaptophysin. Peritoneal serous adenocarcinomas were CK20 negative. These cases were clinically aggressive, and 1 patient had multiple recurrences and responded partially to chemotherapy.     

Composite glandular-endocrine cell carcinoma of the stomach. Report of two cases with goblet cell carcinoid component

Composite glandular-endocrine cell carcinoma (CGECC) is recognized as a special type of gastric tumor composed of ordinary adenocarcinoma and neuroendocrine tumors. Goblet cell carcinoid (GCC) is a well-established type of appendiceal carcinoid, but the GCC component has not been well delineated in CGECC of the stomach. We report on two gastric CGECCs with a GCC component, analyzing the histologic components by immunohistochemistry. On initial biopsy, both cases were diagnosed as signet-ring cell carcinoma. However, the resected tumors consisted of three components: signet-ring cell carcinoma, GCC, and glandular adenocarcinoma. Although some signet-ring carcinoma cells and goblet carcinoid cells were indistinguishable by hematoxylin and eosin staining, E-cadherin immunostaining disclosed a definitive difference regarding the staining pattern in these cells. Both patients are well, with no recurrent tumor for about 10 years of follow-up. CGECC with a GCC component may have been confused with conventional adenocarcinoma with signet-ring cells. In cases of advanced signet-ring cell carcinoma with good prognosis, the possibility of such CGECC has to be considered.     

Minute carcinoid tumor of the uterine cervix associated with microinvasive adenocarcinoma, with reference to its histogenesis

A rare case of carcinoid tumor of the uterine cervix associated with adenocarcinoma was reported. The carcinoid tumor was composed of round to polygonal cells showing solid or trabecular proliferation. Most of these cells and a small number of isolated cells wedged in neoplastic glands were positive with either Grimelius or Fontana-Masson stains, and also positive for serotonin by immunostain (PAP method). Positively stained cells were thus considered to have the same histochemical nature as enterochromaffin cell. The carcinoid tumor was minute, about 2 X 2 mm and the adenocarcinoma was a microinvasive one. In some parts, smooth transition between both tumor components was observed. From these findings, it is suggested that both the carcinoid tumor and the adenocarcinoma in the present case were derived from a primitive precursor cell of common mesodermal origin.     

Adenocarcinoid of the vermiform appendix

Summary Four cases of adenocarcinoid of the appendix were studied. Two tumours were found among 28 cases primarily diagnosed as appendiceal carcinoids. They showed characteristic histological structures with features of both a conventional carcinoid tumour and a mucinproducing adenocarcinoma with goblet cells. All tumours were small and ill-defined; three were associated with fibrous obliteration of the appendiceal lumen. All were diagnosed incidentally by the pathologist in appendices removed en passant or because of acute appendicitis. Three of the tumours appeared well differentiated with a low degree of malignancy similar to that of the conventional carcinoid tumour. In one case however, the tumour was less differentiated with atypical foci and a high mitotic count and had metastasised to peritoneum and both ovaries.     

Immunohistochemical study of chromogranin in 100 cases of pheochromocytoma,carotid body tumour,medullary thyroid carcinoma and carcinoid tumour

Summary Neuroendocrine cells have histologically common features represented by argyrophilic cytoplasm containing neuroendocrine granules. Neuroendocrine granules are composed of various kinds of peptide hormones, amines, carrier proteins and ATP. Although various kinds of peptide hormones have been detected in neuroendocrine tumours, a peptide hormone has not been required as a standard marker for these tumours. Chromogranin is a purified protein which binds catecholamines specifically and is recognized as a carrier protein. We carried out an immunohistochemical study of chromogranin immunoreactivity in 100 neuroendocrine tumours including pheochromocytomas, carotid body tumours, medullary thyroid carcinomas and carcinoid tumours. Marked immunoreactivity was observed in 85% of carcinoid tumours and 100% of the other tumour types. A non-functioning paraganglioma and a malignant carcinoid tumour without any other detectable marker also showed strong immunoreactivity to chromogranin. Chromogranin immunoreactivity is a useful tool for neuroendocrine tumours.     

MINUTE CARCINOID TUMOR OF THE UTERINE CERVIX ASSOCIATED WITH MICROINVASIVE ADENOCARCINOMA, WITH REFERENCE TO ITS HISTOGENESIS

A rare case of carcinoid tumor of the uterine cervix associated with adenocarcinoma was reported. The carcinoid tumor was composed of round to polygonal cells showing solid or trabecular proliferation. Most of these cells and a small number of isolated cells wedged in neoplastic glands were positive with either Grimelius or Fontana-Masson stains, and also positive for serotonin by immunostain (PAP method). Positively stained cells were thus considered to have the same histochemical nature as enterochromaffln cell. The carcinoid tumor was minute, about 2×2 mm and the adenocarcinoma was a microinvasive one. In some parts, smooth transition between both tumor components was observed. From these findings, it is suggested that both the carcinoid tumor and the adenocarcinoma in the present case were derived from a primitive precursor cell of common mesodermal origin. ACTA PATHOL. JPN. 37:1183–1198, 1987.     

Carcinoid tumour of the middle ear. A morphological and immunohistochemical study with comments on histogenesis and differential diagnosis

Primary carcinoid tumours of the middle ear are extremely rare, only nine cases having been reported. However, their true incidence is probably greater, since they are very difficult or impossible to distinguish from adenomas and adenocarcinomas with conventional histological stains. We describe the clinical, histological, immunohistochemical and ultrastructural findings in a carcinoid tumour of the middle ear in a 50-year-old woman. Immunohistochemical studies on non-neoplastic middle ear mucosa undertaken to investigate the histogenesis of such tumours are also reported. Histologically, the tumour consisted of both solid areas and areas of tubular structures containing intraluminal mucus. All the tumour cells reacted with the anti-keratin antibody KL 1; some were argyrophil and reacted with antibodies against neuron-specific enolase, chromogranin A, Leu-7, serotonin, pancreatic polypeptide, glucagon and lysozyme. Electron microscopy revealed dense core granules in the tumour cells. Endocrine cells could not be detected in non-neoplastic middle ear mucosa. Pancreatic-polypeptide-like immunoreactivity was demonstrated immunohistochemically in all three other published cases of carcinoid tumour of the middle ear investigated for this peptide, and glucagon-like immunoreactivity was also exhibited by one of these. Since carcinoid tumours of the middle ear often, as in this case, exhibit some degree of glandular differentiation, immunohistochemical or electron-microscopic investigation to detect neuroendocrine differentiation is of particular importance in adenomatous middle ear neoplasms.     

The endocrine component of prostatic carcinomas, mixed adenocarcinoma-carcinoid tumours and non-tumour prostate. Histochemical and ultrastructural identification of the endocrine cells

Two types of endocrine-paracrine (EP) cells have been detected histochemically and ultrastructurally in normal and hyperplastic prostates; i.e. type I cells resembling intestinal EC (enterochromaffin) cells and type 2 cells similar to urethral EP cells previously reported by Casanova et al. (1974). About one-third of the 40 prostatic carcinomas studied contained EP cells: two of these were composite tumours exhibiting both adenocarcinomatous and carcinoid patterns. These four tumours have also been studied histochemically and ultrastructurally. ACTH and beta-endorphin immunoreactive cells, ultrastructurally resembling pituitary corticotrophic cells, have been identified in three tumours. Cells identical with type I and type 2 cells of the normal prostate were detected in two cases and in a further case, respectively.     

Enteroendocrine cell hyperplasia, carcinoid tumours and adenocarcinoma in long-standing ulcerative colitis

Chronic ulcerative colitis may be accompanied by a variety of epithelial changes, including loss of goblet cells, Paneth cell metaplasia, villous metaplasia, and dysplasia. Total colitis is also accompanied by an increased incidence of adenocarcinoma. All these changes are assumed to be secondary to repeated mucosal damage, but how they develop is unknown. Little attention has been paid to the enteroendocrine cell population, despite the postulated role of these cells as producers of trophic hormones. We describe two patients with long-standing ulcerative colitis who developed both adenocarcinoma and carcinoid tumours. In both, there were increased numbers of enteroendocrine cells in the uninvolved colonic mucosa. We suggest that an increased enteroendocrine cell mass may be part of a non-specific reaction to chronic mucosal injury, and by producing an elevated level of trophic hormones may act as a promoter in the development of neoplasia.     

Sox10-positive sustentacular cells in neuroendocrine carcinoma of the lung

Tsuta K, Raso M G, Kalhor N, Liu D C, Wistuba I I & Moran C A
(2011) Histopathology  58, 276–285
Sox10‐positive sustentacular cells in neuroendocrine carcinoma of the lung Aims: Sustentacular cells are found in approximately half of pulmonary carcinoid tumours. However, most studies of sustentacular cells have used the less‐specific antibody to the S100 protein, and any correlation between the presence of sustentacular cells and other clinicopathological factors is unclear. The aim of this study was to analyse the significance of sustentacular cells in pulmonary neuroendocrine carcinomas (NECs). Methods and results: A Sox10 antibody was used to investigate 113 pulmonary NECs. Sustentacular cells were observed in 66.7% of typical carcinoid (TC) and 58.3% of atypical carcinoid (AC) cases, but not in high‐grade NECs. Sustentacular‐rich tumours had a statistically significant correlation with peripheral locations. We found no statistical differences in age, gender, smoking history, overall survival, or the occurrence of lymph node metastasis. In all but one case, when sustentacular cells were present in the primary site, they were also present in the metastatic lymph nodes. The presence of sustentacular cells differed in morphological subtypes, with the spindle pattern being the most common subtype. Conclusions: Sox10‐positive sustentacular cells were observed in carcinoid tumours but not in high‐grade NECs. Sustentacular‐rich carcinoid tumours did not show a correlation with the occurrence of lymph node metastasis or survival. The sustentacular cells found differed in morphological subtypes.     

Expression of occludin in human rectal carcinoid tumours as a possible marker for glandular differentiation

AIMS: To examine whether or not the tight junction-associated transmembrane protein occludin is expressed in rosette or gland-like structures in human rectal carcinoid tumours. The tight junction is crucial for the formation and maintenance of organized tubular structures in glandular epithelia. Previous studies have reported the presence of glandular structures in carcinoid tumours, though they are not believed to arise from glandular epithelium. METHODS AND RESULTS: The expression profiles of occludin in 40 carcinoid tumours were examined immunohistochemically, using an anti-occludin monoclonal antibody. In eight (20%) samples of typical carcinoid tumours, a small number of rosette-like tubular structures outlined by occludin were detected. CONCLUSIONS: Tight junction-associated molecules, including occludin, are thought to be one of the most characteristic structural markers of polarized glandular structures. The results of the present study provide supportive evidence that carcinoid tumour cells are capable of glandular differentiation.     

Gastrin releasing peptide and gastrin releasing peptide receptor expression in gastrointestinal carcinoid tumours

AIMS: To establish whether gastrin releasing peptide (GRP) and the GRP receptor (GRPR) are expressed together in gastrointestinal carcinoid tumours. METHODS: Twenty six carcinoid tumours from the stomach, small intestine, appendix, and colorectum were investigated by immunohistochemistry for GRP and GRPR. RESULTS: GRP was detected in nine of 19 tumours and GRPR in 22 of 26. Coexpression of both the ligand and receptor was seen in six of 19 cases. GRPR but not GRP was more strongly expressed in appendix and colonic tumours. CONCLUSIONS: GRP and GRPR are produced by a large number of gastrointestinal carcinoid tumours. An autocrine/paracrine pathway may exist for GRP stimulated cell proliferation in some of these neoplasms, analogous to that seen in small cell anaplastic carcinoma of the lung.     

Prostate-specific acid phosphatase in carcinoid tumors

Summary Although prostate-specific acid phosphatase (PASP) has been recognized as a specific marker of tissue of prostatic origin, several investigators have pointed out that some of the carcinoid tumours and islet cell tumours of the pancreas reacted immunohistochemically to PSAP. We investigated 50 cases immunohistochemically comprising 44 carcinoids of the G-I tract, 3 of the bronchus, 1 each of the ovary, kidney and middle ear. PSAP positive cases were, 30 in G-I tract, one each in ovary and kidney. Eighty percent of tumours of hindgut origin were positive. Apart from the immunohistochemical study, the content of PSAP in preoperative serum and tumour tissue was estimated in a case with a rectal carcinoid. Extremely elevated PSAP was confirmed in both the serum and tumour tissue. Neuroendocrine tumours such as pheochromocytoma, medullary thyroid carcinoma, and islet cell carcinoma were investigated as controls. No cells immunoreactive to PSAP were observed in these control cases. Prostate specific antigen was definitely negative in carcinoids. We would emphasize that PSAP may be an excellent marker of carcinoids especially when derived from hindgut.     

Prealbumin in the diagnosis of bronchopulmonary carcinoid tumours.

The reliability of prealbumin as a diagnostic marker was studied in 60 cases of bronchopulmonary carcinoid tumours. There were differences in the incidence of positivity between typical and atypical carcinoids (well differentiated neuroendocrine carcinomas). Seventy five per cent of the carcinoid tumours were positive for prealbumin; (86.7% typical and 63.3% atypical carcinoids). In 15 cases, which were Grimelius negative, 10 were prealbumin positive. Only 8.3% carcinoids were negative with both prealbumin and Grimelius stains. Ten squamous, 10 adeno- and 10 small cell carcinomas showed only occasional scattered prealbumin positive cells. It is concluded that prealbumin is a useful marker for bronchopulmonary carcinoid tumours. It is cheap, readily available, and should be considered part of routine diagnostic procedures for the diagnosis of carcinoid tumours.     

Prostatic adenocarcinoma evolving into carcinoid: selective effect of hormonal treatment?

Two patients, aged 72 and 65 years, each underwent two prostatic resections spaced four and two years apart, respectively. In both cases the earlier procedure showed widespread adenocarcinoma with only occasional endocrine cells, while tissue from the later operations showed prostatic carcinoids. It is suggested that the conventional adenocarcinomas were sensitive to hormonal manipulations used in treatment, but that the originally sparse carcinoid components were resistant to this form of treatment and hence became the predominant tumours. These findings imply that endocrine differentiation in prostatic carcinoma leads to lack of sex steroid sensitivity.