Amphicrine--composite calcitonin and mucin-producing--carcinoma of the thyroid

A case of thyroid carcinoma in a 38-year-old male with a high serum level of calcitonin is reported. The tumor was composed of polygonal argyrophilic cells, signet ring Alcian blue-positive cells, and a minority of amphicrine elements. The same polymorphic cellular component was seen at the ultrastructural level. Anticalcitonin immunoperoxidase revealed that the majority of cells were positive, including the amphicrine cells. In spite of calcitonin production it is felt that cases similar to the present one should be distinguished from "ordinary medullary" carcinoma and the terms "amphicrine" or "composite calcitonin and mucin-producing carcinoma" are proposed.     

Amphicrine — Composite Calcitonin and Mucin-Producing — Carcinoma of the Thyroid

A case of thyroid carcinoma in a 38-year-old male with a high serum level of calcitonin is reported. The tumor was composed of polygonal argyrophilic cells, signet ring Alcian blue-positive cells, and a minority of amphicrine elements. The same polymorphic cellular component was seen at the ultrastructural level. Anticalcitonin immunoperoxidase revealed that the majority of cells were positive, including the amphicrine cells. In spite of calcitonin production it is felt that cases similar to the present one should be distinguished from “ordinary medullary” carcinoma and the terms “amphicrine” or “composite calcitonin and mucin-producing carcinoma” are proposed.     

Amphicrine carcinoma of the pancreas. Report of two cases

Amphicrine carcinomas are rare tumors defined by the presence of tumor cells showing evidence of both exocrine and endocrine differentiation. We here report two cases of amphicrine carcinomas of the pancreas, an exceedingly rare localization for this type of tumors. Diagnosis was made in respectively, a 32-year-old woman and a 66-year-old man; tumors measured 7 and 3 cm in diameter; metastatic dissemination was present in both cases. The first patient, treated by surgery and chemotherapy, is alive, without disease progression, after 26 months; the second patient deceased early after the diagnosis. In both cases, the first diagnosis considered at cytological and histological examination was endocrine carcinoma. The amphicrine nature of the lesion was ascertained by the combined demonstration of mucus staining and chromogranin A expression in the same cells. In one case, the amphicrine nature of tumor cells was confirmed by the ultrastructural examination. The identification of the amphicrine nature of an apparently endocrine tumor is of relevance, because of the poor prognosis of amphicrine carcinomas as compared to endocrine carcinomas and the requirement for aggressive therapy.     

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.     

Composite adenocarcinoma and large cell neuroendocrine carcinoma of the rectum

Composite glandular-endocrine tumors of the gastrointestinal tract are rare neoplasms. Even more uncommon are the so-called amphicrine tumors, lesions in which dual epithelial and endocrine differentiation occurs in the same cell. We describe a patient who complained of rectal pain and bleeding with a mixed or composite adenocarcinoma and neuroendocrine carcinoma of the rectum. Histological examination revealed a distinct adenocarcinoma of conventional type with glandular structures admixed intimately with a neuroendocrine carcinoma. The latter component was deeply infiltrative, while the adenocarcinoma occupied the more superficial aspect of the tumor. What was interesting was the immunophenotype of the lesion: cytokeratin (CK) 20 expression was very focal in the adenocarcinoma component and negative in the neuroendocrine carcinoma, while CK 7 was expressed strongly in the adenocarcinoma and only focally in the neuroendocrine component. This cytokeratin profile suggests a possible origin from the anal transitional zone.     

Insulinoma with Fibrillar Inclusions and Acinar Cell Elements

Islet cell tumors associated with exocrine elements are rare. An insulinoma was removed from the head of the pancreas of a 33 -year-old woman. Ultrastructural and immunohistochemical studies demonstrated that, in addition to the endocrine cells, the tumor had a small population of cells with an acinar cell morphology. Rare cells exhibiting both endocrine and exocrine features (amphicrine cells) were also identified. Another unusual finding in this case was the presence of a large number of intracytoplasmic filamentous inclusions that, even though they have been observed in other neoplasms, have not previously been reported in endocrine tumors of the pancreas. The demonstration of cells with mixed endocrine features supports the concept that both the endocrine and exocrine portions of the components of the pancreas have a common embryologic origin.     

Insulinoma with Fibrillar Inclusions and Acinar Cell Elements

Islet cell tumors associated with exocrine elements are rare. An insulinoma was removed from the head of the pancreas of a 33 -year-old woman. Ultrastructural and immunohistochemical studies demonstrated that, in addition to the endocrine cells, the tumor had a small population of cells with an acinar cell morphology. Rare cells exhibiting both endocrine and exocrine features (amphicrine cells) were also identified. Another unusual finding in this case was the presence of a large number of intracytoplasmic filamentous inclusions that, even though they have been observed in other neoplasms, have not previously been reported in endocrine tumors of the pancreas. The demonstration of cells with mixed endocrine features supports the concept that both the endocrine and exocrine portions of the components of the pancreas have a common embryologic origin.     

Amphicrine carcinoma of the liver

Amphicrine tumors are defined by evidence of both glandular and neuroendocrine differentiation in the same cell. These are extremely rare tumors, with only scattered case reports in the pancreas and stomach. We here report a case of amphicrine carcinoma occurring in apparent isolation in the liver. The tumor was characterized by signet ring cell morphology, mucicarmine, and periodic acid Schiff with diastase (PASD) positivity, and expression of chromogranin, synaptophysin, villin, and CDX2. No other tumor was identified by radiological or endoscopic examination of the gastrointestinal tract. The patient is disease-free 22 months after the resection. We speculate that this represents the first reported occurrence of primary amphicrine carcinoma of the liver.     

Toll-like receptors TLR4, TLR5 and TLR9 on gastric carcinoma cells: an implication for interaction with Helicobacter pylori

In the human stomach Toll-like receptors (TLRs) expressed by the gastric epithelium interact with Helicobacter pylori and mediate production of proinflammatory cytokines and chemokines during H. pylori infection. This results in chronic active gastritis, the background from which gastric carcinoma arises via the epithelial precursor lesions, intestinal metaplasia and dysplasia. Therefore, the question is arising whether gastric carcinoma cells are also able to interact with H. pylori. In this study, TLR4, TLR5 and TLR9 expression was investigated on tumor cells of gastric carcinoma and on its precursor lesions, intestinal metaplasia and dysplasia, by immunohistochemistry. Gastric epithelium with intestinal metaplasia (n=10) and dysplasia (n=3) expressed TLR4 and TLR5. TLR4 was strongly expressed by tumor cells of 17 out of 22 and TLR5 by tumor cells of all 22 patients with gastric carcinoma. TLR9, however, was not detectable in intestinal metaplasia or dysplasia and only focally in 6 out of 22 gastric carcinomas. In contrast to H. pylori gastritis, epithelial TLR expression in intestinal metaplasia, dysplasia and gastric carcinoma was diffusely distributed without subcellular polarization as demonstrated by confocal microscopy. This is the first study describing TLR expression on tumor cells of gastric carcinoma and its precursor lesions. Expression of TLRs enables gastric carcinoma cells to interact with H. pylori. As H. pylori can induce gastric carcinoma-promoting factors, such as IL-8, via epithelial TLR expression, TLR expression by gastric carcinoma cells may have a dangerous potential.     

Amphicrine Medullary Carcinoma of the Thyroid with Luminal Differentiation: Report of an Immunohistochemical and Ultrastructural Study

A case of amphicrine medullary carcinoma of the thyroid is presented. The patient was an 18-year-old female with nonhereditary MEN lib, submucosal neuromas in the oral cavity, and a thyroid tumor that metastasized to regional lymph nodes. Histologically the thyroid tumor was composed of polygonal cells arranged in a solid/trabecular pattern admixed with mucus-producing goblet cells and displaying focal cytoplasmic lumen formation. Immunohistochemical stains were positive for calcitonin, carcinoembryonic antigen, and chromogranin. Electron microscopy demonstrated C-cells containing neurosecretory granules as well as intestinal-type microlumina. The presence of goblet cells and intestinal-type microlumina in medullary carcinoma of the thyroid is reminiscent of amphicrine tumors of the gastrointestinal tract and supports the hypothesis that the parafollicular C-cells of the thyroid may be of endodermal derivation.     

The detection of serotonin and gastrin in gastric carcinoma

It is believed that the immature precursor cells of gastric mucosa have multidirectional potency of differentiation and these cells can differentiate into both endocrine and nonendocrine tumor cells. Fifteen cases of surgically resected stomach with gastric nonendocrine carcinoma were studied by the three-layer immunoperoxidase method. Serotonin was found in five cases, gastrin in one case, and both serotonin and gastrin in three cases. Serotonin also was detected in the noncancerous mucosa in thirteen cases: ten showing positive cells in the antrum and seven in the body. Gastrin was found in the noncancerous mucosa in 13 cases: eight in the antrum, five in the body. In four cases, a few serotonin positive cells were found in glands showing intestinal metaplasia. No correlation was found between the endocrine tumor cells and the types of carcinoma. Because endocrine cells can be detected in general types of gastric carcinoma, these findings suggest that the different kinds of cancer cells (endocrine and nonendocrine) may have a common origin.     

Amphicrine Differentiation in Bronchioloalveolar Cell Carcinoma

We report for the first time a classical bronchioloalveolar cell carcinoma with both exocrine and endocrine differentiation (amphicrine) in the same cell. At electron microscopy the tumor cells showed a mixed type II alveolar cell/Clara cell and mucous differentiation. In addition, there were many dense-core neurosecretory granules at the base of the majority of the cells. Immunocytochemically the tumor showed positivity for surfactant and a panel of neuroendocrine antibodies, including NSE, PGP9.5, synaptophysin, and chromogranin A. The presence of neuroendocrine differentiation was not hinted at by routine histology and did not indicate a more aggressive behavior in this case since the patient is well 3 years after the resection.     

Amphicrine Medullary Carcinoma of the Thyroid with Luminal Differentiation: Report of an Immunohistochemical and Ultrastructural Study

A case of amphicrine medullary carcinoma of the thyroid is presented. The patient was an 18-year-old female with nonhereditary MEN lib, submucosal neuromas in the oral cavity, and a thyroid tumor that metastasized to regional lymph nodes. Histologically the thyroid tumor was composed of polygonal cells arranged in a solid/trabecular pattern admixed with mucus-producing goblet cells and displaying focal cytoplasmic lumen formation. Immunohistochemical stains were positive for calcitonin, carcinoembryonic antigen, and chromogranin. Electron microscopy demonstrated C-cells containing neurosecretory granules as well as intestinal-type microlumina. The presence of goblet cells and intestinal-type microlumina in medullary carcinoma of the thyroid is reminiscent of amphicrine tumors of the gastrointestinal tract and supports the hypothesis that the parafollicular C-cells of the thyroid may be of endodermal derivation.     

Amphicrine Differentiation in Bronchioloalveolar Cell Carcinoma

We report for the first time a classical bronchioloalveolar cell carcinoma with both exocrine and endocrine differentiation (amphicrine) in the same cell. At electron microscopy the tumor cells showed a mixed type II alveolar cell/Clara cell and mucous differentiation. In addition, there were many dense-core neurosecretory granules at the base of the majority of the cells. Immunocytochemically the tumor showed positivity for surfactant and a panel of neuroendocrine antibodies, including NSE, PGP9.5, synaptophysin, and chromogranin A. The presence of neuroendocrine differentiation was not hinted at by routine histology and did not indicate a more aggressive behavior in this case since the patient is well 3 years after the resection.     

Multiple carcinoid tumor combined with mucosal carcinoma in the stomach. A case report

A case of gastric multiple carcinoid tumor combined with mucosal carcinoma in a 63-year-old female is reported. The carcinoid tumors, larger than 0.5 mm in diameter, and endocrine cell micronests, smaller than 0.5 mm in diameter, were mostly located in areas of chronic atrophic gastritis. Their distribution was coincident with that of multiple carcinoid tumor in type A gastritis. The majority of the tumor cells were positive for human chorionic gonadotropin (HCG) and Leu 7 by immunohistochemistry and contained various numbers of intracytoplasmic secretory granules as revealed by electron microscopy. Two mucosal carcinoma foci did not show endocrine characteristics. These carcinoid tumors were thought to have originated in HCG-producing argyrophil cells which had been stimulated by hypergastrinemia accompanying chronic atrophic gastritis. The mucosal carcinomas were regarded as incidental.     

MULTIPLE CARCINOID TUMOR COMBINED WITH MUCOSAL CARCINOMA IN THE STOMACH

A case of gastric multipe carcinoid tumor combined with mucosal carcinoma in a 63-year-old female is reported. The carcinoid tumors, larger than 0.5 mm in diameter, and endocrine cell micronests, smaller than 0.5 mm in diameter, were mostly located in areas of chronic atrophic gastritis. Their distribution was coincident with that of multiple carcinoid tumor in type A gastritis. The majority of the tumor cells were positive for human chorionic gonadotropin (HCG) and Leu 7 by immunohistochemistry and contained various numbers of intracytoplasmic secretory granules as revealed by electron microscopy. Two mucosal carcinoma foci did not show endocrine characteristics. These carcinoid tumors were thought to have originated in HCG-producing argyrophil cells which had been stimulated by hypergastrinemia accompanying chronic atrophic gastritis. The mucosal carcinomas were regarded as incidental.     

Mixed acinar-endocrine carcinoma of the pancreas--a case report.

A case of pancreatic carcinoma with both acinar and endocrine features is presented. The patient was a 52-year-old female presenting with jaundice of 3 weeks'' duration. The tumor was a 6 x 6 cm-sized round solid mass in the head of pancreas, invading the superior mesenteric vein. Histologically, it was composed of monotonous ovoid cells with eosinophilic granular cytoplasm in solid nests and sheets with occasional acinar and glandular differentiation. Immunohistochemical study revealed coexpression of acinar and endocrine markers; amylase, chromogranin, neuron-specific enolase, glucagon, somatostatin, and gastrin in tumor cells. This is the first documented case of mixed acinar-endocrine carcinoma of the pancreas in Korea, and its amphicrine nature reflects a close histogenetic relationship between pancreatic exocrine and endocrine cells.     

Endocrine Precursor Lesions of Gastroenteropancreatic Neuroendocrine Tumors

This review focuses on precursor lesions of gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs). There are three conditions that are associated with hyperplastic changes in endocrine cells preceding GEP-NETs: autoimmune chronic atrophic gastritis or multiple endocrine neoplasia type 1 (MEN1) with gastric enterochromaffin-like (ECL) cell hyperplasia; MEN1 with gastrin and somatostatin cell hyperplasia in the duodenum and glucagon cell hyperplasia in the islets of the pancreas; and inflammatory bowel disease with endocrine cell hyperplasia in the colon. In gastric ECL cell hyperplasia, it is assumed that hypergastrinemia promotes the growth of the ECL cells of the corpus mucosa and leads to hyperplasia and neoplasia. In the duodenum and the pancreas, the MEN1-associated germline mutation of the menin gene obviously causes hyperplasia of the gastrin and somatostatin cells (duodenum) and the glucagon cells (pancreas), resulting in multifocal development of tumors. These tumors show allelic deletion of the MEN1 gene, whereas the precursor lesions retain their heterozygosity. The endocrine cell hyperplasia in the colon described in inflammatory bowel disease has neither a genetic nor a definite hormonal background.     

Melanin-producing medullary carcinoma of the thyroid gland

An unusual case of medullary carcinoma of the thyroid gland with melanin production is described. In addition to typical histologic characteristics, some tumor cells show strong positive reaction for calcitonin by immunohistochemical study. Ultrastructurally dense-core granules and immature melanosomes are found in the same tumor cell. The tumor is thought to arise from a common precursor cell of neural crest origin with both C cell and melanocytic differentiation capable of producing both calcitonin and melanin.