Carcinoid tumor of the middle ear containing serotonin and multiple peptide hormones. A case report and review of the pathology literature.

A 69-year-old man complaining of longstanding hearing loss and mild otorrhea was found to have a mass obliterating the external auditory canal and polypous tympanic mucosa with accompanying absence of the tympanic membrane and ossicular chain. Tumors excised from the external auditory canal and tympanum showed histologic features essentially characteristic of a carcinoid tumor: a ribbon or festoon arrangement of tumor cells, formation of anastomosing cords and glandular spaces, presence of numerous argyrophilic as well as argentaffin secretory granules within many of the tumor cells, and ultrastructural evidence of neurosecretory granules in the tumor cell cytoplasm. Immunohistochemically, the tumor was found to contain not only neuronal marker substances such as neuron-specific enolase, S-100 protein and chromogranin A, but also serotonin and multiple peptide hormones such as pancreatic polypeptide, glucagon, cholecystokinin and leucine-enkephalin. A review of the pathology of 17 previous cases of carcinoid of the middle ear suggested that this type of carcinoid may have a variegated hormone profile among carcinoids of foregut origin, and hormonally may resemble ileal carcinoid arising from the midgut, although their histogenetic origins may differ, because of frequent production of serotonin.     

Tumor of glomus jugulare report of a case.

A typical case of glomus jugulare tumor was presented. This 42-year-old man suffering from a left-sided impaired hearing progressive over a five year period was found to have a small hemorrhagic polypoid tumor in the left external auditory canal. After repeated surgical treatments the tumor removed was light and electron microscopically diagnosed as glomus jugulare tumor which corresponded to the 13th case in this country. The implication that this tumor may constitute a distinctive group of tumor among the neuroendocrine tumors from other sites was discussed from the facts of the presence of a large number of rather small argyrophilic granules of secretory type in the cytoplasm of tumor cells including the present case and of the appearance of increasing cases with functioning glomus jugulare tumor secreting catecholamine in the recent medical literature.     

Neuroendocrine adenoma of the middle ear with extension into the external auditory canal

We report a case of middle ear adenoma (neuroendocrine adenoma of the middle ear) protruding into the external ear canal. The patient was a 65-year-old man with hearing alterations and a headache in whom an otoscopy disclosed a sessile, pea-sized, brown-reddish, focally bleeding mass located in the posterior-superior aspect of the right external auditory canal. Histopathologically, there was a neoplasm composed of closely packed, sometimes back-to-back glandular structures formed by small uniform cuboidal or cylindrical cells. Small solid islands were also present. Following the histopathologic examination, a high resolution computed tomography was performed showing an extensive osteolytic defect mostly involving the mastoid air cells of the mastoid process with a partial destruction of the middle ear cavity. This defect was filled with a mass-like lesion with the density of soft tissue which bulged to the external auditory canal. Histopathologic examination of the mass in the middle ear cavity revealed findings identical to those seen in the original biopsy, confirming diagnosis of middle ear adenoma extending into the external ear canal. Keywords: skin - external auditory canal - neuroendocrine adenoma of the middle ear - carcinoid tumor.     

TUMOR OF GLOMUS JUGULARE REPORT OF A CASE

A typical case of glomus jugulare tumor was presented. This 42-year-old man suffering from a left-sided Impaired hearing progressive over a Ave year period was found to have a small hemorrhagic polypoid tumor in the left external auditory canal. After repeated surgical treatments the tumor removed was light and electron microscopically diagnosed as glomus jugulare tumor which corresponded to the 13th case in this country. The Implication that this tumor may constitute a distinctive group of tumor among the neuroendocrine tumors from other sites was discussed from the facts of the presence of a large number of rather small argyrophilic granules of secretory type in the cytoplasm of tumor cells including the present case and of the appearance of increasing cases with functioning glomus jugulare tumor secreting catecholamine in the recent medical literature.     

Argentaffin endocrine carcinoma (carcinoid) of the pancreas with concomitant breast metastasis: an immunohistochemical and electron microscopic study

A pancreatic carcinoid tumor that metastasized to the breast is reported. The breast tumor was originally diagnosed as adenocarcinoma of the breast. Silver impregnation revealed the presence of argentaffin cytoplasmic granules. Immunocytochemical studies demonstrated immunoreactivity for serotonin but not for lactalbumin, a marker for breast epithelial cells. These features, together with the electron microscopic observation of pleomorphic secretory granules, permitted recognition of the tumor as metastatic carcinoid. This report illustrates the importance of the combined histochemical, immunocytochemical, and electron microscopic studies of breast tumors with a carcinoid pattern.     

Primary carcinoid tumor of the urinary bladder.

A 62-year-old woman who presented with urinary frequency and microscopic hematuria was found to have a 1.2 x 1.0 x 0.6-cm polypoid carcinoid tumor of the urinary bladder. The tissue resected from the base after removal of the polypoid lesion disclosed a small focus of residual carcinoid tumor, associated with Brunn's epithelial nests, cystitis cystica, and cystitis glandularis. Tumor cells exhibited strong argyrophilia and weak argentaffinity. Immunohistochemical staining reactions were strongly positive for chromogranin and serotonin, and electron microscopy revealed characteristic dense-core granules. Flow cytometric evaluation revealed an aneuploid cell population with a DNA index of 1.20.     

Ultrastructural study of a rectal carcinoid showing direct contact with nerves

A small carcinoid was found in the rectum of a 55-year-old man, who had neither subjective symptoms nor the carcinoid syndrome. His serum serotonin level was within normal limits. Under a light microscope, the tumor was found to be a mixed type carcinoid which had infiltrated the submucosal layer, and showed a negative reaction to Grimelius' argyrophil staining. The ultrastructural study indicated that the tumor cells possessed the characteristically round granules and occasional direct contact with unmyelinated nerve fibers. But, no synaptic figure was encountered. Schwann-like cells were often observed surrounding these tumor cell-nerve fiber complexes. These findings may indicate that carcinoids have an affinity to the nervous tissue. This study was presented at the 25th Annual Meeting of the Clinical Electron Microscopy Society of Japan, Matsumoto, September 28–30, 1993.     

Pigmented squamous cell carcinoma with dendritic melanocyte colonization in the external auditory canal

A case of pigmented squamous cell carcinoma (SCC) with dendritic melanocyte colonization in the external auditory canal is reported and the previous cases are reviewed. A 65-year-old Japanese female was referred with a 7-year history of otitis. The patient also had a darkly pigmented 9 x 8 mm nodule in the external auditory canal. Microscopically, the tumor was SCC, but in some areas melanin pigments were found in the cytoplasm of the tumor cells. The tumor was thus diagnosed as pigmented SCC. As well as the tumor cells, dendritic-shaped cells colonized the tumor parenchyma and were immunohistochemically defined as melanocytes. The authors believe this is the first case of pigmented SCC with dendritic melanocyte colonization in the external auditory canal.     

A carcinoid tumor of the stomach with features of a midgut tumor

This report is, to our knowledge, the first of a gastric carcinoid tumor that, by electron microscopy, revealed pleomorphic neurosecretory granules similar to those found in carcinoid tumors arising from the midgut. On the basis of silver staining, this lesion would be classified as an argentaffin and argyrophil carcinoid tumor, of the type usually associated with midgut derivation. Immunostaining showed the presence of serotonin granules, and there was clinical evidence of intraoperative hyperserotoninemia. The lesion is believed to have arisen from foci of complete intestinal metaplasia, many of which were present in proximity to the site of the lesion and elsewhere in the stomach.     

Bronchial carcinoid tumor mimicking acinic cell tumor

A rare case of carcinoid tumor mimicking an acinic cell tumor is presented. A bicameral tumor measuring 8 x 6 mm in size was recognized in the right lung (B5bi) upon gross examination. Microscopically, the tumor consisted of basophilic polygonal cells forming an acinar pattern. Ultrastructurally, the majority of tumor cells had large membrane-bound cytoplasmic granules, measuring about 600 nm in diameter, which were similar to secretary granules of serous acinar cells (zymogen granules). These findings suggested that the tumor might be an acinic cell tumor originating from the bronchial gland. However, tumor cells were shown to be negative for periodic and Schiff (PAS) stain or lactoferrin, lysozyme and amylase immunohistochemically. On the other hand, they were shown to be argyrophilic by Grimelius stain and showed immunohistochemically positive reaction for serotonin, suggesting that the granules were neurosecretory granules and not zymogen granules. Based on these findings, we concluded that this tumor was an unusual variant of carcinoid tumor mimicking acinic cell tumor. Although carcinoid tumor has a wide histological spectrum, there has been no reported case, to our knowledge, of acinic cell tumor-like carcinoid tumor.     

“Carcinoid” tumor of the breast: A variant of conventional breast cancer?

A breast tumor with the morphologic features of a carcinoid tumor and containing large amounts of estrogen receptor protein was associated with areas of typical in situ and infiltrating lobular carcinoma. The carcinoid areas were argyrophilic and ultrastructurally contained electron dense granules on which silver grains were localized. Of 21 other examples of ordinary breast cancer, five showed histologic similarities to carcinoid tumors. Focal argyrophilia was observed in 11 invasive tumors. The presence of argyrophilic granules could not be correlated with the presence of “neurosecretory” granules, although groups of such granules were found in one case of in situ lobular carcinoma. Argyrophilic and “neurosecretory” granules imply the presence of hormonal substances, although in breast tumors these granules have not yet been chemically or immunochemically characterized. Until such evidence becomes available it would appear that most cases reported as primary carcinoid tumors of the breast have much more in common with conventional breast cancer than with the usual carcinoid tumor. Within this context it can be acknowledged that some breast cancers may focally exhibit a carcinoid-like differentiation.     

Goblet Cell Carcinoid of the Vermiform Appendix with Ovarian Metastasis Mimicking Mucinous Cystadenocarcinoma

We describe a case of goblet cell carcinoid of the vermiform appendix, which metastasized to the bilateral ovaries, uterus, vagina and peritoneum three years and four months after appendectomy. The appendiceal tumor showed transmural infiltration of carcinoembryonic antigen-positive goblet cell-type tumor cells, intermingled with a small number of argyrophilic cells immunoreactive for serotonin and chromogranin A. The presence of neurosecretory-type granules was confirmed ultrastructurally in some mucin negative tumor cells. The pattern of proliferation was typical of carcinoid tumor originating from the lowermost part of the mucosa, and showed lymphatic permeation. The metastatic lesions in the pelvic organs showed either diffuse infiltration of goblet cell-type tumor cells or mucinous cystadenocarcinoma like features, the latter being evident in the right ovary. No neuroendocrine component was identified in the metastatic deposits. The kinship of appendiceal goblet cell carcinoid to adenocarcinoma is discussed. Acta Pathol Jpn 41: 455–460,1991.     

Carcinoid tumor of the middle ear. An immunohistochemical and electron microscopic study. Report of a case

A primary tumor of the middle ear was examined histologically, histochemically, immunohistochemically and ultrastructurally. Neuroendocrine cell differentiation, a carcinoid feature, was demonstrated by the presence of numerous argyrophil granules, as well as positive serotonin, glicentin, glucagon, and human pancreatic polypeptide (hPP) granules in some of the Grimelium-positive cells. Chromogranin A was also detected in the cells, but much less frequently than Grimelius-positive staining. Neither neuron-specific enolase (NSE) nor epithelial membrane antigen (EMA) was demonstrated in the tumor. Mucin was demonstrated only intraluminally. Electron microscopy revealed many typical neurosecretory granules in tumor cells, but no apical mucin granules. The tumor appeared to be benign, and there has been no sign of recurrence during a postoperative period of one year.     

CARCINOID TUMOR OF THE MIDDLE EAR: An Immunohistochemical and Electron Microscopic Study Report of a Case

A primary tumor of the middle ear was examined histologically, histochemi-cally, immunohistochemically and ultrastructurally. Neuroendocrine cell differentiation, a carcinoid feature, was demonstrated by the presence of numerous argyrophil granules, as well as positive serotonin, glicentin, glucagon, and human pancreatic polypeptide (hPP) granules in some of the Grimelium-positive cells. Chromogranin A was also detected in the cells, but much less frequently than Grimelius-positive staining. Neither neuron-specific enolase (NSE) nor epithelial membrane antigen (EMA) was demonstrated in the tumor. Mucin was demonstrated only intraluminally. Electron microscopy revealed many typical neurosecretory granules in tumor cells, but no apical mucin granules. The tumor appeared to be benign, and there has been no sign of recurrence during a postoperative period of one year. ACTA PATHOL JPN38: 1453–1460, 1988.     

BRONCHIAL CARCINOID TUMOR MIMICKING ACINIC CELL TUMOR

A rare case of carcinoid tumor mimicking an acinic cell tumor is presented. A bicameral tumor measuring 8 × 6 mm in size was recognized in the right lung (B⁵bi) upon gross examination. Microscopically, the tumor consisted of basophilic polygonal cells forming an acinar pattern. Ultrastructurally, the majority of tumor cells had large membrane-bound cytoplasmic granules, measuring about 600 nm in diameter, which were similar to secretary granules of serous acinar cells (zymogen granules). These findings suggested that the tumor might be an acinic cell tumor originating from the bronchial gland. However, tumor cells were shown to be negative for periodic and Schiff (PAS) stain or lactoferrin, lysozyme and amylase immunohistochemicaly. On the other hand, they were shown to be argyrophilic by Grimelius stain and showed immunohistochemically positive reaction for serotonin, suggesting that the granules were neurosecretory granules and not zymogen granules. Based on these findings, we concluded that this tumor was an unusal variant of carcinoid tumor mimicking acinic cell tumor. Although carcinoid tumor has a wide histological spectrum, there has been no reported case, to our knowledge, of acinic cell tumor-like carcinoid tumor.     

Peripheral carcinoid tumor of the lung with focal melanin production

A case of carcinoid tumor of the lung with focal melanin production was encountered in a 56 year old Japanese woman. The tumor was found 16 years previously by mass survey chest X-ray and had enlarged two-fold in the intervening period. The tumor consisted of a variety of tumor cells showing a spindle, polygonal and pleomorphic appearance with abundant vasculature in the stroma. All tumor cells showed argyrophilia, together with a few showing argent-affinity. Melanin-containing tumor cells were also present in parts. Ultrastructurally, most tumor cells possessed various numbers of neurosecretory granules and a few of them contained granular type rnelanosomes. Tumor cells were connected with desmosomes and a few of them contained tonofilament-like microfilaments. Only a few contained both neurosecretory granules and melanin. By immunohistochemistry, serotonin, metenkephalin and β-endorphin positive cells were observed scattered throughout the tumor. A few tumor cells positive for tyrosine hydroxylase were also detected. Additionally, most tumor cells were positive for keratin. On the basis of these findings, the tumor of the current case is a pulmonary carcinoid tumor with focal melanin production.     

Human chorionic gonadotropin alpha-subunit in rectal carcinoids. Its mode of presence and the change of granule morphology.

To investigate the nature of endocrine cells immunoreactive for human chorionic gonadotropin alpha-subunit (hCG alpha), rectal carcinoid tumors were studied with immunohistochemistry and immunoelectron microscopy. There were two types of rectal carcinoids: Type A (n = 5) was diffusely argyrophilic and immunoreactive for serotonin with many hCG alpha-positive cells (16.7%-91.1%). Type B (n = 5) was dispersedly argyrophilic and contained, at most, 5% positive cells for pancreatic polypeptide (PP) with hCG alpha cells in 1.4% to 9.7%. By double immunostaining, 55.0% to 89.7% of hCG alpha cells were synchronously immunoreactive for serotonin in Type A and 3.2% to 11.8% of hCG alpha cells showed PP-positivity in Type B. HCG alpha-positive granules had a constant relationship between perimeter (P) and area (A), log10 A approximately D log10 P, in each case (n = 5). The inverse correlation was found between the value of D and the frequency of hCG alpha in the tumor or in the neoplastic cells (P less than 0.05). HCG alpha may represent the quantitative difference of rectal carcinoids and its expression may have some relation with granule morphology in neoplastic endocrine cells of the rectum.     

Goblet cell carcinoid of the vermiform appendix with ovarian metastasis mimicking mucinous cystadenocarcinoma

We describe a case of goblet cell carcinoid of the vermiform appendix, which metastasized to the bilateral ovaries, uterus, vagina and peritoneum three years and four months after appendectomy. The appendiceal tumor showed transmural infiltration of carcinoembryonic antigen-positive goblet cell-type tumor cells, intermingled with a small number of argyrophilic cells immunoreactive for serotonin and chromogranin A. The presence of neurosecretory-type granules was confirmed ultrastructurally in some mucin-negative tumor cells. The pattern of proliferation was typical of carcinoid tumor originating from the lower-most part of the mucosa, and showed lymphatic permeation. The metastatic lesions in the pelvic organs showed either diffuse infiltration of goblet cell-type tumor cells or mucinous cystadenocarcinoma-like features, the latter being evident in the right ovary. No neuroendocrine component was identified in the metastatic deposits. The kinship of appendiceal goblet cell carcinoid to adenocarcinoma is discussed.     

Mucinous carcinoid tumor of the appendix presenting as bilateral ovarian tumors

Mucinous carcinoid tumor of the vermiform appendix, an uncommon variant of appendiceal carcinoid, may present clinically with ovarian metastases. We studied a tumor by immunohistochemistry and electron microscopy and reviewed eight similar cases from the literature. The primary and metastatic tumors in our case were composed of mucin-producing cells and small argyrophilic cells arranged in cords and acini. Tumor cells in both primary and metastatic sites exhibited identical patterns of immunoreactivity for epithelial antigens (epithelial membrane antigen, carcinoembryonic antigen) and neuroendocrine antigens (serotonin, vasoactive intestinal polypeptide, adrenocorticotropic hormone). Ultrastructurally, the cells contained either mucin vacuoles or dense-core neurosecretory granules; rare individual cells contained both types of inclusions. When bilateral solid mucinous ovarian tumors are discovered at laparotomy, diagnostic appendectomy is indicated if no obvious extraovarian primary tumor can be found.     

Cardiovascular lesion of carcinoid syndrome. An autopsy case of bronchial carcinoid

An autopsy case of a 67-year-old Japanese male is presented. He had been suffering from carcinoid syndrome for 5 years and showed a typical picture of carcinoid heart disease. In Japan, carcinoid heart disease is rare and we can find only four reported cases (33% of reported carcinoid syndrome). The patient had high urinary secretion of 5-HIAA and high serum serotonin, and finally he died of heart failure and bronchopneumonia. The primary site of this carcinoid tumor was of the bronchus of the right B10c , and it had large hepatic metastases. Electronmicroscopically, the tumor cells had secretory granules measuring 1500-3500 A in diameter. Immunohistochemically, the tumor cells were markedly positive for human chorionic gonadotropin (hCG) and antidiuretic hormone (ADH) and positive for serotonin, in both the primary site and hepatic metastases. Characteristic fibrous plaques were detected in the right atrium, tricuspid valve, right ventricle, and left atrium. Electron-microscopically, the fibrous plaques consisted of smooth muscle cells and myofibroblasts surrounded by basement membrane-like material. The abundant matrix of the fibrous plaques contained acid mucopolysaccharide, microfibrils and collagen fibers. The same fibrous plaques were also found in hepatic veins. Furthermore, retroperitoneal fibrosis was present, which showed proliferation of myofibroblasts, fibroblasts and immature mesenchymal cells.