Atypical bronchial carcinoid with oncocytoid features. Its ultrastructure, with special reference to its granular content

A case of atypical bronchial carcinoid with oncocytoid features was studied. The tumor contained mitochondria-laden cells with scanty neurosecretory granules, heavily granulated cells, and intermediate forms. The neurosecretory granules were of three types as reported in previous cases: type P, type 3, and a double-core granule. The ultrastructural findings are characteristic of this type of 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.     

Pancreatic Polypeptide-immunoreactive Gallbladder Carcinoid Tumor

Gallbladder carcinoid tumor seen in a 62 year old woman is described. The neoplasm with typical histologic features of classic carcinoid tumor was a 10 × 8 × 3 mm polyp at the neck of the gallbladder. The argyrophilic tumor cells were diffusely immunoreactive for neuron-specific enolase, cystatin C, chromogranin A and pancreatic polypeptide. A few cells were further positive for somatostatin. The presence of neurosecretory type granules was confirmed ultrastructuraily. The cfinicopathoiogic significance of polypoid presentation of gallbladder carcinoid tumor is emphasized.     

Atypical Carcinoid Tumor of the Larynx: An Immunohistochemical, Ultrastructural, and Flow Cytometric Analysis

The clinicopathologic features, including a detailed immunohistochemical, ultrastructural, and flow cytometric analysis, are described in three cases of atypical carcinoid tumor of the larynx. All patients had metastatic disease within cervical lymph nodes at presentation and eventually developed distant metastases. Special stains revealed focal intracytoplasmic mucin accumulation, and immunohistochemistry showed the tumors to be positive for CAM 5.2, CEA, chromogranin A, and calcitonin. In two cases, double-staining techniques revealed occasional cells that stained for both mucin and chromogranin A. The histochemical and immunohistochemical findings in these two cases were confirmed at the ultrastructural level, with most tumor cells containing many neurosecretory granules. Smaller numbers of cells contained mucin vacuoles and, in occasional cells, both mucin and neuroendocrine granules were identified. The three tumors exhibited positive staining with D07 (anti-p53), and flow cytometric analysis revealed DNA aneuploidy and polyploidy. The double-staining and ultrastructural features indicate that laryngeal atypical carcinoid qualifies for the designation of true amphicrine carcinoma. Further study is necessary to determine whether mutation of the p53 gene is important in the evolution of laryngeal neuroendocrine tumors and whether DNA aneuploidy or polyploidy identifies a subset of these tumors with a poor prognosis.     

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.     

Malignant Mixed Exocrine-Endocrine Tumor of the Pancreas with Unusual Intracytoplasmic Inclusions

A case of malignant mixed exocrine-endocrine tumor of the pancreas is reported. Electron microscopy revealed abundant neurosecretory granules in most cells. Zymogen granules indicating acinar differentiation were seen in a few cells. Ductal features, including microvilli with prominent filamentous cores and intracytoplasmic mucin granules, were also noted in this lesion. Immunocytochemical stains were positive for serotonin and glucagon. Unusual intracytoplasmic fibrillary inclusions are described and their possible origin discussed.     

A BREAST CARCINOID TUMOR WITH SPECIAL REFERENCE TO ULTRASTRUCTURAL STUDY

A case of a carcinoid tumor of the left breast of an 83-year-old male is reported. On light microscopy the tumor showed the classical pattern of a carcinoid tumor. Neurosecretory granules were verified ultrastructurally, membrane-bound, about 180 nm in diameter, and possessing electron-dense contents. Some tumor cells had long slender cytoprocesses with small clear round granules other than neurosecretory ones.     

Primary carcinoid tumor in a polycystic kidney

A case of a primary carcinoid tumor within a polycystic kidney is reported. A 51-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) underwent a bilateral nephrectomy because of an infection in her polycystic kidneys. A tumor (1.5 cm in diameter) was incidentally found close to the hilum of the left kidney. Histologically, the tumor exhibited a predominantly trabecular pattern of cuboidal or columnar cells. Grimelius staining showed numerous silver-stained neurosecretory granules in most of the tumor cells; the tumor cells were also positive for chromogranin, synaptophysin, prostatic acid phosphatase (PAP) and neuron-specific enolase (NSE). The tumor was diagnosed as a primary carcinoid tumor of the kidney. Primary renal carcinoid is a very rare neoplasm, and this is the first report of such a lesion arising in a polycystic kidney.     

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.     

Pigmented intraosseous odontogenic carcinoma of the maxilla: a pediatric case report and differential diagnosis

We report a pigmented intraosseous odontogenic carcinoma of the maxilla occurring in a 6-year-old Japanese boy. Grossly, the tumor showed solid, gray-yellow, and markedly pigmented appearance. Histology showed neoplastic growths of atypical epithelial cells that occasionally contained melanin pigments. Melanocytes with dendritic processes were often found in the tumor cell clusters, and solitary or aggregated melanophages were scattered within the dense fibrovascular stroma. The tumor cells were diffusely positive for cytokeratins and epithelial membrane antigen, and focally positive for vimentin, neuron specific enolase, neurofilament protein, carcinoembryonic antigen, and amelogenin. Ultrastructural studies showed well-developed intercellular junctions, mainly desmosomes, and glycogen particles. In addition, some tumor cells contained melanosomes and/or a few neurosecretory granules. We consider that the present tumor suggests a close association of ectoderm, mesenchyma, and neuroectoderm in embryogenesis of the tooth, and can raise a diagnostic confusion with melanotic neuroectodermal tumor.     

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.     

Paraganglioma of the Cauda Equina: An Ultrastructural and Immunohistochemical Study of Two Cases

The ultrastructural and immunohistochemical features of 2 paragangliomas arising in the cauda equina are described. In both cases the tumor cells were arranged in small nests or cords and contained characteristic neurosecretory granules, lamellar stacks of rough endoplasmic reticulum (RER), and some well-developed Golgi apparatuses in their cytoplasm. The cells varied in electron density; the darker cells, occasionally resembling sustentacular cells, were probably dehydrated light cells because they contained a few neurosecretory granules. Sustentacular cells were difficult to identify by electron microscopy, but irregularly distributed S-100 protein and glial fibrillary acidic protein (GFAP) were found in these cells by immunostaining. Many tumor cells contained abundant neurofilaments. Curiously, a few cytokeratin-positive cells were found in 1 case. On microscopic examination, a small area of ganglioneuroma was found associated with the paraganglioma in 1 case. Ganglionic differentiation was concluded to be frequent in paragangliomas of the cauda equina region as in duodenal paragangliomas.     

Paraganglioma of the Cauda Equina: An Ultrastructural and Immunohistochemical Study of Two Cases

The ultrastructural and immunohistochemical features of 2 paragangliomas arising in the cauda equina are described. In both cases the tumor cells were arranged in small nests or cords and contained characteristic neurosecretory granules, lamellar stacks of rough endoplasmic reticulum (RER), and some well-developed Golgi apparatuses in their cytoplasm. The cells varied in electron density; the darker cells, occasionally resembling sustentacular cells, were probably dehydrated light cells because they contained a few neurosecretory granules. Sustentacular cells were difficult to identify by electron microscopy, but irregularly distributed S-100 protein and glial fibrillary acidic protein (GFAP) were found in these cells by immunostaining. Many tumor cells contained abundant neurofilaments. Curiously, a few cytokeratin-positive cells were found in 1 case. On microscopic examination, a small area of ganglioneuroma was found associated with the paraganglioma in 1 case. Ganglionic differentiation was concluded to be frequent in paragangliomas of the cauda equina region as in duodenal paragangliomas.     

Carcinoid Tumor of the Kidney with Morphologic and Immunohistochemical Profile of a Hindgut Endocrine Tumor: Report of a Case

A 54-year-old man underwent a radical nephrectomy for a presumed renal cell carcinoma. The tumor was large, showed areas of cystic degeneration and calcification, and had completely obliterated the normal renal parenchyma. The light microscopic appearance was atypical for renal cell carcinoma, and when electron microscopy revealed innumerable neurosecretory granules a diagnosis of carcinoid tumor was made. The tumor cells were argentaffin- and argyrophil-negative but were chromogranin-, neuron-specific enolase-, and leu-7-positive. When tested with a battery of antibodies against specific polypeptide hormones, the tumor exhibited diffuse pancreatic polypeptide and focal somatostatin immunoreactivity.

Our case represents only the 16th case of carcinoid tumor of the kidney to be reported and the first with demonstrated pancreatic polypeptide immunoreactivity. The predominantly trabecular histology, nonreactivity with silver stains, and immunohistochemical profile of this case are common characteristics of hindgut carcinoids, suggesting that, like rectal carcinoids, renal carcinoids are tumors of hindgut endocrine cells.     

Carcinoid Tumor of the Kidney with Morphologic and Immunohistochemical Profile of a Hindgut Endocrine Tumor: Report of a Case

A 54-year-old man underwent a radical nephrectomy for a presumed renal cell carcinoma. The tumor was large, showed areas of cystic degeneration and calcification, and had completely obliterated the normal renal parenchyma. The light microscopic appearance was atypical for renal cell carcinoma, and when electron microscopy revealed innumerable neurosecretory granules a diagnosis of carcinoid tumor was made. The tumor cells were argentaffin- and argyrophil-negative but were chromogranin-, neuron-specific enolase-, and leu-7-positive. When tested with a battery of antibodies against specific polypeptide hormones, the tumor exhibited diffuse pancreatic polypeptide and focal somatostatin immunoreactivity.

Our case represents only the 16th case of carcinoid tumor of the kidney to be reported and the first with demonstrated pancreatic polypeptide immunoreactivity. The predominantly trabecular histology, nonreactivity with silver stains, and immunohistochemical profile of this case are common characteristics of hindgut carcinoids, suggesting that, like rectal carcinoids, renal carcinoids are tumors of hindgut endocrine cells.     

CarcinoÏde oncocytaire bronchique

Summary We describe a bronchial tumor with a biphasic pattern. The main cellular population is composed of large cells with eosinophilic cytoplasm packed with mitochondria. These oncocytes countain few dense-core membrane limited granules. The secondary cell population has the morphological and histochemical features that characterize the typical bronchial carcinoid. A third cell type, recognizable at ultrastructural level, contains numerous neurosecretory granules and abundant large mitochondria, seeming therefore to represent a transitional cell form. We assume that oncocytes and carcinoid cells, found in the same tumor with intermediate forms, represent the extremes of a morphological spectrum. Furthermore, the oncocytic cytoplasmic components (neurosecretory granules and the mitochondria) are present in reciprocal arrangement in the carcinoid cells. These observations, together with similar reported cases suggest that the oncocytic state corresponds to a functional stage. We consider that oncocytes from this endobronchial tumor and from similar pathologic conditions reported in the literature correspond to carcinoid cells with mitochondrial hyperplasia and with diminished endocrine activity. This oncocytic carcinoid tumor is associated, in the same pulmonary lobe, with a second neoplasm that has the histological and ultrastructural features of a poorly differentiated carcinoid (oat-cell carcinoma).

Tirés-à-part: Dr. P. Walter     

Carcinoid tumor of the uterine cervix

Summary A case of carcinoid tumor of the uterine cervix is reported. The patient was a 76-year-old Japanese woman with a complaint of vaginal bleeding. She was clinically diagnosed as stage IVb carcinoma of the uterine cervix. Light microscopically, the tumor was characterized by formation of solid cell nests and, in limited areas, glandular structures. The tumor cells in solid cells nests showed positive argyrophil reaction but were negative for argentaffin reaction. At the ultrastructural level, the cytoplasm of the tumor cells contain numerous neurosecretory granules, microfilaments and well-developed Golgi complexes. On the bases of histochemical and electron microscopic features of tumor cells, the tumor was diagnosed as carcinoid tumor of the uterine cervix.     

Concomitant neuropeptide-producing endometrial carcinomas and ileal carcinoid tumors

The concomitant occurrence of neuropeptide-reactive endometrial carcinoma and ileal carcinoid tumor represents an observation that has been unreported until now. We have seen two patients with this rare combination of tumors. The endometrial carcinomas in these cases manifested focal immunoreactivity for neuron-specific enolase; in addition, one contained rare cells showing positive staining for gastrin, and the other displayed focal content of substance P. The carcinoid tumors seen in each case demonstrated immunocytochemical positivity for neuron-specific enolase and vasoactive intestinal polypeptide, and one also exhibited immunoreactivity for gastrin. Whether this association of neoplasms represents a syndromic complex or a coincidence is a matter of speculation at present.     

Abnormal pigmentation of schwannoma attributed to excess production of neuromelanin-like pigment

Five cases of non-melanotic pigmented schwannoma with excess accumulation of neuromelanin are presented. The tumors were composed basically of spindle or fusiform tumor cells, compatible with those of classical schwannoma, together with varying numbers of tumor cells containing various amounts of light brown or grayish pigment. Fontana-Masson stain demonstrated argentaffin granules in some tumor cells of each tumor and bleaching with potassium permanganate abolished argentaffin reaction. Ultrastructural examination demonstrated the granules contained fine particles with heterogeneous density, occasionally together with coarse granular materials or amorphous high-density areas, indicating lysosome or autophagosome. Neither typical melanosomes nor neurosecretory granules were detected. In immunohistochemistry, neurogenic markers as well as CD68 were expressed in most tumor cells in each case and various numbers of tumor cells were positive for Leu7 and CD34. Lysozyme was also frequently positive in tumor cells, especially in granular cells. HMB45 was not expressed in any of the cases. These findings indicate that these cases are schwannomas with abnormal accumulation of neuromelanin-like pigment.     

Primary renal carcinoid

A case of primary renal carcinoid in a 34-year-old man is reported. The lesion was morphologically identical to carcinoid tumors arising in the gastrointestinal or respiratory tracts. The renal carcinoid was focally argyrophilic and contained chromogranin and neuron-specific enolase disclosed by immunohistochemical studies. The diagnosis was further confirmed by membrane-bound cytoplasmic neurosecretory granules visualized by electron microscopy. The possible histogenesis of this unusual tumor and a review of the literature are discussed.