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.     

Multiple endocrine neoplasia type 1‐associated cystic pancreatic endocrine neoplasia and multifocal cholesterol granulomas

A novel combination of tumors was found in a 68 year‐old female with Multiple Endocrine Neoplasia type‐1 (MEN 1) that included a cystic pancreatic endocrine neoplasm (CPEN), a pituitary adenoma, and multifocal cholesterol granulomas (MCGs) in the breast, pleura, and the extremities. The pancreatic tumor displayed a single central locule surrounded by a thin rim of neoplastic parenchyma. The tumor showed heterogeneity in the architecture that included glandular, trabecular and solid patterns. The tumor cells of the pancreas were immunohistochemically positive for both endocrine and pancreatic acinar markers including chromogranin A, synaptophysin, glucagon, lipase, and reg protein. Electron microscopy revealed that there were numerous smaller dense‐cored neurosecretory granules, larger zymogen‐like granules and microvilli on the apical side of the tumor cells. The pancreatic tumor was diagnosed as CPEN with acinar cell features. Analysis of the DNA extracted from the tissues revealed that there is a MEN1 germline mutation in exon 10 codon 527, and somatic mutation in exon 2 codon 32 in the pancreatic tumor, and one base pair deletion in exon 2 codon 79 in the pituitary adenoma. Here, we report the case and discuss possible pathogenesis of CPEN and MCGs in a patient with MEN 1.     

Ultrastructure and Electron Inununocytochemistry of Insulin-producing B-Cell Tumors from Transgenic Mice: Comparison with Counterpart Human Tumors

This paper reports on an ultrastructural and electron-microscopic immunocytochemical study of pancreatic B cells from normal mice, pancreatic B cells and derivative tumors from transgenic mice, and tissue from human pancreatic B-cell tumors. In normal and neoplastic B cells from both species, typical immature and mature β-granules (with spherical cores of variable density) were observed, whereas typical β-granules with a crystalloid core were only present in human B cells (normal and tumor). A small number of atypical granules were found in distinct neoplastic cells which contained no typical β-granules. The atypical granules were smaller (100–200 nm diameter) than typical β-granules (250–450 nm diameter) seen in other cells. Immunoreactivity for proinsulin was localized only to immature granules, whereas insulin and C-peptide immunoreactivities were demonstrated in atypical, immature, and mature granules. In transgenic mouse and human B-cell tumors, insulin immunoreactivity was consistently weaker than the immunostaining for C-peptide. An intragranular, topographic segregation of immunoreactive C-peptide was observed in a population of transgenic tumor cells. Our results showed similarities in antigenic distribution and only slight differences in morphology between human and mouse B cells. Therefore, the transgenic mouse system may prove to be an effective model for studying mammalian B-cell tumorigenesis.     

Oncocytic non-functioning endocrine tumor of the pancreas

Herein is presented the case of a malignant non-functioning endocrine tumor of the pancreas with oncocytic features, and a discussion on the high incidence of malignancy in oncocytic endocrine pancreatic tumors. The patient was a 65-year-old woman who showed no paraneoplastic symptoms produced by functioning pancreatic endocrine tumors. The primary tumor was located in the body and tail of the pancreas, and had metastasized to the liver. Tumor cells were arranged in a ribbon-like or trabecular pattern and had an abundant eosinophilic cytoplasm containing numerous mitochondria and neurosecretory granules. The cytoplasm of the tumor cells was intensely stained with an antimitochondrial antigen antibody. Most tumor cells stained positively with Grimelius stain and for chromogranin A. Some tumor cells also stained for synaptophysin. However, the tumor cells negatively stained for hormones such as insulin, glucagon, somatostatin, gastrin, vasoactive intestinal peptide and pancreatic polypeptide, for serotonin, and for pancreatic enzymes such as amylase and trypsin. Analysis of 18 oncocytic pancreatic endocrine tumors, consisting of those reported previously and that in the present case, suggests that the high incidence of malignancy in oncocytic endocrine tumors is associated with the high incidence of non-functioning endocrine tumors among them, most of which are malignant.     

Ultrastructure and Electron Inununocytochemistry of Insulin-producing B-Cell Tumors from Transgenic Mice: Comparison with Counterpart Human Tumors

This paper reports on an ultrastructural and electron-microscopic immunocytochemical study of pancreatic B cells from normal mice, pancreatic B cells and derivative tumors from transgenic mice, and tissue from human pancreatic B-cell tumors. In normal and neoplastic B cells from both species, typical immature and mature β-granules (with spherical cores of variable density) were observed, whereas typical β-granules with a crystalloid core were only present in human B cells (normal and tumor). A small number of atypical granules were found in distinct neoplastic cells which contained no typical β-granules. The atypical granules were smaller (100-200 nm diameter) than typical β-granules (250-450 nm diameter) seen in other cells. Immunoreactivity for proinsulin was localized only to immature granules, whereas insulin and C-peptide immunoreactivities were demonstrated in atypical, immature, and mature granules. In transgenic mouse and human B-cell tumors, insulin immunoreactivity was consistently weaker than the immunostaining for C-peptide. An intragranular, topographic segregation of immunoreactive C-peptide was observed in a population of transgenic tumor cells. Our results showed similarities in antigenic distribution and only slight differences in morphology between human and mouse B cells. Therefore, the transgenic mouse system may prove to be an effective model for studying mammalian B-cell tumorigenesis.     

Serous cystic neoplasm in an intrapancreatic accessory spleen

Serous cystic neoplasm (SCN) of the pancreas is a benign epithelial neoplasm, except in extremely rare malignant cases. Development of SCN in tissues other than the pancreas has been never reported. Here we present the first reported case of SCN in an intrapancreatic accessory spleen (IPAS). A 54‐year‐old female patient with von Hippel‐Lindau (VHL) syndrome was found to have pancreatic tail mass. Pathologically the 25‐mm solid mass was an IPAS showing proliferation of clear cuboidal tumor cells without atypia, forming numerous small cysts. The tumor cells were rich in cytoplasmic glycogen and distributed in the splenic tissue almost diffusely. Immunohistochemically, tumor cells were positive for cytokeratins, MUC6, and neuron‐specific enolase, and negative for neuroendocrine markers. From these findings, we diagnosed the lesion as SCN in IPAS. This tumor is suggested to develop as a VHL‐associated SCN from coexisting pancreatic tissue in IPAS rather than as a metastatic tumor.     

Solid and cystic papillary neoplasm of the pancreas: A clinico-cytopathologic and immunocytochemical study of five new cases diagnosed by fine-needle aspiration cytology and a review of the literature

We report here on five new cases of solid and cystic papillary neoplasm (SCPN) of the pancreas diagnosed by fine-needle aspiration cytology (FNAC). All cytologic samples were obtained by ultrasonography, and the smears were conventionally fixed and stained. Special histochemical and immunocytochemical stains were also performed in some samples. Cytology revealed in all but one case numerous pseudopapillary structures composed of fibrovascular stalks lined with one or more layers of bland-appearing, uniform tumor cells. The tumor cells had round-to-oval euchromatic nuclei with frequently folded smooth contours and one or two small nucleoli. Their cytoplasm often contained eosinophilic, PAS-positive, and diastase-resistant inclusions. Foamy cells, psammoma bodies, blood, and cellular debris were found in the background. The criteria for the differential diagnosis versus other pancreatic lesions are discussed in some detail, as is the role of immunocytochemistry (ICC). In the literature, only 28 cases of cytologically investigated SCPN have been reported to the best of our knowledge. The most helpful criteria for the conclusive identification of SCPN by FNAC include the pseudopapillary arrangement with bland-appearing tumor cells, and, especially, the finding of acidophilic, PAS-positive, and diastase-resistant cytoplasmic granules. © 1995 Wiley-Liss, Inc.     

Pancreatic acinar cell carcinoma. An analysis of cell lineage markers, p53 expression, and Ki-ras mutation.

In a series of 22 pancreatic acinar cell carcinomas, including two acinar cystadenocarcinomas, cellular differentiation was analyzed by immunocytochemistry and electron microscopy. In addition, overexpression of p53 protein and Ki-ras codon 12 mutation was studied. Four of the 20 noncystic acinar cell carcinomas showed a pure acinar pattern, nine an acinar-solid, and seven a solid pattern. All tumors stained for at least one of the following pancreatic acinar markers: trypsin (21 of 22), lipase (19 of 22), chymotrypsin (13 of 22), phospholipase A2 (nine of 22), and pancreatic stone protein (19 of 22). One-third of the tumors expressed neuroendocrine markers (synaptophysin, eight of 22; chromogranin A, six of 21) and duct cell markers (CA19.9, nine of 21; B72.3, six of 21). Cellular coexpression of trypsin and synaptophysin was demonstrated in one tumor. Electron microscopy revealed zymogen granules (nine of nine). In only one of 16 tumors a Ki-ras mutation at codon 12 was found, whereas in none of 19 tumors could overexpression of p53 protein be demonstrated. The results suggest that acinar cell carcinomas show obvious capacity to differentiate into several directions, but nevertheless constitute an entity different from ductal adenocarcinomas or endocrine tumors.     

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.     

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 x 8 x 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 ultrastructurally. The clinicopathologic significance of polypoid presentation of gallbladder carcinoid tumor is emphasized.     

Pigmented granules in functional black adenoma of the adrenal gland: A histochemical and ultrastructural study

A black adenoma of the adrenal gland was laparoscopically removed from an 61-yr-old Japanese female who had clinical and laboratory findings characteristic of Cushing’s syndrome. The tumor consisted of polygonal cells that contained numerous brown pigmented granules of various sizes by routine hematoxylin-eosin staining. The histochemical study showed that the pigment had the characteristics of lipofuscin, not of melanin or neuromelanin. Electron microscopic study revealed tumor cells with two types of pigmented granules. These results show that there might be differences in the lipid metabolism of individual tumor cells in black adenomas of adrenal; which suggests an interesting histogenesis for these granules.     

Pigmented "black" pheochromocytoma of the adrenal gland: a case report and review of the literature

A pigmented "black" mass was discovered incidentally in a 72-year-old woman. The tumor, which was detected near the upper pole of the left kidney, was cystic and intensely black throughout with the presence of abundant, coarse, dark brown to black pigment granules. Histologic examination showed a proliferation of monomorphous neoplastic cells arranged in a typical zellballen growth pattern. These features indicated a diagnosis of pheochromocytoma. Immunostains for chromogranin A, synaptophysin, and neuron-specific enolase were positive. The immunostain for HMB-45 was negative. Electron microscopy showed neurosecretory-type granules and larger pleomorphic granules, which were considered most consistent with neuromelanin, a waste product of catecholamine metabolism. The evidence of melanin or melanin-like pigment in the adrenal gland has been described in only 10 cases in the literature and is always a microscopic finding. The case reported here is unique for the characteristic black macroscopic appearance and the abundance of pigment.     

BENIGN CLEAR CELL TUMOR OF THE LUNG A Histopathologic Study

Benign clear cell tumor of the lung is extremely rare, and its histogenesis is still in dispute. We experienced a case of this neoplasm in the lung of a 28-year-old man, and carried out a study using both light and electron microscopy and immunohistochemistry. Histologically, the tumor was composed of sheets of large round or polygonal cells with abundant clear cytoplasm surrounded by thin-walled blood vessels. Electron microscopy showed granules (180 nm in diameter) in the cytoplasm. Immunohistochemically, S-100 protein-positive tumor cells were seen, but other neural markers and the markers for epithelial, muscular, vascular, histiocytic and endocrine cell origins were negative. The histogenesis of this pulmonary neoplasm could not be definitively determined, but its neural cell origin remains a possibility.     

Solid pseudopapillary neoplasm, pancreas type, presenting as a primary ovarian neoplasm

Solid pseudopapillary neoplasm has historically been associated with the pancreas, categorized as a tumor of low malignancy. Recently, solid pseudopapillary neoplasm was reported to arise as a primary ovarian tumor in 3 women. We report a fourth case identified in a 48 year-old woman with an 8-cm left ovarian mass. A left salpingo-oophorectomy was performed. Microscopic examination demonstrated a predominately cystic neoplasm comprised of solid nests of cells with an epithelioid to plasmacytoid appearance, associated with blood vessels, hemorrhage, and degenerative changes, that is, pseudopapillary structures. The tumor cells stained focally for pancytokeratin, progesterone receptor, and CD57 with diffuse nuclear expression of β-catenin. Ki-67 was 5% to 10%. Synaptophysin, inhibin, and E-cadherin stains were negative. Clinical and radiologic follow-up of our patient demonstrated no pancreatic lesions. This is a rare report of a primary ovarian solid pseudopapillary neoplasm. Prolonged follow-up is needed to determine how this case will fare clinically.     

SO-CALLED "PAPILLARY and CYSTIC NEOPLASM OF THE PANCREAS"

A case of so-called "papillary and cystic neoplasm of the pancreas" (PCNP) was reported and investigated immunohistochemically and ultrastructurally. A tumor of the pancreatic head in a 21-year-old female was curatively resected. The tumor was cystic and histologically consisted of uniform cells in papillary and solid structure. Although there was no immunoreactivity for pancreatico-gut hormones or secretory products of the pancreas in the tumor cells, most of the tumor cells were diffusely immunoreactive for neuron-specific enolase (NSE). Some neurosecretory granules were detected in the tumor cells ultrastructurally. Both facts suggested endocrine cell character of the tumor. Certain cases of PCNP might show a differentiation to endocrine cells.     

Benign clear cell tumor of the lung. A histopathologic study

Benign clear cell tumor of the lung is extremely rare, and its histogenesis is still in dispute. We experienced a case of this neoplasm in the lung of a 28-year-old man, and carried out a study using both light and electron microscopy and immunohistochemistry. Histologically, the tumor was composed of sheets of large round or polygonal cells with abundant clear cytoplasm surrounded by thin-walled blood vessels. Electron microscopy showed granules (180 nm in diameter) in the cytoplasm. Immunohistochemically, S-100 protein-positive tumor cells were seen, but other neural markers and the markers for epithelial, muscular, vascular, histiocytic and endocrine cell origins were negative. The histogenesis of this pulmonary neoplasm could not be definitively determined, but its neural cell origin remains a possibility.     

Granular changes in vascular leiomyosarcoma

Summary A 78-year-old male presented a tumor mass in the left arm which was surgically excised. Part of the tumor, when examined by light microscopy, showed the characteristic cytological features of a leiomyosarcoma. Other areas of neoplasm comprised layers of tumoral spindle-cells surrounding abnormal blood vessels. Nests of similar neoplastic cells were observed in the intima and media of these blood vessels. Wide areas of neoformation were made up by interlacing bundles of acidophilic polyedral cells with large irregular nucleus. Mitoses were frequent. The cytoplasm contained a great number of granules intensely PAS stained with and without prior diastase digestion. Electron microscopic examination revealed that the granular cells possessed a continuous basal lamina, numerous pinocytotic vesicles and abundant 80–150 Å microfilament bundles. Within the microfilament bundles, as well as apposed to the plasma membrane, electrondense bodies were often found. Granules contained degenerated organelles and probably corresponded to digestive vacuoles. In the intercellular spaces, fibrous long-spacing collagen was seen. The transition zone between the leiomyosarcoma cells and the granular cells showed intermediate cell types, with few granules and abundant microfilaments. The origin of granular cells from smooth muscle cells of blood vessels is discussed.     

So-called "papillary and cystic neoplasm of the pancreas." An immunohistochemical and ultrastructural study

A case of so-called "papillary and cystic neoplasm of the pancreas" (PCNP) was reported and investigated immunohistochemically and ultrastructurally. A tumor of the pancreatic head in a 21-year-old female was curatively resected. The tumor was cystic and histologically consisted of uniform cells in papillary and solid structure. Although there was no immunoreactivity for pancreaticogut hormones or secretory products of the pancreas in the tumor cells, most of the tumor cells were diffusely immunoreactive for neuron-specific enolase (NSE). Some neurosecretory granules were detected in the tumor cells ultrastructurally. Both facts suggested endocrine cell character of the tumor. Certain cases of PCNP might show a differentiation to endocrine cells.     

Solid and cystic acinar cell tumors of the pancreas. A report of two cases with immunohistochemical and ultrastructural studies

Two pancreatic tumors were found in young women without detectable functional symptoms. These tumors were identical in gross, histological and electron microscopic features. Each of them formed a large abdominal mass. One of them was found because of this abdominal mass, while the other was found incidentally. Grossly, the tumors were well circumscribed by a firm, white, fibrous capsule, and their cut-surfaces showed mainly cystic degenerative changes with necrotic and hemorrhagic material, with only some solid portions. The solid portions were composed of uniform cells forming solid and papillary structures with numerous PAS-positive diastase-resistant granules. Immunohistochemical staining for alpha 1-antitrypsin showed a granular distribution. Electron microscopic examination showed that the tumor cells had numerous mitochondria, zymogen-like granules, and annulate lamellae. These findings strongly suggested acinar cell differentiation, although ductal and endocrine differentiation have also been observed by others. Therefore, this type of tumor can best be termed an acinar cell tumor. There was no recurrence in either patient after the operation. Long survival can be expected, but reports indicate that this neoplasm should be recognized as a lesion of low malignancy.