Multifocal granular cell tumour of the biliary tree.

Fewer than 90 cases of granular cell tumour (GCT) of the biliary tract have been reported, including only five cases of multiple GCTs. We present the unusual case of a 40-year-old woman with multifocal GCTs affecting the intrahepatic biliary tree, which were initially suspected to be hepatic multiple metastases from a malignancy of unknown origin. The surgical specimen consisted of a hepatic segment in which five whitish nodular lesions were observed. On microscopic examination, nodular lesions were found in the portal tracts; these were composed of large polygonal cells with abundant highly granular cytoplasm. The nuclei were small and centrally located. The tumour cells tested diffusely positive for CD68-PGM1, S100 protein and α-inhibin, so a diagnosis of multifocal GCT of the biliary tree was made. Three years later, the patient is still alive and a MRI has shown no changes.

Granular cell ameloblastoma: A rare case report and review of literature.

Ameloblastoma is a benign locally aggressive type of odontogenic tumor derived exclusively from the epithelium. Histologically, ameloblastoma is classified into many variants, of which granular cell ameloblastoma (GCA) is a rare type, characterized by nest of large eosinophilic granular cells. This article describes a case of GCA in a 50-year-old female patient with clinical, radiological, and histological features along with a systematic review of the literature.

Malignant granular cell tumors: the role of electron microscopy in the definitive diagnosis of an extremely aggressive soft tissue neoplasm.

Granular cell tumors (GCTs) are rare soft tissue neoplasms which may be multicentric. The vast majority are benign, however approximately 100 malignant GCTs have been reported, with only 8 originating in the vulva. Malignant GCTs are very aggressive with very poor survival rates. As the diagnosis of malignant GCT carries an extremely poor prognosis, the utilization of EM ensures that the most accurate diagnosis possible can be rendered.

The origin and role of autophagy in the formation of cytoplasmic granules in canine lingual granular cell tumors.

Granular cell tumors (GCTs) are histologically characterized by polygonal neoplastic cells with abundant eosinophilic cytoplasmic granules. In humans, these cells are considered to be derived from Schwann cells, and the cytoplasmic granules are assumed to be autophagosomes or autophagolysosomes. However, the origin and nature of the cytoplasmic granules in canine GCTs have not been well characterized. The present study examined 9 canine lingual GCTs using immunohistochemistry, transmission electron microscopy (TEM), and cell culture and xenotransplantation experiments. In some cases, the tumor cells expressed S100, CD133, and desmin. The cytoplasmic granules were positive for LC3, p62, NBR1, and ubiquitin. TEM revealed autophagosome-like structures in the cytoplasm of the granule-containing cells. The cultured GCT cells were round to spindle shaped and expressed S100, nestin, Melan-A, CD133, LC3, p62, NBR1, and ubiquitin, suggesting that they were of neural crest origin, redifferentiated into melanocytes, and exhibited upregulated autophagy. The xenotransplanted tumors consisted of spindle to polygonal cells. Only a few cells contained cytoplasmic granules, and some had melanin pigments in their cytoplasm. The xenotransplanted cells expressed S100, nestin, Melan-A, and CD133. P62 and ubiquitin were detected, regardless of the presence or absence of cytoplasmic granules, while LC3 and NBR1 were detected only in the neoplastic cells containing cytoplasmic granules. These findings suggest that some xenotransplanted cells redifferentiated into melanocytes and that autophagy was upregulated in the cytoplasmic granule-containing cells. In conclusion, canine lingual GCTs originate from the neural crest and develop cytoplasmic granules via autophagy. In addition, the microenvironment of GCT cells affects their morphology.

Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma.

Pituicytomas are neoplasms that arise from pituicytes, which are specialized glia of the posterior pituitary. Pituicytes have 5 ultrastructural variants: light, dark, granular, ependymal, and oncocytic. Granular cell tumors of the pituitary gland are thought to arise from granular pituicytes. Spindle cell oncocytomas are considered to arise from folliculostellate cells, which are sustentacular cells of the adenohypophysis. Recent data suggest that, whereas pituicytes and all 3 tumor types are positive for TTF-1, folliculostellate cells are negative for TTF-1. We investigated 7 spindle cell oncocytomas, 4 pituicytomas, and 3 granular cell tumors for their genetic (BRAF(V600E) mutation and BRAF-KIAA fusion), immunohistochemical (GFAP, vimentin, S100 protein, olig2, IDH1-R132H, NF, galectin-3, chromogranin-A, CD56, EMA, CAM5.2, CD68, TTF-1, and bcl-2), and ultrastructural features to refine their classification. All tumors had nuclear positivity for TTF-1 and were negative for CAM5.2, chromogranin-A, and NF. GFAP, vimentin, S100, galectin-3, EMA, and CD68 were variably positive in the majority of the 3 tumor groups. Olig2 was only positive in 1 pituicytoma. Whereas granular cell tumors were negative for bcl-2 and CD56, pituicytomas and spindle cell oncocytomas showed variable positivity. All tumors were negative with the IDH1-R132H mutation-specific antibody, and none had evidence of BRAF alterations (BRAF(V600E) mutation and BRAF-KIAA fusion). Diffuse TTF-1 expression in nontumorous pituicytes, pituicytomas, spindle cell oncocytomas, and granular cell tumors indicates a common pituicyte lineage. The ultrastructural variants of pituicytes are reflected in these 3 morphologic variants of tumors arising from these cells. We propose the terminology "oncocytic pituicytomas" and "granular cell pituicytomas" to refine the classification of these lesions.

Granular cell tumor of the breast.

Granular cell tumor is a rare benign soft-tissue neoplasm, usually appearing in the tongue, the oral cavity and subcutaneous tissue. Examples of granular cell tumor of breast are encountered in 30-50-year-old women. Herein, we report ultrasonographic and mammographic imaging findings of a 59 years old woman presented with a painless palpable mass, which was diagnosed as granular cell tumor on histopathological analysis.

Histopathologic, immunohistochemical and ultrastructural features of a granular cell tumour in an Australian parakeet (Melopsittacus undulatus).

An adult male Australian parakeet (Melopsittacus undulatus) presented a firm nodular lesion in the lateral metacarpal region of the right wing. Microscopically, there were neoplastic cells, round and polyhedral in shape, with abundant, slightly eosinophilic granular cytoplasm; they were strongly periodic-acid Schiff-positive and resistant to diastase digestion. Some groups of neoplastic cells were immunopositive for smooth muscle actin and desmin. There was no immunopositivity for S-100 protein, CD68 and cytokeratin. Ultrastructurally, the neoplastic cells were round and polygonal in shape, and they were characterized by abundant cytoplasm with numerous homogeneous osmophilic bodies covered by an electron-dense membrane (lysosomes). The histopathologic, immunohistochemical and ultrastructural features of the neoplastic tissue are consistent with a granular cell tumour, which has been described in different animal species and anatomic locations; however, this seems to be an infrequent neoplasm in Australian parakeets. The immunopositivity of the neoplastic cells for smooth muscle actin and desmin, as well as slight positivity for muscle with Masson's trichrome, suggest that this is a tumour of myogenic origin.

Characterization of uterine granular cell tumors in B6C3F1 mice: a histomorphologic, immunohistochemical, and ultrastructural study.

The granular cell tumor is most often a benign neoplasm of uncertain origin. Four uterine granular cell tumors in control and treated female B6C3F1 mice were identified in chronic studies at the National Toxicology Program. Two tumors occurred in untreated control animals and 2 in treated animals receiving different compounds. Tissue sections were evaluated histologically and stained with hematoxylin and eosin, periodic acid-Schiff with diastase resistance, Masson's trichrome, toluidine blue, phosphotungstic acid-hematoxylin, and stained immunohistochemically with a panel of antibodies to muscle (desmin, alpha smooth muscle actin), neural (S-100, neuron specific enolase), epithelial (wide-spectrum cytokeratin), and macrophage (F4/80) markers. The main histomorphologic feature of tumor cells was the presence of abundant cytoplasmic eosinophilic granules that stained positive for periodic acid-Schiff with diastase resistance. Tumors varied in appearance and were comprised of sheets and nests of round to polygonal cells with distinct borders. Nuclei were hyperchromatic, pleomorphic, and centrally to eccentrically located and often contained single nucleoli. Occasional multinucleated giant cells were observed. Tumors were pale pink and homogeneous with trichrome stain and negative with toluidine blue. Three tumors had positive to weakly positive immunoreactivity for desmin, and 1 was positive for alpha smooth muscle actin. Expression of S-100, wide-spectrum cytokeratin, and neuron-specific enolase was negative for all tumors. Ultrastructurally, prominent electron-dense cytoplasmic granules were abundant and contained secondary lysosomes with heterogeneous lysosomal contents. The characteristics of these uterine granular cell tumors were suggestive of a myogenic origin.

Granular cell astrocytoma. A case report with immunohistochemical and ultrastructural characterization.

Granular cell astrocytoma (GCA) is an uncommon type of granular cell tumours (GCTs) in the central nervous system. Granular cells in these tumours are of enigmatic origin. We report a case of cerebral GCA in a 59-year-old man who suffered from diabetes and Addison-Biermer disease. The tumour was localized in the left parietal lobe. Microscopically, the tumour was almost entirely composed of large, polygonal cells with round to oval, granular eosinophilic, PAS-positive cytoplasm. The nuclei were located centrally or eccentrically and sometimes exhibited nucleolar vacuoles. The tumour cells were arranged in nests surrounded by blood vessels and connective tissue. Immunohistochemically, the granular tumour cells were reactive for GFAP and vimentin. They were intensively stained for ubiquitin and some of them were reactive for CD68. Moreover, a lot of stromal cells expressed CD68 reactivity. Ultrastructurally, most tumour cells were round or oval with only a few or without filaments. Their cytoplasm was filled with electron-dense granular material limited by a single membrane and autophagic vacuoles. Another type of tumour cells, present in a significantly lower number, revealed abundant cytoplasm with numerous intermediate filaments, swollen rough endoplasmic reticulum, mitochondria and a few clusters of granular material. Cells with numerous condensed electron-dense, bizarrely-shaped mitochondria and few filaments were occasionally observed. Among granular cells, macrophages with vacuoles and/or lamellar structures were visible. In our case, both immunohistochemical and ultrastructural analysis supported astroglial origin of the granular cell tumour.

Morphometry of pseudoepitheliomatous hyperplasia: objective comparison to normal and dysplastic oral mucosae.

OBJECTIVE: To compare the architectural and morphometric features of pseudoepitheliomatous hyperplasia (PEH) associated with oral granular cell tumors (GCT), normal oral mucosa and oral epithelial dysplasia. STUDY DESIGN: Quantitative comparisons between the diagnostic entities were carried out at the tissue level by estimating the fractal complexity of the epithelial connective tissue interface and at the cellular level by analyzing the morphometric features of algorithmically segmented epithelial cell areas. RESULTS: Casewise multivariate analysis showed that the fractal properties produced a correct discrimination rate of 96.4% between PEH and normal mucosa. Cellular parameters gave a 100% correct discrimination rate between PEH and mild dysplasia. Combining the fractal and cellular properties also showed 100% discrimination between PEH and normal mucosa and between PEH and mild dysplasia. CONCLUSION: The results show that PEH associated with GCT displays quantifiable morphometric features that make it differentiable from normal oral mucosa and oral epithelial dysplasia.

Granular cell tumor of the parotid gland. A case report.

BACKGROUND: Granular cell tumor (GCT) is a relatively uncommon soft tissue tumor of putative Schwann cell origin. This tumor can occur in multiple sites as a small, nontender nodule, but the parotid gland is unusual, and only several cases have been reported. CASE: A 46-year-old woman presented with a slowly growing mass in the left preauricular region for three years. Imaging studies confirmed a nodular lesion in the superficial lobe of the left parotid gland. Fine needle aspiration (FNA) cytology revealed scattered cellular clusters and single cells with abundant granular cytoplasm and indistinct cell borders. Background exhibited eosinophilic, granular, cytoplasmic material, and some scattered naked nuclei were also noted. Histologic examination with supportive immunohistochemical and ultrastructural studies confirmed GCT. CONCLUSION: GCT of the parotid gland is very unusual. Recognition of this tumor is important to make a definitive diagnosis before an operation. FNA is useful procedure in GCT of parotid gland for a preoperative diagnosis and proper treatment.

S-100-negative atypical granular cell tumor: report of a case.

A 38-year-old man presented with a solitary, round, 1.2 x 1.2 cm, bluish-colored, dome-shaped, hard nodule on the left side of the neck, which had grown over 2 months (Fig. 1). The nodule was nontender and nonmovable. Light microscopy revealed that the neoplasm was situated in the reticular dermis with extension into the papillary dermis. The tumor showed expansile growth with smooth and round borders, and was made up of sheets of cells arranged in nests or lobules separated by thin delicate connective tissue septa. The tumor cells were round, oval, or polygonal in shape with distinct cellular borders. The cells had abundant eosinophilic granular cytoplasm, and considerable variation of cellular and nuclear size was noted (Fig. 2a). The tumor cell nuclei were vesicular and some had pleomorphism (Fig. 2b). Sometimes multiple nucleoli were seen. Mitoses and necrosis were virtually absent. Immunohistochemical staining revealed that some of the cytoplasmic granules stained positively with periodic acid-Schiff (PAS) after diastase treatment. Tumor cells showed strong reactivity for CD68 and neuron-specific enolase, and negative results for S-100, factor XIIIa, cytokeratin, desmin, CD34, and smooth muscle actin. Electron microscopy revealed that the tumor was composed of polygonal cells with round to irregular nuclei, and the cytoplasm contained numerous secondary lysosomes. The tumor was completely excised.

Granular cell tumor of the canine central nervous system: two cases.

Although pure granular cell tumors have been reported in various sites in the dog, only one tumor has been reported in the central nervous system. Two dogs presented with neurologic signs had brain lesions detected by magnetic resonance imaging in the area of the olfactory bulbs and frontal cortex. In both dogs, a clinical diagnosis of a granular cell tumor was made from tissues obtained from stereotactic biopsies guided by computed tomography. Surgical removal of the tumors was followed by histopathologic, ultrastructural, and immunocytochemical characterization. Although not conclusive, these studies indicated that the granular cells were not of leucocyte origin but may have been derived from the meninges. One dog died 12 months after surgery, and the other was alive 4 months later.

Nine cases of granular cell tumors in B6C3F1 mice.

The histological characteristics of 9 cases of granular cell tumors (GCTs) observed in B6C3F1 mice were examined to determine their cellular origin. Seven of the 9 cases were found in the uterus and other 2 cases were in the subcutaneous tissue. Tumor cells had abundant granules in the cytoplasm which were stained with PAS and were resistant to diastase treatment. Ultrastructurally, the granules were identified as lysosomes. The cell surface had cytoplasmic processus showing interdigitation with adjacent cells. A character feature of the tumor cells was the presence of a desmosome-like structure on their cell surface but no basal lamina was demonstrated. Although GCTs have been considered to be derived from Schwann cells on the basis of their ultrastructural features and S-100 protein-immunopositive findings, the absence of basal lamina in the present cases may raise a controversy as to their origin.

Symptomatic granular cell tumor involving the pituitary gland in a dog: a case report and review of the literature.

A granular cell tumor involving the pituitary gland, optic chiasm and ventral pyriform lobes was discovered in a 12-year-old Labrador Retriever. Clinical signs included acute blindness, seizures, ataxia, weakness, and behavioral changes. The diagnosis was established by histopathologic and ultrastructural examination of neoplastic tissues collected at necropsy. Granular cell tumors involving the central nervous system are well documented in humans but rarely have been described in dogs. The location of the neoplasm and the clinical symptoms seen in this dog closely parallel those of a rare syndrome in humans commonly described as symptomatic parasellar or pituitary granular cell tumors. The cell of origin for these tumors is still highly debated, and attempts to characterize human granular cell tumors through immunohistochemistry have produced conflicting results. An immunohistochemical profile of this neoplasm revealed focal positive staining for vimentin with a lack of staining for neuron-specific enolase, glial fibrillary acidic protein, S-100, and synaptophysin. All neoplastic cells were strongly positive with the periodic acid-Schiff reaction.

Granular cell tumor: a review of the pathology and histogenesis.

As the name suggests, the histogenesis of the granular cell tumor is uncertain, but this intriguing neoplasm has occasioned much speculation and controversy since its description in 1926 as a myoblastoma. Though ubiquitous in its anatomic location, it is usually small, solitary, benign, and readily recognized by routine light microscopy, and questions concerning it are principally academic. However, a small number of cases are malignant and they can be difficult to identify in paraffin sections. The combined input from immunohistochemistry and electron microscopy has greatly clarified understanding of the morphology of this lesion and both methods are helpful when the differential diagnosis is a problem. The cell of origin is still undecided, and although distinct neural features argue for Schwannian origin, the noncommittal term granular cell tumor continues to be appropriate.

Granular cell tumor: a review and update.

The histogenesis of granular cell tumor (GCT) has been a source of controversy since its recognition as an entity by Abrikossoff in 1926. These lesions can occur in virtually any location. Benign GCTs are not uncommon, but malignant ones are rare and at times difficult to diagnose. The main morphologic feature is the granularity of the cytoplasm which is caused by a massive accumulation of lysosomes. Early suggestions that GCT may have a myoblastic origin have been discounted and use of the term granular cell myoblastoma as a designation for this tumor is discouraged. Although most investigators currently favor a Schwann cell derivation based on immunohistochemical and electron microscopic findings and advocate the designation of granular cell schwannoma, some differences exist between schwannomas and GCTs in their ultrastructural characteristics and the expression of some immunohistochemical markers. Other investigators believe that GCT is not a specific entity but rather a degenerative change that can occur not only in Schwann cells but also in a variety of other normal and neoplastic cells. Until more information becomes available, particularly that derived from cytogenetic studies, this lesion should be considered a separate entity and the descriptive designation of granular cell tumor continues to be appropriate.