Immunohistochemical study of autophagy associated molecules and cell adhesion molecules in canine intracranial granular cell tumors.

Granular cell tumors (GCTs) are characterized by abundant eosinophilic cytoplasmic granules. Based on the hypothesis that canine intracranial GCT is a subtype of meningioma and its cytoplasmic granules are formed through autophagy processes, histopathological and immunohistochemical examination were performed on biopsy samples from 7 cases of canine intracranial GCTs and 15 cases of conventional meningiomas. Histopathologically, 7/7 cases of GCTs involved the meninges; foci of meningothelial-like cells were observed in 3/7 cases; brain invasion was observed in 2/7 cases. Immunohistochemically, neoplastic cells of GCTs were positive for E-cadherin and negative for S100, cytokeratin, CD204, and ß-catenin in 7/7 cases. Neoplastic cells of 15/15 cases of meningiomas were positive for E-cadherin, and negative for S100 and CD204. Immunoreactivity of meningiomas for cytokeratin and ß-catenin was observed in 6/15 cases and 8/15 cases, respectively. Cytoplasmic granules of GCTs were positive for ubiquitin (5/7), p62 (5/7), and LC3 (7/7). Compared to GCTs, the ratios of ubiquitin (6/15) and p62 (3/15) positive cases were lower in meningiomas, and 15/15 cases were negative for LC3. These findings indicate that the biological natures of GCTs including anatomical location, histopathological features and immunoreactivity for E-cadherin are almost in conformity with those of meningiomas. The immunoreactivity for autophagy associated molecules may suggest the possible involvement of autophagy in cytoplasmic granule formation of canine intracranial GCTs.

S100 negative granular cell tumor of the oral cavity: dermoscopy and surgical approach.

We report the case of a 47-year-old male patient with S100 negative granular cell tumor of the oral cavity, focusing on dermoscopic features as well as surgical approach, not previously reported in the literature. The study contributes to the literature on dermoscopy and surgical treatment for this tumor and provides a practical approach to differentiating non-neural granular cell tumors and granular cell tumors.

S100 negative granular cell tumor of the oral cavity: dermoscopy and surgical approach

Abstract: We report the case of a 47-year-old male patient with S100 negative granular cell tumor of the oral cavity, focusing on dermoscopic features as well as surgical approach, not previously reported in the literature. The study contributes to the literature on dermoscopy and surgical treatment for this tumor and provides a practical approach to differentiating non-neural granular cell tumors and granular cell tumors.

[The histopathology and immunohistochemistry of granular cell tumour. A study of 12 cases with a brief historical note]. / Análisis histopatológico e inmunohistoquímico del tumor de células granulares. Estudios de 12 casos con una breve nota histórica.

INTRODUCTION AND OBJECTIVE: Granular cell tumour (GCT) is a benign neoplasm of neural/schwannian origin, usually presenting as a single asymptomatic lesion, mainly located in the dermis and subcutaneous tissue or submucosa, although multiple tumours may occur. Microscopically, GCTs are composed of large cells with abundant eosinophilic, granular cytoplasm arranged in sheets, nests, cords or trabeculae. Based on the cytological characteristics and the presence of necrosis, three types are recognized: benign, atypical and malignant. We aim to present the cytological and immunohistochemical characteristics of 12 granular cell tumours. MATERIALS AND METHODS: 12 cases of GCT were selected from the consultation files of one of the authors (COH) The paraffin embedded tissue was processed for immunostaining with S-100 protein, calretinin, CD68, α-inhibin, PGP9.5, CD57 (Leu7), CD63 (NKI / C3), Gap43 (growth-associated protein-43), SOX10, TFE-3 and Ki-67. RESULTS AND CONCLUSIONS: 6 male and 6 female patients, with an average age of 40, made up the study group. The most frequent location for the tumours was in the subcutaneous soft tissues of the arms. There were no malignant cases. All tumours were positive for S-100, CD57, SOX10, calretinin, CD68, PGP9.5, α-inhibin and TFE-3, with a low Ki-67 (1-5%). Additionally, we reported, for the first time, the positive immunoreaction to Gap43 (growth-associated protein-43) in GCT.

Peripheral nerve sheath tumors of the breast.

Benign and malignant peripheral nerve sheath tumors can involve the breast, presenting as masses in the dermis, deep breast parenchyma or axillary soft tissue. Although the histologic features are frequently characteristic, diagnosis can be challenging on core needle biopsy, and the differential diagnosis includes a variety of other benign and malignant spindle cell lesions of the breast. Here, we review the key clinical and pathological features of breast schwannoma, neurofibroma, granular cell tumor, and malignant peripheral nerve sheath tumor.

Eosinophilic Esophagitis and Esophageal Granular Cell Tumor: An Unexpected Association.

Esophageal granular cell tumors (GCTs) are rare. Eosinophilic esophagitis (EoE) is an immune-mediated disease characterized by esophageal eosinophilia despite proton pump inhibitor (PPI) therapy. Given that GCTs occur at sites of scarring and inflammation, we sought to determine the prevalence of EoE in patients with esophageal GCTs. Our center's pathology database was searched for GCT specimens from 1995 to 2014. Slides were blindly rereviewed. GCTs were scored for atypical cytological features. Presence and number of eosinophils in the tumor and the surrounding esophageal epithelium and any EoE features were recorded. Medical records were reviewed. From >30,000 esophageal cases, 23 esophageal GCTs were identified, with 18 available for review (16 adult, 2 pediatric). Median patient age was 38.7 years. Four adults had esophageal intraepithelial eosinophilia (peak 38 to 68 eosinophils/high power field [HPF]); 2 confirmed to have EoE, 1 with PPI-responsive esophageal eosinophilia, and 1 had not received PPI therapy. Both pediatric cases had confirmed EoE (peak 24 and 34 eosinophils/HPF). In total, 12/18 GCTs had intratumoral eosinophilia (peak 1 to 16 eosinophils/HPF). All 6 cases with esophageal eosinophilia had intratumoral eosinophilia. Two GCTs displayed atypical cytologic features. Esophageal eosinophilia was present in 25% of adult and 100% of pediatric GCTs, the majority confirmed to have EoE. Overall, 67% of cases had intratumoral eosinophilia and 2 had atypical features. On the basis of these findings, we propose evaluating surrounding tissue for eosinophilia when esophageal GCT is diagnosed, and adding GCT as a potential complication of untreated EoE. Research for an immunologic link between EoE and esophageal GCTs is needed.

Mediastinal Granular Cell Tumor in a 16-Year-Old Boy: A Surgical and Pathologic Perspective.

Granular cell tumor is a benign tumor of likely neural or neuroectodermal origin that occurs most commonly in the subcutaneous tissues of the trunk, breast, and extremities of adults. Congenital gingival lesions comprise the majority of the pediatric granular cell tumors. Granular cell tumors are generally small and asymptomatic, and while 1 in 10 patients has multiple tumors, recurrence and malignancy are very rare. Mediastinal granular cell tumors have been reported, most occurring in young adult or middle-aged women. We present a case of a 16-year-old asymptomatic boy with a large mediastinal granular cell tumor incidentally identified after a motor vehicle accident, and we review the intraoperative, microscopic, and ultrastructural features of this tumor. Both the patient's age and anatomical location are unusual for this tumor, which presented technical and diagnostic challenges to the patient care team.

Primary cutaneous malignant granular cell tumor: an immunohistochemical study and review of the literature.

Granular cell tumors (GCTs) are uncommon soft tissue tumors characterized by cytoplasmic granular appearance of the neoplastic cells. Malignant granular cell tumors (MGCTs) comprise less than 2% of GCTs and are mostly found in the subcutaneous soft tissues of the lower extremities, especially the thighs. Very few cases have been reported in the skin. The uncommon occurrence of cutaneous MGCTs and their histopathologic similarities with their benign counterpart make difficult the diagnosis of this particular malignancy. We describe a primary cutaneous MGCT that presented as a left posterior chest wall mass in a 51-year-old woman. Local excision was performed for the primary tumor, which was first interpreted as an atypical GCT, but 3 months later a left axillary mass appeared, and subsequent axillary lymph node dissection demonstrated metastatic disease in 4 of 12 excised lymph nodes. We report the immunophenotype of this primary cutaneous MGCT, which was studied with an ample panel of antibodies and compare our results with those of the few previously reported cases in the skin and subcutaneous soft tissues.

Diagnosis and management challenge of a granular cell astrocytoma of the pineal region: case report.

Granular cell astrocytoma (GCA) is a rare type of infiltrative brain tumor with most reported cases occurring in the suprasellar region. A pineal localization is extremely rare, with only 4 previously reported cases in the literature. The authors describe the case of a 16-year-old boy who developed signs of increased intracranial pressure and Parinaud syndrome. Cranial CT and MRI revealed a well-demarcated and enhanced mass in the pineal region accompanied by obstructive hydrocephalus. Subtotal resection was performed via a subtemporal approach. A histological diagnosis of GCA was made. Three years after surgery, the patient was alive and well without adjuvant therapy, and serial MRI showed no signs of progression of a small residual tumor. After a thorough review of the different epidemiological, clinical, and imaging features; treatments; and prognoses of GCAs in other intracranial localizations, the authors analyzed features of this tumor in the pineal region.

[Nerve sheath tumours]. / Les tumeurs des gaines des nerfs périphériques.

Peripheral nerve sheath tumors are common neoplasms in daily practice. Diagnosis and classification of most conventional peripheral nerve sheath tumors are relatively straightforward for the experienced observer; but on occasion, they are diagnostically challenging (especially with locally aggressive and malignant tumors). This article aims to provide an update of the data (clinical, histological, immunohistochemistry and genomic) of benign, intermediate and malignant peripheral nerve sheath tumors, thanks to the latest WHO "Classification of Tumors of Soft Tissue and Bone", published in 2013, which includes a new chapter on "Nerve Sheath Tumors". Advances in molecular biology have provided new insights into the nature of the various peripheral nerve sheath tumors, and have begun to suggest novel targeted therapeutic approaches.

Immunohistochemical assessment of ATG7, LC3, and p62 in ameloblastomas.

BACKGROUND: To investigate the roles of autophagy in tumorigenesis, cytodifferentiation, and prognosis of odontogenic tumors, we analyzed the immunohistochemical expression of ATG7, LC3, and p62 in odontogenic tissues. METHODS: Tissue specimens of nine dental follicles and 69 ameloblastomas were immunohistochemically examined with antibodies against ATG7, LC3, and p62. RESULTS: Immunohistochemical reactivity for ATG7, LC3, and p62 was detected in many odontogenic epithelial cells and several endothelial cells and fibroblasts in dental follicles and ameloblastomas. ATG7 reactivity in ameloblatomas was significantly higher than that in dental follicles. Expression of ATG7, LC3, and p62 was found markedly in neoplastic cells near the basement membrane rather than central polyhedral cells in ameloblastomas. Reactivity for these molecules was significantly higher in unicystic ameloblastomas than in solid ameloblastomas. Granular cells in granular cell ameloblastomas showed obvious reactivity for the autophagy- related molecules, and LC3 reactivity in granular cell ameloblastomas was significantly higher than in other ameloblastoma variations. Recurrent ameloblastomas showed significantly lower reactivity of LC3 and p62 than primary ameloblastomas. CONCLUSIONS: Expression of ATG7, LC3, and p62 in dental follicles and ameloblastomas suggests that autophagy regulation might be affected by microenvironment alterations during tumorigenesis. The molecular machinery for autophagy is possibly involved in tissue architecture, neoplastic cell differentiation, and prognosis of the benign epithelial odontogenic tumor.

Granular cell tumor on perianal region: a case report.

Granular cell tumor (GCT) was first described by Abrikossoff in 1926. GCT is a rarely seen soft tissue tumor and is generally benign. While the tumor can be seen in all parts of the body it is generally located on the head and neck region, and especially on the tongue. GCT is rarely seen in the anal-perianal region. In accordance with literature this case was reported because it was thought to be the 27th anal-perianal located GCT case. In this case report, approximately 0,5-1 cm pedunculated polypoid lesion was determined in the perianal region during the physical examination of a 23 year old female patient who applied with palpable mass complaint in the perianal region. Lesion in the patient was totally excited with healthy skin-subcutaneous tissue under local anesthesia. A benign granular cell tumor was detected in the histopathological examination. Positive staining was monitored immunohistochemically with S-100 and neuron specific enolase (NSE). GCT is a rarely seen tumor in the anal-perianal region and its malign transformation rate is very low. Even lesions seen in the perianal region have clinically a benign appearance, a histopathological examination should be conducted and also GCT should be kept in mind during diagnosis. Malign-benign separation of these lesions is difficult so histopathological examination should be conducted with great care. Large local excision in the treatment provides curative treatment. But for those presenting malign transformation further examination must be performed for metastasis. After the treatment local recurrence and metastasis should be considered carefully. Prognosis of metastatic disease is very bad.

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.

Vulvar atypical granular cell tumor in a preadolescent patient.

BACKGROUND: Granular cell tumor is an uncommon benign neoplasm with a predisposition for upper aerodigestive tract, skin and soft tissue involvement. Malignant and atypical granular cell tumors account for less than 2% of the lesions and in the pediatric population they are extremely rare and atypia has not been previously reported. CASE: We present a case of a rapidly growing granular cell tumor of the vulva of a 12-year-old girl exhibiting atypical histology. The lesion demonstrated prominent Ki-67 proliferation index (up to 20%), localized areas of spindling of tumor cells, scattered apoptotic bodies and p53 overexpression. CONCLUSION: The current histologic diagnostic criteria of atypical granular cell tumors are evaluated while physician awareness and the need for follow-up of patients for potential recurrences of this rare entity are emphasized.

Granular cell variant of epithelioid cell histiocytoma.

Classic granular cell tumors (GCTs) stain strongly and uniformly positive for S100 protein and are believed to show Schwann cell derivation. Polypoid cutaneous tumors composed of cells with large nuclei and abundant granular cytoplasm that do not stain for S100 protein or show apparent Schwannian differentiation have been reported by several groups under names including "primitive polypoid granular cell tumors," "dermal nonneural granular cell tumor," and "primitive nonneural granular cell tumors of skin." We report a polypoid tumor composed of S100-negative epithelioid cells with abundant eosinophilic granular cytoplasm that meets diagnostic criteria for (primitive polypoid dermal) nonneural GCT but also meets criteria for a granular cell variant of epithelioid cell histiocytoma. We have identified a single previous report of a similar lesion. We report the immunohistochemical characteristics of these lesions and address how they are best classified.

Unexpected granular cell tumor in abdominal wall: case report and literature review.

Granular cell tumors (GCTs) are uncommon benign neoplasms deriving from Schwann cells of the peripheral nerve fibers. Although these tumors can be found anywhere in the body, the most frequent site is the tongue, followed by the chest wall and the arm. The abdominal wall is an extremely rare site for GCTs. These tumors are generally asymptomatic and have a slow growth rate. Today, thanks to their immunoreactivity to S-100 and CD68, the differential diagnosis is more straightforward than in the past. We report on a young patient affected by a GCT located in the upper third of the right rectus abdominis muscle. En bloc excision through a diamond-shaped skin incision allowed us to make a correct histological diagnosis, which was confirmed by the immunohistochemical findings. GCT, which is very rare in abdominal wall muscles, should be considered in the differential diagnosis, and surgical excision is the treatment of choice.

[Granular cell tumor of the esophagus: description of an infrequent benign tumor]. / Tumor esofágico de células granulares: descripción de un tumor benigno poco frecuente.

Granular cell tumors (GCT) are infrequent tumors first described by Abrikossoff in 1926. Gastrointestinal involvement occurs in about 6% of GCT, the esophagus being the most frequent location. These tumors are usually benign and asymptomatic and are usually found incidentally when an upper gastrointestinal endoscopy is carried out for another reason, showing an isolated polyp or sessile submucosal nodule, covered by intact yellowish mucosa and with firm consistency. Endoscopic ultrasonography has significantly improved the diagnosis of these lesions. Nowadays endoscopic mucosectomy is the treatment of choice of esophageal GCT with a low frequency of complications. Histologic analysis of the surgical specimen shows specific characteristics such as positivity for S-100 protein. We present two new cases of esophageal GCT that were diagnosed recently and discuss the most relevant features of this infrequent disease.

Malignant granular cell tumor: a look into the diagnostic criteria.

Fanburg-Smith et al. classified granular cell tumors (GCTs) using six criteria with high Ki-67 and p53 in malignant cases. We aim to refine their classification and reproduce their immunohistochemical findings. We, first, classified our 48 cases according to Fanburg-Smith criteria (37 benign, seven atypical, and four malignant), and performed Ki-67 and p53 on a sample of tumors. Then, we reclassified them into 44 benign and four with uncertain malignant potential (GCT-UMP) using only necrosis and/or mitoses. (1) According to Fanburg-Smith criteria: Malignant cases were significantly younger than benign and atypical ones; occurred predominantly in males; were significantly larger in size; and showed a higher Ki-67 expression but an insignificant difference in p53 staining. (2) Comparative findings: The four malignant cases according to Fanburg-Smith corresponded to our four cases with UMP. The seven atypical cases and our benign group shared similar means, except for age. None of these atypical cases recurred or metastasized. Despite its small number, our preliminary study showed similar selectivity of two more reproducible criteria (vs six) in the classification of cases of GCT with potential aggressive behavior, preserving a role for Ki-67 in difficult cases. However, metastases remain the sole definite criterion for malignancy.