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.

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.

[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 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.

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.

[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.

Congenital granular cell lesion: clinical, microscopic and immunohistochemical aspects in a case of multiple lesions.

Congenital granular cell lesion of the newborn, also known as congenital epulis, is a rare benign oral cavity tumor presenting at birth. Usually, it appears as a solitary mass arising in the mouth and originates from the anterior alveolar ridge. The objective of the present article is to report a case of congenital granular cell lesion in an 8-day-old female newborn. The patient presented four intraoral pedunculated lesions. Diagnosis, treatment, microscopic and immunohistochemical characteristics are also discussed.

Granular cell tumor of the penis shaft: case report and literature review.

INTRODUCTION: Granular cell tumors (GCT) are uncommon soft tissue neoplasms of presumed neural origin that rarely involve the male external genitalia. Penile lesions are distinctly uncommon with less than 20 cases reported till now. OBJECTIVE: In the present paper we describe the clinicopathological and immunohistochemical findings in a case of GCT of the penis shaft in a 31-years-old man. RESULTS AND CONCLUSIONS: On physical examination the patient was found to have a small ovoid mass, 20 x 10 mm in diameter, at the left postero-lateral area of the penis' base. The mass was firm on palpation with no fixation on the neighboring tissues. The lesion was completely excised under loco-regional anesthesia. The surgical specimen was an ovoid, gray-white, elastic mass, of 10 x 5 mm. Microscopically, the tumor was moderately cellular and was composed of polygonal-shaped cells with abundant granular eosinophilic cytoplasm. Tumor cells were disposed in nests, cords, and trabeculae and showed perineural invasion. The tumor presented bland cytological features with only focal slight nucleo-megaly. Mitotic activity was undetectable. The tumor cells showed diffuse immunohistochemical expression for S100 protein. At 6 month after surgery the patient was free of persistent/recurrent disease or metastatic spread of the tumor. We discuss the clinical, histo-immunohistochemical and therapeutical features of this unusual penile tumor, the single one encountered in the Department of Pathology from Timisoara County Hospital and, to our knowledge, the only one reported in the Romanian medical literature.

[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.

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.

Granular cell tumor of the parotid gland: an exceptionally rare occurrence.

The authors report on a case of a granular cell tumor of the parotid gland, which constitutes an extremely rare neoplasm. The infiltrative growth of the tumor may pose the question of malignancy, especially on frozen section. The objective of this report was to function as a reminder of this entity for every pathologist that deals with a biopsy from a lesion of the parotid gland, and furthermore, to keep the unwary away from a possible diagnostic pitfall. A meticulous search of the literature revealed only 4 similar cases.

[Endoscopic mucosal resection of Abrikosoff's tumor of the esophagus]. / Mucosectomía endoscópica de un tumor de Abrikosoff esofágico.

Abrikosoff's tumor (AT), or granular cell tumor (GCT), is relatively rare in the gastrointestinal tract, where the most common site is the esophagus. This tumor is usually found incidentally when an upper gastrointestinal endoscopy is carried out for another reason. Endoscopically, GCT appears as a small, yellow and submucosal lesion covered by normal mucosa. Endoscopic ultrasonography shows a homogeneous hypoechoic lesion with well defined margins. The definitive diagnosis is histological. The origin of GCT is neurogenic and the tumor is composed of eosinophilic granular cytoplasm and PAS-positive cells, which show the S-100 protein on immunohistochemistry. Although GCT is usually clinically and histologically benign, some malignant cases have been reported. Consensus is lacking on the treatment and follow-up of this tumor. Currently, endoscopic mucosal resection is a safe and effective technique to treat submucosal esophageal lesions, allowing subsequent histologic analysis. We present three patients with esophageal CGT, who were definitively treated with endoscopic mucosal resection.

Granular cell tumour of the urinary bladder: a case report and review of the literature.

Granular cell tumor of the urinary bladder is an exceedingly rare disease, with only 10 cases reported so far in literature. We report a case of granular cell neoplasm of the bladder incidentally found in a 44-year-old woman during an abdominal ultrasound examination for evaluation of stress urinary incontinence. The patient underwent a transurethral resection of the mass and histological examination revealed the presence of a granular cell tumor. Immunohistochemical staining for neuron-specific enolase and S100 protein was positive. At a 6-month follow-up the patient is free of bladder recurrence.

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.

Granular cell tumor arising metachronously in the bronchus and esophagus.

We present a case of granular cell tumor (GCT) occurring in the esophagus 7 years after operation for bronchial GCT. A 59-year-old Japanese man complained of epigastralgia, and endoscopic examination of the upper digestive tract disclosed a submucosal tumor in the lower esophagus. Histological examination of the endoscopic mucosal resection of the esophageal tumor showed a proliferation of neoplastic cells with an eosinophilic and granular cytoplasm. The cytoplasm of the neoplastic cells was histochemically positive for PAS stain and immunohistochemically positive for S-100. This tumor did not fulfill any of the diagnostic criteria for malignancy at either the macroscopic or microscopic level. I believe that this is the first case of GCT occurring metachronously in the respiratory and digestive tracts. Clinicians and pathologists should bear in mind that GCT may arise metachronously in the respiratory and digestive tracts.

[Primitive nonneural granular cell tumor of skin (case report)]. / Primitivní nonneurální nádor kuze z granulárních bunek (kazuistika).

Primitive nonneural granular cell tumor was recognized in an 82-year-old man, mimicking a granuloma in the scalp. Despite its disturbing cytomorphology, this histogenetically enigmatic tumor with unusual immunoprophile (NK1-C3, CD 68 and NSE positivity; S-100 protein negativity) behaves indolently.

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.