A rare case of cutaneous granular cell tumor with unusual Melan-A expression in a child.

Granular cell tumors (GCTs) are rare, indolent neoplasms classically characterized by eosinophilic granular cytoplasm, infiltrations of polygonal cells in the collagenous stroma, and pustulo-ovoid bodies of Milian. We describe a case of a 10-year-old female presenting with a GCT of the upper arm, remarkable for positive Melan-A expression without additional melanocytic features. The differentiation between granular cells versus melanocytic neoplasms carries significant implications for clinical management, and such diagnoses should be considered carefully in the setting of unusual immunophenotypes.

[Clinicopathological characteristics and differential diagnosis of 6 cases of congenital granular cell tumor].

To provide references for the diagnosis and treatment of congenital granular cell tumor (CGCT), by comprehensive analysis of the clinical data, histopathological and immunohistochemical results. Patients with CGCT were involede, from March 2015 to November 2020, at the Department of Oral and Maxillofacial Surgery of the First Affiliated Hospital of Zhengzhou University. A total of 6 children, aged 3-16 days, 1 male and 5 female, 5 maxillary and 1 mandibular, with maximum tumor diameter of 6-70 mm, were included. The lesions of CGCT were single and connected to the alveolar ridge by a pedicle. The surface of the tumor was covered with a vascular network, and two cases had ulcers on the surface of the tumor. All 6 cases had the tumor removed surgically and there was no recurrence or metastasis in the follow-up visit. Although CGCT is rare, it is a benign tumor and generally does not recur or metastasize after surgery, and has a good prognosis. The prenatal imaging, clinical manifestations after delivery, pathological characteristics and immunohistochemical analyses may provide reference for early diagnosis and treatment of CGCT.

Clear Cell Proliferations of the Skin: A Histopathologic Review.

ABSTRACT: Cutaneous clear cell proliferations encompass a heterogenous group of several primary cutaneous neoplasms and metastatic tumors with different histogenesis. Many of these clear cell proliferations may seem strikingly similar under the microscope resulting in challenging diagnosis. In many of these clear cell lesions, the reason for the clear or pale appearance of proliferating cells is unknown, whereas in other ones, this clear cell appearance is due to intracytoplasmic accumulation of glycogen, mucin, or lipid. Artifacts of tissue processing and degenerative phenomenon may also be responsible for the clear cell appearance of proliferating cells. Awareness of the histopathologic findings as well as histochemical and immunohistochemical techniques are crucial to the accurate diagnosis. This review details the histopathologic features of clear cell cutaneous proliferations, classifying them according their type of differentiation and paying special attention to the histopathologic differential diagnosis among them.

Immunohistochemical ALK Expression in Granular Cell Atypical Fibroxanthoma: A Diagnostic Pitfall for ALK-Rearranged Non-neural Granular Cell Tumor.

ABSTRACT: Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harbors ALK rearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of an ALK rearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT.

Squash smear cytology of pituitary granular cell tumor: A case report and review of literature with special emphasis on cytological differential diagnosis in pituitary region.

Neurohypophysis granular cell tumor (NGCT) is a rare entity and is classified under thyroid transcription factor 1 (TTF-1) expressing tumors of pituitary. It is considered as an uncommon differential during sellar and suprasellar mass evaluation. Its intraoperative squash cytology is distinct and has rarely been reported in literature. A 65-year-old female presented with reduced vision of right eye and history of seizures. Radiological findings revealed a sellar/suprasellar mass with mass effect on optic chiasma. Intraoperative squash neurocytology examination showed a spindle cell lesion with abundant granular cytoplasm in tumor cells. Subsequent histopathology and immunohistochemistry confirmed the diagnosis of granular cell tumor. Granular cell tumor remains one of the sellar/suprasellar surprises. Its intraoperative neurocytology is unique and should be considered while evaluating a sellar/suprasellar mass. A case of sellar granular cell tumor with its intraoperative squash cytology, histopathology along with a review of literature is being presented with special emphasis on cytological differential diagnosis in pituitary region.

Clinical-Pathological, Immunohistochemical, and Genetic Characterization of a Series of Posterior Pituitary Tumors.

Posterior pituitary tumors are supposed to represent the morphological spectrum of a single entity. Herein, we report the clinical-pathological, immunohistochemical, and genetic features of 5 spindle cell oncocytomas (SCOs), 3 pituicytomas, and 1 granular cell tumor (GCT). SCOs had the highest local invasiveness and affected older subjects. The 3 histotypes differed in the content of spindle cells (predominant in pituicytoma and absent in GCT), presence of lymphocytic infiltrate (in SCO and GCT, but not in the pituicytoma) and EMA/GFAP staining (negative in GCT; EMA-positive/GFAP-negative in 4/5 SCO and GFAP-positive in 3/3 pituicytomas). Three SCOs and 1 pituicytoma analyzed with next-generation sequencing had no mutations in 409 genes. However, 1 SCO had previously unreported homozygous deletion of CDKN2A/B and another of SMARCA4, SMARCB1, and NF2. All 3 SCOs had loss of heterozygosity of chromosome 1p, while the pituicytoma had chromosome 19 homozygous loss and chromosomes 10, 13q, and 18q loss of heterozygosity. Since 1p and 13q losses were previously reported in 1 pituicytoma and 1 SCO, respectively, our data demonstrate that posterior pituitary tumors share common genetic alterations. The possibility that posterior pituitary tumors are SMARCA4/SMARCB1-deficient should be kept in mind in the differential diagnosis toward other entities.

Intraneural granular cell tumor: Histologic spectrum and histogenetic implication.

Granular cell tumor (GCT), despite its putative neural origin, commonly occurs in extraneural sites; only six single case reports of intraneural GCT have been described. We report an unique case as the only one with motor dysfunction, the longest duration of symptoms, and largest tumor size with resultant muscle atrophy and fatty infiltration. Upon review of these cases, the striking feature of intraneural GCT lies in its histologic variety, ranging from benign GCT, through plexiform, hybrid GCT and perineurioma to malignant GCT, encompassing the full spectrum of extraneural GCT. As the immunophenotypes of schwannoma and GCT are not exactly identical, together with evidence from ultrastructural studies, the more reasonable and likely possibility is that GCT originates from undifferentiated mesenchymal cells acquiring partial schwannian differentiation. Such postulation by virtue of the widespread occurrence of mesenchymal cells in the soft tissue, better explains the topographic distribution of GCT in extraneural and intraneural location.

Desmoplastic stromal changes in cutaneous neural granular cell tumors: An under-recognized histopathologic feature of diagnostic and prognostic importance.

BACKGROUND: Granular cell tumors (GCTs) are uncommon mucocutaneous and soft tissue neoplasms with distinctive histopathologic appearance but controversial histogenesis. Herein, we report a variant of cutaneous GCT featuring extensive desmoplastic stroma which may result in diagnostic difficulties with mesenchymal proliferations, particularly a dermatofibroma. METHODS: Following a recent case of GCT with prominent stromal desmoplasia, we reviewed all cases diagnosed as GCT during the past 10 years accessioned at the dermatopathology unit in a tertiary university hospital. RESULTS: Three additional cases with a similar excessive connective tissue were identified out of a total of 49 GCTs. Cytoplasmic granularity was often subtle and focal, S100 expression was weak, and nuclei had a tendency to show spindling in tumor cells entrapped within the desmoplastic areas. Of note, nuclear spindling is one of the criteria used to diagnose an atypical/malignant GCT. CONCLUSION: We propose the term "desmoplastic GCT" for these tumors, which not only appropriately addresses the stromal changes but also raises an awareness of GCT being one of the cutaneous tumors which may show stromal desmoplasia. Differential diagnostic difficulties apart, awareness of this phenomenon is important so that desmoplasia and resultant spindling are not linked with potential aggressive behavior.

Rare Thyroid Transcription Factor 1-Positive Tumors of the Sellar Region: Barrow Neurological Institute Retrospective Case Series.

OBJECTIVE: Granular cell tumors (GCTs), pituicytomas, and spindle cell oncocytomas are rare, nonfunctioning pituitary tumors sharing positive staining of thyroid transcription factor 1. We present our series, the first single-institutional report with long-term surgical follow-up of all 3 tumor types. METHODS: Our institutional pathology database was queried for these 3 pathologic diagnoses. Clinical records were assessed for clinical presentation, preoperative and postoperative endocrine status, tumor location on imaging, surgical characteristics, pathology results, and tumor recurrence. RESULTS: Data were analyzed for 4 patients with GCTs, 4 with pituicytomas, and 3 with spindle cell oncocytomas. The most common symptoms at presentation were vision changes (64%), headache (55%), endocrine abnormalities (55%), and fatigue (46%). GCTs were the only subtype to present exclusively in the infundibulum and the only subtype in our series to be treated with a transcranial transsylvian approach to resection (n = 2). In our study, in contrast to other reports, estimated blood loss was less than 300 mL in all patients. Imaging confirmed gross total resection in all 11 cases with no known recurrences at a mean (standard deviation) follow-up of 4.7 (3.7) years. CONCLUSIONS: We present a single-institution series of rare thyroid transcription factor 1-staining posterior pituitary tumors of the sellar region. Key novel findings include gross total resection with no tumor recurrence at nearly 5 years of mean follow-up and no cases of excess or uncontrolled blood loss. Our findings reinforce the observation that GCTs present in the suprasellar space.

Granular cell astrocytoma: an aggressive IDH-wildtype diffuse glioma with molecular genetic features of primary glioblastoma.

Granular cell astrocytoma (GCA) is a rare adult infiltrating glioma subtype. We studied a series of 39 GCAs. Median age of presentation was 57.8 years and most cases developed in the frontal or temporal lobes. Tumors included grade II (n = 14), grade III (n = 11), and grade IV (n = 14) by WHO criteria. Granular cell morphology was diffuse in 31 (79%) cases and partial in eight (21%). Immunohistochemistry showed frequent positivity for GFAP (28 of 31), OLIG2 (16 of 16), and CD68 (27 of 30), but HAM56, CD163, and IBA-1 histiocytic markers were all negative (22 of 22). IDH1(R132H) was negative in all the cases tested (16 of 16), while ATRX expression was retained (12 of 12). Cytogenetics demonstrated monosomy 10 (6 of 6) cases, +7 in 4 (of 6), -13q in 4 of 6, and -14 in 4 of 6. Next-generation sequencing demonstrated mutations in PTEN/PIK3 genes in 6/13 (46%), NF1 in 3 of 10 (30%), TP53 in 3 of 13 (23%), PALB2 in 3 of 10 (30%), STAG2 in 3 of 10 (30%), EGFR mutation/amplification in 3 of 13 (23%), and AR in 2 of 10 (20%). CDKN2A/B deletion was identified in 5 of 13 (30%) cases (homozygous deletion in 4). The TERT C228T mutation was identified in 9 of 13 (69%). No mutations were encountered in IDH1, IDH2, CIC, FUBP1, H3F3A, BRAF or ATRX genes. The mean overall survival was 11.3 months. Patients >60 years old at diagnosis had a worse survival than patients <60 years (P = 0.001). There were no statistically significant differences in survival by WHO grade, extent of granular cell change, sex or MIB-1 (P > 0.05). GCA is a variant of IDH-wildtype diffuse glioma with aggressive behavior irrespective of grade and extent of granular cell morphology, and with molecular genetic features corresponding to primary glioblastoma.

Up-Regulation of Long Noncoding RNA SRA Promotes Cell Growth, Inhibits Cell Apoptosis, and Induces Secretion of Estradiol and Progesterone in Ovarian Granular Cells of Mice.

BACKGROUND Increasing evidence indicates that long noncoding RNAs (LncRNAs) play a key role in multiple pathological processes. It has been shown that LncRNA steroid receptor RNA activator (SRA) is elevated in peripheral blood of patients with polycystic ovary syndrome (PCOS). The aim of this study was to assess the effect of elevated LncRNA SRA on ovarian granular cells of mice in vitro. MATERIAL AND METHODS We firstly isolated granular cells from mouse ovaries and over-expressed the LncRNA SRA by means of lentiviral transfection in this cell line. Then, we assessed the effects of LncRNA SRA on granular cells through real-time PCR, CCK-8 assay, flow cytometry, Hoechst staining, and Western blot assay. RESULTS We demonstrated that elevated LncRNA SRA stimulated cell growth, changed distribution of cell cycle phases with increase of Cyclin B, Cyclin E, and Cyclin D1, and inhibited cell apoptosis with up-regulation of bcl2 and down-regulation of bax, cleaved-caspase 3, and cleaved-PARP. Moreover, the contents of estradiol (E2) and progesterone (PG) and expressions of their key enzymes (CYP19A1 and CYP11A1) were up-regulated following over-expression of LncRNA SRA. CONCLUSIONS Taken together, our results indicate that abnormal LncRNA SRA may be a risk factor for evoking PCOS.

Immunoprofiling of glial tumours of the neurohypophysis suggests a common pituicytic origin of neoplastic cells.

PURPOSE: To analyse the antigen expression profiles of 27 cases of pituicytoma, spindle cell oncocytoma, and granular cell tumour of the sellar region concerning a common pituicytic origin of neoplastic cells. METHODS: Material from 12 female and 15 male patients (13 granular cell tumours of the sellar region, 10 pituicytomas, four spindle cell oncocytomas) collected in the German Registry of Pituitary Tumours between 1993 and 2015 was re-evaluated according to the current WHO classification of tumours of the central nervous system and supplementary immunohistochemistry including S100-protein, CD56, CD68, thyroid transcription factor-1 (TTF-1), and Ki-67 was performed. RESULTS: S100-protein was detected in all 27 tumours and TTF-1 in all 16 tumours that were assessed. Vimentin was expressed in all 13 cases investigated whereas broad spectrum cytokeratin was not detected in any of 14 evaluated cases. GFAP was observed in nine out of 21 cases. 15 out of 17 investigated lesions showed some CD68 expression and five out of 14 cases were labelled with CD56 antibodies. Proliferative activity did not differ significantly between the three tumour subgroups although one primary and one recurrent pituicytoma showed exceptionally high Ki-67-proliferation indices of 15.3 and 12.7 %, respectively (means: granular cell tumour of the sellar region 2.0 %, pituicytoma 2.8 %, spindle cell oncocytoma 2.7 %). CONCLUSIONS: The study confirms and expands earlier data and is in line with the notion that the three tumour types are variants of pituicytoma.

A study of cell proliferation using immunohistological staining: A case report of congenital granular cell epulis.

An unusual case of a 1-day-old Chinese female neonate with a solid tumor mass in the maxillary anterior ridge of the edentulous jaw is reported. Based on the clinical and histopathological features, the diagnosis was of obstructive congenital granular cell epulis (CGCE) which is an uncommon benign tumor that preferentially develops in female infants. Immunohistochemical analysis of the lesion was performed and the rate of cell proliferation was determined by immunostaining with Ki-67 and PCNA, which showed labeling indexes of 11.1% and 33.3%, respectively. No recurrence was observed in the follow-up.

Lack of Utility of Cytokeratins in Differentiating Pseudocarcinomatous Hyperplasia of Granular Cell Tumors from Oral Squamous Cell Carcinoma.

Granular cell tumor (GCT) of the oral cavity is a benign lesion. Half of oral GCTs demonstrate pseudocarcinomatous hyperplasia (PCH) of the mucosa which can mimic invasive islands of oral squamous cell carcinoma (SCC). Such similarity can be confusing when diagnosing or evaluating the two conditions, potentially leading to misdiagnosis or misclassification. Indeed, several misdiagnosed cases of oral GCT have been reported in the literature as OSCC or malignant oral GCT that resulted in unnecessary aggressive treatment for the affected patients. The aim of this study was to investigate if the cytokeratin pattern of the PCH can help in differentiating GCT from oral SCC. To distinguish between these two entities, we examined 12 patient specimens of oral GCT-PCH and oral SCC histologically and via immunohistochemistry (IHC) for CK13, CK17 and P75. The results suggest that the cytokeratin profile of PCH is similar to that of oral SCC. Therefore, consideration of IHC findings for epithelial markers alone may lead to erroneous diagnosis; thus, the presence of the granular tumor underneath the PCH and its immunopositivity for P75 or other neural definition markers can be essential to identify the underlying tumor and exclude oral SCC. Finally we recommend more studies on the molecular biology of PCH to understand how it can mimic oral SCC histologically without harboring its malignant phenotype clinically, which could have significant translational potential for understanding invasive oral SCC.

Orbital granular cell tumours: clinical and pathologic characteristics of six cases and literature review.

OBJECTIVE: To retrospectively assess the clinicopathological characteristics of orbital granular cell tumours (GCTs). METHODS: A non-comparative review of the clinical characteristics, imaging, histopathological features, management, and prognosis of five cases of benign GCT and one case of malignant GCT (MGCT) was conducted, along with a review of the English language literature. RESULTS: Among the six cases, four tumours were adherent to the extraocular muscle (EOM), and three tumours to the optic nerve (ON). Morphologic examinations revealed polygonal cells containing periodic-acid-Schiff-positive eosinophilic granules. All tumours (100%) were positive for VIM and NSE, five (83.3%) tumours were positive for S-100, and three (50%) tumours were positive for CD68. The follow-up examination of the MGCT witnessed recurrence and brain metastasis despite several thorough resections, but the patient remained alive; the follow-up examination of the four benign GCTs that had received incomplete excision revealed recurrence in one patient and dramatic shrinkage of the residual tumour in another; there was no recurrence in the other two patients. CONCLUSIONS: GCT should be considered in the differential diagnosis of orbital tumours, which may affect EOMs and ON. The natural course of GCT can include tumour progression, stability, or spontaneous regression. To avoid recurrence, complete resection is recommended for orbital GCT. To the best of our knowledge, primary orbital MGCT is reported for the first time.

MIOBLASTOMA GRAINYCLY CELL OF ESOPHAGEAL.

PURPOSE OF THE STUDY: Pay attention endoscopists doctors, oncologists surgeons, gastroenterologists on the ability to detect mioblastoma in the esophagus, as well as to present its endoscopic semiotics. MATERIAL AND METHODS: 32583 A primary esophagogastroduodenoscopy and only one patient S., 39 years old (0.0031%) showed polypoid masses in the lower third of the esophagus. Esophagogastroscopy underwent endoscopy XP iSON system Exera II. Patients underwent clinical evaluation and morphological study of endoscopically resected of education. RESULTS: Patient 39 years old 20.01.2012, in the lower third of the esophagus revealed polypoid formation with a flat, smooth surface covered with a mucous membrane, not different from the surrounding mucosa. Morphologic study after endoscopic resection of the tumor - grainycly cell mioblastoma. When viewed within four years of changes in the mucosa and not detected change in the esophageal wall. CONCLUSION: Abrikosov tumor in the esophagus is extremely rare localization has exophytic growth after endoscopic rernoval requires regular endoscopic surveillance.

Granular Cell Tumors on Unusual Anatomic Locations.

Granular cell tumors (GCTs) are soft tissue tumors, which are thought to be derived from Schwann cells. Although most GCTs are reported to arise in tongue and oral cavity (30-50%), they can appear on any anatomic sites, even visceral organs. Herein, we report 5 cases of GCTs on unusual anatomic locations, such as palm, arm, thigh, finger, and vulvar area. Complete surgical excision is preferred treatment of choice to prevent recurrence. These cases emphasize that GCTs not involving oral cavity are more prevalent than expected, and the diagnosis should be histopathologically confirmed.