Non-neural Granular Cell Tumor Research Articles

A case report and literature review of non-neural granular cell tumour

A case report and literature review of non-neural granular cell tumour

Inter-Sphincteric Resection of Rectum for Ulcerated S-100 Negative Large Granular Cell Tumour

Non-neural granular cell tumor was first described in 1991 as an unusual primitive, polypoid variant of the conventional GCT (granular cell tumor). To date, this neoplasm remains as a rare entity and the cell of origin is uncertain. While the histological features are similar to the conventional (traditional) GCTs, it represents a distinct entity, as it is negative for S-100 and lacks true nerve sheath differentiation. We report here a case of a 49-year-old male patient with S-100 negative, vimentin positive large benign, ulcerated, bleeding non-neural GCT in the lower rectum. We confirmed the diagnosis histopathologically and immunohistochemically. We treated it by ISRR (Inter-Sphincteric Resection of Rectum) and primary colo-anal anastomosis. We find no other report of non-neural GCT located in the rectum in surgical literature. This is probably the first case of non-neural GCT identified in the rectum. This case report is presented here to document a non-neural GCT located in the rectum for the first time ever reported, and also to highlight the optimum best surgical approach, as we deemed here for this large ulcerated bleeding tumor in the rectum. This rectal non-neural GCT posed here as an unusual differential diagnosis from such more common neoplastic bleeding lesions in the rectum as carcinoma rectum, hemorrhoid, rectal polyp, etc. Here we like to discuss our experience, reviewing in brief the available literature implicating the biological behavior, histopathological and immunohistochemical features, differential diagnosis and therapeutic considerations of neural and non-neural GCTs. KYAMC Journal Volume: 14, No: 03, October 2023: 181-187.

Granular Cell Tumors

GCTs (Granular Cell Tumors) are rare, uncommon STTs (Soft Tissue tumors) that may develop at any location in the human body. Though the initial one was identified first as a non-capsulated granular cell myoblastoma of the tongue, they are now identified immunohistochemically as principally of neural Schwann cell origin (S-100 marker positive). Still more rarely, non-neural GCTs are also described that are probably of mesenchymal origin (as evidenced by S-100 marker negativity and vimentin positivity). Though they are more common in females and black people in the third to sixth decades of life, no sex, no race, and no age group are immune to this disease. They are mostly benign and very rarely malignant. Exact history taking, physical examination and laboratory investigations, including histopathological, histochemical, and immunohistochemical examinations, are essential to arrive at a concrete diagnosis, as many other tumors (e.g., malignant melanoma, small cell lung cancer, etc.) in the body resemble GCTs both histologically (granularity) and by biological behavior (benign, malignancy, recurrency at primary and metastatic sites). Benign variants have clinical features depending on location and are universally cured by wide surgical excision. The malignant variant carries a worse prognosis. These rare GCTs are to be kept in mind always in the differential diagnosis of soft tissue swellings anywhere in the body. Their biological and pathological features, differential diagnosis, and therapeutic implications are discussed here, briefly reviewing the available literature.KYAMC Journal Vol. 14, No. 02, July 2023: 96-101.

Gene fusions in superficial mesenchymal neoplasms: Emerging entities and useful diagnostic adjuncts.

Cutaneous mesenchymal neoplasms are diagnostically challenging because of their overlapping morphology, and, often, the limited tissue in skin biopsy specimens. Molecular and cytogenetic techniques have identified characteristic gene fusions in many of these tumor types, findings that have expanded our understanding of disease pathogenesis and motivated development of useful ancillary diagnostic tools. Here, we provide an update of new findings in tumor types that can occur in the skin and superficial subcutis, including dermatofibrosarcoma protuberans, benign fibrous histiocytoma, epithelioid fibrous histiocytoma, angiomatoid fibrous histiocytoma, glomus tumor, myopericytoma/myofibroma, non-neural granular cell tumor, CIC-rearranged sarcoma, hybrid schwannoma/perineurioma, and clear cell sarcoma. We also discuss recently described and emerging tumor types that can occur in superficial locations and that harbor gene fusions, including nested glomoid neoplasm with GLI1 alterations, clear cell tumor with melanocytic differentiation and ACTIN::MITF translocation, melanocytic tumor with CRTC1::TRIM11 fusion, EWSR1::SMAD3-rearranged fibroblastic tumor, PLAG1-rearranged fibroblastic tumor, and superficial ALK-rearranged myxoid spindle cell neoplasm. When possible, we discuss how fusion events mediate the pathogenesis of these tumor types, and we also discuss the related diagnostic and therapeutic implications of these events.

Lip Granular Cell Tumor (GCT) in a Pediatric Patient: Critical Literature Review on Pediatric Intraoral GCT and Acquired and Congenital Intraoral Non-Neural GCT.

Granular cell tumor (GCT) is an uncommon benign neoplasm derived from Schwann cells, frequently affecting the oral cavity, skin, and gastrointestinal tract. On microscopy, pseudocarcinomatous squamous hyperplasia (PSH) and perineural involvement are potential diagnostic pitfalls. GCT should be differentiated from non-neural GCT (NN-GCT). A 13-year-old male patient was referred presenting a nodular lesion on the upper lip several months ago. After excisional biopsy, microscopy revealed GCT without PSH but presenting multifocal perineural involvement. By immunohistochemistry, ALK was negative, whereas Rb and INI1 expression was intact. Moreover, with few intraoral NN-GCTs being assessed, recent studies suggest that acquired dermal NN-GCT subgroup seems to correspond to ALK-rearranged variants of epithelioid fibrous histiocytoma. Accordingly, further research on this topic is strongly encouraged.

ALK Positive Non-Neural Granular Cell Tumour in Two Paediatric Patients- A Case Report

ALK Positive Non-Neural Granular Cell Tumour in Two Paediatric Patients- A Case Report

Dermal nonneural granular cell tumor: a case report

Dermal nonneural granular cell tumor is a rare neoplasm of uncertain histogenesis that Le Boit and colleagues originally described in 1991. It arises commonly from the back, extremities and head and neck. To the best of our knowledge, only 50 cases have been reported in adults in the English literature. A 42-year-old man presented with a polypoid skin nodule of the front side of the chest wall, measuring 1,8 × 1,5 cm. The lesion was removed completely with tumor-free margins. Microscopically, the tumor was composed of a diffuse infiltrate of polygonal cells, S 100 negatives, with abundant granular cytoplasm and vesicular nuclei. The diagnosis of dermal nonneural granular cell tumor was retained. No recurrence was noted during follow up of 6 months. The prognosis is good.

A case of non-neural granular cell tumor of the lower lip

A case of non-neural granular cell tumor of the lower lip

Recent advances in the diagnosis, classification and molecular pathogenesis of cutaneous mesenchymal neoplasms.

The diagnosis of cutaneous mesenchymal neoplasms remains challenging, due to a combination of overlapping histological features, the rarity of some diagnoses and often inadequate sampling in superficial biopsies. Here, we describe recent advances in cutaneous mesenchymal neoplasms. We discuss improvements in our understanding of the molecular pathogenesis of non-neural granular cell tumour, epithelioid fibrous histiocytoma, composite and retiform haemangioendothelioma and dermatofibrosarcoma protuberans. We also discuss recently described tumour types, including some discovered via molecular testing: EWSR1::SMAD3-rearranged fibroblastic tumour, clear cell neoplasm with MITF::CREM rearrangement and melanocytoma with CRCT1::TRIM11 rearrangement, and some discovered via traditional histopathology: superficial CD34-positive fibroblastic tumour, plexiform myofibroblastoma and clear cell neoplasm with melanocytic differentiation and ACTIN::MITF translocation.

Clinicopathological features of primitive non-neural granular cell tumor

目的： 探讨原始非神经性颗粒细胞瘤（primitive non-neural granular cell tumour，PNNGCT）的临床病理特征、诊断及鉴别诊断。 方法： 回顾性分析1例皮肤PNNGCT的临床表现、组织学、免疫表型及分子生物学特征，并复习相关文献。 结果： 患儿男，5岁，左侧鼻梁与内眦交界处包块，镜下肿瘤境界较清楚，由梭形及上皮样细胞组成，胞质内含有大量嗜伊红色颗粒，可见泡状细胞核及嗜酸性核仁。肿瘤细胞呈波形蛋白、CD10、CD68阳性，不表达S-100蛋白和SOX-10。荧光原位杂交检测显示ALK基因重排。随访24个月，未见肿瘤复发和淋巴结转移。 结论： PNNGCT是一种罕见的低级别间叶性肿瘤，不确定分化，不表达S-100蛋白，部分病例出现ALK基因融合。.

Congenital cutaneous non‐neural granular cell tumor mimicking herpetic infection: Case report and review of the literature

We present a case of a female neonate with a cluster of six skin colored to yellowish pseudovesicular papules on her right forearm present since birth, initially thought to be a herpes simplex virus infection. Punch biopsy with immunostaining revealed a diagnosis of S100-negative, CD163-positive congenital cutaneous non-neural granular cell tumor. Only four other reports are presented in the literature of this entity, three of which also presented on the arm with somewhat similar clinical findings. We briefly reviewed the subtypes of classic and S100-negative non-neural granular cell tumors.

Non-Neural Granular Cell Tumor of the Eyelid: Case Report with Immunohistochemical and Ultrastructural Correlation

Skin and soft tissue granular cell tumours (GCTs) are uncommon, but well-described, neoplasms that are favoured to arise from Schwann cells. Nonneural GCTs (nnGCTs) are morphologically indistinguishable from classic GCT but lack the necessary S100 positivity. nnGCTs are usually benign, although three cases with metastasis have been reported. The histogenesis of nnGCTs is uncertain. Here we report a case consistent with nnGCT arising in the skin of the eyelid with immunohistochemical and ultrasctructural correlation. This is only the second reported case of nnGCT from this site.

Cutaneous Non-Neural Granular Cell Tumors Harbor Recurrent ALK Gene Fusions.

Non-neural granular cell tumor (NNGCT; also known as primitive polypoid granular cell tumor) is a rare neoplasm composed of large ovoid cells with abundant granular cytoplasm, variable nuclear pleomorphism, and the potential for regional lymph node spread. In contrast to conventional granular cell tumor (GCT), NNGCT lacks S100 expression and can exhibit greater nuclear atypia and mitotic activity. Therefore, we investigated clinicopathologic features of 12 NNGCT, and also used next-generation sequencing to identify potential driver events in a subset of NNGCT and 6 GCT. NNGCT demonstrated mild-to-moderate nuclear pleomorphism, variable mitotic activity (0 to 10/10 high-power fields), and were S100. Genetic analysis of 5 cutaneous NNGCT revealed gene fusions involving the anaplastic lymphoma kinase gene (ALK) in 3 cases (60%). Specifically, an interstitial deletion of chromosome 2 resulting in an in-frame fusion of dyanactin 1 (DCTN1) to ALK was identified in 2 cases, and a translocation resulting in a fusion between sequestosome 1 (SQSTM1) on chromosome 5 and ALK was identified in one case. Two of 6 GCT (33%) showed gains of chromosome 7. No other molecular or chromosomal alterations were detected in NNGCT and GCT. ALK immunohistochemistry revealed weak-to-moderate positivity in 4/9 cutaneous NNCGT (44%) including all 3 tumors with ALK fusions. Three oral NNGCT lacked ALK expression. NNGCT with ALK immunostaining did not have morphologic features distinguishing them from those without ALK staining. Our results demonstrate that a subset of NNGCT harbor ALK fusions, suggest that NNGCT are molecularly diverse, and further substantiate NNGCT as distinct from GCT.

Non-neural granular cell tumor of the uterine corpus mimicking uterine leiomyoma: A case report.

Non-neural granular cell tumors (GCTs) are clinically rare, whereas cases arising in the uterine corpus are exceedingly rare. Only three uterine cervical cases of GCTs have been reported to date and, to the best of our knowledge, there are no reports of GCT of the uterine corpus in the literature. We herein describe the first case of non-neural GCT arising from the uterine corpus reported to date. A 55-year-old premenopausal woman was referred to the Department of Obstetrics and Gynecology of Hashimoto Municipal Hospital (Wakayama, Japan) with a suspected uterine tumor. The tumor presented as a uterine leiomyoma-like mass on radiological examinations, but the diagnosis of non-neural GCT was established based on pathological and immunohistochemical examinations. Microscopically, histological examination of the entire surgical specimen revealed large polygonal cells with abundant eosinophilic granular cytoplasm and round to oval nuclei. Immunohistochemistry revealed positive periodic acid-Schiff staining of the cytoplasmic granules, which was resistant to diastase. In addition, the tumor cells stained positive for CD68, but negative for S-100, neuron-specific enolase, cytokeratin, CD34, α-smooth muscle actin, desmin, estrogen receptor and progesterone receptor. It is important for gynecologists to be aware of the possibility of non-neural GCT of the uterine corpus, for which accurate diagnosis, complete resection and long-term follow-up are crucial, as it may be easily misdiagnosed as uterine leiomyoma.

Dermal primitive non-neural granular cell tumour: a case report

Primitive non neural granular cell tumour (PNGCT) is a rare tumour of uncertain origin. Unlike conventional granular cell tumour, PNGCT is not of neural or Schwannian lineage and precise line of differentiation is still unclear.

Solitary, multiple, benign, atypical, or malignant: the "Granular Cell Tumor" puzzle.

The clinical evolution and biology of granular cell tumors (GCT) are poorly understood and treatment remains an issue of discussion. The majority of GCT are benign, although some display malignant behavior. The distinction between benign, atypical, and malignant GCT is controversial due to morphological and immunohistochemical overlap and lack of consistent histological and phenotypic criteria that predict behavior. Although histological criteria may indicate increased risk of malignant evolution, some GCT with evident benign appearance exceptionally progress towards metastatic disease. In this review, we discuss current knowledge on GCT, including histologic, immunophenotypic, and molecular characteristics and differential diagnosis. We focus on the following problematic items in GCT: (1) evolution of classification, (2) neural versus non-neural GCT, (3) neoplastic versus reactive disease, (4) malignant transformation of benign GCT, and (5) multiple versus metastatic GCT. We conclude that although a Ki-67 index >10% and the presence of mitoses and/or of necrosis are frequently associated with malignant behavior, metastasis remains the only unequivocal sign of malignancy in GCT. An infiltrative growth pattern and vascular and/or perineural invasion are not indicative of malignancy. GCT with atypical/uncertain features almost never metastasize, and many of these tumors either behave in a benign fashion or only recur locally (similar to incompletely excised benign tumors). We therefore propose that classical and atypical histological variants form a single group of GCT. GCT with various unfavorable histological features might be labeled as "GCT with increased risk of metastasis" rather than malignant GCT.

Non-neural granular cell tumor of the oral cavity

Classic granular cell tumors (GCTs) show strong cytoplasmic and nuclear expression of S100 and are believed to be of neural or Schwannian origin. We report a case of intraoral GCT that was negative for S100 but strongly positive for expression of CD10. A 52-year-old woman with a history of hypertension, diabetes, and hypothyroidism presented with an ulcerated, sessile, 1 cm nodule of the left buccal mucosa. The clinical diagnosis was “traumatic fibroma”. Microscopic examination revealed ulcerated fibrovascular connective tissue that contained a cellular population of large, ovoid cells with round, euchromatic nuclei and granular cytoplasm. Pleomorphism was not observed and mitoses were rare. Acute and chronic inflammatory cells were noted throughout the lesion with focal germinal center-like aggregates in the deeper connective tissue. Occasional binucleated and multinucleated and cells, including Touton giant cells, were observed. Immunohistochemical studies revealed the lesional cells to be negative for S100 protein, CD1a, Melan-A, HMB-45, synaptophysin, smooth muscle actin and cytokeratins. CD163 and Factor XIIIa expression was identified among interspersed dendritic cells consistent with histiocytes, however, the granular cells were negative. Lesional cells demonstrated uniformly strong expression of CD10. Besides congenital epulis of the newborn, intraoral examples of non-neural GCT have rarely been described. Non-neural GCT is a diagnosis of exclusion based largely upon immunohistochemical findings and we cannot completely exclude the possibility that this lesion might represent a variant of fibrous histiocytoma.

MITF Positivity in Atypical Fibroxanthoma

Microphthalmia transcription factor (MITF) is an established melanocytic marker originally credited with a high degree of specificity. We report a series of 11 atypical fibroxanthoma (AFX) from 2 laboratories showing positive MITF staining. Although there are multiple case reports illustrating MITF staining in a range of tumors, aberrant staining in AFX has not been previously reported. Awareness of the possibility of MITF positivity in AFX is important to avoid a misdiagnosis of melanoma. We also report positive MITF staining in 2 nonneural granular cell tumors and discuss the overlap with the granular subtype of AFX.

A case of metastatic non-neural granular cell tumor in a 13-year-old girl

Conventional granular cell tumor represents a mesenchymal neoplasm observed in a variety of locations and is now believed to be of Schwann cell origin. Granular cell change has also been observed in a variety of different tumors, but recently described in the skin has been a distinct entity termed non-neural granular cell tumor, which lacks expression of S100 protein and is of uncertain histogenesis. This tumor typically displays a greater degree of nuclear atypia and mitotic activity than conventional granular cell tumor but appears to behave in a relatively benign fashion, as only two previous instances of lymph node metastasis have been documented. Herein, we report a case of non-neural granular cell tumor arising on the back of a 13-year-old girl, and later axillary lymph node metastasis with extracapsular extension was observed.

Pleomorphic Dermal Neoplasms

Pleomorphic neoplasms are typically associated with high-grade malignant behavior, but this does not readily apply to primary cutaneous tumors. Despite morphologic features suggestive of malignancy, atypical fibroxanthoma, the classic example of a pleomorphic dermal neoplasm, is characterized by indolent clinical behavior. Atypical fibroxanthoma is a distinctive clinicopathologic disease affecting sun-damaged skin of elderly males. Histologically, it is often ulcerated and dermal based with pushing growth, characterized by a sheet-like and fascicular growth of pleomorphic epithelioid, spindled, and multinucleated tumor cells with brisk and atypical mitotic activity. However, no positive discriminatory histologic or immunohistochemical features exist. Its diagnosis is one exclusion with a wide differential diagnosis, mainly including other mesenchymal, melanocytic, and epithelial neoplasms. Particular considerations are pleomorphic dermal sarcoma, invasive melanoma, squamous cell carcinoma, metaplastic carcinoma, poorly differentiated cutaneous angiosarcoma, cutaneous leiomyosarcoma, myxofibrosarcoma, variants of fibrous histiocytoma (FH), pleomorphic fibroma, and non-neural granular cell tumor. The behavior of these tumors is varied and ranges from outright malignant to entirely benign, requiring confident diagnosis to reliably predict behavior and guide treatment. Although challenging, because of significant clinical and pathologic overlap, it is usually possible to establish a definitive diagnosis when attention is paid to the often subtle differentiating features. This requires careful tumor sampling, recognition of the subtle distinguishing morphologic features, judicious use and analysis of immunohistochemistry, and interpretation of the findings in the appropriate clinical setting.