Granular Cell Tumor

Alveolar soft-part sarcoma (ASPS) is a rare soft tissue tumor with a broad morphologic differential diagnosis. While histology and immunohistochemistry can be suggestive, diagnosis often requires exclusion of other entities followed by confirmatory molecular analysis for its characteristic ASPSCR1-TFE3 fusion. Current stain-based biomarkers (such as immunohistochemistry for cathepsin K and TFE3) show relatively high sensitivity but may lack specificity, often showing staining in multiple other entities under diagnostic consideration. Given the discovery of RNA in situ hybridization (RNA-ISH) for TRIM63 as a sensitive and specific marker of MiTF-family aberration renal cell carcinomas, we sought to evaluate its utility in the workup of ASPS. TRIM63 RNA-ISH demonstrated high levels (H-score greater than 200) of expression in 19/20 (95%) cases of ASPS (average H-score 330) and was weak or negative in cases of paraganglioma, clear cell sarcoma, rhabdomyosarcoma, malignant epithelioid hemangioendothelioma, as well as hepatocellular and adrenal cortical carcinomas. Staining was also identified in tumors with known subsets characterized by TFE3 alterations such as perivascular epithelioid cell neoplasm (PEComa, average H-score 228), while tumors known to exhibit overexpression of TFE3 protein without cytogenetic alterations, such as melanoma and granular cell tumor, generally showed less TRIM63 ISH staining (average H-scores 147 and 96, respectively). Quantitative assessment of TRIM63 staining by RNA-ISH is potentially a helpful biomarker for tumors with molecular TFE3 alterations such as ASPS.

Granular cell tumors occur in all ages and many anatomic sites. In the craniofacial region, they typically arise in soft tissue, not bone. We present a primary intra-osseous granular cell tumor of the sphenoid and central skull base arising in a 12- year- old girl.

A 12-year-old female with sickle cell disease and Jeavons syndrome presented with seizures. Imaging and partial resection revealed an expansile benign granular cell tumor (GCT) involving the sphenoid body, pterygoid process, and central skull base. The disease has remained stable after 36-month follow up.

GCT primarily involving the osseous sphenoid/skull base has not been previously reported in a child. Although mostly benign, some are aggressive, with malignant transformation in 1-2%. Surgery is the mainstay of treatment, but in the skull base this may be limited by adjacent critical structures. Decision-making is guided by anatomic extent, histology, and clinical behavior.

Granular cell tumor, which is thought to recapitulate a Schwann cell phenotype, is a very rare neoplasm that belongs to soft tissue tumors. It can be classified as benign, atypical or malignant, based on specific histological criteria, with the majority of cases exhibiting an indolent behavior. Its biology and clinical course are poorly understood and its optimal management is yet to be defined, given the rarity of cases. Here we describe an atypical granular cell tumor in the upper middle back skin that evolved after a thirty-year indolent period. Despite complete surgical removal, the patient experienced a recurrence, both local and in the lungs, following an aggressive clinical course. Data on management of metastatic disease are extremely scarce, comprised exclusively of case reports. Therefore, we administered to the patient systemic therapy according to soft tissue sarcoma guidelines, which led to disease progression, with fatal outcome. In conclusion, recurrent and/or metastatic granular cell tumor is a rare disease that can be life-threatening, for which response to different therapies is unknown. The biologic behavior of atypical and malignant granular cell tumor is quite different from its benign counterpart, evoking soft tissue sarcomas, and its diagnosis should alert clinicians. The role of adjuvant chemotherapy and radiation therapy in this setting should be explored, to limit disease recurrence.