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Novel TFG‐NTRK2 Fusion in Spitz/Reed Tumor: Case Report

By: Celeste L. Dixon
Posted: Sunday, August 1, 2021

RNA sequencing revealed a novel genetic alteration in a Spitz/Reed neoplasm. The in-frame TFG-NTRK2 fusion expands the spectrum of NTRK2-rearranged tumors, wrote Arnaud de la Fouchardière, MD, PhD, of Centre Léon Bérard in Lyon, France, and colleagues in their case report, published in the Journal of Cutaneous Pathology.

“These findings fulfilled the diagnostic criteria of a pigmented spindle cell nevus of Reed (a variant of Spitz nevus),” detailed the authors. “Histopathologically, the lesion was a junctional melanocytic nevus composed of large nests of spindled melanocytes with abundant eosinophilic cytoplasm associated with a hyperplastic epidermis.” The patient was a 39-year-old man whose shoulder was the site of the quickly growing pigmented macule.

Previously, fusions of ALK, ROS1, NTRK3, RET, MET, MERTK, FGFR1, ERBB4, LCK, BRAF, MAP3K8, MAP3K3, and PRKDC, as well as mutation of HRAS, had all been discovered as genetic alterations associated with Spitz neoplasms. In this tumor, Dr. de la Fouchardière and co-investigators reiterated, immunohistochemistry for pan-TRK revealed the cells had diffuse cytoplasmic positivity but no immunoexpression of ALK, ROS1, and BRAF V600E.

Most often, Spitz neoplasms are benign, but in the occasional case of progression to a Spitz melanoma, NTRK2 could represent a therapeutic target, noted the authors. Currently, the tyrosine kinase inhibitors that most effectively target NTRK fusion proteins are larotrectinib and entrectinib.

Disclosure: The study authors reported no conflicts of interest.



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