Malignant <scp>CRTC1</scp>::<scp>TRIM11</scp> Cutaneous Tumor With Lethal Outcome: Histopathologic and Molecular Findings
Meghan Beatson, James W. Smithy, Dylan Domenico, Gunes Gundem, Elli Papaemmanouil, Andrea P. Moy, Joyce M. Chen, Melissa Pulitzer, Charlotte E. Ariyan, Klaus J. Busam
Abstract
While early reports of CRTC1::TRIM11 cutaneous tumors suggested a predominantly indolent clinical course, a few cases have been documented with lymph node and distant metastases. We report herein a metastasizing tumor with a lethal outcome. It presented as a subcutaneous mass on the back of a 17-year-old teenager. Histopathologically, the tumor was subepidermal and composed of amelanotic spindle and epithelioid cells with nuclear pleomorphism. The tumor cells were immunoreactive for Sox10 and S100, focally positive for Melan-A, and negative for PRAME. Whole genome and whole transcriptome sequencing revealed a CRTC1::TRIM11 fusion as well as a number of additional genetic and genomic aberrations. No TERT promoter gene mutation was identified. The patient developed metastases to the lung, lymph nodes, and soft tissue. The tumor was refractory to various treatments. The patient died of widely metastatic disease 18 months after clinical presentation. This case expands our knowledge of the clinical, pathologic, and molecular findings of CRTC1::TRIM11 cutaneous tumors. In contrast to other reported cases, the tumor of our patient contained additional genomic aberrations. More cases are needed to assess what factors are relevant for the prognosis of CRTC1::TRIM11 cutaneous tumors to help distinguish those with indolent from those with aggressive behavior.