ERBB2/ERBB3-mutated S100/SOX10-positive uterine sarcoma: something new

Area of Science:

• Oncology
• Pathology
• Molecular Biology

Background:

• Uterine mesenchymal tumors often involve receptor tyrosine kinase fusions.
• A distinct genetic fusion-negative uterine sarcoma subtype has been recently identified.
• This subtype is characterized by ERBB2/ERBB3 mutations, CDKN2A deletion, ATRX mutation, and S100+/SOX10+ immunohistochemistry.

Purpose of the Study:

• To describe another case of this emerging uterine sarcoma entity.
• To review the literature on epidermal growth factor receptor family aberrations in uterine mesenchymal tumors.
• To support the classification of this tumor as a distinct entity based on its molecular and pathological profile.

Main Methods:

• Case report of a 57-year-old woman with an 8-cm cervical tumor.
• Immunohistochemical analysis including SOX10, S100, CD68, CD56, MITF, PRAME, HMB-45, ER, PR, HER2, Melan-A/MART1, STAT6, pan-TRK, ALK, CD34, desmin, CD10, myogenin, pancytokeratins, and H3K27me3.
• Molecular analysis for genetic alterations including ERBB2, ATRX, CDKN2A, NF1, and SMARCA4.

Main Results:

• The tumor exhibited spindle cell morphology and was immunoreactive for SOX10, S100, CD68, CD56, MITF, and PRAME.
• Key molecular findings included ERBB2 p.Val777Leu, ATRX p.F2113Sfs*, CDKN2A deep deletion, NF1 p.W2317*, and SMARCA4 p691Sfs*.
• Retained H3K27me3 expression and negative results for various other markers confirmed the distinct profile.

Conclusions:

• The described case represents another instance of an emerging uterine sarcoma entity with a unique molecular and pathological profile.
• Aberrations in the epidermal growth factor receptor family, particularly ERBB2/ERBB3 mutations, are significant in this tumor type.
• The distinct profile and potential for targeted therapy support its classification as a separate entity.