Morphologic shift associated with aberrant cytokeratin expression in a GIST patient after tyrosine kinase inhibitors therapy. A case report with a brief review of the literature

We present a 52-year old patient, diagnosed with high risk, spindle-cell, GIST (CD117 positive, Pankeratin negative) in 2003, showing a c-Kit exon 11 mutation. After TKI therapy, he developed drug resistance and disease progression. Pathological assessment of the last surgical specimen showed a pure epithelioid/clear cell histology, without evidence of cellular anaplasia. Tumor cells were CD117 positive, DOG1 positive but also E-cadherin positive and Pankeratin positive, whereas molecular analysis confirmed the presence of the c-Kit exon 11 mutation, with no additional mutations. We describe an unusual case of GIST showing peculiar (immuno)phenotypic changes under therapy, different from the vast majority of therapy-driven changes, which include marked cellular pleomorphisms and KIT immunonegativity. Possible molecular explanations to understand these phenomena and a brief review of the literature are also addressed.