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

Vincenzo Canzonieri, Daniela Gasparotto, Lara Alessandrini, Gianmaria Miolo, Elena Torrisi, Tiziana Perin, Paolo De Paoli, Roberta Maestro, Angela Buonadonna

Research output: Contribution to journalArticle


After an initial benefit from tyrosine kinase inhibitors (TKI), most gastrointestinal stromal tumors (GISTs) eventually develop disease progression or secondary resistance. An altered tumor (immune)phenotype with anaplasia and morphological changes secondary to therapy have occasionally been described in 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.

Original languageEnglish
Pages (from-to)63-67
Number of pages5
JournalPathology Research and Practice
Issue number1
Publication statusPublished - Jan 1 2016


ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology

Cite this