title: 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.
abstract: 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.
authors.affiliation: Department of Pathology, CRO Aviano National Cancer Institute IRCCS, Aviano, PN, Italy. Electronic address: vcanzonieri@cro.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Canzonieri
authors.affiliation: Experimental Oncology, CRO Aviano National Cancer Institute IRCCS, Aviano, PN, Italy. Electronic address: dgasparotto@cro.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gasparotto
authors.affiliation: Department of Pathology, CRO Aviano National Cancer Institute IRCCS, Aviano, PN, Italy. Electronic address: boxlara@tin.it.
authors.forename: Lara
authors.initials: L
authors.lastname: Alessandrini
authors.affiliation: Medical Oncology B Units, CRO Aviano National Cancer Institute IRCCS, Aviano, PN, Italy. Electronic address: gmiolo@cro.it.
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Miolo
authors.affiliation: Medical Oncology B Units, CRO Aviano National Cancer Institute IRCCS, Aviano, PN, Italy. Electronic address: etorrisi@cro.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Torrisi
authors.affiliation: Department of Pathology, CRO Aviano National Cancer Institute IRCCS, Aviano, PN, Italy. Electronic address: tperin@cro.it.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Perin
authors.affiliation: CRO Aviano National Cancer Institute IRCCS, Scientific Directorate, Aviano, PN, Italy. Electronic address: pdepaoli@cro.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: De Paoli
authors.affiliation: Experimental Oncology, CRO Aviano National Cancer Institute IRCCS, Aviano, PN, Italy. Electronic address: rmaestro@cro.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Maestro
authors.affiliation: Medical Oncology B Units, CRO Aviano National Cancer Institute IRCCS, Aviano, PN, Italy. Electronic address: abuonadonna@cro.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Buonadonna
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015820:Cadherins / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007633:Keratins / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D047428:Protein Kinase Inhibitors; D007633:Keratins
keywords: Aberrant cytokeratin expression; GISTs; Imatinib-resistance; Immunephenotype; Therapy-induced changes