Case of Rectal GI Stromal Tumor Demonstrating that KIT and PDGFRA Mutations Are Not Always Mutually Exclusive

A 52-year-old woman presented with complaints of anal pain/ constipation/tenesmus for 3 months before being referred to our hospital. There were no relevant prior illnesses. Rectal digital exami- nation revealed a 6-cm smooth elastic mass on the rectal posterior left side 2 cm from the anal verge. Colonoscopy showed a rectal submu- cosal bulging. Computed tomography (CT) scan and magnetic reso- nance imaging confirmed the presence of a single 6-cm well-delimited mass, compressing and infiltrating the wall of the medium to low rectum. The tumor was completely removed, although ruptured, by transanal excision to save the organ. The specimen (2- to 22-mm fragments) was almost entirely composed of tumor, highly cellular and with necrosis, consisting of spindle cells with perinuclear vacuol- ization and several mitoses (80/50 high-power fields; Fig 1A, magnifi- cation 400). Scarce rectal wall smooth muscle was present (Fig 1B, left, magnification 100). The tumor stained for CD117 (Fig 1C, magnification 400), DOG1 (Fig 1D, magnification 400), CD34, and S100 (patchy cytoplasmic pattern); desmin, melan-A, and HMB45 were negative. The diagnosis was spindle-cell GI stromal tumor (GIST). The patient’s disease was considered high-risk because of the fragmentation during removal, morphology, and site.1,2 Given that a subsequent positron emission tomography/CT scan was negative, a conservative approach was maintained, leaving additional surgery as an option in case of relapse. By using polymerase chain reaction direct sequencing3-6 on independent DNA templates from four different tumor fragments, two mutations were consistently found: a 6-nucleotide– insertion GCCTAT between 1509-1510 nucleotides (CDS mutation: c. 1509_1510insGCCTAT) causing an insertion of two amino acids: alanine and tyrosine (p.Y503_F504insAY) in KIT exon 9 (Fig 2A; arrow indicates the start point of the GCCTAT insertion), and a point mutation (A3 T at 2525) determining a Val for Asp substitution at 842 (D842V) of exon 18 of platelet-derived growth factor receptor alpha (PDGFRA; Fig 2B; arrow indicates point mutation). KIT and PDGFRA were wild type in the rectal wall smooth muscle.