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 examinationrevealeda6-cmsmoothelasticmassontherectalposteriorleft side 2 cm from the anal verge. Colonoscopy showed a rectal submucosalbulging.Computedtomography(CT)scanandmagneticresonanceimagingconfirmedthepresenceofasingle6-cmwell-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 andwithnecrosis,consistingofspindlecellswithperinuclearvacuolizationandseveralmitoses(80/50high-powerfields;Fig1A,magnification 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).Thepatient’sdiseasewasconsideredhigh-riskbecause ofthefragmentationduringremoval,morphology,andsite.1,2 Given thatasubsequentpositronemissiontomography/CTscanwasnegative,a conservativeapproachwasmaintained,leavingadditionalsurgeryasan option in case of relapse. By using polymerase chain reaction direct sequencing3-6onindependentDNAtemplatesfromfourdifferenttumor fragments, two mutations were consistently found: a 6-nucleotide– insertion GCCTAT between 1509-1510 nucleotides (CDS mutation: c. 1509_1510insGCCTAT)causinganinsertionoftwoaminoacids:alanine andtyrosine(p.Y503_F504insAY)inKITexon9(Fig2A;arrowindicates thestartpointoftheGCCTATinsertion),andapointmutation(A3Tat 2525)determiningaValforAspsubstitutionat842(D842V)ofexon18of platelet-derived growth factor receptor alpha (PDGFRA; Fig 2B; arrow indicatespointmutation).KITandPDGFRAwerewildtypeintherectal wallsmoothmuscle.