title: An unusual and potentially misleading phenotypic change in a primary gastrointestinal stromal tumour (GIST) under imatinib mesylate therapy.
abstract: We present a unique case of a 62-year-old female who was diagnosed with a huge gastric gastrointestinal stromal tumour (GIST). Core needle biopsy revealed a cellular spindle cell GIST with diffuse expression of CD117 and CD34. Four mitotic figures were counted in ten available HPFs, indicating a high-risk tumour. Computed tomography scan, performed after 8 months of neoadjuvant imatinib mesylate treatment (Glivec, 400 mg/day), revealed a partial response with reduction of tumour size from 20 × 15 × 15 cm to 13.3 × 8 × 7.6 cm. The patient underwent complete tumour resection. The tumour revealed extensive cystic changes and hyalinisation in 90% of the tumour mass. Multiple viable tumour clones, measuring up to 1 cm, showed highly anaplastic, large epithelioid cells with vesicular nuclei and prominent, centrally located nucleoli, strikingly mimicking the appearance of proximal-type epithelioid sarcoma, anaplastic carcinoma, melanoma or epithelioid angiosarcoma. These anaplastic tumour cells expressed pankeratin (KL-1) and vimentin, but they were completely negative for CD117, DOG-1, CD34, S100, desmin, α-smooth muscle actin, HMB45, CD30, CD45, CK7, CK20 and 34βE-12. Sufficient tissue for molecular analysis was available from the resected tumour. No mutations were detected in KIT exons 9, 11, 13, 17, PDGFRA exons 12, 14, 18, KRAS and BRAF. The patient was alive with no evidence of recurrence 28 months later. To our knowledge, this represents the first report on this unusual type of trans-differentiation in GIST under imatinib therapy. Awareness of this phenomenon would help to avoid diagnostic confusion when evaluating post-treatment resections from GISTs.
authors.affiliation: Department of Surgery, University Hospital, Erlangen, Germany.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Vassos
authors.forename: Abbas
authors.initials: A
authors.lastname: Agaimy
authors.forename: Anne
authors.initials: A
authors.lastname: Schlabrakowski
authors.forename: Werner
authors.initials: W
authors.lastname: Hohenberger
authors.forename: Regine
authors.initials: R
authors.lastname: Schneider-Stock
authors.forename: Roland S
authors.initials: RS
authors.lastname: Croner
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000378:metabolism; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate; D008875:Middle Aged; D010641:Phenotype; D010879:Piperazines / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit