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Gastrointestinal stromal tumor of the rectum

Published:January 07, 2023DOI:https://doi.org/10.1016/j.amjms.2022.12.031

      Case Presentation

      A 78-year-old active man with hypertension and chronic kidney disease (creatinine 2.0 mg/dL, eGFR 30ml/min; Hb 11 gr/dL) palpated an asymptomatic perianal subcutaneous mass and was referred to Oncology. Rectal examination and anoscopy/rectoscopy demonstrated 6-8 cm perianal mass without mucosal penetration. Colonoscopy and tumor markers were normal. Sagittal non-contrast computed tomography (CT) showed a large para-rectal mass (M) (Fig. 1A), with intense radiotracer uptake in positron-emission-tomography scan (Fig. 1B). Despite its size, the mass did not obstruct the lumen but was adherent to the rectum and left levator ani muscle. As expected, there was concentrated radiotracer in the urinary bladder (B). Biopsy (H&E staining) showed a mesenchymal lesion composed of spindle cells arranged in short fascicles (Fig. 2A), immunostaining with CD34, DOG1 (Fig. 2B) and c-KIT[exon 11 mutation identified], (2 mitoses/hpf), consistent with gastrointestinal stromal tumor (GIST) of the rectum, locally advanced disease. Abdominoperineal resection was unlikely to achieve tumor-free margins. Imatinib (Gleevec) 200 mg/day (GFR-adjusted dose) was started, and continued. A repeat PET-CT at one year showed no radiotracer uptake and the mass had shrunk >50%.
      Mesenchymal neoplasms account for just 1-3% of gastrointestinal cancers. Gastrointestinal stromal tumors are mostly sporadic, developing in the seventh decade, in any location of the gastrointestinal tract (infrequently in other intra-abdominal or pelvic locations), but mostly in the stomach (60-70%) or small intestine (25-30%).
      • Miettinen M.
      • Lasota J.
      Gastrointestinal stromal tumors – definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis.
      Rectal GISTs are unusual (≤5%), diagnosed at an annual frequency of 10-14.5 per one million of the population. Clinical presentation is variable, and pain, bleeding, change of bowel habits/constipation, or urinary symptoms may occur alone or combined, though some patients first notice the tumor, as in our case. Computed tomography (CT) is the standard mode of imaging, revealing a highly-vascularized contrast-enhancing exophytic mass, but MRI better detects adjacent organ involvement.
      • Kameyama H.
      • Kanda T.
      • Tajima Y.
      • et al.
      Management of rectal gastrointestinal stromal tumor.
      Complete surgical resection with tumor-free margins is the preferred treatment of non-metastatic tumors, but rectal GISTs pose a special problem. Anatomical considerations make curative resection hard, most patients (∼70%) are in the high-risk category, and a high rate of local recurrence was reported, regardless of the surgical procedure used.
      • Kameyama H.
      • Kanda T.
      • Tajima Y.
      • et al.
      Management of rectal gastrointestinal stromal tumor.
      The advent of molecularly-targeted kinase-inhibitors afforded the first effective systemic treatment. It was found highly useful as a preoperative adjuvant therapy for locally advanced as well as in recurrent/metastatic GISTs.
      • Blanke C.D.
      • Demetri G.D.
      • von Mehren M.
      • et al.
      Long-term results from a randomized phase II trial of standard versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT.
      Diagnosis depends on immunohistochemical markers and gene mutation analysis. Most tumors (95-96%) stain for KIT protein (CD117) and DOG-1 and ∼75% have an oncogenic mutation in KIT, most often occurring in exon 11; or in platelet-derived growth factor receptor alpha (∼10%). These encode type III receptor tyrosine-kinase inhibitors enabling the use of tyrosine-kinase inhibitors (TKI) such as imatinib. In rectal GISTs, imatinib treatment was associated with shrinking tumor size while preserving surrounding organs and avoiding extensive surgery,
      • Blanke C.D.
      • Demetri G.D.
      • von Mehren M.
      • et al.
      Long-term results from a randomized phase II trial of standard versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT.
      as in our patient. Patients with KIT exon 11 mutations had a higher rate of objective response (86%) and long event-free and overall survival (median 57 months). In our patient, imatinib (Gleevec) treatment controlled tumor growth while preserving his quality of life and avoiding extensive surgery. This case is also a reminder of the continuing importance of patients checking themselves.

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      Funding

      Not applicable.

      Declaration of Competing Interest

      None identified.

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