Ultra-late recurrence of gastrointestinal stromal tumour. case report and literature review

A 79-year-old Caucasian man presented with a 2-month history of central abdominal pain. An ultrasound revealed an 11 × 7 cm lesion in the segments 5 and 6 of the liver subsequently confirmed on computed tomography (Fig. 1a,b), with no other evidence of metastatic disease. The patient underwent gastric resection for an antral-pyloric neoplasm labelled ‘benign leiomyoblastoma’ 23 years prior to admission. The primary tumour was reanalysed histologically and immunohistochemically, and reclassified as high-risk gastrointestinal stromal tumour (GIST): the neoplastic elements were strongly positive for CD117, DOG-1 and Vimentin, with a proliferative index >10 mitoses/50 high power fields. The patient underwent right inferior bisegmentectomy. Histopathologic examination of the lesion (measuring 11 × 10 × 7 cm with clear resection margins; Fig. 1c,d) showed identical morphology and immunohistochemical characteristics to the previously resected gastric tumour, thus being consistent with the diagnosis of recurrent GIST. Post-operative course was uneventful. The patient is alive without evidence of recurrent disease 48 months after hepatic resection. The term GIST was first used in 1983 by Mazur and Clark to describe gastrointestinal non-epithelial tumours that lacked the immunohistochemical features of Schwann cells and did not have the ultrastructural characteristics of smooth muscle cells.1 GIST account for approximately 1–3% of all malignant gastrointestinal tumours. Men and women are equally affected, with stomach (52%) and small bowel (25%) being the most common site of origin. The distribution of metastases is predictable, with the liver dominating.2 The majority of GIST metastasize to liver on an average of 16–38 months after resection of the primary tumour. Although very rare, ultra-late hepatic metastases (>10 years from the primary diagnosis of GIST) question the need for a lifelong follow-up after surgical resection with curative intent. So far, only eight cases of ultra-late hepatic metastases of GIST have been described in the literature (range 11–29 years after resection of primary tumour).3–5 The median age of the patients was 58 years (range 39–71 years), with equal gender ratio. The sites of primary tumour were small bowel (n = 4), stomach (n = 2), duodenum (n = 1) and rectum (n = 1). In all cases, the metastasis had reached a substantial size before triggering abdominal pain, with onset varying from 3 to 6 months prior to diagnosis. Pre-operative percutaneous biopsy is contraindicated due to a significant risk of tumour rupture or dissemination.6 Late GIST recurrences raised a number of considerations, including the duration of follow-up regimen after curative surgery and the need of pathological reanalysis of previously labelled ‘benign looking leiomyoblastomas’ or ‘leiomyosarcomas’. A recent multicentre trial7 showed that large tumour size, small bowel location and high mitotic rate (but not tumour genotype) were associated with delayed recurrence development. Integration of all clinical pathological and molecular parameters is essential for planning the duration of the follow-up. At the present time, however, there is no evidence indicating the optimal time intervals, although a computed tomography scan every 3–4 months for 3 years, then every 6 months until 5 years and yearly thereafter has been recommended for high and intermediate risk GIST (i.e. tumours >5 cm or with a mitotic index >5/ 50 high power fields). Therapy with imatinib, a selective tyrosine kinase inhibitor, may achieve a stable or responding disease in about 80% of patients with unresectable/metastatic GIST. Recent evidence suggests that combining surgery with perioperative imatinib therapy can be more effective than either treatment alone in patients with both advanced primary GIST and recurrent or metastatic GIST.8 Indeed, a recent study showed that recurrence-free survival rate after R0 resection for high-risk GIST was significantly better in patients receiving imatinib for >5 years than <5 years.9 Furthermore, the 10-year estimate of overall survival was 23% in a study of 695 patients with advanced (not surgically curable) GIST harbouring the most common KIT and platelet-derived growth factor receptor (PDGFRA) mutations.10 However, controversy exists regarding its utility in very late, isolated and resectable recurrences. Notably in our case, adjuvant systemic therapy was not considered due to the imatinib-insensitive D842V mutation of PDGFRA showed on genotype analysis. Nevertheless, radical surgery conferred a 4-year disease-free survival to our patient despite the highrisk nature of his primary tumour. Whether this is indicative of a more indolent nature of the disease is unknown. Among the eight patients with ultra-late metastases reported so far, two underwent imatinib therapy instead of surgical excision. However, the disease-free follow-up of these patients is either short4 or not reported.3