GIST was first described by Mazor and Clark (1983)
. It originates from the interstitial cells of Cajal (ICC), located in the muscularis propria (myenteric plexus) responsible for triggering smooth muscle contraction
[2, 3]. The basic pathology is an activating mutation (gain in function) of chromosome 4 which codes for c-Kit resulting in uncontrolled proliferation of stem cells that differentiate towards ICC. GIST is sporadic
. Familial forms with autosomal dominant inheritance have also been documented
Isolated reports of GIST occurring concomitantly with paraganglioma, pulmonary chondroma, nerofibromatosis, pancreatic neuro-endocrine tumours, burkitt’s lymphoma, osteosarcoma, neuroblastoma and melanoma have been documented
90% of GIST occurs in adults more than 40 years of age (median age 63 years). There is slight male preponderance
. No documented elements indicating any association with geographic location, ethnicity, race or occupation has been elucidated
The commonest site of GIST is stomach (60-70%)
[2, 3]. Jejunum accounts for 10% of all GI tract GIST’s
[1, 3]. Sporadic reports of GISTs arising from the omentum, mesentery or retroperitoneum, have been documented but most of these are metastatic from gastric or intestinal primaries
. Extra-GIST has been reported in gall bladder, pancreas, liver and urinary bladder
Presentation is erratic. Seventy percent are symptomatic at presentation, 20% are asymptomatic and 10% are detected at autopsy
[5, 6]. Common presentations include abdominal pain, palpable mass, gastro intestinal bleeding, fever, anorexia, weight loss and anaemia
. Isolated jejunal GIST associated with perforation and peritonitis is a rare and unique
Perforation is usually attributed to replacement of bowel wall by tumour cells, tumour embolization leading to ischemia, necrosis together with raised intra-luminal pressure
[4, 5, 7]. In view of the exophytic nature of the growth, intestinal obstruction occurs due to compression rather than luminal obstruction. As such intetstinal obstruction is a rare occurrence until the tumour attains enormous size.
Clinical diagnosis of GIST is based on index of suspicion
[6, 7]. Specific diagnostic signs and symptoms are absent. Chronicity is a rule. Acute atypical presentation includes hemorrhage and perforative peritonitis
[1–10]. Preoperative imaging modalities like contrast enhanced abdominal computerized tomography (CT) aids in diagnosis
. The extent of the tumor, metastases and involvement of other organs can be assessed. A dedicated magnetic resonance imaging (MRI) provides better information than CT in the preoperative staging workup
[7, 8]. Endoscopy can diagnose gastric GISTs. Endoscopy demonstrates smooth, mucosa-lined protrusion of the bowel wall which may or may not show signs of bleeding or ulceration. Endoscopic ultrasound with guided fine-needle aspiration is diagnostic for primary lesions in 89% of the cases
[8–10]. However, the relative usefulness of images depends on the site, duration and suspicion of GIST in patients presenting with undiagnosed abdominal lumps. The decisive diagnosis rests on the pathological and immunohistological tests
[2, 5–10]. Histopathologically GISTs are composed of spindle (70%), epithelioid and round cell or an admixture
[6, 8]. Similarities with histological picture of gastrointestinal leiomyosarcoma, leiomyoblastoma and poorly differentiated carcinomas may cause diagnostic dielemma, Immuno-histochemical assays for CD117 antigen (KIT) is the mainstay for diagnosis
Diagnosis of asymptomatic GIST with acute presentation like perforation remains elusive. Accordingly, our provisional diagnosis was peptic perforation as free gas under diaphragm was noted in erect abdominal rhoentgenogram.
Optimal surgical treatment of GIST entails complete removal of the tumor with clear surgical margins including the adjacent involved organs
[5–10]. Complete surgical resection entails 48-65% five-year survival
. Perforation of the tumor lowers the five-year survival to 24%, probably due to peritoneal dissemination
. Local and regional lymph node involvement is infrequent in GIST
[6, 8, 10]. GIST’s presenting with perforation, attention needs to be paid, in view of possible recurrence of the tumor. Abundant peritoneal lavage should be performed with distilled water to reduce the risk of peritoneal tumour spillage. Distilled water is used because of its cytolytic activity on suspended cells
[7, 9, 10].
GIST response to conventional chemotherapy is very poor (<10%), while radiotherapy is only used in cases of intraperitoneal hemorrhage, when the precise location of the tumor is known, or for analgesic purposes
STI571 (imatinib), acts as a powerful selective inhibitor of tyrosine-kinase, PDGFR (platelet derived growth factor receptor) and c-kit receptor
. Oral imatinib at doses >300 mg per day achieves curative results.
The prognostic factors of GIST include age at presentation, anatomic location, size (most important), histomorphology, immuno-histochemistry and molecular genetics
Positron-emission tomography with 18F-fluoro-2-deoxy-D-glucose is a very useful tool for the postoperative follow-up of patients receiving imatinib
[4, 5, 9, 10].
The 5-year survival rate is 35%. It increases to 54% after complete surgical excision
[1–10]. However 40% will recur within 18 – 24 months. Once recurrence has occurred median survival is 9–16 months
[3, 5, 7, 8, 10].