Clinical Profile:

A 65 year old man presented with a two year history of vague upper abdominal pain and an abdominal lump The patient also complained of loss of appetite and weight loss since the last two months. There was no history of fever, joint pains or jaundice. e had not suffered from pancreatitis,Diabetes mellitusor tuberculosis. e has had no surgeries performed.

Clinical examination of the abdomen revealed a well-defined, transversely mobile, firm intra-abdominal lump in the umbilical, right and left lumbar regions. The mass measured approximately approx 15x10 cm. The superior margin of the mass could be distinctly felt separate from the liver .

Radiological Investigations:

Ultrasonography of abdomen was requested; the images are as shown:

There is a well defined, solid, heterogeneous, lobulated lesion of 13.7x10.9 cm . It had areas of necrosis. Linear hyperechoic areas with dirty posterior shadowing is seen within the core of lesion an luminal air. The lesion shows arterial and venous vascularity.

A small bowel series was then performed:

Axial and coronal reconstructed images of CECT of the abdomen show a large, well defined soft tissue density - heterogeneously enhancing, lobulated, exophytic mass arising from the small bowel loops occupying the umbilical and both lumbar quadrants with areas of necrosis within. The central core shows is opacified with contrast and air. No calcification is seen in the mass,. No enlarged mesenteric or retroperitoneal lymph nodes are seen.

3D reconstructed images of the colon shows normal findings with superolateral displacement of the caecum and transverse colon

Radiological Diagnosis:

In view of the long segment of involvement and large mass lesions, a diagnosis of a gastrointestinal stromal tumor or a malignant mesenteric lesion was considered.

Pathological examination

USG guided biopsy was done.

Biopsy tissue shows multiple spindle shaped cells arranged in sheets and vague storiform pattern. They have moderate amount of eosinophilic cytoplasm, which at places, is vacuolated and oblong. Pleomorphic nuclei with prominent nucleoli are seen. Histopathological findings are suggestive of a spindle cell tumour.

The sample was found to be c-KIT positive.

Hence the diagnosis of GIST was made.

Treatment:

Surgical resection of the mass was planned and the patient was started on Imatinib This drug inhibits several tyrosine kinase receptors with varying affinity, including KIT. However, in the interim, the patient suffered myocardial infarction and succumbed.

Discussion:

Gastrointestinal stromal tumors (GISTs), though the most common mesenchymal tumors of the GI tract, are rare accounting approximately 1% to 3% of all gastrointestinal tumors.

Mazur and Clarke coined the term GIST in 1983 for a distinct set of mesenchymal tumors of the GI tract having no ultrastructural or immunohistochemical features characteristic of smooth muscle differentiation.(1)

Kindblom and associates in 1998 demonstrated that the actual cell of origin of these tumors is a pluripotent mesenchymal stem cell programmed to differentiate into interstitial cells of Cajal, the GI tract "pacemaker cells" - the cells responsible for initiating and co-coordinating GI motility.(2)

The most critical development that distinguished GIST as a unique clinical entity was the discovery of c- kit proto-oncogene gain-of-function mutations in these tumors by Hirota and collegues in 1998.(3)

•Approximately 85% GISTs are associated with an abnormal c-KITpathway. c-KIT is a gene that encodes for a transmembrane receptor for a growth factor termed stem cell factor(scf). The abnormal c-KIT pathway most commonly (85%) arises from mutation . The c-KIT product/CD117 is expressed on ICCs .In the gut, a mass staining positive for CD117 is likely to be a GIST, arising from ICC cells.(4)

Awareness of GIST as a distinct GI tract lesion is paramount in managing these rare and often aggressive tumors, which, given the risk factors now known, show a significant preponderance for recurrence and behave as a malignant lesion.

The ue of adjuvant imatinib mesylate has successfully increased the overall survival (OS) and progression free survival (PFS). Some patients develop resistance to Imatinib during long-term therapy. The acquired resistance to the drug occurs commonly via a secondary mutation in the KIT kinase domain, located in exon 17. Mutations in exon 9 and 11 have been reported. (5)

Guidelines indicate that radical surgical resection is the gold standard for localized primary GIST. Increasing cure rates, overall survival and progression-free survival should be the aim of all adjuvant therapy which should be reserved only for patients having significant prognostic indicators for disease recurrence.(6)

References:

1. Mazur MT, Clark HB. Gastric Stromal Tumours: Reappriasal of Histogenesis. Am J Surg Pathol1983;•••:7509-7519

2. Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol1998. May;152(5):1259-1269 [

3. Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998. Jan;279(5350):577-580 10.1126/science.279.5350.577 [

4.Demetri, G., chapter author; DeVita, L; Lawrence, TS; Rosenberg, SA., editors (2011). "Chapter 87". DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology (9th ed.). ISBN 978-1-4511-0545-2.

5. Sakurai S, Oguni S, Hironaka M, Fukayama M, Morinaga S, Saito K. Mutations in c-kit gene exons 9 and 13 in gastrointestinal stromal tumors among Japanese. Jpn J Cancer Res 2001. May;92(5):494-498 10.1111/j.1349-7006.2001.tb01121.x

6. Casali PG, Blay JY, ESMO/CONTICANET/EUROBONET Consensus Panel of Experts Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010. May;21(Suppl 5):v98-v102 10.1093/annonc/mdq208

Acknowledgement:

We are grateful to the Department of Pathology at our institution for providing us slides of the histologic material and their description.