Pancreatic Extra-Gastrointestinal Stromal Tumour with Documentation of C-Kit Mutation: A Case Report

Abstract

A 60-year-old male presented with pain in left side of abdomen for several months. Physical examination revealed an abdominal mass in left hypochondrium. Basic laboratory investigations were non contributory. MRI scan of the abdomen showed a 21x18x14 cm solid and cystic mass lesion in relation to the body and tail of pancreas.CT guided FNAC of pancreatic mass yielded low cellularity consisting of few round to oval atypical cells with eccentric nuclei and moderate amount of cytoplasm. The cytology was suggestive of neoplastic pathology however the definite typing was not possible. Abdominal laparoscopy was carried out which revealed a large solid and cystic mass involving body and tail of pancreas. The biopsy on histopathology examination showed a tumour composed of sheets of round to epithelioid cells with hyalinised stroma and intervening blood vessels. The tumour cells showed mild pleomorphism, oval to mildly irregular nuclei and scant to moderate amount of eosinophilic to vacuolated cytoplasm. No tumour necrosis was seen however the mitotic count was around 1/10HPF [Table/ Fig-1,2]. Immunohistochemistry staining revealed diffuse cytoplasmic positivity for CD117 (c-kit) [Table/ Fig-3], CD34 and variable positivity for vimentin and focal positivity for SMA. The cells were completely negative for S-100, neuron specific enolase, chromogranin A, CD99 and synaptophysin. The morphological and immunohistochemical findings were favouring epithelioid subtype of GIST. Hence, the diagnosis of pancreatic GIST with high risk of malignancy was made. Subsequently, C-kit mutation analysis was done which revealed a deletion mutation of exon 11 resulting in loss of aminoacid at positions 554 to 559. Wild or normal gene sequence was observed in exon 9 of c-kit gene. Patient was put on imatinib therapy. Follow up MRI after 3 months showed metastatic deposits in lung and patient died within 9 months of initial diagnosis. EGIST originate from the soft tissues of the abdomen and retroperitoneum such as the omentum, mesentery, retroperitoneum and gall bladder [3]. EGIST arising in the pancreas are rare neoplasm (pEGIST) and only 19 cases have been reported in the literature [4]. The age range was 38 to 84 yrs and most of the patients presented with gastric pain and abdominal mass. The index case was 60-years-old and had similar clinical presentation. The majority (42.1%) of pEGIST occurred in the head of the pancreas, 26.3% in tail, 21.1% in both body and tail and 5.3% in the uncinate process [4]. In the current case, tumour was detected in body and tail of the pancreas. The tumour ranged from 2.4cm to 35 cm in size in various studies and in present case, the maximum tumour size was 21cm. DISCUSSIONThe immunohistochemical marker for GIST is the expression of the C-kit receptor tyrosine kinase (CD117 antigen). Approximately 5% of GIST are C-Kit negative and harbour PDGFR -alpha mutation [1]. In addition, 40 to 70 % GIST's show positivity for CD34 and variable positivity for other mesenchymal markers such vimentin, myoid (smooth muscle...

Duodenal gastrointestinal stromal tumor masquerading as an uncinate process pancreatic neoplasm

“…DOG1 positivity is considered independent of KIT or PDGFRA mutational status and highly significant in diagnosing GIST. 13 In a recent study, H-caldesmon was expressed in all GISTs and E-GISTs, including those with CD117-negative expression. 14 The learning point here is that CD117 negative and H-caldesmon positive tumors should not be misdiagnosed as smooth muscle tumors, necessitating the inclusion of specific markers like DOG1 and molecular testing.…”

“…Approximately 5% of tumors are c‐Kit negative and harbor PDGFRA gene mutation. DOG1 positivity is considered independent of KIT or PDGFRA mutational status and highly significant in diagnosing GIST 13 . In a recent study, H‐caldesmon was expressed in all GISTs and E‐GISTs, including those with CD117‐negative expression 14 .…”

Recurrent and metastatic extragastrointestinal stromal tumors of the mesentery with C-KIT and PDGFRA mutations: a case report

“…However, roughly 5% of the cases presented negative immunohistochemistry for it. 8 So, we can use the results of DOG-1 and gene mutation report to help diagnose the diseases. The vast majority of GISTs carry activating mutations of the C-KIT or PDGFRA genes (85%-90%).…”

“…[4][5][6][7] CD117 showed a strongly and diffusely positive immunohistochemical response, which can support the diagnosis of GISTs/EGISTs. 5 However, roughly 5% of the cases presented negative immunohistochemistry (IHC) for CD117, 8 which is quite accessible for some GISTs/EGISTs to be misdiagnosed as other tumors.…”

Pancreatic GIST in a Patient with Limited Stage Small Cell Lung Cancer: A Case Report and Review of Published Cases

“…Padhi et al reported nineteen cases of pancreatic GIST gathered from 2000 to 2012 [ 30 ]. In 2015, Joseph et al reported a case of a patient with pancreatic GIST that was started on imatinib but later developed metastatic disease and died 9 months later [ 31 ]. If the tumor can be resected, then treatment of choice would be surgery.…”