CASE REPORT ON RARE DE-DIFFERENTIATED GIST OF STOMACH OCCURRING DENOVO

We present a rare case of de-differentiated GIST. GIST being the most common mesenchymal tumor of alimentary canal is commonly reported. However, de-defferentiation of GIST is a rare phenomenon which may occur denovo or with imatinib therapy. A 57 year old female patient presented with generalized weakness and anemia. On evaluation, a submucosal lesion on the body of stomach along the greater curvature was identied on UGI endoscopy. On CECT scan of abdomen, polypoidal intraluminal mass was seen. After sleeve gastrectomy histopathological examination showed dedifferentiated GIST, stomach which was conrmed on IHC. The patient had no prior history of Imatinib therapy/ any chemotherapy. We present this case as de-differentiated GIST occurring denovo without prior imatinib therapy is rare and not much is known about its clinical course and prognosis of such cases.

A Case Presentation of Gastrointestinal Stromal Tumor of Duodenum

A gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. It is caused by the mutation in KIT and PDGFRα genes. It constitutes <1% of all gastrointestinal tumors. Duodenal GISTs constitute 4.5% of all GISTs. We report a 61-year-old lady, presented with generalized abdominal pain, vomiting, abdominal distension, and nausea for the last 3 years. Physical exam-ination showed a pallor and on abdominal examination, a large palpable mass was extending from the pelvis to the right upper quadrant of the abdomen. The CT scan showed a large heterogeneously echogenic mass in the abdomen and pelvis with no lymphadenopathy and distant metastasis in this region. Laparotomy showed a large globular mass extending from the pelvis to the right upper quadrant of the abdomen adherent to the wall of a third part of the duodenum. Complete surgical resection of tumor done with an intact capsule. Microscopic examination showed neoplastic spindle cells with tumor necrosis. An immunohistochemical study confirmed GIST.

Differential Expression of CADM1 in Gastrointestinal Stromal Tumors of Different Sites and with Different Gene Abnormalities

Gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the human gastrointestinal tract, differentiating toward the interstitial cell of Cajal (ICC), arises predominantly in the stomach and small intestine. Small intestinal GISTs appear to have worse prognosis than gastric GISTs. In a pilot study of a cDNA expression chip using several GISTs, we found that Cell Adhesion Molecule 1 (CADM1), which could contribute to tumor growth and infiltration, is expressed more strongly in small intestinal GISTs than gastric GISTs. In the present study, we examined CADM1 expression in GISTs of different sites and with different gene abnormalities using a large number of gastric and small intestinal GISTs. First, immunoblotting confirmed significantly higher CADM1 expression in small intestinal GISTs with exon 11 c-kit mutation than gastric GISTs with exon 11 c-kit mutation. Real-time PCR also revealed that small intestinal GISTs with exon 11 c-kit mutation showed significantly higher CADM1 mRNA than gastric GISTs with exon 11 c-kit mutation. Although most small intestinal GISTs showed high CADM1 mRNA expression regardless of gene abnormality types, different CADM1 expression was detected between gastric GISTs with c-kit mutation and those with PDGFRA mutation. Immunohistochemistry showed that many small intestinal GISTs were CADM1-positive but most gastric GISTs CADM1-negative or -indefinite. In the normal gastric and small intestinal walls, immunoreactivity of CADM1 was detected only in nerves, but neither in gastric ICCs nor small intestinal ICCs, indicating that the high CADM1expression in small intestinal GISTs might be acquired during tumorigenesis. Different CADM1 expression between gastric and small intestinal GISTs might be related to different prognoses between them. Further functional experiments are needed to elucidate the role of CADM1 on GIST biology, and there is a possibility that targeting therapy against CADM1 has a preventive effect for tumor spreading in small intestinal GISTs.

Curative resection of a duodenal gastrointestinal stromal tumor in the setting of von Willebrand’s disease

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the alimentary tract and usually presents with gastrointestinal hemorrhage. The diagnosis of GIST is typically made with upper endoscopy after excluding other causes of bleeding. The surgical management of GIST can be challenging depending upon the location of the tumor. We present a unique case of duodenal GIST in the setting von Willebrand’s disease diagnosed after emergent laparotomy for massive gastrointestinal hemorrhage. Key strategies in curing our patient were treating the underlying bleeding disorder, collaborating with radiology and gastroenterology teams, and early exploratory laparotomy for refractory hemorrhage. This case demonstrates the challenges of diagnosing and managing GIST in patients with underlying coagulopathies.

Gastrointestinal stromal tumor – A review of clinical studies

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. With the advent of Imatinib, the treatment of gastrointestinal stromal tumor has been revolutionized as both the progression-free and overall survival rates have increased dramatically. Unfortunately, gastrointestinal stromal tumor patients on Imatinib do eventually fail due to resistance. Even though sunitinib and regorafenib have been shown to be highly effective as second- and third-line treatments, both have limited effects. New treatments are highly warranted for this reason. In this present review, 25 registered pharmacological clinical trials at ClinicalTrials.gov have been reviewed and show promising and encouraging results.

Gastrointestinal Stromal Tumor- An unusual presentation

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract which earlier was classified as leiomyomas, leiomyosarcomas and leiomyoblastomas. These are known to have specific markers and are important to diagnose as targeted chemotherapy is available. Our case represents one of the ends of the spectrum of clinical presentation of gastrointestinal tumors – an aggressive large mass at a younger than the usual age of presentation. Though challenging, imaging diagnosis of GIST is very important as it can guide the confirmation of the same by identification of the markers on pathology.

Utility of DOG1 Immunomarker in Fine Needle Aspirates of Gastrointestinal Stromal Tumor

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. DOG1 is a sensitive and specific immunohistochemical marker for the diagnosis of GIST. To date, no study has reported the utility of DOG1 immunocytochemistry on aspirate smears. Methods: Aspirates with a cytological diagnosis of GIST were retrieved. DOG1 immunocytochemistry was performed on aspirates with adequate material. Results: 23 cases were included (11 primary, 2 recurrent, 10 metastatic). Primary tumors were most frequently located in the stomach; most metastatic tumors were in the liver. Tumor cells were arranged in cohesive clusters with high cellularity. Cells were spindled, had a low N:C ratio, and a moderate amount of cytoplasm, which was elongated and tapering. Characteristic nuclear features included elongated nuclei with blunt or tapering ends, fine chromatin, mild anisonucleosis, and longitudinal grooves. The mitotic count was low, including in metastatic tumors. DOG1 immunopositivity was noted in 57% of the cases examined. Histopathology was available in 5 cases, all diagnosed as GIST. Conclusion: Cytology is a sensitive investigative modality for the preoperative diagnosis and confirmation of metastasis of GISTs. In ambiguous cases, DOG1 immunocytochemistry can serve as a valuable adjunct. Cytologic assessment, however, cannot predict malignant potential of GISTs as even metastatic tumors display bland nuclear features.

A retrospective, multicenter analysis of the clinicopathologic features of extra-gastrointestinal stromal tumor (EGIST).

36 Background: GIST is the most common mesenchymal tumor of the gastrointestinal tract although it constitutes only 1 percent of primary GI malignancy. Some GIST develops outside the alimentary canal such as omentum, mesentery, and retroperitoneum. These types are called extra-gastrointestinal stromal tumors (EGISTs). In this study, we retrospectively analyzed the clinicopathologic features of EGIST patients from 4 institutes in Korea Methods: From 2004 to 2012, a total of 43 patients with EGIST were identified. The clinicopathologic features including gender, age, location, tumor size, hisology, mitotic rate, IHC features, and genetic status were collected along with survival analysis. Results: The median age was 55 (range 29-80) and M:F ratio was 20:23. The most common sites were mesentery (11) and retroperitoneum (11) followed by omentum (7) and vagina (3). Other primary sites were liver (2), ovary (2), pancreas (2), perianal area (2), chest wall (1), pleura (1) and prostate (1). The median tumor size was 8.0 cm (range 2.6 – 30) and median mitotic rate was 5.0/50HPF (0 – 185) 4 cases were negative for c-Kit IHC, which were all confirmed by either IHC for DOG1 or mutational analysis. KIT analysis was performed in 10 cases with 6 wild-types and 4 exon 11 mutation were found. As for PDGFRα, 4 cases were analyzed which were all exon 18 mutation. Among 43 patients, 26 patients had undergone curative resection and 8 patients had unresectable disease and had taken palliative imatinib. Among 26 patients who had undergone curative resection, 12 patients had taken adjuvant imatinib and 14 patients had been observed without imatinib. The median tumor size of two groups were 11.0 (3.0 – 19.0) vs. 5.85 (2.6 – 18.9) and the median mitotic rate was 7.0 (2 – 18.5) vs. 1.0 (0 – 45). Regarding the 9 patients taken palliative imatinib, median tumor size was 20.9 (16.5 – 30.0), median mitotic rate was 15.0 (3 – 60) and median PFS was 22.7 months (95% CI 7.7 – 37.7). Conclusions: As the biologic behavior of GISTs is different by location, a more stratified strategy is needed for managing EGISTs including incorporation of molecular features. We are planning to perform further mutation analysis in this cohort.

Ki67 and p53 in gastrointestinal stromal tumors - GIST

CONTEXT: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor. Cellular proliferation and apoptosis is gaining importance for predicting prognosis in several cancers. OBJECTIVE: To investigate the Ki67 and p53 immunostaining in GISTs. METHODS: Specimens from 40 patients with GIST were assessed for immunohistochemical expression of Ki67 and p53. The tumors were divided according the risk of recurrence in two groups: I with high or intermediate risk and; II with low or very low risk. RESULTS: Among the 40 patients, 21 were men, the mean age was 56 years, 16 occurred in the small intestine and 13 in the stomach, 5 in the retroperitonium, 4 in the colon or rectum and 2 in the mesenterium. Thirty two tumors were from group I and 8 from group II. Half of the patients developed recurrence, being 90% of the group I (P = 0.114). The tumor Ki67 labelling index ranged from 0.02 to 0.35 (mean level 0.12). This index was marginally higher in the group I patients with recurrence (P = 0.09) compared to the patients of the same group without recurrence. p53 staining was expressed in 65% of the GISTs. A higher frequency of p53 and Ki67 had been found in the group I tumors when compared to the other group (P = 0.022; OR = 8.00 - IC 95%: 1.32-48.65). CONCLUSION: The most common site was the small intestine and 80% had a malignant potential justifying the high recurrence observed. No significant correlation was found between p53 and overall outcome of the patients. In group I patients, the evaluation Ki67LI may be a marker of prognosis. The positivity of both markers is higher among the patients with worst prognosis than in the others.