Malignant gastrointestinal stromal tumors (GISTs) of the duodenum – A rare occurrence: Case report

Malignant gastrointestinal stromal tumors (GISTs) of the duodenum ISSN: 2394-0026 (P)Case Report ISSN: 2394-0034 (O)Malignant gastrointestinal stromal tumors (GISTs) of the duodenum – A rare occurrence: Case reportKandukuri Mahesh Kumar1*, Ch. Krishna Reddy1, T. Divyagna1, R. Swarupa2, Chintakindi Sravan3, K. Shashi Kiran41Assistant Professor, Malla Reddy Institute of Medical Sciences (MRIMS), Hyderabad, Telangana State, India2Assistant Professor, Malla Reddy Medical College for Women (MRMCW), Hyderabad, Telangana State, India 3Pathologist, Vijaya Diagnostic Center, Hyderabad, Telangana State, India 4Pathologist, Omega Cancer Hospital, Hyderabad, Telangana State, India *Corresponding author email: [email protected] to cite this article: Kandukuri Mahesh Kumar, Ch. Krishna Reddy, T. Divyagna, R. Swarupa,Chintakindi Sravan, K. Shashi Kiran. Malignant gastrointestinal stromal tumors (GISTs) of theduodenum – A rare occurrence: Case report. IAIM, 2015; 2(3): 188-192. Available online at www.iaimjournal.comReceived on: 17-02-2015 Accepted on: 23-02-2015AbstractGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of thegastrointestinal (GI) tract. Most of the cases are located in the stomach followed by the smallintestine. They arise from the interstitial cells of cajal, which are located in the wall of the intestine.Malignant GISTs are rare type of tumors in GIT. Small intestine GIST is more likely to be malignantcompared to stomach. Here we reported such a rare case of malignant GIST in a 54 years old femalepatient who came to the hospital with complaints of pain and mass in abdomen. Ultrasoundrevealed a mass originating from the duodenum. Provisional clinical diagnosis of duodenalcarcinoma was considered preoperatively. Patient underwent complete surgical excision of thetumor. Histopathological examination confirmed the diagnosis of malignant GIST. As the recurrencerate for malignant GIST is high, patient was kept on follow up.Key wordsGIST, Malignancy, Mesenchymal, Small intestine, C-KIT, DOG-1.International Archives of Integrated Medicine, Vol. 2, Issue 3, March, 2015. Page 188Copy right © 2015, IAIM, All Rights Reserved.

Malignant gastrointestinal stromal tumors (GISTs) of the duodenum ISSN: 2394-0026 (P) ISSN: 2394-0034 (O)Introduction microscopy, tumor tissue was arranged inThe gastrointestinal stromal tumor (GIST) is the fascicles and interlacing bundles with increasedmost common mesenchymal neoplasm of the cellular content and thin stroma. (Photo – 1)gastrointestinal (GI) tract. GIST accounts for Individual cells were aggressive looking spindleapproximately 0.1-3% of all gastrointestinal tract to oval cells with high nuclear cytoplasmic ratiotumors [1, 2]. They occur mostly in stomach and coarse dispersed chromatin. (Photo - 2)followed by the small intestine. However, they Mitotic index was very high per field. At fewmay occur anywhere in the GI tract including the areas there were areas of necrosis noted.mesentery, retroperitoneum and omentum [2, Diagnosis of malignant GIST was made.3]. These tumors arise from the interstitial cells Photo – 1: Photomicrograph showing tumorof cajal, pace maker cells located between tissue arranged in fascicles and interlacingmyenteric plexus cells and smooth muscle cells bundles with increased cellular content and thinof the GIT [3]. Gastrointestinal stromal tumors stroma. (Low power view)(GISTs), were formerly classified as leiomyomasor leiomyosarcomas, are mesenchymal tumorsof the gastrointestinal tract (GIT). The definitionof GIST was first proposed by Mazur and Clark(1983) [1, 2]. Malignancy in GIST is common incases occurring in small intestine compared tothe stomach. Several factors are taken intoconsideration for diagnosing malignancypotential of GIST.Case report DiscussionA 54 years old female patient came to our Gastrointestinal stromal tumors (GIST) are thehospital with complaints of pain and mass in the most common non-epithelial tumors ofabdomen since 1 year and complaints of loss of gastrointestinal tract arising from the interstitialappetite and loss of weight since 5 months. cells of cajal and constitute 80% of mesenchymalThere were three episodes of vomiting since last neoplasm of the gastrointestinal tract and2 months. She was a known case of represents about 5% of all sarcomas [4]. On ultrahypertension and on medication regularly. Other structural examination, the cells of Cajal showthan that she had no significant past history. On both smooth muscle and neural differentiation,examination, there was a lump noted in the accounting for different variants of GIST. GISTright hypochondriac region measuring 6x2 cm. most commonly arises from the stomach (60 -Routine blood investigation were normal. 70%) and small intestine (20 - 30%) with < 10%Ultrasound abdomen revealed mass originatingfrom the duodenum. Clinical diagnosis of theduodenal carcinoma was made and patientposted for surgery. Complete excision of themass was done and specimen was sent forhistopathological examination. Sections weremade from the tissue, stained with hematoxylinand eosin and examined under microscope. OnInternational Archives of Integrated Medicine, Vol. 2, Issue 3, March, 2015. Page 189Copy right © 2015, IAIM, All Rights Reserved.

Malignant gastrointestinal stromal tumors (GISTs) of the duodenum ISSN: 2394-0026 (P) ISSN: 2394-0034 (O)arising from the rest of the gastrointestinal tract clinical and ultrasonographic findings of GISTslike esophagus, colon, rectum or extra intestinal are non-characteristic and therefore asites such as omentum, mesentery and preoperative presumptive diagnosis based onretroperitoneum [2, 4]. The peak incidence of these features is difficult [2]. Definitive diagnosisGIST was found in the 4th and 5th decades with a made only by the histopathological examination.male preponderance in a ratio of 3: 1 [5] but ourcase was seen in female patient. Most GISTs Microscopically, GISTs are well-circumscribed(95%) have a mutation in the c-kit proto- smooth lobulated, uncapsulated tumors. Theyoncogene, leading to the constitutive expression are composed of spindle cells or epithelioidof KIT protein and 5% of cases have activating cells, or a mixture of both, and may show areasmutation in the PDGFRA gene [6]. of cystic degeneration, necrosis or focal hemorrhage [2, 5]. Most of the GIST cases are ofPhoto – 2: Photomicrograph showing aggressive benign or of low malignant potential, but caseslooking spindle to oval cells with high nuclear arising from small intestine are highly malignantcytoplasmic ratio and coarse dispersed and aggressive when compared to stomach.chromatin. High mitotic index was present. Histological criteria have not been well established to predict the malignant potential of GIST. Prognosis of the GIST correlated well with mitotic count, tumor size, tumor cellularity, tumor necrosis, anatomical location, invasive growth and expression of Ki-67 and PCNA index [7]. Most pathologists use a combination of tumor size and mitotic rate to assess the malignant potential of these tumors. Features favoring malignancy are: size > 5 cm, mitotic rate > 5/50 hpf (high power field), high cellularity, nuclear pleomorphism, and necrosis [8]. Our case showed size >5 cm, high cellularity, mitotic activity >10/50 hpf, nuclear pleomorphism and high proliferative rate, hence classified under malignant category.Clinical symptoms are related to the size and The differential diagnosis of spindle cell tumorslocation of the GISTs. GISTs of the esophagus of gastrointestinal tract consists of leiomyoma,typically present with dysphagia. Gastric and schwannoma, and fibromatosis. Thesmall intestinal GISTs often present with vague immunohistochemical marker, c-Kit (CD117)symptoms, but sometimes they cause upper identifies tumors originating from thegastrointestinal bleeding. Colorectal GISTs may pacemaker cells of Cajal, seems to be the mostmanifest with lower gastrointestinal bleeding, specific diagnostic marker, and helps incolonic perforation, pain, obstruction or differentiation from tumors.combination [2, 5]. In present case patientpresented with abdominal pain and mass. The Five percent of the tumors with morphological features of GIST were negative for CD117, whichInternational Archives of Integrated Medicine, Vol. 2, Issue 3, March, 2015. Page 190Copy right © 2015, IAIM, All Rights Reserved.

Malignant gastrointestinal stromal tumors (GISTs) of the duodenum ISSN: 2394-0026 (P) ISSN: 2394-0034 (O)is attributed to the presence of activating intestine GISTs, they have to be evaluatedmutation of platelet-derived growth factor carefully. Definite criteria are followed forreceptor alpha (PDGFRA) and they are identified diagnosing malignancy, which include tumorby the immunostaining with PDGFR marker. size, cellularity, mitotic count, necrosis,Recently, a new marker was discovered on GIST pleomorphism and proliferative index.(DOG-1) expressed independently of c-KIT or Treatment includes surgical excision andPDGFRA status and can therefore be useful for targeted therapy with Imatinib mesylate. Patientthe identification of CD117-negative tumors [1]. with malignant GIST have high recurrence hence, followed regularly.GIST mostly metastasizes within the abdomen,and the most common sites for the Referencesdevelopment of metastasis are the liver andperitoneum however, rare metastasis to central 1. Qi Y, Zhao W, Wang Z, Li T, Meng X.nervous system [9] has also reported. Lymph Tumor sites and microscopic indicatorsnodal metastasis is rare hence, nodal resection are independent prognosis predictors ofduring surgery is not mandatory. gastrointestinal stromal tumors. Tohoku J Exp Med., 2014; 233(1): 65-72.The treatment of choice for malignant GISTs 2. Varras M, Vlachakos N, Akrivis C,should be surgical resection, along with imatinib Vasilakaki T, Skafida E. Malignantmesylate therapy [8, 9]. Recently, however, gastrointestinal stromal tumorimatinib mesylate has been introduced as a presenting with hemoperitoneum inmolecular-targeted chemotherapeutic agent. puerperium: Report of a case withImatinib mesylate is the first effective systemic review of the literature. World J Surgtherapy for locally unresectable or metastatic Oncol., 2010; 8: 95.GIST. Following resistance to imatinib mesylate,sunitinib, a multi targeted small-molecule 3. Agaimy A. Gastrointestinal stromaltyrosine kinase inhibitor that selectively blocks tumors (GIST) from risk stratificationvascular endothelial growth factor receptors systems to the new TNM proposal:(VEGFRs) with potent activity against KIT and More questions than answers? A reviewPDGFA, has proven effective as a second-line emphasizing the need for a standardizedtherapy [4, 9]. GIST reporting. Int J Clin Exp Pathol., 2010; 3(5): 461-71. 4. Bayraktar UD, Bayraktar S, Rocha-LimaRecurrences are extremely rare for low CM. Molecular basis and managementmalignant potential GISTs, while >80% of high of gastrointestinal stromal tumors.malignant potential GISTs will recur and hence World J Gastroenterol., 2010; 16(22):close follow-up by imaging techniques is 2726-34.required [8]. 5. Lakshmi VA, Chacko RT, Kurian S. Gastrointestinal stromal tumors: A 7-Conclusion year experience from a tertiary care hospital. Indian J Pathol Microbiol.,GISTs are the most common mesenchymal 2010; 53(4): 628-33.tumors of gastrointestinal tract. They arise 6. Hou YY, Lu SH, Zhou Y, Qi WD, Shi Y, Tanmostly in the stomach followed by the small YS, et al. Stage and histological grade ofintestine. As malignancy is common with small gastrointestinal stromal tumors basedInternational Archives of Integrated Medicine, Vol. 2, Issue 3, March, 2015. Page 191Copy right © 2015, IAIM, All Rights Reserved.

Malignant gastrointestinal stromal tumors (GISTs) of the duodenum ISSN: 2394-0026 (P)on a new approach are strongly ISSN: 2394-0034 (O) 9. Sato K, Tanaka T, Kato N, Ishii T, Terao T,associated with clinical behaviors. Mod Murayama Y. Metastatic cerebellarPathol., 2009; 22(4): 556-69. gastrointestinal stromal tumor with7. Wang X, Mori I, Tang W, Utsunomiya H, obstructive hydrocephalus arising fromNakamura M, Nakamura Y, et al. Helpful the small intestine: A case report andparameter for malignant potential of review of the literature. Case Rep Oncolgastrointestinal stromal tumors (GIST). Med., 2014; 2014: 343178.Jpn J Clin Oncol., 2002; 32(9): 347-51.8. Shukla S, Singh SK, Pujani M.Multicentric malignant gastrointestinalstromal tumor. Saudi J Gastroenterol.,2009; 15(1): 45-8.Source of support: Nil Conflict of interest: None declared.International Archives of Integrated Medicine, Vol. 2, Issue 3, March, 2015. Page 192Copy right © 2015, IAIM, All Rights Reserved.