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CASE SERIES
Year : 2022  |  Volume : 49  |  Issue : 1  |  Page : 76-80

Clinicopathological spectrum of gastrointestinal stromal tumors: A case series


1 Department of Pathology, Thanjavur Medical College and Hospital, Thanjavur, Tamil Nadu, India
2 Department of Surgical Gastroenterology, Thanjavur Medical College and Hospital, Thanjavur, Tamil Nadu, India
3 Department of Surgical Oncology, MR Hospitals, Thanjavur, Tamil Nadu, India

Date of Submission11-Jul-2021
Date of Acceptance05-Nov-2021
Date of Web Publication22-Apr-2022

Correspondence Address:
Padmanaban Krishnan Govindaraman
Department of Pathology, Thanjavur Medical College Hospital, Thanjavur, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jss.jss_96_21

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  Abstract 


Gastrointestinal stromal tumor (GIST) is the most common primary mesenchymal neoplasm of the gastrointestinal tract, and they are potentially malignant tumors with varied biological behavior. The objective of this study was to investigate the clinicopathological characteristics and prognostic factors of GISTs in our institution. Medical records of nine cases of GISTs diagnosed during January 2018 to March 2021 were reviewed. Details of patient demographics, clinical presentation, treatment details, and gross and histopathological features were noted. GISTs were commonly seen in stomach in 50–60-year age group with slight male preponderance. Abdominal pain was the most common symptom. Other sites encountered were colon, mesentery, peritoneum, and omentum. Most of the gastric GISTs were in low-risk group. Mean size of the tumor was 9.3 cm. Spindle cell type was the most common histological pattern with diffuse hypercellularity subtype. All cases were positive for CD117 (c-kit). One case was inoperable due to dissemination in abdominal cavity, surgery was done in all other cases, and imatinib therapy was given for high-risk cases postoperatively. GIST is uncommon with diverse clinical presentation. CD117 is a very sensitive marker for making a diagnosis of GIST. Successful management of GISTs requires complete surgical resection and adjuvant imatinib therapy for intermediate- and high-risk patient.

Keywords: CD-117, gastrointestinal stromal tumors, c-kit


How to cite this article:
Govindaraman PK, Aravindan U, Michael R. Clinicopathological spectrum of gastrointestinal stromal tumors: A case series. J Sci Soc 2022;49:76-80

How to cite this URL:
Govindaraman PK, Aravindan U, Michael R. Clinicopathological spectrum of gastrointestinal stromal tumors: A case series. J Sci Soc [serial online] 2022 [cited 2022 Nov 30];49:76-80. Available from: https://www.jscisociety.com/text.asp?2022/49/1/76/343713




  Introduction Top


Gastrointestinal stromal tumor (GIST) is the most common primary mesenchymal tumor of the gastrointestinal tract, and the clinical behavior ranges from benign to malignant. Before the pathogenesis of GIST was understood, most GISTs were formerly diagnosed as leiomyoblastomas and gastrointestinal autonomic nerve tumors. GIST arises from Interstitial cells of Cajal (ICC), the pacemaker cells of gastrointestinal tract and generally characterized to be immunohistochemically positive for KIT (CD117) and contains KIT-or PDGFRA-activating mutations.[1]

The annual incidence of GIST in various studies ranges between 6.5 and 14.5 per million.[1],[2],[3] The common age group involved is 55–65 years.[1],[2] The most common location of GISTs is the stomach, which accounts for 60%, followed by jejunum and ileum (30%), duodenum 5%, and colorectum 5%, and minority of cases occur in esophagus, appendix, gallbladder, mesentery, omentum, and retroperitoneum.[1],[2],[3],[4],[5] GISTs are rare in children and almost occur exclusively in stomach.[5]

The presentation of GIST is nonspecific and varies from abdominal pain, gastric ulcer, gastrointestinal bleeding, palpable mass, and incidental finding from imaging studies.[1],[2],[3],[4] External involvement of pancreas and liver can simulate primary tumor in these organs. In general, gastric tumors have a more favorable prognosis than the intestinal ones with similar parameters.[5]

The diagnosis of GISTs is based on morphology, positive immunohistochemistry (IHC) results for CD117 and DOG1, and mutation analyses of KIT and platelet-derived growth factor receptor α polypeptide gene (PDGFRA). Large tumor size, high mitotic rate, nongastric tumor location, and tumor ulceration are commonly accepted to be associated with a poor prognosis in patients with GIST.[3]

The number of studies on the clinicopathological characteristics of GIST in India is limited. The aim of the present study is to update the clinicopathological and immunophenotypic characteristics of GISTs in Indian population and to investigate the prognostic factors of GISTs based on these profiles.


  Results Top


During the study period from January 2018 to March 2021, we encountered nine cases of GISTs. The medical records of these cases were reviewed, and details of the cases such as age, gender, clinical and radiological findings, operative details, histopathology, and IHC reports were collected. Risk stratification was done based on the prognostic factors-size, mitotic index, and site of the tumor.[6],[7]

Of the nine patients in our study, five were male, the mean age at presentation was 65 years, and the most common age group involved was 50–60 years. Abdominal pain was the most common symptom. Stomach was the most common site involved. For gastric GISTs, wedge/sleeve resection [Figure 1] was done in all the cases. Surgical resection was done in all cases except disseminated mesenteric GIST in a 72 year female, as it was inoperable, and the entire abdominal cavity was studded with multiple nodules [Figure 2]. Clinically, it was mimicking ovarian malignancy with dissemination in peritoneal cavity. One case was found in omentum adherent to splenic capsule, it was a recurrent mass, high-risk category, and a multivisceral resection of the mass with splenectomy and omentectomy was done. Two cases of gastric GISTs had associated gall stone disease.
Figure 1: Cut surface of gastric gastrointestinal stromal tumor with sleeve of normal gastric mucosa

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Figure 2: Disseminated mesenteric gastrointestinal stromal tumor with multiple nodules involving the entire mesentery and peritoneum

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The size of tumor ranged from 3 cm to 18 cm, average size being 9.3 cm. The clinicopathological characteristics of the GISTs encountered in our study are summarized in [Table 1]. Risk stratification of aggressive behavior of tumor was done based on the tumor size, mitosis, and tumor site as proposed by Miettinen and Lasota[6],[7] into none, very low, low, intermediate, and high-risk categories [Table 2].
Table 1: Clinicopathological features of gastrointestinal stromal tumor

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Table 2: Risk stratification of aggressive behaviour of Gastrointestinal stromal tumor

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  Discussion Top


GISTs are the most common mesenchymal tumor in gastrointestinal tract, it has been in spotlight since the “KIT revolution” provided a firm framework for its diagnosis and treatment. In this study, we have tried to study the diverse clinicopathological presentations of GISTs.

In the past, most GISTs were thought to be smooth muscle or neural origin due to their morphological resemblance to these lesions. In 1998, discovery of activating mutations in the receptor tyrosine kinase c-kit gene and over expression of its product CD117 in these tumors, now they are believed to arise from ICC, the “pacemaker cells” of GI tract, which they resemble at morphologic, ultrastructural, and IHC level (CD117+, DOG1+).[2]

GIST commonly present in 55–65-year age group and stomach being the most common site.[1],[2],[3] The common age group involved in our study was 50–60 years, and stomach was the most common site. GISTs are often incidentally detected during evaluation for other conditions. We encountered two cases with symptomatic cholelithiasis both had gastric GIST on evaluation. Symptomatic gastric and small bowel GISTs usually present with nonspecific complaints such as early satiety and bloating. Occasionally, they can ulcerate and bleed or grow large enough to cause pain or obstruction. Symptomatic colorectal GISTs may present with lower GI bleeding, perforation, pain, or obstruction.[6] The common symptoms noted were abdominal pain and mass in our study.

The most common location of metastatic GIST is in the liver and peritoneum. Lung metastases are rare, although this is the most common site of metastatic disease for other soft-tissue mesenchymal tumors.[6] One case had disseminated multiple nodules in peritoneum, mesentery, and omentum clinically mistaken for disseminated ovarian malignancy, which was inoperable and hence biopsy of nodules was done and later proved to be CD117-positive GIST.

GISTs contain a spectrum from minute indolent tumors to sarcomas at all sites of occurrence. Their gross patterns are diverse including nodular, cystic, and diverticular tumors.[5] We saw prominent cystic component in a case of gastric GIST which was filled with serous fluid. All other cases were nodular.

GISTs range in size of diameter between a few millimetres and >30 cm,[8],[9] we had tumors varying in sizes from 3 to18 cm. When the size of the mass measures >10 cm, the GIST is referred to as giant GIST.[8],[9] Both colonic GISTs in our study were giant GISTs.

Histologically, GIST is composed of the following: spindle cells (70%), epithelioid cells (20%), mixed spindle and epithelioid cells (10%),[1],[2],[4] and rarely pleomorphic morphology.[2] Spindle cell type [Figure 3] was the most common histological type encountered in our study as reported in literature. Epithelioid feature was seen in disseminated mesenteric GIST [Figure 4]. Spindled GISTs can be divided into histologic subtype: sclerosing, palisaded-vacuolated, diffuse hypercellularity, and sarcomatoid features with significant nuclear atypia and mitotic activity. Histologic subtype of epithelioid GISTs consists of sclerosing, discohesive, diffuse hypercellularity, pseudopapillary pattern, and sarcomatous morphology with significant atypia and mitotic activity.[1],[2],[10] Diffuse hypercellularity pattern [Figure 3] was common in our study (67%), which correlates with literature,[1] two cases had nuclear palisaded-vacuolated morphology [Figure 5] and omental GIST had sarcomatoid features. Few cases had mixed patterns. Coagulative necrosis was seen in 44% of the cases which correlates with literature.[1] Intestinal GISTs are a histologically more homogeneous group and often contain distinctive extracellular collagen globules and skeinoid fibers.[5] It was found that most of the gastric tumors were in lower risk group, nongastric tumors were in high-risk group and they correlated well with tumor size and mitotic count as reported in literature.[6],[7]
Figure 3: Photomicrograph showing interlacing fascicles of spindle cells - ×100, H and E

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Figure 4: Photomicrograph showing nuclear palisding pattern - ×100, H and E

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Figure 5: Photomicrograph showing epithelioid areas in gastrointestinal stromal tumor - ×100, H and E

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Around 95% of GISTs are immunoreactive for CD117. Staining is diffuse, strong, and often cytoplasmic. Membrane staining is more often seen in epithelioid GISTs. DOG1 (discovered on GIST 1) is a highly sensitive marker staining in 95% of these tumors, and it is more specific than CD117. PDGFRA has been reported to be sensitive and specific for CD117 negative tumors in some studies.[2] In our study, we saw strong diffuse cytoplasmic immunoreactivity for CD117 in all the cases [Figure 6].
Figure 6: Photomicrograph showing diffuse strong immunoreactivity for CD117 - ×100 immunohistochemistry

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For resectable localized GIST, surgery is the treatment of choice and it has been found in many studies that minimally invasive surgeries had similar or even superior perioperative outcomes without compromising the oncological outcomes.[3],[9] Imatinib mesylate is a tyrosine kinase inhibitor used in the treatment of GIST, serves an important role in the treatment of advanced cases and as adjuvant to reduce risk of recurrence and metastasis.[2],[3] Sunitinib may be used in patients intolerant or resistant to imatinib.[2],[4] All cases were offered surgery in our study, and imatinib was used postoperatively in all high-risk cases.


  Conclusion Top


Our study validates that GIST is commonly seen in stomach with spindle cell histology. Nongastric GISTs tend to be in high-risk category than gastric GIST. With newer diagnostic techniques both imaging and molecular markers-CD117/DOG1, we are able to diagnose GIST at earlier stage not infrequently. Successful management of GISTs is complete surgical resection and adjuvant imatinib therapy for intermediate- and high-risk patients. Larger studies with follow-up are needed to validate the outcome of these cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jumniensuk C, Charoenpitakchai M. Gastrointestinal stromal tumor: Clinicopathological characteristics and pathologic prognostic analysis. World J Surg Oncol 2018;16:231-9.  Back to cited text no. 1
    
2.
Klaus J Lewin, Wilfred M Weinstein and Robert H Riddell, editors. Gastrointestinal Pathology and its Clinical Implications. 2nd ed., Vol. 1. Philadelphia: Wolters Kluwer; 2014. p. 290-377.  Back to cited text no. 2
    
3.
Yang ML, Wang JC, Zou WB, Yao DK. Clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumors in Chinese patients. Oncol Lett 2018;16:4905-14.  Back to cited text no. 3
    
4.
Sreeramulu PN, Dave P, Vikranth SN, Karthik Hareen TV, Suma S. Gastrointestinal stromal tumors –A case series – Our experience over four years in a tertiary care medical college hospital. J Med Sci Clin Res 2017;5:25420-4.  Back to cited text no. 4
    
5.
Miettinen M, Lasota J. Gastrointestinal stromal tumors: Pathology and prognosis at different sites. Semin Diagn Pathol 2006;23:70-83.  Back to cited text no. 5
    
6.
Gerrish ST, Smith JW. Gastrointestinal stromal tumors – Diagnosis and management: A brief review Stephen. Oschner J 2008;8:197-204.  Back to cited text no. 6
    
7.
Miettinen M, Lasota J. Gastrointestinal stromal tumors: Review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med 2006;130:1466-78.  Back to cited text no. 7
    
8.
Wang Y, Peng J, Huang J. Giant and high-risk gastrointestinal stromal tumor in the abdomino-pelvic cavity: A case report. Oncol Lett 2016;11:2035-8.  Back to cited text no. 8
    
9.
Altinton Y, Bayrak M. Gastrointestinal stromal tumor: Diagnosis and management. Int J Surg Res Pract 2019;6:093:1-6.  Back to cited text no. 9
    
10.
Miettinen MM, Lasota J, Corless CL, Rubin BP, Debiec-Rychter M, Sciot R, et al. Gastrointestinal stromal tumors. In: Fletcher DM, Bridge JA, Hogendoorn PC, Mertens F, editors. WHO Classification of Tumors of Soft Tissue and Bone. 4th ed., Vol. 2013. Lyon: IARC; 2013. p. 164-7.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2]



 

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