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 Table of Contents  
ORIGINAL RESEARCH REPORT
Year : 2021  |  Volume : 18  |  Issue : 2  |  Page : 98-102

Gastrointestinal stromal tumor experience in a surgical oncological unit in sub-Saharan Africa: A retrospective analysis


1 Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria
2 Department of Histopathology, College of Medicine, University of Ibadan, Ibadan, Nigeria
3 Department of Surgery, University College Hospital, Ibadan, Nigeria
4 Department of Histopathology, University College Hospital, Ibadan, Nigeria
5 Department of Radiation Oncology, College of Medicine, Ibadan, Nigeria

Date of Submission10-Jul-2020
Date of Acceptance09-Sep-2020
Date of Web Publication24-Apr-2021

Correspondence Address:
Dr. Akintunde T Orunmuyi
Department of Radiation Oncology, College of Medicine, University of Ibadan/University College Hospital, Ibadan
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcls.jcls_60_20

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  Abstract 


Background: Gastrointestinal stromal tumors (GISTs) are characterized by specific immunohistochemical and genetic features. This study investigated the clinicopathologic features and surgical outcomes of 54 patients with GIST in a major referral hospital in sub-Sahara Africa. Methods: This retrospective cross-sectional single-center study describes 54 patients who underwent surgery for GIST between 1999 and 2019 in a Nigerian Tertiary Hospital. All cases were confirmed by immunohistochemistry and were analyzed for clinical characteristics, clinical management, and histopathologic data. The risk of recurrence was determined using the Fletcher National Institutes of Health criteria. Results: The mean age of the patients was 57.6 years ± 15.3 (11–81 years), and most patients (67%) underwent abdominal computed tomography scans preoperatively. The most common presentation was an abdominal mass (48%). The stomach was the most common site of GIST (37%). The mean tumor size was 8.9 cm (5–18 cm), and tumor morphology showed spindle cell type (75.9%), mixed spindled-epithelioid (20.3%), and epithelioid (3.7%) cell types. Overall, 51% had a high risk for recurrence. Conclusion: The clinicopathologic features of GIST in this study are consistent with reports in the literature. Slight variations in risk profile may be due to late presentation in our settings.

Keywords: Africa, gastrointestinal stromal tumor, immunohistochemistry, risk, surgery


How to cite this article:
Ayandipo OO, Ogun GO, Ajagbe OA, Adegoke OO, Adepoju OJ, Rahman A, Ajuyah CM, Orunmuyi AT, Shittu OB. Gastrointestinal stromal tumor experience in a surgical oncological unit in sub-Saharan Africa: A retrospective analysis. J Clin Sci 2021;18:98-102

How to cite this URL:
Ayandipo OO, Ogun GO, Ajagbe OA, Adegoke OO, Adepoju OJ, Rahman A, Ajuyah CM, Orunmuyi AT, Shittu OB. Gastrointestinal stromal tumor experience in a surgical oncological unit in sub-Saharan Africa: A retrospective analysis. J Clin Sci [serial online] 2021 [cited 2021 May 16];18:98-102. Available from: https://www.jcsjournal.org/text.asp?2021/18/2/98/314452




  Introduction Top


Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors that occur at any site of the gastrointestinal (GI) tract.[1] They may occur without a direct connection to the GI tract and are appropriately termed extra-gastrointestinal GIST (E-GIST),[2] but are objectively identified by immunohistochemistry (IHC). GIST and the description of its epidemiology in sub-Sahara Africa are scanty. This retrospective study evaluates the clinicopathologic characteristics of GIST at a major surgical oncology unit in Ibadan, South-Western Nigeria.

Background

GISTs can develop at any age but are mostly found in people over the age of 50 years and predominantly in the sixth decade.[3] Population-based epidemiological reports show an equal gender distribution among patients with GIST.[4],[5],[6],[7],[8],[9],[10],[11] However, the incidence of GISTs shows a wide variation across geographical regions.[5],[7],[8],[11] The most common sites where GISTs occur are the stomach and small intestine.[10] While small-sized GISTs tend to be asymptomatic and discovered incidentally, 80% of GISTs are symptomatic, presenting with gastrointestinal bleeding, abdominal pain, or abdominal masses.[12]

The gain of function mutations, which appear to occur in several oncogenes but mainly in the tyrosine-protein kinase (c-KIT) receptors and platelet-derived growth factor receptor alpha (PDGFRA), objectively identify GISTs. In addition to sporadic mutations expressed in GIST, familial GIST may also occur as an additional component of specific syndromes, including neurofibromatosis type 1 (NF1) and Carney dyad.[12] The presence of multiple GIST at the time of diagnosis may depict familial GIST, which are inherited germline mutation of the c-KIT or PDGFRA genes.[13] However, some GISTs do not express c-KIT ab-initio (wild type GIST), while others may become refractory to first-line selective c-KIT inhibitors following secondary c-KIT mutations. Thus, other immunohistochemical evaluations for GIST include succinate dehydrogenase (SDH) complex deficiency, smooth muscle actin, S-100, and vimentin.[14],[15]

Management of gastrointestinal stromal tumor

Curative surgical resection is the mainstay of treatment, and up to 60% of patients are cured with surgery alone. However, the tyrosine kinase inhibitors (TKIs) are of great significance in the management of GISTs. Presurgical biopsy, preferably endoscopic, enhances the surgical resection of large GISTs and identification of patients who are more likely to develop recurrence.[1],[6],[16] Clinical prognostic and predictive factors are commonly used to estimate the risk of recurrence and predict the potential benefit of TKI therapy. The tumor size, anatomical location, and mitotic count are the main prognostic factors for GIST.[17] Contrast-enhanced computed tomography (CT) imaging is the standard for evaluation of tumor size, location, and metastases and is of immense value for guiding biopsy. TKI therapy is recommended for patients with high risk, metastatic or unresectable GIST and is associated with improved prognosis and treatment outcomes. However, the development of secondary mutations while on TKI therapy is not uncommon.[3],[6] Consequently, positron emission tomography (PET) imaging plays a valuable role in early evaluation and confirmation of treatment response to TKI and encourages curative surgery for excision of non-responsive metastatic GIST.[18]


  Methods Top


This study was conducted in compliance with the guidelines of the Helsinki declaration on biomedical research on human subjects.[19],[20] The medical records of all cases of GIST confirmed by IHC using CD 117 or DOG 1, between 1999 and 2019, were identified from the database of the Departments of Pathology and Surgery of a tertiary center in Southwest Nigeria. Anatomical origin, histologic cell type, and IHC were collated from the final pathology report, while a description of the tumor size, subcutaneous fat layer, and tumor appearance was collated from surgery notes. Demographic data and clinical presentation were collated from the case files. All cases managed had their records archived, retrieved, and analyzed. A high mitotic rate was taken as >5/50 and <5/50 high power field (HPF) as low. The risk of recurrence was determined using the Fletcher classification based on tumor size and mitotic count in 50 HPFs. Briefly: Very low risk if tumor size <2 cm and mitotic count <5/50 HPF; low risk if tumor size between 2 and 5 cm and <5/50 HPF; intermediate risk if size <5 cm and 6–10/50 HPF or size 5–10 cm and <5/50 HPF; and high risk for >5 cm and >5/50 HPF or any size >10 cm or mitotic count >10.[21] Descriptive statistics estimated the means and standard deviations for continuous variables, while percentages were computed for categorical variables.


  Results Top


Overall, 54 cases of histologically confirmed GIST presented during the study period and were analyzed.

Demographic data

There were 26 (48%) men and 28 (52%) women demonstrating a male-to-female gender ratio of 1:1.07. The mean age was 57.6 ± 15.3 years (range 11–81 years), and nearly two-thirds were aged >50 years [Table 1].
Table 1: Clinco-epidemiological characteristics: age, gender, clinical presentation

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Clinical data

The most common presentation was an abdominal mass (26 cases, 48%), followed by abdominal pain (15 cases, 27.7%) and gastrointestinal bleeding (7 cases, 12.9%). In 6 (11.1%) patients, GIST was an incidental finding. Overall, 36 (67%) patients underwent CT scans prior to surgery. Tumor appearance was a classical fleshy exophytic mass in all cases and there was no loss of the submucosa layer reported. The stomach was the most common site of GIST (20 cases, 37%) followed by the omentum, while the esophagus was the least common site [Table 2]. Although tumor sizes ranged from 5 cm to 18 cm with a mean size of 8.9 cm, most of the tumors (62.9%) were between 5 and 10 cm. Microscopic examination revealed complete tumor resection (R0) in 28 (51.8%) patients, microscopically positive margins (R1) in 13 (24.0%) patients and macroscopically positive margins in (R2) 10 (18.5%) patients [Table 3]. Three patients (5.5%) had unresectable masses which were biopsied for pathologic and immunohistochemical analysis.
Table 2: Surgical characteristics: gross appearance, anatomical location

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Table 3: Pathologic characteristics: resection margins, morphology, mitotic activity, mutational analysis

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Pathologic data

The spindle cell tumor was the most common histologic type (75.9%), followed by mixed spindled and epithelioid type in 11 cases (20.3%) and epithelioid type in 2 cases (3.7%). Overall, mitotic counts ranged from 1 to 60 per HPF, with 32 (59%) patients showing high mitoses and low mitoses in the remainder. Risk stratification by National Institutes of HealthNIH-Fletcher's criteria placed 28 (51.8%) patients and 1 patient (1.8%) into high- and low-risk categories, respectively. The remainder were the intermediate-risk category. IHC findings using CD117 and DOG1 was positive in 34 and 20 patients, respectively [Table 3].


  Discussion Top


This study of 54 patients with GIST managed over a 20 years period is the largest in this part of the world. Following a systematic review by Ogun et al.,[22] this study represents the largest single-center study from Africa. The demography of GIST patients in this study is consistent with other reports that indicate a male-to-female gender ratio close to 1:1. Søreide et al. reported a fairly consistent equal distribution between males and females.[10] The mean age of 57.6 ± 15.3 years in our cohort compares fairly with larger study populations by Lv et al. in which the mean was 60 ± 12.9 years[8] and 61.18 ± 14.13 years by Ud Din et al.[23] The age range is also consistent with the reported range of 10–100 years from a systematic review by Søreide et al.[10] However, in patients younger than 50 years, GIST is significantly associated with a favorable outcome.[9] Our study shows the stomach as the most common site, as reported fairly consistently reported between studies.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] The lower occurrence of esophageal and colorectal GISTs in this study varies with other studies. This is likely due to the rare occurrence and possibly underreported incidence of GISTs generally.[10] Overall, the colorectal, esophagus, and extra-gastrointestinal sites including, the mesentery and spleen, were few and in keeping with other studies that reported <10% of those with GIST in these locations.[24],[25],[26]

The average size of tumors in this study was 8.9 cm and size ranged from 5 cm to 18 cm. Various studies have reported sizes ranging from a few millimeters to >20 cm for small intestinal, and a few millimeters to >40 cm for gastric GISTs.[23] In a large review of gastric GISTs, the mean size for gastric GISTs was 6 cm.[27] In two separate studies, from Iceland and China, the mean tumor size was 4.6 cm and 7.02 cm, respectively.[5],[23] Consequently, the majority (51%) of our patients were classified as high-risk for recurrence. The larger size of tumors in our study may be contribute to the high mitosis rates observed in majority (59%) of our patients. Late presentation among patients in low-income settings and the hospital-based nature of this study may explain the variation with studies reported in the literature, which are mostly population-based studies from the West. Risk classification may contribute toward identification of patients who will require targeted therapy postoperatively.[16] Patients at high risk of recurrence were referred to a regional center for free drug assistance in a program that is still ongoing.[22] The retrospective nature of this study precludes further analysis of recurrence rates in this cohort.

Symptoms in our cases were variable; the most common were vague abdominal pain, abdominal mass, bleeding per rectum, hematemesis, etc., Grossly, majority of our gastric tumors were exophytic submucosal or intramural, pedunculated masses, nodular bulging masses. Some protruded into the gastric lumen. Similarly, gross appearances have been described by various authors.[28]

On histological examination, almost 80% of our cases showed spindle cell morphology, while cases with epithelioid morphology comprised barely 5%, although various international studies have reported the epithelioid type to comprise between 20% and 25%, with mixed tumors comprising the remaining 5%–10% cases.[23],[29]

Immunohistochemically, CD117 was strongly positive in over 60%. DOG1 showed diffuse strong positivity in over 30%. Although DOG1 is found to be more sensitive and specific as a GIST marker,[23] it would be put to more use in our future publications. Most studies record as high as 90% and 80% positivity for CD117 and DOG1, respectively,[21] the fact that immunochemical analysis was done in retrospect on archival samples collected in the early part of the study period would explain the low values as protein/receptor degradation is inevitable over time. Moreover, DOG1 analysis came into existence only in the past 7 years.[23]

Although different imaging techniques, such as 18 fluorodeoxyglucose (FDG) PET, magnetic resonance imaging, and ultrasonography (US), show utility for diagnostic imaging of GIST, CT is currently the modality of choice.[7] Whereas FDG PET is highly sensitive in the detection of GISTs, its access is limited worldwide.[30] Thus, none of our patients had it. Although access to CT in low resource settings is relative, preoperative diagnosis was complimented with abdominal CT in most of our patients. Before routine availability of CT in our center, the absence of cancer cachexia in a patient presenting with an abdominal mass has been a useful “clinical marker” to suspect GIST, as reported by Ekeblad et al.[31] However, the definitive diagnosis of GIST relies on appropriate sample preservation after surgery for gene analysis and IHC. Therefore, understanding the clinical course and pathology of GIST including the subtle differences that distinguish it from carcinomas is vital in our low resource centres. The well-known symptomatology and clinical profiling at disease presentation should prompt a high index of suspicion.[32] This is important for anticipating the added logistics of fresh frozen sections for intraoperative assessment of negative tumor margins.

While surgical resection remains the mainstay of treatment, meticulous dissection is employed to prevent intraoperative rupture of the tumors and avoid injuries to contiguous structures.[33] Complete resection was possible in 30 (55.3%) of our patients according to the intention to treat principle. This is consistent with the reported spectrum of 48%–89%.[18] Achieving microscopically negative resection margins (R0) however, may not deter recurrence while whole organ removal (e.g., total gastrectomy), is usually not required if a negative resection margin is guaranteed.[34] Although lymphatic metastasis is an extremely rare event in GIST,[35] a “radical” approach, including a lymphadenectomy for metastatic gist, appears to be the consensus.[34] In the rare SDH-deficient GIST, which is present in Carney-Stratakis syndrome, enlarged lymph nodes should be removed.[32]

It is important to resect the tumor with the capsule intact otherwise, seeding on the visceral or somatic peritoneum will occur, leading to recurrence.[1],[34] For GIST in the stomach, the size of the tumor, location, and its proximity to adjacent intra-abdominal viscera may influence the surgical approach undertaken and the extent of stomach resected. In nongastric GIST, en-bloc resection of adjacent organs might be necessary to obtain a clear margin, and care is required to avoid rupture, which may compromise oncological outcomes.[34] In up to 10% of abdominal GISTS, the risk of rupture during surgery is substantial due to extensive neovascularization and the friable nature of the tumor. Rupture into the abdominal cavity has catastrophic sequelae as it almost inevitably leads to peritoneal sarcomatosis.[32]


  Conclusion Top


GISTs are rare tumors. Although most of our patients had larger tumors and fall into the high-risk category, the clinical epidemiology of GIST in this study is similar to global reports. Surgery remains the mainstay of management, and a high index of suspicion preoperatively presents an opportunity to anticipate the unique diagnostic and treatment features of GIST. Slight variations in risk profile in this study may be related to late presentation in our settings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3]



 

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