Extra-gastrointestinal stromal tumour of the lesser omentum presenting as a massive intra-abdominal swelling: A case report and literature review

Abstract

Extra gastrointestinal stromal tumour(EGIST) is rare and is regarded as gastrointestinal stromal tumour(GIST) that originates outside of the gastrointestinal tract. They originate from other intraabdominal tissues such as the omentum, mesentery and peritoneum. The cell of origin is the interstitial cell of Cajal(ICC), a pacemaker cell that controls gastrointestinal peristalsis and the tumor is characterized by the expression of KIT(CD117) a transmembrane tyrosine kinase receptor. Here, a 49-year-old female who presented with a 6 month history of abdominal pain, progressive abdominal swelling and the presence of an upper abdominal mass. She had surgical resection and adjuvant imatinib for the intraabdominal mass diagnosed on histology and immunohistochemistry as EGIST of the lesser omentum. Serial CT 14 months after surgery revealed no evidence of recurrence or metastasis. Clinicians should consider EGIST in the differential diagnosis of abdominal masses.

Introduction

Extra gastrointestinal stromal tumour(EGIST) is defined as gastrointestinal stromal tumour(GIST) that originates outside of the gastrointestinal tract. ¹ They are rare and represent 5–10% of all GIST which accounted for <0.05% of all gastrointestinal tumours.^1,2 GIST, originate from other intraabdominal tissues such as the omentum and mesentry. ³ EGIST was first described in 1999 by Miettinen et al. ¹ Prior to this, GIST was believed to originate from mesenchymal cells of the gastrointestinal tract. Kindbloom and colleagues in 1998 found that these tumours originated from the interstitial cells of Cajal(ICC), a pacemaker cell that controls gastrointestinal tract peristalsis.^3,4 CD117 antigen(c-kit) was discovered by Hiroto and colleagues. A gain in function from mutation is responsible for activating the growth of these tumours through the tyrosine signal pathway.^3–5 Clinical presentation is variable and depended on the primary location and size with parameters of abdominal pain, mass being significant and included weight loss. Smaller lesions may be diagnosed incidentally at imaging or laparotomy.^2,4,5 Imaging studies of choice include CT and MRI and most tumours stain positive for CD117(c-kit), CD34 and or DOG-1.^2,6 Standard treatment of localized, resectable, non-metastatic GIST and EGIST is surgery and a combination of surgery and imatinib in high risk, recurrent and metastatic disease.^2,4,5 The clinical behavior of EGIST and GIST is variable depending on tumour size and mitotic activity as most useful in metastatic risk stratification. ³ We present this 49 year old female with a massive tumour arising from the lesser omentum and confirmed as EGIST because of its rarity and to highlight the favorable outcome following surgical resection and adjuvant imatinib in a high risk tumour.

Case report

Presented is a 49-year-old female who sought medical care in our facility with a 6 month history of abdominal pain, progressive abdominal swelling and the presence of an upper abdominal mass. Notably absent were symptoms of anorexia, nausea, vomiting, change in bowel habit. There was no history of jaundice, haematochezia or malena stool. She complained of weight loss noticed a month to presentation and had a history of two Caesarian sections. She did not admit to a history of similar disease or malignancy in the family. Examination revealed a healthy looking patient and vital signs that were essentially normal. Abdominal examination exhibited marked distension mainly in the upper abdomen with a midline sub umbilical scar. There was a palpable, non-tender mass in the upper part mainly in the epigastrium and extending to the left and right hypochondria that measured 25 cm × 20 cm in the widest dimensions.

Blood tests included, full blood count, electrolyte/urea, liver function test (remarkably serum albumin) were normal. Urinalysis was also normal. Further work up included abdominal CT reported as showing an exophytic heterogenous enhancing gastric mass with central necrosis consistent with Gastrointestinal stromal tumour, gastric lymphoma, Figure 1(a) and (b).

Figure 1.

(a) Abdominopelvic CT, sagittal section showing a heterogenous tumour.(red arrows). (b) Abdominal CT, coronal section, showing a heterogenous tumour(red arrows).

She underwent a laparotomy under general anaesthesia with endotracheal intubation following which a resection of the tumour was done. Access was hindered initially by omental reaction with fibrous adhesions plastered to the anterior abdominal wall. The adhesions were divided between haemostats transfixed with vicryl 2/0 and haemostasis secured using diathermy. The duration of surgery was 2 h; blood loss was estimated at 1 L and was transfused 2 units of blood. The tumour that arose from the lesser sac, Figure 2(a), was mobilized and resected, Figure 2(b). Intraoperative findings was an oval tumour from the lesser omentum that occupied the entirety of the lesser sac extending into the peritoneal cavity anteriorly and posteriorly to the retroperitoneum. The intraperitoneal aspect of the tumour measured about 30 cm in its widest dimension, Figure 2(a). The tumour compressed part of the stomach at the lesser curvature that was tumour free as adjudged by palpation. There was no tumour spillage. Inspection revealed no evidence of tumor deposit on the peritoneum and the intestine as adjudged by palpation. The liver appeared normal. Postoperative period was uneventful and patient discharged to the outpatient department after 10 days of admission for follow up.

Figure 2.

(a) GIST in situ(blue arrows at tumour margin). (b) Post resection showing tumour bed(blue arrows).

Two weeks postoperative visit in the outpatient, she presented with the report of histology and immunohistochemistry. The histology was reported as: macroscopy- Tumour measured 15 × 12.5 × 7 cm, external surface covered by fibrous capsule. Cystic to firm areas and prominent blood vessels. Microscopy showed mesenchymal tissue with tumour composed of bland spindle cell and epithelioid cells diffusely infiltrating a myxoid scanty stroma with herring bone and syncytial patterns. Mitotic activity was brisk. There were focal areas of lipoblastic differentiation. Extensive areas of haemorrhage and necrosis with chronic inflammatory cellular infiltration mainly lymphocytes. The deep resection margin was reported as tumor free. A definitive diagnosis of gastrointestinal stromal tumour of the lesser omentum-mixed type was made, Figure 3. Immunohistochemistry showed, SMA-non reactive, Pck-non reactive, c-kit- moderate diffuse positivity, CD34-strongly diffuse positivity, S-100- non reactive, vimentin-positive, Desmin-strong diffuse positivity. She was commenced on imatinib 400 mg daily. Follow up in the clinic by clinical evaluation and CT revealed no evidence of tumour 14 months after surgery.

Figure 3.

Mesenchymal tissue with tumor composed of bland spindle cell(blue arrow) and epithelioid cells with herring bone and syncytial patterns(red arrow)- Mixed gastrointestinal stromal tumour.

Discussion

Extra gastrointestinal stromal tumour is known to be tumor not arising from the gastrointestinal tract. This rare subtype accounts for 10% of all GIST.^1,2 The major distinction between GIST and EGIST is the site of origin of the primary tumor as GIST occurs throughout the gastrointestinal tract(from oesophagus to anus).^5,7 EGISTs originate primarily from the omentum, mesentery, peritoneum or retroperitoneum. Some isolated cases have been reported in the pleura, pancreas, mesoappendix, abdominal wall, urinary bladder, rectovesical septum, seminal vesicle, prostate and, pelvic cavity. ² Kanamori et al reported EGISTs to occur in the mesentery(7.7–15.7%), retroperitoneum(25.5–25.6%) and omentum(7.7–15.7%). ⁸ The importance of primary EGIST in the omentum is emphasized as few cases are reported in literature.^3,9 We report the first case in our facility.

The origin of omental GIST is still a matter of debate. It is believed to originate from extraintestinal mesenchymal cells derived from mesenchymal undifferentiated stem cells from the loss of extramural contact with intestinal wall capable of differentiating to ICCs. The origin however remains unclear due to its rarity. There is need for accumulation of EGISTs by collaboration and further related studies.^3,8 There is no difference in the incidence between lesser and greater omentum. ³ The median age is about 65 years with a slight prevalence in males.^2,3

The most frequent complaint is an abdominal mass; however, diagnosis is often incidental during investigation or surgery for other medical conditions. Omental EGIST can remain clinically silent despite the large size of tumor and overtime large solid masses may exhibit cystic changes.^2,3 A preoperative diagnosis may not be considered with patient undergoing a surgical exploration for a diagnosis of intraabdominal mass as was our experience. ³ This tumor can present as an emergency, Fagkrezos et al reported EGIST that presented with peritonitis. ³ It is difficult to differentiate clinically between a mass in the lesser omentum and lesser curvature of the stomach. ³

Diagnostic modalities include CT, MRI and PET. Many classification systems have been proposed overtime but none have proved to be superior. ² On imaging, the “Embedded organ” sign is useful and valid tool for the identification of organ of origin, Figure 1(a) and (b). GIST shows intense homogenous enhancement but large lesions show necrosis and appear heterogenous as depicted in the CT of our patient, Figure 1(a). However, EGISTs still have no typical radiologic features. ¹⁰ Despite the use of advanced radiological imaging, it’s difficult to differentiate GIST of the lesser omentum from GIST of the lesser curvature of the stomach. ³ About half of all omental GISTs are misdiagnosed as extramucosal tumor of the stomach as depicted in the CT report of the index patient. ³

The origin of EGIST is uncertain but as a rule, their appearance on histology, immunohistochemistry and molecular biology present same as GIST.^2,3 The most common histological pattern is spindle cell type(fusiform cells with intersecting whorls)-70%, followed by epithelioid type(round cells in a nested pattern)-20% and mixed(10%), the later was found in our index patient, Figure 3. Mitosis may be little to abundant, the later was the finding in our patient.^3,8 The tumor is characterized to have strong presence and positivity for CD117(>95%) and CD34(70%), occasional positivity for smooth muscle actin-SMA(30%), S-100(5%), Desmin(2%) and cytokeratin(2%). ² This is comparable with the result of our patient. About 80% of GIST has KIT mutation and 10% have platelet derived growth factor receptor alpha(PDGRA) mutation, ⁷ our patient had c-kit strong positivity. In omental EGIST the degree of KIT and PDGFRA is like gastric GIST. ⁷ There are molecular variants with clinical significance. Kanamori et al reported a rare patient with an omental EGIST with a PDGFRA mutation considered clinically to be a high risk for recurrence without adjuvant imatinib with favorable outcome 29 months following surgery. ⁸ Fagkrezos et al also reported a case with omental EGIST without myogenic or neurogenic differentiation. Only 16 cases have been reported to date. ³

Tumor size, mitotic count, location, rupture, metastasis are well documented prognostic factors in terms of recurrence, metastasis and consideration for adjuvant therapy. ² Tumors generally metastasize to the liver(28%), mesentery and omentum(20%), lungs(7%), subcutaneous tissue(4.7%), lymph nodes(4.7%) and bone(2.3%). Tumors greater than 10 cm with any mitotic rate are regarded as high-risk of aggressive clinical course stratification described by modified National Institute of Health(NIH) consensus criteria. ² The risk stratification of our patient was a large size of tumor greater than 10 cm(25 cm across the widest dimension at surgery) with mitosis described as brisk and being extra gastrointestinal even without rupture was high risk. ⁹ Up to 66% of patients with high risk GISTs who had resection experience recurrence. ⁵ The risk of recurrence has been associated with inadequate resection and may involve the loss of the c-Kit gene. This occurs in the first 2 years and involved the liver and peritoneal surfaces. ⁵

The preferred treatment for high risk patients is surgical resection in addition to adjuvant specific tyrosine kinase inhibitor such as imatinib, sunitinib and ponatinib as other options when resistance or partial response to imatinib is identified. Our patient had surgical resection and adjuvant treatment with imatinib 400 mg daily. Follow up with serial CT is recommended to detect recurrence and metastasis in high risk patients as was indicated in our patient. Laparoscopic surgery is indicated in GISTs less than 5 cm up to 8 cm in size with the advantages of less duration of hospitalization and wound complications. ¹¹

Clinicopathological, molecular biological features and prognosis of conventional GISTs are well described. The clinical implications of EGISTs have not been investigated and defined due to its rarity. This calls for collaborative research. Prognosis of EGIST including omental EGIST following resection is thought to be less favorable than that of GIST. ⁹ Tumor size may not be reliable prognostic parameter in omental GISTs ³ as shown by our patient. However, the average large tumor size and high mitotic count have a remarkable negative impact on the overall survival. These parameters are of poor prognostic features in line with the prognostic indicators of Miettinen et al. ¹⁰ Aschor and Barefah reported a favorable outcome after 5 months of surgery and imatinib of a large EGIST having been diagnosed as smooth muscle tumor of undetermined malignant potential(SMTUMP) 20 years ago. ¹⁰

There are no published data to indicate the optimal surveillance therapy of surgically treated tumors with localized disease. CT is recommended every 3-4 months for the first 2 years and 6-12 months for 10 years following the withdrawal of imatinib. High risk patients relapse within 1-3 years from cessation of adjuvant therapy. ¹⁰

In conclusion, presented is a rare EGIST of the lesser omentum with many clinicopathological similarities with GIST. The outcome following surgical resection and adjuvant therapy with imatinib for this high risk EGIST is favorable with the absence of tumour recurrence or metastasis 14 months after surgery. Clinicians should consider this pathology in the differential diagnosis of abdominal masses.