Succinate dehydrogenase–deficient gastrointestinal stromal tumor of the stomach: EUS and contrast-enhanced EUS features (with videos)

A 22-year-old lady with unremarkable history was admitted to our department due to severe microcytic anemia (hemoglobin on admission 2.8 g/dL). Following hemotrasfusion, esophagogastroduodenoscopy revealed a widely ulcerated submucosal bulge in the lesser curvature of the gastric body [Figure 1]. Subsequent computed tomography showed a large pseudocapsulated round mass likely originating from the gastric body, with a mixed cystic-solid component and heterogenous contrast-enhancement. No distant metastases were detected [Figure 2]. Thus, EUS revealed a 11-cm heterogeneous hypoechoic subepithelial lesion (SEL) with well-defined borders, arising from the muscularis propria of the gastric body, with prevalent extraluminal growth, intratumoral cystic spaces and echogenic foci [Figure 3]. Following intravenous administration of ultrasonographic contrast agent (Sonovue, Bracco), the lesion showed inhomogeneous hyperenhancement [Video 1]. EUS-guided fine needle biopsy using a 22-gauge needle (SharkCore, Medtronic) revealed a mixed epithelioid and spindle cell morphology, with positive immunostaining for CD117 (KIT) and DOG1, and negative for CK8/18, synaptophysin, CD99, desmin, and succinate dehydrogenase (SDH) complex subunit B [Figure 4]. Mitotic rate could not be assessed. Mutational analysis showed no mutation in KIT/PDGFRA. These findings were consistent with “wild-type” SDH-deficient gastrointestinal stromal tumor (GIST).Figure 1: Urgent esophagogastroduodenoscopy. (A–C) Endoscopic view showing a widely ulcerated submucosal bulge in the lesser curvature of the gastric body, compressing on the gastric lumen (A–B), in the absence of active bleeding.Figure 2: Contrast-enhanced computed tomography. (A–B) Axial (A) and coronal (B) computed tomography venous phase showing a large roundish lesion in the left hypochondrium (asterisk), likely originating from the lesser curvature of the gastric body, with inhomogeneous hyperdense internal components and partial enhancement, dislocating the pancreatic body and tail and the left kidney, and contiguous with the left liver lobe. (C) Coronal subtraction perfusion computed tomography better demonstrating the perfusion of the lesion (asterisk) and the predominant peripherical disposition of the enhanced solid components within the lesion.Figure 3: EUS. Linear EUS showing a 11-cm heterogeneous hypoechoic subepithelial lesion (SEL) with well-defined borders (A), originating from the muscularis propria of the gastric body (B; arrow), with intralesional small echogenic foci (C; arrow) and anechoic areas (D; arrow). {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_sfp0s3iz"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} Figure 4: Cytohistology of EUS-guided fine needle biopsy sample. (A) Hematoxylin-eosin stain (×100) showing monotonous epithelioid and spindle cells. (B) Immunohistochemical stain for DOG1 strongly positive.Following multidisciplinary evaluation, the patient underwent robot-assisted wedge gastrectomy [Video 2]. Final pathology showed complete resection of SDH-deficient GIST with a mitotic index <5/50 high-power fields [Figure 5]. Next-generation sequencing analysis revealed a pathogenic 223C > T heterozygous germline mutation of the SDH subunit A gene. No adjuvant treatment was conducted [1], and no disease recurrence was observed up to 36 months of follow-up. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_nd0w8ava"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} Figure 5: Histology of surgical specimen. (A) Hematoxylin-eosin stain (×40) showing nests of neoplastic cells within the muscularis propria of the gastric wall. (B) Immunohistochemical stain for CD117 (c-KIT) strongly positive. (C) Immunohistochemical stain for Ki-67 (MIB-1) showing a proliferation index Ki67 <10%.SDH-deficient GISTs are a rare subset of GIST with a commonly indolent behavior and unique clinicopathological features as compared with oncogene-driven GIST.[2,3] Existing risk classifications based on mitotic activity and tumor size are generally not reliable in this subsetting, and dedicated criteria need to be developed.[2–4] Our case clearly depict the EUS and the contrast-enhanced EUS appearance of a gastric SDH-deficient GIST. Notably, despite the presence of several high-risk EUS features, such as cystic spaces, ulceration, echogenic foci, and heterogeneity, final pathology showed a low mitotic rate.[5] Similarly to risk classifications, the high-risk EUS features used for oncogene-driven GIST may be not reliable in SDH-deficient GIST. However, further studies are needed.