Subepithelial tumors in the upper gastrointestinal tract Staff lecture Subepithelial tumors in the upper gastrointestinal tract Jung-Wook Kim

M/66, 건강검진 Next step? Biopsy EUS or CT Resection Observation & regular follow up

F/74, Abdominal discomfort 다음 검사는? 치료는?

Overview Definition Epidemiology Clinical features Diagnosis Natural history Management

Definition SMT SET

Definition SMT SET Subepithelial tumor (SET) Mass lesion appearing as mass, bulge, or impression covered with normal appearing overlying mucosa Included both those of intramural or extramural origin Mass can arise from outside the wall or from layers other than the submucosa. → The term subepithelial is favored than submucosal SMT SET

Epidemiology Prevalence in upper GI endoscopy: 0.36% - 8-year data, retrospective study - 54 out of 15104 endoscopy Equal frequency in both sexes Generally after the fifth decade Surg Endosc 1991;5:20-23

Clinical Features Majority of SET Large SET Firm SET Asymptomatic Discovered incidentally during endoscopy Large SET May outgrow their blood supply → ulcerate the mucosa → present with upper GI bleeding Firm SET Can cause obstructive Sx: GE junction or pylorus Jaundice and pancreatitis: papilla Surg Endosc 1991;5:20-23 J Gastroenterol Hepatol 2008;23:556-566

M/64, Alcoholic LC, melena

F/49, Vomiting

Cross sectional imaging Diagnostic Tools Endoscopy EUS Histologic Diagnosis Cytology Histology Immunohistochemistry Surgical specimen Cross sectional imaging Ultrasound

Endoscopy Size estimation Intramural vs Extramural Type of SET Open biopsy forceps Intramural vs Extramural Suboptimal in identifying the origin Overall accuracy of 89% (sensitivity 98%, specificity 68%) Type of SET Lipoma (yellowish, pillow or cushion sign) Ectopic pancreas (antrum, umbilication) Mucosal biopsies To confirm that the mucosa is histologically normal Carcinoid tumor

Endoscopy Color Size Consistency

Ectopic pancreas

Pillow sign (+)

Endoscopy (size) Gastrointest Endosc 2005;62:202-8

EUS Most accurate method for characterizing SET Reliably distinguish intra- vs extramural Large lesions which extend beyond the penetration depth of the ultrasound cannot be accurately measured. High accurate in predicting the size (compared to the surgical pathology)

EUS Layer of origin Size Echotexture Border Internal structure 1 Layer of origin 2 Size 3 Echotexture 4 Border 5 Internal structure 6 Vascularization 7 Lymphadenopathy

Normal five-layered wall structure 1st mucosa 2st muscularis mucosa 3rd submucosa (SM) 4th muscularis propria (MP) 5th Serosa

① ② ③ ④ ⑤ Granular cell tumor carcinoid Varix, cyst leiomyoma GIST Lymphangioma Ectopic pancreas lipoma ③ Varix, cyst GIST leiomyoma ④ ⑤

EUS (Layer of origin) 4. Muscularis propria 2. Muscularis mucosa 3. Submucosa

EUS (intra- vs extramural)

Extrinsic compression (esophagus) Normal organ and structure Upper/lower esophageal sphincter Vascualr structure; aortic arch, heart Left main bronchus Vertebra Pathologic lesion Aneurysm Vascular abnormalities Left atrial dilatation Mediastinal LAP/tumor Lung cancer Lymphoma

Extrinsic compression (stomach) Normal structure; Spleen (m/c): gastric fundus or upper corpus Vascular structures in splenic hilum Left lobe of the liver GB: antrum The images of temporary compression: intestinal loops Tail of pancreas Abnormal structure Pancreatic pseudocyst Aortic aneurysms Left atrial dilatation

F/55, SET? Hepatic hemangioma

EUS (Echotexture) Generally Suggestive of malignancy in GIST Hypoechoic: Leiomyoma / GIST Anechoic: cystic lesions Hyperechoic: lipomas Suggestive of malignancy in GIST Size > 3cm Cystic space Echogenic foci Adjacent malignant-appearing lymph nodes

EUS (Echotexture) Mesenchymal tumor Lipoma Cyst

Extrinsic compression EUS Interpretation of the EUS images is operator dependent. High agreement Cystic lesion Lipoma Extrinsic compression Vascular lesions Leiomyoma or GIST Carcinoid Pancreatic rest Metastatic lesions Poor agreement

Histologic diagnosis Cytology Histology Immunohistochemisty Tissue can be obtained for histology in a number of ways; Stacked ‘jumbo’ forceps Trucut style biopsy EMR ESD Surgical resection

Histologic diagnosis Bite on bite Removal of overlying mucosa and SM by strip biopsy Bleeding risk Insufficient tissue for pathologic diagnosis or counting of mitotic index

Management of SETs 악성화 가능성? 자연 경과는? 치료 방법은? (수술 or 내시경적 절제)

Common SET in stomach GIST Leiomyoma Schwannoma Lymphangioma Carcinoid tumor Ectopic pancreas Lipoma Malignant potential Benign

GIST The most common intramural subepithelial lesion encountered during upper GI endoscopy Originated from the intestitial cells of Cajal Kit expression C-kit (CD117) / CD 34 (+) Desmin negative 2nd (muscularis mucosa) or 4th (muscularis propria) Well-defined border Hypoechoic Homogenous

GIST 10~30%; malignant Characteristics of malignant GIST Mitotic index and dimension of lesion No lesion can be definitively labeled as benign Characteristics of malignant GIST Heterogenous structure Hyperechoic foci and/or anechoic necrotic areas Irregular extraluminal border Associated LAP with malignant features Large dimension (> 4cm)

GIST (risk stratification) Hum Pathol 2007;38:679-687

Malignant risk of GIST Very low < 1% Low 1-10% Moderate 10-50% High >50%

Neuroendocrine tumors (carcinoid) Originate from enterochromaffin-like cells located in the gastric mucosa 2nd or 3rd layer Homogenous, well-defined border, hypoechoic /isoechoic Malignant potential is present EMR < 2 cm 3rd layer No associated LAP

Natural course of incidental SETs Follow up (84 months) 8mm in initial mean size - Moderate risk GIST (2, 0.8%) - Schwannoma (1) World J Gastroenterol 2010;16:439-444

Natural course of incidental SETs Retrospective study 989 SETs (≤ 30 mm), f/u median 24 months (3-123mo) 84 (8.5%): significant change (size, EUS/endoscopic findings) → 25 (2.5%): endoscopic/surgical resection → 19 (1.9%) GIST (3 high risk) J Clin Gastroenterol 2011;45:330-336

Mx algorithm in SETs SET < 1cm Consider EGD f/u in 6 mo or 1 year lipoma Extramural Lipoma Vascular lesion cyst or lymphangioma… EUS > 3 (2) cm Hypoechoic Surgery Dependent on clinical availability and risk 1~3rd layer: endoscopic resection 4th layer - < 2cm: follow up - > 2cm: punctured by EUS

M/66, 건강검진 Next step? Biopsy EUS or CT Resection Observation & regular follow up

F/74, Abdominal discomfort 다음 검사는? 치료는? EUS

F/74, Abdominal discomfort 3.8x3.0cm → Wedge resection → GIST, low risk