Management of Subepithelial tumors of esophagus and stomach.pptb

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Management of Subepithelial tumors of esophagus and stomach : 

Management of Subepithelial tumors of esophagus and stomach Dr. Ajesh Bansal Gastroenterology DMC, LDH

Overview : 

Overview Definition Epidemiology Clinical features Different varieties Natural history Diagnosis Treatment

Introduction : 

Introduction Subepithelial tumors: Mass lesion in the upper gastrointestinal tract appearing at endoscopy as mass, bulge, or impression covered with normal appearing overlying mucosa. Includes both those of intramural or extramural origin.

Introduction : 

Introduction The term subepithelial is favored than submucosal as mass can arise from outside the wall or from layers other than the submucosa.

Epidemiology : 

Epidemiology One retrospective study had reported a prevalence of 0.36% during upper endoscopies. Equal frequency in both sexes, generally after the fifth decade. Surg. Endosc. 1991; 5: 20–3.

Clinical Features : 

Clinical Features The majority of SEML are asymptomatic and are discovered incidentally during endoscopy. Large SEML may outgrow their blood supply, ulcerate the mucosa, and present with upper gastrointestinal bleeding. Firm SEML can cause obstructive symptoms especially if located at or near the cardio-esophageal junction or pylorus, and SEML located at the papilla may cause jaundice and pancreatitis. Surg. Endosc. 1991; 5: 20–3 JGH 2008; 23- 556-566.

SEML ‘s : 

SEML ‘s Benign GIST – benign Leiomyoma Lipoma Varices Neural origin – schwannoma, neuroma, neurofibroma Granular cell tumor Inflammatory fibroid polyp Duplication cyst Lymphangioma Pancreatic rest Malignant (potential) GIST – malignant Carcinoid Lymphoma Metastasis Glomus tumor


SEML Leiomyomas are more common than GIST in the esophagus GIST more common than leiomyomas in stomach Granular cell tumors occur primarily in the esophagus. Pancreatic rests are more likely to be found in the gastric antrum Duplication cysts are most likely to occur in the distal esophagus or esophagogastric junction and duodenum, although they may occur in the distal stomach.

Natural History : 

Natural History Natural History is still unclear. Few data available.

Yeun Jung Lim et al : 

Yeun Jung Lim et al Retrospective analysis at Tertiary medical Center, Seoul N= 104159 endoscopies SEML- 795 252 followed for mean of 82 months ± 29.2 World J gastro 2010, Jan 28; 16 (4): 439-444

Yeun Jung Lim et al : 

Yeun Jung Lim et al Mean pt age- 53 yrs Male to female : 2.36 :1 Average Initial size: 8.9 mm Stomach- M.C. site (51 %) Out of 252 lesions 96.8 % were unchanged and only 3.2 % were significantly increase in size (from 12.9 ± 6.0 to 21.2 ± 12.2 mm) after a mean interval of 59.1 ± 27.5 mo In these 8 lesions, there was an increase of over 25% and more than 5 mm in diameter at surveillance Six of the 8 lesions arose from the 4th layer, corresponding to the muscularis propria, and appeared hypoechoic; they were considered to be GISTs Surgical resection of lesions was performed when the lesions were ≥ 3 cm in diameter. Two lesions- GIST with malignancy One lesion- Schwannoma World J gastro 2010, Jan 28; 16 (4): 439-444

Yeun Jung Lim et al : 

Yeun Jung Lim et al Most small subepithelial lesions do not change as shown by endoscopic examination, and regular follow-up with endoscopy may be considered in small subepithelial lesions, especially lesions < 1 cm in size. World J gastro 2010, Jan 28; 16 (4): 439-444

Kanwar RS Gill et al : 

Kanwar RS Gill et al Goal- To evaluate the natural course of <3-cm SEML by EUS and to determine the appropriate timing for EUS follow-up. Fifty-one patients Mean age- 61 Asymptomatic <3 cm upper gastrointestinal hypoechoic SETs of second and fourth echolayer were identified. Follow-up period was 29.7 months. Initial evaluation included location, echolayer involved Tumor diameter Internal echopattern, and Outer margin of lesions by EUS. Additional features including change in size and echogenic features were noted on the follow-up examinations. J Clin Gastroenterol Volume 43, Number 8, September 2009

Kanwar RS Gill et al : 

Kanwar RS Gill et al <3-cm SETs does not change during a median period of 23 months (mean, 30 mo). The change in echogenicity and increase in size may indicate a GIST. According to the study, follow-up EUS examination for asymptomatic, <3-cm SETs, every 2 years seems reasonable J Clin Gastroenterol Volume 43, Number 8, September 2009

Diagnostic Means : 

Diagnostic Means Endoscopy- Bronze EUS- Silver Histological Diagnosis: Gold Cytology Histology Immunohistochemistry Surgical specimen Cross sectional Imaging and ultrasound

Diagnosis : 

Diagnosis SEML are characterized by their Location (extramural vs intramural), Size, and Echogenicity Gold standard being histology with immunohistochemistry.

Endoscopy : 

Endoscopy Size estimation Intramural vs Extra Type of SEML (Lipoma) Mucosal Biopsies

Endoscopy : 

Endoscopy Open biopsy forceps (6- 8 mm) as a criterion standard, the size of intramural lesions can be estimated with reasonable accuracy; If the lesion is extramural this method is inaccurate. Therefore if SEML is confirmed by EUS to be intramural, serial endoscopy rather than repeated EUS may be an option in follow-up. Volume 62, No. 2 : 2005 GASTROINTESTINAL ENDOSCOPY

Slide 19: 


Endoscopy : 

Endoscopy Suboptimal in identifying the origin of the lesion (extramural vs intramural) overall accuracy of 89% (sensitivity 98%, specificity 68%). In as many as 30% of cases of suspected intramural lesions, the mass arises extramural. Many pathologies sharing common mucosal appearances.

Endoscopy : 

Endoscopy Lipomas can be diagnosed with confidence with demonstration of a positive ‘pillow or cushion sign’ defined as a mobile lesion which indents when probed gently. Specificity- 99% Sensitivity- 40 % Mucosal biopsies should also be obtained to confirm that the mucosa is histologically normal

EUS : 

EUS EUS is the most accurate method for characterizing SEML. EUS is able to reliably distinguish intramural lesions vs extramural compression. Large lesions which extend beyond the penetration depth of the ultrasound cannot be accurately measured.

EUS : 

EUS Data shows that EUS is highly accurate in predicting the size of intramural masses when compared to the surgical pathology.

Slide 25: 

Journal of Gastroenterology and Hepatology 23 (2008) 556–566

EUS : 

EUS At a scanning frequency of 5–12 mHz five distinct layers of the wall are seen at EUS, whereas the sonographic layers do not directly correspond to the histologic layers but approximate to mucosal interface, muscularis mucosae, submucosa, muscularis propria, and serosa or adventitia.

EUS : 

EUS Extramural lesions are seen to cause compression of the five normal layers. Lesions are also characterized by echogenicity being either hyperechoic, isoechoic, hypopechoic, or anechoic, relative to the surrounding normal parenchyma (submucosa as a reference point for a hyperechoic lesion and muscularis propria for a hypoechoic lesion).

EUS : 

EUS Lesions that are anechoic should be further assessed with color flow Doppler. Generally Hypoechoic: Leiomyomas/GIST Anechoic: cystic lesions Hyperechoic : lipomas

EUS : 

EUS EUS features suggestive of malignancy on EUS include size >3 cm, cystic spaces, echogenic foci, and adjacent malignant-appearing lymph nodes.

EUS : 

EUS Overall EUS is a moderately accurate method of evaluating SEML. In one series the accuracy of EUS for hypoechoic lesions where tissue was obtained was 44% with all incorrect diagnoses occurring for hypoechoic lesions in the 3rd and 4th layers. Therefore histologic confirmation should be obtained in these lesions where possible. Volume 62, No. 2 : 2005 GASTROINTESTINAL ENDOSCOPY

EUS : 

EUS EUS can accurately delineate depth of penetration and thus whether a lesion is suitable for submucosal resection.

EUS : 

EUS Interpretation of the EUS images is operator dependent. Agreement highest for Cystic lesions, Lipomas, and Extrinsic compressions; Lower for Vascular lesions and Leiomyoma or gastrointestinal stromal tumor (GIST); Poor for other lesions such as carcinoid, pancreatic rest, or Metastatic lesions

Cross sectional Imaging and USG : 

Cross sectional Imaging and USG Cross-sectional imaging of SEML is of limited value and its primary use is in extramural lesions

USG : 

USG Extracorporeal ultrasound after the ingestion of water has been proposed as an alternative to EUS for diagnosis of SEML. Able to detect 69–97% of SEML >30 mm, but is able to ascertain the type in only 60% of cases

Histology Diagnosis- Gold : 

Histology Diagnosis- Gold Cytology Histology Immunohhistochemistry

EUS FNAB: Cytology : 

EUS FNAB: Cytology Less useful for differentiating intramural mesenchymal tumors due to similar spindle cell morphology; accuracy of only 38% For neoplasms such as lymphomas and stromal tumors, the diagnosis and malignant potential is difficult based on cytology specimens alone. Gut 1999; 44: 720–6.

Cytology : 

Cytology Complications from EUS FNAB are rare but include perforation, hemorrhage, and infections, including bacteremia.

Immunohistochemistry : 

Immunohistochemistry Diagnosis of SEML has improved with the application of immunohistochemistry. Indeed, with very few exceptions the diagnosis of GIST is based on positivity for CD117 or c-kit. Common markers used in addition to CD117 include CD34, smooth muscle actin, S100, vimentin.

Histology : 

Histology Tissue can be obtained for histology in a number of ways: Stacked ‘jumbo’ forceps Trucut style biopsy Endoscopic mucosal resection (EMR) Submucosal resection (ESMR), and Surgical resection

Jumbo : 

Jumbo Diagnostic yield for 3rd-layer lesions using stacked ‘jumbo’ forceps biopsy (‘bite on bite’) was 42% using 10 bites compared with 89% for EMR-ESMR. Complications - uncommon Low diagnostic yield with only one-third of forceps biopsies containing a significant amount of submucosa. Gastrointest. Endosc. 2003; 57: 68–72.

Trucut Biopsy : 

Trucut Biopsy Trucut biopsy has been introduced that can be used with linear echoendoscopes. This device utilizes a 19-gauge needle with a 18-mm tissue tray with a built in springloaded mechanism allowing a core of tissue to be obtained for histologic diagnosis. Trucut may have an advantage as fewer passes are needed and ‘back and forth’ motion is not required as with FNAB. GASTROINTESTINAL ENDOSCOPY Volume 62, No. 3 : 2005

Trucut Biopsy : 

Trucut Biopsy Evolving Technique Early reports suggest that the trucut biopsy is a safe procedure. The device functions well in the esophagus, rectum, and most of the stomach. Use is difficult and less often yields an adequate specimen due to echoendoscope angulations Its use is not recommended beyond the apex of the duodenal bulb. GASTROINTESTINAL ENDOSCOPY Volume 62, No. 3 : 2005

EMR : 

EMR EMR involves lifting a lesion away from the muscularis propria either by injection of saline solution (‘strip biopsy’) or suction of the lesion into a cap fitted to the endoscope (‘aspiration lumpectomy’), followed by electrosurgical snare resection. Lesions confined to layers 1–3 and up to 20 mm are able to be safely resected.

EMR : 

EMR In one series aspiration lumpectomy vs strip biopsy (95% vs 77%). Complications hemorrhages, ( 4–9%) and are usually managed endoscopically. Perforation uncommon


ESMR ESMR is a technique for the removal of subepithelial tumors from the 4th layer (muscularis propria) utilizing an insulated-tip knife. This technique may be able to replace surgical resection for some subepithelial tumors.

Leiomyomas : 

Leiomyomas They are benign tumors composed of well-differentiated smooth muscle cells. Common in the esophagus. They are found most frequently in the lower and middle thirds of the esophagus..

Leiomyomas : 

Leiomyomas These tumors are classically very slow growing and rarely ulcerate or bleed. They are identified immunohistochemically by positive staining for smooth muscle actin and desmin Negative staining for CD117, CD34, s100 proteins

Leiomyomas : 

Leiomyomas At EUS leiomyomas appear as well circumscribed hypoechoic masses originating from the 2nd, 3rd, or 4th layers with homogenous echotexture and smooth borders.

Leiomyomas : 

Leiomyomas Asymptomatic lesions do not require any intervention; can be monitored with endoscopy or EUS every 1–2 years. Surgical resection has been the standard treatment for lesions which are symptomatic, enlarging, ulcerated, for histopathological diagnosis, or to facilitate other esophageal procedures.

Leiomyomas : 

Leiomyomas Endoscopic resection has been employed for lesions arising from muscularis mucosa with lesions <2 cm safely resected with aspiration lumpectomy and larger tumors up to 4 cm treated with ethanol injection followed by lumpectomy.


GISTS GISTs are the most commonly identified intramural SEML in the upper gastrointestinal tract. Approximately 80% of sporadic GIST are caused by this gain of function mutation in the KIT gene which leads to constitutive activation of the c-kit. A subset (5%) of GIST have activating mutations in the PDGFRa


GIST EUS findings of benign GIST are those of a hypoechoeic lesion with a homogeneous echotexture that is contiguous with the muscularis propria (4th layer). EUS features suggestive of malignancy on EUS include size >3 cm, cystic spaces, echogenic foci, and adjacent malignant-appearing lymph nodes. The simultaneous presence of 2 out of 3 EUS features irregular extraluminal margins, cystic spaces, and lymph nodes with a malignant pattern has been shown to have a positive predictive value of 100% for malignant or borderline GISTs All GIST are considered potentially malignant and may need to be resected. Gastrointest Endosc. 1997;45:468–473.


GIST Medical Management: Imatinib Mesylate : 400 mg by mouth daily. 55-80% of patients with metastatic GIST achieve a partial or stable disease reponse 38% had reduction in tumor size by 50% or greater (partial response). The adverse reactions of imatinib are manageable and include edema, rash, diarrhea, nausea, abdominal pain, and fatigue. FDA approved sunitinib malate (SU-11248, Sutent) for the treatment of patients with GISTs whose disease has progressed or who are unable to tolerate treatment with imatinib Newer drug- Dasatinib Despite the proven success of imatinib and other newer tyrosine-kinase inhibitors, surgical resection remains the treatment of choice and offers the only chance for cure from GIST

Granular cell tumors (GCT) : 

Granular cell tumors (GCT) GCTs are relatively rare tumors of Schwann cell origin. The majority of GCT are asymptomatic. Dysphagia and GI bleed can occur if tumor is large. GCT are generally benign

GCT : 

GCT 2–4% are considered malignant with nearly all of these having a diameter >4 cm, rapid recent growth, and/or rapid recurrence after excision. At endoscopy they appear as slightly elevated, firm, white-gray to yellow, smooth nodular tumors usually <10 mm in diameter. On EUS they originate from the 2nd or 3rd layer appearing as hypoechoic lesions with mild heterogeneity and smooth margins. EUS features are able to reliably predict the malignant potential and it is mandatory to predict the feasibility of endoscopic mucosal resection

GCT : 

GCT Lesions <10 mm without malignant changes can be followed with a repeat endoscopy in 12 months Surgical excision for large (>20 mm), symptomatic, and suspected malignant lesions. EMR can be therapeutic if the lesion is < 20 mm and separated from the muscularis propria.

Duplication Cysts : 

Duplication Cysts Duplication cysts are benign lesions They are most frequently found in the proximal small intestine but can occur in the esophagus and stomach (ileum > esophagus > colon > stomach). In adults they are usually asymptomatic and are more common in women (M:F = 1:8).

Duplication Cysts : 

Duplication Cysts Management has traditionally consisted of surgical resection. In asymptomatic individuals observation alone is a reasonable option if the diagnosis is certain. Endoscopic therapy includes aspiration, which is not always successful; needle knife cystostomy; and removal with snare electrocautery.

Lipomas : 

Lipomas Lipomas account for <1% of gastric intramural lesions. Common in the colon but can appear anywhere in the gastrointestinal tract. Approximately 75% of gastric lipomas are located in the antrum.

Lipomas : 

Lipomas At endoscopy they are typically solitary lesions with a yellow hue their consistency is soft giving rise to a positive ‘pillow sign’ and the overlying mucosa may be easily retracted with the biopsy forceps, which is termed ‘tenting’ may exhibit some mobility. The presence of a positive pillow sign has a specificity of 98% for lipoma but a sensitivity of only 40%

Lipomas : 

Lipomas For those lesions that lack characteristic features, EUS may be indicated. . They are characteristically a well-circumscribed hyperechoic mass in the 3rd layer. These features are essentially diagnostic for lipomas, avoiding the need for further diagnostic testing.

Pancreatic rest : 

Pancreatic rest Pancreatic rest refers to ectopic pancreatic tissue. It has a prevalence of 1–2% in autopsy studies. Pancreatic rests are most often found in the gastric antrum; in 90% of cases they are found in stomach, duodenum, and proximal jejunum.

Pancreatic rest : 

Pancreatic rest Pancreatic rests generally asymptomatic , but symptoms associated with pancreatitis, cyst formation, ulceration, bleeding, obstructive jaundice, and gastric outlet obstruction have been noted. Rare reports of lesions undergoing malignant change

Pancreatic rest : 

Pancreatic rest At endoscopy they often show central umbilication, and EUS findings are those of a hypoechoic lesion with a heterogeneous echotexture within the submucosa (2nd or 3rd layer). The presence of ductal structures within the tissue is a distinctive finding, but is found in only a minority of cases. Histologic diagnosis is recommended, as the differential diagnosis of hypoechoic 3rd-layer lesions includes those with malignant potential.

Conclusions : 

Conclusions Evaluation of any SEML greater than 1 cm in diameter with EUS is suggested unless the endoscopic features of lipoma are obviously present. EUS is able to accurately differentiate intramural from extramural lesions and potentially remove the need for further investigation. EUS can characterize a lesion in terms of its size, layer of origin, and additional features, including those suggestive of malignancy. Patients with a cyst, vessel, or lipoma at EUS require no further follow-ups.

Slide 78: 

In many cases, EUS will not provide a specific diagnosis and will not exclude malignancy. Hypoechoic lesions in the 4th layer that are over 3 cm in diameter with features suggestive of malignancy should be referred for consideration of surgery.

Conclusion : 

Conclusion Other hypoechoic 3rd- and 4th-layer lesions should undergo EUS with FNAB and immunohistochemistry. If a diagnosis is not obtained, then trucut biopsy or submucosal resection (lesions not involving muscularis propria) can be considered.

Conclusions : 

Conclusions Those lesions which remain undiagnosed after investigation should undergo periodic follow-ups with EUS, a suggested interval being yearly for 2 years, which may be extended if the lesion remains unchanged.

Slide 81: 


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