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Approach to Subepithelial Lesions

ACG Postgraduate Course October 13th, 2013

Jonathan M. Buscaglia, MD Associate Professor of Medicine Director, Interventional Endoscopy Program School of Medicine, Stony Brook University

Objectives

• Review the epidemiology and pathology of the major subepithelial lesions in the GI tract

• Discuss various approaches to the diagnosis and management of these lesions

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Background

• Subepithelial lesions are frequently encountered

– ~1% of EGD procedures diagnose a subepithelial leison1

– ~13% of lesions are malignant at diagnosis2

– Many lesions are benign, but have malignant potential

• Most lesions are discovered incidentally

• Most likely symptom is anemia and/or GI bleeding3

– Other symptoms include abdominal pain and obstruction

1. Hedenbro JL, et al. Surg Endosc 1991; 5:20-3. 2. Polkowski M. Endoscopy 2005; 37: 635-45. 3. Humphris JL, et al. J Gastroenterol Hepatol 2008; 23:556-66.

Background

• M:F ratio=1; most patients >50 years old

• CT/MRI/US usually not sensitive enough to detect and characterize most subepithelial lesions

• EUS is able to:

– Differentiate extramural compression from intramural growth – Determine layer of origin – Accurately measure size – Evaluate for regional lymphadenopathy – Obtain tissue – Help to determine appropriate management

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Normal Gastrointestinal Wall Layers

MM

MM MP

MP

MP

SM

Mary Lee Krinsky, DO and Kenneth Binmoeller, MD

Radial EUS Imaging

Differential Diagnosis

Pathology Muscularis Mucosa

Submucosa Muscularis Propria

Serosa

GIST x X

Leiomyoma x X

Lipoma X

Granular Cell Tumor X X

Pancreatic Rest X

Carcinoid (NET) X

Duplication Cyst X X X X

Fibroid lesion X

Varices X

Lymphangioma X

Neural Tumors (e.g. Schwannoma)

X X

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Differential Diagnosis

Pathology Muscularis Mucosa

Submucosa Muscularis Propria

Serosa

GIST x X

Leiomyoma x X

Lipoma X

Granular Cell Tumor X X

Pancreatic Rest X

Carcinoid (NET) X

Duplication Cyst X X X X

Fibroid lesion X

Varices X

Lymphangioma X

Neural Tumors (e.g. Schwannoma)

X X

GIST Lesion

• Originate from the interstitial cells of Cajal (MP layer)

• Gain of function mutation in KIT gene activation of the c-kit protein (tyrosine kinase receptor)1

• IHC staining is positive for CD117 in 95% cases (corresponds to c-kit activation)

• All have malignant potential

1. Hirota S, et al. Science 1998; 279:577-80.

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GIST Lesion

GIST Lesion

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GIST Lesion

GIST Lesion

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GIST Lesion

GIST Lesion

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GIST Lesion

• Higher risk of malignancy1-3

– Lesion size >3cm on EUS

– Intestinal (jejunum) >> gastric lesions

– Mitotic rate >5-10/50 HPF

1. Palazzo L, et al. Gut 2000; 46:88-92. 2. Hunt GC, et al. Gastrointest Endosc 2003; 57:469-74. 3. Humphris JL, et al. J Gastroenterol Hepatol 2008; 23:556-66.

Risk of Malignancy Size Mitotic Count

Very low <2cm <5/50 HPF

Low 2-5cm <5/50 HPF

Moderate <5cm 6-10/50 HPF

>5cm <5/50 HPF

High >5cm 6-10/50 HPF

Any size >10/50 HPF

GIST Lesion

• Management:

– Symptomatic lesions surgical resection*

– Asymptomatic, large lesions (>2cm) surgical resection*

– Asymptomatic, small lesions (<2cm): • Annual EGD/EUS for surveillance vs. surgical resection

*Simultaneous referral to medical oncologist for consideration of adjuvant therapy with Imatinib (Gleevec®) for high risk lesions

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Leiomyoma

• Originate from the MP layer (occasionally MM layer)

• Most common location is the mid-distal eophagus1

• IHC staining is negative for CD117, CD34, and s100

– Positive for desmin and α-smooth muscle actin proteins

• Risk of malignancy is extremely rare1,2

1. Seremetis MG, et al. Cancer 1976; 38:2166-77. 2. Humphris JL, et al. J Gastroenterol Hepatol 2008; 23:556-66.

Leiomyoma

MM

SM

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Leiomyoma

MM

SM

Leiomyoma

MM

SM

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Leiomyoma

MM

SM

Leiomyoma

MM

SM

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Leiomyoma

• Management:

– Surveillance EGD/EUS every 1-2 years1

• For asymptomatic, small lesions (<1-2cm)

– Surgical resection • Symptomatic, enlarging, structural changes during surveillance

– Endoscopic resection • Small lesions (<2cm) arising from the MM layer on EUS exam

1. Lee LS, et al. J Am Coll Surg 2004; 198:136-46.

Lipoma

• Fatty tumors arising from the SM layer

• Most commonly occur in the colon and gastric antrum

• Positive “pillow sign” 98% specific for lipoma1

• Essentially no malignant potential

• Characteristic EUS features • Jumbo biopsies often reveal yellow, adipose tissue2

1. Hwang JH, et al. Gastrointest Endosc 2005; 62:202-8. 2. Buscaglia JM, et al. Gastrointest Endosc 2012; 75:1147-52.

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Lipoma

• Fatty tumors arising from the SM layer

• Most commonly occur in the colon and gastric antrum

• Positive “pillow sign” 98% specific for lipoma1

• Essentially no malignant potential

• Characteristic EUS features • Jumbo biopsies often reveal yellow, adipose tissue2

1. Hwang JH, et al. Gastrointest Endosc 2005; 62:202-8. 2. Buscaglia JM, et al. Gastrointest Endosc 2012; 75:1147-52.

Lipoma

• Fatty tumors arising from the SM layer

• Most commonly occur in the colon and gastric antrum

• Positive “pillow sign” 98% specific for lipoma1

• Essentially no malignant potential

• Characteristic EUS features • Jumbo biopsies often reveal yellow, adipose tissue2

1. Hwang JH, et al. Gastrointest Endosc 2005; 62:202-8. 2. Buscaglia JM, et al. Gastrointest Endosc 2012; 75:1147-52.

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Lipoma

• Fatty tumors arising from the SM layer

• Most commonly occur in the colon and gastric antrum

• Positive “pillow sign” 98% specific for lipoma1

• Essentially no malignant potential

• Characteristic EUS features • Jumbo biopsies often reveal yellow, adipose tissue2

1. Hwang JH, et al. Gastrointest Endosc 2005; 62:202-8. 2. Buscaglia JM, et al. Gastrointest Endosc 2012; 75:1147-52.

Lipoma

• Fatty tumors arising from the SM layer

• Most commonly occur in the colon and gastric antrum

• Positive “pillow sign” 98% specific for lipoma1

• Essentially no malignant potential

• Characteristic EUS features • Jumbo biopsies often reveal yellow, adipose tissue2

1. Hwang JH, et al. Gastrointest Endosc 2005; 62:202-8. 2. Buscaglia JM, et al. Gastrointest Endosc 2012; 75:1147-52.

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Granular Cell Tumor

• GCTs are of Schwann cell in origin

• Arise from the MM or SM layer

• Most GI tract GCTs are located within the esophagus

• Risk of malignancy is extremely low

– ~2-4% at time of diagnosis; all >4cm in size1

1. Orlowska J, et al. Am J Gastroenterol 1993; 311-15.

Granular Cell Tumor

• Management:

– Small lesions (<1cm) annual EGD exam

– Large lesions (>2cm) surgical resection

– Intermediate lesions (1-2cm) surveillance EGD exams vs. endoscopic resection1

1. De Ceglie A, et al. Dig Dis Sci 2005; 50:1875-9.

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Pancreatic Rest

• Prevalence of 1-2% in autopsy studies

• 90% located in the stomach; mostly gastric antrum

• Symptoms present in minority of patients:1

– Ulceration and pain

– Pancreatitis

– Bleeding

– Gastric outlet obstruction

– Dysphagia

• Characteristic central umbilication on endoscopy

• Arise from the SM layer on EUS

• Essentially no malignant potential

1. Shalaby M, et al. Am J Gastroenterol 2002; 97:1046-9.

Pancreatic Rest

SM

MP

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Pancreatic Rest

SM

MP

Pancreatic Rest

SM

MP

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Carcinoid Tumor

• Most frequent neoplasm of the small intestine (ileum>jejunum>duodenum)1

– Small bowel accounts for 25% of all carcinoids

• Slight female predominance (M:F ratio=1:1.6)

• Originate from mucosal layer and penetrate deep

• Gastric carcinoids account for 9% of all carcinoids2

– 3 subtypes of gastric carcinoids

– Varying levels of malignant potential

1. Modlin IM, et al. Cancer 2003; 97:934-59. 2. Modlin IM, et al. Am J Gastroenterol 2004; 99:23-32.

Gastric Carcinoid Tumors

• Type I: associated with atrophic gastritis, pernicious anemia and hypergastrinemia – Low malignant potential

• Type II: associated with MEN 1, Zollinger-Ellison Syndrome, and hypergastrinemia – Intermediate malignant potential

• Type III: sporadic form, normal gastrin levels – High malignant potential

Modlin IM, et al. Gastroenterol 2005; 128: 1717:51.

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Management of Gastric Carcinoid Tumors

• Type I and II lesions (hypergastrinemia):

– Endoscopic resection for small lesions, <1-2cm

– Surgical resection for large lesions, or multiple lesions (>5)

– Consideration or surgical antrectomy or fundectomy • Removal of G-cells or ECL cells, respectively

– Surveillance EGD every 6-12 months

• Type III lesions (normal gastrin levels):

– Surgical resection with lymph node dissection1

1. Ramage JK, et al. Gut 2005; 54:1-16.

Rectal and Duodenal Carcinoid Tumors

• Management of rectal tumors:1

– Small lesions (<1cm), confined to SM endoscopic resection

– Large lesions (>2cm), or invasion to MP layer, or regional lymph node involvement surgical resection

– Intermediate lesions (1-2cm), confined to SM endoscopic vs. surgical resection

• Management of duodenal tumors:

– No guidelines exist for non-ampullary tumors

– Reasonable to adopt the same approach to rectal lesions

1. Kobayashi K, et al. Dis Colon Rectum 2005; 48:285-91.

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Rectal and Duodenal Carcinoid Tumors

• Management of rectal tumors:1

– Small lesions (<1cm), confined to SM endoscopic resection

– Large lesions (>2cm), or invasion to MP layer, or regional lymph node involvement surgical resection

– Intermediate lesions (1-2cm), confined to SM endoscopic vs. surgical resection

• Management of duodenal tumors:

– No guidelines exist for non-ampullary tumors

– Reasonable to adopt the same approach to rectal lesions

1. Kobayashi K, et al. Dis Colon Rectum 2005; 48:285-91.

Rectal and Duodenal Carcinoid Tumors

• Management of rectal tumors:1

– Small lesions (<1cm), confined to SM endoscopic resection

– Large lesions (>2cm), or invasion to MP layer, or regional lymph node involvement surgical resection

– Intermediate lesions (1-2cm), confined to SM endoscopic vs. surgical resection

• Management of duodenal tumors:

– No guidelines exist for non-ampullary tumors

– Reasonable to adopt the same approach to rectal lesions

1. Kobayashi K, et al. Dis Colon Rectum 2005; 48:285-91.

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Rectal and Duodenal Carcinoid Tumors

• Management of rectal tumors:1

– Small lesions (<1cm), confined to SM endoscopic resection

– Large lesions (>2cm), or invasion to MP layer, or regional lymph node involvement surgical resection

– Intermediate lesions (1-2cm), confined to SM endoscopic vs. surgical resection

• Management of duodenal tumors:

– No guidelines exist for non-ampullary tumors

– Reasonable to adopt the same approach to rectal lesions

1. Kobayashi K, et al. Dis Colon Rectum 2005; 48:285-91.

Rectal and Duodenal Carcinoid Tumors

• Management of rectal tumors:1

– Small lesions (<1cm), confined to SM endoscopic resection

– Large lesions (>2cm), or invasion to MP layer, or regional lymph node involvement surgical resection

– Intermediate lesions (1-2cm), confined to SM endoscopic vs. surgical resection

• Management of duodenal tumors:

– No guidelines exist for non-ampullary tumors

– Reasonable to adopt the same approach to rectal lesions

1. Kobayashi K, et al. Dis Colon Rectum 2005; 48:285-91.

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Rectal and Duodenal Carcinoid Tumors

• Management of rectal tumors:1

– Small lesions (<1cm), confined to SM endoscopic resection

– Large lesions (>2cm), or invasion to MP layer, or regional lymph node involvement surgical resection

– Intermediate lesions (1-2cm), confined to SM endoscopic vs. surgical resection

• Management of duodenal tumors:

– No guidelines exist for non-ampullary tumors

– Reasonable to adopt the same approach to rectal lesions

1. Kobayashi K, et al. Dis Colon Rectum 2005; 48:285-91.

Rectal and Duodenal Carcinoid Tumors

• Management of rectal tumors:1

– Small lesions (<1cm), confined to SM endoscopic resection

– Large lesions (>2cm), or invasion to MP layer, or regional lymph node involvement surgical resection

– Intermediate lesions (1-2cm), confined to SM endoscopic vs. surgical resection

• Management of duodenal tumors:

– No guidelines exist for non-ampullary tumors

– Reasonable to adopt the same approach to rectal lesions

1. Kobayashi K, et al. Dis Colon Rectum 2005; 48:285-91.

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Algorithm for the Approach to Subepithelial Lesions

• Biopsy overlying mucosa • Estimation of lesion size Repeat EGD in 1 year

EGD

Lesion<1cm

Lesion>1cm

EUS

• Characterize the lesion • Evaluate for signs of malignancy • Tissue acquisition for definitive Dx

Growing in size, Or >1cm

yes

no

Methods of Tissue Acquisition

• EUS-FNA1 or EUS-FNB (core needle)

• Tunneled, jumbo biopsy forceps2

• Unroofing, enucleation, other techniques3,4 • Endoscopic resection

Significant Malignant Potential

yes no

Surgery Endoscopic Surveillance

1. Hoda KM, et al Gastrointest Endosc 2009; 69:1218-23. 2. Buscaglia JM, et al. Gastrointest Endosc 2012; 75:1147-52. 3. Lee CK, et al. Gastrointest Endosc 2010; 71:188-94. 4. Jeong ID, et al. Surg Endosc 2011; 25:468-74