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All topics are updated as new evidence becomes available and our ,1 _;. *lli{, . |, ti.,$s is complete. Literature review current through: May 2012. I This topic last updated: Nov 17, 2010. INTRODUCTION A subepithelial mass or a bulge encountered during an endoscopy can arise from within any layer of the gastrointestinal tract wall (intramural) or outside of the wall (extramural). They are usually found incidentally during routine imaging with **riilrrcontrast radiography orendoscopy. The differential diagnosis includes a number of benign and malignant non-epithelial gastric wall tumors, intramural vessels, and extrinsic compression f rom extramural structures. Endoscopy alone cannot accurately distinguish between intramural and extramural lesions t"il By contrast, endoscopic ultrasonography (EUS) has provided a major breakthrough for characterizing such masses. This topic review will provide an overview of the most common subepithelial lesions that can be identified endosonographically. Discussions on the individual lesions are also available on the corresponding topic
reviews.

GENERAL PRINCIPLES FOR IMAGING subepithelial lesions:

EUS provides a number of methods for characterizing

lt provides an understanding of whether the lesion arises from the bowel wall (intramural) or from a structure outside the bowelwall (extramural) compressing the gastrointestinal wall. Extramural lesions
may be a normal adjacent structure (eg, spleen, aorta, gallbladder) or pathologic structures (eg, splenic artery aneurysm, cyst, tumor). Rarely, the distinction between an intra- and extramural lesion may be difficult when there is invasion into the gastrointestinalwall.

lt can determine the originating layer of intramural lesions, an important clue for achieving a diagnosis (i*iilt J ) Stromal cell tumors, for example, can typically be seen as evolving from the muscularis propria or muscularis mucosa, whereas lipomas typically evolve from the submucosa.
lymph

o The echogenicity, vascularity, margins, size of the lesion, and absence or presence of adjacent
nodes also help to narrow the differential diagnosis.

EUS-guided fine-needle aspiration or trucut biopsy of the lesion may be helpful in some settings. (See
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Technical considerations
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The following are basic principles that should be understood by to visualize subepithelial lesions.

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The lesions should be localized endoscopically or by cross-sectional imaging (CT, MRl, US) prior to

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endosonographic evaluation. The gastrointestinal tract wall echo structure, five layers of alternating bright (hyperechoic) and dark (hypoechoic) lines of approximately 3 to 4 mm thickness should be understood (J_t*i,:.* l). Endoscopic ultrasound imaging should be performed adjacent to the lesion. Water instillation may be helpful to provide adequate acoustic coupling while achieving a focal distance that permits optimal imaging. The focal length for a7.5 MHztransducer is approximately 2.0 centimeters. lmaging can be optimized by using a minimally inflated, water filled balloon and instilling deaerated water to distend the lumen while providing a medium to transmit the ultrasound waves without reflection. For small (<1 cm) or flat lesions, imaging with through-the-scope, high frequency catheter ultrasound probes ("miniprobes") may be technically easier than using a dedicated echoendoscope. Miniprobes are approximately 3 mm in diameter and operate at 12, 15,20, and 30 MHz frequencies, permitting more detailed imaging of the gastrointestinal wall compared with the lower-frequency standard echoendoscopes. However, they have relatively shallow depth of penetration limiting visualization of large tumors and surrounding lymph nodes. The miniprobes can be introduced through the working
channel of a diagnostic endoscope and directed to the lesion endoscopically. A balloon sheath can be used to optimize acoustic coupling, although it increases the diameter of the probe, requiring use of a

therapeutic endoscope.

Description of the lesion's characteristics Primary characteristics that should be determined include the layer of origin or extramural origin, size, echogenicity, and vascularity. Echogenicity has been described as
the following:

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Anechoic

- The echogenicity of water or clear fluid (ie, black with no internal echoes). Anechoic lesions are typically associated with acoustic enhancement, which is a brighter echo located behind a fluid filled structure. Common examples are cysts, vessels, and the gallbladder.

Hypoechoic - Echogenicity that is equivalent or lower than that of the second (lamina propria) and fourth wall layers (muscularis propria). Common examples include leiomyomas, gastrointestinal stromal tumors (GIST), or mucirVdebris filled cysts. Hyperechoic - Echogenicity that is equivalent to or higher than the first (superficial mucosa), third (submucosa), and fifth layers (serosa). The most common example is a lipoma. lsoechoic - Echogenicity that is equivalent or nearly equivalent to the involved layer of the lesion. This appearance can be somewhere in between hyperechoic and hypoechoic.

General principals of tissue sampling

A number of methods are available for obtaining tissue samples.

Standard biopsy - Specimens obtained by standard endoscopic forceps have a low diagnostic yield due to their superficial sampling. Taking a biopsy within the site of a previous biopsy ("tunnel" or "well,' biopsies) may permit sampling of deeper lesions. Endoscopic mucosal resection (EMR) - The diagnostic yield of a tissue biopsy can be improved by resecting the overlying mucosa or a portion of the lesion using a snare, a maneuver that creates access to deeper tissue. This technique has also been referred to as "unroofing". Various approaches are used

to facilitate EMR, including the use of a double channel endoscope, band ligation, and a cap attachment (EMR-c). A prospective study comparing biopsy and EMR techniques showed a marked increase in diagnostic yield between the two modalities (17 versus 87 percent, respectively) [,:i].

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Although this technique improved diagnostic yield, it may also increase complications such as bleeding
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Endoscopic submucosal dissection - An alternative to EMR is the use of the needle-knife to incise the overlying mucosa. This approach, known as endoscopic submucosal dissection, was first described in 2003 in a patient with a metastasis from colon cancer presenting as a submucosal gastric tumor [:i]. Endoscopic submucosal dissection has been used primarily for the treatment of mucosal gastric and esophageal cancers in Japan and Germany resection of subepithelial tumors [,:,*].

[fr,iij More recently,

ESD has been described for the

Carefuldissection using a modified needle-knife such as the lnsulated Tip (lT) knife enables en bloc resection of a submucosal tumor. ESD requires an exceptional level of operator skill, is time consuming, and is associated with significant complication rates, especially bleeding and perforation. As a result, ESD should be reserved for centers specialized in this advanced procedure. (See "{ii;;q1:11;1t;;;;;; 1:!
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Fine needle aspiration (EUS-FNA) - Standard 19,22, or 25 gauge needles may be used for fine needle aspiration to provide an adequate tissue sample for cytological diagnosis. This is often used in conjunction with immunohistochemical staining, such as for c-kit (CD 117). A larger guillotine biopsy needle has been used [t]1, but larger needles increase the risk of bleeding and it is unclear if these
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Trucut biopsy EUS-FNA typically yields a small tissue sample that is insufficient for histological examination. Large caliber cutting needles were designed to acquire larger tissue specimens with preserved tissue architecture that can provide a histologic diagnosis. (See "il:*d*s-c+ilf ril|irltr::tii:.rj

ACCURACY

Multiple studies have evaluated the accuracy of EUS in characterizing subepithelial lesions. Studies focusing on specific lesions are presented below. As a general rule, the ability of EUS alone to distinguish among subepithelial lesions is variable. As a result, histology is still considered to be the "gold standard."

Some representative studies have shown the following:

A prospective study evaluating the accuracy of EUS in characterizing 100 consecutive patients with subepithelial lesions found that EUS findings alone correctly predicted the specific lesion type in only 48 percent of cases where biopsy confirmation had been obtained [j]. Most misclassifications occurred in hypoechoic lesions in the third and fourth layers, which include carcinoids, GlSTs, aberrant pancreas,
and granular cell tumors.

ln a second study, the results of endoscopic resection or biopsies after unroofing in 54 submucosal lesionswerecomparedwiththeEUSfindings[11] Theoverallaccuracyof EUSindeterminingthelayer of origin and location of lesion was 80 percent; six lesions were located deeper in the Gl wall than estimated by EUS and five were more superficial. EUS and pathology findings coincided in 74 percent of lesions.

ln a third study, 22 patients underwent EUS prior to endoscopic resection of gastric subepithelial lesions Iif i]. EUS alone correctly diagnosed 10 (46 percent) of the lesions. The lesions that were incorrectly diagnosed included pancreatic rests (n = 5) and gastritis cystica profunda (n = 2)

EXTRAMURAL LESIONS

Normal anatomic structures and extraluminat benign and malignant tumors can

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compress the gastrointestinaltract and mimic an intramuraltumor. lncidental lesions are being detected more commonly with the increasing use of total body scans in healthy patients. EUS can assist in further characterizing such findings.

Endoscopic appearance - Extramural lesions are commonly seen as a bulge located in the gastrointestinal (Gl) tract with normal overlying mucosa, usually with a smooth border and no significant irregularity (lt$.r*,--). Endosonographic findings - A normal appearing five-layer gastrointestinal wall structure is seen interposed between the lesion and the bowel lumen. Specific echo features vary depending upon the type of structure identified. As an example, the splenic vessels appear as an anechoic structure that can be followed longitudinally' The spleen may appear to have a homogeneous echogenicity. A pancreatic pseudocyst originates from a region of the pancreas, and is commonly hypoechoic or anechoic.
Diagnosis - Knowledge of normal endoscopic ultrasound anatomy is required to determine if a structure is normal or abnormal. Common normal extrinsic structures include the splenic artery, spleen, gallbladder, left lobe of the liver, and the pancreas [1li]. Abnormalstructures include pancreatic pseudocysts, enlarged lymph nodes, aneurysms, omental metastasis, and hepatic and pancreatic tumors. one group reported 100 percent accuracy in distinguishing extramural from intramural structures
[1L].

GASTRoINTESTINAL STRoMAL TUMoRS types of tumors

[i4:i1]. One of the most common mesenchymaltumors in the gastrointestinaltract, gastrointestinal stromal tumors (GlSTs), were initially thought to be of smooth muscle origin. However, a more complete understanding of their molecular markers and biologic behavior has demonstrated that they encompass a heterogeneous group of tumors with respect to cell of origin, cellular differentiation,
and

evolving with an increased understanding of molecular, histologic, and clinical features that distinguish different

The nomenclature of gastrointestinal mesenchymal tumors is

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leiomyomas' leiomyosarcomas, schwannomas, inflammatory myofibroblastic tumors in children, Iipomas, liposarcomas, metastatic tumors, and desmoid tumors. Distinction from these other tumors is made based upon clinical, histological, and molecular features.

Glsrs are most frequently diagnosed in older individuals, in whom they are most common in the stomach (60 to 70 percent), small intestine (20 to 25 percent), colon/rectum (5 percent), and esophagus (<5 percent) [:f]. The differential diagnosis includes a multitude of lesions that can occupy the submucosal layers. These

include

A distinguishing molecular feature of Glsrs is that they are positive for c-kit (a stem cell factor receptor referred to as cD117). This immunohistochemical stain distinguishes Glsr from other kinds of spindle cell tumors [4]' other tumors that are positive for c-kit (such as angiosarcomas and metastatic melanomas) can usually be distinguished based upon clinical and histologic features. Additional markers found in GISTs include cD34 (a hematopoietic cell progenitor cell antigen present in approximately 70 percent), smooth muscle actin (present in 20 to 30 percent), and s100 protein (marker of neuraldifferentiation)

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It was previously thought that some GlsTs (less than 1 to 2 cm in size and with a low mitotic rate) were benign However, the current thinking is that virtually all GlSTs, especially those greater than .1 cm, have malignant potential. The main factors associated with malignant potential are tumor size, mrtotic rate, and primary location (with small intestinal GISTs being more aggressive than those in the stomach) (rlr.ilr.:. il). (See
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Endoscopic appearance - A GlsT commonly appears as a bulge located in the Gl tract with normal overlying mucosa and can vary in size from several millimeters to over 30 centimeters. lt usually has a smooth and regular appearance without major mucosal irregularities. ln some cases, the overlying mucosa can be ulcerated or appear inflamed.
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Endosonographic findings in GISTs are typically hypoechoic, homogeneous lesions with - GISTs have well-defined margins, although they can rarely irregular margins and ulcerations. Most GISTs originate from within the muscularis propria (fourth layer of the Gl tract); small lesions may originate from the muscularis mucosa (second layer). lnfrequently, the tumors are inhomogeneous, which has been attributed to liquefaction necrosis, connective tissue, and cystic and hyaline degeneration fif,.11)l
Specific endosonographic characteristics can be helpful for predicting benign versus malignant tumors. Large tumors with a heterogeneous echo texture (particularly those in the esophagus) are more likely to be leiomyosarcomas and leiomyoblastomas. One study demonstrated that endosonographically determined tumor size (diameter >4 cm), irregular extraluminal border, heterogeneity, echogenic foci, and cystic spaces greater than 4 mm were associated with malignancy Iii]1. The sensitivity for detecting malignancy by preoperative EUS ranged from 80 to 100 percent. However, overall interobserver agreement for specific echo features was poor. Other endosonographic features suggestive of malignancy in another report that included 56 histologically proven tumors were irregular extraluminal margins, the presence of cystic spaces, and enlarged lymph nodes [i!]. The presence of at least one of these features had a sensitivity, specificity, and positive predictive value of 91, 88, and 93 percent, respectively. The presence of two of these features had a positive predictive value of 100 percent for malignant or borderline malignant tumors. The features most predictive of benign tumors were regular margins, a tumor size s3 cm, and a homogeneous echo pattern. All lesions that demonstrated all three of these features were benign.

Histologic diagnosis - A definitive diagnosis of a GIST can only be made histologically. Endoscopic biopsy is unlikely to be helpful because the lesion is beyond the mucosa and thus the grasp of the forceps. Endosonography-guided fine needle aspiration (EUS-FNA) can target the lesion, but the diagnostic yield of
cytology is low. Some investigators have found that the addition of immunohistochemical characterization of specimens obtained by EUS-FI'.IA may improve ihe accuracy for diagnosis of malignant GISTs compared to EUS alone

with EUS alone for determining malignancy was 91 versus 78 percent

[:,iJ,?:i] lnonereport,theoverall accuracyof EUSwithfineneedleaspirationandhistologicstainingcompared [?l] The addition of Ki-67 immunohistochemical staining increased the accuracy to 100 percent. Experience with EUS guided trucut biOpSyiSlimited.(See ,'t. --. ::, ' ' 'ii':il f ;;' ., ,, ,,'t 'ili,' ;r'!' : ,r t'i.r' f :* iilniliand il*d***+li:i t':tt _+ td 'r"_ .tiilt liiitil*rj )

Endoscopic resection using endoscopic submucosaldissection has been described in two series Ir',ir1]. Successful endoscopic resection is reported, but remains controversial because of the risk of positive margins, tumor spillage, and perforation [I"i]. Surgical and endoscopic options for treatment of localized GISTs are discussed in detail elsewhere, as is neoadjuvant rm*tlnih for large or borderline resectable tumors. (See "i.-,-;;:t

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Observation versus resection lt was previously thought that intramural mesenchymal tumors of the gastrointestinal tract smaller than 3 cm in maximal diameter had a low enough malignant potential to justify observation rather than resection. However, many of these tumors prove to be GlSTs, and the current thinking is that all GISTs have the potential to behave in a malignant fashion, particularly if they are over '1 cm in size. :tr.: 1: #r:(See"t'; lt::r+l+g;.i* ii' ;ll 11. , 'l' :rii: -',.'-'-r:1'l-.; r .'.''rr+tl *l
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Stable submucosal lesions <1 cm with EUS findings suggestive of benignity may be followed conservatively. An optimal surveillance strategy for asymptomatic lesions has not been established. We suggest following a protocol similar to that used for esophageal leiomyomas (ie, performing an EUS every 12 months). Resection

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is advised if lesions become symptomatic, increase in size, or show sonographic malignant features. (See

Given that endoscopic appearance is almost never diagnostic, and that an EUS-guided fine-needle aspiration

biopsy may not be sufficient to distinguish between a GIST and a leiomyoma, larger tumors should be surgically resected. ln addition, these lesions should be resected because of an increased frequency of complications and the difficulty in excluding malignancy preoperatively. (See 111".;,;;*1!r*qj,:,:f *t

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i). These lesions arise from the fourth and rarely the second gastric wall layer. lmmunohistochemical studies on aspirates are positive for smooth muscle actin and desmin and negative for c-kit (CD 117). (See llLpttllrl::*i*1,ii;,
and distinguishing them from other submucosal lesions including leiomyosarcomas (i-:ii":i.r":i*
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Lipomas are benign intramucosal tumors of mature lipocytes that are commonly incidental findings on colonoscopy and endoscopy. They can be seen in any part of the gastrointestinaI tract, although they are most common in the lower gastrointestinal tract. Lipomas are rarely symptomatic, but may result in hemorrhage, abdominal pain, and intestinal obstruction [i{]. They have no malignant potential. LIPOMA

Endoscopic appearance A lipoma commonly appears as an isolated solitary bulge located in the Gl tract with normal overlying mucosa, a yellowish hue, and a smooth regular appearance. When probed, they are soft and usually collapse to create an indentation known as the "pillow or cushion sign." Biopsy forceps may grasp the overlying mucosa to create the "tenting sign," by pulling the mucosa away from the submucosal growth. They are commonly small (less than 4 centimeters). ln one report of seven lesions (six of which were proven to be a lipoma by EUS) a pillow sign on endoscopy had low sensitivity (40 percent) but high specificity (99
percent) [1].

Endosonographic findings - The five layers of the gastrointestinal tract should be easily identified using low frequency imaging. Lipomas are hyperechoic, homogeneous lesions with regular margins arising from the submucosa (third layer of the Gl tract) (i::r;lrrr"ii .5).
Diagnosis and treatment The diagnosis is almost always made by a characteristic endoscopic and endosonographic appearance. Biopsies usually show only normal mucosa. However, a tissue diagnosis may be made by either fine needle aspiration or a technique called a "tunnel biopsy," which permits the acquisition of lipocytes. The technique involves creation of a mucosal defect (using a needle knife incision, the biopsy forceps itself, or electrocoagulation) through which deeper biopsies can be obtained.
Lipomas found incidentally should be followed expectantly. Endoscopic and endosonographic surveillance are not necessary. Local excision is advised for symptomatic lipomas or when the lesion cannot be distinguished from a malignant neoplasm (such as a liposarcoma). Endoscopic snare resection using polypectomy technique has been described l?i;*?.fi However, snare excision may be associated with perforation and hemorrhage, the risk of which is particularly increased for lesions greater than 2 cm in diameter [!l;i,ff;]. To reduce the risk, endoloop ligation prior to resection has been reported ffii-1. Endoloop ligation as stand-alone therapy (without resection) has also been reported [r'-r,] This approach was successful in a series of 10 patients with

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pedunculated submucosal tumors [tt:], six of whom had lipomas, with no reported complication. However, a drawback was the lack of a reliable surgical specimen for pathology. Patients were instructed to retrieve specimens from stool, but this was successful in only 60 percent of cases. CARCINOID TUMOR Carcinoids are rare intramucosal tumors of endocrine cell origin with malignant potential and are commonly asymptomatic. (See,,i.i.ri:ir:;ii *j.iirt;"frtij: ri,t+t 'l r.*r ;it.'il l. "r't,;.;is".) They are commonly discovered incidentally during endoscopy, surgery, orautopsy. lnthe United States, carcinoids are most commonly found in the appendix, rectum, and ileum, while in Japan they are often located in the stomach, rectum, and duodenum [?*,.1i1] Rare complications include hemorrhage, abdominal pain, intestinalobstruction, and endocrine syndromes due to secretion of functionally active substances (particularly when they

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Carcinoids appear as small, round sessile or polypoid lesions with normal Endoscopic appearance overlying mucosa that rarely ulcerates ["f]1. They range in size from a few millimeters to a few centimeters. Gastric and ilealcarcinoids are commonly multiple, while those arising elsewhere are typically solitary (fit;,;litt-ll
4)

Carcinoids are homogeneous hypo- or isoechoic with regular margins. Endosonographic appearance - propria (second layer of the Gl tract) and can invade the submucosal layer They arise from the mucosai lamina (third layer)
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Diagnosis and treatment

The diagnosis and treatment of carcinoid tumors is discussed separately. (See

Granular cell tumors (GCT) are rare submucosal tumors of Schwann cell origin GRANULAR CELL TUMOR that are usually incidental findings on endoscopy and colonoscopy. They are most common in the oropharynx, skin, subcutaneous tissue, or breasts, but they can involve any part of the intestinal tract and the biliary tree [.i.i:.iii] Most intestinaltract lesions are found in the middle to lower third of the esophagus. lmmunostaining is usually positive for the S-100 protein. (See ,$g*l,i;-:ltriti:* tf *t-i:ii1rlfi:,i.i;.1;;*.) Granular cells tumors are considered benign, although malignant GCTs have been reported particularly when larger than 4 cm []lLl. These lesions are rarely associated with complications such as bleeding and lumen obstruction []/ :i[] Granular cell tumors usually appear as small isolated nodules or polyps located Endoscopic appearance in the Gl tract with normal overlying mucosa and a yellowish hue. The majority are small (<4 cm) and solitary, although multifocal lesions have been described ({i*Ut* 2) GCTs are usually hypoechoic, homogeneous lesions with smooth margins Endosonographic findings - submucosa (second or third layer of the Gl tract) (i1;,rr-*1,1) [;ilrj] arising from the mucosa and/or

Diagnosis and treatment Surveillance endoscopy is recommended for asymptomatic GCTs. GCTs that are not excised should be monitored by EUS for an increase in size every one to two years [2#]. Local endoscopic snare excision or removalwith multiple biopsies can be performed for small tumors limited to the mucosa. Thermal ablation of granular cell tumors by laser was reported in four patients [.li]1.
Duplication cysts (DC) are benign, rare anomalies that arise during early embryonic development. They are most frequently found in the proximal small intestine, although they can also be found in the esophagus, stomach, and colon. There are two general types. those that are adjacent to the lumen (having lost communication to the gastrointestinalwall), and those that are tubular and communicate directly with the lumen [.11.4t]. Duplication cysts are lined with stratified, ciliated, or columnar epithelium and contain a mucoid DUPLICATION GYSTS

fluid [4?,"{'li].

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The cysts are typically discovered incidentally on endoscopy or radiologic imaging since they only uncommonly cause symptoms. Complications are rare but may include dysphagia, abdominal pain, bleeding, and pancreatitis when located near the ampulla of Vater hl:l!]. While they are believed to have a low malignant potential, case reports have described malignant transformation ['i'i]. Duplication cysts can appear as a bulge with normal overlying mucosa, or as a Endoscopic appearance diverticulum that can vary in size from several millimeters to over 5 cm. They have a smooth and regular appearance without mucosal irregularities. They are most commonly diagnosed by CT scan or MRI since they are infrequently seen endoluminallY (fii.i:.rit* j)

cysts are usually anechoic homogeneous lesions with regular Endosonographic findings - Duplication margins arising from the submucosal (third layer) or extrinsic to the gastrointestinalwall. Their walls can be characterized by three- or five-layer structures. They also can contain septae, fluid levels, or echogenic material conslsting of layering debris or mucin (piri;,;;,i. r,i). Occasionally, a cyst appears as a solid lesion on CT scan due to the higher density elicited from debris particles within a cyst. EUS is helpful in discriminating a duplication cyst from a solid mass.
diagnosis can usually be made by the characteristic endoscopic and Diagnosis and treatment - The endosonographic appearance. EUS-guided FNA has been used to establish a diagnosis of an esophageal cyst [,lil], although this is not necessary and has a risk of causing infection ['ri;:r]. Management of asymptomatic cysts is usually expectant, but resection has been recommended based upon their potentialfor complications, including malignant transformation. However, prospective studies evaluating the natural history of duplication cysts are lacking. When symptomatic, duplication cysts can be treated surgically or endoscopically [",:]. Successfulendoscopic management of endoluminalcysts has been described using fine needle aspiration, needle knife cystostomy, and, when small, snare excision [411]
PANCREATIC REST

heterotopic consist of cystically dilated exocrine cells. Endocrine pancreatic tissue or a combination of exocrine and endocrine celltypes may also be seen ['1]il.

rest A pancreas) refers to ectopic pancreatic tissue. These rare submucosal tumors most commonly

pancreatic

(also known as ectopic pancreas, aberrant pancreas, and

Pancreatic rests are most frequently found in the distal stomach, duodenum, or proximaljejunum, but have also been reported within a Meckel's diverticulum, the gallbladder, bile ducts, and the minor and major papillae surgery, or autopsy. They are also [,.;:,:]. They are typically discovered incidentally during endoscopy, pancreatic rests from other submucosal help differentiate that may occasionally found on CT scan. CT findings lesions identified in one study included [:i#]:

. . . .

A flat-ovoid shape (long diameter to short diameter ratio of greater than 1.4) Location of the lesion in the antrum, pylorus, or duodenum An endoluminal growth pattern An ill-defined border o Prominent enhancement of the overlying mucosa

The study found ihat the presence of at least two of the above findings had a sensitivity of '100 percent and a specificity of 82.5 percent for diagnosing a pancreatic rest in the upper gastrointestinaltract []']1. The specificity increased to 100 percent if three of the above findings were present.
However, while pancreatic rests may be detected with CT scan, if a submucosal lesion is noted on upper

endoscopy, we suggest endoscopic ultrasound with endoscopic mucosal resection for further evaluation, as small lesions may be missed on CT scan. (See lf;:rllt,;r,;ll illltq1li;1elr,: ilj lis*t,t* i!*.1lli::1';l!ll above.) Complications of pancreatic rests are rare, but may include ulceration, gastric outlet obstruction, and

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malignancy

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Endoscopic appearance

A pancreatic rest appears as a submucosal nodule, usually with a central umbilication that corresponds to a draining duct.

Endosonographic findings Pancreatic rests are hypoechoic or intermediate echogenic heterogeneous lesions with indistinct margins. They most commonly arise from the third or fourth layer, or a combination of the two layers of the Gl tract. Anechoic areas within the lesion correlate with ductal structures [..1r1].
Diagnosis and treatment - The diagnosis can be made histologically from tissue obtained by biopsy forceps or snare excision, although techniques to obtain deeper biopsies (using jumbo biopsy forceps, tunnel biopsy, endoscopic mucosal resection, or EUS-guided Ff,lA) may be required [a*]. The management strategy should be guided by symptoms and suspicion for malignancy. Asymptomatic lesions can be followed expectantly. Endoscopic resection can be performed by standard snare, band ligation-assisted, or cap-assisted polypectomy technique [fi:]. Surgical resection is preferred to endoscopic resection when the muscularis
propria is involved.
VARICES

system.

Varices are blood vessels that distend as a result of a hypertensive portal or splenic venous

Endoscopic appearance Varices can be visualized in the esophagus, stomach, duodenum, and rectum. They typically appear as bluish enlarged vessels that are commonly tortuous and easily compressed with instrumental pressure. Gastric varices may be confused with thickened folds or a submucosal lesion. Endosonographic findings Varices are round anechoic structures arising from the lamina propria or submucosa Color Doppler can be used to detect blood flow, which will immediately confirm a vascular structure, distinguishing a varix from other anechoic subepithelial lesions such as a cyst. A potential problem using a dedicated echoendoscope to image small varices is the tendency to compress the varix by the instrument or with inflation of the transducer balloon. This can be overcome by using a catheter ultrasound probe (miniprobe) inserted through the working channel of an endoscope. The miniprobe permits precise endoscopic targeting of the varixwith a small diameter (about 3 mm) transducer that will not compress the varix. However, miniprobes lack Doppler capability.
Diagnosis and treatment

The diagnosis is based on the typical endoscopic and endosonographic

UNCOMMON LESIONS

including esophageal fibrovascular polyps, inflammatory fibroid polyps, pneumatosis cystoides, thickened

A variety of uncommon submucosal lesions can be seen endosonographically,

folds, fibromas, Brunner's gland nodules, gastrointestinalwall hematomas, and esophageal hemangiomas. However, their endosonographic descriptions have been heterogeneous and scarce [::j;]il. Thus, use of EUS to diagnose these lesions should be made on an individual case basis. AMERICAN GASTROENTEROLOGICAL ASSOCIATION GUIDELINES - The American Gastroenterological Association has issued a guideline on the management of gastric subepithelial masses [li-,,i], which can be general comments were included: Endoscopy alone is not reliable for detecting the etiology of a subepithelial gastric mass. Cross-sectional imaging techniques such as transabdominal ultrasonography, computed tomography, and magnetic resonance imaging are adequate for detecting the presence of normal or abnormal structures outside the gastric wall, but do not reliably distinguish between the various causes of masses

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arising within the gastric wall.

. . .

EUS is the most accurate imaging test for detecting the component of the gastric wall from which the

mass arises, information which, combined with the echogenicity of the mass, helps narrow the differential diag nosis. Patients with symptoms attributable to the mass should undergo endoscopic or surgical resection. Optimal management of incidentally detected, asymptomatic masses is unclear.

SUMMARY AND RECO MME NDATIO NS

r .

Endoscopic ultrasonography (EUS) has provided a major breakthrough for characterizing subepithelial lesions. lt is complementary to other methods for diagnosis (and treatment) of subepithelial lesions (i:il**,itii:iu .j) The sonographic appearances of some lesions are highly suggestive of the diagnosis for some lesions, while for others EUS provides complementary information to other diagnostic modalities. Hypoechoic lesions in the third and fourth layers are most prone to misclassification.

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GRAPHICS

Originating gastrointestinal tract layer of submucosal tumors

SMT/layer
GIST

Mucosa

Muscularis mucosa
Rare

submucosa

I I

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Most common

Lipoma Fibroma Carcinoid

Always Always Most common Most common Common Common Always

Granular cell tumor

Pancreatic rest

Duplication cyst (intramural)

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Diagram of the five-tayer echo pattern of the normar gastrointestinal wall

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ADVHT*TIA {SEHfigA} Courtesy of Mary Lee Krinsky, DO and Kenneth Binmoeller, MD.

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Duplication cyst "..':r:+*ax*p* * * **, *., * zz'l,*\\

Endoscopic view of esophageal compression (arrow) due to duplication cYst. Couftesy of Mary Lee Krinsky, DO and Kenneth
Binmoeller, MD.

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Rates of progression-free survival for GISTs of stomach, small

intestine, and rectum grouped by mitotic rate and tumor sizex

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gastric,629 small intestinal, 144 duodenal, and 111 rectal cancers, x Data are combined fortumors >5 cm. . Small number of cases. Adapted from: Miettinen, M, et al. Semin Diagn Pathol 2006; 23:70.
Based on long-term follow-up studies on 1055

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Leiomyoma

Endosonographic view of a leiomyoma. Note that the lesion arises from the muscularis propria (layer 4) and the hypoechoic, homogenous and well demarcated appearance. Couftesy of Mary Lee
Krinsky, DO and Kenneth Binmoeller, MD.

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Endosonographic view of a lipoma. Note the hyperechoic and homogenous character, and originating from the submucosal layer. Courtesy of Mary Lee Krinsky, DO, and Kenneth Binmoeller, MD.

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Duodenal carcinoid

Endoscopic view of a duodenal carcinoid (arrow). Carcinoids can appear as small, round sessile or polypoid lesions, They usually have normal overlying mucosa and rarely ulcerate, Courtesy of
Mary Lee Krinsky, DO and Kenneth Binmoeller, MD.

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Carcinoid tumor

Endosonographic view of a duodenal carcinoid tumor (arrow), Carcinoids are hypo- or isoechoic with regular margins. They arise from the mucosa/lamina propria (second layer of the GI tract) and can invade the submucosal layer. Couftesy of Mary Lee
Krinsky, DO and Kenneth Binmoeller, MD.

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Granular cell tumor

A) Endoscopic image of a subepithelial 3,5 cm esophageal mass later shown to be a granular cell tumor. B) Endosonographic image revealing a hypoechoic mass arising from the submucosa. Courtesy
of Mary Lee Krinsky, DO.

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Duplication cyst

Endosonographic view of an esophageal duplication cyst. Duplication cysts are usually anechoic homogeneous lesions with regular margins arising from the submucosal (third layer) or

extrinsic to the gastrointestinal wall.

and Kenneth Binmoeller, MD.

Courtesy of Mary Lee Krinsky, DO

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Stepwise evaluation of subepithelial tumors

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