0016-5107/91/3704-0449$03.00 GASTROINTESTINAL ENDOSCOPY Copyright © 1991 by the American Society for Gastrointestinal Endoscopy
Evaluation of submucosal upper gastrointestinal tract lesions by endoscopic ultrasound Gregory A. Boyce, MD, Michael V. Sivak, Jr., MD Thomas Rosch, MD, Meinhard Classen, MD David E. Fleischer, MD, H. Worth Boyce, Jr., MD Charles J. Lightdale, MD, Jose F. Botet, MD Robert H. Hawes, MD, Glen A. Lehman, MD Cleveland, Ohio, Munich, Germany, Washington, DC, New York, New York, and Indianapolis, Indiana
The proper diagnosis of submucosal upper gastrointestinal tract mass lesions by endoscopy or barium study is difficult. Differentiation between submucosal tumors, vascular structures, and extrinsic organs is often impossible. We performed endoscopic ultrasound examination of 91 patients with upper gastrointestinal submucosal mass lesions. Endoscopic ultrasound was accurate in determining the site of origin in 48 of 50 cases where pathology or angiography comparison was available. Leiomyoma, lipoma, varices, and carcinoma had characteristic ultrasonographic findings. Endoscopic ultrasound is a useful procedure in the evaluation of upper gastrointestinal submucosal mass lesions. (Gastrointest Endosc 1991;37:449-454)
Precise diagnosis is frequently problematic for upper gastrointestinal submucosal mass lesions seen at endoscopy or demonstrated by gastrointestinal roentgenograms. It is often impossible to determine whether an apparent submucosal lesion is a tumor within the wall of the gut, a contiguous vascular structure, or due to extrinsic compression by an adjacent organ or mass. Several methods for obtaining cytologic and tissue samples from submucosal lesions have been described including aspiration with a needle and obtaining biopsies with various needle devices and large forceps. However, the diagnostic yield of these techniques is relatively low. 1- 4 A "lift and cut" snare technique has also been described, but this entails an increased risk of perforation. 5 Placement of a high frequency transducer in close proximity to the upper gastrointestinal tract wall by endoscopic ultrasonography (EUS) provides a detailed image of the wall structure and adjacent organs. 6- 9 EUS should be useful in determining the origin of submucosal abnormalities noted during upper endosReceived January 7,1991. Accepted March 4,1991. From the Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio; Technical University of Munich, Munich, Germany; Georgetown University, Washington, DC; University of South Florida Tampa, Florida; Memorial Sloan-Kettering, New York, New York; and Indiana University, Indianapolis, Indiana. VOLUME 37, NO.4, 1991
copy. A more accurate appraisal of the nature of such a lesion should therefore be possible. We reviewed our experience with EUS in the evaluation of submucosal abnormalities and compared EUS and pathologic findings in order to assess the accuracy of the procedure in predicting the origin and nature of these lesions. MATERIALS AND METHODS
EUS was performed in 91 patients who were thought to have submucosal lesions in the esophagus, stomach, or duodenum as demonstrated at endoscopy or by upper gastrointestinal x-rays. EUS instruments have an optical system with an oblique orientation and a transducer with a mechanically rotating acoustic mirror in the distal tip (Olympus Corporation of America, Lake Success, N. Y.). The latter feature provides a 360-degree sector scan perpendicular to the long axis of the insertion tube. Ultrasound frequencies of 7.5 mHz (Olympus GF UM-2), 10 mHz (Olympus prototype), or 12 mHz (Olympus GF UM-3) were utilized. These instruments display the gastrointestinal wall as a five-layer sonographic pattern. Various agents, administered intravenously, were used for sedation, and patients were usually placed in the left lateral decubitus position for the procedure. The distal end of the EUS instrument containing the transducer was maneuvered by endoscopic observation to the area of interest and scanning was then performed. For lesions in the esophagus, EUS was performed with a water-filled balloon over the transducer portion of the insertion tube to 449
Figure 1. A, EUS of water-filled stomach demonstrating normal five-layer upper gastrointestinal tract wall structure. B, Five-layer structure of esophageal wall with adjacent azygous vein and aorta. provide a proper interface for ultrasonography. EUS also can be performed by filling an organ with water (Figs. 1 and 2), and this method plus the water-filled balloon was utilized in the stomach and duodenum. Size, echodensity, border characteristics, and apparent site of origin of the submucosal lesions were determined by EUS, and these findings were compared to pathology or angiography in 50 cases.
RESULTS
The EUS diagnosis for 91 submucosal lesions by anatomical site is shown in Table 1. EUS was performed for apparent submucosal lesions of the esophagus in 28 patients. EUS correctly predicted the histologic layer of origin of these lesions in 13 of the 14 cases for which pathology was available (Table 2). Leiomyoma (N = 15) was the most common diagnosis among the esophageal lesions and all of these had a similar EUS appearance of a round hypoechoic mass with smooth margins that was contiguous to the muscularis propria layer (Fig. 2A). There were three cases of esophageal compression by bron450
Figure 2. A, Esophageal leiomyoma, well-demarcated hypoechoic mass contiguous with muscularis propria. B, Bronchogenic carcinoma, irregular hypoechoic mass disrupting wall structure with invasion of aortic wall.
chogenic carcinoma and one of metastatic breast cancer, and in these cases the EUS findings consisted of a hypoechoic mass disrupting the muscularis propria and submucosa layers with an irregular outer margin (Fig. 2B). EUS demonstrated two granular cell tumors as hypoechoic round masses with smooth margins arising from the submucosa layer. EUS was used to evaluate 55 submucosal lesions in the stomach. EUS correctly demonstrated the site of origin of all 29 lesions for which pathologic confirmation was available with the exception of one submucosal neurofibroma that was misinterpreted as an epithelial polyp (Table 3). Leiomyoma was the most common lesion with 18 cases (9 confirmed by pathology). The EUS appearance of this lesion was similar to that of esophageal leiomyoma with the exception of hyperechoic foci in several tumors over 3 em in diameter (Fig. 3). The malignant nature of one of these was suggested by its irregular outer margin and GASTROINTESTINAL ENDOSCOPY
Table 1. Submucosal lesions examined by EUS Diagnosis Esophagus (N = 28) Leiomyoma Bronchogenic carcinoma Granular cell tumor Fibrovascular polyp Breast carcinoma Hematoma Lymphoma Duplication cyst Submucosal cyst Submucosal tumor Stomach (N = 55) Leiomyoma Varix Gastric cancer Gastritis Extrinsic organ Aberrant pancreas Normal wall Leiomyosarcoma Neurolemmoma Fibrous histiocytoma Adrenal cyst Splenic cyst Lipoma Fibroma Neurofibroma Splenic implant Duodenum (N = 8) Lipoma Gallbladder Hyperplastic polyp Brunner's gland nodule Neurinoma Pancreatic pseudocyst Carcinoid Total
Table 2. Comparison of EUS and pathology, esophagus (N No. of patients 15 3
2 2 1 1 1 1 1 1
18
10 5 3 3 3 2 2 2 1 1 1 1 1 1 1
N
EUS findings
Bronchogenic carcinoma
3 Disrupts submucosa and
Lymphoma Leiomyoma
1 5
Fibrovascular polyp Granular cell tumor Metastatic breast carcinoma
2
muscularis, hypoechoic, irregular border Submucosal, hypoechoic Within muscularis propria, hypoechoic (small hyperechoic foci in large tumors), smooth outer border Submucosal with mixed echogenicity Submucosal, hypoechoic, smooth border Disrupts layer structure, irregular outer margin
2 1
1 1 1 1 1 1
91
3/3 1/1 5/5
1/2" 2/2 1/1
" One case interpreted as leiomyoma.
Table 3. Comparison of EUS with pathology, stomach (N Diagnosis Leiomyoma
N
EUS findings
9 Within muscularis propria,
Carcinoma
4
Leiomyosarcoma
2
Neurolemmoma
2
Varix
7
Neurofibroma Adrenal cyst
1 1
Aberrant pancreas
1
2
large size, the diameter of this lesion being over 5 cm. The other was 1.5 cm in diameter with EUS characteristics of a leiomyoma and was found in a patient who had undergone a previous resection of a leiomyosarcoma. The EUS appearance in four cases of infiltrating gastric carcinoma was that of a hypoechoic mass with disruption of the submucosa and muscularis propria. Gastric varices appeared as linear, hypoechoic structures with a smooth outer margin (Fig. 4). Demonstration of the normal five-layer sonographic structure and normal thickness of the gastric wall differentiated compression by adjacent organs, cysts, and extrinsic tumor from intrinsic submucosal lesions. Aberrant pancreas was seen as a well-circumscribed, hypoechoic submucosal lesion with a central cystic structure. Eight duodenal submucosal lesions were evaluated by EUS (Table 1). The site of origin was correctly demonstrated in all seven cases in which pathologic confirmation was available (Table 4 and Fig. 5). VOLUME 37, NO.4, 1991
Diagnosis
=14)
Agree with pathology
Fibrous histiocytoma 1 Splenic remnant 1
hypoechoic (hyperechoic foci in larger tumors), smooth border Within submucosa, muscularis; disruption of layers; (adjacent adenopathy, 1 case) Within muscularis propria, hypoechoic (hyperechoic foci within tumor), irregular margin in one case Mixed exhogenicity within submucosa and muscularis Submucosal, hypoechoic, linear Intermediate echogenicity Extrinsic, hypoechoic with smooth border Submucosal with central hypoechoic area Extrinsic, hypoechoic Hypoechoic mass with multiple vascular structures
=29) Agree with pathology
9/9
4/4
2/2
2/2
7/7"
oN 1/1 1/1 1/1 1/1
" Four pathologic and three angiographic correlation. b Interpreted as epithelial polyp.
DISCUSSION
EUS is the only currently available technique that provides images of the structure of the wall of the gastrointestinal tract. Studies of the wall at EUS frequencies of from 7.5 to 12 MHz consistently demonstrate a sonographic pattern with five layers. The interpretation of this finding has been a matter of some debate, one view being that there is a precise 451
Figure 3. s, Submucosal mass lesion, body of stomach at endoscopy. b, HYPOeChoic mass contiguous with the muscularis propria (arrow) at EUS. L, leiomyoma; A, antrum of stomach; B, body of stomach; e, ultrasound endoscope transducer. Figure 4. s, Submucosal mass lesion, cardia of the stomach at endoscopy (arrow). b, EUS findings of multiple submucosal hYPOeChoic linear structures consistent with gastric varices (arrow). Figure 5. s, Submucosal mass lesion, distal duodenal bulb at endoscopy (arrow). b, Hyperechoic submucosal lesion consistent with lipoma (arrow).
452
GASTROINTESTINAL ENDOSCOPY
Table 4. Comparison of EUS and pathology, duodenum (N Diagnosis
N
EUS findings
=7)
Agree with pathology
2/2 1/1
Lipoma Epithelial polyp
2 Submucosal, hyperechoic 1 Mucosal, intermediate
Brunner's gland nodule Neurinoma Pancreatic pseudocyst Carcinoid
1 Mucosal, hypoechoic
1/1
1 Submucosal, hypoechoic 1 Extrinsic, hypoechoic,
1/1 1/1
echogenicity
smooth border
1 Submucosal, hypoechoic,
1/1
smooth border
relation between individual sonographic layers and the actual anatomic-histologic features of the gut wall. Ultrasonic waves are reflected when they pass through tissues of different acoustic impedance. If the distance between two tissues of different acoustic impedance is less than the resolution power of the instrument, only one echo will be observed. The sonographic appearance of the wall depends in part on the characteristics of the ultrasound imaging system and the distances between acoustic interfaces. 1o Therefore, the sonographic pattern of the gut wall is undoubtedly not the simplistic representation of the various histologic layers. For practical purposes, however, the outermost or fourth hypoechoic layer can be taken as representing the muscularis propria. 6-9 The inner three layers therefore correspond to the mucosa and submucosa including the muscularis mucosae. The outermost (fifth) layer therefore represents the serosa or adventitia. EUS lends itself readily to the staging of gastrointestinal malignancy since it provides a representation of the histologic components of the bowel wall. The extent of disruption of the normal five-layer sonographic pattern of the wall by cancer and lymphoma has been utilized to assess the depth of malignant invasion. n -13 EUS findings can be used in the TNM system of cancer staging and are highly accurate as regards depth of tumor invasion while being somewhat less reliable with respect to lymph node involvement. EUS is also of benefit in a variety of lesions, other than cancer and lymphoma, that arise within the gastrointestinal wall. These have a less destructive appearance at endoscopy. The mucosal surface is smooth, similar in color to the surrounding mucosa, and without ulceration or erosion. Lesions with this appearance are often described as submucosal tumors since they frequently arise from histologic layers of the wall deep to the mucosa. They can also be mucosal in origin and are usually presumed to be benign unless large or ulcerated. However, the true size of submucosal lesions may not be evident at endoscopy, and they are not necessarily benign. VOLUME 37, NO.4, 1991
The typical endoscopic findings of submucosal tumor are usually attributed to a leiomyoma that has arisen in the muscularis propria of the bowel wall since this tumor is relatively common. Leiomyoma was the EUS diagnosis in 33 cases in the present series. All had a similar appearance of a well-circumscribed, hypoechoic mass contiguous with the muscularis propria, a characteristic description that is in agreement with those of other series. 14• 15 Although there are no known pathognomonic EUS findings for leiomyosarcoma, a large lesion with an irregular outer margin is suggestive of malignancy. Although the true size of a submucosal lesion may not be apparent at endoscopy, a much closer estimate can be obtained by EUS. Nakazawa et aI,16 found in a study of resected leiomyosarcomas that irregularly shaped sonolucent areas within a myogenic tumor were indicative of malignancy. However, sonolucent foci were noted in large but nevertheless benign leiomyomas in our series, and hyperechoic foci were demonstrated in one leiomyosarcoma. Certain lesions that arise in the mucosa or submucosa may also have an endoscopic or radiographic appearance that is similar to that of mural tumors or extraluminal abnormalities that compress the gastrointestinal wall. Carcinoid tumor, pancreatic rest, and, on occasion, large polyps may have some of the endoscopic and radiographic characteristics of true submucosal lesions such as the leiomyoma. EUS demonstrates that such lesions arise from one or more of the innermost three sonographic layers and not the fourth hypoechoic layer as with leiomyoma or leiomyosarcoma. Endoscopic biopsy specimens are relatively superficial and do not reveal the pathologic nature of these lesions in all cases. However, a correct diagnosis can often be inferred from a combination of endoscopic appearance and localization of the lesion to a particular sonographic layer by EUS. For example, the EUS findings of a hyperechoic well-circumscribed subepithelial mass are characteristic of lipoma and obviate further intervention to determine the nature of the lesion or to remove it. Extraluminal compression by an adjacent organ or vascular structure, whether normal or abnormal, or a mass can produce endoscopic findings that mimic those of a mural lesion. The extraluminal nature of this type of abnormality is easily demonstrated by EUS since the normal five-layer structure of the wall is preserved in the region of the lesion. However, adjacent malignant tumors can also invade the gastrointestinal wall. All malignant lesions in our series disrupted the five-layer structure of the wall and had markedly irregular outer margins and/or associated enlarged lymph nodes. On occasion, large vascular structures can cause deformity of the gastrointestinal wall that is difficult to differentiate at endoscopy from abnormalities arising within the wall. EUS proved to 453
be especially helpful in these cases as the linear, sonolucent appearance of vascular structures is highly characteristic. The results of this study indicate that EUS is a useful procedure in the evaluation of a variety of upper gastrointestinal lesions that appear to have a submucosal origin at endoscopy or on UGI x-rays. EUS provides accurate information about the size and location of such lesions in relation to the gastrointestinal wall. Although a pathologic diagnosis is not possible by EUS, the procedure demonstrates whether the lesion is cystic, solid, or vascular. EUS can localize a lesion that is intrinsic to the gastrointestinal wall to one or more of the histologic layers so that it is frequently possible to infer a correct diagnosis from this information. Many different types of abnormalities may produce the endoscopic or radiographic findings that are typical of a submucosal tumor. Since EUS provides greater certitude about the nature of these lesions, it may also alter subsequent management. EUS is currently limited by variations in operator interpretation, and the lack of information regarding the EUS findings of less common disorders. Further improvements in the maneuverability and optics of EUS instruments, and the development of a submucosal tissue sampling capability would further enhance the utility of EUS in the evaluation of submucosal lesions in the upper gastrointestinal tract.
REFERENCES 1. Soeda S, Kondo N, Akashi M, Aspiration biopsy of the stomach, efficient procedure for evaluating submucosal tumor. Stomach Intestine 1976;11:425-30. 2. Shimamoto M, Watanabe N, Tuneika K. Histologic diagnosis of gastric submucosal tumor with particular reference to newly devised needle biopsy. Prog Dig Endosc 1980;16:6-12.
454
3. Harasawa K, Asahi S, Nisimura T. Cytological diagnosis of submucosal tumor transendoscopic thorny needle biopsy. Gastroenterol Endosc 1984;26:596. 4. Kaneko E, Kumagai J, Honda N, Nakamura S, Kino I. Evaluation of the new giant-biopsy forceps in the diagnosis of mucosal and submucosal lesions. Endoscopy 1983;15:322-6. 5. Martin TR, Onstad GR, Silvis SE, Vennes JA. Lift and cut biopsy technique for submucosal sampling. Gastrointest Endosc 1976;23:29-30. 6. Tio TL, Tytgat GNJ. Endoscopic ultrasonography of normal and pathologic upper gastrointestinal wall structure. Comparison of studies in vivo and in vitro with histology. Scand J Gastroenterol1986;21(suppl123):27-33. 7. Aibe T, Fuji T, Okita K, Takemoto K. A fundamental study of normal layer structure of the gastrointestinal wall visualized by endoscopic ultrasonography. Scand J Gastroenterol 1986; 21(suppl123):6-15. 8. Bolondi L, Caletti G, Casanova P, Villanacci V, Grigioni W, Labo G. Problems and variations in the interpretation of the ultrasound features of the normal upper and lower GI tract wall. Scand J Gastroenterol 1986;21(suppl 123):16-26. 9. Kimmey MB, Martin RW, Haggitt RC, Wang KY, Franklin DW, Silverstein FE. Histologic correlates of gastrointestinal ultrasound images. Gastroenterology 1989;96:433-41. 10. Boscaini M, Montori A. Transrectal ultrasonography: interpretation of normal intestinal wall structure for the preoperative staging of rectal cancer. Scand J Gastroenterol 1986;21(suppl 123):87-98. 11. Tio TL, Cohen P, Coene PP. Endosonography and computed tomography of esophageal carcinoma. Preoperative classification compared to the new (1987) TNM system. Gastroenterology 1989;96:1478-86. 12. Lightdale CJ, Botet JF, Brennan MF. Endoscopic ultrasonography compared to computerized tomography for preoperative staging of gastric cancer [Abstract). Gastrointest Endosc 1989;35:154-5. 13. Yasuda K, Mukai H, Fujimoto S. The diagnosis of pancreatic cancer by endoscopic ultrasonography. Gastrointest Endosc 1988;34:1-8. 14. Dancygier H, Classen M. Endoscopic ultrasonography in esophageal diseases. Gastrointest Endosc 1989;35:220-5. 15. Yasuda K, Nakajima M, Yoshida S, Kiyota K, Kawai K. The diagnosis of submucosal tumors of the stomach by endoscopic ultrasonography. Gastrointest Endosc 1989;35:10-5. 16. Nakazawa S, Yoshino J, Nakamura T, et a1. Endoscopic ultrasonography of gastric myogenic tumor. A comparative study between histology and ultrasonography. J Ultrasound Med 1989;8:353-9.
GASTROINTESTINAL ENDOSCOPY
Evaluation of submucosal upper gastrointestinal tract lesions by endoscopic ultrasound Gregory A. Boyce, MD, Michael V. Sivak, Jr., MD Thomas Rosch, MD, Meinhard Classen, MD David E. Fleischer, MD, H. Worth Boyce, Jr., MD Charles J. Lightdale, MD, Jose F. Botet, MD Robert H. Hawes, MD, Glen A. Lehman, MD Cleveland, Ohio, Munich, Germany, Washington, DC, New York, New York, and Indianapolis, Indiana
The proper diagnosis of submucosal upper gastrointestinal tract mass lesions by endoscopy or barium study is difficult. Differentiation between submucosal tumors, vascular structures, and extrinsic organs is often impossible. We performed endoscopic ultrasound examination of 91 patients with upper gastrointestinal submucosal mass lesions. Endoscopic ultrasound was accurate in determining the site of origin in 48 of 50 cases where pathology or angiography comparison was available. Leiomyoma, lipoma, varices, and carcinoma had characteristic ultrasonographic findings. Endoscopic ultrasound is a useful procedure in the evaluation of upper gastrointestinal submucosal mass lesions. (Gastrointest Endosc 1991;37:449-454)
Precise diagnosis is frequently problematic for upper gastrointestinal submucosal mass lesions seen at endoscopy or demonstrated by gastrointestinal roentgenograms. It is often impossible to determine whether an apparent submucosal lesion is a tumor within the wall of the gut, a contiguous vascular structure, or due to extrinsic compression by an adjacent organ or mass. Several methods for obtaining cytologic and tissue samples from submucosal lesions have been described including aspiration with a needle and obtaining biopsies with various needle devices and large forceps. However, the diagnostic yield of these techniques is relatively low. 1- 4 A "lift and cut" snare technique has also been described, but this entails an increased risk of perforation. 5 Placement of a high frequency transducer in close proximity to the upper gastrointestinal tract wall by endoscopic ultrasonography (EUS) provides a detailed image of the wall structure and adjacent organs. 6- 9 EUS should be useful in determining the origin of submucosal abnormalities noted during upper endosReceived January 7,1991. Accepted March 4,1991. From the Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio; Technical University of Munich, Munich, Germany; Georgetown University, Washington, DC; University of South Florida Tampa, Florida; Memorial Sloan-Kettering, New York, New York; and Indiana University, Indianapolis, Indiana. VOLUME 37, NO.4, 1991
copy. A more accurate appraisal of the nature of such a lesion should therefore be possible. We reviewed our experience with EUS in the evaluation of submucosal abnormalities and compared EUS and pathologic findings in order to assess the accuracy of the procedure in predicting the origin and nature of these lesions. MATERIALS AND METHODS
EUS was performed in 91 patients who were thought to have submucosal lesions in the esophagus, stomach, or duodenum as demonstrated at endoscopy or by upper gastrointestinal x-rays. EUS instruments have an optical system with an oblique orientation and a transducer with a mechanically rotating acoustic mirror in the distal tip (Olympus Corporation of America, Lake Success, N. Y.). The latter feature provides a 360-degree sector scan perpendicular to the long axis of the insertion tube. Ultrasound frequencies of 7.5 mHz (Olympus GF UM-2), 10 mHz (Olympus prototype), or 12 mHz (Olympus GF UM-3) were utilized. These instruments display the gastrointestinal wall as a five-layer sonographic pattern. Various agents, administered intravenously, were used for sedation, and patients were usually placed in the left lateral decubitus position for the procedure. The distal end of the EUS instrument containing the transducer was maneuvered by endoscopic observation to the area of interest and scanning was then performed. For lesions in the esophagus, EUS was performed with a water-filled balloon over the transducer portion of the insertion tube to 449
Figure 1. A, EUS of water-filled stomach demonstrating normal five-layer upper gastrointestinal tract wall structure. B, Five-layer structure of esophageal wall with adjacent azygous vein and aorta. provide a proper interface for ultrasonography. EUS also can be performed by filling an organ with water (Figs. 1 and 2), and this method plus the water-filled balloon was utilized in the stomach and duodenum. Size, echodensity, border characteristics, and apparent site of origin of the submucosal lesions were determined by EUS, and these findings were compared to pathology or angiography in 50 cases.
RESULTS
The EUS diagnosis for 91 submucosal lesions by anatomical site is shown in Table 1. EUS was performed for apparent submucosal lesions of the esophagus in 28 patients. EUS correctly predicted the histologic layer of origin of these lesions in 13 of the 14 cases for which pathology was available (Table 2). Leiomyoma (N = 15) was the most common diagnosis among the esophageal lesions and all of these had a similar EUS appearance of a round hypoechoic mass with smooth margins that was contiguous to the muscularis propria layer (Fig. 2A). There were three cases of esophageal compression by bron450
Figure 2. A, Esophageal leiomyoma, well-demarcated hypoechoic mass contiguous with muscularis propria. B, Bronchogenic carcinoma, irregular hypoechoic mass disrupting wall structure with invasion of aortic wall.
chogenic carcinoma and one of metastatic breast cancer, and in these cases the EUS findings consisted of a hypoechoic mass disrupting the muscularis propria and submucosa layers with an irregular outer margin (Fig. 2B). EUS demonstrated two granular cell tumors as hypoechoic round masses with smooth margins arising from the submucosa layer. EUS was used to evaluate 55 submucosal lesions in the stomach. EUS correctly demonstrated the site of origin of all 29 lesions for which pathologic confirmation was available with the exception of one submucosal neurofibroma that was misinterpreted as an epithelial polyp (Table 3). Leiomyoma was the most common lesion with 18 cases (9 confirmed by pathology). The EUS appearance of this lesion was similar to that of esophageal leiomyoma with the exception of hyperechoic foci in several tumors over 3 em in diameter (Fig. 3). The malignant nature of one of these was suggested by its irregular outer margin and GASTROINTESTINAL ENDOSCOPY
Table 1. Submucosal lesions examined by EUS Diagnosis Esophagus (N = 28) Leiomyoma Bronchogenic carcinoma Granular cell tumor Fibrovascular polyp Breast carcinoma Hematoma Lymphoma Duplication cyst Submucosal cyst Submucosal tumor Stomach (N = 55) Leiomyoma Varix Gastric cancer Gastritis Extrinsic organ Aberrant pancreas Normal wall Leiomyosarcoma Neurolemmoma Fibrous histiocytoma Adrenal cyst Splenic cyst Lipoma Fibroma Neurofibroma Splenic implant Duodenum (N = 8) Lipoma Gallbladder Hyperplastic polyp Brunner's gland nodule Neurinoma Pancreatic pseudocyst Carcinoid Total
Table 2. Comparison of EUS and pathology, esophagus (N No. of patients 15 3
2 2 1 1 1 1 1 1
18
10 5 3 3 3 2 2 2 1 1 1 1 1 1 1
N
EUS findings
Bronchogenic carcinoma
3 Disrupts submucosa and
Lymphoma Leiomyoma
1 5
Fibrovascular polyp Granular cell tumor Metastatic breast carcinoma
2
muscularis, hypoechoic, irregular border Submucosal, hypoechoic Within muscularis propria, hypoechoic (small hyperechoic foci in large tumors), smooth outer border Submucosal with mixed echogenicity Submucosal, hypoechoic, smooth border Disrupts layer structure, irregular outer margin
2 1
1 1 1 1 1 1
91
3/3 1/1 5/5
1/2" 2/2 1/1
" One case interpreted as leiomyoma.
Table 3. Comparison of EUS with pathology, stomach (N Diagnosis Leiomyoma
N
EUS findings
9 Within muscularis propria,
Carcinoma
4
Leiomyosarcoma
2
Neurolemmoma
2
Varix
7
Neurofibroma Adrenal cyst
1 1
Aberrant pancreas
1
2
large size, the diameter of this lesion being over 5 cm. The other was 1.5 cm in diameter with EUS characteristics of a leiomyoma and was found in a patient who had undergone a previous resection of a leiomyosarcoma. The EUS appearance in four cases of infiltrating gastric carcinoma was that of a hypoechoic mass with disruption of the submucosa and muscularis propria. Gastric varices appeared as linear, hypoechoic structures with a smooth outer margin (Fig. 4). Demonstration of the normal five-layer sonographic structure and normal thickness of the gastric wall differentiated compression by adjacent organs, cysts, and extrinsic tumor from intrinsic submucosal lesions. Aberrant pancreas was seen as a well-circumscribed, hypoechoic submucosal lesion with a central cystic structure. Eight duodenal submucosal lesions were evaluated by EUS (Table 1). The site of origin was correctly demonstrated in all seven cases in which pathologic confirmation was available (Table 4 and Fig. 5). VOLUME 37, NO.4, 1991
Diagnosis
=14)
Agree with pathology
Fibrous histiocytoma 1 Splenic remnant 1
hypoechoic (hyperechoic foci in larger tumors), smooth border Within submucosa, muscularis; disruption of layers; (adjacent adenopathy, 1 case) Within muscularis propria, hypoechoic (hyperechoic foci within tumor), irregular margin in one case Mixed exhogenicity within submucosa and muscularis Submucosal, hypoechoic, linear Intermediate echogenicity Extrinsic, hypoechoic with smooth border Submucosal with central hypoechoic area Extrinsic, hypoechoic Hypoechoic mass with multiple vascular structures
=29) Agree with pathology
9/9
4/4
2/2
2/2
7/7"
oN 1/1 1/1 1/1 1/1
" Four pathologic and three angiographic correlation. b Interpreted as epithelial polyp.
DISCUSSION
EUS is the only currently available technique that provides images of the structure of the wall of the gastrointestinal tract. Studies of the wall at EUS frequencies of from 7.5 to 12 MHz consistently demonstrate a sonographic pattern with five layers. The interpretation of this finding has been a matter of some debate, one view being that there is a precise 451
Figure 3. s, Submucosal mass lesion, body of stomach at endoscopy. b, HYPOeChoic mass contiguous with the muscularis propria (arrow) at EUS. L, leiomyoma; A, antrum of stomach; B, body of stomach; e, ultrasound endoscope transducer. Figure 4. s, Submucosal mass lesion, cardia of the stomach at endoscopy (arrow). b, EUS findings of multiple submucosal hYPOeChoic linear structures consistent with gastric varices (arrow). Figure 5. s, Submucosal mass lesion, distal duodenal bulb at endoscopy (arrow). b, Hyperechoic submucosal lesion consistent with lipoma (arrow).
452
GASTROINTESTINAL ENDOSCOPY
Table 4. Comparison of EUS and pathology, duodenum (N Diagnosis
N
EUS findings
=7)
Agree with pathology
2/2 1/1
Lipoma Epithelial polyp
2 Submucosal, hyperechoic 1 Mucosal, intermediate
Brunner's gland nodule Neurinoma Pancreatic pseudocyst Carcinoid
1 Mucosal, hypoechoic
1/1
1 Submucosal, hypoechoic 1 Extrinsic, hypoechoic,
1/1 1/1
echogenicity
smooth border
1 Submucosal, hypoechoic,
1/1
smooth border
relation between individual sonographic layers and the actual anatomic-histologic features of the gut wall. Ultrasonic waves are reflected when they pass through tissues of different acoustic impedance. If the distance between two tissues of different acoustic impedance is less than the resolution power of the instrument, only one echo will be observed. The sonographic appearance of the wall depends in part on the characteristics of the ultrasound imaging system and the distances between acoustic interfaces. 1o Therefore, the sonographic pattern of the gut wall is undoubtedly not the simplistic representation of the various histologic layers. For practical purposes, however, the outermost or fourth hypoechoic layer can be taken as representing the muscularis propria. 6-9 The inner three layers therefore correspond to the mucosa and submucosa including the muscularis mucosae. The outermost (fifth) layer therefore represents the serosa or adventitia. EUS lends itself readily to the staging of gastrointestinal malignancy since it provides a representation of the histologic components of the bowel wall. The extent of disruption of the normal five-layer sonographic pattern of the wall by cancer and lymphoma has been utilized to assess the depth of malignant invasion. n -13 EUS findings can be used in the TNM system of cancer staging and are highly accurate as regards depth of tumor invasion while being somewhat less reliable with respect to lymph node involvement. EUS is also of benefit in a variety of lesions, other than cancer and lymphoma, that arise within the gastrointestinal wall. These have a less destructive appearance at endoscopy. The mucosal surface is smooth, similar in color to the surrounding mucosa, and without ulceration or erosion. Lesions with this appearance are often described as submucosal tumors since they frequently arise from histologic layers of the wall deep to the mucosa. They can also be mucosal in origin and are usually presumed to be benign unless large or ulcerated. However, the true size of submucosal lesions may not be evident at endoscopy, and they are not necessarily benign. VOLUME 37, NO.4, 1991
The typical endoscopic findings of submucosal tumor are usually attributed to a leiomyoma that has arisen in the muscularis propria of the bowel wall since this tumor is relatively common. Leiomyoma was the EUS diagnosis in 33 cases in the present series. All had a similar appearance of a well-circumscribed, hypoechoic mass contiguous with the muscularis propria, a characteristic description that is in agreement with those of other series. 14• 15 Although there are no known pathognomonic EUS findings for leiomyosarcoma, a large lesion with an irregular outer margin is suggestive of malignancy. Although the true size of a submucosal lesion may not be apparent at endoscopy, a much closer estimate can be obtained by EUS. Nakazawa et aI,16 found in a study of resected leiomyosarcomas that irregularly shaped sonolucent areas within a myogenic tumor were indicative of malignancy. However, sonolucent foci were noted in large but nevertheless benign leiomyomas in our series, and hyperechoic foci were demonstrated in one leiomyosarcoma. Certain lesions that arise in the mucosa or submucosa may also have an endoscopic or radiographic appearance that is similar to that of mural tumors or extraluminal abnormalities that compress the gastrointestinal wall. Carcinoid tumor, pancreatic rest, and, on occasion, large polyps may have some of the endoscopic and radiographic characteristics of true submucosal lesions such as the leiomyoma. EUS demonstrates that such lesions arise from one or more of the innermost three sonographic layers and not the fourth hypoechoic layer as with leiomyoma or leiomyosarcoma. Endoscopic biopsy specimens are relatively superficial and do not reveal the pathologic nature of these lesions in all cases. However, a correct diagnosis can often be inferred from a combination of endoscopic appearance and localization of the lesion to a particular sonographic layer by EUS. For example, the EUS findings of a hyperechoic well-circumscribed subepithelial mass are characteristic of lipoma and obviate further intervention to determine the nature of the lesion or to remove it. Extraluminal compression by an adjacent organ or vascular structure, whether normal or abnormal, or a mass can produce endoscopic findings that mimic those of a mural lesion. The extraluminal nature of this type of abnormality is easily demonstrated by EUS since the normal five-layer structure of the wall is preserved in the region of the lesion. However, adjacent malignant tumors can also invade the gastrointestinal wall. All malignant lesions in our series disrupted the five-layer structure of the wall and had markedly irregular outer margins and/or associated enlarged lymph nodes. On occasion, large vascular structures can cause deformity of the gastrointestinal wall that is difficult to differentiate at endoscopy from abnormalities arising within the wall. EUS proved to 453
be especially helpful in these cases as the linear, sonolucent appearance of vascular structures is highly characteristic. The results of this study indicate that EUS is a useful procedure in the evaluation of a variety of upper gastrointestinal lesions that appear to have a submucosal origin at endoscopy or on UGI x-rays. EUS provides accurate information about the size and location of such lesions in relation to the gastrointestinal wall. Although a pathologic diagnosis is not possible by EUS, the procedure demonstrates whether the lesion is cystic, solid, or vascular. EUS can localize a lesion that is intrinsic to the gastrointestinal wall to one or more of the histologic layers so that it is frequently possible to infer a correct diagnosis from this information. Many different types of abnormalities may produce the endoscopic or radiographic findings that are typical of a submucosal tumor. Since EUS provides greater certitude about the nature of these lesions, it may also alter subsequent management. EUS is currently limited by variations in operator interpretation, and the lack of information regarding the EUS findings of less common disorders. Further improvements in the maneuverability and optics of EUS instruments, and the development of a submucosal tissue sampling capability would further enhance the utility of EUS in the evaluation of submucosal lesions in the upper gastrointestinal tract.
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