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Mitsuhiro KIDA, Yusuke Kawaguchi, Eiji Miyata, Rikiya Hasegawa, Toru Kaneko,
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may lead to differences between this version and the Version of Record. Please cite this
article as doi: 10.1111/den.12854
252-0374, Japan
E-mail: m-kida@kitasato-u.ac.jp
Subepithelial lesions
EUS-FNA
Abstract
originating layer, echo level, and internal echo pattern etc. Lipoma, lymphangioma,
and cyst have characteristic features, therefore they have no need for EUS-FNA.
Ectopic pancreases and glomus tumors, which are originated from 3rd and 4th layer,
fundus or body are large and originated from 3rd and 4th layer (thickening of 4th
imaging differentiation of tumors originated from 4th layer is very difficult, even if
contrast echo is employed. Therefore EUS-FNA should be done in those tumor, but
the diagnostic yield for small lesions is not enough for clinical demands. Generally,
those tumors including small ones should be firstly followed up in 6 months, then
unusual SELs and SELs with malignant findings such as nodular, heterogeneous,
1, Introduction
and Subepithelial lesions etc. Furthermore, Vilmann et al reported the first case of
EUS-guided fine needle aspiration cytology/ biopsy (EUS-FNA) in 1992 (2), EUS,
(7.5-12 MHz) and a 9-layer structure with higher frequency (12-20MHz) (Figure 1).
evaluating its originating layer, its echo level, and its internal echo pattern etc.
Lipomas, Lymphangiomas, fibromas etc. are originated from 3rd layer and
layer (Figure 2). Ectopic pancreases are basically originated from 3rd layer, however
there are two types such as shallow type and deep type. Shallow type generally is
small and locates in the antrum, on the other hand deep type which is originated
from 3rd and 4th layer, is generally large, and locates in the middle and upper part of
sometimes 4th and 3rd layer, and granular cell tumors are mainly originated from 2nd
layer and sometimes 2nd and 3rd layer, especially in the stomach and colon.
Metastatic tumors are generally originated from 3rd layer and multiple lesions with
tumor, and on the other hand lymphangioma and cyst is detected as an anechoic
tumor (Figure 3). Neuroendocrine tumor (NET, called Carcinoid tumor in former
Concerning about the internal echo pattern, most of SELs are revealed as solid
pattern tumors, however cyst and lymphangioma are revealed cystic pattern tumor.
small. Schirrhous type gastric cancer and amyloidosis is basically not Subepithelial
unwell-demarcated contour.
A, GIST (Figure 4)
GISTs are the most commonly identified mesenchymal tumors in the stomach
and have malignant potential. GISTs arise from the interstitial cells of Cajal and
can be identified using immunohistochemical staining C-kit (CD117) and CD34 etc.
GISTs have occupied 70-90 % of SELs originated from 4th layer of the stomach (3,4).
GISTs located 46.4%-58% in the body, 21- 33.3% in the fundus, 13-18.9% in the
antrum, and 1.4-8% in the cardia (3,4). According to the NCCN (national
surgical operation. We have proposed malignant findings for SELs originated from
4th layer of the stomach in 1992 (5), which are ①more than 3cm, ②Nodular, ③
heterogeneous, ④anechoic area, ⑤ulceration. If some tumor has 3 or more
diagnose GIST. Concerning about EUS-FNA, sampling rate and diagnostic accuracy
for SELs less than 2cm is not satisfied clinically. Generally, EUS-FNA has a
diagnostic yield of 40% to 50 % for lesions measuring up to 10mm and 60 to 70% for
11 to 30mm, with a lower diagnostic yield for small lesion (7), although good
using 22-guage needle obtains a high yield (85.7% - 86%) for the diagnosis of gastric
staining such as C-kit (+), DOG1(+), CD34 (+), PDGFRA-mutations etc. can be
(12). Tumors <2cm did not metastasize if the number of mitoses was less than 5/50
HPFs. However, GISTs with a mitotic count greater than 6/50 HPFs showed high
although Aso et al reported a rare case of gastric GIST smaller than 20 mm with
furthermore the doubling time of high grade GISTs is 4.6 months, whereas that of
moderate -low grade GISTs is 14 months (14). In order to detect high grade GISTs,
from 4th layer are small. If the size and feature is not significantly changed, then
yearly follow up is recommended. When those tumors become more than 1-2cm,
EUS-FNA is recommended.
B, Leiomyoma (Figure 5)
Leiomyomas are benign tumors that arise from either the muscularis mucosae or
the muscularis propria. As mentioned before, leiomyoma looks like GIST, therefore
diagnosis. leiomyomas have occupied 60-80% of SMTs originated from 4th layer of
the esophagus. In the stomach leiomyomas are seen 63.6-80 % near the
esophago-cardiac junction, 1.5-14.2% in the body, 1.5-2.9% in the antrum, and 0- 2.9
GISTs and schwannoma is rare (0-3.5% and 0-3.7%) (3,5,16). In order to diagnose
leiomyoma, it is necessary to evaluate by histology with Desmin (+), C-kit (-), and
CD34 (-). Therefore, EUS-FNA are recommended for SELs originated from 4th layer
more than 1-2cm in size, whereas smaller SELs are followed up, except for SELs
with malignant sign such as nodular, heterogeneous, anechoic area, and ulceration.
C, Schwannoma (Figure 6)
Schwannomas are very low malignant potential tumors of spindle cells that
originate from any nerve having a Schwan cell sheath such as Auerbach’s plexus or
like GIST, therefore it is also difficult to differentiate schwannoma from GIST and
stomach SELs. In the stomach schwannomas are seen 57-81% in the body, 7.4-40%
in the antrum, and 0-29.6% in the fundus (3,4,15,16). Calcification is rarely seen in
evaluate by histology with S100 (+), C-kit (-), and CD34 (-). EUS-FNA is also
sometimes introduces gastrointestinal bleeding (17). Using EUS, there are two
types of ectopic pancreases such as shallow type and deep type. Ectopic pancreatic
tissue limited to the 3rd layer in shallow type and extended to 3rd and 4th layer.
Generally shallow type is small and exists in antral area, on the other hand deep
type is large and exists in middle and upper part of the stomach. In 1909, Heinrich
generally large and exists in the middle and upper part of the stomach. Heinrich Ⅱ
contains incomplete or lobular arrangement and lacks endocrine components. And
sometimes seen in ectopic pancreas. And ectopic pancreases rarely have cystic
components (less than 10%), although main part is consisted of solid components
(19). The common site of ectopic pancreas locates in the gastrointestinal tract:
Subepithelial lesion in the antrum with central dimpling (or umbilication) which
and sometimes ductal structure and cystic components. Concerning about deep type
of ectopic pancreas, which is generally located in the middle or upper part of the
stomach and large, is originated from 3rd and 4th layer. We call “thickening of 4th
layer”, this finding is mostly characteristic for ectopic pancreas (Figure 8).
D, Lipoma (Figure 9)
Lipomas are benign tumors composed of mature lipocytes and are frequently seen
lipomas usually present soft, solitary, not so high Subepithelial lesions with
yellowish color and cushion sign when pressed with biopsy forceps. Using EUS,
lipomas are originated from 3rd layer and hyperechoic SELs which are most
Nowadays NETs are classified into G1 (so called “carcinoid tumor” in former age),
G2, and G3 (so called neuroendocrine carcinoma; NEC) (20). NET is frequently
occurred in 40-50 years old, and sex ratio (M: F) is 2:1 (21). NET is often seen in the rectum,
sometimes polypoid lesion with dilated vessels and occasional central depression or
yield of mucosal biopsies from other SELs are usually low. Using EUS, NETs are
originated from 3rd and deep 2nd layer, and hypoechoic SEL. Rendi classified gastric
anaplastic, small- to intermediate-sized cells with high mitotic index and focal necrosis (22).
Ⅰ
For Type and Ⅱ, G-NETs, according to the national comprehensive cancer network
(NCCN) guideline, management of Type Ⅰand Ⅱ, G-NETs are simple surveillance or
endoscopic resection (ER) for tumors that are smaller than 20 mm in size, and without
resection, or ER is recommended for tumor that are greater than 20 mm in size, whether
single or multiple. Type Ⅲ, G-NET are recommended to manage in the same manner of
gastric carcinomas, except for tumors < 2cm can be considered endoscopic or wedge resection.
D-NETs are present in the ampullary region, local surgical resection with lymphadenectomy
D-NETs (>2cm) D-NETs of any size with lymph node involvement, should be treated by
limited surgical resection. However, the NCCN guidelines recommend endoscopic resection
for well localized D-NETs, whenever possible. In Japan, D-NETs less than 1cm are generally
treated by endoscopic technique, whereas D-NETs more than 1 cm in size are removed by
surgery.
from 3rd layer of the duodenum, however these tumors have tendency to invade
deeper layer and have lymph node metastasis, and become advanced, even if they
tumor with pain, but rarely in the stomach. The median age of patients with
Glomus tumors was 45 years old and sex ratio (M: F) is 1: 1.6. Fang reported that 61%
of patients complained of upper abdominal pain or fullness, 25% had bloody stool
and 14% were asymptomatic, and most (85%) of Glomus tumors exist in the antrum
as Subepithelial lesions sometimes with ulceration (23). Using EUS, Glomus tumor
is basically originated from 4th layer and sometimes connects with 3rd layer, various
patterns of echo level. Because Masson classified Glomus tumor into 4 types ; ①
(+), Vimentin (+), Laminin (+), CD34 (rarely), c-kit (-) (24). Most characteristic
and involving the neck or axilla, these tumors are much less common in adults and
present soft, solitary, not so high SELs with cushion sign when pressed with biopsy
forceps. Lymphangioma is cystic tumor which originates from 3rd layer and anechoic
Hamartomas are originated from 3rd layer, and consists of solid and cystic
tumor, in which gastric mucosa gastric gland migrates into the submucosa, and
Granular cell tumors are often seen in the esophagus, rarely in the stomach and
colon and are considered benign, and only small number of cases are malignant,
especially in the stomach. Endoscopically, granular cell tumors are generally small
(less than 20 mm in diameter), sessile SELs with a yellowish-white color and “molar
mainly 2nd layer, sometimes from 2nd and 3rd layer, especially in the stomach and
colon.
Brunneriomas are neoplasms of Brunner gland and are most frequent SELs in
the duodenum, originated from 3rd layer of the duodenum and basically a
6, EUS-FNA
A, Indications
diagnosis GIST from leiomyoma and schwannoma, and diagnosis of rare SELs such
as NET (carcinoid tumor), Glomus tumor, granular cell tumor, etc. Then the
indication of EUS-FNA for SELs is tumors originated from 4th layer, SELs with
malignant sign such as heterogeneous, nodular, ulceration, anechoic area etc., and
As mentioned before, EUS-FNA has a not enough diagnostic yield for small lesion
(8). Although EUS-FNB using 22-guage needle obtains a high yield (85.7% - 86%)
for the diagnosis of gastric SELs ≧2cm (10,11). Therefore, SELs originated from 4th
However, in order to prevent overlooking of high grade GIST, we have to make 1st
with malignant sign or unusual SELs even they are less than 1-2cm in size.
B, New technique
pancreas cancer etc. Because SELs are movable and hard. In this situation, cap
is, target lesion is catched by cap and suction, puncture a needle, make stroke about
7, Conclusions
Using EUS, it is practicable to diagnose SELs with originating layer, echo level
histologically, especially GIST, NET, et. Then EUS-FNA is very helpful for
by means of the ultrasonic endoscope. 1) the structure of layers of the gastric wall.
38(2):172-173,1992.
3) Min YW, Park HN, Min BH, et al: Preoperative predictive factors for
4) Seo SW, Hong SJ, Han JP, et al: Accuracy of a scoring system for the differential
227-237, 2011.
10) Lee JH, Cho CJ, Park YS, et al: EUS-guided 22-guage fine needle biopsy for the
485-492, 2016
11) Lee M, Min BH, Lee H, et al: Feasibility and diagnostic yield of endoscopic
ultrasonography-guided fine needle biopsy with a new core biopsy needle device in
16) Yoon JM, Kim GH, Park DY, et al: Endosonographic features of gastric
schwannoma: A single center experience. Clin Endosc 2016 Mar 15. ahead of print
17) Lee MJ, Chang JH, Maeng H, et al: Ectopic pancreas bleeding in the jejunum
18) Heinrich H: Ein Beitag zur Historogie des sogen akzessorischen pancreas.
19) O’Malley RB, Maturen KE, Al-Hawary MM, et al: Case of the season: ectopic
21) Soga J: Gastric carcinoids: A statistic evaluation of 1094 cases collected from the
23) Fang HQ, Yang J, Zhang FF, et al: Clinicopathological features of gastric
24) Wang ZB, Yuan J, Shi HY: Features of gastric glomus tumor: a clinicopathologic
1438-1448, 2014.
Using lower frequency, GI wall is detected 5-layer structure 1st & 2nd layer means
mucosa, 3rd layer submucosa 4th proper muscle layer and 5th subserosa and serosa.
Using high frequency, muscularis mucosae and border of inner and outer muscle
Endoscopy reveals a slightly elevated lesion in the lesser curvature of the body.
EUS detects a round, hypoechoic tumor originating from 4th layer. Histology shows
Endoscopy reveals an elevated lesion in the lesser curvature of the upper body. EUS
detects a round, hypoechoic tumor originating from 4th layer. Histology shows
Endoscopy reveals a slightly elevated lesion in the posterior wall the body. EUS
detects a round, hypoechoic tumor originating from 4th layer and elastography as a
hard tumor. Histology shows spindle cells with S – 100 positive by EUS-FNA
unwell-defined, hypoechoic tumor originating from 3rd layer with cystic area.
Endoscopy reveals an elevated lesion in the greater curvature of body. EUS detects
Endoscopy reveals an elevated, soft lesion in the antrum, which is measured about
2.5 cm in size by means of measuring rubber ring (outer 1.0 cm, inner 0.5 cm in
Endoscopy reveals an elevated lesion in the greater curvature of the upper body.
EUS detects a round, hypoechoic tumor originating from 3rd layer. Histology shows
Endoscopy reveals an elevated lesion with central dimpling in the duodenum. EUS
detects a hypoechoic tumor originating from 3rd layer and lymph nodes swelling.
Endoscopy reveals an elevated lesion in the antrum. EUS detects an anechoic tumor
Endoscopy reveals an elevated lesion in the greater curvature of body. EUS detects
a tumor originating from 3rd layer with septum and cystic area.
teeth appearance. EUS detects a hypoechoic tumor originating from 2rd layer. And
Endoscopy reveals a polypoid lesion with stalk in the duodenal bulb. EUS detects a
hypoechoic tumor originating from 3rd layer at stalk. And endoscopic polypectomy
Mucosa
{
First layer (border echo)
Second Layer
First layer (border echo)
Second Layer } Proper mucosa
Inner muscle
Sixth Layer
Proper Fourth Layer Seventh layer (border e.) Connective tissue
Muscle Eighth Layer Outer Muscle
Subserosa, Fifth Layer (border Ninth layer Subserosa,
Serosa echo) (border echo Serosa
Brunnerioma
Lymphangioma
Lipoma
Fibroma
Cyst
Ectopic Pancreas
Glomus Tumor
GIST
Leiomyoma
Schwanoma
HE C-kit
HE α-SMA
Figure 6, Schwannoma
EUS Elastography
Endoscopy HE S-100
Radial EUS
HE Synapt CromoG
HE S-100
HE