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E210 Original Article

Endoscopic Ultrasound for Differential Diagnosis of


Duodenal Lesions
Endoskopischer Ultraschall für die Differenzialdiagnose von Läsionen des
Zwölffingerdarms

Authors A. Pavlovic Markovic1, 2, T. Rösch3, T. Alempijevic1, 2, M. Krstic1, 2, D. Tomic1, 2, P. Dugalic4, A. Sokic Milutinovic1, 2,
M. Bulajic1, 5

Affiliations Affiliation addresses are listed at the end of the article.

Key words Zusammenfassung Abstract


● abdomen
"
! !
● duodenum

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"
Ziel: Tumore des Zwölffingerdarms sind selten Purpose: Duodenal tumors are rare and require a
● endoscopic ultrasonography
"
und erfordern eine andere Vorgehensweise als different management from that of esophagogas-
● duodenal lesion
"
ösophagogastrische Neoplasien. Die vorliegende tric neoplasia. The present study retrospectively
Studie analysiert retrospektiv die Merkmale von analyses the endoscopic ultrasound (EUS) fea-
duodenalen Tumoren sowohl epithelialen als tures of duodenal tumors of both epithelial and
auch subepithelialen Ursprungs im endoskopi- subepithelial origin.
schen Ultraschall (EUS). Materials and Methods: During a 12 year period,
Material und Methoden: Über einen Zeitraum von all duodenal tumors with histologic confirma-
12 Jahren wurden alle nach Operation oder Biopsie tion by surgery or biopsy were collected includ-
histologisch bestätigten Tumore des Duodenums ing endoscopic and endosonographic images.
einschließlich der Bilder aus Endoskopie und en- EUS images were analyzed for specific features
doskopischem Ultraschall gesammelt. EUS-Bilder (echogenicity, wall layer structure and relation,
wurden im Hinblick auf spezifische Merkmale outer margins) to possibly distinguish epithelial
(Echogenität, Struktur der Wandschichten und de- (polyps and carcinoma versus lymphoma) and
ren Beziehung, äußere Ränder) analysiert, um epi- subepithelial (tumor type) tumors.
theliale (Polypen und Karzinome im Gegensatz zu Results: 53/80 cases had histologic confirma-
Lymphomen) und subepitheliale (tumorartige) Tu- tion (mean age 53.1 ± 11.4 years, m:f = 33:20),
more zu unterscheiden zu können. 31 were epithelial (13 adenomas, 12 carcinomas,
Ergebnisse: Eine histologische Bestätigung (Durch- 6 lymphomas) and 22 subepithelial (11 GISTs,
schnittsalter 53,1 ± 11,4 Jahre, M:F = 33:20) lag in 7 Brunneromas, 1 lipoma, 3 NETs). EUS did not
received 29.12.2011
accepted 2.7.2012 53/80 Fälle vor, davon waren 31 epithelial (13 Ade- recognize carcinomas in 2/13 adenomas. EUS
nome, 12 Karzinome, 6 Lymphome) und 22 subepi- features suggesting carcinoma were loss of wall
Bibliography thelial (11 GISTs, 7 Brunneromas, 1 Lipom, 3 NETs). layers and irregular margins. 5/6 lymphomas
DOI http://dx.doi.org/
EUS konnte bei 2/13 Adenomen kein Karzinom showed inhomogeneous thickening with layers
10.1055/s-0032-1313135
erkennen. Die EUS-Zeichen, die für ein Karzinom partially recognizable. Tumor type of subepithe-
Published online: November 5,
2012 sprechen, waren der Verlust der Wandschichten lial lesions correlated with echogenicity: GIST
Ultraschall in Med 2012; 33: und unregelmäßige Ränder. 5/6 Lymphome zeig- tumors were mostly (62.5 %) hypocheoic with
E210–E217 © Georg Thieme ten eine inhomogene Verdickung der Schichten the 3 malignant cases being characterized by
Verlag KG Stuttgart · New York · mit teilweise erkennbaren Schichten. Der Tu- heterogeneous echopattern with irregular outer
ISSN 0172-4614 mortypus bei subepithelialen Läsionen korre- margins. Of the hyperechoic lesions, lipomas
Correspondence lierte mit der Echogenität. GIST-Tumore waren had a homogeneous whitish appearance, while
Dr. Aleksandra Pavlovic größtenteils (62,5 %) echoarm, wobei die 3 ma- NET and Brunneromas were less hyperechoic. In
Markovic lignen Fälle durch ein heterogenes Echomuster the latter, the endoscopic aspect was also helpful
Clinic for Gastroenterology, mit irregulären Außenrändern charakterisiert for differential diagnosis. Accuracy of combined
Clinical Center of Serbia wurden. Bei den echoreichen Läsionen zeigten endoscopic/EUS imaging for all duodenal lesions
2 Dr Koste Todorovica St.
die Lipome ein homogenes weißliches Erschei- was 84.9 % (45/53). No procedural complications
11000 Belgrade
nungsbild, während NET und Brunneromas we- occurred among all patients that received EUS
Serbia
Tel.: ++ 381/6 68 30 08 07 niger echoreich waren. Bei Letzteren war für die examinations.
Fax: ++ 381/1 13 04 85 82 Differenzialdiagnose das endoskopische Erschei- Conclusion: EUS contributes to the differential
akica68@yahoo.com nungsbild hilfreich. Die Genauigkeit der kombi- diagnosis of epithelial lesions known to be ma-

Pavlovic Markovic A et al. Endoscopic Ultrasound for … Ultraschall in Med 2012; 33: E210–E217
Original Article E211

nierten endoskopischen/EUS-Bilder bei allen duodenalen Läsio- lignant; in subepithelial tumors, tissue confirmation is still
nen betrug 84,9 % (45/53). Bei keinem der Patienten mit EUS- required.
Untersuchungen traten eingriffsbedingte Komplikationen auf.
Schlussfolgerung: EUS leistet einen Beitrag zur Differenzialdiag-
nostik von epithelialen Läsionen mit malignem Hintergrund;
bei subepithelialen Tumoren ist eine Bestätigung im Gewebe
immer noch notwendig.

Introduction In all patients the examination was undertaken based on the re-
! sults of previously performed upper endoscopy which indicated
Mucosal lesions in the gastrointestinal tract are routinely diag- the presence of lesions in the duodenum. Endoscopy was always
nosed by endoscopy and biopsy usually with high accuracy rates repeated prior to EUS and appearance, as well as location of lesions
[1]; cases with adenoma containing foci of carcinoma or lympho- were documented. On EUS using radial echoendoscopes, size and
ma might occasionally be missed by the biopsy, at least at the first appearance (echogenicity, outer margins) of the lesions were ana-
attempt. Additionally, subepithelial lesions are often difficult to di- lyzed. In clinical practice, patients with epithelial neoplasia either
agnose using imaging and mucosal biopsy only [2]. Therefore, en- underwent polypectomy (adenomas), surgery (carcinoma, adeno-
doscopic ultrasonography (EUS) has been introduced to yield com- mas with cancer, 1 lymphoma) or chemotherapy (after unequivo-
plementary imaging information due to its precise analysis of all cal diagnosis by endoscopic biopsy, i. e. remaining lymphomas). Pa-
layers of the gastrointestinal wall [3]. EUS can contribute in the dif- tients with subepithelial tumors larger than 3.5 cm in diameter
ferential diagnosis between benign and malignant lesions, by deli- were advised to undergo surgery due to a risk of malignancy. EUS
neating size and echogenicity of tumors as well as possible inva- results were compared with the surgical findings and histopatho-

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sion of surrounding structures [4 – 7]. In contrast to esophagus logical analysis of biopsy specimens. EUS layers were used for anal-
and stomach, information on EUS features of duodenal tumors are ysis based on previous descriptions. The first inner hyperechoic
still limited; these are rare lesions and their clinical manifestations layer corresponds to the entry echo, the second inner hypoechoic
vary; they frequently become symptomatic only in the late stages layer corresponds to the mucosa, the third central hyperechoic lay-
of the disease [8]. Therefore, we retrospectively analyzed our cases er corresponds to the submucosa, the outer, fourth, hypoechoic
with various duodenal tumors, both epithelial and subepithelial, layer corresponds to the muscularis propria, and the fifth outer hy-
with respect to characteristic echo features. perechoic layer corresponds to the serosa [6, 9].

Performance of EUS
Materials and Methods Endosonographic examinations were done with the video echoen-
! doscope Olympus GF-UM130 and Olympus GF-UE160-AL5, using
Patients the radial probe of variable frequency range 5/12 MHz and the
All cases with duodenal lesions – excluding lesions of the ampulla Olympus UM-2 R ultrasonic microprobes as a supplement to the
of Vater – that underwent upper EUS were reviewed at the Depart- echoendoscope in order to provide detailed images using frequen-
ment of Gastroenterology and Hepatology of the Clinical Center of cies of 10/20 MHz. All examinations were performed by three ex-
Serbia during the period of September 1998 to September 2010. perienced endosonographers. The preparation of the patients for
The cases were selected by reviewing the EUS case book during endosonographic examination was identical to the one used in
the above-mentioned period that contained 6825 EUS cases. Eigh- conventional upper endoscopy. Twenty-three patients (43.4 %)
ty three patients were found, of whom 3 were excluded due to were sedated with Propofol and Midazolam.
non-neoplastic nature of the lesion (varix) or rare condition with
already established diagnosis (2 melanoma metastases). Of the re- Outcome Parameters and Statistics
maining 80 patients, 53 had histological confirmation by surgery Main outcome parameter of this retrospective analysis was the
or endoscopic biopsy/polypectomy which forms the basis of the descriptive analysis of echo features on the basis of images taken
current analysis (●
" Table 1).

Table 1 Diameter of duodenal lesions and diagnostic methods in correlation with EUS.

EUS Dg no Pt % diameter (cm) mean ± SD endoscopy surgery endoscopy + follow up EUS Dg


surgery consistency
polyp 13 16.2 0.5 – 2 1.27 ± 0.51 12 (92.3 %) 1 (7.7 %) 0 0 11/13 (84.6 %)
carcinoma 12 15 3–7 4.57 ± 1.48 2 (16.7 %) 4 (33.3 %) 6 (50 %) 0 12/12 (100 %)
lymphoma 6 7.5 5 (83.3 %) 0 1 (16.7 %) 0 6/6 (100 %)
GIMT 29 36.3 0.7 – 3.5 1.77 ± 1.08 1 (3.4 %) 7 (24.1 %) 0 21 (72.4 %) 6/8 (75 %)
malignant GIMT 4 5 3.5 – 6 4.63 ± 1.11 0 3 (75 %) 0 1 (25.0 %) 3/3 (100 %)
Brunner’s hyper- 7 8.75 0.4 – 0.8 0.55 ± 0.16 7 (100 %) 0 0 0 5/7 (71.4 %)
plasia
lipoma 6 7.5 1.2 – 3 1.93 ± 0.77 0 1 (16.7 %) 0 5 (83.3 %) 1/1 (100 %)
NET 3 3.75 0.8 – 1.7 1.3 ± 0.46 0 3 (100 %) 0 0 2/3 (66.7 %)
total 80 100 27 (33.75 %) 19 (23.75 %) 7 (8.75 %) 27 (33.75 %) 46/53 (86.8 %)

Pavlovic Markovic A et al. Endoscopic Ultrasound for … Ultraschall in Med 2012; 33: E210–E217
E212 Original Article

during the examination, both with endoscopy and endosonogra- ● Table 1 presents diagnostic verification of the lesions in the duo-
"

phy. The focus was on the following differential diagnoses: denum. Twenty seven patients (33.75 %) were diagnosed using en-
▶ differential diagnosis between the different types of subepithe- doscopic biopsy, 19 (23.75 %) by surgery, while 7 (8.75 %) patients
lial tumors (GIST, leiomyoma, neuroendocrine tumor (NET) and using endoscopy and surgery together. Lesions were most fre-
lipoma); quently located in the duodenal bulb (24/45.3 %), following duode-
▶ recognition of malignancy in duodenal adenoma (malignant nal junction (20/37.7 %) and the descending duodenum (7/13.2 %),
versus benign adenoma); while in 2 (3.8 %) patients with lymphoma wall changes were loca-
▶ differentiation between duodenal cancer and lymphoma. ted in all parts of the duodenum (●" Table 2).

The second outcome parameter was the estimation of the accura-


cy of these parameters in terms of distinguishing between the di- Epithelial (mucosal) lesions
agnoses mentioned above. Statistical analysis was performed Thirteen adenomas which we included in our endosonographic
using the Statistical Package for Social Sciences (SPSS®, version study were localized in the mucosa (● " Fig. 1). In 3 out of 13 pa-

14.0). Basic descriptive statistics included means, standard devia- tients we visualized infiltration into second mucosa layer (mus-
tions, ranges and percentages. cularis mucosa). Tumors were mainly with homogeneous echo
pattern, hypo- (8; 61.5 %) and hyperechoic (4; 30.8 %) with
smooth margins in 12 (92.3 %) patients. EUS did not recognized
Results carcinomas in 2 of 13 adenomas. One of these cases had hetero-
! geneous echo pattern while in the second case, tumor was homo-
The mean age of 53 study patients was 53.1 ± 11.4 years (range geneous but with unclear margins, and both developed from vil-
16 – 75), with 62.3 % and 37.7 % being male and female, respec- lous adenoma.
tively. Indications for endoscopy were: vomiting in 23 (43.4 %), Epithelial malignant tumors, carcinoma (n = 12; 22.6 %) and lym-
nausea in 34 (64.1 %), weight loss in 17 (32.1 %), melena in 12 phoma (n = 6; 11.3 %) spread to the layers of the duodenal wall

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(22.6 %), haematemesis in 2 (3.8 %) and abdominal discomfort in depending on the stage of the disease (● " Table 2). The majority

30 (56.6 %) of our patients. of patients with cancer (n = 10) had heterogeneous and mixed

Table 2 Origin and location of histologicaly confirmed duodenal lesions.

mucosa musc. mucosa submucosa musc. propria bulb junction of bulb descending bulb and
and descending duodenum descending
duodenum duodenum
polyp n = 13 10 (76.9 %) 3 0 0 6 (46.2 %) 5 (38.5 %) 2 (15.4 %) 0
carcinoma n = 12 12 (100 %) 12 (100 %) 2 1+ 10 (100 %) 10 2 (83.3 %) 4 (33.3 %) 7 (58.3 %) 1 (8.3 %) 0
lymphoma n = 6 6 (100 %) 6 (100 %) 2 1+ 4 (100 %) 4 2 (66.7 %) 2 (33.3 %) 1 (16.7 %) 1 (16.7 %) 2 (33.3 %)
GIMT n = 8 0 1 (12.5 %) 0 7 (87.5 %) 2 (25 %) 4 (50 %) 2 (25 %) 0
malignant GIMT 0 0 0 3 (100 %) 2 (66.7 %) 0 1 (33.3 %) 0
n=3
Brunner’s hyper- 0 5 (71.4 %) 2 (28.6 %) 0 7 (100 %) 0 0 0
plasia n = 7
lipoma n = 1 0 0 1 (100 %) 0 0 1 (100 %) 0 0
NET n = 3 0 1 (33.3 %) 2 (66.7 %) 0 1 (33.3 %) 2 (66.7 %) 0 0
total n = 53 29 (54.7 %) 26 (49 %) 23 (43.4 %) 24 (45.3 %) 24 (45.3 %) 20 (37.7 %) 7 (13.2 %) 2 (3.8 %)
1
Infiltrate to submucosa.
2
Infiltrate to muscularis propria.

Fig. 1 Endoscopic a and EUS b scans. Villous ade-


noma is shown as a sessile lesion with heterogenous
and mix echogenicity which is limited to the muco-
sal layer.

Abb. 1 Endoskopische a und EUS- b Bilder. Ein


zottiges Adenom ist als festsitzende Läsion mit he-
terogener und gemischter Echogenität dargestellt,
die auf die Mukosaschicht begrenzt ist.

Pavlovic Markovic A et al. Endoscopic Ultrasound for … Ultraschall in Med 2012; 33: E210–E217
Original Article E213

Fig. 2 Endoscopic a and EUS b scans. Duodenal


carcinoma causes disruption of all layers of the in-
testine wall.

Abb. 2 Endoskopische a und EUS- b Bilder. Das


Karzinom des Duodemums verursacht eine Zer-
störung aller Schichten der Darmwand.

Fig. 3 Endoscopic a and EUS b scans. Malignant


lymphoma is a hypoechoic heterogenous lesion

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with horizontal spreading in all layers of duodenal
wall.

Abb. 3 Endoskopische a und EUS- b Bilder. Das


maligne Lymphom ist eine echoarme heterogene
Läsion mit horizontaler Ausbreitung in alle Schich-
ten der duodenalen Wand.

echo pattern with poor defined margins and total loss of wall ar- by hyperechoic n = 1 (12.5 %) and heterogeneous mixed echo pat-
chitecture (●
" Fig. 2). In all patients with lymphoma the echogeni- tern n = 2 (25 %). In all 3 patients who were suspected of having
city was heterogeneous with unclear margins but with partially malignant GIMTs we found heterogeneous echo pattern with
recognizable wall layers (● " Fig. 3). poorly defined outer margins (● " Table 3). According to tumor

echogenicity we were not able to differentiate GISTs and leio-


Subepithelial lesions myomas. The remaining 21 (72.4 %) patients were subsequently
All patients who were clinically suspicious for presence of gastro- monitored in regular intervals during at least 18 months, without
intestinal mesenchymal tumors (GIMT) (33, 49.3 %) had pre- increase in the size or change in the tumor echogenicity. The suc-
viously undergone endoscopic biopsy and the biopsy results did cess rate of endosonography in differentiating between benign
not indicate pathological changes (● " Fig. 4, 5). In 3 out of 4 pa- and malignant duodenal GIMTs in patients with surgical verifica-
tients who were suspected of having malignant GIMT because of tion was 81.8 % (9/11) (● " Table 1).

the size of the tumor (3.5 – 6 cm; mean 4.63 ± 1.11), inhomogeni- Based on histological analysis we diagnosed 1 lipoma, 3 NETs and
city of lesion and poorly defined outer margins, the diagnosis was 7 Brunneromas. These tumors were mainly hyperechoic (10/11;
surgically confirmed, while the fourth patient refused surgery. 90.9 %), originated from submucosa (5/11; 45.5 %) and muscularis
Out of 29 patients in whom endosonography indicated a benign mucosa (5/11; 45.5 %). Lipomas had a homogeneous whitish ap-
GIMT, 8 (27.6 %) were treated surgically, because of signs of pearance, while NETs and Brunneromas were less hyperechoic
bleeding. In 6 (75 %) of those patients, the diagnosis was con- (● ●
" Table 2, 3) ( " Fig. 6 – 8).

firmed, while in the remaining two patients who had a border- In 46 (86.8 %) of 53 patients the hisotopathological analysis of the
line lesion size (3.5 cm) with relatively homogeneous echo struc- changes in the duodenum confirmed the diagnosis based on en-
ture of the tumors it was found that these were malignant GIMTs. doscopic ultrasonography (● " Table 1). Taking into account the

Histological analysis following surgical treatment revealed 4 be- patients in whom we did not have endoscopic or surgical verifi-
nign and 5 malignant GISTs and 2 leiomyomas (● " Table 1). The cation and who did not show any significant changes during the
origin of the tumors with regard to duodenal wall layers as found follow up, the success rate of the procedure was 91.25 % (73/80).
by endosonography, is shown in ● " Table 2. Based on our results we measured positive (PPV) and negative
The GIMTs were located mainly in the fourth layer of the duode- (NPV) predictive value for homogenicity and appearance of outer
nal wall (muscularis propria) (10/11; 90.9 %) (● " Table 2). Out of 8 margins in predicting malignancy. The counted PPV values were
patients who were suspected to have benign GIMTs, the internal 95.6 % (22/23) and 95 % (20/21), respectively, while the values for
echo pattern was commonly hypoechoic n = 5 (62.5 %), followed NPV were 90 % (27/30) and 84 % (27/32), respectively.

Pavlovic Markovic A et al. Endoscopic Ultrasound for … Ultraschall in Med 2012; 33: E210–E217
E214 Original Article

Table 3 EUS pattern and tumor margins of various hystologicaly confirmed duodenal lesions.

homogenous echo pattern heterogenous echo margins


pattern

hypoechoic hyperechoic anechoic unclear clear


polyp n = 13 8 (61.5 %) 4 (30.8 %) 1 (7.7 %) 1 (7.7 %) 12 (92.3 %)
carcinoma n = 12 2 (16.7 %) 10 (83.3 %) 10 (83.3 %) 2 (16.7 %)
lymphoma n = 6 6 (100 %) 6 (100 %)
GIMT n = 8 5 (62.5 %) 1 (12.5 %) 2 (25 %) 8 (100 %)
malignant GIMT = 3 3 (100 %) 3 (100 %)
Brunner’s hyperplasia n = 7 6 (85.7 %) 1 (14.3 %) 1 (14.3 %) 6 (85.7 %)
lipoma n = 1 1 (100 %) 1 (100 %)
NET n = 3 3 (100 %) 3 (100 %)
total n = 53 15 (28.3 %) 15 (28.3 %) 23 (43.4 %) 21 (39.6 %) 32 (60.4 %)

Fig. 4 Endoscopic a and EUS b scans. Endoscopi-


cally GIMT is shown as a solid mass with centrally
located ulcer; EUS shows hypoechoic lesion with
clear margins that arises from the muscularis pro-
pria.

Abb. 4 Endoskopische a und EUS- b Bilder. Endo-

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skopisch zeigt sich das GIMT als solide Raumforde-
rung mit zentral lokalisiertem Ulkus; EUS zeigt eine
echoarme Läsion mit deutlichen Rändern, die von
der Muscularis propria stammt.

Fig. 5 Endoscopic a and EUS b scans. GIMT is


shown as a hypoechoic lesion that arises from the
muscularis propria.

Abb. 5 Endoskopische a und EUS- b Bilder. GIMT


stellt sich als echoarme Läsion dar, die von der
Muscularis propria stammt.

Fig. 6 Endoscopic a and EUS b scans. Lipoma is


shown as a hyperechoic lesion in the submucosal
layer of the duodenum.

Abb. 6 Endoskopische a und EUS- b Bilder. Das


Lipom stellt sich als echoreiche Läsion in der Sub-
mukosa des Duodenums dar.

Pavlovic Markovic A et al. Endoscopic Ultrasound for … Ultraschall in Med 2012; 33: E210–E217
Original Article E215

Fig. 7 Endoscopic a and EUS b scans. Carcinoid


tumor appears as a medium to hyperechoic lesion
in the submucosal layer of the duodenum.

Abb. 7 Endoskopische a und EUS- b Bilder. Das


Karzinoid tritt als mittlere bis echoreiche Läsion in
der Submukosa des Duodenums auf.

Fig. 8 Endoscopic a and EUS b scans. Brunner


gland hyperplasia is shown as a medium to hypere-
choic lesion in the mucosal layer of the duodenum.

Abb. 8 Endoskopische a und EUS- b Bilder. Die

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Hyperplasie der Brunner-Drüsen stellt sich als mit-
tlere bis echoreiche Läsion in der Mukosa des Duo-
denums dar.

Discussion success rate of EUS in predicting malignancy of epithelial lesions


! in our study was 93.5 %. However, Xu et al. [8] described only one
There are relatively few studies investigating the role of EUS in di- adenocarcinoma in 169 duodenal lesions, while Inai et al. fol-
agnostics of duodenal lesions, either mucosal or subepithelial lowed 3 adenomas and 1 adenocarcinoma without much success
[8, 10 – 14]. EUS is considered to be the most sensitive method in differentiating benign from malignant lesions [13].
in preoperative diagnostics of the duodenal lesions. It allows us Primary lymphomas of the small intestine are very rare and re-
to determine not only the invasion depth of the tumor itself, but present at most 12 % of all NHLs and 19 – 38 % of malignancies of
also the diagnostics of the deeper lesions of the intestinal wall. the small intestine [17]. Lymphomas are tumors where endoso-
Use of EUS represents significant progress in diagnostics of gas- nography detects a diffuse partialy loss of layering of the intes-
trointestinal diseases as it can determine the size, echogenicity, tinal wall which was the case with our patients. Although endos-
homogenicity, origin and margins of the lesion. copy with biopsy represents the gold standard in the diagnosis of
It is very difficult to diagnose primary epithelial tumors on EUS duodenal lymphoma, EUS is capable for detecting multifocal tu-
[15] beyond endoscopy with biopsy. Duodenal adenoma is the mor growth as well as the presence of enlarged lymph nodes.
most common duodenal tumor. In our series they were located Many previous studies indicated that the success rate of endoso-
mainly in the mucosa, with homogeneous echo pattern and nography in detecting gastric lymphoma is 90 – 100 % that is in
smooth margins. Endosonographically signs of duodenal carcino- complete agreement with our results (6/6, 100 %). Moreover,
ma were heterogeneous and mixed echo pattern with poorly de- EUS is significant in proper determination of the stage of lym-
fined margins and total loss of wall architecture. Although con- phoma and using the most appropriate therapy accordingly
ventional endoscopy has a big role in the estimation of the level [18, 19].
of benignancy, but even the macroscopic finding and biopsy does EUS can indicate with a high degree of confidence malignant po-
not provide a definite answer about the spread and malignant tential of GIMTs. All these possibilities are especially important in
potential of the lesion [13, 36]. For the accurate histologic diagno- differential diagnostics of the lesions in the duodenum which are
sis of elevated lesions of duodenal mucosa, large specimens must otherwise difficult to diagnose due to its location and surround-
be obtained. Endoscopic mucosal resection (EMR) can be used to ings. Stromal subepithelial tumors are a heterogeneous group of
obtain the specimens, but there is a risk for duodenal perforation. mesenchymal neoplasms of the gastrointestinal wall which were
However, EMR can be safely used in combination with EUS to es- previously often classified as leiomyomas or leiomyosarcomas,
timate the depth of invasion and to ascertain the extent of the se- recently redefined as GIST and non-GIST lesions [20 – 24]. Review
paration between the lesion and the muscularis propria [13]. The of the literature on GISTs, clearly demonstrates that classifica-

Pavlovic Markovic A et al. Endoscopic Ultrasound for … Ultraschall in Med 2012; 33: E210–E217
E216 Original Article

tions and terminologies are continuously being redefined GISTs less than 20 mm in diameter, surgical treatment should
[21, 22]. 10 – 30 % of these tumors are malignant and the major be suggested to all patients with duodenal hypoechoic subepi-
problem in making the diagnosis is determination of malignant thelial tumors measuring ≥ 20 mm or exhibiting EUS critera of
potential of the neoplasm, considering its very slow biological potential malignancy (heterogenous echo pattern; ulceration;
evolution. The prognosis is based upon a complex relationship irregular outline) [27, 34, 35].
between several parameters: the size of the tumor, the patient’s Other lesions such as lipoma with a low malignant potential
age, EUS results, the mitotic index, cytogenetics and immunohis- [12, 36, 37] and NETs [38, 39] have specific but not pathognomo-
tochemistry [25, 26]. Based on the available literature [27], GIST nic features. EUS was accurate in most of our patients. There are a
of more than 5 cm in diameter clearly indicates malignancy, but few recent studies showing that EMR is successful for the major-
many studies have shown that the nature of a GIST also depends ity of duodenal carcinoids [40, 41]. Finally, brunneromas are be-
on its location. It is more difficult to make the prognosis of the nign polypoid lesions located mostly (57 %) in the posterior wall
disease in case of a GIST in small intestine in comparison to those of the duodenal bulb [42]. Only a few cases of malignant transfor-
in the stomach or colon [26]. The finding that small bowel GISTs mation have been reported. They are usually seen as hyperechoic,
behave more aggressively than gastric GISTs has been reported in small in diameter, located in submucosa (third EUS layer). Five of
some series [21, 22]. our 7 patients, had hyperechoic characteristics of their respective
According to the recommendations of the American Gastroen- lesions, but endoscopically they were less whitish than lipoma.
terological Association (AGA) the EUS characteristics of a benign EUS accuracy for this type of polyps was 71.4 % which demon-
GIST are: smaller size of the lesion, homogeneous and regularly strates the importance of using EUS in the differential diagnosis
margins of the tumor [20]. Endosonographically, GIMTs in our in all types of polypoid lesions [8, 13].
patients, are typically seen as hypoechoic mass located in the In conclusion, we could confirm some endosonographic features
muscularis propria (fourth EUS layer) and very rarely in the that suggestied malignancy in GIMTs (greater size, heterogenicity
muscularis mucosa (second EUS layer) which is in agreement and irregular margins of the lesions), but leiomyomas and GISTs

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with previously published reports [1, 14, 25, 28]. All of our 3 could not be differentiated using the EUS findings. EUS diagnosis
malignant cases were characterized by heterogeneous echo pat- should be confirmed using other diagnostic procedures such as
tern with irregular outer margins. But among 8 symptomatic tissue biopsy. Other subepithelial lesions can be differentiated
mesenchymal lesions suspected to be benign by EUS, two pa- based on EUS according to their localisation, echogenicity, size
tients with a borderline lesion size (3 cm and 3.5 cm) and rela- and wall layer from where the lesion originates. However, the
tively homogeneous echo structure, were surgically diagnosed macroscopic-endoscopic appearance influence the decision
as malignant GIMTs. The overall accuracy of EUS in determining about further diagnostic procedures, as well. In the mucosal le-
the benign nature of a hypoechoic subepithelial duodenal tumor sions, endosonographic features, which suggest malignancy, in-
among our patients who were verified surgically was 81.8 %. clude heterogenicity and unclear margins. Histologically diag-
The sensitivity of EUS for malignant duodenal GIST was consid- nosed villous adenomas have a higher malignant potential and
erable low (3/5 = 60 %). Other studies have also confirmed a high require endocopical removal. In the presence of contraindica-
sensitivity of EUS in diagnostics and determination of malignant tions for surgical treatment, more frequent follow-up examina-
potential of the lesion, but the number of duodenal subepithe- tions using EUS are necessary. EUS features that suggested carci-
lial lesions was smaller than in our group of patients [8, 10, 11]. noma were loss of wall layers and irregular margins, while
There is no doubt that any symptomatic GIST with benign EUS lymphomas showed inhomogeneous thickening with partially
characteristics or suspected malignant GIST should be treated recognizable layers. It is very important that both, a gastroenter-
surgically as soon as possible, as we did in our practice. How- ologist and a surgeon together, decide about the best possible
ever, there is no consensus about optimal therapy of asympto- therapeutic option, taking into account endosonographic charac-
matic smaller size GISTs [20, 28]. Such small lesions most often teristics of duodenal lesions. For duodenal lesions extending not
do not become clinically significant, while on the other hand deeper than submucosa, EMR is recommended, while in case of
there are well-documented cases of small GISTs which metasta- deeper infiltration (muscularis propria) surgery is necessary.
sized even decades after the surgery [28, 29]. Nevertheless, we EUS also has a great role in monitoring of asymptomatic lesions
think that tissue confirmation is still required in smaller GIST and in determination of the effectiveness of the previous endo-
without unequivocal indication for surgery, perhaps using scopic therapy.
EUS-FNA, which however has shown variable results in the di-
agnosis of the SEL in most publications [30, 31]. In Hodas retro- Affiliations
spective database study of 112 patients (among them 8 duode- 1
Faculty of Medicine, University of Belgrade, Belgrade, Serbia
2
nal lesions) undergoing EUS-FNA sampling of subepithelial Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia,
Belgrade, Serbia
lesions, the results were diagnostic in only 61.6 % [32]. In an- 3
Department of Interdisciplinary Endoscopy, University Hospital Hamburg-
other recent study the sensitivity of EUS-FNA for GISTs located Eppendorf
4
in the stomach was 84.4 % (27/32), but poor for lesions located Department of Internal Medicine, Zemun Clinical Hospital, Belgrade, Serbia
5
Department of Gastroenterology, Clinical Centre, Dr. Dragisa Misovic,
in the duodenum because none of these tumors yielded diag- Belgrade, Serbia
nostic cytology (n = 3) [33]. The yield of EUS-guided FNA in the
diagnosis of hypoechoic fourth-layer masses such as GISTs may
be improved with the application of immunohistochemical a-
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