Lymphoepithelial cysts of the pancreas: an EUS case seriesJohn Nasr, MD, Michael Sanders, MD, Kenneth Fasanella, MD, Asif Khalid, MD, Kevin McGrath, MD

Pittsburgh, Pennsylvania, USA

Background: Lymphoepithelial cysts (LEC) of the pancreas are rare benign lesions that can be misdiagnosed aspancreatic masses or cystic neoplasms. With widespread use of abdominal cross-sectional imaging, more pancre-atic lesions are being discovered, with EUS being used to further evaluate the abnormality.

Objective: Our purpose was to describe EUS and cyst aspirate features of LEC of the pancreas.

Design: Case series.

Setting: Single tertiary referral center.

Patients: Nine patients with lymphoepithelial cysts who underwent EUS-FNA.

Results: Five male and 4 female patients were identified (mean age 51 years). All lesions were discovered by CTand described as ‘‘peripancreatic’’ in 67% of cases (6/9). EUS examination described a solid-appearing hypoe-choic and heterogeneous mass with subtle postacoustic enhancement in 5 of 9 cases. Four lesions were de-scribed as purely cystic: 2 were septated, 1 was unilocular, and 1 had internal papillary fronds. Mean cyst sizewas 5.2 cm (range 1.7-12 cm). Cyst aspirates revealed a thick milky, creamy, or frothy aspirate in 56% of cases(5/9). Cyst cytologic examination revealed squamous material (nucleated/anucleated cells or keratin debris) inall cases. Lymphocytes were seen in 56% of aspirates (5/9). Carcinoembryonic antigen (CEA) levels were ob-tained in 5 cases (median 6.5 ng/mL [range 2.9-493.4 ng/mL]). Six patients have avoided surgery on the basisof EUS-FNA cytologic results confirming the diagnosis of LEC. Three patients underwent surgical resection: 2for symptomatic lesions and 1 for concern for a mucinous cystic neoplasm given an elevated aspirate CEA level.Surgical pathologic examination confirmed LEC in each.

Limitations: Retrospective single-center study.

Conclusions: LEC should be considered whenever a large, well-defined solid or cystic peripheral pancreaticlesion is found. A thick milky, creamy, or frothy aspirate is common. The presence of squamous material andlymphocytes on cytologic examination is diagnostic of LEC. Aspirate CEA level may be elevated and shouldbe considered in conjunction with cytologic results to avoid misdiagnosis as a mucinous cystic neoplasm. Asymp-tomatic LEC should be managed conservatively.

Lymphoepithelial cysts (LEC) of the pancreas are rare,benign lesions of the pancreas with only 82 cases de-scribed in the literature to date. Diagnosis usually relieson histologic examination of the resected cyst or on cy-tologic analysis of aspirated cyst fluid. EUS is commonlyused to evaluate cystic lesions of the pancreas; however,the imaging characteristics of these cysts are largelyunknown. We report a case series of 9 patients withLEC and describe characteristic EUS and cyst aspiratefeatures.

Abbreviations: CEA, carcinoembryonic antigen; LEC, lymphoepithelial

cyst.

Copyright ª 2008 by the American Society for Gastrointestinal Endoscopy

0016-5107/$32.00

doi:10.1016/j.gie.2008.02.044

170 GASTROINTESTINAL ENDOSCOPY Volume 68, No. 1 : 2008

PATIENTS AND METHODS

A retrospective review was performed over a 6-year pe-riod to identify patients diagnosed with LEC on the basisof EUS-FNA cytologic examination or surgical histologicexamination as determined through a search of ourEUS database. Clinical history, diagnostic studies, EUSfindings, cytology, pathology, operative records, and surgi-cal pathology reports were reviewed. This study was ap-proved by the institutional review board of our medicalcenter. All patients gave informed consent for the EUSprocedure.

EUS was performed by 1 of 3 endosonographers usinga linear echoendoscope (FG-36 UA, Pentax Medical, Mon-tvale, NJ). EUS-FNA was performed with a 22- or 25-gauge needle (EchoTip, Wilson-Cook Medical, Winston-Salem, NC). All patients received an intraprocedural anti-biotic (levofloxacin or ciprofloxacin), which was

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Nasr et al Lymphoepithelial cysts of the pancreas

TABLE 1. EUS and cyst aspirate features of LEC

Case

No.

Age

(y) Sex

Size

(cm) EUS features Aspirate features Cytologic features

1 46 F 12 � 6 Septated anechoic cyst Thin straw-colored fluid Polymorphous population of

lymphocytes, anucleated

squamous epithelial cells

2 62 M 4.4 Irregular hypoechoic mass Mucinous bloody fluid Hypocellular aspirate with

scattered histiocytes and bland

squamous epithelial cells

3 44 F 1.7 � 1.6 Hypoechoic mass with

well-defined borders

White frothy fluid Anucleated squamous epithelial

cells with degeneration and acinar

cells identified

4 40 F 4.4 � 3.0 Hypoechoic and heterogeneous

mass with well-defined borders

Thick whitish mucoid material Anucleated squamous epithelial

cells with few nucleated squamous

cells and few macrophages

5 59 M 4.4 � 2.6 Hypoechoic mass-like structure

with poorly defined borders

Milky fluid Rare bland epithelial cells,

scattered neutrophils,

lymphocytes, few macrophages

and abundant keratin and

crystalline debris

6 58 M 7.0 � 6.0 Hypoechoic heterogeneous mass Tan-colored fluid Nucleated and anucleated

squamous epithelial cells and

degenerated debris present

7 65 M 4.5 � 3.5 Unilocular cyst Cream-colored fluid Abundant anucleated squamoid

debris and occasional lymphocytes

8 55 M 4.6 �3.4 Unilocular cyst with papillary

fronds

Thin straw-colored fluid Scattered small lymphocytes,

macrophages, few anucleated

squamous cells and rare glandular

cells

9 40 F 3.8 � 1.7 Anechoic, distally enhancing lesion

with thick septations

Thin straw-colored fluid Red blood cells, small lymphocyte,

mature squamous cells

F, Female; M, male.

continued for an additional 3 days. If intraprocedural cy-tologic interpretation was requested, Diff-Quick–stainedslides were prepared for immediate review. Otherwise,slides and cell block material were fixed in alcohol forlater review.

RESULTS

Nine cases of LEC underwent EUS-FNA at our institu-tion between January 2002 and October 2007 (Table 1).There were 5 male and 4 female patients; average age� SD was 51 � 9.1 years (range 40-65 years). All patientswere initially referred for EUS evaluation of a pancreaticlesion discovered by CT. Five lesions were incidental find-ings; 3 patients underwent CT to evaluate abdominal pain,and the other patient was imaged to evaluate weight loss.The lesions were described as ‘‘peripancreatic’’ by CT inthe majority of cases (6/9). A total of 16 EUS-FNA proce-

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dures (range 1-3) was performed on these 9 patients dur-ing the study period.

The mean cyst size � SD was 5.2 � 2.7 cm (range1.7-12 cm). Cyst location was as follows: pancreatic neck(n Z 2), pancreatic body (n Z 4), and pancreatic tail(n Z 3). EUS examination described a well-defined hypo-echoic and heterogeneous mass in 5 of 9 cases. Theselesions appeared solid; however, they had subtle posta-coustic enhancement (Fig. 1). Four lesions were describedas purely cystic: 2 were septated, 1 was unilocular, and1 had internal papillary fronds (Fig. 2). Cyst aspiratesrevealed a thick milky, creamy, or frothy aspirate in 56%of cases (5/9). A viscous bloody fluid was aspirated from1 mass-like lesion. Aspirates from the 4 purely cystic le-sions yielded a serous fluid in 3 cases, where the thirdyielded a thick milky fluid. The mean number of needlepasses was 2.6 (range 1-5). Cyst cytologic examination re-vealed squamous material (nucleated/anucleated squa-mous cells or keratin debris) in all cases. Lymphocytes

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Lymphoepithelial cysts of the pancreas Nasr et al

were seen in 56% of aspirates (5/9). Sufficient fluid for car-cinoembryonic antigen (CEA) level determination was ob-tained in 5 cases. The median CEA level was 6.5 ng/mL(range 2.9-493.4 ng/mL).

One patient underwent 2 EUS procedures 4 years apartbecause the patient subsequently had jaundice. The masshad grown from 4.4 cm to 6 cm; however, there was nobiliary dilatation on cross-sectional imaging. Repeat EUS-FNA again revealed squamous debris and lymphocytes.The patient’s jaundice spontaneously resolved and wasfelt to be of viral origin.

Six patients have avoided surgery on the basis of EUS-FNA cytologic results confirming the diagnosis of LEC.Three patients underwent surgical resection of their cysticmasses and histologic examination confirmed LEC in each.One patient with persistent epigastric pain and pressureunderwent resection of a pancreatic body lesion. The pa-tient’s symptoms resolved postoperatively. The second pa-

Figure 1. A 1.7 � 1.2 cm solid-appearing LEC with subtle posterior en-

hancement in the pancreatic tail.

Figure 2. A 4.6 � 2.6 cm cystic LEC with internal papillary fronds.

172 GASTROINTESTINAL ENDOSCOPY Volume 68, No. 1 : 2008

tient underwent surgical enucleation of a pancreatic necklesion given concern for a possible mucinous cystic neo-plasm. The initial CEA level of the cyst fluid was low at45 ng/mL; however, a 6-month repeat EUS-FNA cyst fluidsample yielded a CEA level of 493 ng/mL. A definitive pre-operative diagnosis of LEC was not made in either of these2 cases; however, the preoperative EUS-FNA cytology re-sults in each were consistent with LEC.

The third patient had a 12-cm cystic mass; EUS-FNA cy-tologic examination diagnosed this as LEC. However, giventhe patient’s clinical presentation with weight loss and thelarge size of the lesion, it was resected. Surgical histologicexamination confirmed LEC.

DISCUSSION

Lymphoepithelial cysts of the pancreas are rare lesionsthat do not harbor malignant potential; however, they canbe misdiagnosed as pancreatic masses or cystic neo-plasms. The etiology of these lesions remains unknown;however, theories include origination from squamousmetaplasia of an obstructed pancreatic duct, from the mis-placement and fusion of a brachial cleft during embryo-genesis, or from benign epithelial inclusions or ectopicpancreatic tissue in a peripancreatic lymph node.1,2 Thelesions were initially described by Luchtrath and Schriefersin 19853; however, the term ‘‘lymphoepithelial cyst of thepancreas’’ was coined by Truong et al1 in 1987. Histologi-cally, LECs are described as being epithelial-lined cysts sur-rounded by a rim of glandular lymphoid tissue. The cystwall is usually composed of stratified squamous cells. Cy-tologic examination of LEC aspirates typically reveals nu-merous anucleated squamous cells with occasionalhistiocytes and lymphocytes. Cholesterol crystals and ker-atin debris may also be seen.4-7

The largest series in the literature reported 12 casesand reviewed a total of 64 cases.8 There is a male predom-inance (4:1), with an average age of 55 years at diagnosis.The mean cyst size was 4.6 cm (range 1.2-17 cm) withoutan anatomic predisposition within the pancreas. Thesecysts are reported to be symptomatic in 50% of cases,with the most common symptom being abdominal pain.CT findings frequently describe a low attenuation masswith a thin enhancing rim. Multilocular or complex cysts(60%) are more common than the unilocular variety,9,10

and wall calcifications have also been described.11-14 ByUS, the characteristic finding is an inhomogeneous echo-genic mass with posterior enhancement.15

With widespread use of abdominal cross-sectional im-aging, more pancreatic lesions are being discovered, andEUS has emerged as the preferred modality for furtherevaluation. Thus, it is important to be aware of LEC be-cause the natural history is benign and only truly symp-tomatic lesions need be resected. Our EUS series, thelargest to date, shows diverse imaging characteristics.

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Nasr et al Lymphoepithelial cysts of the pancreas

The majority of LECs appeared solid; however, they hadsubtle posterior enhancement suggestive of a cystic com-ponent. The remaining lesions were cystic, both simpleand complex appearing. More important, all lesions hadsquamous material present by cytologic assessment; thefinding of such should raise suspicion for LEC. The major-ity of LECs in our series also demonstrated lymphocyteson cytologic examination.

Previous reports show elevated CEA levels in cyst fluidaspirates from LEC.16-18 Only 1 of our cases had anelevated CEA level, which ultimately prompted surgicalresection given concern for a mucinous cystic neoplasm.All other CEA levels were less than 55 ng/mL (median6.5 ng/mL). Two of 3 cases that underwent surgicalresection did not carry a preoperative diagnosis of LEC.Although the typical cytologic findings were present, webelieve it was our initial inexperience with these lesionsthat resulted in failure to make a definitive preoperativediagnosis. We now are more acutely aware of the cytologicfindings, the diverse EUS appearance, and the differencesin the gross cyst aspirate. A thick milky, creamy, or frothyaspirate certainly raises our suspicion given our experi-ence. Chylous lesions may also have a milky aspirate;therefore, if the aspirate is of sufficienct quantity, werecommend sending fluid for a triglyceride level toexclude a chylous cyst. If results are suggestive but notconvincing for the diagnosis of LEC, we recommendrepeating the EUS-FNA for confirmation. This explainsthe 16 EUS examinations in our 9 patient series. We alsobelieve this was part of our learning curve in diagnosingLEC.

In conclusion, we predict that more LECs will bediagnosed in the future given increased use of abdominalimaging modalities and EUS. Given the benign naturalhistory, it is important for endosonographers to be awareof this entity. Large peripheral cystic mass lesions by CTshould raise suspicion for LEC. By EUS, these lesionscan appear predominantly solid, multilocular, or simple.A thick milky, creamy, or frothy aspirate should promptthe endosonographer to consider LEC in the differentialdiagnosis. The presence of squamous material andlymphocytes on cytologic examination is diagnostic ofLEC.

DISCLOSURE

The authors report that there are no disclosures rele-vant to this publication.

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REFERENCES

1. Truong LD, Rangdaeng S, Jordan PH Jr. Lymphoepithelial cyst of the

pancreas. Am J Surg Pathol 1987;11:899-903.

2. Truong LD, Stewart MG, Hao H, et al. A comprehensive characteriza-

tion of lymphoepithelial cyst associated with the pancreas. Am J

Surg 1995;170:27-32.

3. Luchtrath H, Schriefers KH. A pancreatic cyst with features of a so-

called branchiogenic cyst. Pathologe 1985;6:217-9.

4. Liu J, Shin HJ, Rubenchik I, et al. Cytologic features of lymphoepithelial

cyst of the pancreas: two preoperatively diagnosed cases based on

fine-needle aspiration. Diagn Cytopathol 1999;21:346-50.

5. Mandavilli SR, Port J, Ali SZ. Lymphoepithelial cyst (LEC) of the pan-

creas: cytomorphology and differential diagnosis on fine-needle aspi-

ration (FNA). Diagn Cytopathol 1999;20:371-4.

6. Policarpio-Nicolas ML, Shami VM, Kahaleh M, et al. Fine-needle aspira-

tion cytology of pancreatic lymphoepithelial cysts. Cancer 2006;108:

501-6.

7. Centeno BA, Stockwell JW, Lewandrowski KB. Cyst fluid cytology and

chemical features in a case of lymphoepithelial cyst of the pancreas:

a rare and difficult preoperative diagnosis. Diagn Cytopathol

1999;21:328-30.

8. Adsay NV, Hasteh F, Cheng JD, et al. Lymphoepithelial cysts of the

pancreas: a report of 12 cases and a review of the literature. Mod

Pathol 2002;15:492-501.

9. Capitanich P, Iovaldi ML, Medrano M, et al. Lymphoepithelial cysts of

the pancreas: case report and review of the literature. J Gastrointest

Surg 2004;8:342-5.

10. Barbaros U, Erbil Y, Kapran Y, et al. Lymphoepithelial cyst: a rare cystic

tumor of the pancreas which mimics carcinoma. J Pancreas 2004;5:

392-4.

11. Goodman P, Kumar D, Balachandran S. Lymphoepithelial cyst of the

pancreas. Abdom Imaging 1994;19:157-9.

12. Katz DS, Scatorchia GM, Wojtowycz AR, et al. Lymphoepithelial cyst of

the pancreatic head. AJR Am J Roentgenol 1995;165:489.

13. Koga H, Takayasu K, Mukai K, et al. CT of lymphoepithelial cysts of the

pancreas. J Comput Assist Tomogr 1995;19:221-4.

14. Ueno S, Muranaka T, Maekawa S, et al. Radiographic features in lym-

phoepithelial cyst of the pancreas. Abdom Imaging 1994;19:232-4.

15. Kim YH, Auh YH, Kim KW, et al. Lymphoepithelial cysts of the pan-

creas: CT and sonographic findings. Abdom Imaging 1998;23:185-7.

16. Renou C, Giovannini M, Monges G, et al. Pitfalls of cyst fluid findings

obtained by endoscopic ultrasonography fine-needle aspiration on

a pancreatic lymphoepithelial cyst. Am J Gastroenterol 2007;102:

213-5.

17. Schinke-Nickl DA, Muller MF. Case report: lymphoepithelial cyst of the

pancreas. Br J Radiol 1996;69:876-8.

18. Ueno S, Muranaka T, Maekawa S, et al. Radiographic features in

lymphoepithelial cyst of the pancreas. Abdom Imaging 1994;19:232-4.

Received December 29, 2007. Accepted February 18, 2008.

Current affiliations: Department of Medicine, University of Pittsburgh

Medical Center, Pittsburgh, Pennsylvania, USA.

Reprint requests: Kevin McGrath, MD, UPMC Presbyterian, M2, C wing,

200 Lothrop St, Pittsburgh, PA 16046.

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