Cytologic Features ofLymphoepithelial Cystof the Pancreas:Two Preoperatively Diagnosed CasesBased on Fine-Needle AspirationJing Liu, M.D., Ph.D.,1 Hyung Ju C. Shin, M.D.,1* Illana Rubenchik, M.D.,2

Eric Lang, M.D.,2 Sandeep Lahoti, M.D.,3 and Gregg A. Staerkel, M.D.1

We describe the cytologic features seen in fine-needle aspiration(FNA) specimens from two cases of preoperatively diagnosedlymphoepithelial cyst (LEC) of the pancreas. Pancreatic LEC is arare, true cyst of uncertain histogenesis that may clinically andradiologically mimic a pseudocyst or cystic neoplasm. Both our patientswere middle-aged men who presented with vague abdominal pain.Computed tomography (CT) of the abdomen revealed a mass in oraround the pancreas, and CT-guided percutaneous FNA (patient 1) andendoscopic ultrasound-guided FNA(patient 2) yielded paste-like yellow-gray material. Cytologic smears showed numerous anucleated squa-mous cells in a background of keratinous and amorphous debris. A fewbenign nucleated squamous cells and plate-like cholesterol crystalswere also seen. Unlike LEC of the head and neck region, only rarelymphocytes and histiocytes were present. Pancreatic LEC was diag-nosed based on these cytologic findings and was histologically con-firmed following cyst enucleation (patient 1) and partial pancreatec-tomy (patient 2). We conclude that preoperative FNA and recognitionof the characteristic cytologic pattern will enable conservativesurgical management of pancreatic LEC.Diagn. Cytopathol.1999;21:346–350. r 1999 Wiley-Liss, Inc.

Key Words:cytologic features; fine-needle aspiration; lymphoepi-thelial cyst; pancreas

Lymphoepithelial cyst (LEC) of the pancreas is a rare,benign, true cyst that is lined by mature keratinizingsquamous epithelium surrounded by a layer of lymphoidtissue. It may mimic a pseudocyst or cystic neoplasm bothclinically and radiologically. Knowledge and recognition ofthis entity permits conservative management.

The cytologic features of LEC of the pancreas onfine-needle aspiration (FNA) smears have been described inonly two cases.1,2 In this paper, we report two additionalcases that were diagnosed preoperatively by means of FNAcytology.

Case ReportsCase 1A 56-yr-old white man presented to Hermann Hospital,Houston, Texas, with a 6-mo history of vague abdominalpain and occasional episodes of nausea, vomiting, and loosestools. Physical examination was unremarkable. A computedtomography (CT) scan of the abdomen showed a low-density cystic lesion (5.03 5.0 3 2.8 cm) arising from thetail of the pancreas and extending into the splenic hilum(Fig. 1).

A CT-guided transcutaneous FNA yielded 20 ml of thick,paste-like, yellow-gray material. Smears stained with thePapanicolaou and Diff-Quikt methods exhibited predomi-nantly anucleated and rare benign nucleated squamous cellsin a background of keratinous and amorphous debris (Fig.2). Plate-like cholesterol crystals were also noted (Fig. 3). Asmall fragment of keratinized stratified squamous epithe-lium with a distinct granular cell layer and adjacent lym-phoid aggregates were present in a cell block preparation(Fig. 4). Nuclear pleomorphism and mitotic figures wereabsent. A diagnosis of LEC was suggested.

A laparotomy was subsequently performed. A thin-walledunilocular cyst with a smooth inner surface containing 30 mlof brown fluid was excised from the region of pancreatic tail.The surgical specimen consisted of multiple fragments ofcyst wall with attached adjacent soft tissue. Both frozen andformalin-fixed paraffin-embedded tissue sections showed acyst wall lined by keratinizing stratified squamous epithe-lium without columnar or goblet cells and an underlying

1Department of Pathology, The University of Texas, M.D. AndersonCancer Center, Houston, Texas

2Department of Pathology and Laboratory Medicine, The University ofTexas Health Science Center, Houston, Texas

3Department of Gastrointestinal Medical Oncology, The University ofTexas, M.D. Anderson Cancer Center, Houston, Texas

*Correspondence to: Hyung Ju C. Shin, M.D., Department of Pathology,Section of Cytopathology, Box 53, The University of Texas, M.D. AndersonCancer Center, 1515 Holcombe Blvd. Houston, TX 77030.

Received 5 February 1999; Accepted 10 June 1999

346 Diagnostic Cytopathology, Vol 21, No 5 r 1999 WILEY-LISS, INC.

dense band of lymphoid tissue. The squamous epithelialcells showed no atypia. No dermal appendages were seen. Asmall fragment of pancreatic acinar tissue was identifiedadjacent to the cyst. A diagnosis of pancreatic LEC wasrendered.

Case 2A 49-yr-old white man presented to his primary doctor withcomplaints of recurrent abdominal pain. He denied anyhistory of acute pancreatitis or any abdominal trauma. A CTscan of the abdomen showed a 6-cm retrogastric mass thatappeared fluid-filled. The mass was located in the region ofthe splenic artery and did not appear to arise from thepancreas or the adrenal gland. He was referred to TheUniversity of Texas M.D. Anderson Cancer Center, Hous-ton, Texas, for further evaluation and treatment. An endo-scopic ultrasound-guided FNA of the mass was performed

through the wall of the stomach. Creamy, liquid materialwas obtained. Papanicolaou-stained smears showed similarcytologic features as those in Case 1. A diagnosis of LEC ofthe pancreas was suggested.

A partial pancreatectomy, after frozen section confirma-tion, was subsequently performed. The surgical specimencontained the distal pancreas and spleen. A unilocular cyst(7.53 4.53 3.0 cm) filled with thick green-yellow fluid wasidentified adjacent to the pancreas and attached to thesplenic artery and vein. Subsequent microscopic examina-tion confirmed the diagnosis of LEC. The cyst wall was linedby mature stratified squamous epithelium surrounded bylymphoid tissue containing a few germinal centers. An areaof pancreatic parenchyma was seen adjacent to the lymphoidtissue. A few foci of columnar and mucous cells werepresent on the surface of the squamous epithelial liningwhere the granular cell layer was absent (Fig. 5). No dermalappendages were seen. Both Mayer’s mucicarmine andAlcian blue (pH 2.5) stained these mucous cells (Fig. 6).

Fig. 1. CT scan shows a 5.03 5.0 3 2.8 cm low-density lesion arisingfrom the tail of the pancreas and extending into the splenic hilar region.

Fig. 2. Predominantly anucleated squamous cells with single nucleatedsuperficial squamous cell (arrow) in a background of keratinous andamorphous debris (Papanicolaou stain,3400).

Fig. 3. Anucleated squamous cells and a plate-like cholesterol crystal(arrow) (Diff-Quikt stain,3200).

Fig. 4. Cell block shows a small fragment of keratinized stratifiedsquamous epithelium that includes a distinct granular cell layer andadjacent lymphoid aggregates in a background of keratinous debris (H&E,3100).

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DiscussionTo our knowledge, 34 cases of LEC of the pancreas with asimilar morphology, despite some differences in name, havebeen reported in the literature. These are summarized inTable I.3–28 LEC of the pancreas usually occurs in patientswho are middle-aged or older (mean 55 yr; range 26–74 yr).Eighty-eight percent of reported patients (29 of 33 patients)are older than 40 years old. Men are affected more com-monly than women (ratio 4:1). Patients are often asymptom-atic (12 of 33 reported patients) or present with abdominalpain (16 of 33 reported patients). The vast majority ofabdominal LECs are located in pancreatic parenchymaaffecting the pancreas from head to tail equally. Occasion-ally, an LEC may occur in ectopic pancreatic tissue.5,26,28

Because of their location and lack of symptoms, LECs of thepancreas are large, with a mean maximum dimension of 5.1

cm and a range of 2–13 cm. These cysts occur as multilocu-lar, bilocular, or unilocular masses.

Histologically, LEC of the pancreas is similar to thebranchial cleft cysts that occur in the head and neck region.Cytologic features from the two previously reported cases1,2

and the two presented cases are summarized in Table II. Weexcluded two other reported cases because one29 appeared tobe a dermoid cyst (sebaceous glands were seen in histologicsection), and the cytologic description in the other case27

was based on a cell block preparation only. Cytologic smearstypically show numerous anucleated squamous cells. Benignnucleated squamous cells ranged from few to many. Threecases with bi- or unilocular cysts showed only a fewnucleated squamous cells, while a single case with amultilocular cyst was reported to have many nucleatedsquamous cells. This difference may be related to thelocularity of the cysts, i.e., increased locularity yieldsincreased numbers of nucleated squamous cells becausemore cyst-lining epithelium exists. Unlike LECs of the headand neck region, LECs of the pancreas have only a fewlymphocytes and histiocytes on cytologic smears. Thisfinding is thought to be due to the difference in size of theLECs. The larger size of LEC of the pancreas at the time ofinitial diagnosis is ascribed mainly to the voluminousaccumulation of cystic content, i.e., keratinous materials. Inaddition, cholesterol crystals can be seen on the Diff-Quikt-stained smears.

Clinically and radiologically, the differential diagnosesfor LEC of the pancreas include the far more commonpseudocyst and other cystic neoplasms of the pancreas. Thepseudocyst of the pancreas has a fibrous capsule and is linedby granulation tissue without an epithelial lining. The FNAof a pseudocyst typically contains inflammatory cells andnecrotic debris without epithelium. In general, it is notdifficult to rule out pseudocyst if FNA specimens areadequate.

Unlike pseudocyst, true cysts and cystic neoplasms of thepancreas are lined by epithelium. Differential diagnoses oftrue cysts lined by squamous epithelium in the pancreasinclude metastatic well-differentiated squamous cell carci-noma, dermoid cyst, and LEC. A cell block preparationcontaining a fragment of the cyst wall can sometimes be ofhelp. In adequate FNA specimens obtained from multiplepasses, cystic squamous cell carcinoma can be expected toshow more nucleated cells with some atypia in a necroticbackground. Dermoid cysts characteristically show skinappendages and/or, occasionally, respiratory, gastrointesti-nal, and mesodermal tissues in addition to squamous epithe-lium. If components other than squamous cells are absent,the distinction from LEC is problematic.29,30 However,treatment for these two entities should not differ.

Among the cystic neoplasms of the pancreas, serouscystadenoma and mucinous cystic tumors are relatively

Fig. 5. Histologic section reveals a cyst wall lined by stratified squamousepithelium without atypia surrounded by an adjacent band of denselymphoid tissue containing a germinal center. No dermal appendages areseen (H&E,3100).

Fig. 6. Goblet cells (arrows) are seen on the surface of the squamousepithelial lining and are stained with Alcian blue (Alcian blue stain at pH2.5,3200).

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more common than LEC. Both serous cystadenoma andmucinous cystic tumors lack squamous epithelial compo-nents. Tumor cells of serous cystadenoma are cuboidal tocolumnar and are present singly or in cohesive clusters.Nuclei are uniform, small, and round, without prominentnucleoli. The cytoplasm is moderate in amount and usuallyis clear, containing glycogen. Background of the smears may

be clean or proteinaceous without mucus. Aspirates ofmucinous cystic tumors usually display cohesive clusters ofcolumnar cells with intracytoplasmic mucin in a mucinousbackground. It usually is not difficult to distinguish thesetwo tumors from LEC.

Awareness of the cytologic features of LEC of thepancreas on smears is essential not only in rendering a

Table I. Clinical Characteristics of Lymphoepithelial Cyst of the Pancreas and Peripancreatic Region

ReferenceAge

(yr)/sex Symptoms LocationLocularity/size (cm)

1 42/M Abdominal pain, fever Head Multilocular/62 44/M Abdominal and back pain Head Bilocular/63 36/M Weight loss, leukocytosis Body/tail Multilocular/94 35/M Abdominal pain, diarrhea Body Unilocular/65 50/F Asymptomatic Celiac lymph node Multilocular/36 72/M Asymptomatic Body Bilocular/47 64/M Asymptomatic Body Multilocular/48 32/F Abdominal pain Tail Unilocular/69 73/M Asymptomatic Body Unilocular/2

10 65/M Asymptomatic Body Multilocular/511 53/M Fatigue Tail Multilocular/812 66/F Abdominal pain, weight loss Head Unilocular/413 43/M Asymptomatic Tail Unilocular/314 59/M Asymptomatic Head Multilocular/6.515 66/M Asymptomatic Tail Unilocular/516 68/M Abdominal pain, nausea/vomiting Body Unilocular/1317 69/M Abdominal pain Body Unilocular/317 58/M Abdominal pain Body Multilocular/NA18 62/M Asymptomatic Head Multilocular/818 56/M Asymptomatic Head Multilocular/3.519 N/A N/A N/A N/A19 N/A N/A N/A N/A19 N/A N/A N/A N/A20 42/F Abdominal pain, fever Head Multilobular/521 59/? Diarrhea, abdominal cramps Head Multilocular/622 57/M Abdominal pain Head Unilocular/2.523 48/M Fatigue Tail Multilocular/2.524 26/M Abdominal pain ? NA/424 50/M Epigastric pain Body Multilocular/925 74/M Asymptomatic Body Multilocular/426 42/F Abdominal pain, fever Body Multilocular/427 64/M GI complaints Head and body Unilocular/5.528 59/M Asymptomatic Tail Bilocular/428 67/F Abdominal pain Tail Multilocular/3Present case 1 56/M Abdominal pain Tail Unilocular/5Present case 2 49/M Abdominal pain Tail Unilocular/7.5

N/A, not available; GI, gastrointestinal.

Table II. Gross and Cytologic Features of Lymphoepithelial Cyst of the Pancreas

Features Reference 1 Reference 2 Present Case 1 Present Case 2

Size (cm*) 6.0 6.0 5.0 7.5Locularity Multiloculi Biloculi Uniloculus UniloculusAnucleated squamous cells Numerous Numerous Numerous NumerousBenign nucleated squamous cells Many Few Few FewCholesterol crystals N/A Present Present N/ALymphocytes N/M Rare Rare Rare

*Measurement of greatest dimension.N/A, Diff-Quik-stained smears not available to evaluate cholesterol crystals; N/M, not mentioned.

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diagnosis but also in correctly evaluating the adequacy ofFNA specimens. One may consider aspirates as inadequatebecause only a few viable bland squamous cells can berecognized. The possibility of contamination from the skinduring CT-guided FNAs and from the esophageal mucosaduring endoscopic ultrasound-guided FNAs should also bekept in mind, especially in scanty specimens.

The histogenesis of LEC of the pancreas is uncertain. Inone of our cases, focal areas of goblet cells were present onthe surface of the squamous epithelial lining. Mucicarmineand Alcian blue stains were positive in the goblet cells. Arecent immunohistochemical study demonstrated that cyto-keratin phenotypes of the epithelial lining of the LEC weresimilar to those of pancreatic retention cysts with squamousmetaplasia.28 These findings lend support to the hypothesisof the LEC arising from an obstructed dilated pancreaticduct with squamous metaplasia. However, the presence of azone of lymphoid tissue, as seen in branchial cleft cysts,cannot be explained. In addition, the incidence of LEC of thepancreas is far lower than that of squamous metaplasia inpancreatic ducts. Another hypothesis is that LEC maydevelop from an ectopic pancreas in a peripancreatic lymphnode. In our two cases, the cysts appeared to locate in theperipancreatic tissue, which might support this theory. Otherpossible origins for LEC of the pancreas include its genesisfrom benign epithelial inclusions embedded in the pancreas,or its genesis from aberrant branchial cleft cysts that fusewith the pancreatic anlage during embryogenesis.3,4

In summary, LEC of the pancreas is a rare, true cyst forwhich FNA reveals a characteristic cytologic pattern. Preop-erative recognition of its benign nature enables conservativesurgical management.

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