Lymphoepithelial Cyst of the Pancreasin a Young Woman

May 25, 2007
Surgical Rounds®, January 2006, Volume 0, Issue 0

Dimitris P. Korkolis, Consultant Surgeon, First Department of Surgery, Hellenic Anticancer Institute, St. Savvas Hospital, Athens, Greece; Dana Osborne, Research Fellow, Department of Surgery, University of South Florida; Brian A. Boe, Medical Student I, Department of Surgery, University of South Florida; Osama Al-Saif, Fellow in Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH; Americo A. Gonzalvo, Affiliate Associate Professor, Department of Pathology, Tampa General Hospital; Larry C. Carey, Professor of Surgery, Department of Surgery, University of South Florida; Alexander S. Rosemurgy, Professor of Surgery, Department of Surgery, University of South Florida; Emmanuel E. Zervos, Assistant Professor of Surgery, Department of Surgery, University of South Florida, Tampa, FL

Dimitris P. Korkolis, MD, PhD Consultant Surgeon First Department of Surgery Hellenic Anticancer Institute St. Savvas Hospital Athens, Greece Dana Osborne, MD Research Fellow Department of Surgery University of South Florida

Brian A. Boe, BS Medical Student I Department of Surgery University of South Florida Osama Al-Saif, MD Fellow in Surgical Oncology Department of Surgery The Ohio State University Columbus, OH Americo A. Gonzalvo, MD Affiliate Associate Professor Department of PathologyTampa General Hospital Larry C. Carey, MD

Professor of Surgery Department of Surgery University of South Florida

Alexander S. Rosemurgy, MD Professor of Surgery Department of Surgery University of South Florida

Emmanuel E. Zervos, MD Assistant Professor of Surgery

Department of Surgery

University of South Florida Tampa, FL

Establishing a preoperative diagnosis of lymphoepithelial cyst is difficult, because it resembles other cystic neoplasms of the pancreas. This is particularly true when the lesion is found in the body or tail of the pancreas in a young woman, because these lesions are predominantly associated with middle-aged men. The authors report the case of lymphoepithelial cyst of the pancreas in a young woman who presented with vague abdominal discomfort. They also provide a review of the literature.

Advances in diagnostic imaging tec?hniques have allowed cystic lesions of the pancreas to be detected.1,2 Lymphoepithelial cysts of the pancreas, which constitute a rare but distinctive oncologic entity, are characterized by the presence of mature stratified squamous lining that is surrounded by abundant lymphoid tissue with germinal center formation.3 These lesions may mimic a pseudocyst or a cystic neoplasm both clinically and radiographically.4 There have been approximately 50 reported cases in the world literature, with most describing these lesions in middle-aged men.5 We report the case of a lymphoepithelial cyst of the pancreas in a young woman. Only seven other cases have been reported in women, with our patient being the youngest. We also provide a review of the literature.

Case report

A 33-year-old woman presented with a 2-week history of nonspecific poorly localized abdominal and lower back pain, which was accompanied by malaise, low-grade fever, nausea, and diarrhea. She reported no weight loss, biliary colic, jaundice, vomiting, abdominal trauma, previous pancreatitis, or ethanol abuse. Her surgical history included a diagnostic laparoscopy for an ovarian cyst and endometriosis. Her medical history was otherwise unremarkable. Abdominal computed tomography (CT) scanning revealed a well-circumscribed, 3.0 x 2.5-cm, multilocular cystic lesion of low attenuation within the body of the pancreas (Figure 1). No abnormal adenopathy or intra-abdominal fluid collections were detected.

On admission to the hospital, she was afebrile but reported persistent, dull abdominal discomfort. Laboratory studies revealed an elevated white blood cell count of 14,600/mm3, with a shift to the left. The remainder of the workup, in?cluding liver function tests, amylase and lipase levels, coagulation profile, and serum carcinoembryonic antigen and CA19-9 levels, was unremarkable. Based on the patient's age and sex, as well as the location and radiologic features of the lesion, the diagnosis of a mucinous cystadenoma or cystadenocarcinoma, rather than an intraductal papillary neoplasm of the pancreas, seemed to be the most probable.

The patient was taken to the operating room and a cystic mass was found in the anterior and upper part of the body of the pancreas. It protruded from the surface and firmly adhered to the splenic artery. With a line of transection located immediately to the left of the superior mes-enteric vein, a distal pancreatectomy, en block total splenectomy, and radical peripancreatic lymph node dissection, were undertaken. The operation was completed with a cholecystectomy and liver biopsy. Intraoperative frozen section of the specimen demonstrated no evidence of malignancy and confirmed that the resection margins were free of disease.

Gross examination showed a 3 x 3 x 2-cm, multiloculated, cystic lesion in the body of the pancreas. It was clearly separated from the adjacent normal pancreatic tissue by a thin external fibrous capsule. The lining of the cyst was tan-pink and predominantly smooth. The contents of the cyst were similar to that of a sebaceous cyst. Microscopic pathology re?vealed a cystic lesion lined by mature, stratified, keratinizing squamous epithelium, and surrounded by abundant be?nign lymphoid tissue (Figure 2). No evidence of peripancreatic lymph node infiltration was demonstrated. Biopsies of the spleen, gallbladder, and liver showed no pathologic diagnosis. These findings were consistent with the diagnosis of a benign lymphoepithelial cyst of the pancreas. The patient had an uneventful hospital recovery and was discharged to home on postoperative day 5.

Classification of true cystic lesions of the pancreas

Primary cystic neoplasms ? Serous cystadenoma/cystadenocarcinoma

? Mucinous cystadenoma/cystadenocarcinoma

? Acinar cell cystadenocarcinoma

? Cystic islet cell tumors

? Cystic choriocarcinoma

? Cystic teratoma

? Angiomatous cyst neoplasms

Angiomas

Lymphagiomas

Hemangioendotheliomas

Parasitic cysts

? Echinococcal (hydatid) cyst

? Taenia solium cyst

Congenital cysts

? Simple cyst

? Polycystic diseases

Polycystic kidney disease von Hippel?Lindau disease

Cystic fibrosis Isolated pancreatic polycystic disease

? Enteric cyst

? Endometriosis

Extrapancreatic cysts

? Paraduodenal duplication cyst

? Splenic cyst

? Adrenal cyst

? Lymphoepithelial cyst

Discussion

Cystic lesions of the pancreas may be classified as pseudocysts or true cysts based on the presence or absence of an epithelial lining.6 Pseudocysts account for 75% of pancreatic cystic lesions and true cysts make up the remaining 25%. True cysts have a broad histologic spectrum and may be further divided into neoplastic, congenital, or acquired le?sions. Cystic neoplasms are relatively common, ac?counting for 10% to 15% of all pancreatic cysts. Unlike pseudocysts, congenital cysts have no ductal communication. Heredi?tary cystic disorders, such as von Hippel?Lindau disease, polycystic kidney disease, and cystic f?i?brosis, may be associated with multiple pancreatic cysts. Endometriotic, enter?o?genous, dermoid, and lymphoepithelial cysts of the pancreas are much more uncommon (Table).

Lymphoepithelial cysts of the pancreas are an extremely rare oncologic entity. The first case was reported by Luchtrath and Schriefers in 1985 and described as a branchiogenic cyst of the pancreas.7 The term pancreatic lymphoepithelial cyst was initially proposed by Truong and colleagues.8 The pathogenesis of lymphoepithelial cysts of the pancreas is unclear. Hypotheses in?clude (1) an aberrant bran?chial cleft remnant that fused with the pancreatic orifice during development7; (2) epithelial inclusions or ectopic pancreatic tissue in peripancreatic lymph nodes8; (3) squamous metaplasia of an obstructed and dilated pancreatic duct followed by expansion into the peripancreatic lymph nodes8; and (4) an intrapancreatic accessory spleen.6 The hy?po?th?esis of squamous metaplasia seems to be the most accepted. It is supported by Carr and associates and Mur?ayama and colleagues who described heterotopic pancreatic tissue with squamous metaplasia of the ductal epithelium in the celiac and common hepatic lymph nodes, respectively.9,10

To our knowledge, only 50 other cases of pancreatic lymphoepithelial cysts have been reported in the literature.5,6,11-28 The patients ranged in age from 35 to 74 years, with a mean age of 57 years. There is a significant male predominance, with a male to female ratio of 7: 1. Only seven other cases of lymphoepithelial cysts of the pancreas have been diagnosed in women thus far. Approximate-ly 75% of the reported cases were asymptomatic and the cyst was an incidental finding at autopsy or during an unrelated surgery. Symptomatic patients reported vague abdominal discomfort, lower back pain, nausea, vomiting, diarrhea, malaise, fe?ver, or weight loss. It is unclear, however, whether these symptoms were dir?ectly attributable to the lymphoepithelial cyst.

An elevated serum CA19-9 level was found in almost half of patients and normalized postoperatively. Abnormal serum amylase or lipase levels were never de?tected. Most of the reported lesions were located in the head and body of the pancreas (38 cases), arising from the anterior aspect of the pancreatic surface. These lesions were uniloculated or multiloculated (more common) and ranged in size from 2 to 13 cm in maximal diameter.

Histologically, lymphoepithelial cysts of the pancreas have distinctive pathologic features that enable an accurate diagnosis after resection.26,27 The cyst is composed of mature, keratinizing, nonneoplastic squamous epithelium that is surrounded by a fibrous capsule associated with dense lymphoid tissue, often with prominent follicles. Occasionally, sebaceous or mucinous differentiation may be seen.16,24,28 The caseous content of the cyst is accounted for by the presence of keratin, which is not seen in other types of pancreatic cysts except for the equally rare dermoid cyst. Although usually encapsulated and separated from the surrounding pancreas, the cyst may erode into the pancreas, duodenum, and re?tro?peritoneum, causing a marked in?flam?matory response and making resection more technically challenging. Cytologic smears typically show numerous anucleated squa?mous cells. Benign, nucleated, keratinized cells range from few to many. This variability may be related to the locularity of the cysts, with increased locularity yielding more nucleated squamous cells. Lymph?o?ep?i?thelial cysts of the pancreas have only a few lymphocytes and histiocytes on cytologic smears.3,4

CT scanning is probably the most useful diagnostic imaging modality for identifying a lymphoepithelial cyst of the pancreas. The lesion is typically a well-circumscribed round mass that protrudes from the surface of the pancreas into the lesser sac.14,17 It is described to be cystic with a "low" or "water" density and may exhibit thin septations.23 Using radiologic features to establish a preoperative differential diagnosis between a lymphoepithelial cyst of the pancreas and other potentially malignant cystic neoplasms, however, is difficult due to the internal protrusion, wall calcification, and loculated architecture.22,23

Endoscopic retrograde cholangiopancreatography findings were normal in all reported cases because there is no communication between the lymphoepithelial cyst and the pancreatic duct. Fine-needle aspiration biopsy guided by CT scanning or endoscopic ultrasonography has limited usefulness due to its low diagnostic accuracy (less than 15%)25,26 and the risk of dissemination in cases of a cystic neoplasm. In addition, the high frequency of elevated serum CA19-9 levels, particularly in young wom?en, necessitates a more aggressive approach.

Enucleation or local resection, when technically feasible, is the surgical treatment of choice. When this is not possible or there is a cystic component to the tumor, partial pancreatectomy is recommended to perform complete removal of the lesion and achieve a curative surgical resection. Overall prognosis of lymphoepithelial cysts of the pancreas is excellent. Surgery offers complete relief of symptoms and minimizes the risk of recurrence.29

Conclusion

Lymphoepithelial cysts are rare but distinctive lesions that may be seen in the head, body, or tail of the pancreas where most cystic pancreatic neoplasms are encountered. Despite the reports in the literature, lymphoepithelial cysts may also affect young women and should be considered in the differential diagnosis of a patient who presents with a cystic lesion in the pancreas. Complete surgical removal offers the safest diagnostic and therapeutic approach.

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