A lymphoepithelial cyst in the pancreatic accessory spleen: A case report

Abstract We present the first report of a lymphoepithelial cyst. As additional cases will likely be encountered in the future, our study sets the precedent for future research.


| INTRODUCTION
There are 57 reports of epidermoid cysts in the accessory spleen in the pancreas, but none of lymphoepithelial cysts (LECs) in this location. The pathological diagnostic criteria for LECs are still unclear and controversial. We describe an LEC in the accessory spleen, including the pathological findings.
Pancreatic cysts are broadly categorized as neoplastic or non-neoplastic. The former category includes intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), and serous cystic neoplasms (SCNs), and the latter includes pancreatic pseudocysts and lymphoepithelial, epidermoid, and dermoid cysts. 1 There are also pancreatic neuroendocrine tumors (pNETs), which are tumors that have degenerated into cysts. These classifications are laid out in several documents including the International Association of Pancreatology guidelines, 2 the European expert consensus statements, 3 and the American Gastroenterological Association guidelines. 4 However, there are no guidelines or clear diagnostic criteria for pancreatic pseudocysts.
Pancreatic lymphoepithelial cysts (LECs) are rare benign lesions initially described by Luchtrath and Schriefers in 1985 5 and named by Truong et al in 1987. 6 LECs are typically observed in middle-aged and elderly men; they occur equally in the pancreatic head, body, or tail, and may present | 3 of 20 HIROI et al.
as a single or multilocular lesion. This study is the first to document a case of an LEC in the pancreatic accessory spleen, and thus, in this respect, we believe it is valuable. Furthermore, the knowledge acquired in this study will enable the development of international diagnostic criteria for LECs and similar epidermoid cysts and dermoid cysts in the future. A 43-year-old man was found to have a pancreatic tail cyst on abdominal ultrasonography at a previous hospital. He had no subjective symptoms or medical history. Laboratory examinations showed normal results for the following: complete blood cell counts, hepatic and renal function, and serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen , amylase, lipase, and glucose.

| PRESENTATION OF THE CASE
The patient was referred to our hospital, and the presence of the cyst in the pancreatic tail was confirmed via computed tomography (CT) (Figure 1). The cystic lesion was 15 cm in diameter, monocystic, and surrounded by an area of low intensity. Magnetic resonance imaging (MRI) revealed a lesion with depleted and enhanced intensity on T1-and T2-weighted images, respectively (Figure 2A, B). Diffusion-weighted MRI displayed increased signal potency in the peripheral portion of the cystic lesion (the wall and the septa) ( Figure 2C); the cystic contents had reduced intensity on enhanced MRI ( Figure 2D). Additional observations included a cyst with high-echoic lesions, a pancreatic tail, and calcification on the cyst margin on endoscopic ultrasonography ( Figure 3A), and a slight displacement of the pressure superior to the duct with F I G U R E 4 Macroscopic findings and histopathology: A, The pancreatic parenchyma at the tail of the pancreas (white arrowhead) contains spleen tissue (white arrow) and a multilocular cyst with a maximum diameter of 17 mm (yellow arrow). B, The cystic wall is lined by mature keratinized squamous epithelium and underlying lymphoid tissue (×20 magnification, hematoxylin and eosin staining). C, The epithelial lining is surrounded by splenic pulp and pancreatic tissue (×40 magnification, hematoxylin and eosin staining). D, Lymphoid follicles and lymphoid tissue are observed (×100 magnification, hematoxylin and eosin staining)  no narrowing or disruption on endoscopic retrograde cholangiopancreatography ( Figure 3B). The CT and T1-and T2-weighted MRI data suggested cyst degeneration, which is a characteristic of pNETs. Hence, the preoperative diagnosis was a pNET. Distal pancreatectomy was performed with concomitant splenectomy; the guidelines mentioned above recommend surgery as the firstline treatment for pNETs.
The postoperative course was uneventful. The excised surface of a resected specimen indicated a multilocular cyst with solid nodules ( Figure 4A). Histopathological examination revealed the presence of spleen tissue, both red and white pulp, in the parenchyma of the pancreatic tail. Hence, we diagnosed the tumor as an intrapancreatic accessory spleen cyst, with the tumor originating in the accessory spleen rather than in the tissue between the tail of the pancreas and the spleen. The major and minor multilocular cysts had a maximum diameter of 17 mm. The luminal epithelium consisted of mature squamous epithelium and subepithelial lymphoid tissue ( Figure 4B), and the cyst lumen contained keratin and cholesterol deposits in the clefts. The lymphatic tissue occupied the majority of the cyst ( Figure 4D), which is a diagnostic criterion for LECs. Ultimately, the patient was diagnosed with an LEC of the pancreatic accessory spleen.

| DISCUSSION
An accessory spleen is not uncommon. Halpert et al reported 291 (10.8%) accessory spleens in 2700 autopsied cases; 215 (62.1%) were in the vicinity of the splenic hilum, followed by 78 (22.5%) in the pancreatic tail. 7 However, a cyst occurring in a pancreatic accessory spleen is extremely rare, with only 57 reported cases (Table 1).  The lesion site was the pancreatic tail in all 57 cases. The primary complaints were abdominal pain and vomiting, although 33 of the 57 cases were asymptomatic. Tumors with smaller diameters are often asymptomatic.
The cyst in the accessory spleen in our study was 1.5 cm in diameter, making it the smallest of those previously reported (range, 15-134 mm), and apparently had no symptoms. Levels of CEA or CA 19-9 were elevated in some previous cases, but within normal limits in others. In many cases, the lesion was asymptomatic and detected by imaging. Cyst morphology was multilocular in 33 cases and unilocular in 15. Most cysts had low intensity on T1-weighted MRI and high intensity on T2-weighted MRI. Preoperative diagnoses, such as an IPMN, pNET, epidermoid cyst, and malignant tumor, suggest case complexity. The preoperative diagnosis in our case was a pNET, whereas the histopathologically confirmed diagnosis was an LEC in the accessory spleen. This is the first report of an LEC in this location. Pancreatic LECs are extremely rare, accounting for only 0.5% of pancreatic cysts. Mege et al examined pancreatic LECs in 91 middle-aged to elderly men (mean age, 55 years; range, 20-82 years); the lesion was occasionally accompanied by abdominal pain (43%) and an elevated serum CA 19-9 level (55%). 54 Pancreatic cysts are classified as true cysts, pseudocysts, or cystic neoplasms. LEC is considered to be a type of true cyst, with a lining of squamous epithelium and dense subepithelial lymphoid tissue. The cystic contents are typically white in color and may include keratinized material or cholesterol crystals. Adsay et al classified cystic lesions covered by the squamous epithelium of the pancreas as LECs as epidermoid (those occurring in the subpancreatic epithelium) or dermoid (those with cutaneous appendages). 55 The pathological diagnostic criteria for LECs are ambiguous. Presently, the predominant diagnostic criterion of an LEC is a lumen surface with a stratified squamous epithelium and abundant lymphoid tissue underneath. The reports so far classified cysts as guided by Adsay et al 55 : "LECs are characterized microscopically by stratified squamous epithelium surrounded by a band of mature lymphoid tissue with intervening wellformed germinal centers." Adsay et al also added the following: "The second type of squamous-lined cyst in the pancreas is the epidermoid cyst arising in intrapancreatic accessory spleen." These investigators did not mention lymphoid-rich cysts in the accessory spleen. Some of the cases epidermoid cysts described by Truong et al in 1987 are now thought to be LECs. Owing to the unclear classification criteria, it is possible that other cases reported as epidermoid cysts are also LECs.
In the present case, the lumen epithelium of the multilocular cyst consisted of mature squamous material with developed subepithelial lymphoid tissue. In addition, white and the red pulp were detected in the pancreatic accessory spleen; hence, the cyst was diagnosed as a splenic LEC. There are three theories regarding the pathogenesis of pancreatic LECs. 6 The first theory suggests that LECs originate in the misplaced branchial cleft tissue because of the histologic resemblance. The second suggests that squamous metaplasia in an obstructed pancreatic duct, which subsequently protrudes into a peripancreatic lymph node, gives rise to LECs. The third links LECs to cyst development from an ectopic pancreas in a peripancreatic lymph node. At present, a consensus has not been reached. Tateyama et al summarized the findings of their immunohistochemical study as follows: "The cytokeratin phenotypes of the epithelial lining of LEC were similar to those of the epithelial retention cysts but different from those of branchial cleft cysts. In addition to the cytokeratin pattern, the presence of some islets and ducts in the fibrous wall of the LEC might support the second hypothesis." In the present case, the LEC was found in the accessory spleen in the pancreas, which is consistent with the second hypothesis. However, further consideration and discussion are required.