LECs of the pancreas are extremely rare, nonneoplastic, intrapancreatic or peripancreatic keratinizing cysts with surrounding stroma that resemble lymph nodes.20 LECs are lined by a stratified squamous epithelium and contain subepithelial lymphoid tissue and follicles.14 In 1985, Lüchtrath and Schriefers23 first described the distinctive morphological features of LECs, which were similar to the branchial cleft cysts of the lateral neck. The term "LEC of the pancreas" was proposed by Truong et al.24 in 1987.

LECs, which comprise about 0.5% of all pancreatic cysts, predominantly occur in middle-aged men (mean age, 55; M:F, 4:1). LECs have well-delineated multilocular (60%) or unilocular (40%) masses of variable size, ranging from about 1 to >15 cm.25 The cyst contents vary from serous to caseous-like, depending on the degree of keratin formation.26 The largest series in the surgical pathology literature was reported by Adsay et al.27 and included a total of 12 patients. Because of their rarity, the cytologic features of LECs have been described in small case reports. It occurs at any age and no gender preference was reported. The pathogenesis of LECs is imprecise. One theory suggests an origin from misplaced brachial cleft tissue, because the two lesions histologically resemble one another.8 Another theory suggests they originated from squamous metaplasia of an obstructed pancreatic duct, which subsequently protrudes into a peripancreatic lymph node.24,25 Finally, some investigators have suggested that cysts develop from ectopic pancreatic tissue in peripancreatic lymph nodes.24 This theory would explain the often extrinsic location of the lesions and the fact that pancreatic tissue can be found throughout these lesions.28 Furthermore, benign ectopic pancreatic tissue has been reported in peripancreatic lymph nodes.29 In contrast to LECs of the head and neck, which are frequently associated with viral or systemic illness, there has been no recorded evidence of such diseases with pancreatic LECs.8 The lesions are not believed to be neoplastic, and no malignant behavior has been recorded to date. Additionally, there have been no reports of LECs becoming malignant or recurring after surgical resection. LECs have appeared as both multilocular and unilocular cysts. No characteristic findings of conventional imaging tools like transabdominal sonography or abdominal CT scan. However, recent evidence suggests that MRI with a high signal on T1-weighted images and a low signal on T2 images, which reflects the keratin content of the cysts, may facilitate correct diagnosis of LECs.30 In an EUS case series conducted by Nasr et al.,31 pancreatic LECs commonly appeared as solid, hyperechoic, heterogeneous masses with subtle postacoustic enhancement. Occasionally, fine or coarse sludge like hyperechoic echo architecture was also seen, which was likely due to debris within the cyst.

The first description of cytologic findings of LECs was published by Mitchell32 in 1990. The FNA samples typically showed abundant, anucleated squamous cells with few benign-appearing nucleated squamous cells, debris (keratinous and amorphous), occasional multinucleated giant cells and cholesterol crystals.8 FNA is the only tool for diagnosis of LECs when keratinizing squamous epithelium and lymphoid tissue are observed; however, the specificity and sensitivity of FNA remains poor; the detection of LEC was occurred in almost half of all cases to which FNA has been applied.30

Pseudocysts and cystic neoplasms of the pancreas are differential diagnoses of LEC. Lack of squamous epithelium in the aspirate from pseudocysts and elevation of amylase with low carcinoembryonic antigen (CEA) levels are essential to differential diagnosis. Aspirates from mucinous cysts usually show background extracellular mucus with or without mucinous epithelium. However, the degenerated squamous material of LECs may be misinterpreted as mucoid material.8,33 Chemical analysis of pancreatic LECs fluid has rarely been reported. Occasional elevation of CEA and CA 19-9 could lead to false diagnosis of mucinous neoplasms, especially because EUS-guided FNA samples may show both squamous and glandular contaminants.34 However, the presence of abundant anucleated squamous epithelium should favor a diagnosis of pancreatic LEC.

If the patient is asymptomatic and EUS-FNA firmly established the diagnosis of LEC based on cytological examination of the cyst fluid, surgery can be avoided and the patient may be followed with serial cross-sectional imaging of the upper abdomen.35 Because the absence of cytological proof of LECs, even with high cystic fluid CEA and CA 19-9 levels, does not completely exclude LEC diagnosis, surgical resection is considered when making a confident preoperative diagnosis (Figs. 4,5,6).

The term mucinous nonepithelial cyst was first described by Kosmahl et al.41 in 2002. They reported five cases of a novel nonneoplastic cystic change in pancreas. This benign cyst is lined with a monolayer of cuboidal to columnar mucinous epithelium and appears as unilocular or multilocular. Communication with the pancreatic duct has not been observed.

The pathology of MNCs are characterized by mucinous differentiation of the lining epithelium, lack of cellular atypia or increased proliferation, a thin rim of almost acellular supporting stroma and the absence of communication with the pancreatic ducts.41 MNCs are considered benign and have not been found to demonstrate any neoplastic features such as dysplasia, proliferative activity, invasive growth patterns, or metastatic spread to date.

The incidence of MNCs is 2.1% to 3.4% in resected pancreatic lesions. MNCs are found over a wide age range (20 to 88 years), but tend to be more common in females over 50 years of age.42 Pancreas head (65%, 13/20) is the most frequently location of MNCs. Most MNCs present as a single cyst (70%, 14/20), with only 30% presenting with multiple lesions.42 Finally, most MNCs have been found incidentally and their clinical presentations are usually nonspecific. The pathogenesis of MNCs is unclear. Cao et al.43 proposed that they might be related to acinar-ductal mucinous metaplasia. The key clinicopathological features of MNCs include: (1) mucinous differentiation of the lining epithelium; (2) lack of cellular atypia or increased proliferation; (3) a thin rim of supporting, almost acellular stroma; (4) lack of communication with the duct or biliary system; and (5) preferential localization in the pancreatic head.41 It is currently not clear if these cysts are entirely benign or represent the earliest elements of the neoplastic spectrum, which is seen in most mucinous cysts. In the case of MNC, it is clear that further molecular analysis must be pursued to assess this novel lesion's place on the spectrum of adenoma to carcinoma.44 MNCs represent a diagnostic challenge, as they often mimic IPMNs and MCNs clinically and radiographically. EUS-FNA obtained cyst fluid often demonstrates elevated CEA levels, making differentiation between benign and premalignant lesions difficult.44 The absence of characteristic ovarian type stroma can be used to distinguish MCNs from MNCs, and absence of pancreatic ductal communication can exclude IPMNs from MNCs. Atypical epithelial cells, if present, favor neoplastic mucinous cystic lesions and may be a marker to exclude MNCs. A recent study reported that MNCs have a positive apomucin phenotype, which may distinguish them from IPMNs.43,44 Nevertheless, these analyses can only be carried out on postoperative gross specimens, and are not useful for preoperative diagnosis.

In a previous investigation of mucin expression in MNCs, expression of Muc 5Ac and Muc1 was reported in 14 of 20 (70%) and five of 20 cases (25%), respectively. Expression of Muc2 was not observed in any of these cases.41,43 The images of MNCs upon MRI may be indistinguishable from that of MCNs, especially if the cysts are large and have thick walls. FNA cytology of the epithelium of MNCs shares that of retention cysts. Retention cysts can be excluded based on the absence of potential causes or evidence of ductal obstructions; however, this is not always possible. Nonetheless, although EUS-FNA could not distinguish MNCs from retention cysts, treatment and prognosis will not be affected owing to the benign nature of both diseases.6 If the diagnosis of MNCs is doubtful, surgical resection is a reasonable strategy (Figs. 10,11,12).

Lymphangiomas are rare, benign, and congenital malformations of the lymphatic systems.45 Most lymphangiomas occur in the neck (75%) and axillary regions (25%),46 while lymphangiomas of the pancreas are extremely rare, accounting for only 1% of all occurrences.47 Pancreatic lymphangiomas are predominantly found in women, with a female:male ratio of approximately 2:1.48 The average age at presentation is 25.6 years, and most patients are asymptomatic. In the only histologic study of pancreatic lymphangiomas conducted to date, the characteristic histological features included multiple cystic spaces lined by flattened endothelial cells, irregularly distributed smooth muscle cells, and lymphoid aggregates in the walls of the cysts.48 Although the pathogenesis of lymphangiomas is still unclear, a well-established theory suggests that lymphangiomas arise from sequestrations of lymphatic tissue during embryonic development.49 However, it has been suggested that abdominal trauma, lymphatic obstruction, inflammatory processes, surgery or radiation therapy lead to the secondary formation of lymphangiomas.50 A diagnosis of pancreatic cystic lymphangioma is made if the aspirated fluid is chylous in appearance and has an elevated triglyceride level.51 If the fluid aspirated is serous and has only a mildly elevated triglyceride level, then further diagnostic workup or surgical referral may be necessary.52

No malignant transformation of pancreatic cystic lymphangiomas has been reported to date. Expectant management with follow-up is a reasonable approach; however, the possibility remains for hemorrhage, torsion, rupture, obstruction and infection in these patients, especially in the setting of any abdominal trauma. This potential should be weighed against the risks of surgery, which by most reports is curative.53