MCN is a rare but distinctive pancreatic cystic neoplasm, defined by the lack of communication with the pancreatic duct system and the presence of a mucinous epithelium usually supported by an ovarian stroma. In our patient, the distinction from other reported typical MCNs was the extensive squamous metaplasia. This feature might be an indication of a longstanding MCN in which gradual replacement of the mucinous epithelium by squamous epithelial cells occurred. The pathogenesis is unclear, and there are two theories : (1) the squamous element is derived from squamous transdifferentiation of the adenomatous element; (2) the squamous element of the pancreatic tumor arises from pluripotent stem cells. In our case, the adenoma and squamous elements were mixed, and a gradual transition was identified. The glandular epithelial cells with LCK immunoreaction tended to be located on the surface of the squamous element in the area of significant hyperplasia. We speculate that the squamous component of the pancreas may be derived from pluripotent stem cells, and may be induced in our case by cystojejunostomy and drainage. Furthermore, an inflammatory reaction was found both in the anastomotic stoma biopsy and complete resection specimens, and the squamous metaplasia may be related to the inflammation.
The preoperative diagnosis of MCN is very important, since other types of pancreatic neoplasm may be treated differently and the grade of neoplasm does accurately predict the outcome [4, 5]. The main differential diagnosis includes other neoplastic cystic lesions (serous cystic neoplasm and the intraductal papillary mucinous neoplasm) and non-neoplastic cystic lesions. MCN must be distinguished in particular from an inflammatory pseudocyst, because drainage is appropriate for the latter, but long-standing drainage can transform apparently histologically benign MCNs into invasive MCNs [6, 7]. In our patient, the tumor also needed to be differentiated from a squamoid cyst of pancreatic ducts and mixed-epithelial papillary cystadenomas of borderline malignancy of mullerian type with squamous overgrowth (MEBMMSO). A squamoid cyst of pancreatic ducts usually has a thin wall lined by transitional/squamous cells without keratinization or a granular layer. The cyst is more commonly unilocular and typically contains distinctive acidophilic concentric enzymatic concretions which indicate their communication with the acinar system . MEBMMSO was defined as an ovarian cystic tumor composed of major squamous intracystic fronds accompanied by minor epithelial components of mullerian types, such as mucinous, serous, and endometrioid, and prominent intraepithelial infiltration by neutrophilic leukocytes . However, to date, this has not been reported in the pancreas, and there was no squamous element in the stoma biopsy in our patient. Lymphoepithelial cyst (LEC) of the pancreas may also present as pancreatic multilocular mass with cysts lined by squamous epithelium in the tail. However, it was characterized by cysts, some containing keratin, and lined by mature stratified squamous epithelium surrounded by dense lymphoid tissue, often with prominent follicles . LEC lacks the ovarian-type stroma, furthermore, papillary changes and mucinous cells are exceedingly rare, and if present, are very focal. Although it has been demonstrated that endoscopic ultrasonography can provide detailed images of internal structures and can be effective for the diagnosis of MCN , the best approach to obtain an accurate preoperative diagnosis is the comprehensive evaluation of all available clinical, serological, radiological, and pathological findings .
All MCNs should be resected to prevent malignant transformation but can be monitored for an appropriate time if the lesion is small without the presence of mural nodules [13–15]. Our patient underwent a cystojejunostomy at the age of thirty-four years, presumably with an underlying misdiagnosis of a pancreatic pseudocyst without characteristic clinical finding except for an incidental mass. Two years later, the diagnosis of “noninvasive MCN with intermediate-grade dysplasia” was diagnosed using stoma tissue sample. The complete resected specimen showed extensive squamous metaplasia, distinct papillary proliferation, and obviously decreased stroma, which might indicate a poorer outcome . Furthermore, IHC results showed that P53 nuclei expression increased in the squamous element, which may also suggest a poor prognosis . More studies of series of patients with MCN and longer follow-up times are needed to explore whether extensive squamous metaplasia represents neoplasm progression and/or predicts a poor prognosis.