Mucinous cystadenoma of the pancreas with predominant stroma creating a solid tumor
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Mucinous cystic neoplasm (MCN) of the pancreas is basically cystic epithelial neoplasm, unilocular or multilocular, occurring almost exclusively in women.
A 51-year-old female presented with a pancreatic mass incidentally found on the abdominal computed tomography. She underwent distal pancreatectomy. The sectioned surface of the pancreas revealed a circumscribed, whitish gray ovoid firm mass with some cystic spaces. Microscopically, glandular or small cystic structures were scattered in the predominant stroma creating a solid appearance. The subepithelial stromal component was composed of cytologically bland looking spindle cells, which resembled ovarian stroma. The stromal cells were reactive to CD 34, vimentin, progesterone receptor and calretinin. The microscopy was consistent with mucinous cystadenoma of the pancreas.
This case of mucinous cystadenoma of the pancreas showed very interesting pathology: It was solid rather than cystic, and accompanied by abundant benign transitional epithelia, which was a very unusual and novel finding in the mucinous cystic neoplasm of the pancreas.
KeywordsMain Pancreatic Duct Solitary Fibrous Tumor Inflammatory Myofibroblastic Tumor Mucinous Cystic Neoplasm Mucinous Cystadenoma
Mucinous cystic neoplasm (MCN) of the pancreas is a cystic neoplasm, unilocular or multilocular, occurring almost exclusively in women. The overwhelming majority of cases occur in the body-tail of the pancreas. MCNs show two distinct components: an inner mucinous epithelial layer and an outer dense cellular ovarian-type stromal layer [1, 2, 3, 4, 5].
The case reported here is an exceptional case of MCN of the pancreas with predominant stromal component creating a solid tumor, and abundant transitional cell differentiation.
Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections by the avidin-biotin peroxidase complex method. The primary antibodies used were as follow as; Pancytokeratin (1:50, AE and AE3, Zymed, San Francisco, USA), high molecular weight cytokeratin (1:100, 34betaE12, DAKO, Denmark), cytokeratin 7 (1:50, OV-TL 12/30, DAKO), cytokeratin 20 (1:40, Ks20.8, DAKO), calretinin (1:50, polyclonal, DAKO), estrogen receptor (1:40, 6F11, Novocastra, Newcastle, UK), progesterone receptor (1:80, 1A6, Novocastra), chromogranin A (1:200, LK2H10 and PHE5, NeoMarker, Fremint, CA, USA), CD34 (1:40, QBEnd 10, DAKO), vimentin (1:50, V-9, Biogenex, san Ramon, CA), α-smooth muscle actin (1:50, α-sm-1, Novocastra, Newcastle, UK), desmin (1:100, D33, DAKO), S-100 protein (1:150, B32.1, Biomeda, Foster city, CA), CD99 (1:100, HO36-1.1, NeoMarker, Fremint, CA), CD99 (1:100, HO36-1.1, Neomarker), c-kit (1:300, 104D2, DAKO). Both mucinous and transitional epithelia were diffusely immunoreactive to pancytokeratin and cytokeratin 7, but not reactive to cytokeratin 20 except for goblet cells. Transitional epithelia were diffusely reactive to high molecular weight cytokeratin (Figure 3G), whereas mucinous epithelia were not reactive to it. Scattered endocrine cells were highlighted by positive reactivity to chromogranin A (Figure 3E). The stromal cells were diffusely positive for CD 34 and vimentin, and focally positive for calretinin (Figure 3B) and progesterone receptor (Figure 3C), while negative for estrogen receptor, alpha-smooth muscle actin, desmin, c-kit, CD99, S100 protein and cytokeratin.
MCNs of the pancreas are defined by cystic epithelial neoplasms composed of columnar mucin-producing epithelium. This tumor occurs almost exclusively in women and shows no communication with the pancreatic duct system. According to the grade of dysplasia, tumors may be classified as adenoma, borderline and non-invasive or invasive carcinoma [1, 2, 3, 4, 5].
The present tumor was composed of mucin producing epithelium with an ovarian type stroma. The stroma was predominant overgrowing epithelial element and creating a solid tumor. From this point of view, the main differential diagnoses of the present case include MCN with sarcomatous stroma, benign mesenchymal tumors and solid-pseudopapillary neoplasm. MCN with sarcomatous stroma is a rare variant of MCNs associated with a malignant sarcomatous stroma. This sarcomatous stroma is extremely hypercellular, contains mitotic figures, and shows marked atypia and pleomorphism of stromal cells . Unlike the sarcomatous stroma, the stroma of the present case showed neither significant cellular atypia nor mitoses. Primary mesenchymal tumors of the pancreas are extraordinarily rare. Examples of benign pancreatic mesenchymal tumors composed of bland looking spindle cells include inflammatory myofibroblastic tumor , extragastrointestinal stromal tumor  and solitary fibrous tumor . The possibility of primary mesenchymal tumors of the pancreas can be excluded by reason of the following points. Although the predominant stromal component overgrew the epithelial element in the present case, the epithelial element was distributed in the periphery as well as the center of the tumor, suggesting that the epithelial component is a true tumor element, not non-neoplastic tissue entrapped in the tumor. Moreover, inflammatory myofibroblastic tumor can be excluded from the viewpoint of no significant mixture of chronic inflammatory cells in the present case. Recently, the pancreatic counterpart of gastrointestinal stromal tumor was described and was based on its c-kit positivity . Although in the present case the spindle cells within stroma were reactive to CD34, they were not reactive to c-kit. To the best of my knowledge, only a case of solitary fibrous tumor of the pancreas has been reported in English literature . Although the CD34 positivity of stromal cells in the present case mimicked solitary fibrous tumor, the characteristic histology of solitary fibrous tumor, which correspond to patternless growth of short fascicles, a short storiform arrangement of the spindle or ovoid cells and vascularization with slit-like space was not observed in the present case. In my investigation of CD34 reactivity for normal ovarian tissue, the normal ovarian stroma was also documented to be reactive to CD34 (unpublished data). Solid- pseudopapillary neoplasm is somewhat similar to the present case from the viewpoint of mixed solid and cystic features but different by reason that solid-pseudopapillary neoplasm is composed of monomorphic polyhedral cells forming solid and pseudopapillary structures .
The epithelial component of MCN is composed of columnar cells which can also reveal pseudopyloric, gastric foveolar, small and large intestinal, and squamous differentiation, as is also observed in ovarian MCN [1, 2, 3, 4]. In the present case, abundant pseudopyloric and intestinal metaplasia as well as transitional differentiation was observed. Transitional epithelia were distinguished by high molecular weight cytokeratin positivity. The mixed mucinous cystadenoma and benign Brenner tumor were described in the ovary [10, 11, 12]. However, the accompaniment of transitional epithelium was not reported in MCN of the pancreas. The stroma adjacent to the transitional epithelium was denser and more hyalinized than that adjacent to the columnar epithelium. These histologic findings suggest the possibility of a pancreatic counterpart of mixed mucinous cystadenoma and benign Brenner tumor of the ovary.
The stromal component of MCN is composed of ovarian-type stroma which express vimentin and in a high proportion, progesterone receptor, estrogen receptor, calretinin, and alpha inhibin [11, 13, 14, 15]. Calretinin has been shown to recognize testicular Leydig cells and hilar ovarian cells. In the present case, stromal cells were reactive for progesterone and calretinin. The possible derivation of the stromal component of MCNs from the ovarian primordium is supported by morphology, tendency to undergo luteinization, presence of hilar-like cells, and immunophenotypic sex cord-stromal differentiation [11, 13, 14, 15]. It has been hypothesized that ectopic ovarian stroma incorporated during embryogenesis in the pancreas may release hormones and growth factors causing nearby epithelium to proliferate and form cystic tumors [11, 13, 14, 15].
This case is a pancreatic tumor showing very interesting and unusual pathology. According to the current WHO classification of pancreas, this case belongs to the mucinous cystadenoma. But this case was solid rather than cystic, and showed abundant benign transitional epithelia, which are very unusual and a novel finding that has not been described in MCNs of the pancreas. This histopathology is very similar to the mixed mucinous cystadenoma and benign Brenner tumor of the ovary [10, 12].
This research was conducted by the research funds of Dankook University in 2004.
Permission of the patient was obtained for publication of her case records.
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