Pancreatic adenosquamous carcinoma and intraductal papillary mucinous neoplasm in a CDKN2A germline mutation carrier

Abstract

A 69-year-old woman from a kindred with familial atypical multiple mole melanoma and carrier of a germline mutation in CDKN2A, presented with abdominal pain caused by a solid-cystic pancreatic mass. The patient had an abdominal computed tomography three years before in which there was no evidence of pancreatic lesion. The endoscopic ultrasound guided fine needle aspiration showed adenocarcinoma with squamous component. After surgical resection the final diagnosis was adenosquamous pancreatic carcinoma (ASPC) arising in an intraductal papillar mucinous neoplasm (IPMN). Adenosquamous carcinomas are uncommon in the pancreas and have rarely been described in association with IPMNs. It has worse prognosis than the ordinary pancreatic ductal adenocarcinoma and some distinct features. We review the clinical, imaging, pathologic and molecular aspects of ASPC. Differential diagnosis with contamination, squamous metaplasia and pancreatic metastases from a distant squamous carcinoma is discussed. Besides, the case is an accelerated model of the adenoma (IPMN)-carcinoma sequence probably due to the CDKN2A germline mutation. Somatic CDKN2A mutations are common events in the early steps of sporadic pancreatic cancer, but germline mutation carriers have a significantly higher risk of pancreatic carcinoma.

Keywords: Adenosquamous carcinoma; CDKN2A; Intraductal papillary mucinous neoplasia; Melanoma-pancreatic cancer syndrome; Pancreatic carcinoma.

Figure 1

Computed tomography image. A: Computed tomography (CT) image of the solid-cystic pancreatic mass with distal atrophy of the pancreas and pancreatic duct dilatation; B: CT three years before in which no pancreatic lesions were present.

Figure 2

Endoscopic ultrasonography image. A: Radial endoscopic ultrasonography (EUS) view of the mass; B: Lineal guided EUS fine needle aspiration of the solid component of the mass.

Figure 3

Endoscopic ultrasonography fine needle aspiration biopsies and surgical specimen. A and B: Positive cytology from the pancreatic mass (adenocarcinoma with a significant keratinizing component suggestive of adenosquamous carcinoma), Papanicolaou staining 20 × and 40 ×, respectively; C and D: A solid-cystic pancreatic mass (gross pathology).

Figure 4

Microscopic pathology of the surgical specimen. A: Intraductal papillary mucinous neoplasm with adenocarcinoma component, hematoxylin and eosin (H and E) 10 ×; B-D: Squamous metaplasia and evident infiltrative squamous carcinoma, H and E 10 ×, 20 × and 40 ×, respectively; E: Adenocarcinoma with perineural invasion, alcian blue 20 ×; F: Peripancreatic lymph node metastasis (adenocarcinoma component), H and E 20 ×.

Figure 5

Immunohistochemical study in the surgical specimen. A: CK5/6 strong positivity in squamous component (metaplasia and carcinoma), × 20; B: Strong nuclear p63 immunopositivity in the invasive squamous carcinoma. The adenocarcinoma area display poor p63 nuclear positivity, × 20; C: MUC5a negativity in the squamous carcinoma component and strong positive in ductal epithelial cells, × 20; D: MUC1/EMA positivity in the squamous metaplasic component, × 20.