Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review

Abstract

Adenosquamous carcinoma of the pancreas (ASCP) is a rare entity. Like adenocarcinoma of the pancreas, overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalcemia. Various theories exist as to why this histological subtype exists, as normal pancreas tissue has no benign squamous epithelium. Due to the rarity of this disease, limited molecular analysis has been performed, and those reports indicate unique molecular features of ASCP. In this paper, we characterize 23 patients diagnosed with ASCP through molecular profiling using immunohistochemistry staining, fluorescent in situ hybridization, chromogenic in situ hybridization, and gene sequencing, Additionally, we provide a comprehensive literature review of what is known to date of ASCP. Molecular characterization revealed overexpression in MRP1 (80%), MGMT (79%), TOP2A (75), RRM1 (42%), TOPO1 (42%), PTEN (45%), CMET (40%), and C-KIT (10%) among others. One hundred percent of samples tested were positive for KRAS mutations. This analysis shows heretofore unsuspected leads to be considered for treatments of this rare type of exocrine pancreas cancer. Molecular profiling may be appropriate to provide maximum information regarding the patient's tumor. Further work should be pursued to better characterize this disease.

Keywords: Adenosquamous carcinoma of the pancreas; Molecular profiling; Review.

Figure 1

Typical pathology of adenosquamous carcinoma of the pancreas. H and E slides of two patient’s tissues, showing the adeno vs squamous component (arrowheads = adeno; arrows = squamous component). A: Tissue from head of pancreas; B: Tissue from tail of pancreas; both are G2, moderately differentiated cancers.

Figure 2

Collection of images from three separate patients with adenosquamous carcinoma of the pancreas. The typical complex enhancing mass and mixed morphology of necrosis and enhancing tissue is demonstrated in this figure. A-E are taken from a four phase contrast enhanced CT (pre-contrast, arterial, venous and delayed images). This type of scanning technique can be helpful to define the tumor and its invasion into surrounding structrures. A-E represent a coronal (A) and axial (B-E) images through a large, infiltrating, necrotic tumor with islands of slow enhancement (B-E). Note the islands of soft tissue enhancement increasing from arterial to delayed phase contrast enhanced CTs. These features are usually signs of very aggressive tumors. In another subject (F-I) there is again a central area of necrosis (arrowheads) surrounded by a ring of slowly enhancing tumor (red circle). Note the relative lack of surrounding soft tissue infiltration compared to the tumor on Panels A-E. Panels J-O are taken from a third subject and are an example of an atypical adenosquamous carcinoma involving the pancreas tail with a slowly enhancing, non-infiltrating lesion both on CT (J-L) and post gadolinium subtraction MRI (M-O). The white outline in Panels M-O outlines the contour of the pancreas with the enhancing lesion seen towards the tail of the pancreas. There is a small focus of necrosis present (arrow), a feature typical of adenosquamous carcinoma of the pancreas. The corresponding FDG PET/CT (P and Q) is unusual in that it shows that this mass is not hypermetabolic unlike most adenosquamous pancreas carcinomas. Ao: Aorta; IVC: Inferior vena caval; SMA: Superior mesenteric artery; SMV: Superior mesenteric vein.