Intraductal papillary squamous neoplasm of the pancreas: Cyto-histologic correlation of a novel entity

Abstract

We correlate the cytologic and histologic features of a squamous-lined pancreatic cystic lesion with a complex papillary architecture and an associated KRAS mutation, which to our knowledge has not been previously described. A 69 year-old woman presented with intermittent left upper quadrant pain. CT imaging revealed a 1 cm solid lesion in the pancreatic tail with peripheral calcification. Endoscopic ultrasound-guided fine needle biopsy showed a proliferation of epithelial cells with fibrovascular cores. An immunohistochemical stain for p40 was positive in the lesional cells. A distal pancreatectomy revealed a unilocular, cystic, well-circumscribed, soft and friable mass measuring 1.0 × 1.0 × 0.8 cm. Histologically, the cyst was lined by nonkeratinizing stratified squamous epithelium with a complex papillary architecture, filling the cyst lumen. Molecular sequencing revealed a KRAS G12V missense mutation. While the lesion shared some histologic features with the previously described "squamoid cyst of the pancreatic ducts", the complex papillary architecture and presence of a KRAS mutation are unique to the entity we describe herein and we propose the name "intraductal papillary squamous neoplasm of the pancreas." Reporting the cytomorphologic features of this novel entity may help in identification of similar lesions and understanding of the clinicopathologic significance.

Keywords: Fine needle biopsy; KRAS; Pancreas cyst; Papillary; Squamous.

Figure 1:

Cytologic features. Cell block material from fine needle biopsy demonstrating papillary cores with epithelial lining (4x)(A). Higher power view of papillary core showing cells with evidence of squamous differentiation. The cells lack significant cytologic atypia and no mitotic activity is seen (40x)(B). Papinicolaou stain showing scattered squamous cells with abundant cytoplasm and smaller clusters of epithelial cells (40x) (C). Immunohistochemical stain for p40 showing nuclear staining in the epithelial cells (40x) (D).

Figure 2:

Histologic features of resection specimen. Low power view of cyst demonstrating circumscription and papillary cores filling the cyst lumen (2x) (A). Higher power view of cyst lining showing low columnar cells with basal nuclei and apical cytoplasmic snouts lining the luminal aspect of the squamous epithelium (20x)(B). Higher power view of papillary core demonstrating foci of extracellular mucin (20x)(C). Microscopic cysts in background pancreas lined by attenuated squamous lining and demonstrating eosinophilic luminal concretions (10x)(D).