Diffuse expression of p16 in pancreatic neuroendocrine tumors (PanNETs) and the association of morphology variants

Distinguishing grade 3 pancreatic neuroendocrine tumors (PanNETs) from neuroendocrine carcinomas (PanNECs) is sometimes challenging. Recently, a diffuse p16-positive pattern was reported in PanNECs but not in grade 3 PanNETs, suggesting that p16 could help differentiate these entities. This study aimed to investigate p16 expression in PanNETs of various grades and its association with clinicopathologic features.

A total of 114 PanNETs were selected, and their H&E resection slides were reviewed for pathologic features, with a focus on morphologic variants. Tissue microarrays were constructed, and p16 immunohistochemistry was performed. The results were categorized as diffuse positive, partial positive, or negative. Patient electronic health records were reviewed for follow-up data.

Among the 114 PanNETs reviewed, 13 (11.4%) exhibited diffuse p16 expression, 40 (35.1%) were negative, and 61 (53.5%) had partial expression. Diffuse p16 expression occurred in 6 of 38 (15.8%) grade 1, 6 of 60 (10.0%) grade 2, and 1 of 16 (6.3%) grade 3 tumors. Expression did not differ substantially with patient demographics, tumor size, grading, staging, or survival, but diffuse p16 expression was more frequent in body/tail tumors (12/65 [18.5%], P = .019) and in stromal-rich tumors (10/23 [43.5%], P < .001).

Diffuse p16 expression is not uncommon in PanNETs and may be associated with stroma-rich variants.