Clear cell
carcinoma as a variant of
ductal carcinoma of the pancreas is not well recognized.
Hepatocyte nuclear factor-1beta as a
transcription factor has been identified as a specific
biomarker of clear cell
tumor of the female genital tract. The aim of this study was to systematically analyze clear cell
carcinoma of the pancreas and its unique
biomarker hepatocyte nuclear factor-1beta. A total of 84 pancreatic
adenocarcinomas were analyzed pathologically and with an immunohistochemical approach with
hepatocyte nuclear factor-1beta antibody. The identified clear cell
carcinomas were further studied by PAS, DPAS, and
mucicarmine stains. Pathologic features and clinical follow-up were documented. Of them, 20 (24%) pancreatic
adenocarcinomas were identified with clear cell features, including 12 clear cell
carcinomas and 8 ductal
adenocarcinomas with clear cell component (defined as less than 75% of
tumor with clear cells). Cytologically, the clear cell
carcinomas exhibited clear cytoplasm with centrally located, atypical nuclei. PAS, DPAS, and
mucicarmine stains confirmed that the clear cytoplasm was not due to accumulation of
glycogen or
mucin. The results of immunostaining showed that
hepatocyte nuclear factor-1beta is overexpressed in
all clear cell
carcinomas and in the clear cell components of eight
ductal carcinomas with clear cell features. In contrast, in usual ductal
adenocarcinoma,
hepatocyte nuclear factor-1beta exhibited overall weak or focally moderate staining; only eight cases were strongly positive (15%) of which 38% were high grade and 63% were moderate grade. However, when included with the strong staining cases in mixed and clear cell
carcinoma, this group regardless of morphology appeared to correlate with worse survival compared to the group with weak
hepatocyte nuclear factor-1beta staining across morphologies (P<0.01). Thus, clear cell
carcinoma of the pancreas is not an uncommon variant of pancreatic ductal
adenocarcinoma.
Hepatocyte nuclear factor-1beta is a useful marker to identify these clear cell
carcinomas, and its overexpression may aid in stratifying survival rate.