Tumor-infiltrating neutrophils in pancreatic neoplasia

Abstract

The interaction between tumor cells and inflammatory cells has an important role in cancer initiation and progression; however, this interaction has not been systematically investigated in pancreatic neoplasia. In this study, the presence of tumor-infiltrating neutrophils within and/or adjacent to neoplastic cells was investigated in pancreatic neoplasms. Areas with >10 tumor-infiltrating neutrophils/100 epithelial cells were arbitrarily classified as positive. Those with 11-15 tumor-infiltrating neutrophils were considered 'borderline' while those with >15 tumor-infiltrating neutrophils were considered 'significant'. Among 363 invasive ductal carcinomas, 15 showed significant tumor-infiltrating neutrophils (8 were micropapillary carcinomas and 7 were undifferentiated carcinomas). Of 19 mucinous cystic neoplasms with a carcinomatous high-grade papillary component, 11 showed significant tumor-infiltrating neutrophils (mean, 25; range, 14-63 tumor-infiltrating neutrophils). Among intraductal papillary mucinous neoplasms, significant tumor-infiltrating neutrophils were identified in 4/16 pancreatobiliary type, but were uncommon in other types (1/11 oncocytic and 1/23 intestinal types had borderline tumor-infiltrating neutrophils, and 0/10 gastric type had tumor-infiltrating neutrophils). Non-carcinomatous (low-grade and non-papillary) components of these neoplasms did not have tumor-infiltrating neutrophils. Tumor-infiltrating neutrophils were not striking in neuroendocrine tumors (40), serous cystadenomas (18), acinar cell carcinomas (9) or solid-pseudopapillary neoplasms (8). In conclusion, significant tumor-infiltrating neutrophils are uncommon in pancreatic ductal adenocarcinoma, and when they occur it is typically in the micropapillary and undifferentiated types with a known poor prognosis. Among pre-invasive neoplasia, tumor-infiltrating neutrophils show a predilection for papillary in-situ carcinomas of mucinous cystic neoplasms, or less commonly, pancreatobiliary-type intraductal papillary mucinous neoplasms (both of which express cell surface-associated mucin 1 (MUC1)). MUC1 expression by these tumors may have biologic implications, considering its recently established relationship with inflammatory cells in carcinogenesis, and the differential expression of mucins in pancreatic neoplasia. Larger studies are needed to investigate the association between tumor-infiltrating neutrophils and pancreatic neoplasms and their role in their clinical behavior.

Figure 1

(a) Invasive micropapillary carcinoma composed of clusters of tumor cells within cleft-like spaces, characteristic inverse cell polarity and abundant intraepithelial and stromal tumor-infiltrating neutrophils (hematoxylin and eosin stain, magnification ×200). (b) MUC1 staining of the stroma-facing surface of cell clusters in invasive micropapillary carcinoma (magnification ×200).

Figure 2

Undifferentiated carcinoma with prominent osteoclast-like giant cells, resembling osteoclastic giant cell carcinoma. Note significant numbers of tumor-infiltrating neutrophils within the stroma (hematoxylin and eosin stain, magnification ×200).

Figure 3

Colloid carcinoma of pancreas with abundant extracellular mucin and borderline numbers of intraepithelial and background tumor-infiltrating neutrophils (hematoxylin and eosin stain, magnification ×400).

Figure 4

(a) Mucinous cystic neoplasm with bland mucinous columnar epithelium (at bottom), underlying ovarian-like stroma and papillary carcinoma in-situ (at top). Neutrophils are condensed around papillae and are both intra- and extraepithelial (hematoxylin and eosin stain, magnification ×200). (b) Mucinpoor variant of mucinous cystic neoplasm with papillary carcinoma in-situ containing significant numbers of intra- and extraepithelial neutrophils (hematoxylin and eosin stain, magnification ×200).

Figure 5

Papillary in-situ carcinoma in mucinous cystic neoplasm. (a) The neoplastic epithelium contains abundant intraepithelial neutrophils with focal microabscess formation (hematoxylin and eosin stain, magnification ×400). (b) Note MUC1 expression on the apices of the papillae (magnification ×200).

Figure 6

(a) Pancreatobiliary-type intraductal papillary mucinous neoplasm with complex papillae lined by mucin-containing cells and (b) abundant intraepithelial and stromal neutrophils concentrated within papillae (hematoxylin and eosin stain, magnification ×200).

Figure 7

(a) High-power view of neutrophils concentrated within and adjacent to neoplastic cells in pancreatobiliary-type intraductal papillary mucinous neoplasm (hematoxylin and eosin stain, magnification ×400). (b) Intraductal papillary mucinous neoplasm with pancreatobiliary-type papillae expressing MUC1 on the apical aspects of the neoplastic papillae (magnification ×200).