Invasive micropapillary carcinomas of the ampullo-pancreatobiliary region and their association with tumor-infiltrating neutrophils

Abstract

Invasive micropapillary carcinoma, originally described as a distinctive type of invasive carcinoma in the breast, is being increasingly recognized as a separate entity in many other organs; however, it has not yet been documented in the pancreas or periampullary region. In this study, 313 pancreatic and 73 periampullary carcinomas were reviewed to investigate the micropapillary pattern in this location. Eight periampullary and eight pancreatic cases (4%) were composed at least focally (>20%) of invasive micropapillary carcinoma. The patients were 10 males and six females, mean age 69 years. The mean tumor size was 3.2 cm. Lymph node metastasis was detected in 11/15 cases. The median survival was 8 months (all were resected). Invasive micropapillary carcinoma was characterized by small, closely packed micropapillary clusters (without fibrovascular cores) lying within clefts. The cells had moderate degree of nuclear atypia. In nine cases, there was abundant inflammation composed of neutrophils concentrating around the tumor cells, both intraepithelial (‘cannibalism') and stromal. Molecules implicated in abnormalities of tumor cell–stroma adhesion, galectin-3 and E-cadherin were expressed in the cytoplasm of 11/11 and 9/11 cases, respectively. Reversal of cell polarity was observed by MUC 1 in all 11 cases tested, which showed labeling in the stroma-facing surfaces of the micropapillary clusters, also confirming that the clefts are not merely a processing artifact, but indeed a true biologic alteration. In conclusion, invasive micropapillary carcinoma constitutes 4% of carcinomas in the pancreatic/periampullary region and is commonly associated with abundant neutrophilic infiltrates. Invasive miropapillary carcinoma appears to be more common in periampullary than in pancreatic invasive micropapillary carcinoma would qualify as poorly differentiated both based on pattern and the median survival (8 months).