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 (420%) 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). Modern Pathology (2005) 18, 1504-1511.

Invasive micropapillary component and its clinico-histopathological significance in patients with colorectal cancer

“…The invasive properties of IMPC structures are associated with respective adhesion proteins: Outer membrane expression of MUC1 was confirmed to indicate cancer cell adhesion disorders and induce disturbances in their association with the extracellular matrix (23). Furthermore, positive expression of E-cadherin was identified in the cytoplasm of cells with a micropapillary structure as compared with neoplastic glandular ducts and normal ducts (24).…”

“…It may be hypothesized that IMPC may induce suppression of the immune system, thus creating an optimal microenvironment for the primary tumor to grow and metastasize. In the digestive system, massive inflammatory infiltrate composed of neutrophilic granulocytes, which form clusters in the stroma and focal endothelial microabscesses, have only been identified in patients with pancreatic IMPC (24).…”

Cancer as a Metabolic Disease

“…Metastatic behavior would be an expected outcome following impaired respiratory function in hematopoietic or myeloid-type cells, as macrophages are already mesenchymal cells that embody the capacity to degrade the extracellular matrix, to enter and to exit tissues from the blood stream, to migrate through tissues, and to survive in hypoxic environments. A sampling of human metastatic cancers with properties of macrophage-like cells include brain [204,[217][218][219][220], breast [221][222][223][224][225], lung [202,[225][226][227][228][229], skin [203,205,209,210,[230][231][232][233], gastric [234], colon [235,236], pancreas [237,238], bladder [239], kidney [240], ovarian [241,242], and muscle [243,244]. It is important to mention that these macrophage properties are expressed in the tumor cells themselves and are not to be confused with similar properties expressed in the non-neoplastic TAM, which are also present in tumors and can facilitate tumor progression [190,213,215,216,245].…”

Micropapillary component in gastric adenocarcinoma: an aggressive variant associated with poor prognosis

“…Overall survival of subtype II MPCs (follow-up of 16 cases) was significantly worse than that of subtype I MPCs in gastric carcinomas (P = 0.040). c However, no significant differences in survival were found between an MPC component\50 % and an MPC component [50 % (P = 0.733) pieces of evidence indicate that tumor-infiltrating neutrophils may promote tumor progression and a poor prognosis [22,23]. Poor prognosis and shortened survival associated with micropapillary carcinoma may be in part related to the presence of abundant tumor-infiltrating neutrophils.…”