Novel Surrogate Marker Described for Pancreatic Neuroendocrine Tumors

Tumors of the endocrine pancreas are a collection of tumor cell types collectively referred to as PanNETs. These tumors originate in islet cells. Although they may be similar or identical in histologic appearance to carcinoid tumors of the gastrointestinal tract, differences in their underlying biology and likely differences in response to therapeutic agents suggest that they should be treated and investigated as a distinct entity.

Pancreatic neuroendocrine tumor (PanNET) is the second most common solid neoplasm of the pancreas, accounting for 3% to 4% of all pancreas neoplasms. The incidence of this tumor has increased owing to advances in various imaging techniques and increasing awareness. Surgical resection is the main treatment option for localized PanNETs, both functioning and nonfunctioning, without distant metastasis.

Pathologists at the University of Ulsan College of Medicine (Seoul, Republic of Korea) assessed the significance of tumor border, a well-known prognostic indicator in other cancers, in the PanNETs. They evaluated the macroscopic growth pattern (expansile [Exp] versus infiltrative [Inf]) and the microscopic tumor border (pushing [Pus] versus Inf) of 203 surgically resected PanNETs and compared them with other clinicopathologic factors.

Growth pattern and tumor border were evaluated at the junctions between tumor and normal pancreatic parenchyma or between tumor and other adjacent organs by both gross and microscopic examination. First, macroscopic growth pattern was evaluated in PanNET cases with available gross images of the cut surface of the PanNETs and was classified as expansile or infiltrative pattern. Expansile growth pattern was defined when the tumor had well-delineated margin from adjacent parenchyma. Microscopic tumor border was categorized as pushing or infiltrative. When the tumor boundary was well circumscribed under microscopic examination, this was referred to as a pushing border. Tissue microarray (TMA) was constructed from archived, formalin-fixed, paraffin-embedded tissue blocks with a manual tissue microarrayer (UNITMA Co Ltd, Seoul, Korea).

The scientists reported that based on macroscopic growth pattern, 83 cases had Exp patterns whereas 84 had Inf patterns. According to microscopic tumor border, 122 PanNETs had Pus borders whereas 81 had Inf borders. Combining macroscopic growth pattern and microscopic tumor border, 65 PanNETs had Exp/Pus, 34 had Inf/Pus, 18 had Exp/Inf, and 50 had Inf/Inf status. PanNETs with Inf/Inf status were associated with higher tumor grade, pT classification, and American Joint Committee on Cancer stage grouping; lymph node metastasis; and lymphovascular and perineural invasion.. Patients with PanNET having Inf/Inf status had significantly shorter overall survival (OS) and recurrence-free survival (RFS). Further, using multivariate analysis, Inf/Inf status was identified as an independent poor prognostic factor of OS and RFS.

The authors concluded that the combined Inf/Inf status was observed in approximately 25% of PanNETs and was associated with aggressive biological behavior and short OS and RFS. Therefore, assessing combined macroscopic growth pattern and microscopic tumor border can provide additional information regarding survival and recurrence in PanNET patients. The study was published on May 9, 2022 in the journal Archives of Pathology and Laboratory Medicine.

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