Histomorphological and Immunohistochemical Subtyping of Ampullary Adenocarcinoma and Its Association With Survival Status: An Ambispective Observational Study

Abstract

Background: Periampullary adenocarcinoma (PAC) is a rare and unique malignancy arising from structures around the ampulla. Based on the histomorphology, two common subtypes include pancreatobiliary (PB) and intestinal (INT), which have therapeutic and prognostic significance. There are limited studies that highlighted the magnitude of interobserver variability in subtyping. The aims of the study were primarily to assess the morphologic and IHC expression of CK7, CK20, and CDX2 to differentiate between pancreatobiliary and intestinal types of PAC and secondarily to compare the subtype with pathological grade, stage, lymph node status, lymphovascular invasion, and survival status. Materials and methods: This was an ambispective study of six years' duration, including prospective cases from June 2022 to May 2024 (two years) and retrospective cases from January 2018 to May 2022 (four years) in the Department of Pathology, Kalinga Institute of Medical Sciences (KIMS) and Pradyumna Bal Memorial Hospital (PBMH), Bhubaneswar. All pancreaticoduodenectomy specimens received for adenocarcinoma were included in the study. The histomorphologic features were studied and documented. The cases were sub-classified as PB and INT based on standard criteria. Discrepant cases were reviewed for consensus morphology (CM). CK7 was used as a marker for PB type, while CK20 and CDX2 were used for INT type. The CM and immunomorphologic subtype (IMS) were studied and documented. Statistical tools like correlation analysis and comparative analysis were used in the study. Results: A total of 33 pancreaticoduodenectomy specimens were received during this period. Our study comprised subjects belonging to 32 to 74 years with a mean age of 55.9 years, including 19 males (57.6%) and 14 females (42.4%). Histomorphological subtyping was done by two different observers as per the criteria, which showed slight agreement in architecture (k = 0.2), desmoplastic stroma (k = 0.1), luminal necrosis (k = 0.2), and presence of goblet cells (k = 0.1); however, no agreement was observed in cytomorphology (k = -0.2) and nuclear features (k = -0.2). Interobserver variation was noted in 51.5% cases (17/33) with no agreement between the observers (k = 0.1, p = 0.6). IMS showed a significant moderate degree of agreement with the diagnosis made on CM (k = 0.6, p ≤ 0.001). Conclusion: With optimal sampling, the use of CM along with adjunct immunohistochemistry to recognize the IMS, accurate classification of PAC is possible in most cases, which has therapeutic and prognostic significance.