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World J Gastrointest Surg. May 27, 2021; 13(5): 406-418
Published online May 27, 2021. doi: 10.4240/wjgs.v13.i5.406
Benign vs malignant pancreatic lesions: Molecular insights to an ongoing debate
Mahmoud Aldyab, Tony El Jabbour, Megan Parilla, Hwajeong Lee
Mahmoud Aldyab, Hwajeong Lee, Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
Tony El Jabbour, Megan Parilla, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States
Author contributions: Aldyab M, El Jabbour T and Lee H drafted the manuscript; Aldyab M and Lee H prepared the figures, Parilla M and Lee H contributed to the editing of the manuscript; Lee H and Aldyab M provided the microscopic images; Aldyab M, El Jabbour T, Parilla M and Lee H gave final approval of the version to be published and are agreeable to be accountable for all aspects of the work in ensuring that questions that arise are investigated and the information is accurate.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hwajeong Lee, MD, Associate Professor, Department of Pathology and Laboratory Medicine, Albany Medical Center, 47 New Scotland Ave MC81, Albany, NY 12208, United States. leeh5@amc.edu
Received: February 5, 2021
Peer-review started: February 5, 2021
First decision: March 16, 2021
Revised: March 30, 2021
Accepted: May 7, 2021
Article in press: May 7, 2021
Published online: May 27, 2021
Processing time: 105 Days and 1.5 Hours
Abstract

Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis, and paraduodenal pancreatitis can present as mass lesions and may mimic pancreatic ductal adenocarcinoma (PDAC) clinically and radiologically. Thorough histologic examination with attention to certain morphologic features can assist in deciphering neoplastic from reactive, however small biopsies often remain a challenge. Variable histologic patterns in conventional PDAC may also confound the diagnosis of PDAC. Uncommon subtypes of pancreatic carcinoma such as adenosquamous and squamous cell carcinoma, colloid carcinoma, medullary carcinoma, hepatoid carcinoma and signet ring cell carcinoma necessitate excluding metastasis from other sites prior to rendering the diagnosis of pancreatic carcinoma. The use of immunohistochemical staining and molecular markers can aid in separating benign from malignant and PDAC from metastasis. PDAC expresses a few non-specific epithelial and mucin immunomarkers such as CK7, CK19, MUC1, MUC4 and MUC5AC. However, the only immunohistochemical marker that is specific for PDAC in the right clinical context is SMAD4. Loss of SMAD4 within atypical glands and ducts supports the diagnosis of PDAC in a limited sample. Unfortunately, this finding is seen only in 50% of PDAC cases. The identification of certain mutations can help support a diagnosis of PDAC when benign conditions are in the differential. At the molecular level, KRAS oncogene mutations are seen in approximately 93% of PDACs. Subsequent neoplastic progression is driven by additional mutations of tumor suppressor genes, such as CDKN2A, TP53, and SMAD4. Molecular markers can also provide an insight to the prognosis. For instance, the loss of SMAD4 is associated with a poor outcome whereas mutations in MLL, MLL2, MLL3, and ARID1A are associated with improved survival.

Keywords: Pancreas; Pancreatitis; Autoimmune; SMAD4; Molecular

Core Tip: Multiple benign entities share clinical and radiological features with pancreatic ductal adenocarcinoma requiring histologic examination to render the final diagnosis. However, the diagnosis of well differentiated adenocarcinoma can be challenging in a limited sample. Certain morphologic features and molecular markers can be used to resolve this issue.