Context.—

Histopathologic evaluation of bile duct and ampullary biopsies can be challenging. Biopsies from these sites are often tiny, scant, and/or fragmented. When assessing these biopsies, there is significant overlap between reactive atypia and malignancy, in situ precursor lesions can be misinterpreted as malignancy, and nonprimary tumors can mimic primary disease.

Objective.—

To provide diagnostic pearls and pitfalls in the evaluation of small biopsies from the biliary tract.

Data Sources.—

Literature review of published studies and the author’s own observations.

Conclusions.—

Because the procedures for obtaining specimens from the bile duct and ampulla are invasive, pathologists need to try to make definitive diagnoses. Diagnostic clues/pearls, ancillary studies, and recognition of various pitfalls can assist in providing accurate and confident diagnoses.

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Author notes

Presented in part at the Companion Meeting of the Pancreatobiliary Pathology Society at the 2023 United States and Canadian Academy of Pathology Annual Meeting; March 12, 2023; New Orleans, Louisiana.

Competing Interests

The author has no relevant financial interest in the products or companies described in this article.

Supplementary data