BRIEF REPORT Cytological diagnosis of Brunner's gland adenoma (hyperplasia): A diagnostic challenge Domenika Ortiz Requena MD 1 | Claudia Rojas MD 2 | Monica Garcia-Buitrago MD 1 1 Department of Pathology and Laboratory Medicine, Jackson Memorial Hospital/ University of Miami Miller School of Medicine, Miami, Florida 2 Department of Pathology, Memorial Healthcare System/Joe DiMaggio Children Hospital, Miami, Florida Correspondence Monica Garcia-Buitrago, MD, Jackson Memorial Hospital, University of Miami Miller School of Medicine, Department of Pathology and Laboratory Medicine, 1611 NW 12th Avenue, Holtz Bldg, room 2042. Miami, FL 33136. Email: mgarcia22@med.miami.edu Abstract Brunner's gland adenoma (hyperplasia) (BGA/H) is a benign gastrointestinal lesion, usually asymptomatic and frequently detected incidentally by endoscopy as a sub- mucosal nodule. Most BGA/Hs are diagnosed by their typical cytological morphol- ogy and immunohistochemical features, characterized by monomorphic cells arranged as loosely clusters of epithelial cells with abundant, clear, and granular cytoplasm, eccentrically located nuclei, and immunoreactivity for MUC-6. The com- bination of the clinical and pathological features is essential for rendering a correct diagnosis. Herein, we report two cases of BGA/H, including their cytologic and his- tologic features, and a literature review of the clinicopathologic findings along with its differential diagnoses. KEYWORDS Brunner's gland adenoma, Brunner's gland hyperplasia, duodenum, fine-needle aspiration cytology 1 | INTRODUCTION Brunner's gland adenoma (hyperplasia) (BGA/H) is a rare and benign duodenal lesion that comprises less than 1% of gastrointestinal neo- plasms. This lesion is not a true neoplasm but rather a hyperplastic proliferation of mature Brunner glands. Thus, the term adenoma is technically as misnomer. BGA/Hs occur most frequently during the fifth and sixth decades of life, have no gender predilection, and usually present as asymptomatic lesions; however, occasionally they may be large lesions that lead to obstruction or hemorrhage. The absence of a specific clinical history, the inconspicuous cytological features, and its immunocytochemical profile makes the diagnosis difficult on cytopa- thology alone. This review highlights the difficulties in diagnosing this lesion and aims to determine the cytomorphological characteristics encountered in BGA/Hs evaluated by endoscopic ultrasound fine- needle aspiration (EUS-FNA), their differential diagnoses, and diagnos- tic pitfalls. 2 | CASE HISTORY 2.1 | Case 1 A 64-year-old woman with a past medical history of Hepatitis C and left nephrectomy, who consulted due to significant weight loss of 20 pounds and melena. Laboratory data showed a hemoglobin concentration of 12.5 g/dL (reference range, 12-16 g/dL) and a hematocrit of 38%. CT scan demonstrated a 6.5 × 4.8 × 3 cm complex soft tissue mass encasing the hepatic artery and portal vein. It abutted the underside left lower side of the liver and appeared to invade the distal stomach, duo- denum, anterior wall of the hepatic flexure colon, and anterior edge of the pancreas (Figure 1A). The possibility of a gastrointestinal stromal tumor (GIST) was considered. EUS-FNA was performed. The cytology smears revealed high cellularity represented by a monotonous popula- tion arranged as loose clusters of epithelial cells with low nuclear-to- cytoplasmic ratio and showing abundant, clear, and granular cytoplasm Received: 29 September 2020 Revised: 17 November 2020 Accepted: 23 November 2020 DOI: 10.1002/dc.24680 Diagnostic Cytopathology. 2020;1–4. wileyonlinelibrary.com/journal/dc © 2020 Wiley Periodicals LLC 1