Whipple Disease Initial Presentation as Supraclavicular Lymphadenopathy in a Patient With Rheumatoid Arthritis: A Diagnostic Challenge

Authors

• Sara E Amin
• Swati Gite
• Audrey Wanger
• Violeta Chavez
• Jacob Armstrong
• Beenu Thakral
• Patricia Navarro
• Jennifer Makhoul
• Amer Wahed
• Navneet Narula
• Karan Saluja

Language

English

Publication Date

12-1-2025

Journal

International Journal of Surgical Pathology

DOI

10.1177/10668969251342475

PMID

40398847

PMCID

PMC12446694

PubMedCentral® Posted Date

5-21-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Whipple disease is a rare systemic disease caused by Tropheryma whipplei. It can present with a wide range of nonspecific symptoms that might overlap with underlying medical conditions, posing a diagnostic challenge. We present a 61-year-old man with a past medical history of rheumatoid arthritis and chronic inflammatory demyelinating polyneuropathy, who presented with persistent leukocytosis and supraclavicular lymphadenopathy. A positron emission tomography scan revealed hypermetabolic activity in the supraclavicular, abdominal, and pelvic lymph nodes along with a myocardial hypermetabolic lesion, concerning a lymphoproliferative disorder versus sarcoidosis. A supraclavicular lymph node excisional biopsy revealed complete architectural effacement by a diffuse foamy histiocytic infiltrate without granuloma formation or necrosis. The differential diagnosis included underlying infection, histiocytic neoplasm, lymphoproliferative disorder, storage disorder, and others. Immunostains show the histiocytic cells were positive for CD68 and CD163, while negative for S100, CD1a, kappa, lambda, and BRAF V600E. Grocott-Gömöri's methenamine silver and periodic acid–Schiff (PAS) stains demonstrated diffuse intracytoplasmic granular staining that was resistant to diastase treatment. Gram, acid fast bacilli, and Fite stains were negative. Electron microscopy revealed rod-shaped organisms with a trilaminar plasma membrane, morphologically consistent with T whipplei. Polymerase chain reaction was positive for T whipplei, confirming the diagnosis. Although rare, Whipple disease should be considered in immunocompromised patients presenting with nonspecific nongastrointestinal symptoms and lymphadenopathy clinically simulating lymphoma. Periodic acid–Schiff D-positive inclusions, along with confirmatory molecular results, are crucial for diagnosis. Whipple disease is a curable disease that can be lethal if unrecognized, emphasizing the importance of heightened awareness for early diagnosis and timely treatment.

Keywords

Humans, Whipple Disease, Male, Middle Aged, Arthritis, Rheumatoid, Lymphadenopathy, Lymph Nodes, Diagnosis, Differential, Tropheryma, Whipple disease, tropheryma, lymphadenopathy, histiocytosis, electron microscopy, ultrastructure, PCR

Published Open-Access

yes

Recommended Citation

Amin, Sara E; Gite, Swati; Wanger, Audrey; et al., "Whipple Disease Initial Presentation as Supraclavicular Lymphadenopathy in a Patient With Rheumatoid Arthritis: A Diagnostic Challenge" (2025). Faculty, Staff and Student Publications. 4072.
https://digitalcommons.library.tmc.edu/uthmed_docs/4072