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Rheumatoid nodules: a narrative review of histopathological progression and diagnostic consideration

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Abstract

Rheumatoid nodules (RNs) are the most common extra-articular manifestation of rheumatoid arthritis and are also seen in patients with other autoimmune and inflammatory diseases. The development of RNs includes histopathological stages of acute unspecified inflammation, granulomatous inflammation with no or minimal necrosis, necrobiotic granulomas typically with central fibrinoid necrosis surrounded by palisading epithelioid macrophages and other cells, and likely an advanced stage of “ghost” lesions containing cystic or calcifying/calcified areas. In this article, we review RN pathogenesis, histopathological features in different stages, diagnostically related clinical manifestations, as well as diagnosis and differential diagnosis of RNs with an in-depth discussion about challenges in distinguishing RNs from their mimics. While the pathogenesis of RN formation remains elusive, it is hypothesized that some RNs with dystrophic calcification may be in transition and may be in coexistence or collision with another lesion in patients with RA or other soft tissue diseases and comorbidities. The diagnosis of typical or mature RNs in usual locations can be readily made by clinical findings often with classic RN histopathology, but in many cases, particularly with atypical or immature RNs and/or unusual locations, the clinical and histopathological diagnosis can be challenging requiring extensive examination of the lesional tissue with histological and immunohistochemical markers to identify unusual RNs in the clinical context or other lesions that may be coexisting with classic RNs. Proper diagnosis of RNs is critical for appropriate treatment of patients with RA or other autoimmune and inflammatory diseases.

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  1. Faiha Fareez and Jinesa Moodley contributed equally to this paper.

Authors and Affiliations

  1. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

    Faiha Fareez, Snezana Popovic & Jian-Qiang Lu

  2. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Jinesa Moodley

  3. Department of Pathology and Molecular Medicine, Hamilton General Hospital, 237 Barton Street, Hamilton, Ontario, L8L 2X2, Canada

    Jian-Qiang Lu

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FF, JM, and JQL contributed to the conception and design of the study, as well as the collection of the data. All authors contributed to the writing, critical review, revision, and approval of the manuscript. The authors meet the criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).

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Fareez, F., Moodley, J., Popovic, S. et al. Rheumatoid nodules: a narrative review of histopathological progression and diagnostic consideration. Clin Rheumatol 42, 1753–1765 (2023). https://doi.org/10.1007/s10067-023-06589-6

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