Orbital Rosai-Dorfman disease initially diagnosed as IgG4-related disease: a case report

Abstract

Inflammatory orbital lesions include a broad list of diagnoses, many of them with overlapping clinical and radiographic features. They often present a diagnostic conundrum, even to the most experienced orbital specialist, thus placing considerable weight on surgical biopsy and histopathological analysis. However, histopathological diagnosis is also inherently challenging due to the rarity of these lesions and the overlaps in histologic appearance among distinct disease entities. We herein present the case of an adolescent male with a subacutely progressive orbital mass that generated a significant diagnostic dilemma. Early orbital biopsy was consistent with a benign fibro-inflammatory lesion, but corticosteroid therapy was ineffective in halting disease progression. After an initial substantial surgical debulking, histopathological analysis revealed several key features consistent with IgG4-related disease (IgG4-RD), a systemic fibro-inflammatory process typically accompanied by multifocal tumor-like lesions. Surprisingly, within months, there was clear evidence of clinical and radiographic disease progression despite second-line rituximab treatment, prompting a second surgical debulking. This final specimen displayed distinctive features of Rosai-Dorfman disease (RDD), a systemic inflammatory disease characterized by uncontrolled histiocytic proliferation. Interestingly, certain features of this re-excision specimen were still reminiscent of IgG4-RD, which not only reflects the difficulty in differentiating RDD from IgG4-RD in select cases, but also illustrates that these diagnoses may exist along a spectrum that likely reflects a common underlying pathogenetic mechanism. This case emphasizes the importance of surgical biopsy or resection and histopathological analysis in diagnosing—and, ultimately, treating—rare, systemic inflammatory diseases involving the orbit, and, furthermore, highlights the shared histopathological features between RDD and IgG4-RD.

Plasma cell IgG4 positivity in orbital biopsies of non-IgG4-related conditions

“…The literature review disclosed 20 reports (37 patients) of inflammatory non-IgG4-RD orbital lesions with significant IgG4 positivity[ 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 ] and 14 reports (108 patients) of IgG4 positivity in orbital lymphoid proliferations. [ 30 31 32 33 34 35 36 37 38 39 40 41 42 43 ] As shown in Table 1 , plasma cells IgG4 + satisfying the criterion established for the diagnosis of IgG4-RD are found in a large spectrum of non-IgG4-RD conditions affecting the orbit including xanthogranulomas (adult-onset or adult-onset xantogranuloma, n = 14 and necrobiotic or necrobiotic xantogranuloma, n = 6), C-anti-neutrophil cytoplasmic antibody vasculitis ( n = 11), Kimura disease ( n = 2), and RosaiDorfman disease (RDD) ( n = 2).…”

Rosai-Dorfman Disease With Features of IgG4-Related Sclerosing Disease: A Case Report

“…RDD with features of IgG4RD is seen in various age groups with a mean age of 30 years (1-69 years) in nodal and extra-nodal distribution. The cervical lymph node is the most involved site in some cases of multiple organ systems involvement [5,6].…”