Recurrent Cutaneous Swellings Unmasked: A Case of Rosai–Dorfman Disease

Dear Editor, Rosai–Dorfman disease (RDD) is a rare, benign histiocytic proliferative disorder, described by Destombes in 1965. The estimated incidence is 1 in 200,000, predominantly affecting children and young adults, with a slight male predominance.[1] The typical presentation includes painless bilateral cervical lymphadenopathy accompanied by constitutional symptoms like fever, night sweats, fatigue and weight loss. Extra-nodal involvement is reported in nearly 43% of cases.[2] Isolated cutaneous Rosai-Dorfman disease (CRDD) accounts for about 3% of all cases, and typical presentation includes papules, plaques, or nodules involving face, trunk, or extremities, which may closely mimic other dermatological conditions, often leading to diagnostic delay.[3] Histopathology of both lymph node and cutaneous lesions is similar, with emperipolesis being the hallmark feature. We report a case of recurrent CRDD, highlighting the diagnostic challenges and importance of vigilant follow-up. A 62-year-old woman presented with a two-month history of a gradually progressive swelling on the left lumbar region, associated with mild pruritus and occasional pricking pain. Cutaneous examination revealed a single, non-tender, pale erythematous plaque measuring 6 cm × 4 cm with a non-scaly lobulated surface, ill-defined margins, with surrounding hyperpigmentation on left lumbar region [Figure 1a]. There was no associated lymphadenopathy. Initial differential diagnoses considered were cutaneous tuberculosis, subcutaneous mycosis, and pseudolymphoma. An initial biopsy showed a mixed dermal inflammatory infiltrate sans granuloma, thereby ruling out tuberculosis. The patient was treated empirically with oral itraconazole for three weeks without improvement. A repeat incisional biopsy demonstrated dense dermal infiltrates composed of lymphocytes and plasma cells admixed with sheets of histiocytes, suggestive of pseudolymphoma. Special stains for infectious agents were negative. With the probable diagnosis of pseudolymphoma, the patient was treated with oral corticosteroids and intralesional triamcinolone acetonide but showed no significant response.Figure 1: (a) Single, non-tender, pale erythematous plaque, with lobulated surface and surrounding hyperpigmentation noted on left lumbar region. (b) Histopathology showing a dense dermal infiltrate of large histiocytes exhibiting emperipolesis (boxed area) (Hematoxylin and eosin, 400 x)In an attempt to provide a cure, complete surgical excision was performed, and the specimen was sent for histopathology. Histopathological examination revealed extensive dermal histiocytic proliferation with emperipolesis, consistent with RDD [Figure 1b]. Hence, the patient’s history was reviewed. There was no history suggestive of systemic involvement, such as fever, cough, dyspnea, weight loss, diplopia, recurrent headaches, seizures, flank pain, hematuria, or constipation. With the lesion excised and no systemic features, the condition was presumed treated. One year later, she presented with recurrence at the previous lumbar surgical site along with a new plaque on the epigastric region [Figure 2a].Figure 2: (a) The recurrent, single, non-tender, erythematous plaque noted on epigastric region. (b) Histopathology demonstrating recurrent disease with similar features, including emperipolesis (Hematoxylin and eosin, 400×)Histopathology from the epigastric lesion again showed features of RDD [Figure 2b], and immunohistochemistry demonstrated CD68 positivity in histiocytes [Figure 3]. Serum lactate dehydrogenase, complement levels, and IgG4 levels were within normal limits. Line immunoassay did not detect any autoantibodies. Bone marrow examination showed reactive marrow with no abnormal cells. A whole-body positron emission tomography- computerised tomography (PET- CT) scan revealed an fluorodeoxyglucose (FDG)-avid soft-tissue lesion at the left lumbar region and a mildly FDG-avid nodule in the left breast. Both lesions were surgically excised. Owing to the recurrent and multifocal nature of the disease, the patient was initiated on oral thalidomide and weekly methotrexate. The patient continues to be under regular followup for more than 12 months and no further recurrences have been observed.Figure 3: Immunohistochemistry demonstrating strong CD68 positivity in large dermal histiocytesCRDD is an uncommon entity, and recurrent disease is even rarer.[2] Clinically, lesions may present as papules, plaques, or nodules involving the face, trunk, or extremities and may mimic infections, inflammatory disorders, and lymphoproliferative conditions.[3] Owing to histopathological heterogeneity characteristic of RDD, multiple biopsies are frequently necessary. In this case, three biopsies were required, findings consistent with a series of 64 patients who reported a median of 2 biopsies (range 1-6) to reach a definitive diagnosis.[4] Histopathology shows large histiocytes exhibiting emperipolesis, and immunohistochemistry demonstrates CD68 and S100 positivity, with CD1a and CD207 (Langerin) negativity, which aids in distinguishing RDD from Langerhans cell disorders.[5] While localized CRDD generally follows an indolent course and may be managed with observation or surgical excision, recurrences, including at sites of excision as observed in our patient, can complicate the course. Imaging modalities, such as PET-CT can be crucial in identifying subclinical cutaneous lesions, as in the present case. Oral corticosteroids, sirolimus, and radiotherapy are indicated in symptomatic localized or systemic disease. In recurrent, multifocal cases, systemic immunomodulatory agents, including methotrexate, thalidomide, and cladribine, are indicated. In severe refractory cases, targeted therapies, such as imatinib, have been reported with variable success.[1,4] The present case underscores the necessity of multiple biopsies for definitive diagnosis and the diagnostic utility of PET-CT in staging the disease, and thus guiding the management. Vigilance and proper patient follow-up are essential for optimal treatment. Authors’ contributions The manuscript has been read and approved by all authors. All authors meet authorship criteria and that the manuscript represents honest work. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.