Cutaneous Rosai-Dorfman Disease: A Report of 2 Cases and a Review of Recent Literature (2018–2023) Open Access

Rosai-Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare, acquired, idiopathic, benign systemic proliferative disorder of histiocytes [1]. The typical Clinical features of the disease include bilateral painless massive lymphadenopathy, as well as general symptoms such as fever, night sweats, weight loss, and fatigue [2]. Skin lesions are the most common form of extra nodal involvement approximately 43% [3]. However, a cutaneous variant of RDD (CRDD) is very rare and occurs without lymphadenopathy or internal organ involvement. CRDD, also known as cutaneous sinus histiocytosis, accounts for approximately 3% of RDD cases [4]. The histopathological features of CRDD closely resemble those of systemic RDD, particularly in lymph nodes. However, some studies indicate that CRDD tends to exhibit more pronounced fibrosis and sclerosis, along with a reduced number of histiocytes and less prominent emperipolesis [5, 6]. RDD typically presents with cervical lymphadenopathy, most commonly in children or young adults, with a median age of onset around 20 years. It is more frequently observed in males, particularly those of African descent [7]. In contrast, CRDD is more commonly seen in middle-aged females, predominantly of Asian or Caucasian backgrounds [8].

CRDD often presents as yellowish or violaceous nodules or plaques and an erythematous base, primarily affecting the head and neck region [9]. Its diagnosis can be challenging due to similarities with conditions such as xanthomas, Kaposi sarcoma, cutaneous lymphoma, tuberculosis, and Langerhans cell histiocytosis [10, 11]. There is no standardized treatment for RDD, so management is tailored to each case. Systemic RDD may not require intervention in asymptomatic cases, but symptomatic or severe forms are treated with corticosteroids, thalidomide, methotrexate, imatinib, rituximab, chemotherapy, or radiotherapy [12].

CRDD is usually managed with topical or intralesional corticosteroids, imiquimod, cryotherapy, or surgical excision for symptom relief. Systemic therapies are rarely required, but may be considered for severe or persistent cases [8, 13]. The diagnosis and management of CRDD are particularly challenging due to its variable presentation, numerous differential diagnoses, and the absence of standardized treatments. Sharing case experiences is crucial to improving understanding and guiding care. This manuscript highlights two cases of CRDD, offering valuable insights into this rare condition.

A 30-year-old Caucasian male presented with a 1-year history of generalized papulonodular cutaneous lesions. The first lesion appeared as a painful nodule on the plantar surface, followed by the gradual development of additional papulonodular lesions on the face, hands, and axilla.

The initial lesions were painful purple papules, some of which progressed into nodules, while others spontaneously resolved, leaving post-inflammatory hyperpigmentation. The initial lesions were painful purple papules. Some progressed into nodules, while others spontaneously resolved, leaving post-inflammatory hyperpigmentation.

The patient denied symptoms like pruritus, malaise, or weight loss. Laboratory investigations showed no abnormalities or indications of underlying systemic disease. Physical examination showed no fever, lymphadenopathy, or organomegaly. Clinical examination revealed grouped purple to skin-colored papules and plaques with a hyperpigmented patch due to the healing of previous lesions (Fig. 1).

Dermoscopy at 20-fold magnification (FotoFinder Handyscope^®) of trunk and limb lesions revealed a pink-brown background, large yellow ovoid structures, and linear vessels. Dermoscopy of the plantar lesion showed cotton-like white globular structures over a pink background accompanied by hemorrhagic dots and peripheral scaling (Fig. 2).

Histopathologic evaluation revealed a dense dermal infiltrate of histiocytes and lymphocytes. The histiocytes had vesicular nuclei, abundant eosinophilic cytoplasm, and areas of emperipolesis (Fig. 3). Once pathology confirmed the diagnosis of RDD, computed tomography of the chest and neck, along with abdominopelvic ultrasonography, revealed no evidence of organomegaly or lymphadenopathy.

Given the absence of systemic involvement, a diagnosis of CRDD was made. During follow-up, intralesional triamcinolone acetonide (0.5 cc of 10 mg/mL) was administered, leading to mild improvement.

A 35-year-old Caucasian man presented with a 9-month history of two facial lesions. The initial lesion appeared as an asymptomatic, erythematous, scaly plaque on the right cheek, which gradually enlarged into an exophytic papillomatous mass. A similar but smaller lesion later developed on the opposite cheek. The patient was otherwise healthy, with no significant past medical history or family history of malignancies. As a welder and had no significant exposure to irritants other than grease. He had not traveled in the past year and denied contact with pets. Physical examination revealed a red, exophytic papillomatous mass approximately 7 cm in diameter, on the right cheek and an erythematous plaque approximately 2 cm in diameter on the left cheek (Fig. 4).

Dermoscopy showed large yellow ovoid structures, well-defined linear vessels, follicular plugging, perifollicular scaling, and interfollicular linear white opaque structures (Fig. 5). No systemic symptoms, such as fever, malaise, or weight loss, or lymphadenopathy were noted. Detailed laboratory analyses, including a complete blood count and biochemical tests, were within normal ranges. In culture from lesion secretions, coagulase-negative staphylococcus was reported. Fungal culture and smear were reported as negative. Leishmanin and PPD skin tests were also negative.

He had previously been treated with antibiotics and antifungal agents by another clinician, but no significant improvement was observed. A biopsy specimen was obtained from the lesion, and a histopathological study followed by immunohistochemical (IHC) staining for the patient. Histopathologic analysis revealed hyperkeratosis and acanthosis of the epidermis. In the dermis, there was diffuse infiltration of histiocytes and lymphoplasma cells. Most histiocytes had abundant clear cytoplasm with engulfment of lymphocytes (emperipolesis) in their cytoplasm (Fig. 6). The histiocytes were positive for S-100 and CD68, but negative for CD1a (Fig. 7). Abdominal ultrasound and chest X-ray were unremarkable, confirming the absence of systemic involvement. A surgical approach was selected due to the localized nature of the lesions.

Four months of follow-up showed no recurrence of the large lesion on the right cheek. A new lesion developed on the forearm, which was excised and confirmed as CRDD on pathology.

Classic cutaneous RDD presents as slow-growing, multifocal, grouped satellite lesions, presenting as firm, red to red-brown or xanthomatous macules, papules, nodules, or plaques [14, 15]. Soft tissues, especially the skin, subcutaneous tissue, orbit, and eyelids, are commonly affected [3].

Regarding clinical presentation, our CRDD cases involved multifocal, painful lesions on the face, plantar region, hands, and soles. In contrast, Banbury et al. [16] reported four patients of African descent with localized, asymptomatic or mildly tender papules and nodules, primarily on the face, abdomen, knees, and thighs. Additionally, these patients experienced prolonged disease durations, with some lesions persisting for over a decade. This highlights the variability in CRDD presentations influenced by racial and ethnic factors.

Recent studies have described dermoscopic features of cutaneous RDD, including red-orange background, yellowish ovoid structures, linear vessels, white opaque structures, cotton-like white globular structures, and white crystalline structures [17‒20]. The large yellow ovoid structures in our cases likely represent compact multinodular infiltration of lipid-rich lymphohistiocytes in the dermis. The prominent follicular plugging in our second case may be attributed to a dilated follicular infundibulum containing keratotic debris [17].

Bennouna et al. [21] reported a case involving a 25-year-old woman with a gradually enlarging facial lesion, characterized by dermoscopic findings including orange-yellowish areas, radial hairpin vessels, and follicular keratotic plugs set against a red-orange background. The presence of hairpin vessels, more commonly linked to keratinizing tumors, in this case of CRDD highlights the diverse and atypical dermoscopic patterns that can be observed in this rare disorder [21].

Cotton-like structures in palmoplantar RDD have been described by Rodríguez-Blanco et al. [20]. Our observation of these structures in the first case suggests they could be a distinctive dermoscopic feature of palmoplantar RDD.

Histopathologic examination is essential for diagnosing RDD, with emperipolesis as a hallmark. In the cutaneous form of RDD, emperipolesis may be less prominent, which increases the risk of misdiagnosis compared to the nodal form [22]. Typical histologic findings include histiocytic infiltrates, eosinophilic cytoplasm, vesicular nuclei, the presence of plasma cells, and lymphocytes [18].

Immunohistochemistry reveals S-100 and CD68 positivity with CD1a negativity, distinguishing RDD from other histiocytic disorders such as Langerhans cell histiocytosis, histiocytic sarcoma, Erdheim-Chester disease, tuberculosis, and leprosy [23]. Both cases in our study exhibited these characteristic histopathologic and IHC features.

Systemic and cutaneous RDD has an uncertain etiology. However, laboratory findings frequently indicate an immune dysfunction triggered by an antigen or infectious organism, an autoimmune process, or a neoplastic condition, as suggested by case reports and small studies [3, 24, 25]. Coagulase-negative staphylococcus was found in Case 2, but further research is required to determine the specific cause.

Other histiocytic lesions, such as Langerhans cell histiocytosis, histiocytic sarcoma, Hodgkin lymphoma, and Erdheim-Chester disease, as well as inflammatory/reactive disorders, including infectious granulomatous diseases, should be considered in the differential diagnosis [26]. RDD may also coexist with lymphoproliferative disorders, including non-Hodgkin or Hodgkin lymphoma and mycosis fungoides [6, 27].

Treatment for CRDD requires an individualized, multidisciplinary approach. For patients with minimal or slowly progressing lesions, observation may be appropriate [28]. Localized lesions may respond to topical or intralesional corticosteroids, such as triamcinolone acetonide, which led to mild improvement in our first case. Cryotherapy is an alternative for smaller lesions, while surgical excision is preferred for larger or cosmetically significant lesions, as demonstrated in our second case. Systemic corticosteroids, methotrexate, and rituximab are alternatives, requiring careful monitoring for adverse effects [13].

In more complex cases, recent studies have proposed alternative treatment options. Al-Ghawas et al. [29] explored the use of lenalidomide and dexamethasone for a patient with CRDD who did not respond to intralesional steroids, prednisone, or rituximab, and where surgery was not viable due to potential facial defects. This combination therapy resulted in notable improvement and appears to be a potential option for refractory CRDD [29].

Localized radiotherapy may be a suitable option for managing CRDD, especially when other treatments have not been effective or have only provided partial relief. It has been associated with moderate lesion improvement and minimal side effects, such as radiodermatitis. Thus, radiotherapy could be considered a viable option, particularly for cases confined to the skin [30].

To improve understanding of CRDD’s uncommon presentation, A literature review was conducted, focusing on studies published between January 2018 and December 2023. This period was chosen to build on a previous evaluation completed in 2018 [2]. The search was conducted using Google Scholar and PubMed with the query “Cutaneous Rosai-Dorfman Diseas.” Inclusion criteria were limited to original publications, including case reports, case series, and letters to the editor confirming CRDD through histopathologic analysis.

Initially, 54 articles were identified. After reviewing abstracts and full texts, eight were excluded for not focusing on CRDD or lacking original case data. Ultimately, 46 articles met the inclusion criteria and were analyzed. The selected studies are summarized in Table 1.

The rarity of CRDD and limited case reports challenged the establishment of robust evidence-based conclusions. However, this review provides a valuable synthesis of recent findings and highlights the current understanding of this rare condition.

Our analysis of 53 cases from 46 articles reinforces the diverse clinical spectrum of CRDD. The reviewed cases showed a mean patient age of 49 years (range: 13–76), with a predominance of females (58%). Most cases (64%) involved multiple lesions, primarily located on the trunk (52%), and extremities (43%). Histopathologic examination consistently revealed large histiocytes with emperipolesis, and immunohistochemistry confirmed the S100+CD68+CD1a pattern in 69% of cases. CRDD was frequently associated with lymphoma, malignancies, and infections, such as HIV, cytomegalovirus, and Borrelia burgdorferi. Treatment varied, with corticosteroids (49%) and excision (28%), being the most common options. Among the 39 patients with follow-up data, 64% achieved full or partial remission, suggesting a generally favorable prognosis. These findings align with recent literature and emphasize the heterogeneity of CRDD, highlighting the importance of a multidisciplinary approach to treatment.

CRDD is a rare condition that poses diagnostic challenges, particularly when systemic involvement is absent, providing insights into uncommon presentations such as painful, multifocal lesions on the palms and soles. Unique dermoscopic features, including cotton-like white globular structures in palmoplantar lesions and follicular plugging in facial lesions, provide new diagnostic clues. In conjunction with hallmark histopathologic features, such as emperipolesis, and characteristic immunohistochemical staining patterns, these observations enhance the understanding of CRDD.

By highlighting these novel aspects, we aim to improve awareness of CRDD’s diverse features and stress the importance of a comprehensive diagnostic approach. Early detection and tailored treatment, as illustrated in our cases, are key to improving clinical outcomes and guiding best practices for managing this rare disorder.

The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000546382).

We wish to thank in particular the patients for their collaboration.

This case report was approved by the Ethics Committee of Isfahan University of Medical Sciences on December 2023. Written informed consent was obtained from the patients for publication of this case report and any accompanying images.

The authors declare that they have no competing interests and no financial intentions related to this manuscript.

No funding was involved in the creation of this text.

Dr. Fatemeh Mohaghegh was responsible for collecting the initial clinical data for the two cases, performing biopsies and related examinations, and establishing the final diagnoses. Dr. Mina Saber conducted the dermoscopic evaluations, contributed dermoscopy-related data to the manuscript, and provided consultation to enhance the accuracy of the content. Dr. Parvin Rajabi was responsible for the pathology-based diagnosis. Dr. Haniyeh Sohrabi gathered additional supporting information, compiled the data into tables, and prepared the final version of the manuscript.

All data generated or analysed during this study are included in this article and its supplementary material files. Further inquiries can be directed to the corresponding author.