Cutaneous Rosai-Dorfman Disease Research Articles

Cutaneous Rosai-Dorfman Disease: Comprehensive Review of Cases Reported in the Medical Literature since 1990 and Presentation of an Illustrative Case

The latest comprehensive review of primary cutaneous Rosai-Dorfman disease was published as part of an exhaustive survey of sinus histiocytosis with massive lymphadenopathy in 1990. Since then, much progress has been made in the understanding of malignant lymphoma and benign disorders of lymphoid and histiocytic origin. We reviewed cases of primary cutaneous Rosai-Dorfman disease published since 1990 and discuss their clinical and pathologic features, comparing them with cases of systemic Rosai-Dorfman disease. We conducted a search of the National Library of Medicine PubMed database for cases of cutaneous Rosai-Dorfman disease reported in the English-language medical literature since February 1990. We identified 72 patients with cutaneous Rosai-Dorfman (female to male ratio 1:0.5). The gross appearance and number or distribution of lesions were highly variable. Abnormal laboratory data included peripheral blood cytopenias (10 patients) and increased gammaglobulin fraction (10 patients). The response to treatment was variable. Purely cutaneous disease without the characteristic lymphadenopathy is rare but has been increasingly reported in the literature. Compared with patients with systemic Rosai-Dorfman disease, patients with primary cutaneous Rosai-Dorfman disease are older, women are more commonly affected, and whites are more likely than blacks to be afflicted.

Dapsone as a Potential Treatment for Cutaneous Rosai-Dorfman Disease With Neutrophilic Predominance

A 31-year-old Taiwanese woman, who from her medical history was generally well, presented with 1 slowly enlarging elevated plaque on the posterior aspect of her right shoulder. This had first been detected 3 months before the visit to our clinic. The lesion had originated as a small, tender, erythematous papule and had since grown into a large confluent plaque with satellite papules. She claimed that the lesion was increasing in size, and this was accompanied by intense itching and fever. On physical examination, there was 1 palm-sized, dusky red, elastic firm plaque on the right shoulder. The main lesion was surrounded by multiple 2to 8-mm erythematous satellite papules (Figure 1). There were no palpable cervical, supraclavicular, axillary, or inguinal lymph nodes. A systemic workup that included head, neck, and chest computed tomographic scans showed no involvement of other organs. Workups done to determine the source of her febrile episodes yielded no evidence of active infection. The only abnormal laboratory finding was polyclonal hypergammaglobulinemia found on serum protein electrophoresis. An incisional biopsy was performed. Microscopically, a dense dermal infiltrate extended from the upper dermis deep to the subcutis (Figure 2). The infiltrating cells were mainly composed of histiocytes with large vesicular nuclei. They also had abundant cytoplasm with spidery borders. Neutrophils, lymphocytes, and plasma cells were scattered between the histiocytes, and the presence of lymphocytes engulfed within the histiocytic cytoplasm, a feature called emperipolesis, was also noted. The mixed infiltration was neutrophil predominant. Immunohistochemical studies revealed histiocytes that stained positively for S100 protein and CD-68. Notably, the dermis surrounding the histiocytes was infiltrated by numerous neutrophils. Clinically and histologically, she was diagnosed as having cutaneous Rosai-Dorfman disease (CRD). Before visiting our hospital, she had been treated at a dermatologic clinic for 2 months, first with topical triamcinolone, oral prednisolone (30 mg/d), and then with oral isotretinoin (100 mg/d). However, the lesion had continued to worsen and the symptoms of pruritus and intermittent episodes of fever had progressed during the treatments. Superficial irradiation was suggested, but the patient refused owing to its potential hazards.

Cutaneous Rosai-Dorfman disease

Sinus histiocytosis with massive lymphadenopathy, or Rosai-Dorfman disease, is a benign idiopathic histiocytic proliferative disorder that commonly involves the lymph nodes but secondarily may involve the skin. However, purely cutaneous disease without lymphadenopathy or internal organ involvement rarely may occur. We present case reports of three patients who presented with asymptomatic nonspecific enlarging skin nodules without evidence of lymphadenopathy or internal disease. Histopathologic examination of skin lesions in all patients showed proliferation of large histiocytes with phagocytosed inflammatory cells characteristic of Rosai-Dorfman disease. However, the diagnoses of dermatofibroma, other spindle cell neoplasm, infectious granulomatous process, and other xanthohistiocytic proliferations were also considered due to the presence of storiform spindle cells and foamy cells in the first case. One patient experienced regression during a course of oral steroids, while another patient cleared spontaneously. In the absence of massive lymphadenopathy characteristic of Rosai-Dorfman disease, the diagnosis of purely cutaneous Rosai-Dorfman disease may be complicated by the rarity, non-specific clinical appearance of skin lesions, and broad histopathological differential diagnosis of this disorder. A high index of suspicion of the clinician and pathologist is often required.

Cutaneous Rosai-Dorfman disease: clinicopathological profiles, spectrum and evolution of 21 lesions in six patients

An uncommon histiocytosis primarily involving the lymph nodes, Rosai-Dorfman disease (RDD, originally called sinus histiocytosis with massive lymphadenopathy) involves extranodal sites in 43% of cases; cutaneous RDD (C-RDD) is a rare form of RDD limited to the skin. The clinicopathological diagnosis of C-RDD may sometimes be difficult, with different clinical profiles from those of its nodal counterpart, and occasionally misleading histological pictures. There have been few multipatient studies of C-RDD and documentation of its histological spectrum is rare. To identify the clinical and histopathological profiles, associated features, and the chronological changes of this rare histiocytosis. From 1991 to 2002, patients diagnosed as having C-RDD were collected in four academic hospitals. Clinical presentations, treatments, and courses of each case were documented. In total, 21 biopsy specimens obtained from these patients were re-evaluated and scored microscopically with attention to the uncommon patterns and chronological evolution both clinically and histologically. We examined six patients with C-RDD, three men and three women. The mean age at the first visit was 43.7 years. The clinical presentations were mostly papules, nodules and plaques, varying with the duration and depth of lesions. Although the anatomical distribution was wide, the face was most commonly involved. Evolutional changes were identified clinically, as the lesions typically began with papules or plaques and grew to form nodules with satellite lesions and resolved with fibrotic plaques before complete remission. No patient had lymphadenopathy or extracutaneous lesions during follow-up (mean 50.5 months). At the end of follow-up, the lesions in four patients had completely resolved irrespective of treatment; two patients had persistent lesions. The histopathological pattern of the main infiltrate, the components of cells and the stromal responses showed dynamic changes according to the duration of lesions. The characteristic Rosai-Dorfman cells (RD cells) were found in association with a nodular or diffuse infiltrate in 15 lesions (71%). Four lesions (19%) demonstrated a patchy/interstitial pattern. One lesion (5%) assumed the pattern of a suppurative granuloma. RD cells were less readily found in these atypical patterns. Conspicuous proliferation of histiocytes associated with RD cells was found in three lesions, including xanthoma, localized Langerhans cell histiocytosis and xanthogranuloma. Along with lymphocytes, plasma cells were present in all lesions, often in large numbers with occasional binucleated or trinucleated cells. Variably found in the lesions were neutrophils (nine lesions, 43%) and eosinophils (13 lesions, 62%). The former occasionally formed microabscesses, while the latter were often few in number. Vascular proliferation was a relatively constant feature (90%). Fibrosis was found in 10 lesions (48%). Our study further confirms that C-RDD is a distinct entity with different age and possibly race distributions from RDD. Compared with its nodal counterpart, C-RDD demonstrates a wider histopathological spectrum with different clinicopathological phases depending on duration of the lesions. Awareness of these features is helpful in making a correct diagnosis. The associations of C-RDD with other histiocytoses may have important implications for the pathogenesis of this rare histiocytosis.

Crystal Deposition in a Case of Cutaneous Rosai-Dorfman Disease

Rosai-Dorfman Disease (RDD) is an idiopathic reactive proliferation of distinctive histiocytes that have abundant cytoplasm and commonly exhibit intracytoplasmic ingestion of inflammatory cells (emperipolesis). The histiocytes are immunopositive for S100 protein and are typically associated with an infiltrate of lymphocytes, plasma cells, and neutrophils. The classic clinical presentation is massive enlargement of (usually) cervical lymph nodes with a histologic appearance that mimics exaggerated sinus histiocytosis. RDD can also involve extra-nodal sites and skin involvement is common either as part of disseminated disease or as a result of primary disease. We report an exceptional case of cutaneous RDD with crystal deposition in a young male presenting with skin nodules. Skin biopsy showed classic features of cutaneous RDD with the additional feature of conspicuous rhomboidal and needle-shaped crystals within the cytoplasm of many lesional plasma cells, histiocytes, and also in an extra-cellular location. The plasma cells were polyclonal by light chain immunostaining. Crystal deposition has not been reported to date in RDD and is likely a result of the reactive plasma cell proliferation.

New entities in dermatopathology

This article discusses some recently described entities in dermatopathology that are uncommon but important to recognize. The interstitial granulomatous drug reaction was described in 1998 and shares some differential diagnoses with palisaded neutrophilic and granulomatous dermatitis, an entity that has been given many different names. Nephrogenic fibrosing dermatopathy and calciphylaxis are rare but important conditions occurring in patients with renal failure. The seriousness of a diagnosis of calciphylaxis and of cholesterol embolization syndrome must be communicated to clinicans as a matter of urgency. Cutaneous Rosai Dorfman disease and acute generalized pustulosis are important in that their prognosis is excellent and good news for the patient. Superficial pyoderma gangrenosum and granuloma faciale are included as not-so-new entities whose features are not commonly known and which may be underdiagnosed.

Rosai-Dorfman disease presenting as multiple soft tissue masses

Rosai-Dorfman disease is a rare clinical disorder which may present in many forms. While classically a disease of lymph nodes, soft tissue involvement is fairly common. Soft tissue involvement can occur without any lymphatic or systemic involvement, and may be difficult to diagnose. We describe a patient presenting with multiple soft tissue masses which on biopsy proved to be isolated cutaneous Rosai-Dorfman disease. MR imaging showed two well-defined nonspecific superficial masses that enhanced intensely. Review of the literature suggests that when this disease presents in soft tissue, multiple foci of involvement may be common. Although rare, Rosai-Dorfman disease should be considered in the differential diagnosis of patients presenting with multiple soft tissue masses.

Cutaneous Rosai-Dorfman disease

To investigate the clinicopathologic feature, immunophenotype and differential diagnosis of cutaneous Rosai-Dorfman disease (CRDD). Clinical manifestation, morphologic features and immunohistochemical staining were studied in 8 cases of CRDD. All 8 patients presented with multiple papules, nodules and/or coalescent patches or plaques distributing over the extremities or trunk, without lymphadenopathy or other systemic abnormalities. Microscopically, the lesions were located intradermally and/or subcutaneously. CRDD was characterized by the presence of S-100 positive histiocytic cells exhibiting emperipolesis, accompanying with infiltration of mixed inflammatory cells. Fibrosis, somewhere in vague storiform pattern due to stromal responses, with distribution of individual neutrophil microabscess was seen in cases with a long course of illness. Dilated vascular spaces in dermis containing numerous large typical histiocytes were seen in 2 cases. CRDD is a benign, persistent proliferative disease of histiocytes. Systemic involvement is rare, outcome favorable. It should be differentiated from other types of histiocytosis, dermatofibrosarcoma protuberans, xanthoma and lymphoproliferative disorders. Immunohistochemical staining for S-100 protein and CD68 is helpful in making a correct diagnosis.

Cutaneous Rosai Dorfman Disease

A 61‐year‐old female presented with blurry vision. Questioning revealed “Flu‐like” symptoms preceding the blurry vision by two weeks. An ophthalmologist diagnosed anterior granulomatous dermatitis, which improved with prednisolone drops. One month later, an “itchy rash” and constitutional symptoms including fever, night sweats, and weight loss were reported. Physical examination revealed a viral‐type maculopapular eruption over the trunk and proximal extremities. A few weeks later, repeat examination showed progression to a diffuse, reddish‐brown, slightly edematous, papular eruption. Lymphadenopathy was not present. Laboratory data revealed a normochromic normocytic anemia, a polyclonal gammopathy, and an elevated ESR. Punch biopsies on two occasions showed a proliferation of mononucleated and multinucleated histiocytic cells with abundant pink cytoplasm. Emperipolesis was easily demonstrated. A background of plasma cells and small lymphocytes were noted. Stains for organisms were negative, and polarizable material was not present. By immunohistochemistry, histiocytes marked with S‐100 but were negative for CD1a. A diagnosis of cutaneous Rosai Dorfman was made. The cutaneous symptoms improved over six months without medical therapy. Cutaneous Rosai Dorfman disease with constitutional symptoms and laboratory evidence of systemic involvement but without lymphadenopathy has not been previously described. This unusual case suggests that a wider spectrum of disease presentation may exist.

Clinical and histopathologic spectrum of cutaneous Rosai-Dorfman disease in Taiwan

Background Cutaneous Rosai-Dorfman disease (RDD) is a rare entity of unknown origin and is not well documented, especially in Asian populations. Objective The purpose of this study was to evaluate the clinical manifestation, diagnostic histopathology, clinical course, and response to treatment of cutaneous RDD in Taiwan. Materials and methods This study included 21 patients with cutaneous RDD who presented at our institution from 1995 to 2003. Pathologic examinations with both hematoxylin-eosin and immunohistochemical stains were reviewed, as were associated clinical features and therapeutic methods. Results None of the 21 patients with cutaneous RDD had nodal lesions. The clinical manifestation was variable, but most commonly involved a central noduloplaque with satellite papules. One patient manifested as an ulcerated nodule, something not reported previously. Multifocal involvement only occurred in 4 patients. Concurrent involvement of uvea or vocal cord occurred in two patients. The most prominent histologic feature was a florid and mixed inflammatory infiltration. The phagocytosis of inflammatory cells into the cytoplasm of histiocytes, a process called “emperipolesis,” is a characteristic finding of nodular RDD but usually only focally presented in cutaneous ones. Positivity for S-100 protein helped to confirm the diagnosis. The most effective treatment was surgical excision of solitary lesions. High-dose thalidomide (300 mg/d), but not low-dose, was effective to control the extensive cutaneous diseases in two patients. A total of 3 patients experienced spontaneous remission 1 to 2 years after diagnosis. Conclusions Cutaneous RDD appeared more frequently in Asian populations than in reports from Western countries. The incidence of multifocal involvement in this series is much lower than in other literature. Although treatment of disseminated cutaneous RDD is difficult, high-dose thalidomide (300 mg/d), which was effective in two patients in this series, may be helpful.

Bilateral anterior granulomatous uveitis associated with cutaneous Rosai-Dorfman disease

Rosai-Dorfman disease (RDD) is a benign, rare, histiocytic disorder of unknown etiology. We describe the case of a 61-year-old woman who presented to the ophthalmology clinic with bilateral granulomatous anterior uveitis. The uveitis was controlled on topical prednisolone acetate 1%. One month after presentation, she developed generalized macules and papules, and dermatologic and systemic evaluations were performed. On the basis of skin biopsy, purely cutaneous RDD was established. Anterior granulomatous uveitis may be the presenting sign of cutaneous RDD. Consultation is necessary for accurate diagnosis.

Cutaneous Rosai-Dorfman disease

Presented is a case of a 31-year-old woman with cutaneous Rosai-Dorfman disease, which is a rare, benign, generally self-limited histiocytic proliferative disorder that is characterized by painless lymphadenopathy, fever, neutrophilia, an elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. It primarily involves lymph nodes but can affect extranodal sites such as the skin, where it typically appears as indistinct erythematous papules and nodules. On histopathologic examination, emperipolesis is a consistent finding. The etiology is unknown, and treatment is based on clinical manifestations.

Ｃｕｔａｎｅｏｕｓ Ｒｏｓａｉ‐Ｄｏｒｆｍａｎ ｄｉｓｅａｓｅの１例

We report a case of cutaneous Rosai-Dorfman disease (RDD) rising in a 52-year-old Japanese female with two nodules: one was a red nodule on her cheek and the other was a subcutaneous nodule on her chest. Histopathological analysis revealed that the nodules were composed of many histiocytes that were positive to S100, but negative to CD1a showing “emperipolesis”. We diagnosed her with cutaneous RDD based on the histological findings since she had no other lymphadenopathy or extranodal involvement. RDD derived from the skin without lymph node involvement is rare worldwide with approximately 50 cases reported. No cases have been reported in Japan. [Skin Cancer (Japan) 2004; 19: 124-127]

Cutaneous rosai-dorfman disease is a distinct clinical entity.

Rosai-Dorfman disease (RDD) is a rare but distinctive clinicopathologic entity of unknown etiology affecting lymph nodes as well as extranodal sites. Although cutaneous involvement in RDD is common, purely cutaneous disease is rare and not well documented. We report 22 patients with cutaneous and superficial subcutaneous RDD. The lesions presented as papules and nodules, often with discoloration (9/22) and frequent multifocality (13/22), without predilection for a specific site of the body. Age distribution was wide and ranged from 15 to 68 years, with a median of 43.5 years. Of the 17 patients for whom information on racial background was available, 7 were Asian, 8 were white, and 2 were black, with a marked female predominance (2:1). The lesions resolved in 6 of 13 patients for whom follow-up data were available, regardless of the treatment given. Lesions persisted or recurred in 7 patients. Histologically, the lesions are invariably characterized by a proliferation of polygonal S100-positive histiocytes showing emperipolesis and a mixed inflammatory infiltrate. This study characterizes the histologic spectrum of cutaneous RDD in regard to variation in the numbers of typical S100-positive histiocytes and emperipolesis, variation in the quality and quantity of the inflammatory response, and the degree of stromal fibrosis, which resulted in a strikingly storiform growth pattern in six lesions and a lobulated pattern in two lesions. Whereas the clinical as well as histologic appearance of the cutaneous and subcutaneous lesions in the purely extranodal forms of RDD is indistinguishable from that of systemic RDD, this study emphasizes that purely cutaneous RDD is a distinct clinical entity in regard to its epidemiology and remains localized to the skin even with long-term follow-up. Patients with purely cutaneous RDD are of an older age at onset of disease (median = 43.5 years), with a reversed male/female ratio. There are no significant systemic extracutaneous or serologic manifestations. Whereas systemic RDD is commonly seen in blacks and only rarely reported in Orientals, the majority of the patients in this series with purely cutaneous RDD are Asians and whites.

Pure cutaneous Rosai Dorfman disease (sinus histiocytosis confined to the skin)

Pure cutaneous Rosai Dorfman disease (sinus histiocytosis confined to the skin)

Cutaneous Rosai-Dorfman disease presenting as pustular and acneiform lesions

We report 2 cases of cutaneous Rosai-Dorfman disease (CRD) presenting with pustular and acneiform lesions. To our knowledge, these are the first reports of CRD presenting in this pattern. One patient had spontaneous resolution of the lesions, whereas the other was treated with cryotherapy with clinical improvement. We present a review of the literature regarding CRD and highlight the benign nature of this condition. (J Am Acad Dermatol 1999;41:335-7.)

Purely cutaneous Rosai-Dorfman disease

Cutaneous lesions of Rosai-Dorfman disease (RDD) are usually associated with nodal or other extranodal localization. We describe a female patient with RDD clinically limited to the skin. The patient presented with asymptomatic red-brown papules and nodules on the legs, arms, back, and nose. Histologically, the lesions consisted of a proliferation of large histiocytes occasionally showing emperipolesis. Histiocytes were also observed within dilated lymphatic vessels. Immunohistochemical study showed that histiocytes expressed S-100 protein and both macrophage and monocyte markers. All lesions resolved completely with Roentgen therapy. No recurrence has been observed over a 3-year follow-up period.

Purely cutaneous Rosai-Dorfman disease

Purely cutaneous Rosai-Dorfman disease

Cutaneous Rosai‐Dorfman disease presenting as a suspicious breast mass

Cutaneous Rosai-Dorfman disease in a male patient presented as a clinically malignant left breast mass. The intra-operative frozen section indicated a benign inflammatory lesion and a simple excision was performed. The disease was apparently limited to the skin and subcutis of the left breast with no lymph nodes or other organs involvement. While the lesion demonstrated the characteristic morphology of Rosai-Dorfman disease, the diagnosis of granulomatous mastitis, epithelioid sarcoma and other cutaneous xanthohistiocytic proliferations were considered. In the absence of lymphadenopathy, a high index of diagnostic awareness is required to recognize the uncommon, solitary cutaneous Rosai-Dorfman disease.