Cutaneous Rosai-Dorfman Disease

Abstracts

Doença de Rosai-Dorfman é uma doença benigna e autolimitada. Tem etiologia desconhecida e foi descrita pela primeira vez por Rosai e Dorfman em 1969. As manifestações clássicas incluem linfadenopatia cervical usualmente acompanhada por febre, leucocitose com neutrofilia e hipergamaglobulinemia policlonal. Apesar de a pele ser o principal sítio extranodal da doença, sua manifestação restrita à pele costuma ser bastante rara com poucos casos descritos na literatura. O trabalho tem como objetivo relatar um caso de Doença de Rosai-Dorfman cutânea com revisão da literatura onde são abordados os diferentes aspectos do diagnóstico e do tratamento dessa doença.

Histiocitose de células não langerhans; Histiocitose sinus; Pele

CASE REPORT

Cutaneous Rosai-Dorfman Disease

Fábio Machado Landim^I; Helena de Oliveira Rios^II; Carolina Oliveira Costa^III; Roney Gonçalves Fechine Feitosa^IV; Adriana Alencar Araújo Costa^V

^ISurgeon of the Skin Tumors Service of Instituto do Câncer do Ceará, General Medical Residence Coordinator of Instituto do Câncer do Ceará – Fortaleza (CE), Brazil

^IIDermatologist of Instituto do Câncer do Ceará – Fortaleza (CE), Brazil

IIIMedical Student of Universidade Estadual do Ceará – Fortaleza (CE), Brazil

^IVPathologist of Instituto do Câncer do Ceará – Fortaleza (CE), Brazil

^VPathologist of Instituto do Câncer do Ceará – Fortaleza (CE), Brazil

^{Mailing Address}

ABSTRACT

Rosai-Dorfman disease is a self-limited benign disease. Rosai and Dorfman first described it in 1969, and the etiology of the disease remains unknown. Main manifestations are cervical adenopathy associated with fever, leukocytosis with neutrophilia and polyclonal gamaglobulinemia. Although the skin is the most common site of extra nodal disease, Rosai-Dorfman disease restricted to the skin is very rare with only a few cases described in the literature. This paper reports a rare case of cutaneous Rosai-Dorfman with skin as the sole site, and reviews the controversies of diagnosis and treatment.

Keywords:Histiocytosis, Non-langerhans-cell; Histiocytosis, sinus; Skin

INTRODUCTION

Sinus histiocytosis with massive lymphadenopathy, described in 1969 by Rosai and Dorfman,¹ is a benign and self-limited condition, characterized by cervical lymphadenopathy usually accompanied by fever, leukocytosis with neutrophilia and polyclonal gamaglobulinemia. Lymphadenopathy, is generally bilateral, painless and massive, and may also affect other lymphatic chains. It is seen at any age, but there is a preference for young male adults (1. 4:1).² The disease is more common in white and black individuals, and is rare in Asian descendent individuals.

Purely cutaneous manifestations occur in only 3% of cases, usually as red-brown or red-yellow, restricted or disseminated, papules or nodules, and without a particular site. Regarding disease restricted to the skin, the average age most frequently affected is around 49 years,³ with a slight predominance in females and Asian individuals,^2-4 unlike classical Rosai-Dorfman Disease. Despite most cases having been observed in poorer areas of the globe, no etiological agent has been isolated.

The authors of the present study present a case of skin Rosai-Dorfman Disease with a literature review on the subject, focusing on the different aspects of diagnosis and treatment of the condition.

CASE REPORT

Black, male, 27 year-old, single, Brazilian, nurse technician sought medical care with a history of painless, non erythematous, nodules on his back, without previous draining, maintaining same skin coloration, and that one year before had increased rapidly into nodules in the central region of his back, leading him to pursue medical care, occasion on which an incisional biopsy was performed. The result of the pathology exam was a lesion compatible with sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman Disease). After diagnosis, the patient was sent to a skin tumor reference service for diagnosis and treatment. At the reference service, the patient referred absence of fever, peripheral adenopathy or weight loss. He denied alcohol consumption, smoking or use of illicit substances.

The patient’s physical examination was uneventful, and there were no peripheral lymphadenomegalies or oral mucosa lesions. BP=130x80mmHg; RR=18rpm; HR= 88bpm; T= 36°C. There was a transverse scar on the medium region of the back, where the incision biopsy had been performed; and five adjacent intradermal nodules, without changes in skin color, not adhered to the deep plane, hardened, the largest measuring about 1.5 cm, in its largest diameter. The examination of lungs, heart, abdomen and extremities was uneventful.

Lab tests, such as blood count and electrolytes were normal. Chest and cervical CT was normal, with no lymphadenopathy.

Despite a self-limited condition, we discussed management with the patient, and, due to progressive growth, lack of comfort, and aesthetical reasons, the patient preferred surgical excision of the lesion.

An ample resection was performed resulting in a 6.0 x 5.5 x 2.0 cm surgical specimen, showing a flat and undulated, dark-brown, symmetrical lesion, with irregular edges, measuring 4.0 x 1.7 cm, distant 0.1cm from the closest lateral margin. Slices showed the lesion surface was light-brown and compact, measuring 1.4cm deep, 4.3 cm long and 0.2 cm distant from the deep margin. Microscopy showed an infiltrate consisting of countless lymphocytes, plasmocytes and hystiocytes displaying a nodular arrangement affecting the dermis (Figure 1). Emperipolesis was observed in certain fields (Figures 1 and 2). Immunohistochemistry revealed CD45+, CD68+, S100+ protein (Figure 2), CD1a-. Rotation of a fasciocutaneous flap was performed. There was a small dehiscence in the flap during the post-operative, for which management was conservative. The patient evolved without developing disease in the past six months of outpatient follow-up.

DISCUSSION

Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman Disease is a proliferative histiocyte disorder, which is rare, benign and of unknown etiology. It is classified as a non-Langerhans cell histiocytosis or type II histiocytosis.

It was described for the first time in 1965 and acknowledged as a clinical-pathological entity in 1969 after the publication by Rosai and Dorfman, who described the clinical manifestations of the condition.1,5 The disease may affect any age, but is more common in the first and second decades. It has a slight preference for males (1.4:1) and the most frequently affected ethnical groups are black and white individuals, being rarely reported in Asians.² It is, in general, characterized as extensive, bilateral and painless lymphadenopathy (most commonly cervical), frequently associated with fever, anemia, leucocytosis with neutrophilia, high blood sedimentation rate and polyclonal hipergamaglobulinemia. ^2,4

Extra-nodal involvement is observed in 25-43% of cases.^6,7 Although skin is the most common extra-nodal site (11%),8 the purely cutaneous variant, that is, without lymphonode involvement, of Rosai-Dorfman Disease is very rare. Only about 3% of patients have disease limited to the skin. ⁸

Cutaneous Rosai-Dorfman Disease was described for the first time in 1978, by Thawerani et al⁹ who reported a case in a 48 year-old man with a single shoulder nodule and hypergammaglobulinemia.

Rosai-Dorfman Disease skin lesions may be single or multiple. They present as pápules,¹⁰ nodules,¹⁰ or plaques,^11,12 or a combination of these clinical variants,¹³ with or without change in the color of adjacent skin.

Optical microscopy of skin lesions show dense dermis infiltrate with histiocytes mixed to plasmocytes and lymphocytes. Histiocytes generally have a foamy aspect, and may be multinucleate and result in emperipolesis. In emperipolesis, unlike lympho- phagocytosis, lymphocytes are trapped by histiocytes, but not digested, remaining intact inside the latter. Emperipolesis is a useful criterion, albeit not specific for diagnosing Rosai-Dorfman Disease restricted to skin, given it may also be seen in neoplastic and inflammatory processes.14 Emperipolesis was observed in the microscopy of the present patient’s skin lesion (Figures 1 and 2).

Lymph nodes present capsular fibrosis and dilated nodular sinuses filled by foamy histiocytes, therefore the condition also being known as sinus histiocytosis with massive lymphadenopathy.⁴

The classical immuno-histochemistry and ultramicroscopic profile is characterized by S-100+, CD1a-, without Birbeck granules. This type of immuno-histochemistry spectrum leads to believe that sinus histiocytosis with massive lymphadenopathy is a proliferation of lymph node antigen processing interdigitating dendrite cells.²

The clinical-pathological diagnosis of Rosai-Dorfman Disease limited to the skin may sometimes be difficult due to the clinical profile and undifferentiated histopathological characteristics of the skin lesions of Rosai-Dorfman Disease affecting lymph nodes.²

Differential diagnosis of Rosai-Dorfman Dissease skin lesions is complex and very important, given that the malignant lesion variety should be ruled out, as should the association with Langerhans cells histiocytosis, which is extremely rare and fatal.¹⁵

Cutaneous Rosai-Dorfman Disease generally has a benign development with low risk of systemic involvement. Patients who do not have an association with Langerhans cell histiocytosis, but do have histiocyte pleomorphism with little mitoses, generally resolve spontaneously, or do not need surgical exeresis. Surgical excision of the skin lesion is the exclusive effective treatment for disease limited to the skin, especially for single or located lesions.

Other documented treatment options for Cutaneous Rosai-Dorfman Disease are: radiation therapy, chryotherapy, chemotherapy and isotretionin. 3 High doses of thalidomide (300 mg/dl) may be used to control extensive skin disease. ³ Treatment options depend on the extension of the disease, acceptance by the patient and adverse effects of treatment.

We conclude that, in tumors located exclusively in a single skin anatomical site, with feasible surgical resection, surgery should be considered: 1) in tumors that persist or recur; 2) when histopathology findings are inconclusive; 3) when there are symptoms; 4) if it is the patient’s wish. Surgery should aim for complete resection, with free margins, which is a very good option for loco-regional control. Patient follow-up with skin restricted disease is long (17 months on average), aimed at excluding systematic spread of the disease or local recurrence. ²

REFERENCES

Conflict of interest: None

Financial funding: None

How to cite this article: Landim FM, Rios HO, Costa CO, Feitosa RGF, Rocha Filho FD, Costa AAA. Doença de Rosai-Dorfman cutânea. An Bras Dermatol. 2009;84(3):275-8.

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Publication Dates

• Publication in this collection
  04 Aug 2009
• Date of issue
  July 2009

History

• Received
  02 Apr 2008
• Accepted
  26 Jan 2009