liritisli journal of Dermatology 1996: 134: 749-753.

Purely cutaneous Rosai-Dorfman disease

G.ANNESSI AND A.GIANNETTrCllnica I'k-rmatologiva Vniverslta' dl Modena. Istituto Dermopatico dell' Immacolata IRCCS. Via Monti di Creta 104. 00167.Roma. Italy

Accepted for publication 2 May 1995

S u m m a r y Cutaneous lesions of Rosai-Dorfman disease (RDD) are usually associated with nodal or otherextranodal localization. We describe a female patient with RDD clinically limiled to the skin. Thepatient presented with asymptomatic red-brown papules and nodules on the legs. arms. back, andnose. Histologically. the lesions consisted of a proliferation of large histiocytes occasionally showingemperipolesis. Histiocytes were also observed within dilated lymphatic vessels. Immunohistochem-ical study showed that histiocytes expressed S-l()() protein and both macrophage and monocytemarkers. All lesions resolved completely with Roentgen therapy. No recurrence has been observedover a 3-year follow-up period.

In 1969. Rosai and Dorfman first described a peculiarbenign cervical lymphadenopathy in four patients thatconsisted, histologically, of a proliferation of pale andlarge histiocytes within the subcapsular and medullarysinuses. They named the disease sinus histiocytosis withmassive lymphadenopathy (SHML).' Currently, SHMLencompasses a spectrum of clinical manifestations thatincludes both nodal and extranodal forms." ' The termRosai-Dorfman disease (RDD). therefore, shouldbe preferred to SHML because the latter does notaccurately describe the group of cases without lympha-denopathy. The skin is the most common site of extra-tiodal involvement, but few cases of purely cutaneousKDD have been described.' ' ' We report a patient withRDD clinically limited to the skin, on whom detailedimmunohistochemical studies were performed.

and neurological examinations. Serological tests didnot reveal an elevation of Epstein-Barr virus or cyto-megalovirus titres. Bone marrow examination, chestX-ray, and total-body computed tomographic (CT) scanwere negative. Histological study of two different earlypapules showed the same features, namely a superficialand mid-dermal perivascular and interstitial dermatitisconsisting mostly of histiocytes with vesicular nucleiand scant amphophilic cytoplasm. Several lymphocytesand a few neutrophils, eosinophils and plasma cellswere present around the blood vessels. Histologicalexamination of a nodule of the back revealed a dense,nodular, mostly histiocytic. Infiltrate involving thedermis and the upper part of the subcutaneous fat.The histiocytes had large, round-oval, vesicularnuclei, with a single eosinophilic nucleolus. and an

Case report

A 38-year-old woman gave a 2-week history of numer-ous, asymptomatic, dome-shaped papules. localized tothe anterior part of the legs. They were 1-3 mm indiameter, red-brown in colour, and had a smooth shinysurface. During the following weeks, numerous otherpaptiles developed on the posterior part of the legs(Fig. 1). the nose (Fig. 2), and on the back, wheremerging of the lesions gave rise to red-brown noduleswith tin irreguUir and lumpy surface. Tbe patient nevercomplained of lever and examination Tailed to show anysuperficial lymphadenopathy. Routine laboratory testswere normai, as were ophthalmic, ear. nose and throat.

Correspondence: Dr G.Annessi.

1. Red-brown papules and nodules, with a lumpy surtHce, onthe legs,

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750 G.ANNESSI AND A.GIANNETtl

Figure 2. A nodular lesion on the nose.

abundant, pale, fibriliar cytoplasm (Fig. 3). The cyto-plasmic borders were irregular, giving the cells a spideryconfiguration. The infiltrate also included lymphocytes,neutrophils and plasma cells. The lymphocytes formedsmall nodular aggregates, especially at the periphery ofthe nodule. A common finding was the presence ofleucocytes and red cells within the cytoplasm of severalhistiocytes (emperipolesis) (Fig. 3). Large histiocytes

were also observed within dilated lymphatic spaces(Fig. 4). The results of the immunohistochemicalstudy are summarized in Table 1. Histiocytesstained positively for S-100 protein, a-1-antitrypsin.a-1 -antichymotry psin. lysozyme. HLA-DR. CD 14.CD68. CD36 and MAC-387, whereas they werenegative for CDla. Only a few histiocytes expressedthe CD4 and CD30 antigens.

The patient wanted to be treated as she consideredthe lesions cosmetically disfiguring. We used Roentgentherapy (45kV. 25mA. 0-6mm Al filter. 15cm targetskin distance) to treat the nodules on the back and thenose. An overall dose of 14Gy. subdivided into sevenfractions, was administered over a period of 7 weeks.The numerous lesions on the legs were treated withRoentgen therapy (150kV. 16 mA. 1 mm Cu. Al filter,50 cm target skin distance). The patient received anoverall dose of 40 Gy. in 40 fractions, over a period of 2months. All the lesions underwent complete regressionin 3 months and no side-effects were observed (Fig. 5).The patient has not developed further cutaneouslesions, nor superficial lymphadenopathy. over a 3-year follow-up period. Every (S months, routine labora-tory investigations and a total-body CT scan, havealways been normal.

Discussion

RDD is considered to be a rare idiopathic histiocytosisdefined by its histological features. The disease maydeveiop at any age, although the mean age of onset is

Figure 3. Histiocytes with large, vesicuiarnuclei and an abundant pale cytoplasm,are inlerspersed with lymphocytes andplasma cells. A few leucocytes are observedwithin the cytoplasm of the histiocytes(haematoxylin and eosin. x200).

1996 British Association of Dennatologists. Brilish Journal of Dermatology, 134, 749-753

CUTANEOUS ROSAI-DORFMAN DISEASE 751

i igurc 4. Histiocytes. wilh vesicular nucleiand irregular cytoplasmic borders, arepresent within ;i dilated lymphatic space{haematoxylin and eosin, xlBO).

20 years. It affects both males and females, and showsno racial predominance.' The commonest presentationis as a painless, hilateral cervical lymphadenopathywith fever, an elevated erythrocyte sedimentation rateand a polyclona! gammopathy. RDD occurs in anextranodal location in 43'!{» of cases, with the skinbeing the most frequent site (involved in 27% of caseswith exlranodal disease).^"' Usually, cutaneous mani-festations are associated with nodal or with otherextranodal involvement.^'^'^"'^*'* Our patient, withRDD confined to the skin, illustrates that RDD mayclinically simulate other forms of non-X histiocytosis,

such as diffuse cutaneous reticulohistiocytosis.^^generalized eruptive histiocytoma.^*' nodular progres-sive histiocytoma,^''^* and indeterminate cellhistiocytosis.^"^ All these diseases may present withwell-circumscrihed red-brown or red-yeUow papules,that may become confluent and develop into nodulesor plaques with a characteristic lumpy appearance.

In the absence of lymphadenopathy there are noclinical features specific for a diagnosis of cutaneousRDD. and histological examination is required. Thepapules and nodules show a dense, diffuse infiltrate,mainly composed of large, pale histiocytes with stellateor spidery borders. Lymphocytes, neutrophils and

Table 1. An immunohistochemical study ofthe cutaneous lesions in apatient with Rosai-Dorfman disease

Antibody

s-ino*o-l-antitrypsin*fi-1 -aniichymotrypsin*Lysozyme*CD14t(LeuM3)CU68tCD36t (0KM5)MAC-387*HLA-i)RtCDlaj (OKTfi)CD4t (Lcu3a)CD30t

Source of antibody

OrthoUakoDakoDakoBecton DicitinsonImmanotechOrthoDaiioBecton DickinsonOrthoBecton DickinsonDako

Histiocyte reactivity

PositivePositivePositivePositivePositivePositivePositivePositivePositiveNegativePositive (a few ceQs)Positive (a few cells)

* ParalTm-embedded tissue sections.t Frozen tissue sections.

Figure 5. Complete regression of the nodular lesion of the nose is seenafter Roentgen therapy.

© 1996 British Association of Dennatologists. British Journal of Dermatology, 134. 749-753

752 G.ANNESSI AND A.GIANNETTI

plasma cells are commonly seen within the cytoplasm ofthe histiocytes {emperipolesis). A diagnostic feature isthe present of histiocytes within dilated iymphaticspaces.' "^ In our patient, histological examinationof early papules revealed a superficial and mid-dermal,perivascular and interstitial, mostly histiocytic,dermatitis with lymphocytes, a few plasma cells,neutrophils and eosinophils arranged around theblood vessels. The finding of this pattern in two differentiesions suggests that this could be specific enough toallow identification of early lesions of cutaneous RDD.

The histopathological differential diagnosis includesmalignant histiocytosis and haemophagocyticsyndrotne. Unlike RDD, the histiocytes of malignanthistiocytosis display atypical nuclei.^"'^^ In haemo-phagocytic syndrome, histiocytes do not have a spideryshape, and they are not seen within lymphatic vessels.Moreover, in haemophagocytic syndrome associatedwith iymphoma. the lymphocytes have atypicalnuclei."" In our patient, the histiocytes expressedS-100 protein, a-1-antitrypsin. a-l-antichymotrypsin.lysozyme. MAC-387. and CD68 antigens, but werenegative for CDla. However, the findings of S-100-positive histiocytes should not be considered specificfor RDD as it can be found in other histiocytoses suchas X-histiocytosis. self-healing reticuiohistiocytosis.indeterminate cell histiocytosis. and it has been reportedin a few cases of reticulohistiocytosis.^"'^^"'^^ Wefound that the histiocytes of RDD expressed both themacrophage (CDl 4} and monocyte (CD3f)) markers,supporting the idea that the histiocytes of RDD couldbe considered as functionally activated macrophages,perhaps recently derived from monocytes."''

Although RDD is considered a benign histiocyticdisorder that mostly runs an indolent and self-limitingcourse, a small group of patients may have a moreaggressive form of the disease. In such cases, nodularexpanding lesions may interfere with the function ofvital organs, and this may eventually be fatal."^' Ourpatienl and the reported cases'^" suggest that whenRDD is clinically limited to the skin, the prognosis isusually good and there is only a small risk of developingsystemic disease. Usually, cutaneous lesions do notrequire any treatment as they show a self-limitingcourse and tend to regress spontaneously."' At therequest of our patient, we treated the lesions withRoentgen therapy. Although spontaneous recoverycould not be excluded, a rapid improvement andcomplete regression of all lesions was seen after thistreatment. No side-effects or rectu-rence has beenobserved over 3 years of follow-up, suggesting that

Roentgen therapy could be a useful treatment whencutaneous RDD runs a prolonged course, or when thelesions are aesthetically unacceptable to the patienl.

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1996 British Association of Dermatoiogists. British }ourml of Dermatology. 134, 749-753