Diagnosis: generalized eruptive histiocytosis (histiocytoma)

ARTICLE

A 33-year-old woman presented with a 2-month history of multiple asymptomatic skin lesions irregularly distributed on her trunk and extremities. The patient's general health was good. She had taken no drugs and had no history of insect bites preceding the appearance of these lesions. On examination, about thirty round, red-brownish papular lesions ranging from 2 to 8 mm in diameter were observed. They were firm, discrete and slightly raised-to-hemispheric (Fig. 1). Laboratory tests and X-ray investigations showed no abnormalities.

A diagnostic, excision biopsy specimen was obtained (Fig. 2). The hematoxylin-and-eosin stained sections revealed a relatively monomorphous, wedge-shaped histiocytic infiltrate in the whole dermis. The histiocytes contained a large pale nucleus, with scanty chromatin and poorly limited, foamy cytoplasm. Giant cells were not found. Relatively small numbers of lymphocytic cells were admixed. Immunohistochemical labeling demonstrated that the histiocytic cells were positive for CD14, CD36, CD68, Mac 387, factor XIIIa, HLA-DR, lysozyme and alpha1-antitrypsin, but negative for S100 and CD1a.

Electron microscopy showed the cytoplasm of histiocytes to contain both smooth and rough endoplasmic reticulum, mitochondria and microfilaments 70 Å thick. The most prominent cytoplasmic organelles were dense bodies, multivesicular bodies and the so-called "regularly laminated bodies", namely dense bodies with strongly osmiophilic parallel membranes arranged concentrically. Several worm-like bodies and cytoplasmic pleomorphic inclusions were detected, but Birbeck granules were absent.

The patient was not treated but re-examined monthly. Within a few months, the lesions began to regress spontaneously, and they had completely disappeared without sequelae by 6 months. No relapses occurred over a 3-year follow-up period.

Discussion

In 1963, Winkelmann and Muller [1] reported three cases of a generalized benign papular histiocytic reticulohistiocytosis of adulthood, which they aptly called generalized eruptive histiocytoma (GEH). They listed the following diagnostic features: (i) widespread, essentially symmetric, multiple lesions particularly involving the trunk and proximal limbs and, rarely, the mucous membranes; (ii) distinct red-brown to red-blue papular lesions, evenly distributed without a tendency to grouping; (iii) spontaneous resolution of lesions to brown macules or disappearance without trace; (iv) progressive development of new crops of lesions for years, even decades, permanent remission usually occurring; (v) a benign histological picture of mononuclear histiocytic cells.

Several cases of GEH in children have also been reported [2]. One of us [2] pointed out that the lesions of GEH in children are not always symmetrically distributed but may be localized and they may become xanthomatous. Interestingly, the present case of GEH in a young woman showed no symmetric distribution of lesions. Furthermore, apparently permanent remission occurred over a relatively short period, namely of about 6 months.

It has been suggested by various authors [3, 4] that GEH may represent an early indeterminate stage of more mature non-Langerhans cell (LC) histiocytoses, including multicentric reticulohistiocytosis, xanthoma disseminatum, indeterminate cell histiocytosis, juvenile xanthogranuloma and benign cephalic histiocytosis (BCH), this last one being regarded as a regional form of GEH [5]. The very rare cases of GEH evolving into one of the other non-LC histiocytoses may serve to confirm such a concept [6].

Our case is typical in its clinical presentation and behavior, except for the peculiarities mentioned above. We would, however, emphasize the rarity of this histiocytopathy and the difficulties in diagnosing it. Indeed, GEH mimics various non-LC histiocytoses, most notably BCH, this latter being histologically closely related to GEH. However, the localization of the eruption to the head and neck and the appearance of the disease only in children seem to be distinctive features of BCH. Among the other non-LC histiocytoses, juvenile xanthogranuloma, papular xanthoma and xanthoma disseminatum may be easily excluded in view of the colour of the lesions and the presence of both foamy cells and Touton giant cells. Finally, multicentric reticulohistiocytosis is ruled out because of the absence of arthritis and the lack of giant cells with ground-glass cytoplasm. Other than non-LC histiocytoses, several diseases, such as sarcoidosis, urticaria pigmentosa, lymphoma and xanthomata, may represent a problem in differential diagnosis only from a clinical point of view.

References

1. Winkelmann RK, Muller SA. Generalized eruptive histiocytoma: a benign papular histiocytic reticulosis. Arch Dermatol 1963; 88: 586-96.

2. Caputo R, Ermacora E, Gelmetti C, Berti E, Gianni E, Nigro A. Generalized eruptive histiocytoma in children. J Am Acad Dermatol 1987; 17: 449-54.

3. Winkelmann RK. Cutaneous syndromes of non X histiocytosis. Arch Dermatol 1981; 117: 667-72.

4. Caputo R, Alessi E, Allegra F. Generalized eruptive histiocytoma: a clinical, histologic, and ultrastructural study. Arch Dermatol 1981; 117: 216-21.

5. Gianotti R, Alessi E, Caputo R. Benign cephalic histiocytosis: a distinct entity or a part of a wide spectrum of histiocytic proliferative disorders of children? Am J Dermatopathol 1993; 15: 315-9.

6. Repiso T, Roca-Miralles M, Kanitakis J, Castells-Rodellas A. Generalized eruptive histiocytoma evolving into xanthoma disseminatum in a 4-year-old boy. Br J Dermatol 1995; 132: 978-82.