A 51-year-old woman presented with a localized papular eruption on the forehead. The patient was seen by a 
dermatologist who thought the eruption was rosacea (Figure 1). Standard rosacea treatment was not successful in achieving any type of positive therapeutic response. She then sought a second opinion with Dr Ravits, who performed a biopsy. The patient’s past medical history was fairly unremarkable.
Figure 1. The patient presented with a localized recalcitrant papular eruption localized to the forehead.
On the initial slide, the biopsy showed a somewhat sclerotic dermis with ectatic vessels defining a pattern reminiscent of a fibrous papule. Subsequent deeper sections showed an increase in vascularity. In addition, coursing through the fibrotic interstitium were highly distinctive multinucleated cells with scalloped cytoplasmic borders that seemed retracted from the fibrotic dermis. The cells had multiple nuclei ranging from 3 to 6 nuclei. The cells stained positively for factor XIIIa and CD68, pointing toward a resident dendritic cell ontogeny.
A diagnosis of multinucleate cell angiohistiocytoma was made (Figures 2 and 3).
Discussion
The patient’s combined clinical presentation and biopsy findings were characteristic for the rare entity of multinucleate cell angiohistiocytoma. This name designation is a very precise descriptor of all of the salient histologic features that define this benign condition. Its first description dates back to 1985 by Smith and Wilson Jones1; they reported a benign eruptive condition characterized by a localized papular eruption of reddish brown lesions primarily occurring in women, whereby they emphasized site localization on the dorsum of the hands but also described lesions of the face. Many single case reports and case series have been described over the years.
The classic demographic affected is middle-aged to older women, while the typical case presents as asymptomatic papules. The dorsal aspect of the hand, typically showing localization over joint surfaces, is the most common site. A recent study, however, demonstrated that there was no sex predilection, with cases occurring equally in women and in men.2 While localization over the dorsum of the hands is typically emphasized, cases can occur at other sites such as the legs or the trunk. One study2 reported presentation of papules on the face, though this was considered very rare and, according to their data analysis, reported in roughly 1% of all multinucleate cell angiohistiocytoma cases. Though in another study,3 approximately 30% of the compiled cases from the literature occurred on the face. The important message is that this unusual condition can occur on the face and present in a fashion that mirrors the more common acral presentation. From a clinical perspective, the lesions raise diagnostic considerations of lichen planus, granuloma annulare, and the Gottron papules of dermatomyositis.2
The characteristic hallmarks are well exemplified by this case, comprising the combination of parallel dermal fibrosis, neovascularization, and scattered multinucleated cells with a distinctive scalloped appearance. The superficial pattern of
fibrosis has always been emphasized, as opposed to the other distinctive patterns of fibrosis seen in other conditions that define potential morphologic mimics of multinucleate cell angiohistiocytoma, most notably dermatofibroma and fibrous papule.1,4 Other reproducible features include an increase in stellate-appearing cells, multinucleate scalloped-appearing cells, and increased numbers of vessels that manifest thickened vascular basement membrane zones.
Figure 2. Biopsy shows a fibrotic dermis with enhanced vascularity and cellularity. A number of osteoclast-like giant cells course through the fibrotic dermis.
Phenotypic studies have shown that the interstitial fibrocyte-like cells and those with a multinucleated appearance are of monocytic derivation.2,3 They also stain positively for the resident dendritic cell marker factor XIIIa. Other positive markers that point toward a form of benign, terminally differentiated histiocytopathy include lysozyme, CD68, and CD163, while markers indicative of an alternative line of terminal histiocyte differentiation include CD123, CD1a, S100, and langerin are negative.2,3
It is important to distinguish these lesions from a fibrous papule, dermatofibroma, and a benign vascular proliferation. Typically, in a fibrous papule, the distinctive pattern of increased vascularity is not seen and the fibrosis shows accentuation around hair follicles. In a dermatofibroma, increased vascularity can be seen with noted stellate multinucleate cells, but the fibroplasia has a storiform pattern. As for a benign vascular proliferation, the main consideration would be an involuting hemangioma, given the typical finding of fibrosis. The parallel fibroplasia and multinucleate cells serve as distinguishing histomorphologic features separating multinucleate angiohistiocytoma from a hemangioma.
The exact categorization of multinucleate cell angiohistiocytoma remains debatable. Trauma is one thought, although in most patients there is no clear-cut traumatic trigger. In addition, its categorization as a form of benign clonal histiocytopathy can be questioned. Indeed, significant positivity is observed for factor XIIIa amidst the stellate fibrocytic elements as well as in those cells that have a multinucleate stellate osteoclast-like appearance. It might suggest that this localized eruption could be categorized as a form of benign resident dendritic cell histiocytopathy. Other conditions that fall under this designation include Rosai-Dorfman disease, generalized eruptive histiocytosis, Erdheim-Chester disease, xanthoma disseminatum, and multicentric reticulohistiocytosis (MRH).5
Figure 3. The stromal cells are highlighted by factor XIIIa and CD68.
Among the common features seen in the resident dendritic cell histiocytopathy syndromes and observed in this case is fibrosis and the tendency toward multinucleation of the histiocytic elements. Other features, such as inflammation and xanthomatous change, that are common in the other resident dendritic cell syndromes, are not a morphologic feature of multinucleate cell angiohistiocytoma. While it can be surmised that this histiocytopathy could represent a benign clonal histiocytic disorder, there is no association with any specific hematologic dyscrasia.5 It is not held to represent a paraneoplastic syndrome unlike MRH. Some patients do have evidence of an inflammatory disease, such as reactive cutaneous plasmacytosis and hidradenitis suppurativa.3,6
From a therapeutic perspective, as the condition is completely benign, no treatment is needed. More conspicuous lesions that are cosmetically disturbing can be treated with light and/or laser treatment. Intense pulsed light systems utilize a high-intensity light source emitting polychromatic light and have achieved success in treating multinucleate cell angiohistiocytoma.7 The chromophore target in a vascular lesion is oxyhemoglobin, which absorbs light energy at 418 nm, although penetration is minimal. The absorbed light energy is converted to heat, which leads to red cell destruction and thrombosis of small blood vessels.7 Fractionated ablative carbon dioxide laser treatment has also been used successfully.8
Dr Magro is a distinguished professor of pathology and laboratory medicine in the department of pathology at Weill Cornell Medicine in New York, NY, and section editor of The Dermatologist. Dr Ravits is senior attending at Hackensack University Medical Center in Hackensack, NJ, and a clinical associate professor of dermatology at NY-Presbyterian Hospital in New York, NY. She also has a private practice in River Edge, NJ.
References
1. Smith NP, Wilson Jones E. Multinucleate cell angiohistiocytoma: a new entity. Br J Dermatol. 1985;113(suppl 29):15.
2. Roy SF, Dong D, Myung P, McNiff JM. Multinucleate cell angiohistiocytoma: a clinicopathologic study of 62 cases and proposed diagnostic criteria. J Cutan Pathol. 2019;46(8):563-569. doi:10.1111/cup.13463
3. Frew JW. Multinucleate cell angiohistiocytoma: clinicopathological correlation of 142 cases with insights into etiology and pathogenesis. Am J Dermatopathol. 2015;37(3):222-228. doi:10.1097/DAD.0000000000000075
4. Smolle J, Auboeck L, Gogg-Retzer I, Soyer HP, Kerl H. Multinucleate cell angiohistiocytoma: a clinicopathological, immunohistochemical and ultrastructural study. Br J Dermatol. 1989;121(1):113-121. doi:10.1111/j.1365-2133.1989.tb01407.x
5. Kazi N, Bernert R, Moussa C, Magro C. A case of generalized eruptive histiocytosis in a 23-year-old man. Dermatol Online J. 2014;20(8).
6. Roy SF, Ghazawi FM, Tran D, Bouffard D. Cutaneous plasmacytosis and multinucleate cell angiohistiocytoma-like lesion in a patient with hepatitis B: a fortuitous triad? J Cutan Pathol. 2019;46(9):678-683. doi:10.1111/cup.13491
7. Fernández-Jorge B, del Pozo J, García-Silva J, Barja JM, Yebra-Pimentel MT, Fonseca E. Multinucleate cell angiohistiocytoma: treatment using intense pulsed light. Dermatol Surg. 2009;35(7):1141-1143. doi:10.1111/j.1524-4725.2009.01203.x
8. Moradi Tuchayi S, Garibyan L, Lee KC. Successful treatment of multinucleate cell angiohistiocytoma with fractionated ablative CO₂ laser. JAAD Case Rep. 2019;5(4):297-299. doi:10.1016/j.jdcr.2019.01.004
