Multinucleate cell angiohistiocytoma: clinicopathological correlation of 142 cases with insights into etiology and pathogenesis

Abstract

Introduction: Multinucleate cell angiohistiocytoma (MCAH) is a peculiar dermatopathological entity described as asymptomatic grouped red-to-violaceous papules, developing over weeks to months without spontaneous regression. The histopathological findings comprise bizarre basophilic multinucleated cells (MC), small vessel inflammation, mild dermal fibrosis, and a sparse lymphohistiocytic infiltrate.

Aims and methods: This study aimed to collate and analyze the clinical, histological, and immunohistochemical characteristics of all reported cases of MCAH from the international literature, and the presence or absence of concurrent chronic inflammatory or neoplastic phenomena to investigate any potential clinicopathological correlations, which may hint at the underlying pathophysiology of this condition. A systematic review of the literature was undertaken with information collected by a predeveloped pro forma. New case reports were also sourced from patient records at the Skin and Cancer Foundation Australia Database.

Results: A total of 142 cases of MCAH were collated, including 8 new case reports. The average age of onset was 50.1 years, with 79% of all individuals being female. The most commonly affected areas were the hands (30%) and face (29%). Univariate analysis revealed a positive association between lesion size and MC staining for CD68 (R = 0.488; P = 0.004), and an inverse relationship between size and endothelial staining for CD34 (R = -0.530; P = 0.012). Multiple lesions were significantly associated with an inverse relationship to MC staining of CD68 (R = -0.519; P = 0.002). Moderate correlations were seen between specific sites of vascularity and sites in which MCs were identified (R = 0.734-0.741; P < 0.001), and dermal fibrosis was associated with an increased number of MCs (R = 0.522; P = 0.002) and decreased multinucleate cell immunohistochemical staining (R = -0.655; P = 0.003). An association was found between patients with chronic inflammatory conditions and endothelial staining for CD68 (R = 0.671; P = 0.012), and an inverse relationship with MC staining for factor XIIIa (-0.481; P < 0.001). No statistically significant relationships between neoplasia and MCAH were found.

Discussion and conclusions: From the data examined, we hypothesize that although this condition may be inflammatory and vascular in initial origin, fibrosis and atrophy play a vital role in the pathogenesis, particularly regarding the progression to multiple lesions. A detailed hypothesis is described that may be amenable to more detailed investigations. Limitations in this study include the heterogeneity of results analyzed across case reports; however, our conclusions match those developed through the analysis of our case series. These hypotheses and proposals provide an experimental basis for further research into the pathogenesis and mechanisms underlying MCAH.