Summary: Delineating molecular and cellular events that precede appendage morphogenesis has been challenging due to the inability to distinguish quantitative molecular differences between cells that lack histological distinction. The hair follicle (HF) dermal condensate (DC) is a cluster of cells critical for HF development and regeneration. Events that presage emergence of this distinctive population are poorly understood. Using unbiased single-cell RNA sequencing and in vivo methods, we infer a sequence of transcriptional states through which DC cells pass that begins prior to HF morphogenesis. Our data indicate that Wnt/β-catenin signaling is required to progress into an intermediate stage that precedes quiescence and differentiation. Further, we provide evidence that quiescent DC cells are recent progeny of selectively proliferating cells present prior to morphogenesis and that are later identified in the peri-DC zone during DC expansion. Together, these findings provide an inferred path of molecular states that lead to DC cell differentiation.

Background: Multinucleate cell angiohistiocytoma (MCAH) is an uncommon and likely underdiagnosed entity that is thought to be of vascular and fibrohistiocytic origin. Methods:We retrospectively reviewed all cases diagnosed as MCAH at the Yale Medicine Dermatopathology laboratory between 1 January 1990 and 1 September 2018. Sixty-two cases were retained. We performed immunohistochemistry on the ten most inflamed lesions found and assessed for a possible alteration within the Wnt/ß-catenin signaling pathway, involved in follicular induction in dermatofibroma.We subsequently established histologic diagnostic criteria to differentiate MCAH from its mimickers.Results: MCAH affected both genders equally. The hands or fingers were affected in 51.6% of cases. We found the most specific histologic criteria to be: (a) presence of odd multinucleated fibroblasts, (b) presence of superficial parallel fibrosis, (c) presence and thickening of superficial papillary dermal vessels, and (d) absence of perifollicular fibrosis. As for immunoreactivity, we found positivity to CD138, CD163, and CD117 in the mononuclear inflammatory infiltrate. There was no histopathologic evidence of follicular induction, as can be seen in dermatofibromas, and no expression of nuclear beta-catenin as seen in dermatofibromas with follicular induction.Conclusion: This large case series establishes MCAH as a distinct clinical and histopathologic entity. K E Y W O R D S epidemiology of multinucleate cell angiohistiocytoma, mast cells, multinucleate cell angiohistiocytoma, multinucleated giant cells, stellate fibroblasts

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