Perifollicular Xanthomatosis as the Hallmark of Axillary Fox-Fordyce Disease

BACKGROUND: Fox-Fordyce disease (FFD) or apocrine miliaria is a rare condition with features that are characteristic clinically but not histopathologically. It is traditionally described as a condition that shows infundibular plugging, acanthosis, parakeratosis, spongiosis, and a nonspecific infiltrate. The so-called retention vesicle, which reputedly involves the apocrine duct, is often difficult to find. Recently, 4 uncontrolled observations were described (infundibular dyskeratotic cells, vacuolar alteration, cornoid lamella-like parakeratosis, and perifollicular foamy macrophages). In this study, we evaluated both established and new histopathologic criteria for the diagnosis of FFD and searched for other meaningful findings. OBSERVATIONS: Most established features were observed in both patients with FFD and control patients. All cases occurred during 1995 through 2005. No unequivocal retention vesicle was identifiable in any case. Infundibular vacuolar change and cornoid lamella-like parakeratosis were not corroborated as being diagnostically meaningful. Few dyskeratotic cells were seen in some patients with FFD and in control patients. Perifollicular foam cells were noted in most patients with FFD but not among control patients. These cells expressed CD68 but lacked expression of carcinoembryonic antigen, gross cystic disease fluid protein 15, and periodic acid-Schiff with diastase digestion. Perifollicular mucin, fibrosis, and mast cells in the infiltrate were also observed. CONCLUSIONS: The established histopathologic attributes of FFD are nonspecific, and a retention vesicle is difficult to find even in level sections. In contrast, perifollicular foam cells are a distinct, relatively consistent, and specific feature of FFD. We contend that perifollicular foam cells represent a useful hallmark of FFD.