Histologic variants of periungual fibromas in tuberous sclerosis complex

Abstract

To the editor: Periungual fibroma (PF) is a cutaneous manifestation of tuberous sclerosis complex (TSC). Although a benign tumor, it can bleed, cause pain, and distort the nail. Non-traumatic PFs are among the major diagnostic criteria of tuberous sclerosis complex (TSC).1 The lesions usually develop post-puberty, are more common on toenails than on fingernails, and occur more frequently in women than in men.2,3 We conducted a retrospective review of 32 PFs from 18 TSC patients seen at the NIH between 2000–2008. The clinical features of these cases are summarized in Table 1. All but one patient were females since they were enrolled in studies of lymphangioleiomyomatosis, a pulmonary disease in TSC patients that occurs almost exclusively in women.3 The average age of the patients included in this study was 49.8±7.7 years old. All but two of the PFs were obtained from the toes and the remaining were from the fingers. The duration of the lesions ranged from 2 to 40 years. Table 1 Clinical and histological features of periungual fibromas in TSC Grossly, most PFs are pink to red, firm, conical papules emerging from under the proximal nail fold (Figure 1A, 1C and 1E). A longitudinal nail groove extends from under the tumor to the free edge of the nail.4 The lesions usually measure 1–5 mm from the base to the tip. Histologically, they are non-encapsulated and are comprised of stellate shaped fibroblasts admixed with vertically oriented dense collagen and blood vessels. The lesions can be highly vascular, predominantly fibrotic, or show a mixed pattern. The epidermal changes are characterized by compact hyperkeratosis, acanthosis, thickened granular layer and irregular rete ridges (Figures 1B, 1D, and 1F). Parakeratosis is not observed. Figure 1 Variants of periungual fibroma, showing paired gross and microscopic images. Angiomatous The histological appearance of TSC PFs varied depending on the relative proportions of vascular proliferation and stromal fibrosis. The angiomatous subtype, observed in 5 samples, is characterized by numerous dilated vascular spaces, lined by plumped endothelial cells. The vascular lumens were large compared to that in normal skin. In between the vascular spaces are proliferation of stellate fibroblasts admixed with variable amounts of dense dermal collagen (Figure 1B). The fibrotic subtype, observed in 19 samples, featured predominantly vertically oriented thick collagen bundles in the dermis admixed with thick-walled small blood vessels (Fig. 1D). Elastic tissue (EVG) staining showed significantly decreased amounts of dermal elastic fibers, compared to the non-lesional skins obtained from the same patients (figure not shown). A third histologic subtype, observed in 8 samples, showed histological features intermediate between angiomatous and fibrotic subtypes and therefore was categorized as mixed subtype (Fig. 1F). Some of these changes were consistent with the observations of Nickle and Reed5, and of Kint and Barran6. Lesions categorized histologically as angiomatous subtype generally appeared more red, while the fibrotic subtype tended to be more white and firm; there was no obvious correlation of subtype with tumor location. Although the angiomatous and fibrotic subtypes can be distinguished histologically, they may represent a spectrum of changes of these tumors from angiomatous to fibrotic subtype over time. The proposed histologic sub-typing of periungal fibromas may provide helpful insights into the pathogenesis of these lesions.