Anetodermic pilomatricoma: molecular characteristics and trauma in the development of its bullous appearance

Abstract

Pilomatricoma is a common benign neoplasm of the skin characterized by a solid cutaneous nodule of hair matrix origin. The anetodermal or lymphangiectatic variant of pilomatricoma is rare, and its bullous appearance is often associated with attenuated collagen and elastic fibrils and dilated lymphatic vessels in the overlying dermis. However, the tumors of anetodermic pilomatricoma have never been characterized at the molecular level, and the exact mechanism for their development is unknown. In this study, we evaluated histological and molecular features of a bullous pilomatricoma along with 5 control tumors and determined that tumors of both anetodermic and control pilomatricoma comprise similar molecular features, such as nuclear lymphoid enhancer binding factor 1 (LEF1) localization and the expression of keratins. In addition, we associated the development of the anetodermic pilomatricoma with mechanical trauma, scar tissue formation, and increased numbers of blood and lymphatic vessels. This study suggests that the development of the anetodermic form of pilomatricoma is unlikely to be associated with the intrinsic properties of the tumor but with the mechanical trauma that disrupts the dermal integrity and vascular microenvironment.

Fig. 1

Clinical, histological and molecular characteristics of anetodermic (bullous) pilomatricoma. (a) A 3.5 cm × 2.5 cm, translucent, hemorrhagic bulla with a bluish discoloration on the right shoulder of a patient. (b - e) The tumor is circumscribed with fibrous tissue (arrows) (b). Basoloid cells were restricted to the boundary of the tumour (b). Enlargement of boxed area revealed characteristic organization of basoloid matrix cells (MC), transitional cells (TC) and amorphous shadow cells (SC) (d); extra-vascular red blood cells (asterics) and inflammatory cells (inlet) (c); and increased interstitial space (arrow heads) in the dermis above the tumor (e). (f) Verhoeff-van Gieson staining revealed dramatic disruption and reduction of elastic fibers. (g) LEF1 (red) is restricted to the nuclei. Note that LEF1 (red) overlapped with DAPI (blue), therefore, appeared pink. KRT81 (green) is expressed in transitional cells. (h) KRT17 (green) is expressed in cells at the periphery of the tumour. MC, matrix cells; TC, transitional cell; SC, shadow cell.Scale bar = 2.5 mm in (b); 100 μm in (c and d), 250 μm in (e and f) and 50 μm in (g and h).

Fig.2

Blood and lymphatic vessels in the dermis of pilomatricoma. (a) Histological examination revealed a fibrous scar and vessels (arrows) in anetodermic pilomatricoma. Some vessels are dilated (arrow heads). (b - c) Blood vessels labeled by smooth muscle actin (ACTA2, red) revealed dramatically increased number in anetodermic (b) but not in Control (c) pilomatricoma. Dotted lines indicate the location of the basement membrane. (d - e) Lymphatic vessels labeled with D2-40 revealed increased numbers of lymphatic vessels (arrow heads) in the dermis of anetodermic (d) but not control (e) pilomatricoma. (f - g) Statistical analysis of results demonstrated a significantly increased number of blood (f) and lymphatic vessels (g) in anetodermic (Bullous) than classic (Control) pilomatricoma. n = 5 for Control, p < 0.05. Scale bar = 100 μm.