Benign follicular tumors

Abstract

Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients.

Figure 1:

Different segments of the hair follicle. A. Infundibulum. Keratinization similar to the epidermis, including a granular layer and basket-weave orthokeratosis. B. Isthmus. Trichilemmal keratinization, characterized by absence of granular layer and abrupt compact orthokeratosis. C. Stem. Pale outer root sheath cells surrounded by a hyaline membrane. D. Bulb. Closely packed basophilic keratocytes and interspersed pigmented melanocytes characteristic of the hair matrix

Figure 2:

Pilar sheath acanthoma. A. This is a particularly large and solid example; note the multilobular architecture. B. Predominantly isthmic differentiation with abrupt compact keratinization

Figure 3

Trichilemmoma. A. Typical lobular architecture in close relation with the neighboring hair follicles. B. Detail of the pale cells with a hint of peripheral palisading and surrounding hyaline membrane. C. Detail of a desmoplastic trichilemmoma, with sclerotic stroma and apparently infiltrative architecture. D. CD34 immunohistochemistry, demonstrating positivity in the tumor cells

Figure 4

Multiple tumors of follicular infundibulum (infundibulomatosis). A. Multiple hypopigmented macular or slightly papular lesions in the submandibular region. B. Plate-like proliferation of monomorphous pale keratinocytes, well-demarcated from the adjacent epidermis. C. PAS stain is positive in the cells. D. Condensation of elastic fibers around the base of the proliferation (arrow)

Figure 5

Proliferating trichilemmal cyst/tumor. Partially cystic and solid lesion with keratinocytes increasing in size from the basal layer to the lumen, displaying abrupt keratinization without granular layer

Figure 6

Trichoblastoma. A. Basaloid proliferation with dense stroma separated by clefts from the adjacent dermis. B. Detail of the cellular stroma forming condensations near the basaloid islands (papillary mesenchymal bodies)

Figure 7

Trichoblastoma. A. Trichoblastoma. A. Basaloid proliferation with dense stroma separated by clefts from the adjacent dermis. B. Detail of the cellular stroma forming condensations near the basaloid islands (papillary mesenchymal bodies)

Figure 8

A. Trichoepithelioma. Basaloid proliferation with abundant infundibular keratinization; note the dense stroma separated by clefts from the adjacent dermis. B. Desmoplastic trichoepithelioma. Thin basaloid strands in a dense stroma, and a few A B keratocysts

Figure 9

Trichogerminoma. A. Well-circumscribed intradermal multinodular lesion separated from the adjacent dermis by clefts. B. Detail of the “cell balls” composed of concentrically arranged pale cells surrounded by an outer layer of darker cells

Figure 10

Pilomatrixoma. A. Nodule on the upper arm of a young patient; lesions are typically hard upon palpation, and a bluish color, as seen in this example, is not a rare feature. B. Well circumscribed dermal nodule with a biphasic appearance (basaloid and eosinophilic areas). C. Sharp transition between basaloid cells and keratinized strands. D. Detail of ghost cells, in which only the outline of the nuclei and cytoplasmic borders are discernible

Figure 11

A. Birt-Hogg-Dubé syndrome. Multiple papules distributed on the face and a larger nodular lesion on the right nasal ala. B. Trichodiscoma. Papule containing a centrally located dense stroma that pushes the epithelial component to the periphery; note the small sebaceous lobules (arrows). C. Fibrofolliculoma. Vertically oriented distorted follicular structure with thin anastomosing strands surrounded by a dense stroma

Figure 12

Trichofolliculoma. Cystic cavity from which numerous vellus hair follicles radiate