Secondary Logo

A New Histologic Pattern in 6 Biopsies From Early Frontal Fibrosing Alopecia

Miteva, Mariya, MD; Sabiq, Samar, MD

The American Journal of Dermatopathology: February 2019 - Volume 41 - Issue 2 - p 118–121
doi: 10.1097/DAD.0000000000001247
Original Study
Free
SDC

Abstract: Frontal fibrosing alopecia (FFA) is an irreversible scarring alopecia with unknown etiology and no cure. The goal is to establish the diagnosis in the early stage, before developing a hairless band of atrophy involving the frontal, temporal scalp and sideburns. Pathology is rarely needed once the disease is clinically apparent. The classic histologic features include follicular dropout with the absence or atrophy of the sebaceous glands and lichenoid lymphohistiocytic infiltrate with concentric layered fibrosis at the upper follicular level. We describe a common pattern that was repeatedly seen in 6 horizontally sectioned scalp biopsies from patients with early presentation of FFA suspected on trichoscopy by the focal presence of peripilar casts around terminal hairs. All biopsies revealed overall preserved follicular architecture with average number of 11 vellus follicles, atrophy of the sebaceous glands, and perifollicular lymphohistiocytic infiltrate involving the outer root sheath of the vellus follicles (n = 5). There was no perifollicular fibrosis of the vellus follicles and no lichenoid inflammation and perifollicular fibrosis of the terminal follicles. This new pattern of “inflammatory vellus involvement” most likely corresponds to an early onset of the disease. The absence of the classic features in such biopsies from early FFA can lead to misdiagnosis.

Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, FL.

Correspondence: Mariya Miteva, MD, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue, Miami, FL 33136 (e-mail: mmiteva@med.miami.edu).

The authors declare no conflicts of interest.

Back to Top | Article Outline

INTRODUCTION

Frontal fibrosing alopecia (FFA) is an irreversible scarring alopecia with unknown etiology and no cure. The clinical diagnosis is not a challenge in cases of classic frontotemporal hair line recession, involvement of the eyebrows, sideburns and extremities, and accompanying itching or discomfort. Therefore, a biopsy is rarely necessary at this stage. Nowadays, the goal is to establish the diagnosis at the earliest possible stage, before the development of an advancing hairless band of skin atrophy. The pathology of FFA falls in the category of lymphocytic cicatricial alopecias that are characterized by follicular dropout, absence/atrophy of sebaceous glands, lichenoid inflammatory infiltrate at the upper follicular level, and concentric perifollicular fibrosis around the affected follicles that often form compound follicular structures.1–3 Some have shown that deeper inflammation involving the lower follicular levels is more common in FFA compared with lichen planopilaris,4 and there is more common apoptotic activity in the outer root sheaths,5 whereas according to others, no histologic parameters reliably distinguish both conditions.6 We published previously the “follicular triad” as a helpful clue to the diagnosis of early FFA.7 It is characterized by the concomitant involvement of vellus, terminal anagen, and telogen follicles by lichenoid inflammation and perifollicular fibrosis. Here, we present a series of 6 dermoscopy (trichoscopy)-guided scalp biopsies8 obtained from patients with early FFA without apparent clinical involvement of the hair line. These biopsies demonstrate a common new recognizable pattern for the diagnosis of early FFA in horizontal sections.

Back to Top | Article Outline

CASE SERIES

All patients were women complaining of less hair in the hair line. Their clinical data are summarized in Table 1. On examination, the hair line was preserved with intact vellus hairs in all cases, and only a focal area of peripilar casts around terminal hairs was detected on trichoscopy and selected for the biopsy (Fig. 1). There was no scalp involvement by psoriasis or seborrheic dermatitis. All six 3-mm punch biopsies were submitted to the Dermatopathology laboratory at the Department of Dermatology at the University of Miami as part of the routine diagnostic evaluation. One patient had 2 previous biopsies reviewed and diagnosed by 3 other dermatopathologists as androgenetic alopecia. The 2 remaining biopsies were submitted with a clinical diagnosis of possible FFA by 2 clinicians with expertise in hair loss and trichoscopy. All specimens were bisected transversely according to the Headington technique9 and evaluated at all follicular levels in average number of 25 sections per case.

TABLE 1

TABLE 1

FIGURE 1

FIGURE 1

The histologic results are summarized in Table 2.

TABLE 2

TABLE 2

There was overall preserved follicular architecture without obvious areas of follicular dropout but with hypoplastic (atrophic) appearance of the sebaceous glands in all specimens. The atrophy varied from volumetric decrease in the number and size of the sebaceous lobules (Fig. 2A) to remnants of undifferentiated epithelial strands (mantle-like structures) (Fig. 2B). The average follicular density was 17.6 follicles with an average vellus number of 11.1. The terminal follicles were unaffected by perifollicular lamellar fibrosis or lichenoid/interface lymphohistiocytic infiltrate. No compound follicular structures (eye- or goggle-like structures) were found. The vellus follicles in all but 1 specimen showed lichenoid lymphohistiocytic infiltrate (Fig. 3A) with prominent histiocytic component in 1 case (Fig. 3B) and eosinophils in 2 other cases (Fig. 3C). The infiltrate was organized in layered (surrounding the circumference of the follicle) or patchy (unilateral) collections in approximation to the other root sheath. There was no perifollicular fibrosis around the vellus follicles. In all but 1 specimen, the stroma appeared “busy” by the presence of scattered fibrohistiocytes (Fig. 4), mast cells, and eosinophils. A skin-colored papule of the occipital scalp in 1 patient was biopsied and showed interface dermatitis without follicular involvement.

FIGURE 2

FIGURE 2

FIGURE 3

FIGURE 3

FIGURE 4

FIGURE 4

Back to Top | Article Outline

DISCUSSION

As dermoscopy of hair (trichoscopy) has advanced in the past years and is more widely used for hair loss diagnostics among clinicians, dermatopathologists will be receiving biopsies from clinically minimally apparent or unapparent early FFA. They need to recognize and make the diagnosis of FFA promptly because this will spare the patient the frustration of a delayed diagnosis with its physical and emotional consequences. However, the diagnosis may not be easy when the classic features of follicular dropout, compound follicles, perifollicular fibrosis, and lichenoid inflammation are absent.

We report here a new recognizable pattern in trichoscopy-guided biopsies obtained from early cases of FFA without apparent alopecia of the hairline. The trichoscopy–pathology correlation is the strength of this work and allowed for the correct diagnosis. The inflammatory involvement of the vellus follicles by perifollicular lichenoid layered or patchy infiltrate and the atrophy of the sebaceous glands are the histologic clues to the diagnosis. The reason for the more prevalent involvement of the vellus follicles in FFA is not clear. It has been suggested that FFA may selectively target androgen-dependent terminal follicles from the frontal scalp leading first to their miniaturization and then to their destruction.10 In fact, the absence of vellus follicles from the hair line is considered a trichoscopic feature for the diagnosis of FFA.11 However, all cases reported here had still intact vellus hairs in the frontal line, which can be explained with the hypothesis that it is either an early evolving process or that these patients may later develop the type of FFA known as “pseudofringe sign.”12 This can only be confirmed in continuous follow-up. The inflammatory vellus involvement without perifollicular fibrosis is very similar to the intermediate/vellus follicle involvement in limb alopecia of patents with FFA as reported by us and others in the past.13,14 In our experience, skin biopsies from limb alopecia never show perifollicular fibrosis (Fig. 5) and therefore are sometimes misdiagnosed as alopecia areata (personal experience).

FIGURE 5

FIGURE 5

The atrophy of the sebaceous glands is a well-known histologic feature of scarring alopecias. Although no data exist for FFA, research has shown that peroxisome proliferator-activated receptor (PPAR) gamma (a transcription factor that is critical for the healthy pilosebaceous unit and its lipid metabolism and peroxisome biogenesis) is significantly decreased in expression in lichen planopilaris.15

The busy stroma cannot be considered a specific finding because scalp biopsies from black patients may show increased stromal cellularity including melanophages. However, in the setting of our series, it is curious for 2 reasons: our specimens originate from 5 white patients and 1 Asian patient with early FFA and no skin atrophy. It, therefore, can be assumed that the stroma is involved early in the pathogenesis. In fact, one study that used Snail-1 immunohistochemistry has shown that there is rational to suspect epithelial–mesenchymal transition in the areas of fibrosis in FFA.16 Transition of the epithelial stem cells into mesenchymal cells of fibroblast phenotype is currently a favored mechanism implicated in the pathogenesis of FFA.17

In conclusion, lymphohistiocytic inflammation of the vellus follicles and atrophy of the sebaceous glands in scalp biopsies of the hairline are a clue to the diagnosis of early FFA even in the absence of the classic perifollicular lichenoid inflammation and concentric fibrosis. Future prospective histologic studies are necessary to confirm this observation. Retrospective studies are not useful because this pattern may have been misdiagnosed as androgenetic alopecia because of the absence of classic features for lymphocytic scarring alopecia and the abundance of vellus follicles.

Back to Top | Article Outline

REFERENCES

1. Kossard S, Lee MS, Wilkinson B. Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris. J Am Acad Dermatol. 1997;36:59–66.
2. Miteva M, Torres F, Tosti A. The “eyes” or “goggles” as a clue to the histopathological diagnosis of primary lymphocytic cicatricial alopecia. Br J Dermatol. 2012;166:454–455.
3. Sperling LC. Scarring alopecia and the dermatopathologist. J Cutan Pathol. 2001;28:333–342.
4. Wong D, Goldberg LJ. The depth of inflammation in frontal fibrosing alopecia and lichen planopilaris: a potential distinguishing feature. J Am Acad Dermatol. 2017;76:1183–1184.
5. Poblet E, Jimenez F, Pascual A, et al. Frontal fibrosing alopecia versus lichen planopilaris: a clinicopathological study. Int J Dermatol. 2006;45:375–380.
6. Galvez-Canseco A, Sperling L. Lichen planopilaris and frontal fibrosing alopecia cannot be differentiated by histopathology. J Cutan Pathol. 2018;45:313–317.
7. Miteva M, Tosti A. The follicular triad: a pathological clue to the diagnosis of early frontal fibrosing alopecia. Br J Dermatol. 2012;166:440–442.
8. Miteva M, Tosti A. Dermoscopy guided scalp biopsy in cicatricial alopecia. J Eur Acad Dermatol Venereol. 2013;27:1299–1303.
9. Headington JT. Transverse microscopic anatomy of the human scalp. A basis for a morphometric approach to disorders of the hair follicle. Arch Dermatol. 1984;120:449–456.
10. Tosti A, Piraccini BM, Iorizzo M, et al. Frontal fibrosing alopecia in postmenopausal women. J Am Acad Dermatol. 2005;52:55–60.
11. Lacarrubba F, Micali G, Tosti A. Absence of vellus hair in the hairline: a videodermatoscopic feature of frontal fibrosing alopecia. Br J Dermatol. 2013;169:473–474.
12. Pirmez R, Duque-Estrada B, Abraham LS, et al. It's not all traction: the pseudo “fringe sign” in frontal fibrosing alopecia. Br J Dermatol. 2015;173:1336–1338.
13. Miteva M, Camacho I, Romanelli P, et al. Acute hair loss on the limbs in frontal fibrosing alopecia: a clinicopathological study of two cases. Br J Dermatol. 2010;163:426–428.
14. Chew AL, Bashir SJ, Wain EM, et al. Expanding the spectrum of frontal fibrosing alopecia: a unifying concept. J Am Acad Dermatol. 2010;63:653–660.
15. Karnik P, Tekeste Z, McCormick TS, et al. Hair follicle stem cell-specific PPARgamma deletion causes scarring alopecia. J Invest Dermatol. 2009;129:1243–1257.
16. Nakamura M, Tokura Y. Expression of Snail1 in the fibrotic dermis of postmenopausal frontal fibrosing alopecia: possible involvement of an epithelial-mesenchymal transition and a review of the Japanese patients. Br J Dermatol. 2010;162:1152–1154.
17. Harries MJ, Jimenez F, Izeta A, et al. Lichen planopilaris and frontal fibrosing alopecia as model epithelial stem cell diseases. Trends Mol Med. 2018;24:435–448.
Keywords:

hair pathology; trichoscopy; scarring alopecia; horizontal sections; hair; alopecia; lichen planopilaris

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.