Scarring Alopecia and Risk of Skin Cancer: A Literature Review Free

Primary scarring alopecia is a heterogeneous group of disorders characterized by the progressive destruction of hair follicles, leading to irreversible scarring and permanent hair loss. These conditions are typically classified based on the predominant inflammatory infiltrate into lymphocytic, neutrophilic, or mixed subtypes [1]. Chronic inflammation and follicular destruction are central features in the pathogenesis of scarring alopecia, potentially creating a microenvironment that may facilitate malignant cell proliferation. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are common forms of non-melanoma skin cancer (NMSC) originating from the keratinocytes and the basal cells of the epidermis, respectively. Known risk factors for SCC and BCC include ultraviolet (UV) radiation exposure, chronic trauma, and prolonged inflammation. It is plausible that the chronic inflammatory processes associated with scarring alopecia may contribute to an increased susceptibility to SCC and BCC development on the scalp. The aim of this review was to evaluate the association of primary scarring alopecia with NMSC of the scalp offering insights into potential pathogenic mechanisms, reported cases, and clinical implications.

We performed a literature search on PubMed/Medline, Scopus, and Google Scholar for published articles reporting cases of scalp skin cancers and primary scarring alopecia. Initially, a broad and preliminary search was performed using the terms “Scarring Alopecia, Skin Cancer, Cancer risk in alopecia patients, Alopecia Neoplastica, Alopecia and malignancy, Squamous Cell Carcinoma, Basal Cell Carcinoma, Folliculitis decalvans (FD), Malignancy, Lichen planopilaris (LPP), Discoid lupus erythematosus (DLE), Erosive pustular dermatosis of the scalp (EPDS), Scalp cancer.” Dissecting cellulitis of the scalp and traction alopecia were not included in the search as they are biphasic alopecia, in which scarring occurs in the later stages. Articles were screened by two reviewers and were included if they expressed a correlation between scalp skin cancer and one of the various forms of primary scarring alopecia. Articles were excluded if they were nonhuman studies (e.g., animal or ex vivo), lacked direct relevance (e.g., no scarring alopecia), or were missing the full text (e.g., abstract only) (Fig. 1). Related articles and references were also searched to ensure the inclusion of all relevant articles.

We analyzed 34 articles, of which only 13 met the inclusion criteria (Table 1).

LPP is a type of lichen planus (LP) that affects the hair follicles and causes scarring alopecia. LPP is classically present as scarring alopecia, most commonly in middle-aged women with symptoms including burning, erythema, hyperkeratotic papules coalescing into plaques, inflammation, and scale [2, 3]. The etiology of LPP is unclear; however, T lymphocyte inflammation in the stem cell region of the hair follicle is believed to play a role [2]. Studies have found that LPP patients have a strong association with autoimmune disorders, hyperlipidemia, metabolic syndrome, and thyroid disease [2].

Development of malignancies in the setting of mucosal LP is well known, and the majority of cases that have been reported are SCC from oral, esophageal, or genital mucosa LP [3]. In LPP, BCC, SCC, and porocarcinoma have been reported. In retrospective studies, the rate of BCC and SCC for patients with LPP ranged from 4.5 to 4.7% and 1.7 to 1.8%, respectively [2, 4].

The occurrence of BCC and SCC in LPP is considered coincidental in many cases, especially since the majority of LPP patients are at a greater risk for skin cancer due to their ethnicity and Fitzpatrick skin type [2]. However, a case report of scalp BCC in an area that was sun-protected by hair suggested that triamcinolone therapy used for LPP may have decreased Th1 antitumoral response and contributed to the unmasking of BCC [3]. A case of SCC was also reported in a hairless area after 18 years of LPP in a woman who used a hat regularly and had little exposure to sunlight [5]. Development of SCC in an area not exposed to the sun may be secondary to chronic inflammation. LPP patients who are immunosuppressed may be at risk of rarer skin cancers. A patient who had HIV and a history of hepatitis B infection, latent undetermined syphilis, and dyslipidemia presented with porocarcinoma in an area affected by LPP [6]. Whether porocarcinoma arose due to LPP or comorbidities is unclear.

Although skin cancer at the site of LPP is uncommon, continuous monitoring and early intervention are vital for the patient population affected by LPP. Even hair-protected and sun-protected areas may be sites of skin cancer [3, 5]. Treatment of skin cancer in LPP should follow the standard of care of biopsy and excision.

DLE is commonly present as scaling erythematous papules and/or plaques with an adherent scale extending into follicular orifices on sun-exposed areas of skin. Females are affected three times more than their male counterparts, and the head and neck areas are typically the most involved [7].

The association between DLE and SCC has been recognized since 1953 [7]. Long-standing discoid lesions may develop SCC, which is considered a high-risk carcinoma compared to those arising in apparently normal skin [15]. A systematic review has found that approximately 50% of reported SCC in preexisting DLE lesions were found on the lips and 7.4% on the scalp [8]. Several risk factors contribute to the development of SCC in DLE lesions, including the use of immunosuppressive therapy, chronic exposure to UV light, human papillomavirus infection, and ongoing scarring and inflammatory processes. SCC is notably the most common form of skin cancer among black individuals, with additional predisposing factors such as burns, chronic infections, and conditions that result in pigment loss, like albinism [7, 9].

Hypopigmented plaques associated with DLE can make lesions more susceptible to actinic damage, a significant contributor to SCC. Additionally, the chronic scarring that accompanies DLE, along with persistent local inflammatory stimuli, may be linked to carcinogenesis. The induction of malignancy is also considered a potential long-term side effect of immunosuppressive therapies. This is particularly concerning for patients who are chronically immunosuppressed, such as those following organ transplants, as they have an eighteen-fold increased risk of developing SCC, especially in sun-exposed areas [8].

To date, there have been twelve reported cases of SCC in DLE. Three cases of SCC were reported in black women in their fifties [7, 15]. In contrast, there were nine reported cases in white individuals, with a mean age of approximately 50 years [8].

Accurate diagnosis requires repeat biopsies and careful reevaluation. Early intervention and treatment are crucial to minimize morbidity and mortality when SCC arises in DLE lesions. Patients with DLE should be encouraged to undergo regular follow-up examinations, use broad-spectrum sunscreen, and avoid direct sun exposure to affected areas. SCC is a rare but known complication of long-standing DLE, typically developing 6 to 30 years after the initial diagnosis. Most SCC cases associated with DLE scars have been reported in sun-exposed areas of white individuals, with few cases documented in black patients or in sun-protected regions [7, 15].

FD is a form of primary neutrophilic cicatricial alopecia, which primarily affects the vertex and occipital regions of the scalp in middle-aged adults. Although the exact cause remains unclear, it is thought to involve chronic inflammation driven by an interaction between Staphylococcus aureus and a deficient host immune response [16]. Clinically, FD is present with follicular pustules, a lack of follicular ostia, perifollicular erythema, follicular tufting, and, in some cases, hemorrhagic crusts and erosions [16].

To date, there have been four reported cases of SCC arising from FD. BCC or melanoma has not been reported in FD. All four of the cases were males in their forties to fifties who were reported to have a long history of FD [10‒13]. Although skin cancer is more common in Caucasians, there was a case reported in an African American male [11] and a Hispanic male [13].

Management of SCC in FD begins with performing a biopsy to diagnose. Treatment includes excision followed by grafting if necessary [11, 12] and adjuvant external beam radiation and chemotherapy for metastasis. In a case where there was local metastasis on the scalp, cemiplimab therapy was reported to show a dramatic reduction in the size of tumors after one cycle [13]. For metastasis to neck lymph nodes, external beam radiation therapy was tolerated well in a case with palpable cervical nodes but no distant metastasis on PET [12]. Untreated SCC that progresses is associated with poor prognosis and risk of metastasis [11]. The authors have seen 2 patients with BCC in FD; in both cases, the tumor developed a few years after diagnosis in the central area of the patch (Fig. 2).

EPDS is a chronic inflammatory disorder that occurs on the scalp scar in most patients. It primarily affects sun-damaged skin in older individuals [14]. Key findings include crusting and hyperkeratosis, psoriasiform hyperplasia, erosion, mixed inflammatory infiltrate in the papillary dermis, fibrosis, and neutrophilic pustules in the stratum corneum. The relationship between EPDS and NMSC, such as BCC and SCC, has been increasingly recognized.

Chronic inflammation, a hallmark of EPDS, may contribute to an increased risk of NMSC through mechanisms involving reactive oxygen species, hypoxia-driven angiogenesis, and a perpetuated inflammatory state [14]. Diagnosing EPDS can be difficult as it mimics conditions like actinic keratoses, cicatricial pemphigoid, and bacterial infections. Pathology is crucial to distinguish EPDS from keratinocyte carcinomas and to ensure early detection of malignant transformations. In patients with EPDS, NMSC often manifests as nodules or plaques that rapidly grow, ulcerate, or change appearance. These findings necessitate immediate biopsy to confirm malignancy [14].

To date, there have been three reported cases of SCC and three reported cases of BCC arising from EPDS. Mechanisms of chronic inflammation may link EPDS to cutaneous carcinogenesis. Inflammation in NMSC is a hallmark of tumorigenesis, and clinical data related to NMSC show that anti-inflammatory therapeutic approaches can significantly reduce UVB-induced skin carcinogenesis. Topical corticosteroids, although used, often result in recurrence, while curettage-assisted aminolevulinic acid photodynamic therapy has shown promise in controlling EPDS lesions and reducing tumor progression [14].

Although skin cancer arising from scarring alopecia is rare, cases have been documented in LPP, DLE, FD, and EPDS. BCC and SCC have been reported in LPP, often considered coincidental due to higher skin cancer risk associated with lower Fitzpatrick skin types. However, some cases suggest an increased risk from prolonged steroid therapy and chronic inflammation. In DLE, factors like immunosuppressive therapy, UV exposure, and ongoing inflammation are hypothesized to elevate SCC risk. Similarly, SCC in chronic FD is likely due to chronic inflammatory processes. In EPDS, BCC and SCC have been reported likely due to a combination of chronic inflammation and UV exposure. However, chronic UV exposure may not fully explain the risk, as individuals with alopecia totalis, who lack hair entirely, have been found to have a reduced risk of skin cancer [17, 18]. We believe that chronic inflammation contributes more to carcinogenesis than immunosuppression in scarring alopecia. In the reported cases, patients were not heavily immunosuppressed [3, 5, 10, 12, 13]. Their treatments were limited to intralesional steroids or short courses of oral steroids. Furthermore, in cases of alopecia areata where steroids are used as the main treatment, patients do not experience an increased rate of skin cancer [19]. This suggests that chronic inflammation may be the reason for increased risk of skin cancer in scarring alopecia. Reported skin cancer findings underscore the importance of regular monitoring for skin cancer in chronic alopecia patients. Early detection and intervention are crucial for improving patient outcomes in this population.

A.T. is a consultant for DS Laboratories, MONAT Global, Almirall, Thirty Madison, Eli Lilly, Bristol Myers Squibb, P&G, Pfizer, and Myovant. Prof. A.T. was a member of the journal’s Editorial Board at the time of submission. J.L. and L.G. have no conflicts of interest to declare.

There is no funding source for this study.

J.L. – concept and design, drafting of the manuscript, and revision of manuscript; L.G. – drafting of the manuscript; A.T. – concept and design, and revision of manuscript.