Squamous Cell Carcinoma Arising in Chronic Inflammatory Dermatoses
Squamous cell carcinoma (SCC) is a known sequela of chronic inflammatory conditions of the skin. Labial discoid lupus erythematosus (DLE), oral lichen planus (OLP), and lichen sclerosus have a relatively short lag time from dermatosis onset to manifestation of malignancy; cutaneous DLE, hypertrophic lichen planus, chronic wounds, hidradenitis suppurativa (HS), and necrobiosis lipoidica can be present for decades before an associated malignancy is observed. Vigilant monitoring is essential for orolabial DLE, chronic HS, and chronic wounds because malignancies in these settings are particularly aggressive and often fatal. We summarize what is known about the nature and demographics of SCC arising within chronic inflammatory dermatoses, emphasizing lag time from dermatosis diagnosis to malignancy onset of common inflammatory conditions.
PRACTICE POINTS
- Squamous cell carcinoma can develop within chronic inflammatory dermatoses.
- Orolabial discoid lupus erythematosus (DLE), oral lichen planus, and lichen sclerosus can lead to relatively rapid tumorigenesis. Squamous cell carcinoma arising in cutaneous DLE, hidradenitis suppurativa (HS), necrobiosis lipoidica, chronic wounds, and hypertrophic lichen planus tends to appear after decades of inflammation.
- Be especially mindful of new orolabial DLE cases and chronic cases of HS and Marjolin ulcer because malignancies in these settings are particularly aggressive.
In a prospective Australian cohort of 507 women with LS (mean age, 55.4 years), remission was induced with potent topical corticosteroids.35 Patients who were adherent to a topical regimen did not develop SCC during follow-up. Those who were nonadherent or partially adherent had a 4.7% risk for SCC.35 In a similar prospective study of 83 women in France, the SCC rate was 9.6% in lesions that were untreated or irregularly treated.36 These studies provide essential evidence that appropriately treating LS can prevent SCC at a later date, though longer-term data are lacking.
The rate of SCC arising in male genital LS may approach 8.4%,37 with a lag time of 17 years from onset of LS to SCC diagnosis.38 Although circumcision often is considered curative for male genital LS, patients have been observed to develop penile SCC at least 5 years after circumcision.39 Male penile SCC in a background of LS may not necessarily be HPV associated.40
Marjolin Ulcer
Chronic ulcers or scars, typically postburn scars, may undergo malignant transformation, with SCC being the most common carcinoma.41 Squamous cell carcinoma in the context of a chronic ulcer or wound is known as a Marjolin ulcer (MU). Up to 2% of burn scars have been observed to undergo malignant transformation.42 Marjolin ulcers tend to behave aggressively once they form, and it has been proposed that removal of scar tissue may be a preventive therapeutic strategy.43 Cohort studies of MU on the lower extremities have observed lag times of 26.444 and 37.945 years, with both studies also noting relatively high rates of local recurrence.
The pathogenesis of MU appears to be multifactorial. Chronic inflammation and scar formation have been implicated. Chronic inflammation and irritation of lesions at natural creases are thought to increase mitotic activity,41 and local accumulation of toxin may promote mutagenesis.46 Scar formation may create a locally immunoprivileged site, allowing for developing tumors to evade the immune system47 and become even more aggressive as the tumor accumulates.48 Scar formation also may prevent the ability of immune cells to penetrate the tumor microenvironment and access lymphatic channels.49
Hidradenitis Suppurativa
As many as 3.2% of patients with chronic hidradenitis suppurativa (HS) experience malignant transformation to SCC.50 Early HS displays subclinical lymphedema in affected sites, which can progress to chronic fibrosis, stasis, and accumulation of protein-rich fluid.51 Stasis changes have been associated with altered local inflammatory proteins, such as toll-like receptors, β-defensins, and interleukins.52
A retrospective cohort study of 12 patients revealed a lag time of 28.5 years from HS diagnosis to the manifestation of malignancy.53 After local excision, 7 patients developed recurrence, with 100% mortality. Squamous cell carcinomas were well differentiated and moderately differentiated.53 A 2017 literature review of 62 case reports calculated a mean lag time of 27 years. Despite 85% of SCCs being well differentiated and moderately differentiated, nearly half of patients died within 2 years.54 As seen in other inflammatory conditions, HPV can complicate perineal HS and promote SCC tumorigenesis.55
Squamous cell carcinomas arising within HS lesions are more prevalent in males (6.75:1 ratio),54,56 despite HS being more prevalent in females (2:1 ratio).57 Similar to DLE, SCCs arising in HS are aggressive and are seen more in males, despite both conditions being female predominant. Incidence and mortality rates for primary cutaneous SCC are higher for men vs women58; however, the discordance in aggressive behavior seen more commonly in SCC arising from HS or DLE in male patients has yet to be explained.
