As many as one-quarter of human cancers are related to chronic inflammation, chronic infection, or both.1 Extrinsic inflammation leads to generation of proinflammatory cytokines that in turn recruit other inflammatory cells, which is thought to generate a positive amplification loop.2 Intrinsic stimuli from proto-oncogenes and mutations in tumor suppressor genes lead to transformed cancer cells that also secrete proinflammatory cytokines, thus propagating the cycle.
Numerous factors have been observed in association with tumor growth, progression, invasion, and metastasis.3 One factor for the development of squamous cell carcinoma (SCC) may be chronic inflammatory dermatoses. To date, reviews of chronic inflammation–associated malignancy have focused on solid organ cancers. We sought to provide an up-to-date review of SCC arising within chronic dermatoses, with an emphasis on the anatomic location of dermatoses involved in the transformation of cancer cells, the lag time from onset of dermatosis to diagnosis of SCC, and the distinctive mechanisms thought to be involved in the tumorigenesis in particular dermatoses.
Discoid Lupus Erythematosus
Discoid lupus erythematosus (DLE) is a chronic cutaneous lupus erythematosus variant with a female to male predominance of 3:1,4 and DLE lesions are prone to malignant transformation. Retrospective cohort studies have attempted to characterize who is at risk for SCC and how SCCs behave depending on their location. Cohorts from China,5 India,6 and Japan7 have noted a higher rate of SCC within DLE lesions in men (female to male ratios of 1:2.2, 1:1.6, and 1:2, respectively) and shorter lag times for SCC onset within DLE lesions of the lips (13, 5, and 10 years, respectively) compared to SCC arising in DLE elsewhere (19.2, 11.2, and 26 years, respectively). Studies have noted that DLE lesions of the lips may be prone to more rapid SCC tumorigenesis compared to DLE on cutaneous sites. One study reported SCC in DLE recurrence, metastasis, and death rates of 29%, 16.1%, and 19.4%, respectively,5 which exceeds reported rates in non-DLE SCCs (20%, 0.5% to 6%, and 1%, respectively).5,8
Because SCC arising within DLE is most common on the lips (Figure 1), it has been hypothesized that the high rate of transformation of DLE lesions on the lips may be due to constant exposure to irritation and tobacco, which may accelerate carcinogenesis.5 It also has been hypothesized that atrophic discoid lesions have lost sun protection and are more prone to mutagenic UV radiation,9 as SCCs arising in DLE lesions virtually always display prominent solar elastosis6; however, SCC has been observed to arise in non–sun-exposed DLE lesions in both White and Black patients.10
Photograph courtesy of Andrea Murina, MD.
FIGURE 1. Invasive squamous cell carcinoma arising within a labial discoid lupus erythematosus lesion. This patient’s lesions were present for approximately 6 years prior to presentation for carcinoma.
Additionally, use of immunosuppressant medications may accelerate the emergence of malignancy or more aggressive forms of malignancy; however, patients with autoimmune disease have a greater risk for malignancy at baseline,11 thus making it difficult to determine the excess risk from medications. There also may be a role for human papillomavirus (HPV) accelerating SCC development in DLE lesions, as demonstrated in a case of SCC arising in DLE lesions of the ears, with viral staining evident within the tumors.12 However, testing for HPV is not routinely performed in these cases.
Dermatologists need to be aware of the relatively rapid tumorigenesis and aggressive behavior of transformation and aggression seen with SCC arising within orolabial DLE lesions compared to cutaneous lesions, especially those on the lips.
Lichen Planus
Although patients with typical cutaneous lichen planus lesions do not have an increased risk for SCC,13 variants of lichen planus may predispose patients to SCC.