Discussion

This case highlights the diagnostic and management complexities of perianal SCC, especially in a patient with IP without typical risk factors, where profound inflammation further complicates and obscures the diagnosis. It is hypothesized that chronically inflamed skin fosters the concept of an “immunocompromised cutaneous district” where local immune control becomes dysregulated, leading to malignant transformation.15 Patients with perianal SCC often experience prolonged misdiagnosis and ineffective treatments that further complicate disease progression.2,8 Studies have shown that diagnostic delays can lead to metastasis.7,8 Factors that lead to delayed diagnosis include non-specific symptoms, absence of typical risk factors, biopsy sampling errors, and lack of routine screening.6,8, 9, 10 Anogenital SCCs demonstrate increased susceptibility to superficial infections, particularly in the context of local immune dysregulation and immunosuppression. This susceptibility can both potentiate inflammation and complicate histopathological interpretation. Reflecting these challenges, a 2024 study reported that 71% of patients required multiple biopsies to confirm a diagnosis of SCC secondary to HS.10

Current literature on SCC arising in the setting of psoriasis remains limited. Nevertheless, meta-analyses and observational studies consistently demonstrate that patients with psoriasis have an increased risk of non-melanoma skin cancers (NMSCs), including both SCC and basal cell carcinoma.11,12,16 This elevated risk has been largely attributed to treatment-related exposures, particularly immunosuppressive therapies and prior phototherapy. Among these factors, psoralen ultraviolet A (PUVA) therapy has been most associated with a highly elevated risk of SCC, with studies reporting markedly increased standardized incidence ratios.11,13 Additional risk has been linked to systemic agents such as cyclosporine and, to a lesser extent, methotrexate. Current guidelines, including those from the American Academy of Dermatology (AAD), highlight a clear association between PUVA exposure and SCC, while cyclosporine appears to increase malignancy risk independent of the underlying disease.14

Beyond treatment-related factors, individuals with psoriasis have a higher prevalence of established carcinogenic risk factors, including smoking, excessive alcohol consumption, and obesity, which may further contribute to the observed increase in SCC incidence.13 In the absence of these exposures, chronic immune dysregulation and sustained cutaneous inflammation inherent to psoriasis may create a permissive microenvironment for malignant transformation, positioning chronic inflammation as a potential primary driver of SCC in select cases lacking traditional risk factors.11,13

In the case discussed, the patient underwent months of unsuccessful wound care and non-diagnostic biopsies before receiving the correct diagnosis. Diagnostic accuracy in ulcerated lesions is challenging, as biopsy site selection critically influences yield.2,17 Biopsies are conventionally taken from the periphery of an ulceration to avoid the non-specific inflammatory changes seen beneath an ulcer. However, superficial or peripheral sampling can miss invasive disease, and in this case, given the prior non-diagnostic results, a repeat biopsy was targeted toward the center of the lesion with deep sampling to obtain sufficient tissue beyond superficial dermis. This approach highlights the importance of considering multiple biopsies from different sites when initial sampling is unrevealing.2,17 To ensure prompt, accurate detection of perianal SCC, a structured, multidisciplinary strategy is essential. Clinicians must first consider benign anorectal conditions such as hemorrhoids, anal fissures, and perianal abscesses, while also ruling out other malignancies like anal adenocarcinoma, malignant melanoma, and lymphoma.2,18 Immunohistochemical markers can aid in differentiating these entities.18 In addition, infectious and inflammatory causes, including Crohn disease, syphilis, tuberculosis, and granulomatous processes, should be carefully considered.2,7,9