Giant Basal Cell Carcinomas Express Neuroactive Mediators and Show a High Growth Rate: A Case–Control Study and Meta-Analysis of Etiopathogenic and Prognostic Factors

Abstract

Background Giant basal cell carcinomas (GBCCs), (BCC ≥5 cm), are often painless, destructive tumors resulting from poorly understood patient neglect. Objectives To elucidate etiopathogenic factors distinguishing GBCC from basal cell carcinoma (BCC) and identify predictors for disease-specific death (DSD). Methods Case–control study examining clinicopathologic and neuroactive factors (β-endorphin, met-enkephalin, serotonin, adrenocorticotropic hormone, and neurofilament expression) in GBCC and BCC. Systematic literature review to determine DSD predictors. Results Thirteen GBCCs (11 patients) were compared with 26 BCCs (25 patients). GBCC significantly differed in size, disease duration, and outcomes; patients were significantly more likely to live alone, lack concern, and have alcoholism. GBCC significantly exhibited infiltrative/morpheic phenotypes, perineural invasion, ulceration, and faster growth. All neuromediators were similarly expressed. Adenoid phenotype was significantly more common in GBCC. Adenoid tumors expressed significantly more β-endorphin (60% vs. 18%, P = 0.01) and serotonin (30% vs. 4%, P = 0.02). In meta-analysis (n ≤ 311: median age 68 years, disease duration 90 months, tumor diameter 8 cm, 18.4% disease-specific mortality), independent DSD predictors included tumor diameter (cm) (hazard ratio (HR): 1.12, P = 0.003), bone invasion (HR: 4.19, P = 0.015), brain invasion (HR: 8.23, P = 0.001), and distant metastases (HR: 14.48, P = 0.000). Conclusions GBCC etiopathogenesis is multifactorial (ie, tumor biology, psychosocial factors). BCC production of paracrine neuro-mediators deserves further study.

Conventional versus giant basal cell carcinoma, a review of 57 Cases: Histologic differences contributing to excessive growth

“…Support for this theory stems from an observation that this tumor is most commonly diagnosed in patients with lower socioeconomic status or physical disability, patient characteristics that may lead to delay in diagnosis and seeking treatment. [ 10 11 13 ] Of note, in our study, we found that the average age of diagnosis of GBCC was similar to the age of diagnosis of conventional BCC. This series was designed only to examine the histologic parameters of GBCC and our data collection did not include information from the clinical records such as the duration of tumor growth prior to presentation for medical care.…”

“…[ 17 25 26 ] Our study did not corroborate this anatomic site distinction. In our series, similar to the recent study by Yazdani Abyaneh et al .,[ 13 ] GBCCs were seen with the highest incidence in the head/neck region, similar in incidence to conventional BCCs. This difference may reflect that ours is a retrospective study based on pathology reports from the archives predominantly from an academic hospital rather than a prospective, clinically oriented study.…”

“…[ 1 ] The largest series to date documenting histopathologic features of these unusual neoplasms is a recent case–control study of 13 GBCCs, which also examined the expression of neuromediators by immunohistochemistry as a mechanism to explain their large size. [ 13 ] Most previous reports note that GBCCs commonly occur on the trunk as compared to conventional BCCs' predilection for the head/neck region. [ 17 25 26 ] Our study did not corroborate this anatomic site distinction.…”

“…[ 1 5 9 10 11 ] Some literatures suggest that larger BCC may grow at a faster rate than conventional BCC. [ 12 13 ] While studies examining the clinical characteristics of these rare tumors exist,[ 1 14 ] large case series specifically investigating the histopathologic features of GBCC are lacking in the current literature. It is unknown whether GBCCs possess unique histological features that could contribute to their large size and potentially faster growth rate.…”

Clinicopathological Pattern of Basal Cell Carcinoma among Sudanese Patients

“…Basal cell carcinomas are negative for CK20, but a subset of BCCs is (usually only weakly) positive for chromogranin and/or synaptophysin [50]. BCCs more than 5 cm in diameter were found to express neuroactive factors such as serotonin and adrenocorticotropic hormone [52].…”