Giant Keratinocyte Carcinomas: Clinical, Histopathological, Molecular and Health-System Factors with Therapeutic Implications—A Structured Narrative Review

Abstract

Background/Objectives: Giant keratinocyte carcinomas, comprising basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) with a maximum diameter ≥ 5 cm, pose substantial clinical challenges. This structured narrative review distinguishes giant-specific findings from contextual evidence in advanced or high-risk disease. Methods: The synthesis uses a retained bibliography assembled from searches described in earlier drafts as covering PubMed/MEDLINE and PubMed Central from January 2015 to March 2026, supplemented by citation and guideline searching and a focused update reported through 4 September 2026. A record-level search and screening log is unavailable; historical selection counts cannot be independently reconstructed. The review protocol was not registered, and exhaustive coverage or full PRISMA compliance is not claimed. Sources were classified by design and directness, with descriptive consideration of methodological limitations. Results: The retained set contains 51 sources: nine containing direct giant-specific clinical evidence and 42 providing contextual evidence. Direct evidence consists principally of case reports, retrospective or comparative studies and a giant-cSCC literature synthesis. It links giant BCC with prolonged lesion duration, ulceration, deeper invasion and reconstructive burden. Giant-cSCC outcomes vary substantially between reported series. Evidence for Hedgehog-pathway inhibition, PD-1 blockade and most molecular mechanisms derives mainly from conventional or advanced disease. Conclusions: Management requires multidisciplinary assessment integrating size, pathological risk, resectability and patient factors. Giant-specific molecular and therapeutic evidence remains limited, and contextual treatment effects should not be interpreted as effects established specifically in tumours ≥ 5 cm.