Simple SummaryAs the global burden of skin cancer rises, complex cases of locally advanced skin cancer are rising as well. Rare and aggressive dissemination mechanisms are often the cause for extensive skin cancer. Incohesive spreading patterns complicate correct diagnoses and may result in large tumors with multiple misguided treatment attempts. The aim of this study was to create awareness for cutaneous malignancies with rare, aggressive dissemination mechanisms to improve diagnostic and therapeutic strategies in such complex cases. We identified high-risk characteristics of locally advanced skin cancer warranting extended surgical treatment and a cohesive interdisciplinary approach.AbstractThe globally increasing incidence of cutaneous malignancies leads, in parallel, to increasing numbers of locally advanced skin cancer resulting in reconstructive surgery. Reasons for locally advanced skin cancer may be a patient’s neglect or aggressive tumor growth, such as desmoplastic growth or perineural invasion. This study investigates characteristics of cutaneous malignancies requiring microsurgical reconstruction with the aim of identifying possible pitfalls and improving diagnostic and therapeutic processes. A retrospective data analysis from 2015 to 2020 was conducted. Seventeen patients (n= 17) were included. The mean age at reconstructive surgery was 68.5 (±13) years. The majority of patients (14/17, 82%) presented with recurrent skin cancer. The most common histological entity was squamous cell carcinoma (10/17, 59%). All neoplasms showed at least one of the following histopathological characteristics: desmoplastic growth (12/17, 71%), perineural invasion (6/17, 35%), or tumor thickness of at least 6 mm (9/17, 53%). The mean number of surgical resections until cancer-free resection margins (R0) were achieved was 2.4 (±0.7). The local recurrence rate and the rate of distant metastases were 36%. Identified high-risk neoplastic characteristics, such as desmoplastic growth, perineural invasion, and a tumor depth of at least 6 mm, require a more extensive surgical treatment without concerns about defect size.