Study Background and Disease Burden
Melanoma in situ (MIS) is an early-stage, non-invasive form of melanoma, characterized by malignant melanocytes confined within the epidermis without dermal invasion. The diagnosis of MIS, particularly non-lentigo maligna (non-LM) and non-acral lentiginous melanoma (non-ALM) subtypes, has increased alongside heightened skin cancer screening efforts, raising concerns about overdiagnosis and overtreatment. While lentigo maligna and acral lentiginous MIS subtypes have been extensively studied, there remains limited robust evidence regarding the natural history, local recurrence rates, and optimal management strategies for non-LM/non-ALM MIS. Traditionally, treatment involves excisional biopsy for diagnosis followed by wide local excision to clear any residual disease and prevent progression to invasive melanoma and metastasis. However, the necessity and extent of wide excision in cases with clear margins after initial biopsy remain unclear. This study addresses a critical unmet need to delineate recurrence risks and the impact of margin status and excision width on long-term outcomes in these MIS subtypes.
Study Design
This retrospective cohort study analyzed patients diagnosed with non-LM/non-ALM melanoma in situ from 1991 through 2023 at the Skin Cancer and Melanoma Unit of Andreas Sygros University Hospital in Athens, Greece. Inclusion criteria required a histopathological diagnosis of non-LM/non-ALM MIS and at least one year of clinical follow-up. Patients with a history or concomitant diagnosis of invasive melanoma, or LM/ALM histopathology, were excluded to ensure a homogeneous study population. Data collected included demographic information, lesion characteristics (anatomic locations), excisional biopsy margin status, size of subsequent wide excision margins, and clinical outcomes. The median follow-up was 5.2 years (interquartile range 2.9–7.9 years). The primary outcome measures were local recurrence of MIS or progression to invasive melanoma, development of metastases, and melanoma-specific survival.
Key Findings
The cohort comprised 401 patients with 403 lesions. Women accounted for 53.4% (214 individuals), with a median age of 52 years (IQR 40–62). Lesion distribution was predominantly on the trunk (49.9%), followed by the lower extremities (24.6%), upper extremities (17.6%), and head and neck (7.9%).
All lesions underwent initial excisional biopsy for diagnostic and therapeutic purposes. Following biopsy:
– 372 lesions (92.3%) had a subsequent wide excision.
– 30 lesions had clear excision margins on initial biopsy and were not re-excised.
– 23 lesions had wide excisions narrower than the current standard 0.5 cm margin (mean margin 0.36 cm).
During the follow-up period:
– Only one local recurrence was recorded, occurring in a patient with involved biopsy margins who did not receive wide excision; this patient developed invasive melanoma 14 months later.
– None of the 30 lesions with clear biopsy margins and no further excision recurred over a median 8.1-year follow-up (IQR 4.1–12.9).
– No recurrences were observed in the group with narrower-than-standard wide excision margins (mean 0.36 cm) across a median follow-up of 4.3 years.
– Six patients (1.5%) developed suspicious lesions near the excision site; histopathology confirmed benign entities (nevus or solar lentigo) with no melanoma recurrence.
– Importantly, there were no cases of metastasis or melanoma-specific mortality.
These findings suggest excisional biopsies with histologically clear margins may suffice to control non-LM/non-ALM MIS without the mandatory need for routine wide excision.
Expert Commentary
This landmark 30-year single-center study addresses a critical gap in melanoma research by focusing on non-LM/non-ALM MIS, subtypes less characterized than LM or ALM. The extraordinarily low local recurrence rate, absence of metastasis, and zero melanoma-specific mortality challenge the prevailing paradigm that wide local excision is always necessary following diagnostic excisional biopsy. These data support a more conservative surgical approach, potentially reducing patient morbidity, healthcare costs, and procedural burdens.
However, several limitations warrant consideration. The retrospective design may be prone to selection bias and incomplete data documentation. The single-center setting, while providing consistency in histopathological assessment and treatment protocols, may limit generalizability to diverse populations. Importantly, the median follow-up of around five years may not capture very late recurrences, though the biology of MIS supports that most recurrences manifest earlier.
Current international guidelines typically recommend at least 0.5 cm wide excision margins for MIS. This study provides evidence supporting margin tailoring or observation in cases with fully clear diagnostic biopsy margins. Pending large-scale prospective trials, clinicians should balance patient-specific risks, margin status, and lesion biology in tailoring excision strategies.
Conclusion
This extensive retrospective cohort study demonstrates that in patients with non-lentigo maligna and non-acral lentiginous melanoma in situ, initial excisional biopsies achieving clear histopathological margins may be sufficient to prevent local recurrence and progression. Routine wide excision, especially with standard margins, may not be necessary universally, highlighting the potential for more conservative management protocols. These findings could inform future guideline revisions and encourage personalized surgical approaches, although further prospective studies are essential to validate long-term safety and efficacy.
References
Dessinioti C, Befon A, Plaka M, et al. Local Recurrence and Survival in Patients With Melanoma In Situ. JAMA Dermatol. Published online September 03, 2025. doi:10.1001/jamadermatol.2025.3078
Erdmann F, Lortet-Tieulent J, Schüz J, et al. International trends in incidence of melanoma. Cancer Epidemiol Biomarkers Prev. 2013;22(3):561-570.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Melanoma, Version 2. 2024. https://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf
Grob JJ, et al. A prospective study of 724 patients with lentigo maligna: diagnosis, treatment, outcome. J Am Acad Dermatol. 2023;88(4):912-918.
Merrick A, et al. Prognostic implications of melanoma in situ: a systematic review. J Eur Acad Dermatol Venereol. 2020;34(10):2111-2120.
