Subcutaneous Melanoma

Dear Colleagues,

The majority of locoregional relapses of cutaneous melanoma occur as subcutaneous local recurrences/in-transit metastases. Furthermore, subcutaneous metastases are also common in distant metastases.

According to AJCC 8th edition staging classification, subcutaneous melanoma “in transit” metastases are included in stages IIIB, IIIC and IIID, which are considered local advanced disease with rather poor 5-year survival rates of 83%, 69% and 32%, respectively .

Indeed, loco-regional recurrence is an important risk factor for distant metastatic disease, either synchronous or metachronous. Otherwise, the actual staging system does not reflect the different patterns of in-transit disease that may have a specific impact on disease outcome, because there are patients with few lesions that evolve slowly and others with a great number of lesions that increase very quickly with early systemic diffusion. A classification of these different conditions might be useful to correctly approach their treatment.

The diagnosis is usually clinical, but diagnostic imaging is necessary in order to plan the best therapeutic option. Ultrasound may be required if the disease develops more deeply in the soft tissues.  CT scans can also be helpful to reveal subcutaneous metastasis during melanoma staging.

The therapeutic approach for this pattern of recurrence is less standardized then in other clinical situations, and it should be widely discussed in a multidisciplinary context.

Subcutaneous melanoma metastases therapy depends on the number and volume of lesions, site of disease, depth, clinical behavior and presence of other metastases.

Definitive surgical resection remains the preferred therapeutic approach. If the lesions are localized, sentinel lymph node biopsy might play a role in the staging, because half of patients have locoregional lymph node involvement despite the previous lymph nodal assessment. However, when surgery cannot be performed with a reasonable cosmetic and functional outcome, other options must be used. Treatment options are classified as local, regional or systemic.

In cases of multiple/unresectable lesions, several local modalities can be used in specific situations, such as electrochemotherapy, carbon dioxide laser ablation, radiotherapy, cryotherapy and intralesional injections.

Electrochemotherapy is a simple and attractive method for the rapid ablation of subcutaneous melanoma metastases of the limb as well as cutaneous melanomas in nonextremity locations.

Hyperthermic isolated limb perfusion (HILP) and isolated limb infusion (ILI) are ethods that have been proposed in the past in bulky or grossly recurrent in-transit disease, but are now rarely used due to the complexity and morbidity of the procedure.

The recent advances in the systemic therapy of metastatic melanoma, including immunotherapy (anti-CTLA4 ipilimumab and anti-PD-1 molecules) and targeted therapy (with BRAF/MEK inhibitors), also showed a significant impact on treatment modalities in subcutaneous melanoma.

Purpose of this Issue is to report the various diagnostic and therapeutic options in the management of subcutaneous melanoma. 

Dr. Fabio Sandomenico
Prof. Paolo A. Ascierto
Dr. Corrado Caraco
Guest Editors

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• melanoma
• subcutaneous metastases
• in-transit metastases
• surgery
• electrochemotherapy
• immunotherapy
• imaging
• ultrasound
• computed tomography