Treatment Approach for Internal Melanoma
The treatment of internal melanoma requires a surgical approach for localized disease, followed by systemic therapy with immunotherapy agents like ipilimumab and nivolumab for advanced disease, as these have shown the best outcomes for morbidity and mortality.
Diagnosis and Staging
Before initiating treatment, proper diagnosis and staging are essential:
Biopsy with a 2 mm margin of normal skin around suspicious lesions is mandatory 1
Histology report should include:
- Maximum thickness in millimeters (Breslow)
- Level of invasion (Clark level I-V)
- Presence of ulceration
- Surgical margin clearance
- Presence and extent of regression
Staging workup should include:
- Physical examination focusing on regional lymph nodes
- Blood tests including LDH and alkaline phosphatase
- Imaging: chest X-ray, ultrasound of abdomen and regional lymph nodes for melanomas >1mm thickness
- CT or PET/CT scans for high-risk patients or when metastasis is suspected 1
Treatment Algorithm for Internal Melanoma
1. Localized Disease
Surgical excision with appropriate margins based on tumor thickness:
- 0.5 cm for in situ melanoma
- 1 cm for tumors 1-2 mm thick
- 2-3 cm for tumors >2 mm thick 1
Sentinel lymph node biopsy for melanomas >1 mm thickness, followed by complete lymph node dissection if positive 1
2. Locoregional Metastatic Disease
- Complete surgical removal of affected lymph nodes including the surrounding lymph node region 1
- Isolated limb perfusion with melphalan and TNF for non-resectable in-transit metastases (only in specialized centers) 1
- Radiotherapy for cases with inadequate resection margins when re-excision is not feasible 1
3. Systemic Metastatic Disease (Stage IV)
- Immunotherapy: Ipilimumab (CTLA-4 inhibitor) at 3 mg/kg every 3 weeks for a maximum of 4 doses, either alone or in combination with nivolumab 2
- Combination approach: Ipilimumab 3 mg/kg with nivolumab 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab as a single agent 2
- Surgery for isolated visceral metastases in patients with good performance status 1
- Palliative radiotherapy for symptomatic brain or localized bone metastases 1
Special Considerations for Internal Melanoma
Internal melanomas can be primary (originating from mucosal surfaces) or metastatic from cutaneous melanoma. Primary internal melanomas may occur in:
- Upper respiratory tract
- Gastrointestinal tract
- Anorectal region
- Urogenital area 3
These cases require specialized approaches:
- Detailed imaging to determine the extent of disease
- Multidisciplinary management involving surgical oncology, medical oncology, and radiation oncology
- More aggressive surgical approach when feasible 3
Follow-up Recommendations
- Clinical examinations every 3 months during the first 3 years, then every 6-12 months thereafter 1
- For high-risk patients, consider ultrasound of lymph nodes, CT or whole body PET/CT scans 1
- Monitor serum S-100 levels, which has higher specificity for disease progression than LDH 1
Important Caveats
- Treatment decisions should be made by an interdisciplinary tumor board at centers experienced in melanoma management 1
- The prognosis for internal melanoma is generally worse than cutaneous melanoma, emphasizing the importance of early detection and aggressive treatment
- Patients should be considered for clinical trials evaluating new approaches, especially for advanced disease 1
- Be aware that 8% of melanoma patients develop a secondary melanoma within 2 years of initial diagnosis, requiring continued vigilance 1
The emergence of immunotherapy has significantly improved outcomes for patients with advanced melanoma, making early referral to centers with expertise in these treatments crucial for optimizing survival and quality of life.