What is the management for a 57-year-old female with melanoma of a 4.2 cm right submandibular nodal conglomerate and right lateral retropharyngeal lesion?

Management of Stage III Melanoma with Bulky Nodal Disease

This 57-year-old woman with a 4.2 cm submandibular nodal conglomerate and retropharyngeal involvement from melanoma requires immediate multidisciplinary evaluation, tissue confirmation via FNA, comprehensive staging with CT chest/abdomen/pelvis and brain MRI, followed by therapeutic neck dissection if resectable, and adjuvant immunotherapy with checkpoint inhibitors given the high-risk nodal burden.

Initial Diagnostic Workup

Tissue Confirmation

• Obtain FNA (preferred) or open biopsy of the submandibular nodal mass to confirm metastatic melanoma 1
• Consider genetic analysis (BRAF, c-KIT mutational status) during biopsy if targeted therapy may be considered or for clinical trial enrollment 1

Staging Investigations

• Perform CT chest/abdomen/pelvis to define extent of stage III disease and exclude distant metastases 1
• Obtain brain MRI or CT with contrast - critical given the high incidence of brain metastases in melanoma patients, even with minimal symptoms 1
• Measure serum LDH for prognostic purposes, though it is not sensitive for detecting metastatic disease 1
• For inguinofemoral lymphadenopathy specifically, pelvic CT is recommended to rule out pelvic/retroperitoneal involvement, though this patient has cervical disease 1

Surgical Management

Therapeutic Lymph Node Dissection

• Complete surgical excision of all clinically involved nodes (therapeutic neck dissection) is the standard treatment if disease is resectable 1
• The 4.2 cm nodal conglomerate with retropharyngeal involvement represents bulky stage IIIB or IIIC disease requiring aggressive surgical approach 1
• Imaging with CT prior to surgery is essential for surgical planning in stage IIIB/IIIC disease 1

Considerations for Unresectable Disease

• If nodes are fixed, demonstrate extensive invasion, or involve critical structures making complete resection impossible, radiotherapy becomes an important treatment option 1, 2
• Radiotherapy is indicated for incomplete nodal clearance, fixed nodes, extensive invasion, or capsular disruption 1, 2

Adjuvant Systemic Therapy

Immunotherapy (Primary Recommendation)

• Following complete surgical resection, adjuvant immunotherapy with checkpoint inhibitors (nivolumab or pembrolizumab) is strongly recommended for stage IIIB/IIIC melanoma 3, 4, 5
• Nivolumab dosing: 240 mg IV every 2 weeks or 480 mg IV every 4 weeks 3
• Immunotherapy has dramatically improved survival in advanced melanoma, with 5-year survival rates for stage III disease reaching 74.8% 5
• Treatment duration typically up to 1 year or until recurrence/unacceptable toxicity 3

Special Considerations for Age

• At 57 years, this patient is not considered elderly (geriatric cutoff typically ≥65 years) 3, 6
• Immunotherapy has shown efficacy and tolerability in older patients, though monitoring for adverse reactions is essential 6, 7

Monitoring for Immune-Related Adverse Events

Common Toxicities to Monitor

• Pneumonitis, colitis, hepatitis, endocrinopathies (thyroid dysfunction, hypophysitis), and dermatologic reactions 3
• Serious adverse reactions occur in approximately 30% of patients receiving nivolumab 3
• Discontinuation rate due to adverse reactions is approximately 18% 3

Management Algorithm

• Establish baseline laboratory values: CBC, comprehensive metabolic panel, thyroid function, LDH 1, 3
• Monitor for symptoms suggesting immune-related toxicity at each visit
• Grade 3-4 immune-related adverse reactions typically require systemic corticosteroids and may necessitate permanent discontinuation 3

Follow-Up Schedule

Surveillance Imaging

• Stage IIIB/IIIC patients should undergo CT surveillance every 3 months for 3 years, then every 6 months to 5 years, then annually to 10 years 1
• Brain imaging should be performed if any neurological symptoms develop 1

Clinical Examination

• Patients should be seen every 3 months for 3 years, then every 6 months to 5 years, then annually to 10 years 1
• Lifetime annual skin examinations are mandatory for all melanoma patients 8, 5

Critical Pitfalls to Avoid

• Do not delay brain imaging - melanoma has high propensity for CNS metastases, and retropharyngeal involvement suggests aggressive disease 1
• Do not proceed with surgery without complete staging - approximately 10-15% may have occult distant metastases that would change management 1
• Do not omit genetic testing - BRAF mutation status is critical for treatment planning if disease progresses 1
• Do not underestimate the extent of nodal disease - retropharyngeal involvement may indicate more extensive disease requiring modified surgical approach 1
• In patients ≥75 years, higher discontinuation rates due to adverse reactions occur (29% vs 18% overall), though this patient is younger 3