What is the next step in management for a patient with a history of metastatic melanoma, status post wedge resection of a left upper lobe nodule, now presenting with a new 5 mm nodule in the right lower lobe suspicious for metastatic disease?

Management of New 5mm Pulmonary Nodule in Metastatic Melanoma Post-Resection

Obtain tissue confirmation of the suspicious 5mm right lower lobe nodule via CT-guided biopsy or PET-CT imaging to guide treatment decisions, as pathologic confirmation of recurrence is recommended before initiating therapy. 1

Immediate Diagnostic Workup

Pathologic confirmation is essential before treatment decisions:

• Fine-needle aspiration (FNA) cytology or biopsy should be performed whenever possible to confirm initial clinical recurrence 1
• The 5mm nodule size makes CT-guided biopsy technically feasible and is the preferred approach for tissue diagnosis 1
• Consider PET-CT imaging to characterize this indeterminate lesion and evaluate for additional metastatic sites not visible on routine CT (such as extremities) 2, 3

Additional staging investigations to consider:

• Brain MRI or CT with contrast, given the high incidence of brain metastases in metastatic melanoma patients 1
• Serum LDH level for prognostic assessment 1
• Abdominal/pelvic CT if not already performed, to define full extent of disease 1

Rationale for Tissue Confirmation

The NCCN guidelines explicitly state that initial clinical recurrence should be confirmed pathologically whenever possible 1. This is critical because:

• The punctate <2mm nodules were present on prior imaging, suggesting some nodules may be benign [@CT report context]
• False-positive findings on imaging are common and can lead to unnecessary treatment or patient anxiety [@10@, 3]
• Treatment decisions for stage IV disease differ significantly from surveillance of indeterminate findings [@4@, @8@]

Management Based on Biopsy Results

If Biopsy Confirms Metastatic Melanoma (Stage IV Disease)

Surgical resection is the preferred approach for limited/resectable metastatic disease:

• Complete surgical excision with negative margins is recommended for solitary pulmonary metastases [1, @8@]
• A 5mm nodule is technically resectable via wedge resection or video-assisted thoracoscopic surgery (VATS) [@8@]
• In selected patients with solitary visceral metastasis, a short observation period or systemic treatment followed by repeat scans may help identify rapidly progressive disease before surgery 1

After complete resection, treatment options include:

• Clinical trial enrollment (preferred) [@8@]
• Systemic therapy with immunotherapy or targeted therapy depending on BRAF mutation status [1, @12@, 4]
• Observation is NOT recommended as adjuvant interferon monotherapy outside clinical trials is inappropriate for resected stage IV disease 1

If Disease is Unresectable or Additional Metastases are Found

Systemic therapy options for disseminated disease without brain metastases:

• Clinical trial (preferred) 1
• Ipilimumab (category 1) 1
• Nivolumab 3 mg/kg IV every 2 weeks, which showed 32% overall response rate in previously treated metastatic melanoma [@12@, 4]
• Nivolumab plus relatlimab combination, FDA-approved in 2022, showing superior efficacy to nivolumab alone [@17@]
• Vemurafenib (category 1) if BRAF mutation is documented 1
• Dacarbazine, temozolomide, or high-dose interleukin-2 [@8@]

Critical Pitfalls to Avoid

Do not initiate systemic therapy without tissue confirmation:

• The <2mm nodules present on prior imaging suggest not all pulmonary nodules represent metastatic disease [@CT report context]
• Starting immunotherapy based on imaging alone risks unnecessary toxicity and cost 2, 3

Do not perform routine surveillance imaging without clinical indication:

• For patients with prior stage I-II disease, routine cross-sectional imaging has extremely low yield and exposes patients to cumulative radiation 1
• However, this patient has confirmed metastatic disease (prior wedge resection), making targeted imaging of suspicious findings appropriate 2, 3

Do not delay brain imaging:

• Patients with metastatic melanoma have high incidence of brain metastases (18% in one cohort) 4
• Brain metastases require priority treatment to prevent hemorrhage, seizures, or neurologic dysfunction 1
• Even minimal symptoms or physical findings warrant brain MRI or CT with contrast 1

Follow-Up Strategy Post-Intervention

If nodule is resected or treated:

• Physical examination every 3-6 months for first 2-3 years, then every 6-12 months 1
• Chest imaging and LDH at physician discretion every 6-12 months 1
• The panel recognizes low yield of routine screening but acknowledges value in detecting surgically resectable recurrence 1

Lifetime dermatologic surveillance is mandatory:

• 4-8% lifetime risk of second primary melanoma 1
• Annual skin examination minimum, with frequency adjusted for dysplastic nevi and family history 1