Melanoma in the Parotid Gland: Staging and Treatment
Staging Classification
Melanoma involving the parotid gland is classified as Stage III disease when it represents regional lymph node metastasis from a cutaneous primary, or Stage IV if it represents distant metastasis from a non-head-and-neck primary. 1, 2
Stage III Disease (Regional Metastasis)
When melanoma in the parotid gland represents metastasis from a head and neck cutaneous or mucosal primary, it is classified as Stage III because the parotid contains lymph nodes that serve as regional drainage for head and neck sites 1, 2
The specific Stage III substage depends on tumor burden and characteristics:
- Stage IIIA: Micrometastases without ulceration of the primary tumor 1
- Stage IIIB: Micrometastases with ulceration, or up to three macrometastases without ulceration 1
- Stage IIIC: Macrometastases with ulceration, four or more positive nodes, extranodal extension, or satellite/in-transit metastases with nodal involvement 1
Five-year survival for Stage III disease ranges from 20-70% depending primarily on nodal tumor burden 1
Stage IV Disease (Distant Metastasis)
If the parotid melanoma represents metastasis from a primary site outside the head and neck region (such as trunk or extremity), it is classified as Stage IV distant metastatic disease 1, 2
Long-term survival in Stage IV melanoma is less than 10% overall 1
Unknown Primary Melanoma
Approximately 5% of melanoma patients present with nodal metastases without an identifiable primary tumor 3
When melanoma presents in the parotid gland without a known primary, it should be staged as Stage III if no distant metastases are found 3
The prognosis of unknown primary melanoma is comparable to typical melanoma at the same stage, justifying aggressive surgical management 3
Clinical Context and Diagnostic Considerations
Metastatic vs. Primary Parotid Melanoma
The vast majority (>90%) of melanomas in the parotid gland are metastatic lesions, most commonly from cutaneous head and neck primaries 4, 5
Primary melanoma arising de novo in the parotid gland is extremely rare, with only sporadic case reports in the literature 6, 5
Metastatic parotid melanoma typically involves intraparotid lymph nodes rather than the parotid parenchyma itself 4
Common primary sites that metastasize to parotid lymph nodes include scalp, face, forehead, temple, and conjunctival melanomas 7, 4
Workup Requirements
Complete history and physical examination must focus on identifying a potential primary site, including thorough skin examination of the entire head and neck, scalp, and examination of conjunctivae and oral mucosa 1, 2
For Stage III disease with parotid involvement, baseline imaging should be considered to evaluate for distant metastases, including chest X-ray, CT ± PET, or MRI 1
MRI with contrast provides optimal delineation of parotid masses and assessment of perineural spread, facial nerve involvement, and deep tissue extension 1
Ultrasound can detect and characterize superficial parotid masses and guide fine-needle aspiration, but is insufficient for deep lobe lesions and cannot assess perineural spread or bone invasion 1
Serum LDH should be obtained as it is an independent predictor of poor outcome in metastatic melanoma 1
Treatment Approach
Surgical Management
Wide excision of the primary melanoma (if identified) with appropriate margins (1 cm for tumors ≤2 mm thick, 2 cm for tumors >2 mm thick) combined with complete lymph node dissection is the standard treatment for Stage III disease with clinically positive parotid nodes 1, 2
For parotid involvement, total parotidectomy with ipsilateral neck dissection is typically performed 7, 4
Facial nerve preservation should be attempted when a dissection plane can be created between tumor and nerve, unless the nerve is grossly involved or preoperative facial nerve dysfunction is present 8
Intraparotid lymph node involvement was documented in 5 of 11 patients in one surgical series, emphasizing the importance of complete parotid excision 4
Adjuvant Therapy
Following surgical resection of Stage III disease, options include observation, clinical trial enrollment, or interferon-alfa (category 2B recommendation) 1
For Stage IIIC disease with multiple nodes involved or extranodal extension, radiation therapy to the nodal basin should be considered 1
Adjuvant immunotherapy with checkpoint inhibitors (nivolumab) is FDA-approved for completely resected Stage IIB, IIC, III, or IV melanoma in patients 12 years and older 9
Molecular testing for BRAF, NRAS, and c-kit mutations is mandatory for resectable or unresectable Stage III or IV disease to guide targeted therapy options 2
Advanced/Unresectable Disease
For unresectable Stage III or Stage IV disease, nivolumab as a single agent or in combination with ipilimumab is FDA-approved for treatment 9
Clinical trial enrollment should be strongly encouraged for all stages of melanoma 1
Prognostic Factors
The number of positive lymph nodes is the most significant prognostic factor in Stage III disease 1
Patients with metastasis in only one lymph node have significantly better outcomes, with some achieving disease-free survival of 4-6 years 3
Patients with multiple metastatic lymph nodes typically survive 16 months to 3 years after surgery 3
Extranodal extension and ulceration of the primary tumor are adverse prognostic features 1
Overall prognosis for parotid melanoma is generally poor, with median survival of 11 months in one series, though rare patients may survive long-term following aggressive surgical management 4
Critical Pitfalls to Avoid
Do not assume parotid melanoma is primary without exhaustive search for a cutaneous, conjunctival, or mucosal primary site in the head and neck 7, 4, 5
Do not rely solely on clinical examination to exclude distant metastases in Stage III disease; baseline cross-sectional imaging is recommended 1
Do not sacrifice the facial nerve based on indeterminate frozen section alone; nerve resection should only be performed when grossly involved by confirmed malignancy or when preoperative facial nerve dysfunction is present 8
Do not omit molecular testing for actionable mutations in Stage III/IV disease, as this directly impacts treatment options 2