Metastatic Malignant Melanoma

Key Facts

Clinical Issues

Lung is frequent site of metastasis for malignant melanoma
Middle-aged to elderly patients

Image Findings

Multiple, well-defined nodules in periphery of lungs
Endobronchial metastases

Microscopic Pathology

Can show large variety of morphologic appearances, including epithelioid, spindle, signet ring cell, rhabdoid, and small cell melanoma
Hallmark of malignant melanoma is presence of cells with marked cytologic atypia
Majority of tumor cells are large, pleomorphic, with enlarged nuclei and prominent eosinophilic nucleoli
Cells may also be small and relatively bland-appearing with minimal cytologic atypia

Ancillary Tests

S100 protein is positive in nearly 100% of cases (nuclear and cytoplasmic stain)
In most cases, melanocytic-associated markers are positive: HMB-45, Melan-A, tyrosinase, microphthalmia transcription factor (MiTF)
Aberrant expression of epithelial markers (keratins, CEA, EMA) can be seen in small percentage of cases
Other markers can also be expressed, including CD10, CD56, CD68, CD99, CD117, calretinin, NSE, vimentin, and Bcl-2, but are nonspecific

Gross appearance of a bisected nodule

containing a lung metastasis of malignant melanoma shows a well-circumscribed tan nodule with an area of black discoloration due to melanin pigment deposition.

Histologic appearance of metastatic malignant melanoma in the lung shows nests of large, epithelioid tumor cells with enlarged nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm.

CLINICAL ISSUES

Epidemiology

Incidence
- Lung is frequent site of metastasis for malignant melanoma
Age
- Middle-aged to elderly patients

Presentation

Cough
Hemoptysis
Dyspnea
Atelectasis
Pleural effusion

Treatment

Surgical approaches
- Surgical excision for solitary lesions may improve median survival
Adjuvant therapy
- Chemotherapy may be used for multiple and bilateral tumors

Prognosis

Melanoma metastases to lungs are associated with advanced stage and poor prognosis

IMAGE FINDINGS

General Features

Location
- Multiple, well-defined nodules in periphery of lungs
- Endobronchial metastases
Morphology
- Round, well-defined nodules
- Can show cavitation and necrosis

MACROSCOPIC FEATURES

General Features

Usually well circumscribed but unencapsulated
Tan or white, homogeneous cut surface with areas of hemorrhage and necrosis
Tumors may be deeply pigmented due to heavy melanin deposition

Size

Several millimeters to > 5 cm in greatest diameter

MICROSCOPIC PATHOLOGY

Histologic Features

Epithelioid melanoma
- Nests or islands of large epithelioid cells with abundant eosinophilic cytoplasm that may resemble carcinoma
- Tumor cells contain enlarged nuclei with prominent nucleoli
Spindle cell melanoma
- Nests or short fascicles of atypical spindle cells resembling sarcoma
- Differential diagnosis includes sarcomatoid lung carcinoma, metastatic sarcomatoid renal cell carcinoma, and spindle cell sarcoma
Mixed spindle and epithelioid cell melanoma
- Most common form of metastatic melanoma, showing admixture of both spindle and epithelioid cells
- Can be confused for a variety of other primary and metastatic sarcomas in the lung
Pleomorphic melanoma
- Characterized by sheets of pleomorphic and anaplastic tumor cells with bizarre nuclei and frequent abnormal mitoses METASTATIC MALIGNANT MELANOMA
- Tumors may resemble pleomorphic high-grade sarcoma (MFH) or pleomorphic/anaplastic carcinoma of lung
“Rhabdoid” melanoma
- Composed of sheets of large tumor cells with eccentric, densely eosinophilic cytoplasmic inclusions
- Tumor cells can resemble rhabdomyoblastic cells in rhabdomyosarcoma or in “malignant rhabdoid tumor”
Signet ring cell melanoma
- Sheets of tumor cells characterized by signet ring cell morphology
- Cells will show enlarged, hyperchromatic nuclei displaced to periphery by abundant cytoplasm
Small cell melanoma
- Dense sheets of monotonous small round tumor cells with hyperchromatic nuclei and scant cytoplasm
- Tumors can resemble malignant lymphoma, carcinoid tumors, and other small round blue cell tumors

Cytologic Features

Hallmark of malignant melanoma is presence of cells with marked cytologic atypia
Majority of tumor cells are large, pleomorphic, with enlarged nuclei and prominent eosinophilic nucleoli
Frequent mitotic figures; abnormal mitoses are often encountered
Cells may also be small and relatively bland-appearing with minimal cytologic atypia

ANCILLARY TESTS

Immunohistochemistry

S100 protein is positive in nearly 100% of cases (nuclear and cytoplasmic stain)
In most cases, melanocytic-associated markers are positive: HMB-45, Melan-A, tyrosinase, microphthalmia transcription factor (MiTF)
Aberrant expression of epithelial markers (keratins, CEA, EMA) can be seen in small percentage of cases
Other markers can also be expressed, including CD10, CD56, CD68, CD99, CD117, calretinin, NSE, vimentin, and Bcl-2, but are nonspecific

DIFFERENTIAL DIAGNOSIS

Sarcomatoid Carcinoma

Tumor cells are positive for epithelial markers (cytokeratin, EMA, MOC31) and negative for S100 and melanocytic markers

Metastatic Renal Cell Carcinoma

Can show similar morphology with nests of tumor cells with abundant eosinophilic or granular cytoplasm
Tumor cells are positive for cytokeratin, EMA, and RCC marker, and negative for melanoma-associated markers and S100

Spindle and Epithelioid Cell Sarcomas