Metastatic melanoma

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Dr Aaron Andreas
MBChB(Hons) Genetics BS(Hons) FRCPath
Dr Aaron Andreas graduated from the University of Liverpool in 2014 with MBChB (Honours) and Genetics BSc (Honours) degrees. Aaron began his training in pathology at Leeds Teaching Hospitals in the United Kingdom, achieving fellowship of the Royal College of Pathologists (UK) in 2021
Figure 1. Diff-Quik stained cytological preparation of FNA fluid showing large atypical melanocytes
Figure 2. Breast core biopsy showing sheets of malignant melanoma cells surrounding a vascular structure. Scattered macrophages with pigment can be seen in the background
Figure 3. SOX-10 immunostain showing positive staining of the neoplastic cells, confirming melanocytic differentiation

Metastatic melanoma (MM) refers to the deposition of malignant melanoma cells distant to the primary tumour, usually via lymphatic or haematogenous spread.


Mrs P is a 47-year-old woman who presented to her GP with a three-week history of left breast pain and a palpable lump. Notably she has a past medical history of a left forearm melanoma which had been completely excised with a negative sentinel node several years ago. Ultrasound of her left breast demonstrated an 8cm x 6cm predominantly cystic, partly solid lesion with some mildly atypical features. This was felt most likely to be a haemorrhagic breast cyst. She underwent ultrasound guided fine needle aspiration (FNA) of the cyst fluid and subsequent core biopsy of the more solid components. 

Cytological examination of the FNA showed numerous dispersed large atypical cells as well as background macrophages containing melanin pigment (Figure 1). Histological examination of the breast core biopsy showed sheets of atypical cells, many surrounding small blood vessels with admixed inflammatory cells (Figure 2). Immunohistochemistry confirmed melanocytic differentiation with the tumour cells staining positive for melanocytic markers (SOX-10 – Figure 3) and negative for breast cancer markers (Cytokeratin, estrogen/progesterone receptor). A diagnosis of metastatic melanoma was made. Subsequent molecular testing demonstrated a BRAF somatic mutation was present in the malignant cells.


Metastasis accounts for the vast majority of morbidity and mortality related to melanoma. The most common sites are the skin, lymph nodes, lung, bone, brain and intestines. However any site in the body can be effected. Metastasis can occur even with very early primary melanomas which have been completely excised, and often occur many years and even decades following the removal of the primary tumour. MM has a highly variably cytological/ histological appearance and can mimic many other malignancies, often requiring confirmation with melanoma markers using immunohistochemistry. There should be a low threshold for testing with melanoma markers in patients with a known history of melanoma to ensure cases are not missed or misdiagnosed. Approximately half of MM carries mutations in the BRAF gene which helps them grow and proliferate. Specific targeted therapies now exist which are highly effective against BRAF mutated MM and so newly diagnosed MM are routinely screened for BRAF mutations.

Take home points
  • MM can occur years or even decades after the primary tumour excision
    and can effect any part of the body.
  • MM can mimic many other malignancies both clinically and histologically, therefore it is important to provide a history of melanoma on request form
    for any patients undergoing a FNA or biopsy regardless of the site involved. 
  • Newly diagnosed MM are routinely screened for BRAF mutations to help detect cases which may respond to targeted BRAF inhibiting therapies.

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