Metastatic malignant melanoma of unknown primary diagnosed by fine needle aspiration cytology: Case report and brief literature review

Melanoma of unknown primary (MUP) is a rare form of metastatic melanoma in which nodal or visceral involvement is identified without an evident cutaneous, ocular, or mucosal primary lesion. We report the case of a 49-year-old man who presented with a gradually enlarging, painless mass in the right posterior cervical neck over three months, without constitutional symptoms or a prior history of melanoma.
Fine-needle aspiration (FNA) of the lymph node revealed dyscohesive, pleomorphic malignant cells characterized by eccentric nuclei, prominent macronucleoli, intranuclear cytoplasmic inclusions, and focal brown cytoplasmic pigment. Immunohistochemical (IHC) analysis of the cell block showed positivity for S-100, SOX10, HMB-45, and Melan-A, with negative staining for epithelial, lymphoid, pulmonary, and squamous markers, supporting a diagnosis of metastatic malignant melanoma. An extensive diagnostic workup, including full-body dermatologic examination, ophthalmologic assessment, otolaryngologic and mucosal evaluation, cystoscopy, proctoscopy, whole-body PET-CT, and brain MRI, did not identify a primary lesion. Molecular testing revealed a BRAF V600E mutation.
The patient underwent a right selective neck dissection, which demonstrated metastatic melanoma in three of seventeen lymph nodes without extranodal extension. He subsequently received adjuvant therapy with dabrafenib and trametinib. Surveillance imaging at six and twelve months showed no evidence of recurrent or new disease.
This case underscores the diagnostic utility of FNA cytology with cell block preparation, along with IHC and molecular testing, in establishing a definitive and clinically actionable diagnosis of metastatic MUP.