Progression of Nasopharyngeal Pleomorphic Adenoma to Carcinoma Ex Pleomorphic Adenoma With Metastases: A Case Report.

Pleomorphic adenoma (PA) is the most common benign salivary gland tumour, typically arising in the parotid gland, with minor salivary gland involvement being less frequent and nasopharyngeal localization exceedingly rare. Malignant transformation into carcinoma ex pleomorphic adenoma (CXPA) occurs rarely, but metastatic disease is exceptionally uncommon. To date, no cases of nasopharyngeal PA transforming into CXPA with both nodal and distant metastases have been reported. We describe a 60-year-old man who presented with progressive facial pain, paraesthesia, weight loss, and cervical lymphadenopathy. Imaging revealed a destructive maxillary and nasopharyngeal mass with perineural spread, nodal disease, and disseminated metastases to the lung, liver, and bone. Initial nasopharyngeal biopsy demonstrated only benign PA with cartilaginous stroma and epithelial elements, while lymph node biopsy revealed poorly differentiated carcinoma with positivity for broad-spectrum cytokeratin, GATA3, HER2 (3+ membranous), androgen receptor, but negative for p40 and p16. Fluorescence in situ hybridization (FISH) demonstrated PLAG1 gene rearrangements in both the benign nasopharyngeal lesion and the metastatic carcinoma, establishing the diagnosis of CXPA arising from a nasopharyngeal PA. This case underscores several diagnostic challenges: (1) histology from the primary lesion initially suggested a benign tumour, discordant with aggressive radiological features; (2) ancillary molecular testing with PLAG1 FISH was critical in linking the primary PA with metastatic carcinoma; and (3) HER2 overexpression and androgen receptor positivity highlighted potential therapeutic targets, though the rapid disease course precluded treatment. Correlation of imaging, histology, cytology, and molecular studies is crucial, particularly when biopsy findings appear discordant with clinical behaviour.