266 Synchronous prostate adenocarcinoma and metastatic melanoma diagnoses supported by ctDNA variant analysis in a patient presenting with a left upper lobe mass

Abstract

Introduction Synchronous malignancies are rare, and accurate diagnosis can be challenging when metastatic patterns overlap. Circulating tumour DNA (ctDNA) is tumour-derived fragmented DNA that circulates in the blood, enabling prompt "liquid biopsies" (1). This case emphasises the emerging role of ctDNA variant analysis in differentiating between two primary malignancies, following a patient's referral to a respiratory multidisciplinary team (MDT) for a suspected lung primary. Case: A 64-year-old male presented to primary care with an evolving, pruritic, dark lesion over the left scapula. Initial chest X-ray revealed a left upper lobe (LUL) mass, prompting referral to the respiratory MDT. Cross-sectional imaging showed widespread metastatic disease, including bilateral pulmonary nodules, extensive liver lesions, adrenal masses, and bone involvement in addition to the 45 mm LUL mass. The differential diagnoses included a single primary malignancy with widespread metastases or multiple synchronous malignancies. PSA testing revealed a markedly elevated level (30 ng/mL), raising suspicion for prostate cancer. Prostate MRI under the urology team confirmed a T3bN0 lesion, and transperineal biopsy demonstrated an adenocarcinoma (Gleason 3+4). Analysis of ctDNA (Guardant360) identified a NRAS mutation(c.181C>A p.Q61 K, variant allele frequency (VAF) 36%, tier 2C pathogenicity), strongly suggestive of melanoma (2,3). A TERT promoter mutation (c.-146C>T, VAF 9.76%, tier 3 pathogenicity) and an AR variant (c.1255G>T p.A419S, VAF 3.6%, uncertain significance) were consistent with the diagnosis of prostate adenocarcinoma (3). Concurrently, a biopsy of the scapular lesion confirmed malignant melanoma (BRAF-wildtype). Conclusion The ctDNA analysis provided concurrent molecular confirmation of dual pathologies, highlighting the potential value of ctDNA profiling in facilitating diagnoses of multiple primary tumours. However, there are clear limitations, and large-scale studies are required to validate this use of ctDNA. Disclosure No significant relationships