Use of novel genomic sequencing to characterise carcinoma of unknown primary (CUP) in patient with axillary lymphadenopathy.

Abstract

Carcinoma of unknown primary (CUP) comprises 2-5% of cancer diagnoses worldwide, with a prevalence that has modestly declined with increased availability of advanced diagnostic tools such as next-generation sequencing (NGS). This case presentation illustrates the possibilities and gaps that remain with improving diagnostic capabilities in identifying and effectively treating CUP. This is the case of a rapidly enlarging right axillary mass without a primary tumour site and histological evaluation demonstrating a poorly differentiated neoplasm. Tumour of origin testing using a clinically validated RNA-sequencing-based machine learning classifier unexpectedly suggested greatest probability of metastatic melanoma with lesser likelihood of fibrosarcoma. Subsequent clinical behaviour and lack of response to chemoimmunotherapy conflicted with NGS results, with a multidisciplinary team ultimately agreeing on final diagnosis of aggressive soft tissue sarcoma, specifically malignant peripheral nerve sheath tumour. The patient had a complete clinical response after forequarter amputation and a sarcoma-based chemotherapy regimen. This case highlights both the potential and current shortcomings of NGS and predictive tumour of origin analytic tools in helping with characterisation and categorisation of CUP. There is a need for improvement and optimisation of these diagnostic modalities, but they offer another option to improve historically poor outcomes in CUP.