MMOD-17 INTEGRATION OF MULTIMODAL ADVANCED MOLECULAR TESTING TO CLASSIFY METASTASES OF UNKNOWN PRIMARIES – A CASE OF A PATIENT WITH NO KNOWN MEDICAL HISTORY

Abstract

Metastases are the most common diagnosed brain tumors in adults. In up to 15% of brain metastases, the source of primary malignancy remains unknown despite a thorough workup. Here, we present a case of a 25-year-old male who presented with intracranial hemorrhage and a mass in the left occipital lobe. At the time, his past medical history was unknown to all care providers. He underwent emergent craniotomy for resection of the tumor. Multimodal advanced molecular diagnostic testing, including next-generation sequencing (NGS), chromosomal copy number analysis, and DNA methylation profiling using Northwestern Memorial Hospital’s Cancer of Unknown Primary (CUP) classifier were performed to classify the neoplasm and identify the primary source for his metastatic tumor. Histopathologic sections showed brain parenchyma with acute hemorrhage intermixed with small fragments of a primitive neoplasm. The immuno-profile of the tumor was suggestive of germ cell differentiation. The tumor harbored multiple molecular and cytogenetic alterations including amplification of CCND2 and 12p, gain of chromosomes X,1q, 7 and 8 and loss of chromosomes Y, 1p, 16 and 22. DNA methylation profiling did not match (i.e. score >0.9) with any tumor entity on the CUP classifier, however the tumor clustered closest to non-seminomatous testicular germ cell tumors on the t-distributed stochastic neighbor embedding (t-SNE) plot. This case highlights the value of utilizing multimodality advanced molecular testing when facing a diagnostically challenging case. While none of the molecular tests performed was independently diagnostically conclusive, in concert, they pointed to a definitive diagnosis. Upon diagnosis, imaging revealed a surgically absent left testicle and multiple lung metastases. Patient confirmed diagnosis of a testicular cancer few years prior to his current presentation. He is undergoing