The incidence of bone marrow metastasis (BMM) in newly diagnosed Ewing sarcoma (ES) is variable across studies. An optimal staging strategy for detecting BMM is not defined. While BM biopsy and/or aspirate (BMBA) have been the gold standard, [F-18]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect BM metastasis may decrease reliance on BMBA. We conducted a systematic review to assess incidence of BMM and the role of FDG-PET. We observed a pooled incidence by BMBA of BMM of 4.8% in all newly diagnosed ES patients and 17.5% among patients with metastatic disease. Only 1.2% of patients had BMM as their sole metastatic site. FDG-PET detection of BMM compared to BMBA demonstrated pooled 100% sensitivity and 96% specificity, positive predictive value of 75% and negative predictive value of 100%. In the era of FDG-PET imaging, omission of BMBA may be considered in patients with otherwise localized disease after initial staging studies.
Cancer of unknown primary (CUP) is a common diagnosis in adult oncology, but is extremely rare in pediatrics, with few published reports and none in the era of molecular profiling. Here, we describe a 13-year old boy with metastatic adenocarcinoma of unknown primary that was refractory to conventional chemotherapy. Molecular profiling revealed an activating ERBB2 D769Y variant. He subsequently achieved disease control on a lapatinib-containing regimen, and upon progression, he transiently responded to neratinib prior to dying from disease. Our case reports a rare example of pediatric CUP and highlights the utility of molecular profiling in these cases.