Sarcomatoid carcinoma presenting as cancers of unknown primary: A clinicopathological portrait

Background: Sarcomatoid carcinoma of unknown primary (SCUP) is a rare entity of either poorly differentiated carcinoma with sarcoma-like differentiation or a true mixed lineage neoplasm. Limited data regarding clinicopathological profile and management exists. Methods: We retrospectively reviewed the MD Anderson Cancer of Unknown Primary database and tumor registry to identify 48 SCUP patients between 2001 and 2017. Patient characteristics, pathology, molecular diagnostics, treatments, and outcomes were obtained. Kaplan-Meier method was used to estimate overall survival (OS) and compared using log rank test. Results: Median age at diagnosis was 59 years (range 27-86). Majority of patients were female (58%) and presented with ≥3 metastatic sites (52%), commonly lymph node (50%), bone (42%), lung (27%), and liver (21%). First line treatment included chemotherapy (35%), surgery (27%), and radiation (24%). Gemcitabine and docetaxel (18%) was the most common chemotherapy regimen. Median OS for entire cohort was 11 months (95% CI: 5.6 to 16.4). Poor performance status (PS), > 1 metastatic site, elevated lactate dehydrogenase (LDH), and high neutrophil-to-lymphocyte ratio (NLR) were significantly associated with worse OS on univariate analyses. On multivariate analyses, poor PS (HR 8.7; 95%CI: 3.0-25.0; p < 0.001) and high NLR (HR 3.4; 95%CI: 1.3-8.8; p = 0.011) emerged as independent prognostic factors for OS. Conclusions: SCUP is a rare presentation with an aggressive clinical course and limited survival. Diagnosis is difficult to make and requires careful review and synthesis of histology, immunohistochemistry, and molecular diagnostics. Chemotherapy resistance remains a challenge. Early mutational profiling is warranted, and clinical trial participation should be encouraged for this subset.