Malignant pleural effusions (MPE) are most frequently (50–65%) noted from lung and breast cancers. They are commonly unilateral and are reflective of poorer prognosis. Cancer of unknown primary (CUP) account for 4–5% of all invasive cancers. These are metastatic tumors in which the primary is unknown despite an extensive medical evaluation. About 11% of MPE are from CUP. These MPEs present a clinical dilemma to physicians as there is a paucity of literature on their management and no consensus or guideline statement. This paper provides an overview of MPE from CUP in regard to diagnosis, prognosis, and treatment options. A selective search was performed in Medline and PubMed, with the keywords “Malignant pleural effusion” and “Cancer of unknown primary” up to December 2018. A review of literature would suggest that a thoracentesis is the first step in all cases but additional work up such as thoracoscopy & pleural biopsies is frequently warranted. With advances in immunohistochemical staining and biomarker development, MPE with CUP maybe profiled in a similar manner as lung cancer. Similarly, liquid biopsy or identification of circulating tumor cell free DNA may have a role in the work up of CUP in the future. There is some experience in managing these patients with gene directed therapies and immune checkpoint inhibitors, however, with mixed results. Given the poor prognosis associated with MPE from CUP, symptom alleviating measures such as indwelling pleural catheters should be part of the management strategy.
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