Cancer of Unknown Primary Site

A previously healthy 47-year-old woman presented with abdominal bloating and discomfort that had worsened over the previous 3 months. Her examination was notable for abdominal distention with bulging flanks and shifting dullness consistent with ascites. Further workup revealed a normocytic anemia (hemoglobin level, 10.4 g per deciliter; reference range, 12.0 to 14.0), elevated serum cancer antigen 125 level (168 U per milliliter; reference value, <38), and elevated carcinoembryonic antigen level (14.7 ng per milliliter; reference value, <3.8). A computed tomographic (CT) scan of her chest, abdomen, and pelvis with the use of contrast material showed liver, lymph node, and peritoneal tumors with ascites. She was referred to an oncologist because of suspicion of cancer, and an omental biopsy revealed poorly differentiated carcinoma with immunohistochemical assays positive for CK20, CDX2, and SATB2 (lower gastrointestinal tract immunostains) and negative for multiple other immunostains. A subsequent fluorodeoxyglucose (FDG) positron-emission tomographic (PET) scan showed FDG-avid liver, lymph node, and peritoneal metastases. Further testing with mammography, colonoscopy, and upper endoscopy failed to identify any primary site. Molecular profiling to find the tissue of origin and identify targetable genomic alterations was deemed indeterminate.