Purpose: Accurate identification of tissue of origin (ToO) for patients with carcinoma of unknown primary (CUP) may help customize therapy to the putative primary and thereby improve the clinical outcome. We prospectively studied the performance of a microRNA-based assay to identify the ToO in CUP patients.Experimental Design: Formalin-fixed paraffin-embedded (FFPE) metastatic tissue from 104 patients was reviewed and 87 of these contained sufficient tumor for testing. The assay quantitates 48 microRNAs and assigns one of 25 tumor diagnoses by using a biologically motivated binary decision tree and a K-nearest neighbors (KNN). The assay predictions were compared with clinicopathologic features and, where suitable, to therapeutic response.Results: Seventy-four of the 87 cases were processed successfully. The assay result was consistent or compatible with the clinicopathologic features in 84% of cases processed successfully (71% of all samples attempted). In 65 patients, pathology and immunohistochemistry (IHC) suggested a diagnosis or (more often) a differential diagnosis. Out of those, the assay was consistent or compatible with the clinicopathologic presentation in 55 (85%) cases. Of the 9 patients with noncontributory IHC, the assay provided a ToO prediction that was compatible with the clinical presentation in 7 cases.Conclusions: In this prospective study, the microRNA diagnosis was compatible with the clinicopathologic picture in the majority of cases. Comparative effectiveness research trials evaluating the added benefit of molecular profiling in appropriate CUP subsets are warranted. MicroRNA profiling may be particularly helpful in patients in whom the IHC profile of the metastasis is nondiagnostic or leaves a large differential diagnosis.

As more students with attention-deficit/hyperactivity disorder attend college, studies are emerging that reveal problems in psychosocial and academic functioning. Substance use may magnify deficits in self-regulation. Recommendations are made for comprehensive assessment; however, the usual diagnostic categories may not be developmentally relevant. Students who are identified benefit from medication and nonmedication interventions, strategy support, and accommodations.

Our retrospective study provides encouraging indications that CUP patients with gastrointestinal profiles benefit from site-specific therapy. We recommend all CUP patients, especially those with abdominal nodes, isolated carcinomatosis or liver metastases, to undergo optimal immunohistochemistry (IHC) to check for a gastrointestinal profile of CUP.

Eugen Zuckermann died on November 24 [1997], the cancer finally accomplished what the Nazis did not. . . . He was a tailor by trade and a scholar by inclination. Neither wealth nor fame ever came his way. He never married. He was short, almost elfin, and his trousers, held high by suspenders, seemed to swallow his body up to his chest. His smile could be magically disarming, but his head was crowded with ghosts and his eyes were pools of sadness. His mother, his sister and a brother had left the world as smoke in the air above [Auschwitz]. (Bearak, 1997, p. A19) In this chapter we report on a perspective on loss that supports the way Eugen Zuckermann lived his life, remembering and telling one's story. We Part of the research reported in this chapter was supported by a Fulbright Research Award for the study of loss among Romanian women to John H. Harvey.