Southwestern Internal Medicine Conference
Cancer from an Unknown Primary Site

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ABSTRACT

Cancer from an unknown primary site (CUP) is frequently encountered in clinical practice. This review is designed to help physicians identify those patients with CUP that benefit from specific therapeutic approaches. The utility of pathologic and diagnostic tests in patients with CUP will also be discussed, as will the prognosis and appropriate treatment of these patients.

Section snippets

Biology of CUP

Although CUP represents a heterogeneous group of malignancies, the presence of early metastasis that defines this entity suggests that these tumors may share unique biological features. Specifically, CUP may represent a useful model for understanding the biology of early tumor invasion and distant spread. In fact, surprisingly little is known about the biology of these tumors. Investigators at the M.D. Anderson Cancer Center attempted to identify the cytogenetic changes present in a series of

Pathology

CUP represents a heterogeneous collection of tumor types and clinical presentations. Although it is commonly believed to include only carcinomas, poorly differentiated tumors of unclear origin also fall into this group. With sophisticated pathological evaluation, these tumors may be shown to not be epithelial. Correct identification of certain histologies, such as lymphomas and some chemosensitive sarcomas, may permit prolonged patient survival because of appropriate therapy. Therefore, a

Treatable Subsets of CUP

After a careful review by pathology to exclude treatable histologies such as lymphoma, the vast majority of patients with CUP will be given a diagnosis of carcinoma. The next step in these patients’ evaluation should be to determine whether they fall into 1 of the following treatable subsets of patients with carcinoma from an unknown primary site.

Clinical Evaluation

As discussed above, patients that fall into a treatable subset of CUP may benefit from specific diagnostic and clinical examinations. For the remainder of patients, what constitutes an appropriate clinical evaluation has been debated for many years. The natural inclination for many patients and physicians is that an extensive search for a primary site should be undertaken. The rationale for this approach is 3-fold. 90 The absence of a primary generates anxiety in both patients and their

Conclusions

Patients with CUP are frequently encountered in everyday practice, with between 20,000 and 50,000 new cases diagnosed in the United States each year. Improvements in molecular diagnostics may soon significantly reduce this number; until then, physicians should familiarize themselves with this entity. Approximately 5 to 10% of patients with CUP may benefit from a specific treatment approach. Close communication between the pathologist and the primary physician is critical to insure that a

Acknowledgements

Special thanks to Kristi Willis for her invaluable assistance with the preparation of the manuscript.

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