Skip to Main Content


Cancer of unknown primary site (CUPS) is defined as follows: biopsy-proven malignancy; primary site unapparent after history, physical examination, chest x-ray, abdominal and pelvic CT, complete blood count, chemistry survey, mammography (women), β-human chorionic gonadotropin (hCG) levels (men), α-fetoprotein (AFP) levels (men), and prostate-specific antigen (PSA) levels (men); and histologic evaluation not consistent with a primary tumor at the biopsy site. About 90% of CUPS tumors are adenocarcinomas (60% well or moderately–well differentiated; 30% poorly differentiated), 5% squamous cell, 2% neuroendocrine, and 3% undifferentiated malignancy. CUPS incidence is declining, probably because of better pathology diagnostic criteria; it accounts for about 3% of all cancers today, down from 10–15% 15 years ago. Most pts are age >60. The tumors are often aneuploid. Cell lines derived from such tumors frequently have abnormalities in chromosome 1.


Pts may present with fatigue, weight loss, pain, bleeding, abdominal swelling, subcutaneous masses, and lymphadenopathy. Once metastatic malignancy is confirmed, diagnostic efforts should be confined to evaluating the presence of potentially curable tumors, such as lymphoma, Hodgkin’s disease, germ cell tumor, ovarian cancer, head and neck cancer, and primitive neuroectodermal tumor, or tumors for which therapy may be of significant palliative value such as breast cancer or prostate cancer. In general, efforts to evaluate the presence of these tumor types depend more on the pathologist than on expensive clinical diagnostic testing. Localizing symptoms, a history of carcinogen exposure, or a history of fulguration of skin lesion may direct some clinical testing; however, the careful light microscopic, ultrastructural, immunologic, karyotypic, and molecular biologic examination of adequate volumes of tumor tissue is the most important feature of the diagnostic workup in the absence of suspicious findings on history and physical examination. Immunohistochemical stains can be useful (Table 77-1).

TABLE 77-1Select Immunohistochemical Stains Useful in the Diagnosis of CUPS

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.