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Stage Information for Carcinoma of Unknown Primary

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    Poorly Differentiated Carcinomas

    Investigators have defined a subpopulation of potentially curable patients with 1 or more of the following characteristics:

    • Age younger than 50 years.
    • Midline tumor distribution, multiple pulmonary nodules or lymph nodes, elevated serum levels of beta human chorionic gonadotropins (HCG) or alpha-fetoprotein (AFP).
    • Cells positive for beta HCG or AFP by immunohistochemical stain.
    • The presence of neuroendocrine granules.
    • Clinical evidence for rapid tumor growth.
    • Tumors that were very responsive to chemotherapy or radiation therapy.

    In retrospective review, many of these patients, including some complete responders to chemotherapy, did not have any recognizable histopathologic features of germ cell tumors.[13,14,15] A single study has shown that the i(12p) marker chromosome may be used as a diagnostic tool in patients with suspected midline germ cell tumors.[16]

    Metastatic Melanoma to a Single Nodal Site

    Approximately 5% of patients with malignant melanoma will present without a documented primary site. Special stains and electron microscopy may be important in establishing the diagnosis. Patients with this diagnosis should, like those with stage II melanoma, have a radical lymph node dissection. Survival is actually slightly better than that seen in patients with stage II melanoma with a documented primary site.[5,17,18,19] (Refer to the PDQ summary on Melanoma Treatment for more information.)

    Isolated Axillary Metastasis

    Most patients who present with nodal metastasis above the diaphragm ultimately are documented to have lung cancer, the most common supradiaphragmatic primary malignancy. The presence of isolated axillary metastasis in females, however, raises another possibility. A few studies involving a small number of patients have shown that approximately 50% of patients who present with isolated axillary metastasis of an adenocarcinoma will ultimately be shown to have breast cancer. Although some of these patients will have a positive mammogram after the initial evaluation, approximately 50% of the patients will not. When these patients are treated with local excision, or as having primary breast cancer, 2- to 10-year survival has been obtained in approximately 50% of patients. The availability of estrogen-receptor (ER) and progesterone-receptor (PR) assays may aid in this diagnosis, and these studies should be performed in this setting. If the clinical setting is consistent with breast cancer, and ER and/or PR levels are elevated, CUP with this distribution should be treated as breast cancer.[1,4,20] (Refer to the PDQ summary on Breast Cancer Treatment for more information.)

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