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Stage Information for Carcinoma of Unknown Primary

Opinions are divergent concerning the value and extent of evaluation that should be performed to determine the primary tumor in patients who present with carcinoma of unknown primary (CUP). Clinical and pathological investigations to detect tumors that are potentially responsive to treatment (e.g., lymphoma, germ cell tumor, breast, or ovarian tumor) may be undertaken.

The chest radiograph has become an almost routine procedure in general medical practice. Although chest radiography is routinely performed, in the setting of CUP no distinguishing feature clearly separates primary from metastatic disease within the chest. The abdominal computed tomographic (CT) scan is the only radiographic test that may frequently be of value in defining the primary site, because of the inordinately high representation of pancreatic cancer in the CUP process.[1] With the exception of ovarian cancer, however, CT scans rarely identify treatable primary cancers.[2,3]

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The clinical biology of the disease, the types of tumors most often encountered, and the high level of inaccuracy of unguided radiographic studies raise issues of cost effectiveness for intensive diagnostic work-up. Two studies have indicated that a large negative cost/benefit ratio exists for an extensive unguided clinical evaluation, with a single study citing a 9.5% increase in 1-year survival at a cost of 2 to 8 million dollars. The most reasonable approach is to develop a comprehensive knowledge of the manner in which CUP patients present and to remember that this presentation is associated with tremendous heterogeneity regarding outcome.[4,5,6,7,8,9]

Cervical Lymph Nodes

A histologic diagnosis of metastatic carcinoma in cervical nodes requires a meticulous examination of the upper aerorespiratory tract. Histologically, these tumors are usually squamous cell carcinoma, but occasionally may be adenocarcinoma, melanoma, or anaplastic tumors. Metastatic adenocarcinoma is generally associated with a poor prognosis. Approximately 2% to 5% of patients with primary squamous cell carcinoma of the head and neck region will present with cervical adenopathy as the primary disease manifestation; about 10% of this group will present with bilateral adenopathy. The 3-year survival rate ranges from 35% to 59% when patients with squamous or undifferentiated tumors are treated with radical radiation therapy, surgery, or both.[10,11,12]

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]

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