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. With the exception of ovarian cancer, however, CT scans rarely identify treatable primary cancers.[2,3]
There are several types of plasma cell neoplasms. These diseases are all associated with a monoclonal (or myeloma) protein (M protein). They include monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, extramedullary plasmacytoma, and multiple myeloma.
(Refer to the Lymphoplasmacytic Lymphoma (Waldenström Macroglobulinemia) section in the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information.)
Incidence and Mortality
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]