Carcinoma of Unknown Primary

Physicians encounter patients with metastatic cancer frequently in practice. Although often, the etiology of the cancer and the impaired organ are obvious, occasionally the diagnosis of carcinoma of unknown primary is encountered. Because cancers tend to migrate to lymph nodes, a biopsy result of this type presumes metastatic cancer as, typically, this tissue diagnosis has come from a pathologic review of an identified abnormal lymph node. It is also possible that at the time of presentation of the abnormal lymph node, the primary tumor is still at a subclinical level, making diagnosis of the primary cancer even more difficult.

[Page 346]This biopsy result means one is unable to distinguish the primary site of the tumor, although it does imply there has been metastatic spread. Specific drainage patterns of the lymph system are known, so often the location of the abnormal lymph node can assist in diagnosing the etiology of the carcinoma. When a diagnostic biopsy demonstrates unknown primary tumor site with cervical lymphadenopathy, or enlarged lymph nodes in the neck area, it accounts for just under 5 percent of all head and neck cancers. The majority of patients with metastatic cervical lymphadenopathy often have squamous cell carcinoma or poorly differentiated carcinoma. Adenocarcinoma is rarely identified in a metastatic lymph node in the cervical region. When present, adenocarcinoma in the cervical lymph nodes can indicate a primary cancer found in the salivary glands, sinuses, thyroid, and parathyroid glands. More commonly, these histologically glandular primary cancers are located below the clavicles, including gastrointestinal tract, lung, and breast.

The diagnostic evaluation of a patient with an unknown primary tumor includes a complete history and physical examination. A specific history of tobacco, alcohol, sun exposure, occupational exposure should be obtained, as they are also known risk factors for certain types of cancer. Chronic unintentional weight loss, fever of unknown origin, chronic cough, or localized pain to any area of the body may help with the diagnosis and search of the etiology of the cancer.

In addition, a chest radiograph should be obtained, as well as a computed tomography (CT) scan, and possibly additional plain radiographs, depending upon the location of the abnormal lymph node. Recently, positron-emission tomography (PET) scans have been considered as an adjunct in the evaluation of carcinoma of unknown primary. Theoretically, tumor cells have a higher metabolic rate than normal tissue, which suggests abnormal cells accumulate more of the tracer used in a PET scan. This uptake or “hot spot” may help locate the primary malignant site. Unfortunately, there are limits to PET scans. Lesions smaller that one centimeter may be too small for the resolution of certain PET scan machines and may be missed. In addition, certain tumors do not uptake the tracer consistently, while other tissues in the body may absorb the tracer, as seen in inflammation or normal tissues such as the kidney and bladder. At this point, PET scanning is not considered standard of care for screening, because it is neither reliable nor cost effective.

Blood tests are an additional piece of the diagnostic process. Depending upon coexisting medical problems, it is reasonable to obtain a complete blood count, electrolyte panel, and assessments of liver function and kidney function. Hemoccult testing of stool should be considered and prostate-specific antigen (PSA) should be obtained in male patients, as well as consideration for serum tumor markers. Although certain tumor markers are helpful in monitoring response to therapy and relapse, they are not useful in the general population for screening, due to insufficient sensitivity and specificity. However, in the situation of carcinoma of unknown primary, they should be considered.

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