Cancer of Unknown Primary

Chapter 34 Cancer of Unknown Primary

Epidemiology and Risk Factors

Worldwide, CUP is one of the 10 most frequent cancers constituting about 3% to 5% of all cancer cases.2 In 2011, according to the American Cancer Society, there were an estimated 30,500 cases of “Other & unspecified primary sites” in the United States or approximately 2% of all cancer cases and an estimated 44,260 deaths.2 At presentation, the median age is approximately 60 years and slightly more frequent in males.3

No risk factors have been identified for this heterogeneous group of neoplasms and no screening programs have been described.

Anatomy and Pathology

Because only carcinomas are included in the diagnosis of CUP, four main histologic types of CUP have been described: well to moderately differentiated adenocarcinomas (50%), undifferentiated or poorly differentiated carcinomas (30%), squamous cell carcinomas (15%), and undifferentiated neoplasms (5%). The latter group includes lymphomas, sarcomas, germ cell tumors, poorly differentiated carcinomas, neuroendocrine tumors, and embryonal malignancies that can be characterized by immunohistologichemistry.4 In children, CUPs represent less than 1% of solid tumors and the majority of these tumors are embryonal malignancies.2

Pathologic assessment is a must to characterize a CUP and is usually accomplished by histologic and cytopathologic evaluation. As an adjunct, electron microscopy is occasionally used to evaluate those CUPs that demonstrate indeterminate features that cannot be resolved with routine pathologic evaluation.

Serum tumor markers are mainly overexpressed glycoproteins that are released into the bloodstream by malignant tumors. The serum determination of these tumor markers can help to identify and diagnose, classify, and in patient follow-up, aid in assessment of response to therapy. However, these serum tumor markers have low sensitivity and low specificity, given that they are not expressed specifically by one organ.

The number of serum tumor markers is determined by the attending physician and include but are not limited to carcinoembryonic antigen (CEA), CA125, CA19-9, CDX2, CA15-3, CK-7, CK-20, thyroid transcription factor-1 (TTF-1), PSA, alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG), estrogen receptors, and gross cystic disease fluid protein-15 (GCDFP-15). Some of these serum tumor markers can have elevated levels in benign disease such as CEA in inflammatory bowel disease and CA19-9 in pancreatitis.

More recently, molecular techniques have been used to aid in the determination of the site of origin of these CUPs. Tissue microarrays and transcriptional profiling (reverse transcriptase polymerase chain reaction [RT-PCR]) are examples of the available molecular technologies. Some of these molecular assays are commercialized and available by several vendors.

The chromosomal and molecular abnormalities identified in CUPs are beyond the scope of this chapter.

Clinical Presentation

Patients with known primary malignancy have a neoplasm with a natural history and a predictable metastatic pattern that allows for staging. The opposite is true for CUPs, given that they are very aggressive and have an unpredictable metastatic pattern, and therefore, no formal staging can be made in certain patients.

The clinical presentation is due to the symptoms created by the rapid spread of metastases rather than the primary tumor. The presenting symptoms tend to be of short duration, and on physical examination, there may be visual and palpable masses. Constitutional symptoms can also be elicited during the initial evaluation.

These patients face a grim prognosis with reported survival rates of 6 to 10 months for those enrolled in clinical studies.2

However, those CUP patients not enrolled in clinical trials have reported life expectancies of 2 to 3 months.5 Given the diverse clinical presentation of these patients, it is best to classify them into favorable and unfavorable subsets, with the former having a better prognosis.6

The favorable subsets include

The unfavorable subsets are

To complicate the clinical presentation, more than 50% of CUP patients present with multiple sites of metastatic disease and approximately 30% have three or more organs involved with metastatic disease. In comparison, in patients with known primary tumors, fewer than 15% have metastatic disease in three or more sites.5,7,8

Mar 6, 2016 | Posted by in GENERAL RADIOLOGY | Comments Off on Cancer of Unknown Primary
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