Madam, Carcinoma of unknown primary site (CUP) is defined as the presence of metastatic cancer documented in the absence of identifiable primary tumour site. The criteria for CUP diagnosis includes a biopsy proved malignancy (for a cancer that could not have originated at the biopsy site), no primary tumour found after a thorough examination and normal laboratory tests including complete blood count, blood chemistry, chest x-ray, computer tomography (CT) scan of the chest, abdomen and pelvis, and mammography or prostate specific antigen test. It accounts for 3% and 5% of all cancer cases.^1,2
A number of theories exist to explain CUP. It is possible that the primary cancer is microscopic; however its metastasis is able to proliferate into a more significant tumour in different tissues. It is also possible that in some cases the primary lesion metastasized before undergoing necrosis because of angiogenic incompetence. According to 2003 Surveillance, Epidemiology and End result date 30,000 new cancers of "other and unspecified primary sites" were diagnosed in USA, approximately the same number as the number of new pancreatic cancer reported.
Patients should have a recent colonoscopy with verification that the endoscope reached the caecum. An upper endoscopy is warranted if there is suspicion of an esophageal or gastric tumour. The classical evaluation for CUP presenting as cervical lymphadenopathy is panendoscopy supplemented by imaging studies (including CT and/or MRI). PET scan can be a valuable tool to identify the primary occult tumour particularly if the initial evaluation by CT chest, abdomen and pelvis is inconclusive. The PET-CT fusion allows the physiological details of the nuclear medicine study to be fused onto the anatomical details of the CT imaging. A negatives study, however, cannot rule out presence of a primary.
As a group, such patients have historically poor median survival duration of 3 to 4 months, with fewer than 10% alive at 5 years.³ It is now widely believed that for patients with disseminated disease, poorly differentiated carcinoma or poorly differentiated adenocarcinoma and no strong indications of primary site Cisplatin-Based combination chemotherapy is the preferred treatment.⁴
The absence of primary tumour generates anxiety for both patients and physicians. It is often felt that the prognosis would be improved if a primary tumour could be identified; this frequently leads to an exhaustive and often fruitless diagnostic search. With the increasing number of new diagnostic modalities, physicians must determine how much diagnostic workup is sufficient before accepting a diagnosis of CUP. One should also consider whether a more precise diagnosis would have a substantial effect on the choice of treatment and overall outcome.
 
Mian Muhammad Rizwan, Maria Zulfiqar
Department of Internal Medicine, Prince George\'s Hospital,
3001 Hospital Drive, Cheverly, MD 20785.

1.Dowell JE. Cancer from an unknown primary site. Am J Med Sci 2003; 326: 35-46.
2.Van de Wouw AJ, Janssen-Haijnen ML, Coeberg JW, Hillen HF. Epidemiology of unknown primary tumours; incidence and population-based survival of 1285 patients in Southeast Netherlands, 1984-1992. Eur J Cancer 2002; 38: 409-13.
3.Holmes FF, Fouts TL. Metastatic cancer of unknown primary site. Cancer 1970; 26: 816-20.
4.Hainsworth JD, Johnson DH, Greco FA. Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: result of a 12-year experience. J Clin Oncol 1992; 10: 912-22.