Carcinoma of Unknown Primary

  • Gi-Jeong Cheon


Carcinoma of unknown primary (CUP) represents the group of heterogeneous tumors, which can be defined as the presence of histologically proven metastatic disease and unidentified site of origin at the time of diagnosis in spite of comprehensive diagnostic workup (Pavlidis, Acta Oncol 46:592–601, 2007). CUP tumors are not infrequently encountered in oncologic practice. The incidence of CUP tumors in oncologic patients is 0.5–7% at the time of the initial diagnosis (Abbruzzese et al. J Clin Oncol 12:1272–80, 1994; Daugaard, Cancer Treat Rev 20:119–47, 1994) and its prevalence is between 3% and 15% (Abbruzzese et al. J Clin Oncol 13:2094–103, 1995). Frequent first settings for the metastatic lesions are lymph nodes (37%); of these, 31% are located in the head and neck region, which is the most common site for metastases of unknown origin (Lefebvre et al. Am J Surg 160:443–6, 1990; Scheidhauer et al. PET in clinical oncology, 2000, pp. 169–76). CUP tumors present metastatic dissemination patterns that are different from those observed in oncologic conditions with known primary tumors: (1) Short symptomatic prediagnostic interval exists before the clinical presentation; (2) CUP tumor becomes symptomatic at the time of metastatic disseminations; (3) the most frequent primary sites in patients with CUP tumors do not include the several most common primary tumors in the general population; (4) no specific metastatic location has been consistently associated with a specific primary tumor site (Leinard and Nystrom, Semin Oncol 20:244–50, 1993). These aspects make it difficult to locate the primary tumor, which is one of the most important factors for establishing the most effective treatment (Delgado-Bolton et al. J Nucl Med 44:1301–14, 2003).


Positron Emission Tomography Unknown Primary Tumor Conventional Diagnostic Procedure Frequent Primary Site Curable Tumor Node Metastasis 
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  1. 1.
    Pavlidis N. Forty years experience of treating cancer of unknown primary. Acta Oncol. 2007;46:592–601.PubMedCrossRefGoogle Scholar
  2. 2.
    Abbruzzese JL, Abbruzzese MC, Hess KR, et al. Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. J Clin Oncol. 1994;12:1272–80.PubMedGoogle Scholar
  3. 3.
    Daugaard G. Unknown primary tumours. Cancer Treat Rev. 1994;20:119–47.PubMedCrossRefGoogle Scholar
  4. 4.
    Abbruzzese JL, Abbruzzese MC, Lenzi R, et al. Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin. J Clin Oncol. 1995;13:2094–103.PubMedGoogle Scholar
  5. 5.
    Lefebvre JL, Coche-Dequent B, Van Ton J, et al. Cervical lymph nodes from unknown primary tumors in 190 patients. Am J Surg. 1990;160:443–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Scheidhauer K, Avril N, Bonkowsky VM. Carcinoma of unknown primary. In: Wieler HJ, Coleman RE, editors. PET in clinical oncology. Heidelberg: Springer; 2000. p. 169–76.CrossRefGoogle Scholar
  7. 7.
    Leinard RJ, Nystrom JS. Diagnostic evaluation of patients with carcinoma of unknown primary tumor site. Semin Oncol. 1993;20:244–50.Google Scholar
  8. 8.
    Delgado-Bolton RC, Fernandez-Perez C, Gonzalez-Mate A, et al. Meta-analysis of the performance of 18  F-FDG PET in primary tumor detection in unknown primary tumors. J Nucl Med. 2003;44:1301–14.PubMedGoogle Scholar
  9. 9.
    Altman E, Cadmann E. An analysis of 1539 patients with cancer of unknown primary site. Cancer. 1986;57:120–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Smith PE, Krements ET, Chapman W. Metastatic cancer without a detectable primary site. Am J Surg. 1967;113:633–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Raber MN, Faintuch J, Abbruzzese JL, et al. Continuous infusion of 5-fluorouracil, etoposide, and cisplatin in patients with metastatic carcinoma of unknown primary origin. Ann Oncol. 1991;2:519–20.PubMedGoogle Scholar
  12. 12.
    Dong M, Zhao K, Lin X, et al. Role of fluorodeoxyglucose-PET versus fluorodeoyglucose PET/computed tomography in detection of unknown primary tumor: a meta-analysis of the literature. Nucl Med Commun. 2008;29:791–802.PubMedGoogle Scholar
  13. 13.
    Endo K, Oriuchi N, Higuchi T, et al. PET and PET/CT using 18F-FDG in the diagnosis and management of cancer patients. Int J Clin Oncol. 2006;11:286–96.PubMedCrossRefGoogle Scholar
  14. 14.
    Branstetter BF, Blodgett TM, Brun T, et al. Head and neck malignancy: is PET/CT more accurate than PET or CT alone? Radiology. 2005;235:580–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Syed R, Bomanji JB, Nagabhushan N, et al. Impact of combined 18F-FDG PET/CT in head and neck tumors. Br J Cancer. 2005;92:1046–50.PubMedCrossRefGoogle Scholar
  16. 16.
    Leonard RJ, Nystrom JS. Diagnostic evaluation of patients with carcinoma of unknown primary site. Semin Oncol. 1993;20:244–50.PubMedGoogle Scholar
  17. 17.
    Van der Brekel MPM, Castelijins JA, Steel H, et al. Modern imaging techniques and ultrasound-guided aspiration cytology for the assessment of neck node metastasis A prospective comparative study. Eur Arch Otorhinolaryngol. 1993;250:11–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Wang RC, Goepfert H, Barber AE, et al. Unknown primary squamous cell carcinoma metastatic to the neck. Arch Otolaryngol Head Neck Surg. 1990;116:1388–93.PubMedCrossRefGoogle Scholar
  19. 19.
    Hainsworth JD, Wright EP, Johnson DH, et al. Poorly differentiated carcinoma of unknown primary site: clinical usefulness of immunoperoxidase staining. J Clin Oncol. 1991;9(11):1931–8.PubMedGoogle Scholar
  20. 20.
    Panza N, Lombardi G, Rosa M, et al. High serum ­thyroglobulin levels, diagnostic indicators in patients with unknown primary sites. Cancer. 1987;60:2233–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Rege S, Maass A, Chaiken L, et al. Use of positron emission tomography with fluorodeoxyglucose in patients with extracranial head and neck cancers. Cancer. 1994;73:3047–58.PubMedCrossRefGoogle Scholar
  22. 22.
    Bohuslavizki KH, Klutmann S, Kroger S, et al. FDG PET detection of unknown primary tumors. J Nucl Med. 2000;41:816–22.PubMedGoogle Scholar
  23. 23.
    Lassen U, Daugaard G, Eigtved A, et al. 18F-FDG whole body positron emission tomography (PET) in patients with unknown primary tumors (UPT). Eur J Cancer. 1999;35:1076–82.PubMedCrossRefGoogle Scholar
  24. 24.
    Kwee TC, Kwee RM. Combined FDG-PET/CT for the detection of unknown primary tumors: systemic review and meta-analysis. Eur Radiol. 2009;19:731–44.PubMedCrossRefGoogle Scholar
  25. 25.
    Fencl P, Belohlavek O, Skopalova M, et al. Prognostic and diagnostic accuracy of [18F]FDG-PET/CT in 190 patients with carcinoma of unknown primary. Eur J Nucl Med Mol Imaging. 2007;34:1783–92.PubMedCrossRefGoogle Scholar
  26. 26.
    Nassenstein K, Veit-Haibach P, Stergar H, et al. Cervical lymph node metastases of unknown origin: primary tumor detection with whole-body positron emission tomography/computed tomography. Acta Radiol. 2007;23:1–8.Google Scholar
  27. 27.
    Fleming AJ, Smith SP, Paul CM, et al. Impact of [18F]-2-fluorodeoxyglucose-positron emission tomography/computed tomography on previously untreated head and neck cancer patients. Laryngoscope. 2007;117: 1173–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Bruna C, Journo A, Netter F, et al. On the interest of PET with 18FFDG in the management of cancer of unknown primary (CUP). Med Nucl. 2007;31:242–9.Google Scholar
  29. 29.
    Wartski M, Le Stanc E, Gontier E, et al. In search of an unknown primary tumor presenting with cervical metastases: performance of hybrid FDG-PET-CT. Nucl Med Commun. 2007;28:365–71.PubMedCrossRefGoogle Scholar
  30. 30.
    Ambrosini V, Nanni C, Rubello D, et al. 18F-FDG PET/CT in the assessment of carcinoma of unknown primary origin. Radiol Med. 2006;111:1146–55.PubMedCrossRefGoogle Scholar
  31. 31.
    Fakhry N, Barberet M, Lussato D, et al. Role of [18F]-FDG PET-CT in the management of the head and neck cancers. Bull Cancer. 2006;93:1017–25.PubMedGoogle Scholar
  32. 32.
    Pelosi E, Pennone M, Deandreis D, et al. Role of whole body positron emission tomography/computed tomography scan with 18F-fluorodeoxyglucose in patients with biopsy proven tumor metastases from unknown primary site. Q J Nucl Med Mol Imaging. 2006;50:15–22.PubMedGoogle Scholar
  33. 33.
    Nanni C, Rubello D, Castellucci P, et al. Role of 18F-FDG PET-CT imaging for the detection of an unknown primary tumor: preliminary results in 21 patients. Eur J Nucl Med Mol Imaging. 2005;32:589–92.PubMedCrossRefGoogle Scholar
  34. 34.
    Freudenberg LS, Fischer M, Antoch G, et al. Dual modality of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with cervical carcinoma of unknown primary. Med Princ Pract. 2005;14:155–60.PubMedCrossRefGoogle Scholar
  35. 35.
    Gutzeit A, Antoch G, Kühl H, et al. Unknown primary tumors: detection with dual-modality PET/CT – initial experience. Radiology. 2005;234:227–34.PubMedCrossRefGoogle Scholar
  36. 36.
    Seve P, Billotey C, Broussolle C, et al. The role of 2-deoxy-2-[F-18]fluoro-d-glucose positron emission tomography in disseminated carcinoma of unknown primary site. Cancer. 2007;106:292–9.CrossRefGoogle Scholar
  37. 37.
    Kole A, Niewey O, Bruim J, et al. Detection of known occult primary tumors using position emission tomography. Cancer. 1998;82:1160–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Kolesnikov-Gauthier H, Levy E, Merlet P, et al. FDG PET in patients with cancer of an unknown primary. Nucl Med Commun. 2005;26:1059–66.PubMedCrossRefGoogle Scholar
  39. 39.
    Lonneux M, Reffad A. Metastases from unknown primary tumor. PET-FDG as initial diagnostic procedure? Clin Positron Imaging. 2000;3:137–41.PubMedCrossRefGoogle Scholar
  40. 40.
    Mantaka P, Baum RP, Hertel A, et al. PET with 2-[F-18]- fluoro-2-deoxy-d-glucose (FDG) in patients with cancer of unknown primary (CUP): influence on patients’ diagnostic and therapeutic management. Cancer Biother Radiopharm. 2003;18:47–58.PubMedCrossRefGoogle Scholar
  41. 41.
    Scott CL, Kudaba I, Stewart JM, Hicks RJ, Rischin D. The utility of 2-deoxy-2-[F-18]fluoro-d-glucose positron emission tomography in the investigation of patients with disseminated carcinoma of unknown primary origin. Mol Imaging Biol. 2005;7:236–43.PubMedCrossRefGoogle Scholar
  42. 42.
    Ambrosini V, Tomassetti P, Rubello D, et al. Role of 18F-dopa PET/CT imaging in the management of patients with 111In-pentetreotide negative GEP tumors. Nucl Med Commun. 2007;28:473–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Prasad V, Ambrosini V, Hommann M, et al. Detection of unknown primary neuroendocrine tumours (CUP-NET) using 68Ge-DOTA-NOC receptor PET/CT. Europ J Nucl Med Mol Imag. 2010;37:67–77. doi: 10.1007/s00259-009-1205-y.
  44. 44.
    Ambrosini V, Tomassetti P, Castellucci P, et al. Comparison between 68Ge-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours. Eur J Nucl Med Mol Imaging. 2008;35:1431–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Fleming AJ, Johansen ME. The clinician’s expectations from the use of positron emission tomography/computed tomography scanning in untreated and treated head and neck cancer patients. Curr Opin Otolaryngol Head Neck Surg. 2008;16:127–34.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Nuclear Medicine, Korea Cancer Center HospitalSeoulSouth Korea

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