title: Carcinoma of Unknown Primary - an Orphan Disease?
abstract: Carcinoma of unknown primary (CUP) is an intriguing clinical finding that is defined as biopsy-proven metastasis from a malignancy in the absence of an identifiable primary site after a complete clinical work-up. CUP is a relatively common clinical entity, accounting for approximately 3-5% of all cancer diagnoses, and consists of a heterogeneous group of tumors that have acquired the capacity to metastasize before the development of a clinically evident primary lesion. Notable advances have been made over the past years in the treatment of well-defined clinical subgroups of CUP, such as women with peritoneal carcinomatosis and young adults with poorly differentiated carcinomas of midline distribution, but for the majority of patients, the prognosis still remains poor. In this review, we highlight recent advances in the diagnosis and treatment of patients with CUP syndrome, and emphasize the importance of identifying several favorable subsets of CUP, amenable to specific treatment options. In addition, we will point out novel diagnostic and therapeutic approaches which will hopefully improve both our understanding and the prognosis of this more or less neglected disease.
authors.affiliation: Klinische Kooperationseinheit für Molekulare Hämatologie und Onkologie des Deutsches Krebsforschungszentrums und der Medizinischen Klinik und Poliklinik V der Universität Heidelberg, Germany.
authors.forename: Alwin
authors.initials: A
authors.lastname: Krämer
authors.forename: Gerdt
authors.initials: G
authors.lastname: Hübner
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Gunnar
authors.initials: G
authors.lastname: Folprecht
authors.forename: Kai
authors.initials: K
authors.lastname: Neben
references.citation: Arch Intern Med. 1988 Sep;148(9):2035-9
references.pmid: 3046543
references.citation: Anticancer Res. 2004 Jan-Feb;24(1):297-301
references.pmid: 15015611
references.citation: Cancer Invest. 2001;19(4):335-9
references.pmid: 11405172
references.citation: Cancer. 1986 Jan 1;57(1):120-4
references.pmid: 3940611
references.citation: Eur J Nucl Med Mol Imaging. 2002 Aug;29(8):1024-30
references.pmid: 12173016
references.citation: Oncology. 1998 Mar-Apr;55(2):116-21
references.pmid: 9499185
references.citation: Radiother Oncol. 1989 Aug;15(4):321-5
references.pmid: 2552505
references.citation: Eur Radiol. 1999;9(3):470-3
references.pmid: 10087118
references.citation: Cancer. 2006 Dec 15;107(12):2898-905
references.pmid: 17109447
references.citation: Cancer. 1998 Nov 15;83(10):2181-4
references.pmid: 9827723
references.citation: Br J Cancer. 2003 Aug;89 Suppl 1:S59-66
references.pmid: 12915904
references.citation: Eur J Cancer. 2003 May;39(8):1121-8
references.pmid: 12736112
references.citation: J Clin Oncol. 2002 Dec 15;20(24):4679-83
references.pmid: 12488413
references.citation: Med Pediatr Oncol. 1982;10(6):569-74
references.pmid: 7177043
references.citation: Eur J Cancer. 2002 Feb;38(3):409-13
references.pmid: 11818207
references.citation: Am Surg. 1998 Sep;64(9):906-8
references.pmid: 9731824
references.citation: J Clin Oncol. 1995 Aug;13(8):2094-103
references.pmid: 7636553
references.citation: Cancer. 1998 Mar 15;82(6):1160-6
references.pmid: 9506364
references.citation: J Clin Oncol. 2005 May 10;23(14):3235-42
references.pmid: 15886311
references.citation: Cancer. 2000 Dec 15;89(12):2655-60
references.pmid: 11135228
references.citation: Cancer. 1992 Jul 15;70(2):504-8
references.pmid: 1617600
references.citation: Ann Oncol. 2000 Feb;11(2):211-5
references.pmid: 10761758
references.citation: Tumori. 1993 Oct 31;79(5):321-4
references.pmid: 8116074
references.citation: J Clin Oncol. 2002 Mar 15;20(6):1651-6
references.pmid: 11896116
references.citation: Semin Oncol. 1977 Mar;4(1):53-8
references.pmid: 841350
references.citation: J Clin Oncol. 2006 Aug 1;24(22):3548-54
references.pmid: 16877720
references.citation: J Clin Oncol. 2007 Jun 1;25(16):2171-7
references.pmid: 17538161
references.citation: Cancer J. 2001 May-Jun;7(3):203-12
references.pmid: 11419028
references.citation: Am Surg. 1995 May;61(5):431-4
references.pmid: 7733550
references.citation: Br J Cancer. 2007 Oct 8;97(7):857-61
references.pmid: 17876336
references.citation: Hum Pathol. 1990 May;21(5):518-23
references.pmid: 2338331
references.citation: Eur J Cancer. 2002 Sep;38(13):1810-2
references.pmid: 12175699
references.citation: J Clin Oncol. 1986 Mar;4(3):395-9
references.pmid: 3754004
references.citation: J Neurooncol. 1995;23(1):75-80
references.pmid: 7623072
references.citation: J Clin Oncol. 1994 Jun;12(6):1272-80
references.pmid: 8201389
references.citation: Cancer. 1970 Oct;26(4):816-20
references.pmid: 5506606
references.citation: Clin Cancer Res. 2007 Aug 1;13(15 Pt 2):s4602-5
references.pmid: 17671149
references.citation: Am J Clin Oncol. 1987 Feb;10(1):82-5
references.pmid: 3548315
references.citation: Ann Surg Oncol. 2001 Jun;8(5):425-31
references.pmid: 11407517
references.citation: Cancer. 1995 Jan 1;75(1 Suppl):353-6
references.pmid: 8001006
references.citation: Br J Surg. 1993 Oct;80(10):1299-300
references.pmid: 8242304
references.citation: Eur J Cancer. 2003 Sep;39(14):1990-2005
references.pmid: 12957453
references.citation: Cancer. 2005 Nov 1;104(9):1992-7
references.pmid: 16130138
references.citation: J Nucl Med. 2000 May;41(5):816-22
references.pmid: 10809197
references.citation: Ann Oncol. 2001 Nov;12(11):1605-9
references.pmid: 11822762
references.citation: Pathologe. 2002 May;23(3):183-97
references.pmid: 12089786
references.citation: Cancer. 2001 Feb 1;91(3):592-7
references.pmid: 11169943
references.citation: N Engl J Med. 1980 Jul 10;303(2):87-9
references.pmid: 6991941
references.citation: Cancer. 1987 Feb 1;59(3):572-7
references.pmid: 3791166
references.citation: Clin Cancer Res. 1999 Nov;5(11):3403-10
references.pmid: 10589751
references.citation: Cancer. 2007 Jan 15;109(2):292-9
references.pmid: 17167760
references.citation: Cancer. 1987 Mar 15;59(6):1170-2
references.pmid: 3815292
references.citation: N Engl J Med. 1996 Jan 4;334(1):1-6
references.pmid: 7494563
references.citation: N Engl J Med. 2004 Jul 22;351(4):337-45
references.pmid: 15269313
references.citation: Cancer. 1972 Dec;30(6):1469-72
references.pmid: 4641758
references.citation: Ann Intern Med. 1988 Sep 1;109(5):364-71
references.pmid: 2841895
references.citation: Ann Surg. 1977 Nov;186(5):625-30
references.pmid: 921356
references.citation: J Clin Oncol. 2003 Sep 15;21(18):3479-82
references.pmid: 12972523
references.citation: J Clin Oncol. 1997 Jun;15(6):2385-93
references.pmid: 9196154
references.citation: J Clin Oncol. 2007 May 1;25(13):1747-52
references.pmid: 17470864
references.citation: Eur J Cancer Clin Oncol. 1987 Nov;23(11):1645-8
references.pmid: 2448145
references.citation: Arch Surg. 1982 Sep;117(9):1136-8
references.pmid: 7115059
references.citation: Curr Probl Cancer. 1979 Nov;4(5):4-37
references.pmid: 391494