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| {{SI}}
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| {{CMG}} {{AE}} {{RAK}}{{MV}}
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| {{SK}} Occult cancer; CUP; Metastases of unknown primary origin; Unknown primary origin neoplasm; Cancers of unknown primary site; Neoplasms of unknown primary site; Carcinoma of unknown primary; Cancer of unknown origin; Unknown primary tumors; UPT
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| ==Overview==
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| '''Cancer of unknown primary origin''' or CUP is the diagnosis of metastatic cancer when the anatomic site of origin remains unidentified. Cancer of unknown primary origin is common, and it accounts for 2–5% of all cancers. Cancer of unknown primary origin may be classified according to pathology findings into 5 groups: well and moderately differentiated adenocarcinomas, poorly differentiated carcinomas, squamous cell carcinomas, undifferentiated neoplasms, and carcinomas with neuroendocrine differentiation. The majority of patients with cancer of unknown primary origin may be initially asymptomatic. Early clinical features include [[fatigue]], [[weight-loss]], and [[loss of appetite]]. If left untreated, the majority of patients with cancer of unknown primary origin may progress to develop multiple organ failure, heart failure, and death. Common complications of cancer of unknown primary origin, may include: [[hypercalcemia]], [[adrenal insufficiency]], [[Syndrome of inappropriate antidiuretic hormone|inappropriate antidiuretic syndrome]], [[Hematological malignancy|hematologic disorders]], and [[Pleural effusion|malignant effusions]].<ref name="pmid10697020">{{cite journal |vauthors=Nelson KA, Walsh D, Abdullah O, McDonnell F, Homsi J, Komurcu S, LeGrand SB, Zhukovsky DS |title=Common complications of advanced cancer |journal=Semin. Oncol. |volume=27 |issue=1 |pages=34–44 |year=2000 |pmid=10697020 |doi= |url=}}</ref> The treatment for cancer of unknown primary origin will depend on several factors, such as: metastatic origin, biopsy findings, patients age, and performance status. The 5-year survival of patients with cancer of unknown primary origin is of less than 2%.
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| ==Historical Perspective==
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| *Cancer of unknown primary origin was first described in 1980.
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| *From 1980 to 1990, the definition of unknown primary cancer was based on imaging results.<ref name="pmid25140961">{{cite journal| author=Varadhachary GR, Raber MN| title=Cancer of unknown primary site. | journal=N Engl J Med | year= 2014 | volume= 371 | issue= 8 | pages= 757-65 | pmid=25140961 | doi=10.1056/NEJMra1303917 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25140961 }} </ref>
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| ==Classification==
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| *Cancer of unknown primary origin may be classified into 4 groups initially according to light microscopy of the biopsy:<ref name="pmid19262901">{{cite journal |vauthors=Varadhachary GR |title=Carcinoma of unknown primary origin |journal=Gastrointest Cancer Res |volume=1 |issue=6 |pages=229–35 |year=2007 |pmid=19262901 |pmc=2631214 |doi= |url=}}</ref>
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| :*Adenocarcinomas
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| :*Squamous cell carcinomas
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| :*Poorly differentiated tumors
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| :*Carcinomas with neuroendocrine differentiation
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| ==Pathophysiology==
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| *The exact pathogenesis of cancer of unknown primary origin is not fully understood.
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| *Cancer of unknown primary, like other cancers, arises from one cell that has managed to escape regulation and produces a tumor at a certain site (the site of origin) and consequently metastasizes to other parts of the body.
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| *It is thought that the site of origin of CUP remains unknown due to one of the following theories:<ref name="pmid19262901" />
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| **Remaining small and undetectable clinically
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| **Disappearing after metastasizing
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| **Elimination by body's defense
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| * It remains unknown whether cancers of unknown primaries are genetically or phenotypically distinct from metastasis with known origins.<ref name="pmid19262901">{{cite journal |vauthors=Varadhachary GR |title=Carcinoma of unknown primary origin |journal=Gastrointest Cancer Res |volume=1 |issue=6 |pages=229–35 |year=2007 |pmid=19262901 |pmc=2631214 |doi= |url=}}</ref>
| | {{Cancer of unknown primary origin}} |
| | | {{CMG}}; {{AE}} {{RAK}}, {{MV}} |
| ==Causes==
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| *The cause of CUP has not been identified.
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| *Several studies have evaluated the chromosomal and molecular anomalies found in cancers of unknown primary; however, they could not identify unique causes of metastasis of unknown primaries relative to those with known primary origins.
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| *Overexpression of several genes has been noted in patients with cancer of unknown primary including Ras, p53, Bcl-2, and Her-2.<ref name="pmid10653878">{{cite journal| author=Hainsworth JD, Lennington WJ, Greco FA| title=Overexpression of Her-2 in patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma of unknown primary site. | journal=J Clin Oncol | year= 2000 | volume= 18 | issue= 3 | pages= 632-5 | pmid=10653878 | doi=10.1200/JCO.2000.18.3.632 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10653878 }} </ref><ref name="pmid9677443">{{cite journal| author=Briasoulis E, Tsokos M, Fountzilas G, Bafaloukos D, Kosmidis P, Samantas E et al.| title=Bcl2 and p53 protein expression in metastatic carcinoma of unknown primary origin: biological and clinical implications. A Hellenic Co-operative Oncology Group study. | journal=Anticancer Res | year= 1998 | volume= 18 | issue= 3B | pages= 1907-14 | pmid=9677443 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9677443 }} </ref>
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| ==Differentiating Cancer of Unknown Primary Origin from Other Diseases==
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| *Cancer of unknown primary is a diagnosis of exclusion; hence, all other differentials in addition to primary tumor location must be ruled out prior to diagnosis.
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| *Cancer of unknown primary origin must be differentiated from other diseases that cause sudden weight-loss, fatigue, and loss of appetite, such as:<ref name="pmid19262901" />
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| :*[[Incidentaloma]]
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| :*[[Anemia]]
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| :*[[Tuberculosis]]
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| :*[[Multiple myeloma]]
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| ==Epidemiology and Demographics==
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| * The prevalence of cancer of unknown primary origin is approximately 10 cases per 100,000 individuals worldwide.<ref name="pmid23860528">{{cite journal |vauthors=Urban D, Rao A, Bressel M, Lawrence YR, Mileshkin L |title=Cancer of unknown primary: a population-based analysis of temporal change and socioeconomic disparities |journal=Br. J. Cancer |volume=109 |issue=5 |pages=1318–24 |year=2013 |pmid=23860528 |pmc=3778275 |doi=10.1038/bjc.2013.386 |url=}}</ref><ref name="lonco">Fong T, Govindan R, Morgensztern D. Cancer of unknown primary. J Clin Oncol 2008 ASCO Ann Meet Proc. 2008;26 (15S:22159.</ref>
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| * Cancer of unknown primary origin is common, and it accounts for 3–5% of all malignant epithelial tumors.<ref name="pmid22414598">{{cite journal| author=Pavlidis N, Pentheroudakis G| title=Cancer of unknown primary site. | journal=Lancet | year= 2012 | volume= 379 | issue= 9824 | pages= 1428-35 | pmid=22414598 | doi=10.1016/S0140-6736(11)61178-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22414598 }} </ref>
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| * Cancer of unknown primary origin is the fourth most common cause of cancer-related death.<ref name="pmid23860528">{{cite journal |vauthors=Urban D, Rao A, Bressel M, Lawrence YR, Mileshkin L |title=Cancer of unknown primary: a population-based analysis of temporal change and socioeconomic disparities |journal=Br. J. Cancer |volume=109 |issue=5 |pages=1318–24 |year=2013 |pmid=23860528 |pmc=3778275 |doi=10.1038/bjc.2013.386 |url=}}</ref>
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| ===Age===
| | {{SK}} Occult cancer; CUP; Metastases of unknown primary origin; Unknown primary origin neoplasm; Cancers of unknown primary site; Neoplasms of unknown primary site; Carcinoma of unknown primary; Cancer of unknown origin; Cancer of unknown primary; Unknown primary tumors; UPT; Metastatic malignant neoplasms |
| *Patients of all age groups may develop cancer of unknown primary origin.
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| *Cancer of unknown primary origin is more commonly observed among adults and elderly patients with a mean age of 59 upon presentation.<ref name="pmid8201389">{{cite journal| author=Abbruzzese JL, Abbruzzese MC, Hess KR, Raber MN, Lenzi R, Frost P| title=Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. | journal=J Clin Oncol | year= 1994 | volume= 12 | issue= 6 | pages= 1272-80 | pmid=8201389 | doi=10.1200/JCO.1994.12.6.1272 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8201389 }} </ref>
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| ===Gender=== | | ==[[Cancer of unknown primary origin overview|Overview]]== |
| *Cancer of unknown primary origin affects men and women equally except for squamous cell carcinomas where males are affected twice as frequently as females.<ref name="pmid8001006">{{cite journal| author=Muir C| title=Cancer of unknown primary site. | journal=Cancer | year= 1995 | volume= 75 | issue= 1 Suppl | pages= 353-6 | pmid=8001006 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8001006 }} </ref>
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| ===Race=== | | ==[[Cancer of unknown primary origin historical perspective|Historical Perspective]]== |
| *There is no racial predilection to cancer of unknown primary origin.
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| ==Risk Factors== | | ==[[Cancer of unknown primary origin pathophysiology|Pathophysiology]]== |
| *There are no established risk factors for cancer of unknown primary origin.
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| == Natural History, Complications and Prognosis==
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| *Early clinical features include fatigue, weight-loss, and loss of appetite.
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| *Cancers of unknown primary origin are characterized by their aggressiveness, early dissemination, and unpredictable metastasis.
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| *Upon presentation, around 60% of patients with cancer of unknown primary have two or more affected sites.<ref name="pmid8201389" />
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| *The most common sites of metastasis in cancer of unknown origin are lymph nodes, lungs, liver, bones, and pleura.<ref name="pmid3046543">{{cite journal| author=Le Chevalier T, Cvitkovic E, Caille P, Harvey J, Contesso G, Spielmann M et al.| title=Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients. | journal=Arch Intern Med | year= 1988 | volume= 148 | issue= 9 | pages= 2035-9 | pmid=3046543 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3046543 }} </ref>
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| *If left untreated, the majority of patients with cancer of unknown primary origin may progress to develop multiple organ failure, heart failure, and death.
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| *Common complications of cancer of unknown primary origin, may include: hypercalcemia, adrenal insufficiency, and inappropriate antidiuretic syndrome, hematologic disorders, and malignant effusions.
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| *Prognosis is generally poor, and the average survival time of patients with cancer of unknown primary origin is approximately 6-12 months after diagnosis.<ref name="pmid10697020">{{cite journal |vauthors=Nelson KA, Walsh D, Abdullah O, McDonnell F, Homsi J, Komurcu S, LeGrand SB, Zhukovsky DS |title=Common complications of advanced cancer |journal=Semin. Oncol. |volume=27 |issue=1 |pages=34–44 |year=2000 |pmid=10697020 |doi= |url=}}</ref><ref name="pmid3940611">{{cite journal| author=Altman E, Cadman E| title=An analysis of 1539 patients with cancer of unknown primary site. | journal=Cancer | year= 1986 | volume= 57 | issue= 1 | pages= 120-4 | pmid=3940611 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3940611 }} </ref>
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| *Sites of metastasis and prognosis differ with the types of CUPs:<ref name="pmid10653878" /><ref name="pmid2451881">{{cite journal| author=Hainsworth JD, Dial TW, Greco FA| title=Curative combination chemotherapy for patients with advanced poorly differentiated carcinoma of unknown primary site. | journal=Am J Clin Oncol | year= 1988 | volume= 11 | issue= 2 | pages= 138-45 | pmid=2451881 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2451881 }} </ref><ref name="pmid8125789">{{cite journal| author=Nguyen C, Shenouda G, Black MJ, Vuong T, Donath D, Yassa M| title=Metastatic squamous cell carcinoma to cervical lymph nodes from unknown primary mucosal sites. | journal=Head Neck | year= 1994 | volume= 16 | issue= 1 | pages= 58-63 | pmid=8125789 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8125789 }} </ref><ref name="pmid7804965">{{cite journal| author=Kuttesch JF, Parham DM, Kaste SC, Rao BN, Douglass EC, Pratt CB| title=Embryonal malignancies of unknown primary origin in children. | journal=Cancer | year= 1995 | volume= 75 | issue= 1 | pages= 115-21 | pmid=7804965 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7804965 }} </ref>
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| {| class="wikitable"
| | ==[[Cancer of unknown primary origin causes|Causes]]== |
| ! style="background:#4479BA; color: #FFFFFF;" align="center" + |Type
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| ! style="background:#4479BA; color: #FFFFFF;" align="center" + |Common sites of metastasis
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| ! style="background:#4479BA; color: #FFFFFF;" align="center" + |Characteristics
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| ! style="background:#4479BA; color: #FFFFFF;" align="center" + |5-year survival rates
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| |-
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| | style="background:#DCDCDC;" align="center" + |Adenocarcinoma
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| | style="background:#F5F5F5;" align="center" + |Liver, lungs, bones, axillary lymph nodes, and peritnoneum
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| | style="background:#F5F5F5;" align="center" + |Most common type of CUP
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| | style="background:#F5F5F5;" align="center" + |5%
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| |-
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| | style="background:#DCDCDC;" align="center" + |Squamous cell carcinoma
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| | style="background:#F5F5F5;" align="center" + |Cervical lymph nodes | |
| | style="background:#F5F5F5;" align="center" + |More common in males
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| | style="background:#F5F5F5;" align="center" + |30%
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| |-
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| | style="background:#DCDCDC;" align="center" + |Neuroendocrine carcinoma
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| | style="background:#F5F5F5;" align="center" + |Bone marrow, bone lesions, lymph nodes, and lungs
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| | style="background:#F5F5F5;" align="center" + |Predominating type in children
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| | style="background:#F5F5F5;" align="center" + |17%
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| |-
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| | style="background:#DCDCDC;" align="center" + |Undifferntiated
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| | style="background:#F5F5F5;" align="center" + |Lungs and lymph nodes
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| | style="background:#F5F5F5;" align="center" + |Rapid tumor growth
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| | style="background:#F5F5F5;" align="center" + |13-16%
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| |}
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| == Diagnosis == | | ==[[Cancer of unknown primary origin differential diagnosis|Differentiating Colorectal cancer from other Diseases]]== |
| ===Diagnostic Criteria===
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| *The diagnosis of cancer of unknown primary origin is made when the following diagnostic criteria are met: tissue biopsy indicating malignancy and all known primary origins of cancer are ruled out.
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| *The search of the primary tumor's anatomical location has proven to be very challenging and costly; nevertheless, it is pursued with focus on the types of tumors that might benefit from efficient and targeted treatment.<ref name="pmid3046543">{{cite journal| author=Le Chevalier T, Cvitkovic E, Caille P, Harvey J, Contesso G, Spielmann M et al.| title=Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients. | journal=Arch Intern Med | year= 1988 | volume= 148 | issue= 9 | pages= 2035-9 | pmid=3046543 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3046543 }} </ref><ref name="pmid10388044">{{cite journal| author=Briasoulis E, Pavlidis N| title=Cancer of Unknown Primary Origin. | journal=Oncologist | year= 1997 | volume= 2 | issue= 3 | pages= 142-152 | pmid=10388044 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10388044 }} </ref>
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| *The initial approach may vary on a case-by-case basis; however, the diagnosis is made after histopathological and clinical testing:<ref name="pmid25392080">{{cite journal| author=Collado Martín R, García Palomo A, de la Cruz Merino L, Borrega García P, Barón Duarte FJ, Spanish Society for Medical Oncology| title=Clinical guideline SEOM: cancer of unknown primary site. | journal=Clin Transl Oncol | year= 2014 | volume= 16 | issue= 12 | pages= 1091-7 | pmid=25392080 | doi=10.1007/s12094-014-1244-0 | pmc=4239766 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25392080 }} </ref>
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| **The histopathological examination of the tissue includes microscopic evaluation followed by immunohistochemical analysis and rarely chromosome testing.
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| **Clinical diagnostic tests must be exhausted in order to aid in identifying the primary origin and this includes:<ref name="pmid12915904">{{cite journal |vauthors=Bugat R, Bataillard A, Lesimple T, Voigt JJ, Culine S, Lortholary A, Merrouche Y, Ganem G, Kaminsky MC, Negrier S, Perol M, Laforêt C, Bedossa P, Bertrand G, Coindre JM, Fizazi K |title=Summary of the Standards, Options and Recommendations for the management of patients with carcinoma of unknown primary site (2002) |journal=Br. J. Cancer |volume=89 Suppl 1 |issue= |pages=S59–66 |year=2003 |pmid=12915904 |pmc=2753014 |doi=10.1038/sj.bjc.6601085 |url=}}</ref>
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| **#Detailed medical history and full physical exam
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| **#Complete blood count
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| **#Liver and kidney function tests
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| **#Electrolytes
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| **#Urinanalysis
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| **#Fecal occult blood
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| **#Chest radiography
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| **#Chest, abdominal, and pelvic CT scan (depending on the case)
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| === Symptoms === | | ==[[Cancer of unknown primary origin epidemiology and demographics|Epidemiology and Demographics]]== |
| *Cancer of unknown primary origin may be asymptomatic.
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| *Symptoms of cancer of unknown primary origin may include the following:<ref name="pmid19262901">{{cite journal |vauthors=Varadhachary GR |title=Carcinoma of unknown primary origin |journal=Gastrointest Cancer Res |volume=1 |issue=6 |pages=229–35 |year=2007 |pmid=19262901 |pmc=2631214 |doi= |url=}}</ref>
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| :*[[Fatigue]]
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| :*[[Pain]]
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| :*[[Nausea]]
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| :*[[Vomiting]]
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| :*[[Diarrhea]]
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| :*[[Constipation]]
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| :*[[Insomnia]]
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| === Physical Examination === | | ==[[Cancer of unknown primary origin risk factors|Risk factors]]== |
| *Patients with cancer of unknown primary origin usually appear cachectic.
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| *There are no remarkable findings in the physical examination of these patients; the presentation is variable and depends on many factors including the primary tumor's origin and extent of organs involved.<ref name="pmid19262901" />
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| === Laboratory Findings === | | ==[[Cancer of unknown primary origin screening|Screening]] == |
| *There are no specific diagnostic laboratory findings associated with cancer on unknown primary origin; however, certain abnormal laboratory findings may help in locating the primary origin of the tumor:
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| **Some patients may have reduced blood count due to iron deficiency, which is suggestive of a gastrointestinal malignancy causing chronic blood loss.
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| **Other patients may have microscopic hematuria on urinanalysis, which is indicative of a genitourinary source of malignancy.
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| **Abnormal liver of renal function tests will point toward those relative organs as the site of malignancy.
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| **Patients may have occult blood on stool examination, which favors the diagnosis of a colorectal tumor.
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| === Electrocardiogram === | | ==[[Cancer of unknown primary origin natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| *There are no ECG findings associated with cancer of unknown primary origin.
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| === X-ray === | | == Diagnosis == |
| *A chest x-ray is a prerequisite in the diagnosis of cancer of unknown primary; however, it's value is of less significance when it comes to locating the primary tumor or differentiating it from a metastatic lesion.<ref name="pmid758556">{{cite journal| author=Nystrom JS, Weiner JM, Wolf RM, Bateman JR, Viola MV| title=Identifying the primary site in metastatic cancer of unknown origin. Inadequacy of roentgenographic procedures. | journal=JAMA | year= 1979 | volume= 241 | issue= 4 | pages= 381-3 | pmid=758556 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=758556 }} </ref>
| | [[Cancer of unknown primary origin diagnostic study of choice|Diagnostic study of choice]] | [[Cancer of unknown primary origin history and symptoms|History and Symptoms]] | [[Cancer of unknown primary origin physical examination|Physical Examination]] | [[Cancer of unknown primary origin laboratory findings|Laboratory Findings]] | [[Cancer of unknown primary origin electrocardiogram|Electrocariogram]] | [[Cancer of unknown primary origin x ray|X-Ray Findings]] | [[Cancer of unknown primary origin MRI|MRI Findings]] | [[Cancer of unknown primary origin CT scan|CT Scan Findings]] | [[Cancer of unknown primary origin echocardiography and ultrasound|Echocardiography and Ultrasound]] | [[Cancer of unknown primary origin other imaging findings|Other Imaging Findings]] | [[Cancer of unknown primary origin other diagnostic studies|Other Diagnostic Studies]] |
| *A mammography may be helpful in the identification of the primary origin of the tumor in women presenting with metastatic adenocarcinoma.
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| === Echocardiography or Ultrasound === | | ==Treatment== |
| *There are no specific echocardiography or ultrasound findings associated with cancer of unknown primary origin. However, a testicular or breast ultrasound may be helpful in the localization of the primary origin of the tumor in certain cases.<ref name="pmid12915904">{{cite journal| author=Bugat R, Bataillard A, Lesimple T, Voigt JJ, Culine S, Lortholary A et al.| title=Summary of the Standards, Options and Recommendations for the management of patients with carcinoma of unknown primary site (2002). | journal=Br J Cancer | year= 2003 | volume= 89 Suppl 1 | issue= | pages= S59-66 | pmid=12915904 | doi=10.1038/sj.bjc.6601085 | pmc=2753014 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12915904 }} </ref>
| | [[Cancer of unknown primary origin medical therapy|Medical Therapy]] | [[Cancer of unknown primary origin surgery|Surgery]] | [[Cancer of unknown primary origin primary prevention|Primary prevention]] | [[Cancer of unknown primary origin secondary prevention|Secondary prevention]] | [[Cancer of unknown primary origin follow up|Follow-up]] | [[Cancer of unknown primary origin cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Cancer of unknown primary origin future or investigational therapies|Future or Investigational Therapies]] |
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| === CT scan === | | ==Case Studies== |
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| *CT scan may be helpful in the diagnosis of cancer of unknown primary origin. It is considered one of the most valuable diagnostic tools in the search for the primary origin of the tumor.
| | [[Cancer of unknown primary origin case study one|Case #1]]{{Tumors}} |
| *CT scanning has provided a 20% increase in diagnostic accuracy relative to other imaging modalities.<ref name="pmid7087129">{{cite journal| author=Karsell PR, Sheedy PF, O'Connell MJ| title=Computed tomography in search of cancer of unknown origin. | journal=JAMA | year= 1982 | volume= 248 | issue= 3 | pages= 340-3 | pmid=7087129 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7087129 }} </ref>
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| === MRI ===
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| *There are no MRI findings associated with cancer of unknown primary origin. However, a breast MRI may be helpful in the detection of the tumor's primary origin in females with isolated axillary lymphadenopathy and suspected primary breast carcinoma.<ref name="pmid10894136">{{cite journal| author=Olson JA, Morris EA, Van Zee KJ, Linehan DC, Borgen PI| title=Magnetic resonance imaging facilitates breast conservation for occult breast cancer. | journal=Ann Surg Oncol | year= 2000 | volume= 7 | issue= 6 | pages= 411-5 | pmid=10894136 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10894136 }} </ref>
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| === Other Imaging Findings ===
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| === Other Diagnostic Studies ===
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| *Cancer of unknown primary origin may also be diagnosed using [[Immunohistochemical staining|immunohistochemical testing]], [[FDG-PET]], and [[Biopsy|biopsy (open and closed)]].<ref name="pmid15888766">{{cite journal |vauthors=Briasoulis E, Tolis C, Bergh J, Pavlidis N |title=ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) |journal=Ann. Oncol. |volume=16 Suppl 1 |issue= |pages=i75–6 |year=2005 |pmid=15888766 |doi=10.1093/annonc/mdi804 |url=}}</ref>
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| {{familytree/start |summary= Algorithm for diagnosis of cancer of unknown primary origin}}
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| {{familytree | | | | | | | | | | | A01 | | | | | | | | |A01='''Tumor of unknown primary origin'''}}
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| {{familytree | | | | | | | | | | | |!| | | | | | | | | |}}
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| {{familytree | | | | | | | | | | |boxstyle=text-align: left; | B01 | | | | | | |B01= • Full medical history and physical exam<br> • Basic blood and biochemical analysis<br> • CT scan of chest, abdomen, and pelvis}}
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| {{familytree | | | | | | | | | | | |!| | | | | | | | | }} | |
| {{familytree | | | | | | | | | | | C01 | | | | | | |C01=Histopathologic examination}}
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| {{familytree | | | | | |,|-|-|-|-|-|+|-|-|-|-|-|.| | | }}
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| {{familytree | | | | |D01| | | | D02| | | | D03 |D01='''Squamous cell carcinoma'''|D02='''Neuroendocrine carcinoma'''|D03='''Adenocarcinoma and poorly differntiated carcinoma'''}}
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| {{familytree | | | | | |!| | | | | |!| | | | | |!| | | | }}
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| {{familytree | | | | | |!| | | | |boxstyle=text-align: left;|E01| | | | |!| |E01=• Octreoscan<br>• Plasma chromogranin A}}
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| {{familytree | | | | |F01| | | | | | | | | | F02 | |F01=Additional tests specific to location of metastasis|F02=Additional tests speciifc to gender}}
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| {{familytree | | | | | |!| | | | | | | | | | | |!|| | }}
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| {{familytree | | |,|-|-|+|-|-|-|.| | | | | |,|-|^|-|.| | | }}
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| {{familytree | G01 | | G02 | | G03 | | | | G04 | | G05 | | | |G01=Cervical lymphadenopathy|G02=Inguinal lymphadenopathy|G03=Bone metastasis|G04=Men|G05=Women}}
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| {{familytree | |!| | | |!| | | |!| | | | | |!| | | |!| | | | | }}
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| {{familytree |boxstyle=text-align: left;| H01 | | H02 | | H03 | | | | H04 | | H05 | | | |H01=• Panendoscopy<br>• CT scan of head and neck<br>• Diagnostic bilateral amygdalectomy|H02=• Complete clinical examination of external genital organs<br>• Pelvic CT scan or ultrasound|H03=• Anoscopy<br>• Colposcopy (if female)<br>• Complete clinical examination of head and neck<br>• Panendoscopy<br>• Bone scintigraphy<br>• Xrays of painful areas|H04=• PSA<br>• αFP<br>• βHCG|H05=• Mammography<br>• Pelvic ultrasound or CT scan}}
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| {{familytree | | | | | | | | | | | | | | | |!| | | |!| | | | |}}
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| {{familytree | | | | | | | | | | | | | | | |`|-|v|-|'| | | | |}}
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| {{familytree | | | | | | | | | | | | | | | | | I01 | | | | | | |I01=Additional tests specific to location of metastasis}}
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| {{familytree | |,|-|-|-|v|-|-|-|v|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|v|-|-|-|v|-|-|-|.|}}
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| {{familytree | J01 | | J02 | | J03 | | J04 | | J05 | | J06 | | J07 | | J08 | | J09 |J01=Midline and/or mediastinal lymphadenopathy|J02=Cervical and/or supraclavicular lymphadenopathy|J03=Axillary lymphadenopathy|J04=Liver metastasis|J05=Lung metastasis|J06=Bone metastasis|J07=Single metastasis|J08=Pleural effusion|J09=Periotneal effusion}}
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| {{familytree | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | |!| |}}
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| {{familytree |boxstyle=text-align: left;| K01 | | K02 | | K03 | | K04 | | K05 | | K06 | | K07 | | K08 | | K09 |K01=• Testicular ultrasound<br>• Chest and abdominal CT scan|K02=• Testicular ultrasound<br>• Head and neck CT scan<br>• Panendoscopy<br>• EBV testing (to rule out undifferentiated nasopharyngeal carcinoma)|K03=Women:<br>• Breast ultrasound<br>• Breast MRI|K04=Women:<br>• αFP assay (if undifferntiated carcinoma)<br>• Colposcopy|K05=Women:<br>• βHCG<br>Men:<br>• Testicular ultrasound<br>• Chest and abdominal CT scan|K06=• Bone scintigraphy<br>• Xrays of painful areas|K07=• Full body CT scan<br>• Bone scintigraphy|K08=• Chest CT scan|K09=Women:<br>• Abdominal and pelvic CT scan}}
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| {{familytree/end}}
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| | |
| == Treatment ==
| |
| === Medical Therapy ===
| |
| *There is no treatment for cancer of unknown primary origin; the mainstay of therapy is supportive care.<ref name="pmid15888766">{{cite journal |vauthors=Briasoulis E, Tolis C, Bergh J, Pavlidis N |title=ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) |journal=Ann. Oncol. |volume=16 Suppl 1 |issue= |pages=i75–6 |year=2005 |pmid=15888766 |doi=10.1093/annonc/mdi804 |url=}}</ref>
| |
| *The treatment for cancer of unknown primary origin will depend on several factors, such as: metastatic origin, biopsy findings, patients age, and performance status.
| |
| *Medical therapy for cancer of unknown primary origin should be adjusted on an individual basis and according to well-defined clinicopathologic subsets.<ref name="pmid15888766">{{cite journal |vauthors=Briasoulis E, Tolis C, Bergh J, Pavlidis N |title=ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) |journal=Ann. Oncol. |volume=16 Suppl 1 |issue= |pages=i75–6 |year=2005 |pmid=15888766 |doi=10.1093/annonc/mdi804 |url=}}</ref>
| |
| *The table below summarizes different types of medical therapy strategies for cancer of unknown primary origin.
| |
| | |
| {| class="wikitable"
| |
| ! colspan="2" style="text-align: center;" |''' Treatment for cancer of unknown primary origin'''<br>
| |
| <SMALL> Adapted from the European Society of Medical Oncology<ref name="pmid15888766">{{cite journal |vauthors=Briasoulis E, Tolis C, Bergh J, Pavlidis N |title=ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) |journal=Ann. Oncol. |volume=16 Suppl 1 |issue= |pages=i75–6 |year=2005 |pmid=15888766 |doi=10.1093/annonc/mdi804 |url=}}</ref></SMALL>
| |
| |-
| |
| | style="text-align:left; font-weight: bold;" | Sub-type
| |
| | style="text-align: left; font-weight: bold;" | Proposed treatment
| |
| |-
| |
| |
| |
| Poorly differentiated carcinoma,
| |
| predominately nodal disease
| |
| |
| |
| Platinum based combination
| |
| chemotherapy
| |
| |-
| |
| |
| |
| Peritoneal carcinomatosis
| |
| in female
| |
| |
| |
| Platinum based chemotherapy
| |
| |-
| |
| |
| |
| Isolated axillary nodal
| |
| metastases in female
| |
| |
| |
| Identical to breast cancer with similar
| |
| nodal involvement
| |
| |-
| |
| |
| |
| Squamous carcinoma of
| |
| cervical lymph nodes
| |
| |
| |
| Irradiation for N1-N2 disease.<br>
| |
| For higher stages induction
| |
| chemotherapy with platinum-based
| |
| combination is suggested
| |
| |-
| |
| |
| |
| Liver, bone or multiple-site
| |
| metastases of adenocarcinoma
| |
| |
| |
| Low toxicity chemotherapy of
| |
| palliative orientation or best
| |
| supportive care are acceptable
| |
| |}
| |
| | |
| === Surgery ===
| |
| | |
| * Surgical intervention is not recommended for the management of cancer of unknown primary origin.
| |
| | |
| === Prevention ===
| |
| *There are no primary preventive measures available for cancer of unknown primary origin.<ref name="pmid15888766">{{cite journal |vauthors=Briasoulis E, Tolis C, Bergh J, Pavlidis N |title=ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) |journal=Ann. Oncol. |volume=16 Suppl 1 |issue= |pages=i75–6 |year=2005 |pmid=15888766 |doi=10.1093/annonc/mdi804 |url=}}</ref>
| |
| *There is no evidence that follow-up of asymptomatic patients is needed.<ref name="pmid15888766">{{cite journal |vauthors=Briasoulis E, Tolis C, Bergh J, Pavlidis N |title=ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) |journal=Ann. Oncol. |volume=16 Suppl 1 |issue= |pages=i75–6 |year=2005 |pmid=15888766 |doi=10.1093/annonc/mdi804 |url=}}</ref>
| |
| | |
| ==References==
| |
| {{Reflist|2}}
| |
|
| |
| [[Category: Oncology]]
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| [[Category:Up-To-Date]]
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| [[Category:Oncology]]
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| [[Category:Medicine]]
| |