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{{Cancer of unknown primary origin}}                                                                 
{{Cancer of unknown primary origin}}                                                                 
{{CMG}};  {{AE}} {{RAK}}, {{MV}}
{{CMG}};  {{AE}} {{RAK}}, {{MV}}
   
   
{{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  
{{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  
==Overview==
'''Cancer of unknown primary origin''' or CUP is the diagnosis of [[Metastasis|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 4 groups: [[adenocarcinomas]], poorly differentiated [[carcinomas]], [[Squamous cell carcinoma|squamous cell carcinomas]], and [[Carcinoma|carcinomas]] with [[Neuroendocrine tumors|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. 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 less than 2%.
==Historical Perspective==
*Cancer of unknown primary origin was first described in 1980.
*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>


==Classification==
==[[Cancer of unknown primary origin overview|Overview]]==
*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>
:*[[Adenocarcinoma|Adenocarcinomas]]
:*[[Squamous cell carcinoma|Squamous cell carcinomas]]
:*Poorly differentiated tumors
:*[[Neuroendocrine tumor|Carcinomas with neuroendocrine differentiation]]


==Pathophysiology==
==[[Cancer of unknown primary origin historical perspective|Historical Perspective]]==
*The exact [[pathogenesis]] of cancer of unknown primary origin is not fully understood.
*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.
*It is thought that the site of origin of CUP remains unknown due to one of the following theories:<ref name="pmid19262901" />
**Remaining small and undetectable clinically
**Disappearing after metastasizing
**Elimination by body's defense


* 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 pathophysiology|Pathophysiology]]==


==Causes==
==[[Cancer of unknown primary origin causes|Causes]]==
*The cause of CUP has not been identified.
*Several studies have evaluated the [[Chromosomal anomalies|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.
*Overexpression of several [[genes]] has been noted in patients with cancer of unknown primary including [[Ras gene|Ras]], [[p53]], [[Bcl2|Bcl-2]], and [[Her2 gene|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>


==Differentiating Cancer of Unknown Primary Origin from Other Diseases==
==[[Cancer of unknown primary origin differential diagnosis|Differentiating Colorectal cancer from other Diseases]]==
*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 WikiDoc|diagnosis]].
*Cancer of unknown primary origin must be differentiated from other diseases that cause sudden [[weight-loss]], [[Fatigue (medical)|fatigue]], and [[loss of appetite]], such as:<ref name="pmid19262901" />
:*[[Incidentaloma]]
:*[[Anemia]]
:*[[Tuberculosis]]
:*[[Multiple myeloma]]


==Epidemiology and Demographics==
==[[Cancer of unknown primary origin epidemiology and demographics|Epidemiology and Demographics]]==
* 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>
* Cancer of unknown primary origin is common, and it accounts for 3–5% of all [[Malignant epithelial tumor|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>
* 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>
===Age===
*Patients of all age groups may develop cancer of unknown primary origin.
*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>


===Gender===
==[[Cancer of unknown primary origin risk factors|Risk factors]]==
*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>


===Race===
==[[Cancer of unknown primary origin screening|Screening]] ==
*There is no racial predilection to cancer of unknown primary origin.


==Risk Factors==
==[[Cancer of unknown primary origin natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
*There are no established risk factors for cancer of unknown primary origin.
== Natural History, Complications and Prognosis==
*Early clinical features include fatigue, weight-loss, and loss of appetite.
*Cancers of unknown primary origin are characterized by their aggressiveness, early dissemination, and unpredictable metastasis.
*Upon presentation, around 60% of patients with cancer of unknown primary have two or more affected sites.<ref name="pmid8201389" />
*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>
*If left untreated, the majority of patients with [[cancer]] of unknown primary origin may progress to develop [[Multiple organ failure|multiple organ failure,]] [[heart failure]], and death.
*Common [[complications]] of cancer of unknown primary origin, may include: [[hypercalcemia]], [[adrenal insufficiency]], and [[Siadh|inappropriate antidiuretic syndrome]], [[Hematologic diseases|hematologic disorders]], and malignant effusions.
*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>
*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>


{| class="wikitable"
== Diagnosis ==  
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Type
[[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]]
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Common sites of metastasis
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Characteristics
! style="background:#4479BA; color: #FFFFFF;" align="center" + |5-year survival rates
|-
| style="background:#DCDCDC;" align="center" + |[[Adenocarcinoma]]
| style="background:#F5F5F5;" align="center" + |Liver, lungs, bones, axillary lymph nodes, and peritnoneum
| style="background:#F5F5F5;" align="center" + |Most common type of CUP
| style="background:#F5F5F5;" align="center" + |5%
|-
| style="background:#DCDCDC;" align="center" + |[[Squamous cell carcinoma]]
| style="background:#F5F5F5;" align="center" + |Cervical lymph nodes
| style="background:#F5F5F5;" align="center" + |More common in males
| style="background:#F5F5F5;" align="center" + |30%
|-
| style="background:#DCDCDC;" align="center" + |[[Neuroendocrine tumor|Neuroendocrine carcinoma]]
| style="background:#F5F5F5;" align="center" + |Bone marrow, bone lesions, lymph nodes, and lungs
| style="background:#F5F5F5;" align="center" + |Predominating type in children
| style="background:#F5F5F5;" align="center" + |17%
|-
| style="background:#DCDCDC;" align="center" + |Undifferntiated
| style="background:#F5F5F5;" align="center" + |Lungs and lymph nodes
| style="background:#F5F5F5;" align="center" + |Rapid tumor growth
| style="background:#F5F5F5;" align="center" + |13-16%
|}


== Diagnosis ==
==Treatment==
===Diagnostic Criteria===
[[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]]
*The diagnosis of cancer of unknown primary origin is made when the following diagnostic criteria are met: [[Biopsy|tissue biopsy]] indicating [[malignancy]] and all known primary origins of [[cancer]] are ruled out.
*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>
*The initial approach may vary on a case-by-case basis; however, the diagnosis is made after [[histopathological]] and [[Clinical examination|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>
**The [[histopathological]] examination of the tissue includes [[Microscopic examination|microscopic evaluation]] followed by [[Immunohistochemistry|immunohistochemical analysis]].
**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>
**#Detailed [[medical history]] and full [[physical exam]]  
**#[[Complete blood counts|Complete blood count]]
**#[[Liver function test|Liver function tests]]  
**#[[Electrolyte|Electrolytes]]
**#[[Urinalysis]]
**#[[Fecal occult blood test|Fecal occult blood]]
**#[[Chest radiography]]
**#Chest, abdominal, and pelvic [[CT scan]] (depending on the case)


=== Symptoms ===
==Case Studies==
*Cancer of unknown primary origin may be [[Asymptomatic condition|asymptomatic]].
*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>
:*[[Fatigue]]
:*[[Pain]]
:*[[Nausea]]
:*[[Vomiting]]
:*[[Diarrhea]]
:*[[Constipation]]
:*[[Insomnia]]


=== Physical Examination ===
[[Cancer of unknown primary origin case study one|Case #1]]{{Tumors}}
*Patients with cancer of unknown primary origin usually appear [[cachexic]].
*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" />
 
=== Laboratory Findings ===
*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.
 
=== Electrocardiogram ===
*There are no ECG findings associated with cancer of unknown primary origin.
 
=== X-ray ===
*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|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>
*A [[mammography]] may be helpful in the identification of the primary origin of the tumor in women presenting with [[metastatic]] [[adenocarcinoma]].<ref name="pmid7636553">{{cite journal| author=Abbruzzese JL, Abbruzzese MC, Lenzi R, Hess KR, Raber MN| title=Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin. | journal=J Clin Oncol | year= 1995 | volume= 13 | issue= 8 | pages= 2094-103 | pmid=7636553 | doi=10.1200/JCO.1995.13.8.2094 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7636553  }} </ref>
 
=== Echocardiography or Ultrasound ===
*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>
 
=== CT scan ===
 
*[[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.
*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>
 
=== MRI ===
*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 [[Breast carcinoma|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>
 
=== Other Imaging Findings ===
*There are no other imaging findings associated with cancer of unknown primary origin.
 
=== Other Diagnostic Studies ===
*Other diagnostic studies for cancer of unknown primary that may help establish the origin of the tumor include:
**[[Tumor markers]] such as [[Alpha fetoprotein|αFP]], [[Human chorionic gonadotrophin|βHCG]], [[CA125]], CA 27.29, [[CA19-9|CA 19.9]], and [[CEA]]<ref name="pmid22161237">{{cite journal| author=Molina R, Bosch X, Auge JM, Filella X, Escudero JM, Molina V et al.| title=Utility of serum tumor markers as an aid in the differential diagnosis of patients with clinical suspicion of cancer and in patients with cancer of unknown primary site. | journal=Tumour Biol | year= 2012 | volume= 33 | issue= 2 | pages= 463-74 | pmid=22161237 | doi=10.1007/s13277-011-0275-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22161237  }} </ref>
**Diagnostic [[tonsillectomy]]<ref name="pmid3815873">{{cite journal| author=Tytor M, Olofsson J| title=Cervical lymph node metastases with occult primary. | journal=Clin Otolaryngol Allied Sci | year= 1986 | volume= 11 | issue= 6 | pages= 463-7 | pmid=3815873 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3815873  }} </ref>
**[[Endoscopy|Gastrointestinal endoscopy]], ENT panendoscopy (which is a combination of [[laryngoscopy]], [[esophagoscopy]], and [[bronchoscopy]]), [[proctoscopy]], and [[colposcopy]]<ref name="pmid1932839">{{cite journal| author=Mousseau M, Schaerer R, Lutz JM, Ménégoz F, Faure H, Swiercz P| title=[Hepatic metastasis of unknown primary site]. | journal=Bull Cancer | year= 1991 | volume= 78 | issue= 8 | pages= 725-36 | pmid=1932839 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1932839  }} </ref><ref name="pmid2221252">{{cite journal| author=Lefebvre JL, Coche-Dequeant B, Van JT, Buisset E, Adenis A| title=Cervical lymph nodes from an unknown primary tumor in 190 patients. | journal=Am J Surg | year= 1990 | volume= 160 | issue= 4 | pages= 443-6 | pmid=2221252 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2221252  }} </ref>
 
== 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="background:#4479BA; color: #FFFFFF;" 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="background:#DCDCDC;" align="center" | '''Sub-type'''
| style="background:#DCDCDC;" align="center" | '''Proposed treatment'''
|-
|
Poorly differentiated [[carcinoma]], predominately [[Lymphadenopathy|nodal disease]]
|
Platinum based combination chemotherapy
|-
|
[[Peritoneal carcinomatosis]] in female
|
Platinum based chemotherapy
|-
|
Isolated [[Axillary lymph node|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 ===
 
* [[Surgery operation|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]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]

Latest revision as of 13:17, 21 October 2019


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Roukoz A. Karam, M.D.[2], Maria Fernanda Villarreal, M.D. [3]

Synonyms and keywords: 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

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