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| __NOTOC__ | | __NOTOC__ |
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| {{Cancer of unknown primary origin}} | | {{Cancer of unknown primary origin}} |
| {{CMG}}; {{AE}} {{RAK}}, {{MV}} | | {{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; 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 |
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| ==Overview==
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| '''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%.
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| :*
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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">{{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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| **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 overview|Overview]]== |
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| == Diagnosis == | | ==[[Cancer of unknown primary origin historical perspective|Historical Perspective]]== |
| ===Diagnostic Criteria===
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| *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.
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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 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>
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| **The [[histopathological]] examination of the tissue includes [[Microscopic examination|microscopic evaluation]] followed by [[Immunohistochemistry|immunohistochemical analysis]].
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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 counts|Complete blood count]]
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| **#[[Liver function test|Liver function tests]]
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| **#[[Electrolyte|Electrolytes]]
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| **#[[Urinalysis]]
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| **#[[Fecal occult blood test|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 pathophysiology|Pathophysiology]]== |
| *Cancer of unknown primary origin may be [[Asymptomatic condition|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 causes|Causes]]== |
| *Patients with cancer of unknown primary origin usually appear [[cachexic]].
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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 differential diagnosis|Differentiating Colorectal cancer from other Diseases]]== |
| *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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| === Electrocardiogram === | | ==[[Cancer of unknown primary origin epidemiology and demographics|Epidemiology and Demographics]]== |
| *There are no ECG findings associated with cancer of unknown primary origin.
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| === X-ray === | | ==[[Cancer of unknown primary origin risk factors|Risk factors]]== |
| *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>
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| *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>
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| === Echocardiography or Ultrasound === | | ==[[Cancer of unknown primary origin screening|Screening]] == |
| *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>
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| === CT scan === | | ==[[Cancer of unknown primary origin natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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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.
| | == Diagnosis == |
| *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>
| | [[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]] |
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| === MRI === | | ==Treatment== |
| *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>
| | [[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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| === Other Imaging Findings === | | ==Case Studies== |
| *There are no other imaging findings associated with cancer of unknown primary origin.
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| === Other Diagnostic Studies ===
| | [[Cancer of unknown primary origin case study one|Case #1]]{{Tumors}} |
| *Other diagnostic studies for cancer of unknown primary that may help establish the origin of the tumor include:
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| **[[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>
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| **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>
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| **[[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>
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| == Treatment ==
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| === Medical Therapy ===
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| *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>
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| *The treatment for cancer of unknown primary origin will depend on several factors, such as [[metastatic]] origin, [[biopsy]] findings, patients age, and performance status.
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| *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>
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| *The table below summarizes different types of medical therapy strategies for cancer of unknown primary origin.
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| {| class="wikitable"
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| ! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" |''' Treatment for cancer of unknown primary origin'''<br>
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| <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>
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| | style="background:#DCDCDC;" align="center" | '''Sub-type'''
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| | style="background:#DCDCDC;" align="center" | '''Proposed treatment'''
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| Poorly differentiated [[carcinoma]], predominately [[Lymphadenopathy|nodal disease]]
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| Platinum based combination chemotherapy
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| [[Peritoneal carcinomatosis]] in female
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| Platinum based chemotherapy
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| Isolated [[Axillary lymph node|axillary nodal]] metastases in female
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| Identical to breast cancer with similar nodal involvement
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| [[Squamous carcinoma]] of [[cervical lymph nodes]]
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| Irradiation for N1-N2 disease.<br>For higher stages induction chemotherapy with platinum-based combination is suggested
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| Liver, bone, or multiple-site metastases of [[adenocarcinoma]]
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| Low toxicity chemotherapy of palliative orientation or best supportive care are acceptable
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| |}
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| === Surgery ===
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| * [[Surgery operation|Surgical intervention]] is not recommended for the management of cancer of unknown primary origin.
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| === Prevention ===
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| *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>
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| *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>
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| ==References==
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| {{Reflist|2}}
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| [[Category: Oncology]]
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| [[Category:Up-To-Date]]
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| [[Category:Oncology]]
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| [[Category:Medicine]]
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