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| __NOTOC__ | | __NOTOC__ |
| {{SI}}
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| {{CMG}} {{AE}} {{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
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| ==Overview==
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| '''Cancer of unknown primary origin''' 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 3–5% 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 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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| ==Historical Perspective==
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| *Cancer of unknown primary origin was first described in 1980.
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| *In 1980 to 1990, the definition of unknown primary cancer was based on imaging results.
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| ==Classification==
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| *Cancer of unknown primary origin may be classified according to pathology findings into 5 groups:
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| :*Well and moderately differentiated adenocarcinomas
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| :*Poorly differentiated carcinomas
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| :*Squamous cell carcinomas
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| :*Undifferentiated neoplasms
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| :*Carcinomas with neuroendocrine differentiation
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| ==Pathophysiology==
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| *The pathogenesis of cancer of unknown primary origin is characterized by the migration of stem cells.
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| *Stem cells play a key role in cancer development, it has been proposed that a cancer of unknown primary site may form when deregulated, premalignant or cancerous stem cells migrate away from their natural tissue and give rise to a cancer in the new site before or without generating a tumor in their original tissue.
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| *There are several genetic mutations associated with the development of cancer of unknown primary origin, such as:
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| :*EGFR
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| :*KRAS
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| :*HER2
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| :*BRAF
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| :*ROS-1
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| :*ALK
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| :*AKT1
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| :*MEK1
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| :*MET
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| :*NRAS
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| :*PIK3CA
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| * There are no characteristic findings on gross pathology of cancer of unknown primary origin.
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| * On microscopic histopathological analysis findings will depend on tumor histology.
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| ==Causes==
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| *Common causes of cancer of unknown primary origin, may include:
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| :*Squamous cell carcinomas
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| :*Adenocarcinomas
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| :*Neuroendocrine tumors
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| :*Mixed tumors (such as sarcomatoid, basaloid, or adenosquamous carcinomas)
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| ==Differentiating Cancer of Unknown Primary Origin from Other Diseases==
| | {{Cancer of unknown primary origin}} |
| *Cancer of unknown primary origin must be differentiated from other diseases that cause sudden weight-loss, fatigue, and loss of appetite, such as:
| | {{CMG}}; {{AE}} {{RAK}}, {{MV}} |
| :*[[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 [number or range] per 100,000 individuals worldwide.
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| * In [year], the incidence of Cancer of unknown primary origin was estimated to be [number or range] cases per 100,000 individuals in [location].
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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.
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| ===Gender===
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| *Cancer of unknown primary origin affects men and women equally.
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| ===Race===
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| *There is no racial predilection for cancer of unknown primary origin.
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| ==Risk Factors== | | ==[[Cancer of unknown primary origin overview|Overview]]== |
| *The most important risk factor in the development of cancer of unknown primary origin is an underlying primary cancer.
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| == Natural History, Complications and Prognosis== | | ==[[Cancer of unknown primary origin historical perspective|Historical Perspective]]== |
| *The majority of patients with cancer of unknown primary origin may be initially asymptomatic.
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| *Early clinical features include fatigue, weight-loss, and loss of appetite.
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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
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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.
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| *The 1-year survival rate of patients with cancer of unknown primary origin is less than 15%
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| *The 5-year survival of patients with cancer of unknown primary origin is of 5-10%
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| == Diagnosis == | | ==[[Cancer of unknown primary origin pathophysiology|Pathophysiology]]== |
| ===Diagnostic Criteria===
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| *The diagnosis of cancer of unknown primary origin is made when diagnostic criteria are met:
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| :*[criterion 1]
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| :*[criterion 2]
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| :*[criterion 3]
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| :*[criterion 4]
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| === Symptoms === | | ==[[Cancer of unknown primary origin causes|Causes]]== |
| *Cancer of unknown primary origin may be asymptomatic.
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| *Symptoms of cancer of unknown primary origin may include the following:
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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 differential diagnosis|Differentiating Colorectal cancer from other Diseases]]== |
| *Patients with cancer of unknown primary origin usually appear cachectic.
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| *Physical examination may show no remarkable findings.
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| === Laboratory Findings === | | ==[[Cancer of unknown primary origin epidemiology and demographics|Epidemiology and Demographics]]== |
| *Laboratory findings associated with cancer of unknown primary origin, may include:
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| :*Elevated levels of carcinoembryonic antigen
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| :*Elevated levels cancer antigen 125
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| :*Elevated levels cancer antigen 19-9
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| :*Elevated levels cancer antigen 27.29
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| ===Imaging Findings=== | | ==[[Cancer of unknown primary origin risk factors|Risk factors]]== |
| *CT scan is the imaging modality of choice for cancer of unknown primary origin.
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| === Other Diagnostic Studies === | | ==[[Cancer of unknown primary origin screening|Screening]] == |
| *Cancer of unknown primary origin may also be diagnosed using immunohistochemical testing and 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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| == Treatment == | | ==[[Cancer of unknown primary origin natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| === Medical Therapy ===
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| *There is no treatment for cancer of unknown primary origin; the mainstay of therapy is supportive care.
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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"
| | == Diagnosis == |
| ! colspan="2" style="text-align: center;" |''' Treatment for cancer of unknown primary origin'''<br>
| | [[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]] |
| <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="text-align:left; font-weight: bold;" | Sub-type | |
| | style="text-align: left; font-weight: bold;" | Proposed treatment | |
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| Poorly differentiated carcinoma,
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| predominately nodal disease
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| Platinum based combination
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| chemotherapy
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| |-
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| Peritoneal carcinomatosis
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| in female
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| Platinum based chemotherapy
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| |-
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| Isolated axillary nodal
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| metastases in female
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| Identical to breast cancer with similar
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| nodal involvement
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| |-
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| Squamous carcinoma of
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| cervical lymph nodes
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| Irradiation for N1-N2 disease.<br>
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| For higher stages induction
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| chemotherapy with platinum-based
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| combination is suggested
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| |- | |
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| Liver, bone or multiple-site
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| metastases of adenocarcinoma
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| Low toxicity chemotherapy of
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| palliative orientation or best
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| supportive care are acceptable
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| |} | |
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| === Surgery === | | ==Treatment== |
| | [[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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| * Surgical intervention is not recommended for the management of cancer of unknown primary origin.
| | ==Case Studies== |
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| === Prevention ===
| | [[Cancer of unknown primary origin case study one|Case #1]]{{Tumors}} |
| *There are no primary preventive measures available for cancer of unknown primary origin.
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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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