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Latest revision as of 16:17, 16 October 2019

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

Overview

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.

Diagnostic Study of Choice

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.
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.^[1]^[2]
The initial approach may vary on a case-by-case basis; however, the diagnosis is made after histopathological and clinical testing:^[3]
- The histopathological examination of the tissue includes microscopic evaluation followed by immunohistochemical analysis.
- Clinical diagnostic tests must be exhausted in order to aid in identifying the primary origin and this includes:^[4]
  1. Detailed medical history and full physical exam
  2. Complete blood count
  3. Liver function tests
  4. Electrolytes
  5. Urinalysis
  6. Fecal occult blood
  7. Chest radiography
  8. Chest, abdominal, and pelvic CT scan (depending on the case)

Study of choice

There is no single diagnostic study of choice for the diagnosis of cancer of unknown primary.

The algorithm below explains the specific situations where certain diagnostic studies are recommended:^[5]^[4]

Tumor of unknown primary origin

• Full medical history and physical exam
• Basic blood and biochemical analysis
• CT scan of chest, abdomen, and pelvis

Histopathologic examination

Squamous cell carcinoma

Neuroendocrine carcinoma

Adenocarcinoma and poorly differntiated carcinoma

• Octreoscan
• Plasma chromogranin A

Additional tests specific to location of metastasis

Additional tests speciifc to gender

Cervical lymphadenopathy

Inguinal lymphadenopathy

Bone metastasis

Men

Women

• Panendoscopy
• CT scan of head and neck
• Diagnostic bilateral tonsillectomy

• Complete clinical examination of external genital organs
• Pelvic CT scan or ultrasound

• Anoscopy
• Colposcopy (if female)
• Complete clinical examination of head and neck
• Panendoscopy
• Bone scintigraphy
• Xrays of painful areas

• PSA
• αFP
• βHCG

• Mammography
• Pelvic ultrasound or CT scan

Additional tests specific to location of metastasis

Midline and/or mediastinal lymphadenopathy

Cervical and/or supraclavicular lymphadenopathy

Axillary lymphadenopathy

Liver metastasis

Lung metastasis

Bone metastasis

Single metastasis

Pleural effusion

Peritoneal effusion

• Testicular ultrasound
• Chest and abdominal CT scan

• Testicular ultrasound
• Head and neck CT scan
• Panendoscopy
• EBV testing (to rule out undifferentiated nasopharyngeal carcinoma)

Women:
• Breast ultrasound
• Breast MRI

Women:
• αFP assay (if undifferntiated carcinoma)
• Colposcopy

Women:
• βHCG
Men:
• Testicular ultrasound
• Chest and abdominal CT scan

• Bone scintigraphy
• Xrays of painful areas

• Full body CT scan
• Bone scintigraphy

• Chest CT scan

Women:
• Abdominal and pelvic CT scan

Molecular studies

There is no data to support routine molecular testing for assessment of cancer of unknown primary. In the past, molecular testing was routinely done in an effort to identify the cell or origin.

Diagnostic criteria

There is no single diagnostic study of choice for cancer of unknown primary.

References

↑ Le Chevalier T, Cvitkovic E, Caille P, Harvey J, Contesso G, Spielmann M; et al. (1988). "Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients". Arch Intern Med. 148 (9): 2035–9. PMID 3046543.
↑ Briasoulis E, Pavlidis N (1997). "Cancer of Unknown Primary Origin". Oncologist. 2 (3): 142–152. PMID 10388044.
↑ Collado Martín R, García Palomo A, de la Cruz Merino L, Borrega García P, Barón Duarte FJ, Spanish Society for Medical Oncology (2014). "Clinical guideline SEOM: cancer of unknown primary site". Clin Transl Oncol. 16 (12): 1091–7. doi:10.1007/s12094-014-1244-0. PMC 4239766. PMID 25392080.
↑ ^4.0 ^4.1 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 (2003). "Summary of the Standards, Options and Recommendations for the management of patients with carcinoma of unknown primary site (2002)". Br. J. Cancer. 89 Suppl 1: S59–66. doi:10.1038/sj.bjc.6601085. PMC 2753014. PMID 12915904.
↑ Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G; et al. (2015). "Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Ann Oncol. 26 Suppl 5: v133–8. doi:10.1093/annonc/mdv305. PMID 26314775.

Template:WH Template:WS

[pmid3046543-1] Le Chevalier T, Cvitkovic E, Caille P, Harvey J, Contesso G, Spielmann M; et al. (1988). "Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients". Arch Intern Med. 148 (9): 2035–9. PMID 3046543.

[pmid10388044-2] Briasoulis E, Pavlidis N (1997). "Cancer of Unknown Primary Origin". Oncologist. 2 (3): 142–152. PMID 10388044.

[pmid25392080-3] Collado Martín R, García Palomo A, de la Cruz Merino L, Borrega García P, Barón Duarte FJ, Spanish Society for Medical Oncology (2014). "Clinical guideline SEOM: cancer of unknown primary site". Clin Transl Oncol. 16 (12): 1091–7. doi:10.1007/s12094-014-1244-0. PMC 4239766. PMID 25392080.

[pmid12915904-4] 4.0 ^4.1 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 (2003). "Summary of the Standards, Options and Recommendations for the management of patients with carcinoma of unknown primary site (2002)". Br. J. Cancer. 89 Suppl 1: S59–66. doi:10.1038/sj.bjc.6601085. PMC 2753014. PMID 12915904.

[pmid26314775-5] Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G; et al. (2015). "Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Ann Oncol. 26 Suppl 5: v133–8. doi:10.1093/annonc/mdv305. PMID 26314775.

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Cancer of unknown primary origin}}
-{{CMG}}; {{AE}}
+{{CMG}} {{shyam}}; {{AE}}; {{RAK}}
 == Overview ==
+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.
 == Diagnostic Study of Choice ==
-*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 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 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 [[Therapy|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)
+**#[[Chest]], [[Abdomen|abdominal]], and [[Pelvis|pelvic]] [[CT scan]] (depending on the case)
 === Study of choice ===
-[Name of the investigation] is the gold standard test for the diagnosis of [disease name].
+There is no single diagnostic study of choice for the diagnosis of cancer of unknown primary.
-OR
-The following result of [gold standard test] is confirmatory of [disease name]:
-* [Result 1]
-* [Result 2]
-OR
-[Name of the investigation] must be performed when:
-* The patient presents with [symptom/sign 1], [symptom/sign 2], and [symptom/sign 3].
-* A [name of test] is positive for [sign 1], [sign 2], and [sign 3] in the patient.
-OR
-[Name of the investigation] is the gold standard test for the diagnosis of [disease name].
-OR
-The diagnostic study of choice for [disease name] is [name of the investigation].
-OR
-There is no single diagnostic study of choice for the diagnosis of [disease name].
-OR
-There is no single diagnostic study of choice for the diagnosis of [disease name], but [disease name] can be diagnosed based on [name of the investigation 1] and [name of the investigation 2].
-OR
-[Disease name] is primarily diagnosed based on the clinical presentation.
-OR
-Investigations:
-* Among the patients who present with clinical signs of [disease name], the [investigation name] is the most specific test for the diagnosis.
-* Among the patients who present with clinical signs of [disease name], the [investigation name] is the most sensitive test for diagnosis.
-* Among the patients who present with clinical signs of [disease name], the [investigation name] is the most efficient test for diagnosis.
-==== The comparison of various diagnostic studies for [disease name] ====
-{|
-|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
-! style="background: #4479BA; color: #FFFFFF; text-align: center;" | Test
-! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Sensitivity
-! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Specificity
-|-
-! style="background: #696969; color: #FFFFFF; text-align: center;" |Test 1
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |...%
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |...%
-|-
-! style="background: #696969; color: #FFFFFF; text-align: center;" |Test 2
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |...%
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |...%
-|}
-<small> [Name of test with higher sensitivity and specificity] is the preferred investigation based on the sensitivity and specificity</small>
@@ Line 101: / Line 46: @@
 {{familytree | | | | | | | | | | | | | | | | | I01 | | | | | | |I01=Additional tests specific to location of metastasis}}
 {{familytree | |,|-|-|-|v|-|-|-|v|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|v|-|-|-|v|-|-|-|.|}}
-{{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}}
+{{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=Peritoneal effusion}}
 {{familytree | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | |!| |}}
 {{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}}
 {{familytree/end}}
-===== Sequence of Diagnostic Studies =====
+===Molecular studies===
-The [name of investigation] must be performed when:
+There is no data to support routine molecular testing for assessment of cancer of unknown primary. In the past, molecular testing was routinely done in an effort to identify the cell or origin.
-* The patient presented with symptoms/signs 1, 2, and 3 as the first step of diagnosis.
-* A positive [test] is detected in the patient, to confirm the diagnosis.
-OR
-The various investigations must be performed in the following order:
-* [Initial investigation]
-* [2nd investigation]
-=== Name of Diagnostic Criteria ===
-'''It is recommended that you include the criteria in a table. Make sure you always cite the source of the content and whether the table has been adapted from another source.'''
-[Disease name] is primarily diagnosed based on clinical presentation. There are no established criteria for the diagnosis of [disease name].
-OR
-There is no single diagnostic study of choice for [disease name], though [disease name] may be diagnosed based on [name of criteria] established by [...].
-OR
-The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
-OR
-The diagnosis of [disease name] is based on the [criteria name] criteria, which includes [criterion 1], [criterion 2], and [criterion 3].
-OR
-[Disease name] may be diagnosed at any time if one or more of the following criteria are met:
-* Criteria 1
-* Criteria 2
-* Criteria 3
-OR
-'''IF there are clear, established diagnostic criteria'''
-The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
-OR
-The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
-OR
-The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
-OR
-'''IF there are no established diagnostic criteria'''
+=== Diagnostic criteria ===
-There are no established criteria for the diagnosis of [disease name].
+There is no single diagnostic study of choice for cancer of unknown primary.
 ==References==