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==Overview==
==Overview==
Colorectal cancer is the third most commonly diagnosed [[cancer]] in the world, and accounts for 8% of all cancer-related deaths annually. There are both [[genetic]] and [[Environmental epidemiology|environmental]] factors that can increase the risk of colorectal carcinoma (CRC). The pathogenesis of colorectal carcinoma (CRC) involves the molecular pathways for both sporadic and [[Colitis|colitis-associated CRC]]. There are both [[genetic]] and [[Environmental epidemiology|environmental]] causes of colorectal carcinoma (CRC). Colorectal cancer may be differentiated from other diseases that cause unexplained [[weight loss]], unexplained [[loss of appetite]], [[nausea]], [[vomiting]], [[diarrhea]], [[anemia]], [[jaundice]], and [[fatigue]], such as [[irritable bowel syndrome]] (IBS), [[inflammatory bowel disease]] (IBD), [[hemorrhoids]], [[anal fissures]], and [[diverticular disease]]. Current guidelines recommend that [[colonoscopy]] is the optimal screening tool for colon cancer since it detects 98-99% of the cases. The progression from an [[Polyp|edematous polyp]] to colorectal cancer may take 10-15 years. Colorectal cancer staging is an estimate of the amount of penetration of the cancer. Staging is based on the [[TNM classification|TNM classification system]] which depends on the extent of local invasion, the degree of [[Lymph node metastases|lymph node]] involvement, and whether there is distant [[metastasis]]. The history of a patient with colorectal cancer may include a family history of [[polyps]]/colorectal cancer or a history of [[inflammatory bowel disease]]. Some symptoms that are associated with colorectal cancer are change in bowel habits, [[hematochezia]], and [[rectal pain]]. [[Metastatic]] symptoms include [[dyspnea]], [[abdominal pain]], [[fractures]], and [[confusion]]. Generally, the most common signs of colorectal cancer are [[emaciation]], [[lethargy]], and [[pallor]] Other signs include [[low-grade fever]], discomfort on [[palpation]], [[ascites]], [[rectal bleeding]], [[rectal mass]], and [[jaundice]]. The laboratory findings associated with colorectal carcinoma are the following: [[Complete Blood Count]] ([[Complete blood count|CBC]]), [[Fecal Occult Blood Test|Fecal Occult Blood Tests]] ([[FOBT]]), [[CEA|serum CEA]] and [[CA 19-9|CA 19-9 concentration]], [[Serum iron|serum iron concentrations]], [[Vitamin B12|serum vitamin B12]] and [[folate]] concentrations, [[liver function tests]], and [[pulmonary function tests]]. [[Chest radiography]] (CXR) is the initial imaging modality used in the detection of suspected [[pulmonary metastasis]]. [[CT scan]] is used to determine the extent of involvement on colon cancer, most commonly in the [[abdomen]] and [[lungs]]. Other imaging tests that can be used for colorectal cancer are [[MRI]], [[ultrasound]], [[endoscopy]], [[PET scan]], [[Barium swallow|barium study]], and [[angiography]]. A [[biopsy]] and [[genetic testing]] can be performed when a suspected lesion is found on [[colonoscopy]]. [[Chemotherapy]] is used to reduce the likelihood of [[metastasis]] developing, shrink tumor size, and slow tumor growth. [[Surgery]] remains the primary treatment while [[chemotherapy]] and/or [[radiotherapy]] may be recommended depending on the individual patient's staging and other medical factors. When colorectal cancer metastasizes, there will be a different approach than with a localized tumor. The most common site of metastasis is the [[liver]], and the second most common is the [[lung]].
 
'''Cancer of unknown primary origin''' or CUP is the [[diagnosis]] of [[Metastasis|metastatic]] [[cancer]] when the [[Anatomy|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: [[Metastasis|metastatic origin]], [[biopsy|biopsy findings]], [[age|patients age]], and [[performance status]]. The [[Survival rate|5-year survival]] of patients with cancer of unknown primary origin is less than 2%.
==Historical Perspective==
==Historical Perspective==


Cancer of unknown primary origin was first discovered in the 1980s and was based solely on [[imaging studies]].
==Classification==
Cancer of unknown primary origin may be classified based on [[light microscopy]] of the [[Biopsy|tissue biopsy]] into 4 groups including [[Adenocarcinoma|adenocarcinomas]], [[Squamous cell carcinoma|squamous cell carcinomas]], poorly differentiated tumors, and [[Neuroendocrine tumor|carcinomas with neuroendocrine differentiation]].


==Pathophysiology==
== Pathophysiology ==
The exact [[pathogenesis]] of cancer of unknown primary origin is not fully understood. Several [[Research|studies]] noted consistency between metastatic cancer of unknown primary and metastases with known primary origins based on [[chromosomal abnormalities]] and over [[Gene expression|expression]] of several [[genes]].


==Causes==
==Causes==
 
Several [[Research|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.
 
==Differential Diagnosis==
==Differential Diagnosis==


 
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]].
==Epidemiology and Demographics==
==Epidemiology and Demographics==


 
The [[prevalence]] of cancer of unknown primary origin is approximately 10 cases per 100,000 individuals worldwide. Patients of all age groups may develop cancer of unknown primary origin. In most cases cancer of unknown primary origin affects [[men]] and [[women]] equally. There is no [[racial]] predilection to cancer of unknown primary origin.
==Risk Factors==
==Risk Factors==


 
There are no established [[risk factors]] specific for cancer of unknown primary origin.
==Screening==
==Screening==


 
There is insufficient [[evidence]] to recommend [[Screening|routine screening]] for cancer of unknown primary origin.
==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==


Early clinical features include [[fatigue]], [[weight-loss]], and [[loss of appetite]]. 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 rate|survival time]] of patients with cancer of unknown primary origin is approximately 6-12 months after diagnosis.


==Staging==
==Diagnostic Studies==
 
 
==History and Symptoms==


=== 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 initial approach may vary on a case-by-case basis; however, the diagnosis is made after [[histopathological]] and [[Clinical examination|clinical testing]].


==Physical Examination==
=== History and Symptoms ===
The majority of patients with cancer of unknown primary origin are [[asymptomatic]].


 
=== Physical Examination ===
==Diagnostic Studies==
There are no remarkable findings in the [[physical examination]] of CUP patients; the presentation is variable and depends on many factors including the primary tumor's origin and extent of organs involved.


===Laboratory Findings===
===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.
===X-Ray===


===X-Ray===
A [[chest x-ray]] is a prerequisite in the [[diagnosis]] of cancer of unknown primary; however, its value is of less significance when it comes to locating the primary tumor or differentiating it from a [[Metastatic|metastatic lesion]].


=== 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.


===CT===
===CT Scan===
[[CT scan]] may be helpful in the [[diagnosis]] of cancer of unknown primary origin.


===MRI===
===MRI===


 
There are no [[MRI]] findings associated with cancer of unknown primary origin.
===Ultrasound===
 
 
===Other Imaging Findings===
===Other Imaging Findings===
There are no other imaging findings associated with cancer of unknown primary origin.


===Other Diagnostic Studies===
===Other Diagnostic Studies===
Other diagnostic studies for cancer of unknown primary that may help establish the origin of the tumor include [[tumor markers]], diagnostic [[tonsillectomy]], and [[Gastroscopy|gastrointestinal endoscopy]].


==Medical Therapy==
==Medical Therapy==
The treatment for cancer of unknown primary origin will depend on several factors, such as [[metastatic]] origin, [[biopsy]] findings, [[Age|patients age]], and [[performance status]]. [[Therapy|Medical therapy]] for cancer of unknown primary origin should be adjusted on an individual basis and according to well-defined [[clinical]] and [[pathological]] subsets.


==Surgery==
==Surgery==
 
[[Surgery operation|Surgical intervention]] is not recommended for the management of cancer of unknown primary origin.
==Metastases Treatment==


==Primary Prevention==
==Primary Prevention==
There are no primary preventive measures available for cancer of unknown primary origin.


==Secondary Prevention==
==Secondary Prevention==

Latest revision as of 15:13, 16 October 2019

Cancer of unknown primary origin Microchapters

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Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Cancer of Unknown Primary Origin from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

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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]

Overview

Cancer of unknown primary origin or CUP is the diagnosis of metastatic cancer when the anatomic site of origin remains unidentified. Cancer of unknown primary origin is common, and it accounts for 2–5% of all cancers. Cancer of unknown primary origin may be classified according to pathology findings into 4 groups: adenocarcinomas, poorly differentiated carcinomas, squamous cell carcinomas, and carcinomas with neuroendocrine differentiation. The majority of patients with cancer of unknown primary origin may be initially asymptomatic. Early clinical features include fatigue, weight-loss, and loss of appetite. If left untreated, the majority of patients with cancer of unknown primary origin may progress to develop multiple organ failure, heart failure, and death. 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 discovered in the 1980s and was based solely on imaging studies.

Classification

Cancer of unknown primary origin may be classified based on light microscopy of the tissue biopsy into 4 groups including adenocarcinomas, squamous cell carcinomas, poorly differentiated tumors, and carcinomas with neuroendocrine differentiation.

Pathophysiology

The exact pathogenesis of cancer of unknown primary origin is not fully understood. Several studies noted consistency between metastatic cancer of unknown primary and metastases with known primary origins based on chromosomal abnormalities and over expression of several genes.

Causes

Several studies have evaluated the chromosomal and molecular anomalies found in cancers of unknown primary; however, they could not identify unique causes of metastasis of unknown primaries relative to those with known primary origins.

Differential Diagnosis

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.

Epidemiology and Demographics

The prevalence of cancer of unknown primary origin is approximately 10 cases per 100,000 individuals worldwide. Patients of all age groups may develop cancer of unknown primary origin. In most cases cancer of unknown primary origin affects men and women equally. There is no racial predilection to cancer of unknown primary origin.

Risk Factors

There are no established risk factors specific for cancer of unknown primary origin.

Screening

There is insufficient evidence to recommend routine screening for cancer of unknown primary origin.

Natural History, Complications, and Prognosis

Early clinical features include fatigue, weight-loss, and loss of appetite. Common complications of cancer of unknown primary origin, may include: hypercalcemia, adrenal insufficiency, and inappropriate antidiuretic syndrome, 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.

Diagnostic Studies

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 initial approach may vary on a case-by-case basis; however, the diagnosis is made after histopathological and clinical testing.

History and Symptoms

The majority of patients with cancer of unknown primary origin are asymptomatic.

Physical Examination

There are no remarkable findings in the physical examination of CUP patients; the presentation is variable and depends on many factors including the primary tumor's origin and extent of organs involved.

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.

X-Ray

A chest x-ray is a prerequisite in the diagnosis of cancer of unknown primary; however, its value is of less significance when it comes to locating the primary tumor or differentiating it from a metastatic lesion.

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.

CT Scan

CT scan may be helpful in the diagnosis of cancer of unknown primary origin.

MRI

There are no MRI findings associated with cancer of unknown primary origin.

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, diagnostic tonsillectomy, and gastrointestinal endoscopy.

Medical Therapy

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 clinical and pathological subsets.

Surgery

Surgical intervention is not recommended for the management of cancer of unknown primary origin.

Primary Prevention

There are no primary preventive measures available for cancer of unknown primary origin.

Secondary Prevention

References


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