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[[Image:Bone metastasis.jpg|thumb|200px|right|Cut surface of a [[humerus]] sawed lengthwise, showing a large [[cancer|cancerous]] '''metastasis''' (the whitish tumor between the head and the shaft of the bone).]]
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==Overview==
'''Metastasis''' (Greek: ''displacement, μετά=next + στάσις=placement'', plural: ''metastases''), sometimes abbreviated '''mets''', is the spread of a [[disease]] from one [[Organ (anatomy)|organ]] or part to another non-adjacent organ or part. Only [[cancer|malignant]] [[tumor cell]]s and infections have the capacity to '''metastasize'''.
[[Cancer cell]]s can "break away", "leak", or "spill" from a [[primary tumor]], enter [[lymphatic vessel|lymphatic]] and [[blood vessel]]s, circulate through the bloodstream, and settle down to grow within normal tissues elsewhere in the body. Metastasis is one of three hallmarks of [[cancer|malignancy]] (contrast [[benign tumor]]s).<ref name="Robbins"> Kumar, Abbas, Fausto; ''Robbins and Cotran: Pathologic Basis of Disease''; Elsevier, 7th ed.</ref> Most [[tumor]]s and other [[neoplasia|neoplasms]] can metastasize, although in varying degrees, barring a few exceptions (e.g., [[Glioma]] and [[Basal cell carcinoma]] never metastasize).<ref name="Robbins"/>
When tumor cells metastasize, the new tumor is called a ''secondary'' or ''metastatic'' tumor, and its cells are like those in the original tumor. This means, for example, that, if [[breast cancer]] spreads (metastasizes) to the lung, the secondary tumor is made up of abnormal breast cells, not of abnormal lung cells. The tumor in the lung is then called ''metastatic breast cancer'', not ''lung cancer''.
[[Image:Secondary tumor deposits in the liver from a primary cancer of the pancreas.jpg|thumb|200px|right|Cut surface of a [[liver]] showing multiple metastatic nodules originating from [[pancreatic cancer]].]]


== Modes and sites of metastatic dispersal ==
{{SK}} Metastatic neoplasm; secondary tumor; disseminated cancer; metastases
Metastatic tumors are very common in the late stages of cancer. The spread of metastases may occur via the blood or the lymphatics or through both routes. The most common places for the metastases to occur are the [[adrenal]]s, [[liver]], [[brain]], and the [[bone]]s. There is also a propensity for certain tumors to seed in particular organs. This was first discussed as the "seed and soil" theory by [[Stephen Paget]] over a century ago in 1889. For example, [[prostate cancer]] usually metastasizes to the bones. In a similar manner, [[colon cancer]] has a tendency to metastasize to the liver. [[Stomach cancer]] often metastasizes to the [[ovary]] in women, then it is called a [[Krukenberg tumor]]. It is difficult for cancer cells to survive outside their region of origin, so in order to metastasize they must find a location with similar characteristics.


For example, breast tumor cells, which gather calcium ions from breast milk, metastasize to bone tissue, where they can gather calcium ions from bone. Malignant melanoma spreads to the brain, presumably because neural tissue and melanocytes arise from the same cell line in the embryo.<ref>Robert Weinberg, The Biology of Cancer, cited in [http://www.nytimes.com/2007/04/03/health/03angi.html  Basics: A mutinous group of cells on a greedy, destructive task,] by Natalie Angier, New York Times, April 3, 2007</ref>
== [[Metastasis overview|Overview]] ==


Cancer cells may spread to [[lymph node]]s (regional lymph nodes) near the primary tumor. This is called nodal involvement, positive nodes, or regional disease. Localized spread to regional [[lymph node]]s near the primary tumor is not normally counted as metastasis, although this is a sign of worse [[prognosis]].
== [[Metastasis historical perspective|Historical Perspective]] ==


In addition to the above routes, metastasis may occur by direct seeding, e.g., in the peritoneal cavity or pleural cavity.<ref name="Robbins"/>
== [[Metastasis classification|Classification]] ==


==Factors involved==
== [[Metastasis pathophysiology|Pathophysiology]] ==
Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream or the lymphatic system. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding [[extracellular matrix]] (ECM), which separates the tumor from adjoining tissue. By degrading these proteins, cancer cells are able to breach the ECM and escape. When [[oral cancer]]s metastasize, they commonly travel through the lymph system to the [[lymph node]]s in the neck. The body resists metastasis by a variety of mechanisms through the actions of a class of proteins known as [[metastasis suppressor]]s, of which about a dozen are known.<ref>Yoshida, BA, Sokoloff, MM, Welch, DR, Rinker-Schaeffer CW. 2000. [http://jnci.oxfordjournals.org/cgi/content/full/92/21/1717 Metastasis-suppressor genes: a review and perspective on an emerging field.] Journal of the National Cancer Institute 92: 1717-1730.</ref>


Cancer researchers studying the conditions necessary for cancer metastasis have discovered that one of the critical events required is the growth of a new network of blood vessels, called tumor [[angiogenesis]].<ref> N Weidner, JP Semple, WR Welch, and J Folkman; [http://content.nejm.org/cgi/content/abstract/324/1/1 Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma]; ''The New England Journal of Medicine'', Volume 324:1-8, January 3, 1991; Number 1.</ref> It has been found that [[angiogenesis inhibitor]]s would therefore prevent the growth of metastases. <ref name = "Robbins"/>
== [[Metastasis causes|Causes]] ==


== Metastasis and primary cancer ==
== [[Metastasis differential diagnosis|Differentiating Metastasis from other Diseases]] ==
It is theorized that metastasis always coincides with a primary cancer, and, as such, is a tumor that started from a cancer cell or cells in another part of the body. However, over 10% of patients presenting to [[oncology unit]]s will have metastases without a primary tumor found. In these cases, doctors refer to the primary tumor as "unknown" or "occult," and the patient is said to have cancer of unknown primary origin (CUP) or Unknown Primary Tumors (UPT). It is estimated that 3% of all cancers are of unknown primary origin.<ref name="CUP-Oncologist"> Evangelos Briasoulis, Nicholas Pavlidis; [http://theoncologist.alphamedpress.org/cgi/content/abstract/2/3/142 Cancer of Unknown Primary Origin]; ''The Oncologist'', Vol. 2, No. 3, 142–152, June 1997  </ref> Studies have shown that, if simple questioning does not reveal the cancer's source (coughing up blood -'probably [[lung cancer|lung]]', urinating blood - 'probably [[bladder cancer|bladder]]'), complex imaging will not either.<ref name="CUP-Oncologist"/> In some of these cases a primary may appear later.


The use of [[immunohistochemistry]] has permitted pathologists to give an identity to many of these metastases. However, imaging of the indicated area only occasionally reveals a primary.  In rare cases (e.g., of [[melanoma]]), no primary tumor is found, even on autopsy. It is therefore thought that some primary tumors can regress completely, but leave their metastases behind.
== [[Metastasis epidemiology and demographics|Epidemiology and Demographics]] ==


== Common sites of origin==
== [[Metastasis risk factors|Risk Factors]] ==


* [[Lung cancer|Lung]]
== [[Metastasis screening|Screening]] ==
* [[Breast cancer|Breast]]
* Skin: [[Melanoma]] (other skin tumors rarely metastasize)
* [[Colon cancer|Colon]]
* [[Renal cell carcinoma|Kidney]]
* [[prostate cancer|Prostate]]
* [[Pancreatic cancer|Pancreas]]


== Diagnosis of primary and secondary tumors ==
== [[Metastasis natural history, complications and prognosis|Natural History, Complications and Prognosis]] ==
The cells in a metastatic tumor resemble those in the primary tumor. Once the cancerous tissue is examined under a microscope to determine the cell type, a doctor can usually tell whether that type of cell is normally found in the part of the body from which the tissue sample was taken.


For instance, [[breast cancer]] cells look the same whether they are found in the breast or have spread to another part of the body. So, if a tissue sample taken from a tumor in the lung contains cells that look like breast cells, the doctor determines that the lung tumor is a secondary tumor. Still, the determination of the primary tumor can often be very difficult, and the pathologist may have to use several adjuvant techniques, such as [[immunohistochemistry]], FISH ([[fluorescent in situ hybridization]]), and others. Despite the use of techniques, in some cases the primary tumor remains unidentified.
== [[Metastasis diagnosis|Diagnosis]] ==


Metastatic cancers may be found at the same time as the primary tumor, or months or years later. When a second tumor is found in a patient that has been treated for cancer in the past, it is more often a metastasis than another primary tumor.
[[Metastasis history and symptoms|History and Symptoms]] | [[Metastasis physical examination|Physical Examination]] | [[Metastasis laboratory findings|Laboratory Findings]] | [[Metastasis chest x ray|Chest X Ray]] | [[Metastasis CT|CT]] | [[Metastasis echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Metastasis other imaging findings|Other Imaging Findings]] | [[Metastasis other diagnostic studies|Other Diagnostic Studies]]


== Treatments for metastatic cancer ==
== Treatment ==
Whether or not a cancer is local or has spread to other locations affects treatment and survival. If the cancer spreads to other tissues and organs, it may decrease a patient's likelihood of survival. However, there are some cancers (i.e., [[leukemia]], brain) that can kill without spreading at all.


When cancer has metastasized, it may be treated with [[radiosurgery]], [[chemotherapy]], [[radiation therapy]], [[biological therapy]], [[hormone therapy]], [[surgery]] or a combination of these. The choice of treatment generally depends on the type of primary cancer, the size and location of the metastasis, the patient's age and general health, and the types of treatments used previously. In patients diagnosed with CUP, it is still possible to treat the disease even when the primary tumor cannot be located.
[[Metastasis medical therapy|Medical Therapy]] | [[Metastasis surgery|Surgery]] | [[Metastasis primary prevention|Primary Prevention]] | [[Metastasis secondary prevention|Secondary Prevention]] | [[Metastasis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Metastasis future or investigational therapies|Future or Investigational Therapies]]


The treatment options currently available are rarely able to cure metastatic cancer, though some tumors, such as [[testicular cancer]], are usually still curable.
== Case Studies ==


== References ==
: [[Metastasis case study one|Case #1]]
<references/>


==See also==
== Related chapters ==


*[[Disseminated disease]]
* [[Disseminated disease]]


== External links ==
== External links ==


'''Medical information about metastatic cancer'''
* [http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic Q&A: Metastatic Cancer] – from the [[National Cancer Institute]]
*[http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic Q&A: Metastatic Cancer] – from the [[National Cancer Institute]]
* [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed.chapter.2030 Invasion and Metastases] – from ''Cancer Medicine''
*[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed.chapter.2030 Invasion and Metastases] – from ''Cancer Medicine'' e.5
*[http://www.childrenshospital.org/research/Site2029/mainpageS2029P23sublevel45.html How Cancer Grows and Spreads] – an interactive Flash presentation that explores the progression of a carcinoma from a single cell to metastasis; from the research department of [[Children's Hospital Boston]]
*[http://www.pathologyatlas.ro/Metastasis.html Metastasis photo] at the ''Atlas of Pathology'' website


'''Charities and advocacy groups dealing with metastatic cancer'''
{{Tumors}}
*[http://www.metacancer.org The MetaCancer Foundation] – resources and support for metastatic cancer survivors and their caregivers
*[http://www.mbcnetwork.org Metastatic Breast Cancer Network]
*[http://www.kidcancer.org Children's Cancer Research Charity for Metastatic Cancer in Kids]


'''Not specifically about metastatic cancer'''
[[Category:Disease]]
*[http://cancerguide.org/basic.html Understanding Cancer Types and Staging] – a patients' guide at the ''CancerGuide'' website
*[http://www.cancerforums.net Cancer Forums] – physicians answering questions about cancer


{{Tumors}}
{{SIB}}
[[Category:Oncology]]


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Latest revision as of 13:24, 26 August 2015

Metastasis
CT scan with metastatic tumour in lung (upper left lobe, seen on the right side of picture)
DiseasesDB 28954
MedlinePlus 002260

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Metastatic neoplasm; secondary tumor; disseminated cancer; metastases

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Metastasis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Chest X Ray | CT | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies

Treatment

Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

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Case #1

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