Intracerebral metastases pathophysiology: Difference between revisions
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Genes involved in the pathogenesis of intracerebral metastases are tabulated below:<ref name="RahmathullaToms2012">{{cite journal|last1=Rahmathulla|first1=Gazanfar|last2=Toms|first2=Steven A.|last3=Weil|first3=Robert J.|title=The Molecular Biology of Brain Metastasis|journal=Journal of Oncology|volume=2012|year=2012|pages=1–16|issn=1687-8450|doi=10.1155/2012/723541}}</ref> | Genes involved in the pathogenesis of intracerebral metastases are tabulated below:<ref name="RahmathullaToms2012">{{cite journal|last1=Rahmathulla|first1=Gazanfar|last2=Toms|first2=Steven A.|last3=Weil|first3=Robert J.|title=The Molecular Biology of Brain Metastasis|journal=Journal of Oncology|volume=2012|year=2012|pages=1–16|issn=1687-8450|doi=10.1155/2012/723541}}</ref> | ||
{| class="wikitable" ! Genes ! Cancer site (primary) ! Role and implications ! Chromosome location |- | RHoC | Melanoma | Regulates remodeling of actin cytoskeleton during morphogenesis and motility. Important in tumor cell invasion | 1p21-p13 |- | LOX | BreastHead and neck cancer | Increases invasiveness of hypoxic human cancer cells through cell matrix adhesion and focal adhesion kinase activity | 5q23.1-q23.2 |- | VEGF | LungBreastMelanomaColon | Angiogenic growth factorInhibition decreases brain metastasis formation; reduces blood vessel formation and cell proliferation; increases apoptosis | 6p21.1 |- | CSF1 | BreastLung | Stimulate macrophage proliferation and subsequent release of growth factors | 1p13.3 |- | ID1 | BreastLung | Involved in matrix remodeling, intracellular signaling, and angiogenesis | 20q11.21 |- | TWIST1 | BreastGastricRhabdomyosarcomaMelanomaHepatocellular | Causes loss of E-cadherin-mediated cell-cell adhesion, activates mesenchymal markers, and induces cell motility by promoting epithelial-mesenchymal transition | 7p21.1 |- | MET | Renal cell cancer | Affects a wide range of biological activity depending on the cell target, varying from mitogenesis, morphogenesis, and motogenesis | 7q31.2 |- | MMP-9 | ColorectalBreastMelanomaChondrosarcoma | Extracellular matrix degradation, tissue remodeling | 20q13.12 |- | NEDD9 | Melanoma | Acquisition of a metastatic potential | 6p24.2 |- | LEF1 | Lung | Transcriptional effecter—WNT pathway; predilection for brain metastasisKnockdown inhibits brain metastasis, decreases colony formation; in vitro decreases invasion | 4q25 |- | HOXB9 | LungBreast | Homeobox gene family; critical for embryonic segmentation and patterning. Also a TCF4 targetKnockdown in vitro decreased invasion and colony formation; in vivo appears to inhibit brain metastasis | 17q21.32 |- | BMP4 | LungColorectal | Plays an essential role in embryonic development and may be an essential component of the epithelial-mesenchymal transition | 14q22.2 |- | STAT3 | Melanoma | Cell signaling transcription factorReduction suppresses brain metastasis; decreases angiogenesis in vivo and cellular invasion in vitro | 17q21.2 |} | |||
===Gross Pathology=== | ===Gross Pathology=== | ||
Revision as of 19:37, 10 November 2015
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Intracerebral metastases Microchapters |
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Differentiating Intracerebral Metastases from other Diseases |
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Diagnosis |
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Treatment |
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Case Studies |
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Intracerebral metastases pathophysiology On the Web |
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American Roentgen Ray Society Images of Intracerebral metastases pathophysiology |
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Risk calculators and risk factors for Intracerebral metastases pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]
Overview
Pathophysiology
Pathogenesis
Genetics
Genes involved in the pathogenesis of intracerebral metastases are tabulated below:[1]
Gross Pathology
- Typically metastases are sharply demarcated from the surrounding parenchyme and usually there is a zone of peritumoral edema out of proportion with the tumor size.
- Common intracranial sites associated with subependymal giant cell astrocytoma include:[2]
- Cerebrum (80%)
- Cerebellum (15%)
- Brain stem (5% )
Gallery
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![This solitary brain metastasis from thyroid papillary carcinoma resulted in neurological symptoms. The thyroid primary was clinically occult. (Courtesy of Dr. Nikola Kostich, Minneapolis, MN.).[3]](/images/1/12/THYROID_PAPILLARY_CARCINOMA_METASTATIC_TO_BRAIN.jpg)
This solitary brain metastasis from thyroid papillary carcinoma resulted in neurological symptoms. The thyroid primary was clinically occult. (Courtesy of Dr. Nikola Kostich, Minneapolis, MN.).[3]
![This solitary brain metastasis from thyroid papillary carcinoma resulted in neurological symptoms. The thyroid primary was clinically occult. (Courtesy of Dr. Nikola Kostich, Minneapolis, MN.).[3]](/index.php/File:THYROID_PAPILLARY_CARCINOMA_METASTATIC_TO_BRAIN.jpg)
Microscopic Pathology
The histopathological appearance of intracerebral metastases may vary with the type of primary tumor. Common findings are listed below:[4][5]
- Tubule formation/glands
- Well-circumscribed and sharply demarcated from surrounding tissue (with the exception of melanoma metastasis)
- Mitoses
- Nuclear atypia
- Nuclear hyperchromasia
- Variation of nuclear size
- Variation of nuclear shape
Gallery
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![Very low magnification micrograph demonstrating metastatic adenocarcinoma that from a colorectal primary, i.e. colorectal carcinoma, by immunostains on HPS stain. The cerebellum seen on the image has Bergmann gliosis and Purkinje cell loss.[6]](/images/a/ae/Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg)
Very low magnification micrograph demonstrating metastatic adenocarcinoma that from a colorectal primary, i.e. colorectal carcinoma, by immunostains on HPS stain. The cerebellum seen on the image has Bergmann gliosis and Purkinje cell loss.[6]
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![High magnification micrograph demonstrating metastatic adenocarcinoma that is from a colorectal primary, i.e. colorectal carcinoma, by immunostains on HPS stain. The cerebellum has Bergmann gliosis and Purkinje cell loss.[6]](/images/0/06/Metastatic_adenocarcinoma_-_cerebellum_-_high_mag.jpg)
High magnification micrograph demonstrating metastatic adenocarcinoma that is from a colorectal primary, i.e. colorectal carcinoma, by immunostains on HPS stain. The cerebellum has Bergmann gliosis and Purkinje cell loss.[6]
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![High magnification micrograph of a brain metastasis on HPS stain demonstrating normal brain tissue on the left and tumor cells on the right. The sharp demarcation between tumor and normal is typical of brain metastases.[6]](/images/9/9f/Brain_metastasis_-_high_mag.jpg)
High magnification micrograph of a brain metastasis on HPS stain demonstrating normal brain tissue on the left and tumor cells on the right. The sharp demarcation between tumor and normal is typical of brain metastases.[6]
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![Adenocarcinoma infiltrating the brain in a case of lung cancer on H&E stain.[6]](/images/a/a4/Brain_metastasis_-_high_mag_2.jpg)
Adenocarcinoma infiltrating the brain in a case of lung cancer on H&E stain.[6]
![Very low magnification micrograph demonstrating metastatic adenocarcinoma that from a colorectal primary, i.e. colorectal carcinoma, by immunostains on HPS stain. The cerebellum seen on the image has Bergmann gliosis and Purkinje cell loss.[6]](/index.php/File:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg)
![High magnification micrograph demonstrating metastatic adenocarcinoma that is from a colorectal primary, i.e. colorectal carcinoma, by immunostains on HPS stain. The cerebellum has Bergmann gliosis and Purkinje cell loss.[6]](/index.php/File:Metastatic_adenocarcinoma_-_cerebellum_-_high_mag.jpg)
![High magnification micrograph of a brain metastasis on HPS stain demonstrating normal brain tissue on the left and tumor cells on the right. The sharp demarcation between tumor and normal is typical of brain metastases.[6]](/index.php/File:Brain_metastasis_-_high_mag.jpg)
![Adenocarcinoma infiltrating the brain in a case of lung cancer on H&E stain.[6]](/index.php/File:Brain_metastasis_-_high_mag_2.jpg)
Immunohistochemistry
- The immunohistochemistry profile of intracerebral metastases may vary with the type of the primary tumor.[7]
- Intracerebral metastases are demonstrated by positivity to tumor markers such as:[7]
- General brain metastases: Pankeratin +ve, GFAP -ve
- Lung adenocarcinoma and small cell lung carcinoma: TTF-1 +ve, CK7 +ve, CK20 -ve
- Breast carcinoma: CK7 +ve, ER +ve, PR +ve, BRST2 +ve/-ve
- Colorectal carcinoma: CK20 +ve, CDX2 +ve, TTF-1 -ve, CK7 -ve
- Clear cell renal cell carcinoma: PAX8 +ve, vimentin +ve, CD10 +ve, CK7 -ve, CK20 -ve
- Melanoma: S-100 +ve, HMB-45 +ve, melan-A +ve.
Gallery
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![Immunohistochemistry profile of intracerebral metastases from an adenocarcinoma of lung (primary) demonstrating positivity to CK7, CK20, and TTF1.[8]](/images/8/82/Immunohistochemistry_of_brain_metastasis.jpg)
Immunohistochemistry profile of intracerebral metastases from an adenocarcinoma of lung (primary) demonstrating positivity to CK7, CK20, and TTF1.[8]
![Immunohistochemistry profile of intracerebral metastases from an adenocarcinoma of lung (primary) demonstrating positivity to CK7, CK20, and TTF1.[8]](/index.php/File:Immunohistochemistry_of_brain_metastasis.jpg)
References
- ↑ Rahmathulla, Gazanfar; Toms, Steven A.; Weil, Robert J. (2012). "The Molecular Biology of Brain Metastasis". Journal of Oncology. 2012: 1–16. doi:10.1155/2012/723541. ISSN 1687-8450.
- ↑ Khuntia, Deepak (2015). "Contemporary Review of the Management of Brain Metastasis with Radiation". Advances in Neuroscience. 2015: 1–13. doi:10.1155/2015/372856. ISSN 2356-6787.
- ↑ Gross image of brain metastases. Libre pathology 2015. http://librepathology.org/wiki/index.php/Brain_metastasis. Accessed on November 10, 2015
- ↑ Microscopic features of brain metastasis. Libre pathology 2015. http://librepathology.org/wiki/index.php/Brain_metastasis. Accessed on November 10, 2015
- ↑ Microscopic appearance of brain metastases. Dr Bruno Di Muzio and Dr Trent Orton et al. Radiopaedia 2015. http://radiopaedia.org/articles/brain-metastases. Accessed on November 10, 2015
- ↑ 6.0 6.1 6.2 6.3 Microscopic images of brain metastasis. Libre pathology 2015. http://librepathology.org/wiki/index.php/Brain_metastasis. Accessed on November 10, 2015
- ↑ 7.0 7.1 IHC features of brain metastasis. Libre pathology 2015. http://librepathology.org/wiki/index.php/Brain_metastasis. Accessed on November 10, 2015
- ↑ IHC image of brain metastasis. Libre pathology 2015. http://librepathology.org/wiki/index.php/Brain_metastasis. Accessed on November 10, 2015