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{{Hamartoma}} | {{Hamartoma}} | ||
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==Overview== | ==Overview== | ||
Hamartomas arise from connective tissue and are generally | Hamartomas usually arise from [[connective tissue]] and are generally composed of [[cartilage]], [[fat]], and [[connective tissue]] cells. Hamartomas can be found in the [[lung]]s (most common), [[heart]], [[hypothalamus]], [[kidneys]], or [[spleen]]. The [[pathogenesis]] primarily consist of disorganized replication of normal tissue cells. Many hereditary syndromes are associated with hamartomatous formation. These include [[Peutz-Jeghers syndrome]], PTEN hamartoma [[tumor]] syndrome, and [[Cowden's syndrome]]. [[Genes]] that are involved in the [[pathogenesis]] of hamartomatous syndromes include [[BMPR1A]], [[SMAD4]], [[PTEN]], and [[STK11]]. | ||
==Pathogenesis== | ==Pathophysiology== | ||
=== Pathogenesis === | |||
*Hamartomas occur in the same location as the normal tissue (in the tissue of its origin) as opposed to [[choristoma]]s, which grow in other tissues (different from its origin). | *Hamartomas occur in the same location as the normal tissue (in the tissue of its origin) as opposed to [[choristoma]]s, which grow in other tissues (different from its origin). | ||
*The pathogenesis consists | *The [[pathogenesis]] primarily consists of disorganized replication of normal tissue cells. The underlying mechanisms for the replication abnormality are not fully understood.<ref name="radio1">Splenic hamartoma.Dr Henry Knipe et al Radiopedia.http://radiopaedia.org/articles/pulmonary-hamartoma-1 Accessed on December 09, 2015</ref> | ||
*Hamartomas arise from connective tissue and are generally formed of [[cartilage]], [[fat]], and [[connective tissue]] cells, although they may include many other types of cells. | *Hamartomas arise from [[connective tissue]] and are generally formed of [[cartilage]], [[fat]], and [[connective tissue]] cells, although they may include many other types of cells. | ||
*Hamartomas grow at the same rate as the organ | *Hamartomas grow at the same rate as the normal cells of the organ.<ref name="pmid18418855">{{cite journal |vauthors=Zakharov V, Schinstine M |title=Hamartoma of the lung |journal=Diagn. Cytopathol. |volume=36 |issue=5 |pages=331–2 |year=2008 |pmid=18418855 |doi=10.1002/dc.20790 |url=}}</ref> | ||
*These can be located in the [[lung]]s, [[heart]], [[hypothalamus]], [[kidneys]], or [[spleen]].<ref name="radio1">Splenic hamartoma.Dr Henry Knipe et al Radiopedia.http://radiopaedia.org/articles/pulmonary-hamartoma-1 Accessed on December 09, 2015</ref> | *These can be located in the [[lung]]s (most common), [[heart]], [[hypothalamus]], [[kidneys]], or [[spleen]].<ref name="radio1">Splenic hamartoma.Dr Henry Knipe et al Radiopedia.http://radiopaedia.org/articles/pulmonary-hamartoma-1 Accessed on December 09, 2015</ref> | ||
=== Bone-forming tumors === | |||
* Bone-forming [[tumors]] (bone islands) are most commonly located in the [[intramedullary]] bones of:<ref name="pmid7396066">{{cite journal |vauthors=McCarthy EF, Dorfman HD |title=Vascular and cartilaginous hamartoma of the ribs in infancy with secondary aneurysmal bone cyst formation |journal=Am. J. Surg. Pathol. |volume=4 |issue=3 |pages=247–53 |date=June 1980 |pmid=7396066 |doi= |url=}}</ref><ref name="pmid92857452">{{cite journal |vauthors=Balci P, Obuz F, Göre O, Yilmaz E, Demirpolat G, Aktug T, Kovanlikaya I |title=Aneurysmal bone cyst secondary to infantile cartilaginous hamartoma of rib |journal=Pediatr Radiol |volume=27 |issue=9 |pages=767–9 |date=September 1997 |pmid=9285745 |doi=10.1007/s002470050224 |url=}}</ref><ref name="pmid1409151">{{cite journal |vauthors=Cohen MC, Drut R, Garcia C, Kaschula RO |title=Mesenchymal hamartoma of the chest wall: a cooperative study with review of the literature |journal=Pediatr Pathol |volume=12 |issue=4 |pages=525–34 |date=1992 |pmid=1409151 |doi= |url=}}</ref> | |||
** [[Pelvis]] | |||
** [[Femur]] | |||
** [[Humerus]] | |||
** [[Ribs]] | |||
* Bone-forming [[tumors]] are masses that are small, white-yellow and round. | |||
* Tumors greater than 2 cm in size are known as giant bone islands. | |||
=== Cartilage-forming tumors === | |||
* It is understood that cartilage-forming tumors like [[osteochondroma]] is produced from abnormal cartilaginous epiphyseal growth plate tissue and abnormal regulation of cartilage proliferation.<ref name="pmid73960662">{{cite journal |vauthors=McCarthy EF, Dorfman HD |title=Vascular and cartilaginous hamartoma of the ribs in infancy with secondary aneurysmal bone cyst formation |journal=Am. J. Surg. Pathol. |volume=4 |issue=3 |pages=247–53 |date=June 1980 |pmid=7396066 |doi= |url=}}</ref><ref name="pmid9285745">{{cite journal |vauthors=Balci P, Obuz F, Göre O, Yilmaz E, Demirpolat G, Aktug T, Kovanlikaya I |title=Aneurysmal bone cyst secondary to infantile cartilaginous hamartoma of rib |journal=Pediatr Radiol |volume=27 |issue=9 |pages=767–9 |date=September 1997 |pmid=9285745 |doi=10.1007/s002470050224 |url=}}</ref><ref name="pmid10770690">{{cite journal |vauthors=Göre O, Kiliçalp A, Başdemir G, Ozer E, Aktuğ T |title=Cartilaginous hamartoma of the chest wall with secondary aneurysmal cyst-like areas in an infant: a case report |journal=Turk. J. Pediatr. |volume=41 |issue=1 |pages=139–42 |date=1999 |pmid=10770690 |doi= |url=}}</ref> | |||
* Cartilage-forming tumors are termed as congenital error of epiphyseal development. | |||
=== Fiber-forming tumors === | |||
* It is understood that fiber-forming tumors is produced from continued growth of fibrous [[Cortical bone|cortical]] defects that extrude into the [[medullary]] cavity. | |||
* The most commonly involved bone are tibia and the femur. | |||
===Lung=== | ===Lung=== | ||
*Lung hamartomas mostly arise from connective tissue and are generally formed of [[cartilage]], fat, and connective tissue cells, although they may include many other types of cells. | *Lung hamartomas mostly arise from connective tissue and are generally formed of [[cartilage]], fat, and [[connective tissue cells]], although they may include many other types of [[cells]]. | ||
*About 5-8% of all solitary lung tumors and about 75% of all [[benign]] lung tumors are hamartomas. | *About 5-8% of all solitary lung tumors and about 75% of all [[benign]] [[lung]] [[tumors]] are hamartomas. | ||
*The majority of pulmonary hamartomas form from [[connective tissue]] on the outside of the lungs, although about 10% form in the linings of the bronchi. | *The majority of pulmonary hamartomas form from [[connective tissue]] on the outside of the lungs, although about 10% form in the linings of the bronchi. | ||
*In the majority of patients, it can be difficult to distinguish hamartoma from malignancies.<ref name="pmid18418855">{{cite journal |vauthors=Zakharov V, Schinstine M |title=Hamartoma of the lung |journal=Diagn. Cytopathol. |volume=36 |issue=5 |pages=331–2 |year=2008 |pmid=18418855 |doi=10.1002/dc.20790 |url=}}</ref> | *In the majority of patients, it can be difficult to distinguish hamartoma from [[malignancies]].<ref name="pmid18418855">{{cite journal |vauthors=Zakharov V, Schinstine M |title=Hamartoma of the lung |journal=Diagn. Cytopathol. |volume=36 |issue=5 |pages=331–2 |year=2008 |pmid=18418855 |doi=10.1002/dc.20790 |url=}}</ref> | ||
*Pulmonary hamartomas can be divided into two subtypes | *Pulmonary hamartomas can be divided into two subtypes endobronchial and [[parenchymal]]. | ||
*An endobronchial location is described in 3%–20% of all pulmonary hamartomas. This subtype is mainly composed of cartilage and fibrous tissue. | *An endobronchial location is described in 3%–20% of all [[pulmonary]] hamartomas. This subtype is mainly composed of [[cartilage]] and [[fibrous tissue]]. | ||
*Endobronchial hamartomas typically contain more [[fat]] tissue than parenchymal hamartomas. | *Endobronchial hamartomas typically contain more [[fat]] tissue than [[parenchymal]] hamartomas. | ||
===Heart=== | ===Heart=== | ||
*Cardiac [[rhabdomyomas]] are hamartomas comprised of altered [[cardiac myocytes]] that contain large vacuoles and [[glycogen]]. | *Cardiac [[rhabdomyomas]] are hamartomas comprised of altered [[cardiac myocytes]] that contain large vacuoles and [[glycogen]]. | ||
*Cardiac hamartomas arises from the striated muscle cells (cardiac myocytes), which are normally involved in the coordinated contractions of cardiac muscle cells. | *Cardiac hamartomas arises from the striated muscle cells (cardiac myocytes), which are normally involved in the coordinated contractions of cardiac muscle cells. | ||
*Development of cardiac hamartomas is the result of multiple genetic mutations. | *Development of [[cardiac]] hamartomas is the result of multiple genetic mutations. | ||
*Mutations in the [[TSC1]] or [[TSC2]] genes are related with [[tuberous sclerosis]]. | *Mutations in the [[TSC1]] or [[TSC2]] genes are related with [[tuberous sclerosis]]. | ||
*There is a strong association between cardiac rhabdomyomas and tuberous sclerosis (characterized by hamartomas of the [[central nervous system]], kidneys and [[skin]], as well as pancreatic cysts; 25-50% of patients with cardiac [[rhabdomyomas]] will have [[tuberous sclerosis]]. | *There is a strong association between [[cardiac]] rhabdomyomas and tuberous sclerosis (characterized by hamartomas of the [[central nervous system]], kidneys and [[skin]], as well as pancreatic cysts; 25-50% of patients with cardiac [[rhabdomyomas]] will have [[tuberous sclerosis]]. | ||
*Cardiac hamartoma symptoms will depend on the size of the tumor and location relative to the conduction system. | *Cardiac hamartoma symptoms will depend on the size of the [[tumor]] and location relative to the conduction system. | ||
*For more information on heart hamartoma, See [[Rhabdomyoma|here]] | *For more information on heart hamartoma, See [[Rhabdomyoma|here]]. | ||
===Hypothalamus=== | ===Hypothalamus=== | ||
*Hypothalamic hamartoma is a benign tumor composed of disorganized collections of [[neurons]] and [[glia]]. | *[[Hypothalamic]] hamartoma is a benign tumor composed of disorganized collections of [[neurons]] and [[glia]]. | ||
*Hypothalamic hamartoma is a non-neoplasic heterotopia that typically occurs in the region of the [[hypothalamus]]. This tumor arises from the tuber cinereum, a part of the hypothalamus located between the mamillary bodies and the [[optic chiasm]]. | *[[Hypothalamic]] hamartoma is a non-neoplasic heterotopia that typically occurs in the region of the [[hypothalamus]]. This tumor arises from the tuber cinereum, a part of the [[hypothalamus]] located between the mamillary bodies and the [[optic chiasm]]. | ||
*Unlike other hamartomas, [[hypothalamic hamartoma]] is symptomatic; it most often causes [[gelastic]] [[seizures]], visual problems, and rage disorders associated with hypothalamic diseases. | *Unlike other hamartomas, [[hypothalamic hamartoma]] is symptomatic; it most often causes [[gelastic]] [[seizures]], visual problems, and rage disorders associated with hypothalamic diseases. | ||
*For more information on hypothalamic hamartoma, See [[Hypothalamic hamartoma|here]] | *For more information on [[hypothalamic]] hamartoma, See [[Hypothalamic hamartoma|here]] | ||
===Kidneys, spleen, and other vascular organs=== | ===Kidneys, spleen, and other vascular organs=== | ||
*Spleen and kidney hamartomas may impinge on blood vessels, resulting in a risk of serious [[bleeding]]. | *[[Spleen]] and [[kidney]] hamartomas may impinge on [[blood vessels]], resulting in a risk of serious [[bleeding]]. | ||
*Because hamartoma typically lacks elastic tissue, it may lead to the formation of aneurysms and thus possible [[hemorrhage]]. When a hamartoma impinges into a major [[blood vessel]], such as the [[renal artery]], hemorrhage may be life-threatening.<ref name="radio1">Splenic hamartoma.Dr Henry Knipe et al Radiopedia.http://radiopaedia.org/articles/pulmonary-hamartoma-1 Accessed on December 09, 2015</ref> | *Because hamartoma typically lacks [[elastic tissue]], it may lead to the formation of [[aneurysms]] and thus possible [[hemorrhage]]. When a hamartoma impinges into a major [[blood vessel]], such as the [[renal artery]], hemorrhage may be life-threatening.<ref name="radio1">Splenic hamartoma.Dr Henry Knipe et al Radiopedia.http://radiopaedia.org/articles/pulmonary-hamartoma-1 Accessed on December 09, 2015</ref> | ||
*Hamartoma of the kidney is also called [[angiomyolipoma]] and can be associated with [[tuberous sclerosis]]. | *Hamartoma of the kidney is also called [[angiomyolipoma]] and can be associated with [[tuberous sclerosis]]. | ||
*Spleen hamartomas are often associated with hematologic abnormalities and spontaneous rupture. | *Spleen hamartomas are often associated with [[hematologic]] abnormalities and spontaneous rupture. | ||
*For more information on angiomyolipoma, See [[Angiomyolipoma|here]] | *For more information on [[angiomyolipoma]], See [[Angiomyolipoma|here]]. | ||
==Genetics== | ==Genetics== | ||
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**[[Juvenile polyposis syndrome]] | **[[Juvenile polyposis syndrome]] | ||
**[[Peutz-Jeghers syndrome]] | **[[Peutz-Jeghers syndrome]] | ||
**Hereditary mixed polyposis syndrome | **Hereditary mixed [[polyposis]] syndrome | ||
**PTEN hamartoma | **PTEN hamartoma tumor syndrome | ||
**[[Tuberous sclerosis]] | **[[Tuberous sclerosis]] | ||
**[[Cowden syndrome]] | **[[Cowden syndrome]] | ||
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Hamartoma pathophysiology On the Web |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2] Vamsikrishna Gunnam M.B.B.S [3]
Overview
Hamartomas usually arise from connective tissue and are generally composed of cartilage, fat, and connective tissue cells. Hamartomas can be found in the lungs (most common), heart, hypothalamus, kidneys, or spleen. The pathogenesis primarily consist of disorganized replication of normal tissue cells. Many hereditary syndromes are associated with hamartomatous formation. These include Peutz-Jeghers syndrome, PTEN hamartoma tumor syndrome, and Cowden's syndrome. Genes that are involved in the pathogenesis of hamartomatous syndromes include BMPR1A, SMAD4, PTEN, and STK11.
Pathophysiology
Pathogenesis
- Hamartomas occur in the same location as the normal tissue (in the tissue of its origin) as opposed to choristomas, which grow in other tissues (different from its origin).
- The pathogenesis primarily consists of disorganized replication of normal tissue cells. The underlying mechanisms for the replication abnormality are not fully understood.[1]
- Hamartomas arise from connective tissue and are generally formed of cartilage, fat, and connective tissue cells, although they may include many other types of cells.
- Hamartomas grow at the same rate as the normal cells of the organ.[2]
- These can be located in the lungs (most common), heart, hypothalamus, kidneys, or spleen.[1]
Bone-forming tumors
- Bone-forming tumors (bone islands) are most commonly located in the intramedullary bones of:[3][4][5]
- Bone-forming tumors are masses that are small, white-yellow and round.
- Tumors greater than 2 cm in size are known as giant bone islands.
Cartilage-forming tumors
- It is understood that cartilage-forming tumors like osteochondroma is produced from abnormal cartilaginous epiphyseal growth plate tissue and abnormal regulation of cartilage proliferation.[6][7][8]
- Cartilage-forming tumors are termed as congenital error of epiphyseal development.
Fiber-forming tumors
- It is understood that fiber-forming tumors is produced from continued growth of fibrous cortical defects that extrude into the medullary cavity.
- The most commonly involved bone are tibia and the femur.
Lung
- Lung hamartomas mostly arise from connective tissue and are generally formed of cartilage, fat, and connective tissue cells, although they may include many other types of cells.
- About 5-8% of all solitary lung tumors and about 75% of all benign lung tumors are hamartomas.
- The majority of pulmonary hamartomas form from connective tissue on the outside of the lungs, although about 10% form in the linings of the bronchi.
- In the majority of patients, it can be difficult to distinguish hamartoma from malignancies.[2]
- Pulmonary hamartomas can be divided into two subtypes endobronchial and parenchymal.
- An endobronchial location is described in 3%–20% of all pulmonary hamartomas. This subtype is mainly composed of cartilage and fibrous tissue.
- Endobronchial hamartomas typically contain more fat tissue than parenchymal hamartomas.
Heart
- Cardiac rhabdomyomas are hamartomas comprised of altered cardiac myocytes that contain large vacuoles and glycogen.
- Cardiac hamartomas arises from the striated muscle cells (cardiac myocytes), which are normally involved in the coordinated contractions of cardiac muscle cells.
- Development of cardiac hamartomas is the result of multiple genetic mutations.
- Mutations in the TSC1 or TSC2 genes are related with tuberous sclerosis.
- There is a strong association between cardiac rhabdomyomas and tuberous sclerosis (characterized by hamartomas of the central nervous system, kidneys and skin, as well as pancreatic cysts; 25-50% of patients with cardiac rhabdomyomas will have tuberous sclerosis.
- Cardiac hamartoma symptoms will depend on the size of the tumor and location relative to the conduction system.
- For more information on heart hamartoma, See here.
Hypothalamus
- Hypothalamic hamartoma is a benign tumor composed of disorganized collections of neurons and glia.
- Hypothalamic hamartoma is a non-neoplasic heterotopia that typically occurs in the region of the hypothalamus. This tumor arises from the tuber cinereum, a part of the hypothalamus located between the mamillary bodies and the optic chiasm.
- Unlike other hamartomas, hypothalamic hamartoma is symptomatic; it most often causes gelastic seizures, visual problems, and rage disorders associated with hypothalamic diseases.
- For more information on hypothalamic hamartoma, See here
Kidneys, spleen, and other vascular organs
- Spleen and kidney hamartomas may impinge on blood vessels, resulting in a risk of serious bleeding.
- Because hamartoma typically lacks elastic tissue, it may lead to the formation of aneurysms and thus possible hemorrhage. When a hamartoma impinges into a major blood vessel, such as the renal artery, hemorrhage may be life-threatening.[1]
- Hamartoma of the kidney is also called angiomyolipoma and can be associated with tuberous sclerosis.
- Spleen hamartomas are often associated with hematologic abnormalities and spontaneous rupture.
- For more information on angiomyolipoma, See here.
Genetics
- Genes involved in the pathogenesis of harmatomatous syndromes include:[9]
Associated Conditions
- Hereditary syndromes associated with hamartomatous formation include:[10]
- Juvenile polyposis syndrome
- Peutz-Jeghers syndrome
- Hereditary mixed polyposis syndrome
- PTEN hamartoma tumor syndrome
- Tuberous sclerosis
- Cowden syndrome
- Bannayan-Riley-Ruvalcaba syndrome
Gross Pathology
- On gross pathology, a hallmark feature of hamartoma is a well-circumscribed mass that may show a variegated yellow and white appearance, which corresponds to fat and cartilage, respectively.[11]
- Hamartomas are unencapsulated, lobulated tumors with connective tissue septa.
- Tumor size ranges between 1 and 3 cm in diameter at the time of diagnosis.
Microscopic Pathology
- On microscopic pathology, hamartomas have benign tumors features such as disorganized (non-neoplastic) growth, tissue of the region within it is found, and no invasion to surrounding tissue or structures.[11]
- Common findings include:
- Cartilage single cells in lacunae surrounded by abundant matrix and paucicellular vis-a-vis malignant lesions
- Fat (adipocytes)
- Respiratory epithelium (columnar epithelium with cilia), only present in lung hamartoma
Gallery
-
![Low magnification micrograph of a pulmonary hamartoma. H&E stain.[12]](/images/0/09/Hamartoma_micropathology.jpg)
Low magnification micrograph of a pulmonary hamartoma. H&E stain.[12]
-
![Pulmonary hamartoma: the surrounding lung falls away from the well-circumscribed mass, a typical feature of these lesions. The hamartoma shows a variegated yellow and white appearance, which corresponds respectively to fat and cartilage.[12]](/images/8/8a/Hamartoma_of_the_lung.jpg)
Pulmonary hamartoma: the surrounding lung falls away from the well-circumscribed mass, a typical feature of these lesions. The hamartoma shows a variegated yellow and white appearance, which corresponds respectively to fat and cartilage.[12]
-
![Gross pathology of pulmonary hamartoma.[12]](/images/1/13/Gross_pathology_hamartoma.jpg)
Gross pathology of pulmonary hamartoma.[12]
-
![Epithelial lined clefts within myxoid fibrous connective tissue.[12]](/images/e/e7/Micopathology_hamartoma.jpg)
Epithelial lined clefts within myxoid fibrous connective tissue.[12]
![Low magnification micrograph of a pulmonary hamartoma. H&E stain.[12]](/index.php/File:Hamartoma_micropathology.jpg)
![Pulmonary hamartoma: the surrounding lung falls away from the well-circumscribed mass, a typical feature of these lesions. The hamartoma shows a variegated yellow and white appearance, which corresponds respectively to fat and cartilage.[12]](/index.php/File:Hamartoma_of_the_lung.jpg)
![Gross pathology of pulmonary hamartoma.[12]](/index.php/File:Gross_pathology_hamartoma.jpg)
![Epithelial lined clefts within myxoid fibrous connective tissue.[12]](/index.php/File:Micopathology_hamartoma.jpg)
References
- ↑ 1.0 1.1 1.2 Splenic hamartoma.Dr Henry Knipe et al Radiopedia.http://radiopaedia.org/articles/pulmonary-hamartoma-1 Accessed on December 09, 2015
- ↑ 2.0 2.1 Zakharov V, Schinstine M (2008). "Hamartoma of the lung". Diagn. Cytopathol. 36 (5): 331–2. doi:10.1002/dc.20790. PMID 18418855.
- ↑ McCarthy EF, Dorfman HD (June 1980). "Vascular and cartilaginous hamartoma of the ribs in infancy with secondary aneurysmal bone cyst formation". Am. J. Surg. Pathol. 4 (3): 247–53. PMID 7396066.
- ↑ Balci P, Obuz F, Göre O, Yilmaz E, Demirpolat G, Aktug T, Kovanlikaya I (September 1997). "Aneurysmal bone cyst secondary to infantile cartilaginous hamartoma of rib". Pediatr Radiol. 27 (9): 767–9. doi:10.1007/s002470050224. PMID 9285745.
- ↑ Cohen MC, Drut R, Garcia C, Kaschula RO (1992). "Mesenchymal hamartoma of the chest wall: a cooperative study with review of the literature". Pediatr Pathol. 12 (4): 525–34. PMID 1409151.
- ↑ McCarthy EF, Dorfman HD (June 1980). "Vascular and cartilaginous hamartoma of the ribs in infancy with secondary aneurysmal bone cyst formation". Am. J. Surg. Pathol. 4 (3): 247–53. PMID 7396066.
- ↑ Balci P, Obuz F, Göre O, Yilmaz E, Demirpolat G, Aktug T, Kovanlikaya I (September 1997). "Aneurysmal bone cyst secondary to infantile cartilaginous hamartoma of rib". Pediatr Radiol. 27 (9): 767–9. doi:10.1007/s002470050224. PMID 9285745.
- ↑ Göre O, Kiliçalp A, Başdemir G, Ozer E, Aktuğ T (1999). "Cartilaginous hamartoma of the chest wall with secondary aneurysmal cyst-like areas in an infant: a case report". Turk. J. Pediatr. 41 (1): 139–42. PMID 10770690.
- ↑ Stojcev Z, Borun P, Hermann J, et al. Hamartomatous polyposis syndromes. Hered Cancer Clin Pract. 2013;11(1):4.
- ↑ Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z; et al. (1997). "Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome". Nat Genet. 16 (1): 64–7. doi:10.1038/ng0597-64. PMID 9140396.
- ↑ 11.0 11.1 Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. Elsevier Health Sciences; 2012.
- ↑ 12.0 12.1 12.2 12.3 Hamartoma. Libre Pathology.http://librepathology.org/wiki/index.php/Pulmonary_hamartoma Accessed on December 8, 2015