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==Overview==
==Overview==


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. They can be located in [[lung]] (most common), [[heart]], [[hypothalamus]], [[kidneys]], or [[spleen]]. The pathogenesis consists of the disorganized replication of normal tissue cells. There are many genetic syndromes that cause multiple hamartomas, such as; Peutz-Jeghers syndrome, PTEN hamartoma tumour syndrome and Cowden’s syndrome. Genes involved in the pathogenesis of harmatomatous syndromes include; [[BMPR1A]], [[SMAD4]], [[PTEN]], and [[STK11]].<ref>Stojcev Z, Borun P, Hermann J, et al. Hamartomatous polyposis syndromes. Hered Cancer Clin Pract. 2013;11(1):4.</ref><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 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==
*Hamartomas grow along with, and at the same rate as, the organ from whose tissue they are made, and, as opposed to choristomas, only occur in the same location as the normal tissue.<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>
*Hamartomas result from an abnormal formation of normal tissue, although the underlying reasons for the abnormality are not fully understood. 


===Lung===
=== 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).
*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 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 (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.


*In general, most hamartomas occur in the [[lungs]].
=== Cartilage-forming tumors ===
*About 5-8% of all solitary lung tumors and about 75% of all [[benign]] lung tumors are hamartomas.
* 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>
*They 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.
*The majority of pulmonary hamartomas form of [[connective tissue]] on the outside of the lungs, although about 10% form in the linings of the bronchi.  
*In most cases, 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: endobronchial and parenchymal. Endobronchial location is described in 3%–20% of all pulmonary hamartomas. This subtype is mainly composed of cartilage and fibrous tissue. On the other hand, endobronchial hamartomas typically contain more fat tissue than parenchymal ones.


===Heart===
* Cartilage-forming tumors are termed as congenital error of epiphyseal development.


Cardiac [[rhabdomyomas]] are hamartomas comprised of altered cardiac myocytes that contain large vacuoles and [[glycogen]]. They are the second most common tumor of the heart in children and infants (after fibromas). 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]], and up to 100% of patients with tuberous sclerosis will have cardiac masses by [[echocardiography]].
=== Fiber-forming tumors ===
Cardiac hamartoma symptoms depend on the size of the tumor, its location relative to the conduction system, and whether it obstructs blood flow.  Symptoms are usually from congestive heart failure.  If patients survive [[infancy]], their tumors may regress spontaneously; resection in symptomatic patients has good results.<ref>Stojcev Z, Borun P, Hermann J, et al. Hamartomatous polyposis syndromes. Hered Cancer Clin Pract. 2013;11(1):4.</ref><ref name="kumar">Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. Elsevier Health Sciences; 2012.</ref>
* 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.


===Hypothalamus===
===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]].<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 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.


A hypothalamic or tuber cinereum hamartoma is benign non neoplasic heterotopia in the brain that typically occurs in the region of the hypothalamus, arising from the tuber cinereum, a part of the hypothalamus located between the mamillary bodies and the optic chiasm. Also called "''Tuber cinereum hamartoma''" unlike other hamartomas, a [[hypothalamic hamartoma]] is symptomatic; it most often causes [[gelastic]] [[seizures]], and can cause visual problems, other seizures, rage disorders associated with hypothalamic diseases, and early onset of puberty. The symptoms typically begin in early infancy and are progressive, often into general [[cognitive]] and/or functional disability.<ref>Zhu M, Maeda M, Lee GJ, and Yuh WTC: Chapter 53. Sellar Lesions. In: Stark DD. Bradley WG. (eds): Magnetic Resonance Imaging. (ed 3)St. Louis:Mosby,1999, pp 1225–1230</ref>
===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 [[Rhabdomyoma|here]].


For more information on hypothalamic hamartoma, See [[Hypothalamic hamartoma|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 [[Hypothalamic hamartoma|here]]


===Kidneys, spleen, and other vascular organs===
===Kidneys, spleen, and other vascular organs===


One general danger of hamartoma is that they 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>
*[[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>
 
*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]].  It is one of the more frequently seen hamartomas. The condition is more prevalent in women than men, and generally occurs in the right kidney.  Hamartomas of the spleen are uncommon, but can be dangerous. They  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==
Genes involved in the pathogenesis of harmatomatous syndromes include [[BMPR1A]], [[SMAD4]], [[PTEN]] and [[STK11]].<ref>Stojcev Z, Borun P, Hermann J, et al. Hamartomatous polyposis syndromes. Hered Cancer Clin Pract. 2013;11(1):4.</ref>  
*Genes involved in the pathogenesis of harmatomatous syndromes include:<ref>Stojcev Z, Borun P, Hermann J, et al. Hamartomatous polyposis syndromes. Hered Cancer Clin Pract. 2013;11(1):4.</ref>
 
:*[[BMPR1A]]
:*[[SMAD4]]
:*[[PTEN]]
:*[[STK11]]
==Associated Conditions==
==Associated Conditions==
Many hereditary syndromes are associated with hamartomatous formation. The familial inheritance diseases include;  juvenile polyposis syndrome, Peutz-Jeghers syndrome, hereditary mixed polyposis syndrome (HMPS) and PTEN hamartoma tumour syndrome, tuberous sclerosis, [[Cowden’s syndrome]] and Bannayan-Riley-Ruvalcaba syndrome.
*Hereditary syndromes associated with hamartomatous formation include:<ref name="pmid9140396">{{cite journal| author=Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z et al.| title=Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. | journal=Nat Genet | year= 1997 | volume= 16 | issue= 1 | pages= 64-7 | pmid=9140396 | doi=10.1038/ng0597-64 | pmc= | url= }} </ref>  
 
**[[Juvenile polyposis syndrome]]
===Cowden syndrome===
**[[Peutz-Jeghers syndrome]]
For more information on cowden syndrome, See [[Cowden syndrome|here]]
**Hereditary mixed [[polyposis]] syndrome
 
**PTEN hamartoma tumor syndrome
Cowden syndrome is a serious genetic disorder characterized by multiple hamartomas. <ref name="pmid9140396">{{cite journal| author=Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z et al.| title=Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. | journal=Nat Genet | year= 1997 | volume= 16 | issue= 1 | pages= 64-7 | pmid=9140396 | doi=10.1038/ng0597-64 | pmc= | url= }} </ref> Usually [[skin]] hamartomas exist, and commonly (about 66% of cases) hamartoma of the [[thyroid gland]] exists.  Additional growths can form in many parts of the body, especially in [[mucosa]], the GI tract, [[bone]]s, CNS, the [[eye]]s, and the [[genitourinary tract]].  The hamartomas themselves may cause symptoms or even death, but morbidity is more often associated with increased occurrence of [[malignancies]], usually in the [[breast]] or thyroid.
**[[Tuberous sclerosis]]
 
**[[Cowden syndrome]]
===Tuberous sclerosis===
**Bannayan-Riley-Ruvalcaba syndrome
For more information on tuberous sclerosis, See [[Tuberous sclerosis|here]]
 
Tuberous sclerosis is a syndrome caused by potentially by more than 900 mutations of the tumor suppressor genes for [[tuberin]] (TSC2) and hamartin (TSC1) that cause abnormal cellular signaling through the [[rapamycin]] complex 1. It is characterized by multiple hamartomas, [[angiomyolipoma]]s (in 80%) and lymphangioleiomyomatosis usually in women. Important clinical features include; [[Epilepsy]], learning difficulties, and skin tumors.
 
===Peutz-Jeghers syndrome===
For more information on Peutz-Jeghers syndrome, See [[Peutz-Jeghers syndrome|here]]
 
Peutz-Jeghers syndrome is an autosomal dominant disorder characterised by the concurrence of hamartomatous intestinal polyps with mucocutaneous melanotic macules usually on the lips, buccal mucosa, and digits.The polyps are usually benign but there is a 15x increase in the risk of bowel and other cancer compared to the general population. Females are more likely to develop granulosa cell ovarian tumours. Cancers of the pancreas, stomach, and even multiple myeloma are associated. It is caused by mutations of the STK11 gene at 19p13.3.<ref>Peutz-Jeghers syndrome. http://www.ganfyd.org/index.php?title=Peutz-Jeghers_syndrome Accessed on December 09,2015</ref>


==Gross Pathology==
==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 respectively to fat and cartilage.<ref name="kumar">Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. Elsevier Health Sciences; 2012.</ref> They are unencapsulated, lobulated tumors with connective tissue septa. Tumoral size ranges between 1 and 3 cm in diameter at the time of diagnosis.
*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.<ref name="kumar">Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. Elsevier Health Sciences; 2012.</ref>
*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==
==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.<ref name="kumar">Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. Elsevier Health Sciences; 2012.</ref>
*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.<ref name="kumar">Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. Elsevier Health Sciences; 2012.</ref>
 
*Common findings include:  
Common findings include:
:*[[Cartilage]] single cells in lacunae surrounded by abundant matrix and paucicellular vis-a-vis malignant lesions
 
:*[[Fat]] ([[adipocytes]])
Cartilage
:*Respiratory epithelium (columnar epithelium with cilia), only present in lung hamartoma
:*Single cells in lacunae surrounded by abundant matrix
:*Paucicellular vis-a-vis malignant lesions
 
Fat (adipocytes)
:*Respiratory epithelium (columnar epithelium with cilia) - lung hamartoma


==Gallery==
==Gallery==


<div align="center">
<div align="left">
<gallery heights="150" widths="150">
<gallery heights="150" widths="150">
Image:Hamartoma micropathology.jpg |Low magnification micrograph of a pulmonary hamartoma. H&E stain.<ref name=lp> Hamartoma. Libre Pathology.http://librepathology.org/wiki/index.php/Pulmonary_hamartoma Accessed on December 8, 2015</ref>
Image:Hamartoma micropathology.jpg |Low magnification micrograph of a pulmonary hamartoma. H&E stain.<ref name=lp> Hamartoma. Libre Pathology.http://librepathology.org/wiki/index.php/Pulmonary_hamartoma Accessed on December 8, 2015</ref>
Image: 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.<ref name=lp>Hamartoma. Libre Pathology.http://librepathology.org/wiki/index.php/Pulmonary_hamartoma Accessed on December 8, 2015</ref>
Image: 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.<ref name=lp>Hamartoma. Libre Pathology.http://librepathology.org/wiki/index.php/Pulmonary_hamartoma Accessed on December 8, 2015</ref>
Image:Gross pathology hamartoma.jpg|Gross pathology of pulmonary hamartoma.<ref name=lp>Hamartoma. Libre Pathology.http://librepathology.org/wiki/index.php/Pulmonary_hamartoma Accessed on December 8, 2015</ref>
Image:Gross pathology hamartoma.jpg|Gross pathology of pulmonary hamartoma.<ref name=lp>Hamartoma. Libre Pathology.http://librepathology.org/wiki/index.php/Pulmonary_hamartoma Accessed on December 8, 2015</ref>
Image:Micopathology hamartoma.jpg|Epithelial lined clefts within myxoid fibrous connective tissue.<ref name=lp>Hamartoma. Libre Pathology.http://librepathology.org/wiki/index.php/Pulmonary_hamartoma Accessed on December 8, 2015</ref>
Image:Micopathology hamartoma.jpg|Epithelial lined clefts within myxoid fibrous connective tissue.<ref name=lp>Hamartoma. Libre Pathology.http://librepathology.org/wiki/index.php/Pulmonary_hamartoma Accessed on December 8, 2015</ref>
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Latest revision as of 04:12, 5 April 2019

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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

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

Kidneys, spleen, and other vascular organs

Genetics

  • Genes involved in the pathogenesis of harmatomatous syndromes include:[9]

Associated Conditions

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]

    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]

    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]

    Gross pathology of pulmonary hamartoma.[12]

  • Epithelial lined clefts within myxoid fibrous connective tissue.[12]

    Epithelial lined clefts within myxoid fibrous connective tissue.[12]

References

  1. ↑ 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. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ Stojcev Z, Borun P, Hermann J, et al. Hamartomatous polyposis syndromes. Hered Cancer Clin Pract. 2013;11(1):4.
  10. ↑ 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. ↑ 11.0 11.1 Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. Elsevier Health Sciences; 2012.
  12. ↑ 12.0 12.1 12.2 12.3 Hamartoma. Libre Pathology.http://librepathology.org/wiki/index.php/Pulmonary_hamartoma Accessed on December 8, 2015


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