Hamartoma

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Hamartoma
Spleen hamartom.jpg
A large hamartoma of the spleen. The hamartoma is the dark circular object on the left that dominates the image. This is a cross-section; the growth is about 9 cm in diameter, while the entire spleen is about 11 cm in diameter. [1]
Specialty Medical genetics, pathology   OOjs UI icon edit-ltr-progressive.svg

A hamartoma is a mostly benign, [2] local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended from a single mutated cell (monoclonality), as would typically define a benign neoplasm/tumor. [3] Despite this, many hamartomas are found to have clonal chromosomal aberrations that are acquired through somatic mutations, and on this basis the term hamartoma is sometimes considered synonymous with neoplasm. Hamartomas are by definition benign, slow-growing or self-limiting, [2] [3] though the underlying condition may still predispose the individual towards malignancies.

Contents

Hamartomas are usually caused by a genetic syndrome that affects the development cycle of all or at least multiple cells. [3] Many of these conditions are classified as overgrowth syndromes or cancer syndromes. Hamartomas occur in many different parts of the body and are most often asymptomatic incidentalomas (undetected until they are found incidentally on an imaging study obtained for another reason). Additionally, the definition of hamartoma versus benign neoplasm is often unclear, since both lesions can be clonal. Lesions such as adenomas, developmental cysts, hemangiomas, lymphangiomas and rhabdomyomas within the kidneys, lungs or pancreas are interpreted by some experts as hamartomas while others consider them true neoplasms. Moreover, even though hamartomas show a benign histology, there is a risk of some rare but life-threatening complications such as those found in neurofibromatosis type I and tuberous sclerosis. [4]

It is different from choristoma, a closely related form of heterotopia. [5] [6] The two can be differentiated as follows: a hamartoma is an excess of normal tissue in a normal situation (e.g., a birthmark on the skin), while a choristoma is an excess of tissue in an abnormal situation (e.g., pancreatic tissue in the duodenum). [7] [8] The term hamartoma is from the Greek ἁμαρτία, hamartia ("error"), and was introduced by D.P.G. Albrecht in 1904.

Causes

Hamartomas result from an abnormal formation of normal tissue, although the underlying reasons for the abnormality are not fully understood. They grow along with, and at the same rate as, the organ from whose tissue they are made, and, unlike cancerous tumors, only rarely invade or compress surrounding structures significantly.[ citation needed ]

Diagnosis


Types

Lung

Parenchymal hamartoma of the lung. 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. Hamartoma of the lung.jpg
Parenchymal hamartoma of the lung. 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.

The most common hamartomas occur in the lungs. About 5–8% of all solitary lung nodules, about 75% of all benign lung tumors, are hamartomas. They almost always arise from connective tissue and are generally formed of cartilage, connective tissue, and fat cells, although they may include many other types of cells. The great majority of them form in the connective tissue on the outside of the lungs, although about 10% form deep in the linings of the bronchi. They can be worrisome, especially if situated deep in the lung, as it is sometimes difficult to make the important distinction between a hamartoma and a lung malignancy. An X-ray will often not provide a definitive diagnosis, and even a CT scan may be insufficient if the hamartoma lacks the typical cartilage and fat cells. Lung hamartomas may have popcorn-like calcifications on chest xray or computed tomography (CT scan).

Lung hamartomas are more common in men than in women, and may present additional difficulties in smokers.

Some lung hamartomas can compress surrounding lung tissue to a degree, but this is generally not debilitating and is often asymptomatic, especially for the more common peripheral growths. They are treated, if at all, by surgical resection, with an excellent prognosis: generally, the only real danger is the inherent possibility of surgical complications.

Heart

Cardiac rhabdomyomas are hamartomas composed of altered cardiac myocytes that contain large vacuoles and glycogen. They are the most common tumor of the heart in children and infants. 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. Symptoms depend on the size of the tumor, its location relative to the conduction system, and whether or not it obstructs blood flow. Symptoms are usually from congestive heart failure; in utero heart failure may occur. If patients survive infancy, their tumors may regress spontaneously; resection in symptomatic patients has good results.

Hypothalamus

One of the most troublesome hamartomas occurs on the hypothalamus. Unlike most such growths, 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. Moreover, resection is usually difficult, as the growths are generally adjacent to, or even intertwined with, the optic nerve. Symptoms tend to be resistant to medical control; however, surgical techniques are improving and can result in immense improvement of prognosis. [9]

Kidneys, stomach, spleen and other vascular organs

Hamartoma in breast with ultrasound Hamartoma in breast.jpg
Hamartoma in breast with ultrasound

One general danger of hamartomas is that they may impinge into blood vessels, resulting in a risk of serious bleeding. Because a hamartoma typically lacks elastic tissue, it may lead to the formation of aneurysms and thus possible hemorrhage. Where a hamartoma impinges into a major blood vessel, such as the renal artery, hemorrhage must be considered life-threatening.

Angiomyolipoma of the kidney was previously considered to be a hamartoma or choristoma.

A myoepithelial hamartoma, also known as a pancreatic rest, is ectopic pancreatic tissue found in the stomach, duodenum, or proximal jejunum. When seen on upper gastrointestinal series, a pancreatic rest may appear to be a submucosal mass or gastric neoplasm. Most are asymptomatic, but they can cause dyspepsia or upper gastrointestinal bleeding. [10]

A hamartoma has been identified as a cause of partial outflow obstruction in the abomasum (true gastric stomach) of a dairy goat [11] .

Hamartomas of the spleen are uncommon but can be dangerous. About 50% of such cases manifest abdominal pain, and they are often associated with hematologic abnormalities and spontaneous rupture.

Cowden syndrome

Cowden syndrome is a serious genetic disorder [12] characterized by multiple hamartomas. Usually skin hamartomas exist, and commonly (in about 66% of cases) hamartoma of the thyroid gland exists. Additional growths can form in many parts of the body, especially in bones, CNS, the eyes, the genitourinary tract, the GI tract, and mucosa. 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. Cowden syndrome is considered a PTEN hamartoma tumor syndrome (PHTS), which also includes Bannayan–Riley–Ruvalcaba syndrome, Proteus syndrome and Proteus-like syndrome.

Prognosis

Hamartomas, while generally benign, can cause problems due to their location. For example, when located on the skin, especially on the face or neck, they can be very disfiguring. Cases have been reported of hamartomas the size of a small orange. [13] They may obstruct practically any organ in the body, such as the colon, eye, etc. They are particularly likely to cause major health issues when located in the hypothalamus, kidneys, lips, or spleen. They can be removed surgically if necessary, and are not likely to recur. Prognosis will depend upon the location and size of the lesion, as well as the overall health of the patient.[ citation needed ]

See also

Related Research Articles

Brain tumor neoplasm in the brain

A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: cancerous (malignant) tumors and benign (non-cancerous) tumors. Cancerous tumors can be divided into primary tumors, which start within the brain, and secondary tumors, which have spread from elsewhere, known as brain metastasis tumors. All types of brain tumors may produce symptoms that vary depending on the part of the brain involved. These symptoms may include headaches, seizures, problems with vision, vomiting and mental changes. The headache is classically worse in the morning and goes away with vomiting. Other symptoms may include difficulty walking, speaking or with sensations. As the disease progresses, unconsciousness may occur.

Bone tumor tumor or cancer located in bone tissue or specific bones

A bone tumor is a neoplastic growth of tissue in bone. Abnormal growths found in the bone can be either benign (noncancerous) or malignant (cancerous).

Adenoma Type of benign tumor

An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenomas grow from epithelial tissue in nonglandular areas but express glandular tissue structure. Although adenomas are benign, they should be treated as pre-cancerous. Over time adenomas may transform to become malignant, at which point they are called adenocarcinomas. Most adenomas do not transform. However, even though benign, they have the potential to cause serious health complications by compressing other structures and by producing large amounts of hormones in an unregulated, non-feedback-dependent manner. Some adenomas are too small to be seen macroscopically but can still cause clinical symptoms.

Tuberous sclerosis rare multisystem genetic disease that causes benign tumors to grow in the brain and on other vital organs

Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung disease, and kidney disease.

Rhabdomyoma benign mesenchymal tumor arising from skeletal or cardiac muscle

A rhabdomyoma is a benign tumor of striated muscle. Rhabdomyomas may be either "cardiac" or "extra cardiac". Extracardiac forms of rhabdomyoma are sub classified into three distinct types: adult type, fetal type, and genital type.

Spinal tumors are neoplasms located in either the vertebral column or the spinal cord. There are three main types of spinal tumors classified based on their location: extradural and intradural. Extradural tumors are located outside the dura mater lining and are most commonly metastatic. Intradural tumors are located inside the dura mater lining and are further subdivided into intramedullary and extramedullary tumors. Intradural-intramedullary tumors are located within the dura and spinal cord parenchyma, while intradural-extramedullary tumors are located within the dura but outside the spinal cord parenchyma. The most common presenting symptom of spinal tumors is nocturnal back pain. Other common symptoms include muscle weakness, sensory loss, and difficulty walking. Loss of bowel and bladder control may occur during the later stages of the disease.

Adrenocortical carcinoma adrenal cortex cancer that forms in the outer layer of tissue of the adrenal gland and that has material basis in abnormally proliferating cells derives from epithelial cells

Adrenocortical carcinoma (ACC) is an aggressive cancer originating in the cortex of the adrenal gland.

Benign tumor disease of cellular proliferation that results in abnormal growths in the body which lack the ability to metastasize

A benign tumor is a mass of cells (tumor) that lacks the ability to invade neighboring tissue or metastasize. However, they can sometimes be quite large. When removed, benign tumors usually do not grow back, whereas malignant tumors sometimes do. Unlike most benign tumors elsewhere in the body, benign brain tumors can be life threatening. Benign tumors generally have a slower growth rate than malignant tumors and the tumor cells are usually more differentiated. They are typically surrounded by an outer surface or remain with the epithelium. Common examples of benign tumors include moles and uterine fibroids.

Birt–Hogg–Dubé syndrome human autosomal dominant genetic disorder that can cause susceptibility to kidney cancer, renal and pulmonary cysts

Birt–Hogg–Dubé syndrome (BHD), also Hornstein–Birt–Hogg–Dubé syndrome, Hornstein–Knickenberg syndrome, and fibrofolliculomas with trichodiscomas and acrochordons is a human autosomal dominant genetic disorder that can cause susceptibility to kidney cancer, renal and pulmonary cysts, and noncancerous tumors of the hair follicles, called fibrofolliculomas. The symptoms seen in each family are unique, and can include any combination of the three symptoms. Fibrofolliculomas are the most common manifestation, found on the face and upper trunk in over 80% of people with BHD over the age of 40. Pulmonary cysts are equally common (84%), but only 24% of people with BHD eventually experience a collapsed lung. Kidney tumors, both cancerous and benign, occur in 14–34% of people with BHD; the associated kidney cancers are often rare hybrid tumors.

Hemangioendothelioma group of vascular neoplasms

Hemangioendotheliomas are a family of vascular neoplasms of intermediate malignancy.

Multiple endocrine neoplasia type 1 autosomal dominant disease that has material basis in a mutation in the MEN1 tumor suppressor gene and is characterized by over active endocrine glands frequently involving tumors of the parathyroid glands, the pituitary gland, and the pancreas

Multiple endocrine neoplasia type 1 (MEN-1) is one of a group of disorders, the multiple endocrine neoplasias, that affect the endocrine system through development of neoplastic lesions in pituitary, parathyroid gland and pancreas.

Angiomyolipoma cell type benign neoplasm that from perivascular epithelioid cells

Angiomyolipomas are the most common benign tumour of the kidney. Although regarded as benign, angiomyolipomas may grow such that kidney function is impaired or the blood vessels may dilate and burst, leading to bleeding.

Granular cell tumor Human disease

Granular cell tumor is a tumor that can develop on any skin or mucosal surface, but occurs on the tongue 40% of the time.

Mediastinal germ cell tumors are tumors that derive from germ cell rest remnants in the mediastinum. They most commonly occur in the gonad but occasionally elsewhere.

A gelastic seizure, also known as "gelastic epilepsy", is a rare type of seizure that involves a sudden burst of energy, usually in the form of laughing or crying. This syndrome usually occurs for no obvious reason and is uncontrollable. It is slightly more common in males than females.

An adrenal tumor or adrenal mass is any benign or malignant neoplasms of the adrenal gland, several of which are notable for their tendency to overproduce endocrine hormones. Adrenal cancer is the presence of malignant adrenal tumors, and includes neuroblastoma, adrenocortical carcinoma and some adrenal pheochromocytomas. Most adrenal pheochromocytomas and all adrenocortical adenomas are benign tumors, which do not metastasize or invade nearby tissues, but may cause significant health problems by unbalancing hormones.

Congenital mesoblastic nephroma, while rare, is the most common kidney neoplasm diagnosed in the first three months of life and accounts for 3-5% of all childhood renal neoplasms. This neoplasm is generally non-aggressive and amenable to surgical removal. However, a readily identifiable subset of these kidney tumors has a more malignant potential and is capable of causing life-threatening metastases. Congenital mesoblastic nephroma was first named as such in 1967 but was recognized decades before this as fetal renal hamartoma or leiomyomatous renal hamartoma.

Lhermitte–Duclos disease rare neoformation of the cerebellum due to a mutation in the PTEN-Gen

Lhermitte–Duclos disease (LDD), also called dysplastic gangliocytoma of the cerebellum, is a rare, slowly growing tumor of the cerebellum, a gangliocytoma sometimes considered to be a hamartoma, characterized by diffuse hypertrophy of the granular layer of the cerebellum. It is often associated with Cowden syndrome. It was described by Jacques Jean Lhermitte and P. Duclos in 1920.

Cardiac fibroma, also known as cardiac fibromatosis, cardiac fibrous hamartoma, fibroelastic hamartoma of heart and fibroma of heart is the second highest type of primary cardiac tumor seen in infants and children. This benign tumor made by connective tissue and fibroblast is largely observed in the ventricles of the heart. The left ventricle is the most common location of cardiac fibroma and accounts for approximately 57% of cardiac fibroma cases followed by the right ventricle with 27.5% of cases. Symptoms of the disease depend on the size of the tumor, its location relative to the conduction system, and whether it obstructs blood flow. Two-thirds of children with this tumor are asymptomatic, showing no signs and symptoms. Therefore the cause of cardiac fibroma is unexplained but has been associated with Gorlin Syndrome. Echocardiography is the primarily diagnostic method used to detect if an individual has cardiac fibroma. Resection of the tumor is recommended however heart transplantation is done if surgery is not possible. Overall prognosis of resection is favorable and the chance of recurrence is scarcely reported.

Rhabdomyoma is a benign mesenchymal tumor of skeletal muscle, separated into two major categories based on site: Cardiac and extracardiac. They are further separated by histology: fetal, juvenile (intermediate), and adult types. Genital types are recognized, but are often part of either the fetal or juvenile types. The fetal type is thought to recapitulate immature skeletal muscle at about week six to ten of gestational development.

References

  1. Uthman, Ed (2 January 1999). "Hamartoma of the spleen". [Personal website]. Archived from the original on 15 June 2014. Retrieved 30 July 2014.
  2. 1 2 "Hamartoma definition". Taber's Medical Dictionary. Archived from the original on 7 December 2008. Retrieved 2008-09-25.
  3. 1 2 3 Batsakis, John G. (1984-01-01). "Nomenclature of Developmental Tumors". Annals of Otology, Rhinology & Laryngology. 93 (1): 98–99. doi:10.1177/000348948409300122. ISSN   0003-4894. PMID   6703601.
  4. Kumar, Abbas, Aster. Robbin's Pathologic Basis of Disease (9th ed.). p. 481.CS1 maint: multiple names: authors list (link)
  5. " Choristoma " at Dorland's Medical Dictionary
  6. Lee, Kenneth H.; Roland, Peter S. (2013). Heterotopias, Teratoma, and Choristoma. Encyclopedia of Otolaryngology, Head and Neck Surgery. pp. 1179–1183. doi:10.1007/978-3-642-23499-6_642. ISBN   978-3-642-23498-9.
  7. Jorquera, JessicaPatricia Correa; Rubio-Palau, Josep; Cazalla, AsteriaAlbert; Rodríguez-Carunchio, Leonardo (2016). "Choristoma: A rare congenital tumor of the tongue". Annals of Maxillofacial Surgery. 6 (2): 311–313. doi:10.4103/2231-0746.200342. PMC   5343649 . PMID   28299279.
  8. Goswamy, Monika; Tabasum, Syeda; Kudva, Praveen; Gupta, Shikha (2012). "Osseous choristoma of the periodontium". Journal of Indian Society of Periodontology. 16 (1): 120–2. doi:10.4103/0972-124X.94619. PMC   3357020 . PMID   22628977.
  9. "Hypothalmic Hamartoma". Barrow Neurological Institute.
  10. Shah A, Gordon AR, Ginsberg GG, Furth EE, Levine MS. Case report: ectopic pancreatic rest in the proximal stomach mimicking gastric neoplasms. Clin Radiol. 2007 Jun;62(6):600-2. Epub 2007 Mar 26. No abstract available.
  11. https://vetrecordcasereports.bmj.com/content/5/3/e000515
  12. Mutation of PTEN gene on arm 10q (~85% of cases) or rarely germline mutation in BMPR1A
  13. "Dermatology Images". Dermatology Image Atlas. Archived from the original on 2006-05-15.
Classification
D
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