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Hamartomas

A hamartoma is defined as a focal growth that resembles a neoplasm but results from faulty development in an organ¹. They can occur anywhere in the body. They have been described in many organs but especially the chest, breast, skin and brain. They are also reported in the eye, colon and liver.

Hamartomas are a major feature of tuberous sclerosis.
Hypothalamic hamartoma (HH) is a rare benign brain tumour located near the hypothalamus.
Multiple hamartomas throughout the body is called Cowden's disease. Most isolated hamartomas are benign but in Cowden's disease there is a risk that one or more may undergo malignant change.
Multiple benign hamartomas are called Proteus syndrome. The condition reached public attention with the film "The Elephant Man".

Epidemiology
Incidence It is difficult to give an accurate assessment of incidence as many skin lesions are simply ignored as "birth marks" and many internal lesions are incidental findings. Most cause no trouble but where they represent space-occupying lesions, especially in the brain, they have serious consequences.

Uterine fibroids are a very common hamartoma.
Over 200 cases of Cowden's disease have been described worldwide. It is rare.
Only about 120 cases of Proteus syndrome have been described worldwide.

Risk Factors Cowden's disease and tuberous sclerosis are autosomal dominants with equal sex distribution. The genetics of Proteus syndrome is less certain. It may be sporadic or an autosomal dominant but it is probably due to the absence of a suppressor gene.

Presentation
Symptoms Symptoms depend upon the site of the lesion and they may present at any time from birth to middle age but usually early in life. There may be a disfigurement of the skin. It may be an incidental finding on CXR or mammography . In the brain they can cause epilepsy and mental handicap is common but not inevitable and varies in severity.

In hypothalamic hamartoma (HH) epilepsy begins in infancy with gelastic or laughing seizures². Early childhood development is normal. The laughter is brief, frequent and mechanical in nature. It is often not recognised that the child is having a seizure and so the diagnosis is delayed.

Between 4 and 10, the disorder becomes more ominous. The pleasant giggle changes to seizures that become longer, more severe and sound less natural. Secondary generalized epilepsy may appear. Multiple seizures and progressive cognitive impairment occur. The child may show bouts of extreme rages, poor social adjustment, and often precocious puberty .

Signs Skin and mucous membranes: Papules of various types, fibromas, keratoses, café au lait patches and haemangiomas are all described.

Chest: Hamartomas represent 6 to 8% of the localised masses in the chest. The majority are peripheral and produce no symptoms but some produce respiratory symptoms and chronic cough³. A small number may grow slowly. They are unusual before the third decade. They appear on chest x-ray as a "coin lesion" that has to be differentiated from a granuloma or malignant neoplasm . They are discreet and often have calcification making them radio-opaque. They are usually less than 2 cm and composed mostly of benign cartilage.

Breast: Hamartomas are an uncommon benign breast lesion composed of variable amounts of adipose, glandular and fibrous tissues. They are usually asymptomatic but may be palpable. Most occur in women over 35. A confident diagnosis can be made on mammography when the lesion has a classical appearance.

Head and Neck: It may present as a swelling or lump in the head or neck, as pain in the chin, neck or face or as hoarseness .

Gastrointestinal tract: Polyps can occur anywhere in the gut but are commonest in the colon. The malignant potential of polyps is low, unlike familial polyposis coli.

Differential Diagnosis

• Isolated lesions are usually excised and examined for histology to confirm their nature.
• The main concern is that the lesion may be malignant.
• The classical features of tuberous sclerosis are not always present, especially in the early years.
• Hypothalamic hamartoma is one of the few diseases to cause gelastic seizures. Others are temporal lobe epilepsy , infantile spasm, Angelmann's syndrome , hypothalamic gliomas and tumours of the third ventricle.

Investigations

• If an intracranial hamartoma is suspected a CT or MRI scan is required.
• CT or MRI of the chest or mammography may produce enough confidence in the diagnosis to remove the need for excision biopsy⁴.

Associated Diseases

• Tuberous sclerosis has many other features.
• In Cowden's disease there is a risk of malignant change, especially producing breast cancer in women and follicular carcinoma of thyroid in men. For more details see website listed below.
• More information about hypothalamic hamartomas may also be found on the website below.

Management Management depends upon a firm diagnosis followed by appropriate action. Most isolated lesions can be ignored. If it is part of a syndrome like tuberous sclerosis or Cowden's syndrome the management is as for that disease.

Non-Drug Intracranial lesions may require management of developmental delay or behavioural problems.

Drugs Epilepsy may need treatment.

Surgical Excision biopsy is often required for diagnosis. For skin lesions chemical peels, laser resurfacing, surgery or shave excisions may be required.

Complications

• Malignant change is common in Cowden's syndrome.
• It is less common in tuberous sclerosis.
• In isolated lesions it is rare.
• Hypothalamic hamartomas are benign but the lesion usually straddles the optic nerve, making removal extremely difficult⁵ or impossible.

Prognosis In Cowden's syndrome:

• At least 40% develop at least one malignant tumour.
• 1 in 3 women develop breast cancer and prophylactic bilateral mastectomy is often employed.
• Thyroid cancer occurs in 7% but unlike the general population is more common in men.

References Used

1. Websters Online
2. Brandberg G, Raininko R, Eeg-Olofsson O; Hypothalamic hamartoma with gelastic seizures in Swedish children and adolescents.;Eur J Paediatr Neurol 2004;8(1):35-44.[abstract]
3. Lien YC, Hsu HS, Li WY, et al; Pulmonary hamartoma.;J Chin Med Assoc 2004 Jan;67(1):21-6.[abstract]
4. Georgian-Smith D, Kricun B, McKee G, et al; The mammary hamartoma: appreciation of additional imaging characteristics.;J Ultrasound Med 2004 Oct;23(10):1267-73.[abstract]
5. Polkey CE; Resective surgery for hypothalamic hamartoma.;Epileptic Disord 2003 Dec;5(4):281-6.[abstract]

Internet and Further Reading

• Cowden's  Syndrome on eMedicine
• Hypothalamic  hamartomas
• Proteus  Syndrome on eMedicine

Acknowledgements EMIS is grateful to the Mentor authoring team for writing this article. The final copy has passed peer review of the independent Mentor GP authoring team. ©EMIS 2004.

Last issued 30 Aug 2006