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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. 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.
Because Cowden syndrome can be difficult to diagnose, the exact prevalence is unknown; however, it probably occurs in at least 1 in 200,000 people.
A 2010 review of 211 patients (21 from one center, and the remaining 190 from the external literature) studied the risks for cancer and Lhermitte-Duclos disease in Cowden syndrome patients.
The cumulative lifetime (age 70 years) risks were 89% for any cancer diagnosis (95% confidence interval (CI) = 80%,95%), breast cancer [female] 81% (CI = 66%,90%), LDD 32% (CI = 19%,49%), thyroid cancer 21% (CI = 14%,29%), endometrial cancer 19% (CI = 10%,32%) and renal cancer 15% (CI = 6%,32%). A previously unreported increased lifetime risk for colorectal cancer was identified (16%, CI = 8%,24%). Male CS patients had fewer cancers diagnosed than female patients and often had cancers not classically associated with CS.
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.
Most juvenile polyps are benign, however, malignancy can occur. The cumulative lifetime risk of colorectal cancer is 39% in patients with juvenile polyposis syndrome.
Surgical excision is the preferred method of treatment for benign glomus tumors.
PTEN hamartoma syndrome comprises four distinct hamartomatous disorders characterised by genetic mutations in the PTEN gene; Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome and Proteus-like syndrome. Although they all have distinct clinical features, the formation of hamartomas is present in all four syndromes. PTEN is a tumor suppressor gene that is involved in cellular signalling. Absent or dysfunctional PTEN protein allows cells to over-proliferate, causing hamartomas.
Cowden syndrome is an autosomal dominant genetic disorder characterised by multiple benign hamartomas (trichilemmomas and mucocutaneous papillomatous papules) as well as a predisposition for cancers of multiple organs including the breast and thyroid. Bannayan-Riley-Ruvalcaba syndrome is a congenital disorder characterised by hamartomatous intestinal polyposis, macrocephaly, lipomatosis, hemangiomatosis and glans penis macules. Proteus syndrome is characterised by nevi, asymmetric overgrowth of various body parts, adipose tissue dysregulation, cystadenomas, adenomas, vascular malformation.
The most common adverse effect is pain, which is usually associated with solitary lesions. Multiple tumors are less likely to be painful.
In one report, a patient with more than 400 glomus tumors had thrombocytopenia as a result of platelet sequestration (i.e. Kasabach-Merritt syndrome).
Malignant glomus tumors, or glomangiosarcomas, are extremely rare and usually represent a locally infiltrative malignancy. However, metastases do occur and are usually fatal.
Treatment is varied and depends on the site and extent of tumor involvement, site(s) of metastasis, and specific individual factors. Surgical resection, radiotherapy, and chemotherapy have all been used to treat these masses, although studies on survival have yet to be conducted to delineate various treatment regimens.
Benign tumors are very diverse, and may be asymptomatic or may cause specific symptoms depending on their anatomic location and tissue type. They grow outwards, producing large rounded masses, which can cause what is known as a "mass effect". This growth can cause compression of local tissues or organs, which can cause many effects such as blockage of ducts, reduced blood flow (ischaemia), tissue death (necrosis) and nerve pain or damage. Some tumors also produce hormones that can lead to life-threatening situations. Insulinomas can produce large amounts of insulin leading to hypoglycemia. Pituitary adenomas can cause elevated levels of hormones such as growth hormone and insulin-like growth factor-1, which cause acromegaly; prolactin; ACTH and cortisol, which cause Cushings disease; TSH, which causes hyperthyroidism; and FSH and LH. Bowel intussusception can occur with various benign colonic tumors. Cosmetic effects can be caused by tumors, especially those of the skin, possibly causing psychological effects on the person with the tumor. Vascular tumors can bleed, which in some cases can be substantial, leading to anemia.
A basaloid follicular hamartoma is a cutaneous condition characterized as distinctive benign adnexal tumor that has several described variants.
Large and especially giant congenital nevi are at higher risk for malignancy degeneration into melanoma. Because of the premalignant potential, it is an acceptable clinical practice to remove congenital nevi electively in all patients and relieve the nevocytic overload.
Fibrosarcoma occurs most frequently in the mouth in dogs . The tumor is locally invasive, and often recurs following surgery . Radiation therapy and chemotherapy are also used in treatment. Fibrosarcoma is also a rare bone tumor in dogs.
In cats, fibrosarcoma occurs on the skin. It is also the most common vaccine-associated sarcoma. In 2014, Merial launched Oncept IL-2 in Europe for the management of such feline fibrosarcomas.
Hemangioendothelioma is used to describe a group of vascular neoplasms that may be considered benign as well as malignant, depending on the specific group member's activity.
Choristomas, forms of heterotopia, are closely related benign tumors, found in abnormal locations.
It is different from hamartoma. The two can be differentiated as follows: a hamartoma is disorganized overgrowth of tissues in their normal location, (eg, Peutz-Jeghers polyps) while a choristoma is normal tissue growth in an abnormal location (e.g., gastric tissue located in distal ileum in Meckel diverticulum).
Fibrous hamartoma of infancy is a rapidly growing, painless, ill-defined subcutaneous or intradermal nodule that is generally solitary and less than 5 cm in size, though, rarely, multiple lesions occur synchronously.
By 1999, there were 12 reported cases.
The majority of patients are less than 2 years old, with 25% of cases being congenital. Possible locations include the trunk and limbs; usually the upper arm or shoulder. Local excision is the treatment of choice, but it may recur locally.
Patients are usually managed by a multidisciplinary team including surgeons, gynecologists, and dermatologists because of the complex nature of this disorder. Follow-up for the increased risk of breast cancer risk includes monthly breast self-examination, annual breast examination, and mammography at age 30 or five years earlier than the youngest age of breast cancer in the family. The magnitude of the risk of breast cancer justifies routine screening with breast MRI as per published guidelines.
Folliculosebaceous cystic hamartoma abbreviated as (FSCH) is a rare cutaneous hamartoma consisting of dilated folliculosebaceous units invested in mesenchymal elements. it typically affects adults, have a predilection for the central face or scalp, with less than 1.5 cm dimension. Clinically, the lesions are asymptomatic, rubbery to firm in consistency, and usually occur on or above the neck in (> 90%) of cases, Histopathologically, FSCH shares several similar features to sebaceous trichofolliculoma, but it is usually possible to differentiate these two tumors.
Hidradenoma (also known as acrospiroma, from "akral ""peripheral"" + spiroma ""epithelial tumor of sweat gland") refers to a benign adnexal tumor of the apical sweat gland. Another name for Hidradenoma is Cystadenoma and Hydrocystadenomas. These are 1–3 cm translucent blue cystic nodules.It usually presents as a single, small skin-colored lesion, and is considered distinct from the closely related poroma. Hidradenomas are often sub-classified based on subtle histologic differences, for example:
- clear-cell hidradenoma or acrospiroma
- nodular hidradenoma or acrospiroma
- solid-cystic hidradenoma
Discussion of sweat gland tumors can be difficult and confusing due to the complex classification and redundant terminology used to describe the same tumors. For example, acrospiroma and hidradenoma are synonymous, and sometimes the term "acrospiroma" is used to generally describe benign sweat gland tumors. In addition, a single lesion may contain a mixture of cell-types. There has also been a change in understanding about how tumors that were previously believed to strictly derive from specific sweat gland types may, in fact, derive from both eccrine "or" apocrine glands.
Hidradenomas are by definition benign, with malignant transformation very rare. When tumors show malignant characteristics, they are known as hidradenocarcinoma. Surgical excision is usually curative and local recurrences are rare, although malignant tumors may metastasize.
Lhermitte–Duclos disease is a rare entity; approximately 222 cases of LDD have been reported in medical literature. Symptoms of the disease most commonly manifest in the third and fourth decades of life, although it may onset at any age. Men and women are equally affected, and there is not any apparent geographical pattern.
Juvenile Polyposis Syndrome can occur sporadically in families or be inherited in an autosomal dominant manner.
Two genes associated with Juvenile Polyposis Syndrome are BMPR1A and SMAD4. Gene testing may be useful when trying to ascertain which non-symptomatic family members may be at risk of developing polyps, however having a known familial mutation would be unlikely to change the course of treatment. A known mutation may also be of use for affected individuals when they decide to start a family as it allows them reproductive choices.
While mutations in the gene PTEN were also thought to have caused Juvenile Polyposis Syndrome, it is now thought that mutations in this gene cause a similar clinical picture to Juvenile Polyposis Syndrome but are actually affected with Cowden syndrome or other phenotypes of the PTEN hamartoma tumor syndrome.
Granular cell tumor is a tumor that can develop on any skin or mucosal surface, but occurs on the tongue 40% of the time.
It is also known as Abrikossoff's tumor, Granular cell myoblastoma, Granular cell nerve sheath tumor, and Granular cell schwannoma.)
Congenital causes include:
- Klippel Trenaunay Weber syndrome
- Maffucci syndrome
- macrodystrophia lipomatosa
- neurofibromatosis,
- lipoatrophic diabetes.
- Proteus syndrome, which by one theory accounts for the deformities of the Elephant Man
Mesenchymal neoplasms of the gallbladder are rare and in particular leiomyomas of the gallbladder have been rarely reported, all of them in patients with immune system disorders. Although, recently, a case was reported in absence of associated immunodeficiency at Monash Hospital in Melbourne Australia in a healthy 39-year-old woman with no symptoms.
Eccrine angiomatous hamartoma usually appear as a solitary nodular lesion on the acral areas of the extremities, particularly the palms and soles.
The prognosis for individuals with TSC depends on the severity of symptoms, which range from mild skin abnormalities to varying degrees of learning disabilities and epilepsy to severe intellectual disability, uncontrollable seizures, and kidney failure. Those individuals with mild symptoms generally do well and live long, productive lives, while individuals with the more severe form may have serious disabilities. However, with appropriate medical care, most individuals with the disorder can look forward to normal life expectancy.
A study of 30 TSC patients in Egypt found, "...earlier age of seizures commencement (<6 months) is associated with poor seizure outcome and poor intellectual capabilities. Infantile spasms and severely epileptogenic EEG patterns are related to the poor seizure outcome, poor intellectual capabilities and autistic behavior. Higher tubers numbers is associated with poor seizure outcome and autistic behavior. Left-sided tuber burden is associated with poor intellect, while frontal location is more encountered in ASD. So, close follow up for the mental development and early control of seizures are recommended in a trial to reduce the risk factors of poor outcome. Also early diagnosis of autism will allow for earlier treatment and the potential for better outcome for children with TSC."
Leading causes of death include renal disease, brain tumour, lymphangioleiomyomatosis of the lung, and status epilepticus or bronchopneumonia in those with severe mental handicap. Cardiac failure due to rhabdomyomas is a risk in the fetus or neonate, but is rarely a problem subsequently. Kidney complications such as angiomyolipoma and cysts are common, and more frequent in females than males and in "TSC2" than "TSC1". Renal cell carcinoma is uncommon. Lymphangioleiomyomatosis is only a risk for females with angiomyolipomas. In the brain, the subependymal nodules occasionally degenerate to subependymal giant cell astrocytomas. These may block the circulation of cerebrospinal fluid around the brain, leading to hydrocephalus.
Detection of the disease should be followed by genetic counselling. It is also important to realise that though the disease does not have a cure, symptoms can be treated symptomatically. Hence, awareness regarding different organ manifestations of TSC is important.