Rhabdomyoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2] Synonyms and keywords: Synonym 1; Synonym 2; Synonym 3

Overview

A rhabdomyoma is a benign tumor of striated muscle. Rhabdomyomas develop mostly before the age of one year, almost exclusively in children, and approximately 80 to 90 percent are associated with tuberous sclerosis. The most common primary pediatric tumor of the heart is cardiac rhabdomyoma.

Historical Perspective

• [Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
• In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
• In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

Classification

• Rhabdomyoma may be classified into two types:

• Neoplastic
• Hamartoma

• Neoplastic variety is further classified into three subtypes:

• Adult
• Fetal
• Genital

• Hamartomas are further classified into two subtypes:

• Cardiac rhabdomyoma
• Rhabdomyomatous mesenchymal hamartomas of the skin

Staging

The staging of rhabdomyomas is based on the grade (G), site (T), and metastasis (M), as follows:

• G0 - Benign
• T0 - Intracapsular
• T1 - Extracapsular, intracompartmental
• M0 - None

Stage	Severity	Description
Benign Stage 1	Latent G0T0M0	Remains static or heals spontaneously
Benign Stage 2	Active G0T0M0	Progressive growth but limited by natural barriers
Benign Stage 3	Aggressive G0T1M0	Progressive growth not limited by natural barriers

Pathophysiology

• On gross pathology, round or polypoid mass in the region of the neck are characteristic findings of adult rhabdomyoma.
• On gross pathology round or lobulated, grossly well circumscribed masses that range from 1 mm to 10 cm in their greatest dimension and can be either isolated or multiple, solid tan-white homogeneous consistency often watery and glistening on their cut surface, and infrequent calcification and hemorrhage are characteristic findings of cardiac rhabdomyomas.
• On microscopic histopathological analysis, well-differentiated large cells, which are deeply eosinophilic polygonal with small, peripherally placed nuclei and occasional intracellular vacuoles, which resemble striated muscle cells, are characteristic findings of adult rhabdomyoma.
• On microscopic histopathological analysis, spindle-shaped cells with indistinct cytoplasm and muscle fibres, which resemble striated muscle tissue seen in intrauterine development at 7-12 weeks, are characteristic findings of fetal rhabdomyoma.
• On microscopic histopathological analysis, mixture of fibroblasts cells with clusters of mature cells containing distinct cross-striations and a matrix containing varying amounts of collagen and mucoid material, are characteristic findings of genital rhabdomyoma.
• On microscopic histopathological analysis, cells that closely resemble embryonic cardiac muscle cells, are characteristic findings of cardiac rhabdomyoma.
• On microscopic histopathological analysis, lesions contain poorly oriented or perpendicular bundles of well-differentiated skeletal muscle with islands of fat, fibrous tissue, and occasionally proliferating nerves, are characteristic findings of rhabdomyomatous mesenchymal hamartoma of the skin.

Associated Conditions

• Cardiac rhabdomyoma is a hamartomatous proliferation frequently associated with sebaceous adenomas, tuberous sclerosis of the brain, and various hamartomatous lesions of the kidney and other organs.

Pathogenesis

• The pathogenesis of rhabdomyoma is characterized by [feature1], [feature2], and [feature3].
• Cardiac rhabdomyomas tend to grow up to approximately 32 weeks' gestation, after which point the cells usually lose their ability to divide and undergo apoptosis. This process of apoptosis is mediated by ubiquitin, a regulatory protein that is strongly expressed in rhabdomyoma cells.
• The degradation of myofilaments is expressed by ubiquitin. Apoptosis follow and leads to the eventual regression of the hamartoma. Complete or partial resolution occurs in the majority of cases, regardless of the initial size of the tumor.

Location

• The head and neck area harbors approximately 90% of adult rhabdomyomas.
• Adult rhabdomyoma is localized to the oropharynx, the larynx, and the muscles of the neck.
• Fetal rhabdomyoma occurs most often in the subcutaneous tissues of the head and neck in children
• Genital rhabdomyoma most often involves the vagina or vulva.
• Cardiac rhabdomyoma usually involves the myocardium of both ventricles and the interventricular septum but can be located in the atria, the epicardial surface, or the cavoatrial junction.

Immunohistochemistry

• Cross-striation has been demonstrated by muscle specific actin, phosphotungstic acid hematoxylin (PTAH), desmin, and myoglobin.
• Dystrophin is shown to be expressed in the cell membranes.

Causes

• Adult rhabdomyomas are almost totally matured neoplasms of clonal origin.
• Cardiac rhabdomyoma may be caused by either sporadic mutation or in the setting of certain genetic disorders.
• Approximately more than 50% of rhabdomyomas are caused by sporadic mutations. However, in rare cases, Ebstein abnormality, tetralogy of Fallot, and hypoplastic left heart syndrome can be associated with cardiac rhabdomyoma.
• The genetic disorder commonly associated with cardiac rhabdomyoma is tuberous sclerosis.
• The other genetic disorders associated with cardiac rhabdomyomas include basal cell nevus syndrome and Down syndrome in the setting of tuberous sclerosis.
• The familial form of tuberous sclerosis is an autosomal dominant disorder characterized by widespread hamartomas that may involve the kidneys, heart, skin, brain, and other organs. The association of cardiac rhabdomyoma and tuberous sclerosis is important and has been explained by strong clinical association. Molecular evidence of this association have been identified as the TSC2 gene missense mutation.
• Cardiac rhabdomyoma is caused by a mutation in the TSC-1 on chromosome 9q34 that encodes for protein hamartin, and TSC-2 on 16p13 that encodes for tuberin. These genes are both tumor suppressor genes that assist in the regulation of growth and differentiation of developing cardiomyocytes.

Differentiating rhabdomyoma from other Diseases

• Rhabdomyomas must be differentiated from other diseases, such as: :

• Hibernoma
• Reticulohistiocytoma
• Tuberous sclerosis
• Granular cell tumors

Epidemiology and Demographics

• In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].
• Cardiac rhabdomyomas are usually detected during the first year of life or before birth. Cardiac rhabdomyomas account for over 60% of all primary cardiac tumors.
• Worldwide, rhabdomyoma is rare. Exact data regarding the incidence of cardiac rhabdomyoma within particular populations have not been cited. In the literature, 14 cases of multifocal adult head and neck rhabdomyoma are reported.
• Approximately 50% of patients with tuberous sclerosis develop a cardiac rhabdomyoma. Similarly, approximately 51-86% of children diagnosed with cardiac rhabdomyomas demonstrate radiologic or clinical evidence of tuberous sclerosis or have a positive family history. Rhabdomyoma is extremely rare in the United States. Rhabdomyoma has a relative incidence of 5.8%. Study articles have demonstrated that the incidence of cardiac rhabdomyoma is 0.002-0.25% at autopsy, 0.02-0.08% in live-born infants, and 0.12% in prenatal reviews.

Age

• Adult rhabdomyoma is more commonly observed among patients aged greater than 40 years old.
• Fetal rhabdomyoma is more commonly observed among patients aged between birth and 3 years.
• Cardiac rhabdomyoma is more commonly observed among patients in the pediatric age group.
• Genital rhabdomyoma is more commonly observed among patients in the young and middle-aged women.
• Rhabdomyomatous mesenchymal hamartomas of the skin is more commonly observed among newborns and infants.

Gender

• Cardiac rhabdomyoma affects men and women equally.
• Rhabdomyomatous mesenchymal hamartoma of skin is observed in male and female newborns and infants equally.
• Males are more commonly affected with adult rhabdomyoma than females.
• Males are more commonly affected with fetal rhabdomyoma than females.
• Females are more commonly affected with genital rhabdomyoma than males

Race

• There is no racial predilection for rhabdomyomas.

Risk Factors

• Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

• The majority of rhabdomyomas regress spontaneously, and resection is usually not required unless a child is symptomatic.
• If left untreated, tumors larger than 20 mm in diameter are more likely to cause arrhythmias or hemodynamic disturbances, which are associated with an increased risk of death.
• The morbidity of rhabdomyoma depends on the type of lesion and its location. Rhabdomyoma is a benign tumor of striated muscle. Metastases have not been associated with rhabdomyoma.
• Common complications of cardiac rhabdomyoma include development of cardiac arrhythmias, ventricular outflow tract obstruction, valvular compromise, and disruption of intracardiac blood flow leading to congestive heart failure and hydrops.
• Prognosis is generally good, and the survival rate of patients with rhabdomyoma is approximately 81% to 92%. Rhabdomyomas that alter valve function and lead to regurgitation or that obstruct the inflow or ventricular outflow tracts carry a poor prognosis. The long-term prognosis of cardiac rhabdomyoma is affected by the neurologic manifestations associated with tuberous sclerosis
• The natural history of cardiac rhabdomyomas is that of complete or partial regression with consequent resolution of symptoms. The majority of rhabdomyomas regress spontaneously, and resection is usually not required unless a child is symptomatic.
• The prognosis of patients with rhabdomyomas is chiefly determined by the size, number and location of the lesions as well as the presence or absence of associated anomalies.
• Generally The prognosis for patients who have undergone surgery for the removal of rhabdomyomas ranges from fair to good, depending on the part of the body involved. Patients with cardiac rhabdomyomas have the highest risk.
• Common complications of cardiac rhabdomyoma include flow abnormalities if they grow to sufficient size to restrict the left ventricular outflow tract.
• The majority of patients with cardiac rhabdomyoma remain asymptomatic;however, some affected patients become symptomatic in the perinatal period. The types of clinical manifestations were illustrated in a report that included 15 children with cardiac rhabdomyoma (12 with tuberous sclerosis): the clinical presentation was heart failure or a cardiac murmur in 6 patients each, and arrhythmia in 3.[10]
• Early clinical features include heart failure, cardiac murmur, and arrhythmia.

Diagnosis

Diagnostic Criteria

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:

• [criterion 1]
• [criterion 2]
• [criterion 3]
• [criterion 4]

Symptoms

• [Disease name] is usually asymptomatic.
• Symptoms of adult rhabdomyoma may include the following:

• Hoarseness
• Difficulty breathing
• Difficulty swallowing

• Symptoms of genital rhabdomyoma may include the following:

• Dyspareunia

• In cardiac rhabdomyoma, symptoms if present, are caused by obstruction of blood flow through the heart or consist of rhythm disturbances, such as heart block of ventricular tachycardia.
• Symptoms of cardiac rhabdomyoma may include the following:

• Shortness of breath

Physical Examination

• Physical examination may be remarkable for:
• The presence of a round or polypoid mass in the region of the neck in adult rhabdomyoma.
• Subcutaneous masses in the head and neck regions in fetal rhabdomyoma.
• Vaginal masses in genital rhabdomyoma
• Cardiac rhabdomyomas may present with heart murmurs. If tuberous sclerosis is associated, the patient displays cerebral palsy–type signs. Renal functions may be altered.

Laboratory Findings

• There are no specific laboratory findings associated with rhabdomyoma.
• The usual laboratory studies that are ordered, includes the following:
  • Complete blood count (CBC)
  • Hemoglobin/hematocrit
  • Platelet count
  • Urinalysis

Imaging Findings

• MRI is the imaging modality of choice for rhabdomyoma. Chest CT scan may be helpful in the diagnosis of cardiac rhabdomyoma.
• On ultrasound, rhabdomyoma is characterized by one or more solid hyper echoic mass(es) located in relation to the myocardium. The small lesions can mimic diffuse myocardial thickening.
• Radiographs of the chest and affected areas of the body may be helpful in the diagnosis of rhabdomyomas.

Other Diagnostic Studies

• Rhabdomyoma may also be diagnosed using biopsy.
• Any masses, including those found in the head and neck of patients with adult rhabdomyoma, should be biopsied to establish a diagnosis.

Treatment =

Medical Therapy

• There is no treatment for [disease name]; the mainstay of therapy is supportive care.
• The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
• [Medical therapy 1] acts by [mechanism of action1].
• Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Surgery

• Surgery is the mainstay of therapy for [disease name].
• [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
• [Surgical procedure] can only be performed for patients with [disease stage] [disease name].

Prevention

• There are no primary preventive measures available for [disease name].
• Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

• Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].