Rhabdomyoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nima Nasiri, M.D.[2]

Synonyms and keywords: Rhabdomyomatous neoplasm; Adult rhabdomyoma; Genital rhabdomyoma; Fetal rhabdomyoma; Rhabdomyomatous mesenchymal hamartomas

Overview

Rhabdomyoma is a benign tumor of striated muscle. Rhabdomyomas are rare and can be classified into cardiac type and extracardiac type. The most common primary benign pediatric tumor of the heart is cardiac rhabdomyoma which can be seen mainly in fetal life and children, second most common primary benign cardiac tumor in children is fibroma. Most tumors regress spontaneously, prognosis depends on the location of tumor and size. Cardiac rhabdomyoma is strongly associated with tuberous sclerosis. Cardiac rhabdomyoma is seen almost always in the pediatric age group and is associated with tuberous sclerosis, neurofibromatosis, and sebaceous adenomas. Extracardiac rhabdomyoma can be divided into three groups (adult, fetal, and genital types) with distinct clinical and morphological differences. The adult type is a slowly growing mass which typically involves the head and neck. Fetal type is seen in the head and neck region. The genital type is almost always found in the vulvovaginal region of older women. Treatment of adult type rhabdomyoma of head and neck depends upon the severity of clinical symptoms.

Classification

Rhabdomyoma may be classified into the following subtypes: [1][2][3][4][5][6]

Neoplastic

Neoplastic rhabdomyomas may be further classified into the following types:

Hamartomataous

Hamartamatous rhabdomyomas may be further classified into the following types:

Staging

There have not been sufficient studies for the staging of rhabdomyoma. There is staging based on site, tumor size and metastases for rhabdomyosarcoma, which is a malignant tumor of striated muscle.

Pathophysiology

Pathogenesis

Cardiac Rhabdomyoma

  • Cardiac rhabdomyoma is typically seen in cases of tuberous sclerosis and the pathogenesis involves mutations in the TSC1 and TSC2 genes.[8]
  • Mutations in the TSC1 and TSC2 genes affect downstream molecular signalling pathways, primarily the mTOR pathway that leads to disrupted cellular growth, proliferation and motility.[9][10]
  • Activation of mTOR pathway leads to increased translation and protein production by ribosomal protein S6 kinase beta-1 (p70S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), contributing to the abnormal cell growth and proliferation
  • Cardiac rhabdomyoma is usually diagnosed during the second or third trimester on ultrasound, rhabdomyoma appears as round, homogeneous, hyperechogenic masses in the ventricles, and they sometimes appear as multiple foci in the ventricles and septal wall. Differential diagnosis between rhabdomyoma, fibroma or myxoma using ultrasonography for a single cardiac mass remains difficult. [11][12]
  • Cells usually lose their ability to divide and undergo apoptosis via a ubiquitin-mediated pathway and regression of the hamartoma ensues.[13]
  • Result can be complete or partial regression of hamartoma tumor.

Extracardiac Rhabdomyoma

  • The pathogenesis of extracardiac rhabdomyoma is largely unknown, however, constitutive activation of the Hedgehog signalling (SHH pathway activation) and association with Gorlin’s syndrome have been implicated as the two key mechanisms leading to development of these soft tissue tumors.[14][15]

Location

Immunohistochemistry

Associated Conditions

Gross Pathology

  • On gross pathology, round or polypoid mass in the region of the neck are characteristic findings of adult rhabdomyoma.
    • Round or lobulated, well-circumscribed masses which can be up to 10 cm in diameter.[19]
    • Isolated or multiple.
    • Solid tan-white homogeneous consistency, often watery and glistening on their cut surface.
    • Infrequently, calcification and hemorrhage.
Cardiac rhabdomyoma Gross. Source: http://peir2.path.uab.edu/pdl/dbra.cgi?uid=default&view_search=1


Microscopic Pathology

fetal rhabdomyoma H&E stain [https:https://en.wikipedia.org/wiki/Rhabdomyoma#/media/File:Fetal_intermediate_cellular_type_rhabdomyoma.JPG source:Jerad M Gardner, MD]


Causes

Differentiating Rhabdomyoma from Other Diseases

  • Rhabdomyomas must be differentiated from other diseases, such as:[27]

Differential Diagnosis of Cardiac Rhabdomyoma

Cardiac rhabdomyoma should be differentiated from other cardiac tumors that present as a cardiac mass. The following are the differentials:[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][2][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73]

Site of Tumor Malignant Potential Type of Tumor Tissue of Origin Age of Presentation Location Morphology Signs and Symptoms MRI Findings
Systemic Manifestations Cardiac Manifestations Embolic Manifestations
Primary Cardiac Tumor Primary Benign Myxoma
  • Mesenchymal
  • Between third to sixth decade of life
  • Left atrium (75%)
  • Right atrium (15-20%)
  • Arise from border of fossa ovalis
  • 1-15 cm in diameter
  • Pedunculated
  • Polypoid
  • Smooth and lobulated
  • Villous and pappillary appearance associated with embolization
  • Constitutional symptoms
  • Carney complex:
    • Spotty skin pigmentation
    • Endocrinal tumors such as sertoli testicular tumors, pituitary adenomas, thyroid tumors
    • Schwanomma
  • NAME syndrome:
    • Nevi
    • Atrial myxoma
    • Myxoid neurofibroma
    • Ephelides
  • LAMB syndrome:
    • Lentigo (small brown patches on the skin)
    • Atrial myxoma
    • Blue nevi
  • Dyspnea
  • Mitral regurgitation (LA)
  • Right heart failure (RA)
  • Cardiomegaly
  • Pulmonary hypertension and pulmonary emboli (RA)
  • Oval mobile left atrial lesion
  • Heterogenous enhancement
  • Attachment to fossa ovalis
Rhabdomyoma
  • Striated Muscle
  • Majority (80%) in infants (<12 months)
  • Most common cardiac mass in childhood
  • 50-70% of all pediatric tumors
  • Ventricles
  • Interventricular septum
  • 1-3 cm in size
  • Yellow-gray color
  • Firm
  • Circumscribed lobulated
  • Majority multiple if associated with tuberous sclerosis (of those with no association, 50% are single)
  • Associated with tuberous sclerosis:
    • Developmental delay
    • Renal tumors (angiomyolipomas)
    • Phakomas (white retinal spots)
    • Hypomelanic macules (ash leaf spots)
    • Ungal fibromas
    • Facial angiofibromas
    • Headache
    • Blurred vision
    • Arrhythmias
    • Benign brain tumors (cortical tubers, subependymal nodules)
  • Outflow obstruction (both right and left ventricles)
  • Arrhythmias (ventricular pre-excitation, Wolff-Parkinson White syndrome)
  • Spontaneous regression in young cases (< 4 years); seldom regress in adult cases
  • Multiple masses isointense to muscle tissue on T1 images
  • Hyperintense on T2 images
Fibroma
  • Fibrous
  • Children (1/3rd in infants)
  • Ventricles
  • Ventricular septum >Left ventricular free wall > Right ventricle > Atria
  • Central calcification
  • Solitary
  • Cyanosis
  • Atypical chest pain
  • Heart failure
  • Cardiomegaly
  • Biventricular hypertrophy
  • Atrioventricular nodal block
  • Solitary mass
  • Low intensity on T2 weighted image
Fibroelastoma
  • Valvular endocardium
  • Valvular endocardium (Adults-Aortic, children-Tricuspid)
  • Ventrucular surface of aortic and pulmonary valves and atrial surface of atriventricular valves
  • < 1 cm in diameter
  • Solitary
  • Papillary
  • Flower-like appearance with multiple attachments to valve
  • Short pedicle
  • Asymptomatic
  • Association with hypertrophic obstructive cardiomyopathy (HOCM)
  • Subacute bacterial endocarditis
  • Pulmonary embolism
  • T1 and T2 weighted images show uniform intermediate signal intensity similar to myocardium
  • Homogeneous late gadolinium contrast enhancement
Hemangioma
  • Vascular
  • < 1 year to 70 years
  • < 2 % of primary cardiac tumors
  • Right Ventricle
  • Left ventricle
  • Right atrium
  • Small percentage in interatrial septum and left atrium
  • Polypoid
  • Encapsulated
  • Cyanosis
  • Kasabach-Merritt syndrome (giant hemangiomas):
    • Thrombosis
    • Thrombocytopenia
    • Coagulopathy
  • Pericardial effusions
  • CHF
  • Arrhythmias
  • Pulmonary embolism
  • Ischemic stroke
  • Intermediate density on T1 images
  • Hypointense on T2 images
  • Multicystic enhancing lesion
  • Involvement of epicardium or pericardium
Lipoma
  • Adipose
  • Between fourth to sixth decade of life
  • Left ventricle (most commonly subendocardium)
  • Right atrium
  • Sessile and small (specially subendocardial that protrude into cardiac chambers)
  • Broad pedicle
  • Growth into pericardial space
  • Asymptomatic
  • Dyspnea
  • Local compression (subepicardial)
  • Arrhythmia
  • Ischemic stroke
  • Epicardial on intramural lesion
  • High intensity on T1 weighted image
  • Drop out on fat saturation images
Paraganglioma
  • Nervous (chromaffin cells of the sympathetic ganglia)
  • Average age of presentation is 11-13 years
  • Left atrium (under the aorta and the pulmonary artery)
  • Interatrial septum
  • Left ventricle
  • Right ventricular outflow tract
  • 3-8 cm
  • Well-defined
  • Broad base
  • Encapsulated
  • Heterogeneous
  • Hypervascular
  • Majority asymptomatic
  • May present with symptoms of catecholamine excess:
    • Tachycardia
    • Hypertension
    • Palipitations
    • Fever
    • Diaphoresis
  • Positive for chromogranin and synaptophysin
  • Association with succinate dehydrogenase (SDH) mutation
  • Dyspnea
  • Valvular obstruction (murmurs)
  • Acute coronary syndrome (anginal pain)
  • Enascement of coronary arteries by tumor
  • Well defined lesion arising from atrial walls or septum
  • Bright on T2 weighted imaging
Atrioventricular Node Tumor
  • Endodermal
  • Average age of diagnosis is 38 years
  • Female to male ratio 3:1
  • Triangle of Koch in the AV nodal region of the atrial septum
  • 2 mm to 2 cm
  • Multiple
  • Cystic
  • Thickening of the atrial septum
  • Most common cardiac tumor leading to sudden death
  • Emery-Dreifuss muscular dystrophy
  • Midline developmental defects along the central vertical body axis:
    • Thyroglossal duct cysts
    • Cysts in the ovaries, breasts
    • Ventricular septal defect
    • Encephalocele
  • Positive for:
    • Cytokeratin CAM5.2
    • Cytokeratin AE1/AE3
    • Cytokeratin 34βE12
    • Cytokeratin 5/6 (CK5/6)
    • Cytokeratin 7 (CK7)
    • Epithelial membrane antigen (EMA)
    • Carcinoembryonic antigen (CEA)
    • Carbohydrate antigen (CA)19.9, p63, bcl2, galectin 3
  • Palpitations
  • Dyspnea
  • Chest pain
  • Diziness
  • Syncope
  • Complete heart block
  • Partial AV block
  • Paroxysmal atrial arrhythmia
  • Spontaneous intermittent pre-excitation
  • Myocardial infarction
  • Ischemic stroke
  • Hypointense cardiac mass on standard imaging
  • Hyperintensity on late gadolinium enhancement (LGE) images with heterogeneous contrast enhancement
Lipomatous hypertrophy of the interatrial septum
  • Adipose
  • > 60 years
  • Limbus of the fossa ovalis (sparing fossa ovalis membrane)
  • > 2 cm
  • Interatrial septum maybe upto 7 cm in thickness
  • Mostly asymotmatic
  • May present with obstructive symptoms such as syncope in rare cases of extension into superior vena cava
  • Associated with:
    • Increased age
    • Obesity
    • Arrhythmias
  • Palpitations
  • Dyspnea
  • Fatigue
-
  • Diffuse or nodular thickening of atrial walls
  • Hyperintense to normal myocardium
  • Hypointense to pericardial and posterior mediastinal fat
Primary Malignant Fibrosarcoma
  • Fibrous
  • Left sided (atrial mostly)
  • Sessile or pedunculated protruding masses in ventricular cavities
  • Soft
  • Lobulated
  • Gelatinous
  • Fever
  • Fatigue
  • Malaise
  • Weight loss
  • Cytoplasmatic positivity for a-SMA
  • CHF
  • Pericardial infiltration (effusions)
  • Pulmonary embolism
  • Ischemic stroke
  • Metastasis
  • Heterogenous or isointense to myocardium on T1 weighted images
Angiosarcoma
  • Vascular
  • Third to fifth decade of life
  • Right atrium
  • Broad-based
  • Internal hemmorrhage
  • Fever
  • Fatigue
  • Weight loss
  • Congestion
  • Superior vena cava syndrome
  • Embolic stroke
  • Endothelial marker D2-40
  • Dyspnea
  • CHF
  • Pericardial effusions
  • Cardiac tamponade
  • Pulmonary embolism
  • Ischemic stroke
  • Metastasis
  • Arterial phase enhancement
Rhabdomyosarcoma
  • Mesenchymal
  • Most common primary sarcoma of children
  • Average age of presentation is 20 years
  • Left sided (atrial mostly)
  • Multiple
  • Three types:
    • Embryonic
    • Pleomorphic
    • Alveolar
  • Fever
  • Fatigue
  • Weight loss
  • Metastasize to lung and lymph nodes
  • CHF
  • Arrhythmias
  • Pulmonary embolism
  • Ischemic stroke
  • Metastasis
  • Intermediate-to-hypointensity compared with muscle on T1 images
  • Hyperintense on T2-weighted imaging with heterogeneous contrast enhancement
Lymphoma
  • Lymphoid
  • First to ninth decade of life
  • Males > females
  • Right sided mostly
  • Majority solitary (1/3rd multiple)
  • Associations:
    • Chronic immunosupression
    • Epstein Barr virus
    • HIV
    • Diffuse large B cell lymphoma
  • May involve epicardium and pericardium
  • Pulmonary embolism
  • Ischemic stroke
  • Metastasis
Secondary CardiacTumor Metastastatic Malignant Metastasis
  • Skin (Melanoma)
  • Lung carcinoma
  • Lymph (leukemia and lymphoma)
  • Breast carcinoma
  • Smooth muscle (Esophageal carcinoma)
  • Any age
  • Tumors metastasizing via hematogenous route present as multiple intramyocardial masses:
    • Melanoma
    • Leukemia
    • Sarcoma
  • Tumors metastasizing via venous system as right sided mass:
    • Renal cell carcinoma
    • Hepatocellular carcinoma
  • Lung tumor metastasizes to left atrium
  • Multiple
  • Fever
  • Fatigue
  • Weight loss
  • Dysphagia
  • Lymphadenopathy
  • Night sweats
  • Pericardial effusions
  • Dyspnea
  • Arrhytmia
  • Outflow obstruction
  • Pulmonary embolism
  • Ischemic stroke
  • Metastasis

Epidemiology and Demographics

  • Cardiac rhabdomyomas are usually detected during the first year of life or before birth and accounts for majority of all primary cardiac tumors.[24][74][75]
  • Worldwide, rhabdomyoma is rare.
  • Most of patients with tuberous sclerosis develop a cardiac rhabdomyoma. Similarly, children diagnosed with cardiac rhabdomyomas demonstrate radiologic or clinical findings 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%.

Age

  • Adult rhabdomyoma is more commonly observed among patients aged greater than 40 years old.[12]
  • 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.[1]

Gender

  • Cardiac rhabdomyoma affects men and women equally.[15][76]
  • Rhabdomyomatous mesenchymal hamartoma of skin is extremely rare in both genders.
  • 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

  • There are no established risk factors for rhabdomyoma.

Natural History, Complications and Prognosis

Natural History

Complications

Prognosis

  • prognosis is generally good; the survival rate of patients with benign rhabdomyoma is excellent, depending on location of tumor, prognosis may change.[79]
  • Rhabdomyomas on mitral or tricuspid valves can lead to regurgitation or obstruction of outflow tract thus poor prognosis.[80]
  • The long-term prognosis of cardiac rhabdomyoma is affected by the neurologic manifestations associated with tuberous sclerosis.[81]
  • The prognosis of patients with rhabdomyomas depends mainly on the size, location, number of the lesions, associated anomalies such as tuberous sclerosis.
  • Metastases have not been associated with rhabdomyoma.

Diagnosis

Symptoms

  • Symptoms of adult rhabdomyoma may include:[82]
  • Symptoms of genital rhabdomyoma may include the following:
  • Symptoms of cardiac rhabdomyoma may include the following:

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 rhabdomyoma may present with mitral or tricuspid regurgitation murmur.[85]

Laboratory Findings

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 identified by single or multi foci hyper echoic mass(es) located adjacent to the myocardium.[28]
  • X-Rays of the chest and affected areas of the body may be helpful in the diagnosis of rhabdomyomas.
fetal cardiac rhabdomyoma source:Case courtesy of Dr Effendi Mansoor, <a href="https://radiopaedia.org/">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/17302">rID: 17302</a>


Other Diagnostic Studies

  • Rhabdomyoma may also be diagnosed using biopsy since overlap in morphologic features between rhabdomyosarcoma (RMS) vs. rhabdomyoma makes differential diagnosis difficult.[86]
  • 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

Adult rhabdomyoma

  • Patients with laryngeal rhabdomyoma need immediate care such as nasal oxygen, intravenous fluids and if respiratory distress develops intubation before admission for surgery and surgical excision. [17]
  • Patients with adult rhabdomyoma and shortness of breath should restrain from activities which exacerbate their breathing difficulty.

Cardiac rhabdomyoma

Genital rhabdomyoma

Surgery

Adult rhabdomyoma

  • Surgical resection of the tumor can only be performed for patients with adult rhabdomyoma if airway obstruction is diagnosed, there have been reports of rare cases of laryngeal rhabdomyoma which may cause breathing difficulty for patients.[92]

Cardiac rhabdomyoma

  • In patients with cardiac rhabdomyoma who have symptoms of severe outflow tract obstruction or arrhythmias, surgical intervention can be helpful. Surgical management involves removal of the part of the tumor causing obstruction without complete excision of the entire lesion.[93]

Prevention

  • There are no primary preventive measures available for rhabdomyoma.

References

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