Rhabdomyomas

Synonyms and related keywords: rhabdomyoma, benign tumor of striated muscle, neoplastic, hamartoma, cardiac rhabdomyoma, rhabdomyomatous mesenchymal hamartomas of the skin, muscle tumor



INTRODUCTION

Background: Rhabdomyoma is a lesion of striated muscle. The 2 types of rhabdomyoma are neoplastic and hamartoma. The neoplastic variety is subclassified into adult, fetal, and genital types. Hamartomas are divided into cardiac rhabdomyoma and rhabdomyomatous mesenchymal hamartomas of the skin.

Rhabdomyoma is an exceedingly rare tumor. Some investigators believe that mature striated muscle is unlikely to develop tumorous tissue. Therefore, they believe that rhabdomyoma may arise from fetal rests.

Rhabdomyoma is diagnosed most often in men aged 25-40 years. However, the so-called fetal rhabdomyoma chiefly affects boys between birth and age 3 years.

Most rhabdomyomas involve the head and neck regions. The cardiac rhabdomyoma, which is believed to be a hamartoma, usually is diagnosed in the pediatric age group.

Pathophysiology: The adult rhabdomyoma is a rare tumor. Very few cases have been reported in the literature. This tumor usually presents as a round or polypoid mass in the region of the neck. The head and neck area harbors 90% of adult rhabdomyomas and should be considered in a differential diagnosis in this region (Bjorndal, 2006). Studies in immunohistochemistry confirm that the tumors are almost totally matured neoplasms of clonal origin. The mass is usually asymptomatic. However, the mass may compress or displace the tongue, or it may cause partial obstruction of the pharynx. Consequently, the patient may experience some hoarseness, difficulty breathing, and difficulty swallowing.

The histopathology of adult rhabdomyoma is characterized by the presence of well-differentiated large cells that resemble striated muscle cells. Cross-striation has been demonstrated by phosphotungstic acid hematoxylin (PTAH), muscle specific actin, desmin, and myoglobin while dystrophin is shown to be expressed in the cell membranes. The cells are deeply eosinophilic polygonal cells with small peripherally placed nuclei and occasional intracellular vacuoles. Adult rhabdomyoma usually 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 between birth and age 3 years. The histopathology of fetal rhabdomyoma reveals the presence of a mixture of spindle-shaped cells with indistinct cytoplasm and muscle fibers, which resemble striated muscle tissue observed in intrauterine development at 7-12 weeks. The fetal rhabdomyoma is usually found in the subcutaneous tissues of the head and neck.

Genital rhabdomyoma most often involves the vagina or vulva of young or middle-aged women. Most patients are asymptomatic. However, some patients have dyspareunia. The histopathology of genital rhabdomyoma reveals a mixture of fibroblastlike cells with clusters of mature cells containing distinct cross-striations and a matrix containing varying amounts of collagen and mucoid material. The genital rhabdomyoma usually presents as a polypoid or cystlike mass involving the vulva or vagina.

Cardiac rhabdomyoma is a hamartomatous lesion that occurs most often in the pediatric age group. Cardiac rhabdomyomas typically develop in utero and are often detected on prenatal ultrasound. It usually involves the myocardium of both ventricles and the interventricular septum. Cardiac rhabdomyoma is considered a hamartomatous proliferation frequently associated with tuberous sclerosis of the brain, sebaceous adenomas, and various hamartomatous lesions of the kidney and other organs. The association of tuberous sclerosis and cardiac rhabdomyoma is important and has usually been explained by strong clinical association. Molecular evidence of this association have now been identified as the TSC2 gene missense mutation (E36; 4672 G>A, 1558 E>K TSC2) (Jozwiak, 2005).

Rhabdomyomatous mesenchymal hamartoma is usually diagnosed in male and female newborns and infants. The histopathology of rhabdomyomatous mesenchymal hamartoma of the skin reveals that the lesions are located in the subcutis and contain poorly oriented or perpendicular bundles of well-differentiated skeletal muscle with islands of fat, fibrous tissue, and occasionally proliferating nerves.

Frequency:

• In the US: Rhabdomyoma is an extremely rare tumor compared to other soft tissue tumors. Specifically, in the category of benign primary tumors of the heart, rhabdomyoma has a relative incidence of 5.8%.

• Internationally: Rhabdomyoma is rare. Exact data regarding its incidence within populations have not been cited. In the world literature, 14 cases of multifocal adult head and neck rhabdomyoma are reported.

Mortality/Morbidity:

• The morbidity of rhabdomyoma depends on the type of lesion and its location. This is a benign tumor of striated muscle. Metastases have not been associated with this tumor.

• Cardiac rhabdomyomas are associated with the potential for flow abnormalities if they grow to sufficient size to restrict the left ventricular outflow tract. Although many are asymptomatic, 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 (Webb, 1993). Based on clinical and molecular evidence, the diagnosis of fetal cardiac rhabdomyoma should lead to the careful evaluation of other fetal structures, including brain and renal parenchyma, to search for signs of tuberous sclerosis.

Race: Rhabdomyoma has been identified in all racial groups. No predilection for any particular racial group exists.

Sex: Adult rhabdomyoma has been diagnosed mostly in men. Some reports exist of cases in women. Fetal rhabdomyoma affects boys. Genital rhabdomyoma affects young and middle-aged women. Cardiac rhabdomyoma is observed in men and women. Rhabdomyomatous mesenchymal hamartoma of skin is observed in male and female newborns and infants.

Age: Adult rhabdomyoma occurs in older adults. These patients are usually older than 40 years. Fetal rhabdomyoma occurs between birth and age 3 years. Genital rhabdomyoma is observed in young and middle-aged women. Cardiac rhabdomyomas occur chiefly, but not exclusively, in the pediatric age group. Rhabdomyomatous mesenchymal hamartoma of the skin is observed in newborns and infants.

CLINICAL

History: The presenting history depends in part on the age and sex of the patient.

• Patients with adult rhabdomyoma give a history of having a mass in the region of the neck. They might experience some hoarseness, difficulty breathing, difficulty swallowing, or a combination.

• Patients with fetal rhabdomyoma may have a history of subcutaneous head and neck masses.

• Patients with genital rhabdomyoma are young or middle-aged women who might present with a complaint of dyspareunia.

• Patients with cardiac rhabdomyoma may present with a history of shortness of breath, sometimes associated with signs and symptoms suggestive of cerebral palsy (suggesting the possibility of associated tuberous sclerosis).

Physical:

• The physical examination of a patient with adult rhabdomyoma probably reveals the presence of a round or polypoid mass in the region of the neck.

• Examination of the patient with fetal rhabdomyoma reveals subcutaneous masses in the head and neck regions.

• Examination of women with genital rhabdomyoma reveals vaginal masses.

• Patients with cardiac rhabdomyomas may present with heart murmurs. If tuberous sclerosis is associated, the patient displays cerebral palsy–type signs. Renal functions may be altered.

Causes: Rhabdomyoma probably represents a genetic variant of striated muscle development. Drugs or environmental factors have not been identified as causes of this neoplasm.

DIFFERENTIALS

Granular Cell Tumors

Other Problems to be Considered:

Hibernoma
Reticulohistiocytoma
Tuberous sclerosis

WORKUP

Lab Studies:

• Order the usual laboratory studies, including CBC, hemoglobin/hematocrit, platelet count, and urinalysis.

Imaging Studies:

• Perform routine radiographic studies, including radiographs of the chest and affected areas of the body.

• An MRI of the affected area might be useful.

• Occasionally, a CT scan, particularly of the chest in cases of cardiac rhabdomyoma, might be of value.

Other Tests:

• When rhabdomyoma is suspected, a biopsy of the lesion is indicated. Needle biopsies can reveal sufficient information to make a histopathologic diagnosis.

Procedures:

• Any masses, such as those found in the head and neck of patients with adult rhabdomyoma, should have biopsies performed to establish a diagnosis.

• Make a small incision directly over the mass, and remove a small amount of tumor tissue. Close the wound in the usual manner.

• A needle biopsy can be performed using a Tru-Cut needle. A small stab wound is made directly over the mass. The needle is introduced into the tumor, then it is withdrawn with a small amount of tumor tissue attached. Subsequently, a dressing is applied to the wound.

Histologic Findings: The histopathologic findings from patients with adult rhabdomyoma are characterized by the presence of well-differentiated large cells, which resemble striated muscle cells. The cells are deeply eosinophilic polygonal cells with small, peripherally placed nuclei and occasional intracellular vacuoles.

Fetal rhabdomyoma is identifiable by the presence of a mixture of spindle-shaped cells with indistinct cytoplasm and muscle fibers, which resemble striated muscle tissue seen in intrauterine development at 7-12 weeks.

Genital rhabdomyoma is made up of a mixture of fibroblastlike cells with clusters of mature cells containing distinct cross-striations and a matrix containing varying amounts of collagen and mucoid material.

Cardiac rhabdomyoma consists of cells that closely resemble embryonic cardiac muscle cells.

The histopathology of rhabdomyomatous mesenchymal hamartoma of the skin reveals that the lesions contain poorly oriented or perpendicular bundles of well-differentiated skeletal muscle with islands of fat, fibrous tissue, and occasionally proliferating nerves.

Staging:

• Benign tumors can be staged as follows:

• Stage 1, latent - Remains static or heals spontaneously

• Stage 2, active - Progressive growth but limited by natural barriers

• Stage 3, aggressive - Progressive growth not limited by natural barriers

• Grading, where G = grade; T = site; M = metastasis

• G0 = benign

• T0 = intracapsular

• T1 = extracapsular, intracompartmental

• M0 = none

• Staging
  • Benign stage 1, latent = G0, T0, M0
  • Benign stage 2, active = G0, T0, M0
  • Benign stage 3, aggressive = G0, T1, M0

TREATMENT

Medical Care: Patients with adult rhabdomyoma may experience progressive difficulties in breathing and swallowing. In such instances, nasal oxygen may help patients with breathing difficulties. In circumstances in which swallowing is extremely difficult, supplemental intravenous fluids may be administered until surgery is performed. Patients with cardiac rhabdomyomas should be under the care of a cardiologist.

Surgical Care:

• Patients with adult rhabdomyoma should have surgical resection of head and neck lesions, especially those lesions that compress or displace the tongue and those that may protrude and partially obstruct the pharynx or larynx.

• Fetal rhabdomyomas are usually located in the subcutaneous tissues. In most instances, they can be excised from various parts of the body without much difficulty.

• Local excision is the treatment of choice for genital rhabdomyomas.

• Open heart surgery may be necessary for the treatment of cardiac rhabdomyomas.

Consultations:

• Patients with adult rhabdomyomas should be cared for in consultation with ear, nose, and throat (ENT) specialists.

• Patients with genital rhabdomyoma should be cared for in consultation with gynecologists and urologists.

• Patients with cardiac rhabdomyomas should be cared for by cardiologists and cardiothoracic surgeons.

Diet: Patients with adult rhabdomyoma and problems related to swallowing may need to be placed on a liquid diet.

Activity: Patients with adult rhabdomyoma who are experiencing breathing difficulties should restrict their activities until appropriate treatment can be undertaken. Patients with cardiac rhabdomyoma also must

MEDICATION

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Analgesics -- Generally, the usual pain medications (eg, aspirin with codeine, acetaminophen with codeine) may be used to relieve pain. Many patients with rhabdomyomas are asymptomatic; these patients rarely require strong pain medication.

Drug Name	Aspirin 325 mg with codeine 30 mg (Empirin with Codeine) -- Provides adequate pain relief. However, discontinue aspirin several days before any surgical treatment is undertaken to prevent excessive bleeding.
Adult Dose	1-2 tab PO q4h prn
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; because of association of aspirin with Reye syndrome, do not use in children (less than 16 y) with flu
Interactions	Aspirin effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants and aspirin; aspirin may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; aspirin dosages >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs Toxicity of codeine increases with concurrent administration of tricyclic antidepressants, MAOIs, neuromuscular blockers, CNS depressants, phenothiazines, and narcotic analgesics
Pregnancy	D - Unsafe in pregnancy
Precautions	Patients scheduled for surgery should discontinue use of aspirin several days before surgery is performed (aspirin can cause bleeding problems); aspirin may cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, history of blood coagulation defects, or those who are taking anticoagulants Codeine may depress hypoxic ventilatory rate and respiratory drive during sleep

Drug Name	Acetaminophen 300 mg with codeine 15 mg (Tylenol #2) -- Indicated for the treatment of mild to moderate pain. Acetaminophen can be used safely before surgery.
Adult Dose	1-2 tab PO q4h prn
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Toxicity of codeine increases with CNS depressants, tricyclic antidepressants, MAOIs, neuromuscular blockers, CNS depressants, phenothiazines, and narcotic analgesics Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity of acetaminophen
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in patients who are dependent on opiates because this substitution may result in acute opiate-withdrawal symptoms; caution in patients with severe renal or hepatic dysfunction Hepatotoxicity with acetaminophen possible in those with long-term alcoholism following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; acetaminophen is contained in many OTC products, and combined use with these products may result in cumulative acetaminophen doses and exceed recommended maximum dose

Drug Name	Acetaminophen (Tylenol, Feverall, Tempra) -- DOC for pain in patients with documented hypersensitivity to aspirin or NSAIDs, with upper GI disease, or who are taking oral anticoagulants.
Adult Dose	325-650 mg PO q4-6h or 1000 mg PO tid/qid; not to exceed 4 g/d
Pediatric Dose	less than 12 years: 10-15 mg/kg/dose PO q4-6h prn; not to exceed 2.6 g/d >12 years: 325-650 mg PO q4h; not to exceed 4 g/d
Contraindications	Documented hypersensitivity; known G-6-PD deficiency
Interactions	Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Hepatotoxicity possible in long-term alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; acetaminophen is contained in many OTC products, and combined use with these products may result in cumulative acetaminophen doses exceeding recommended maximum dose

Drug Name	Oxycodone and acetaminophen (Percocet, Tylox) -- Drug combination indicated for the relief of moderate to severe pain.
Adult Dose	1-2 tab or cap PO q4-6h prn pain
Pediatric Dose	0.05-0.15 mg/kg/dose oxycodone PO, not to exceed 5 mg/dose of oxycodone, PO q4-6h prn
Contraindications	Documented hypersensitivity
Interactions	Phenothiazines may decrease analgesic effects of this medication; toxicity increases with coadministration of either CNS depressants or tricyclic antidepressants
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Duration of action may increase in elderly persons; be aware of total daily dose of acetaminophen patient is receiving; do not exceed 4 g/d of acetaminophen, higher doses may cause liver toxicity

FOLLOW-UP

Further Inpatient Care:

• Patients with adult rhabdomyomas may experience breathing difficulties. These patients may need nasal oxygen. If airway obstruction is diagnosed, surgical intervention should be considered.

• Patients with genital rhabdomyomas may require catheterization if they have symptoms of urinary tract obstruction.

• Patients with advanced cardiac rhabdomyomas should be placed in a cardiac care unit.

Further Outpatient Care:

• Patients who have had surgical resection of their rhabdomyomas should have routine postoperative care (eg, dressing changes and suture removal when indicated).

In/Out Patient Meds:

• Acetaminophen and codeine or oxycodone and acetaminophen may be used to control postoperative pain. Oxycodone with acetaminophen (Percocet) can produce drug dependence of the morphine type. Accordingly, the potential for drug abuse exists.

Deterrence/Prevention:

• No measures can be used to prevent the occurrence of rhabdomyoma.

Complications:

• Any surgical procedure can be complicated by infection.

• Patients with cardiac rhabdomyoma may develop congestive heart failure or arrhythmia.

Prognosis:

• The prognosis for patients who have undergone surgery for the removal of rhabdomyomas varies from fair to good depending on the part of the body involved. Patients with cardiac rhabdomyomas have the highest risk.

Patient Education:

• Patients with rhabdomyomas should be aware of the nature of their particular tumors and the type of surgical procedures available for treatment.

MISCELLANEOUS

Medical/Legal Pitfalls:

• Any surgical procedure has a risk of a malpractice claim. The patient must sign a detailed informed consent form before any procedure is performed.

Special Concerns:

• Patients with genital rhabdomyomas who become pregnant need to be monitored closely. They may require a cesarean delivery.

• When fetal cardiac rhabdomyoma is diagnosed, careful evaluation of other fetal structures, including brain and renal parenchyma, should be performed to search for signs of tuberous sclerosis.