Rhabdomyomas

Rhabdomyoma is a lesion of striated muscle. There are two main types, as follows:

• Neoplastic
• Hamartoma

The neoplastic variety is further divided into the following three subtypes:

• Adult
• Fetal
• Genital

Hamartomas are divided into the following two subtypes:

• Cardiac rhabdomyoma
• 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.[1] The cardiac rhabdomyoma, which is believed to be a hamartoma, usually is diagnosed in the pediatric age group. However, hamartomas are benign tumorlike growth made up of normal mature cells in abnormal number or distribution. Whereas malignant tumors contain poorly differentiated cells, hamartomas consist of distinct cell types retaining normal functions. Because their growth is limited, hamartomas are not true tumors.

The adult rhabdomyoma is a rare tumor; very few cases have been reported in the literature.[2, 3] 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.[4]

Studies in immunohistochemistry confirm that the tumors are almost totally matured neoplasms of clonal origin. Although the mass is usually asymptomatic, it 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; 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.[5]  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.[6, 7, 8]  Cardiac rhabdomyomas typically develop in utero and are often detected on prenatal ultrasonography. 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.[9]  Molecular evidence of this association have now been identified as the TSC2 gene missense mutation (E36; 4672 G>A, 1558 E>K TSC2).[10]

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.[11]

Malignant transformation of rhabdomyomas is very rare, though there are a few case reports in the literature.

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

United States statistics

Compared with other soft-tissue tumors, rhabdomyoma is extremely rare in the United States. Specifically, in the category of benign primary tumors of the heart, rhabdomyoma has a relative incidence of 5.8%.

International statistics

Worldwide, rhabdomyoma is rare. Exact data regarding its incidence within particular populations have not been cited. In the world literature, 14 cases of multifocal adult head and neck rhabdomyoma are reported.[12]

Age-related demographics

Adult rhabdomyoma occurs in older adults (usually >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; a 45-year single-institution review found rhabdomyoma to account for 58% of cardiac neoplasms in 64 pediatric patients (age < 18 years) who presented for surgical evaluation of a cardiac tumor.[13]  Rhabdomyomatous mesenchymal hamartoma of the skin is observed in newborns and infants.

Sex-related demographics

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.

Race-related demographics

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

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.

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 consisted of heart failure or a cardiac murmur in six patients each and arrhythmia in three patients.[14]

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.

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

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

The presenting history depends in part on the age and sex of the patient, as follows:

• 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)

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.

Order the usual laboratory studies, including the following:

• Complete blood count (CBC)
• Hemoglobin/hematocrit
• Platelet count
• Urinalysis

Order imaging studies as appropriate.[15]

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

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

Magnetic resonance imaging (MRI) of the affected area might be useful.

Occasionally, computed tomography (CT), particularly of the chest in cases of cardiac rhabdomyoma, might be of value (see the image below).

Atrial rhabdomyoma as seen on cardiac CT scan in a patient with tuberous sclerosis.

Any masses, such as those found in the head and neck of patients with adult rhabdomyoma, should be biopsied 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 with a Tru-Cut needle. A small stab wound is made directly over the mass. The needle is introduced into the tumor, then withdrawn with a small amount of tumor tissue attached. Subsequently, a dressing is applied to the wound.

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 (see the image below).

Histopathology of adult rhabdomyoma. Microscopically, the adult rhabdomyoma contains deeply eosinophilic polygonal cells with peripherally placed nuclei. Cross-striations can be observed (X250).

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.

Rhabdomyomas may be characterized on the basis of grade (G), site (T), and metastasis (M), as follows:

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

Staging is as follows:

• 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

Patients with adult rhabdomyoma may experience progressive difficulties in breathing and swallowing. In such instances, nasal oxygen may help patients with breathing difficulties. If airway obstruction is diagnosed, surgical intervention should be considered. 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. Patients with advanced cardiac rhabdomyomas should be placed in a cardiac care unit. Anecdotal case reports show significant regression of a cardiac rhabdomyoma after receiving everolimus, an mTOR (mammalian target of rapamycin) inhibitor.[16, 17, 18, 19, 20, 21, 22]

Patients with genital rhabdomyomas may require catheterization if they have symptoms of urinary tract obstruction. Patients with genital rhabdomyomas who become pregnant need to be monitored closely. They may require a cesarean delivery.

Studies have explored the expression of anaplastic lymphoma kinase (ALK) and insulinlike growth factor-1 receptor (IGF-1R) as potential therapeutic targets in rhabdomyosarcoma. In one study, IGF-1R and ALK expression was observed in 72% and 92% of alveolar rhabdomyosarcomas and 61% and 39% of embryonal rhabdomyosarcomas, respectively.[23] Coexpression was observed in 68% of alveolar rhabdomyosarcomas and 32% of embryonal rhabdomyosarcomas. Combined inhibition reveals synergistic cytotoxic effects and continues to be a promising area for future study; further investigation is needed.

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

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 restrict their activities.

Patients with adult rhabdomyoma should be treated with 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.[24]

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.

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

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

Any surgical procedure can be complicated by infection.

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

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.

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

Class Summary

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.

Aspirin (Aspercin, Bufferin, Ecotrin, Durlaza)

Aspirin is a short-acting anti-inflammatory agent with rapid absorption in the proximal gastrointestinal (GI) tract. It inhibits inflammatory reactions and pain, probably by decreasing the activity of the enzyme cyclooxygenase and thereby inhibiting prostaglandin synthesis. It provides adequate pain relief. However, aspirin should be discontinued several days before any surgical treatment is undertaken to prevent excessive bleeding.

Codeine/acetaminophen (Tylenol #3)

Acetaminophen is the drug of choice for the treatment of pain in patients with documented hypersensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), as well as in those who have upper GI disease or who are taking oral anticoagulants. Codeine alters perception and response to pain by inhibiting ascending pain pathways. Indicated for the treatment of mild-to-moderate pain. Acetaminophen can be used safely before surgery.

Acetaminophen (Tylenol, Feverall, Acephen, Q-Pap)

Acetaminophen is the drug of choice for pain in patients who have documented hypersensitivity to aspirin or NSAIDs, who have upper GI disease, or who are taking oral anticoagulants. It may inhibit synthesis of prostaglandins in the central nervous system (CNS), and this may in turn work peripherally to block pain impulse generation.

Oxycodone and acetaminophen (Percocet, Endocet, Primlev, Xartemis XR)

This drug combination is indicated for the relief of moderate-to-severe pain. Oxycodone binds to opioid receptors within neuronal membranes of synapses, and this binding blocks pain perception in the cerebral cortex. Acetaminophen inhibits synthesis of prostaglandins in the CNS, and this in turn blocks peripheral generation of pain impulses.

Codeine

Codeine binds to opioid receptors in the CNS. It alters perception and response to pain by inhibiting ascending pain pathways. Codeine is used for the treatment of mild-to-moderate pain. It may be used in combination with acetaminophen, aspirin, or NSAIDs.