Rhabdomyosarcoma

Rhabdomyosarcoma is a malignant tumor originating from skeletal (striated) muscle.

ICD-10 code

• C48. Malignant neoplasm of retroperitoneum and peritoneum.
• C49. Malignant neoplasm of other connective and soft tissues.

Epidemiology

Rhabdomyosarcoma accounts for about half of all cases of soft tissue sarcomas in children. It accounts for 10% of all oncological pathology in childhood. There are two age peaks in the incidence of this tumor - at 1-7 and 15-20 years. The first coincides with the period of manifestation of congenital malignant neoplasms of childhood - neuroblastoma and nephroblastoma, the second - with the typical age of diagnosis of malignant bone tumors.

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Rhabdomyosarcoma and hereditary syndromes

In about a third of cases, rhabdomyosarcoma is combined with various malformations: genitourinary tract (8%), central nervous system (8%), digestive system (5%), cardiovascular system (4%). In 4% of cases, an accessory spleen is detected, in 1% - hemihypertrophy. Rhabdomyosarcoma can be found in syndromes that provide a predisposition to the development of malignant neoplasms - Beckwith-Wondermania, Li-Fraumeni (determines a high frequency of malignant tumors in family members: associated with a mutation of the p53 gene). Recklikhausen. Rubinstein-Taybi (a combination of dwarfism and mental retardation with hypertelorism, facial asymmetry, beak-shaped nose, abnormal bite, hypermetropia, astigmatism, characteristic shortening and thickening of the thumbs and toes, and often with other anomalies of the skeleton and internal organs).

Symptoms of Rhabdomyosarcoma

Rhabdomyosarcoma can be localized in any area of the body, including in places where there is no skeletal muscle (for example, the bladder, bile ducts). This neoplasm is characterized by lymphogenous and hematogenous (to the lungs, bones, bone marrow) metastasis.

Localization of rhabdomyosarcoma in the head and neck area and in the genitourinary tract is more often detected in children under 10 years of age, while neoplasms of the extremities, trunk, and paratesticular rhabdomyosarcomas are typical for adolescents.

Classification of rhabdomyosarcoma

Histological structure and histological clammification

Rhabdomyosarcoma develops in striated muscle tissue, as well as in smooth muscle anatomical structures such as the bladder, vagina, prostate, and spermatic cord. The source of rhabdomyosarcoma growth is not mature skeletal muscle, but immature mesenchymal tissue, its predecessor. Conditions for the development of rhabdomyosarcoma arise, for example, in the area of the urinary bladder triangle as a result of mixing mesoderm and ectodermal tissues in this area, or in the head and neck area, where abnormalities in the development of branchial arch derivatives occur. Several histological types of rhabdomyosarcoma are distinguished.

• Embryonal rhabdomyosarcoma (57% of all rhabdomyosarcomas) histologically resembles the structure of the skeletal muscles of a 7-10-week fetus. It is characterized by loss of heterozygosity of the 11p15 locus, which leads to the loss of maternal genetic information and duplication of paternal genetic material. This variant is encountered mainly in patients aged 3-12 years. Rhabdomyosarcoma affects the head and neck, orbit, and genitourinary tract.
• The botryoid variant (6%) of embryonic rhabdomyosarcoma is characterized by the presence of polypoid or "grape-shaped" masses localized inside organs covered with mucous membranes and in body cavities. The neoplasm is encountered at the age of up to 8 years. It is localized in the urinary bladder, vagina, nasopharynx.
• Alveolar rhabdomyosarcoma (9%) is histologically similar to the skeletal muscle cells of a 10-21-week fetus. It is characterized by the translocation t(2; 13) (q3S; ql4). The neoplasm usually affects the extremities, trunk, and in adolescents - the perineum. It occurs at the age of 5 to 21 years.
• Pleomorphic rhabdomyosarcoma (1%) is histologically dissimilar to fetal muscle tissue, affects the trunk and limbs, and is rarely found in children.
• Undifferentiated rhabdomyosarcoma (10%) arises from mesenchymal cells without signs of differentiation, is localized in the limbs and trunk, and occurs in children under 1 year of age.
• Rhabdomyosarcomas, which cannot be attributed to any of the above-mentioned variants, account for 7%. Histologically, these neoplasms are heterogeneous. They are localized in the extremities and trunk, and are found in patients aged 6 to 21 years.

In rhabdomyosarcomas, chromosomal abnormalities such as 5q+: 9q+: 16p+: 12p+: del(l): and hyperdiploidy with multiple copies of 2,6, 8, 12, 13, 18, 20, 21 are also detected. At the same time, the prognosis for diploid tumors is worse compared to hyperdiploid ones.

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Clinical staging

For rhabdomyosarcoma and other soft tissue sarcomas, staging according to the TNM system is used at the preoperative stage (Table 66-20).

The TNM classification does not provide for the allocation of categories T3 and T4. The presence of more than one neoplasm is considered as a primary tumor and its distant metastases. In modern protocols for the treatment of soft tissue sarcomas, the IRS (Intergroup Rhabdomyosarcoma Study) classification and postoperative pT staging are used for their staging at the stage after radical surgery or biopsy.

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Diagnosis of rhabdomyosarcoma

Symptoms of rhabdomyosarcoma and other soft tissue sarcomas depend largely on their location.

• When the neoplasm is located in the extremities, the presence of a palpable tumor formation is characteristic, causing deformity of the limb and disrupting its functions. The formation is usually quite dense, its palpation does not cause noticeable pain.
• When the neoplasm is localized in the retroperitoneal space, abdominal pain, enlargement and asymmetry, and symptoms of compression of the intestines and urinary tract occur.
• In case of localization of the neoplasm in the area of the trunk, head, neck, the neoplasm can be detected during physical examination: defiguration of the affected part of the body, limitation of movements in this area. In this case, rhabdomyosarcoma of the neck can be combined with coarsening of the voice and dysphagia, neoplasms of the nasopharynx - with local pain, nosebleeds, dysphagia, tumors of the paranasal sinuses with local pain and edema, sinusitis, unilateral discharge and bleeding from the nasal passages, rhabdomyosarcoma of the middle ear - with chronic otitis with purulent and hemorrhagic discharge, the presence of polypond masses in the external auditory canal, peripheral paralysis of the facial nerve, rhabdomyosarcoma of the orbit - with ptosis, strabismus, decreased visual acuity.
• Neoplasms of parameningeal localizations are accompanied by paralysis of the facial nerves, meningeal signs, and respiratory failure due to tumor invasion into the brainstem.
• Neoplasms of the small pelvis are accompanied by obstruction of the intestine and urogenital tract. In case of tumors of the urinary tract, a violation of the passage of urine is noted, up to its acute retention; a dense formation can be palpated above the pubis. In case of neoplasms of the bladder and prostate, macrohematuria occurs in some cases. Vaginal bleeding and the presence of grape-like tumor masses in the vagina are characteristic of tumors of the vagina and uterus. In case of neoplasms of the epididymis, its enlargement and soreness are noted. Laboratory and instrumental studies have shown that the epididymis is enlarged and painful.

The diagnostics of soft tissue sarcomas is based on morphological verification of the diagnosis. However, before it is performed, it is necessary to evaluate the primary tumor focus and localizations of possible metastases. When diagnosing the primary tumor focus, the diagnostic plan includes studies applicable to a given localization of rhabdomyosarcoma: radiography, ultrasound, CT and MRI, excretory urography, histography, etc. Diagnosis of possible metastases is performed according to a standard plan, based on the localizations of metastases characteristic of soft tissue sarcomas. Radiography and CT of the chest, radioisotope study of the skeleton, myelogram study are performed. Ultrasound of regional lymph nodes.

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Mandatory and additional studies of patients with malignant tumors of soft tissues

Mandatory diagnostic tests

• Complete physical examination with assessment of local status
• Clinical blood test
• Clinical urine analysis
• Blood biochemistry (electrolytes, total protein, liver function tests, creatine, urea, lactate dehydrogenase, alkaline phosphate, phosphorus-calcium metabolism)
• Coagulogram
• Ultrasound of the affected area
• X-ray of the chest organs in five projections (straight, two lateral, two oblique)
• Ultrasound of the abdominal organs and retroperitoneal space
• Bone marrow puncture from two points
• Scintigraphy (RID) of the bone system
• ECG
• EchoCG
• The final stage is a biopsy (or complete removal) to verify the gastological diagnosis. It is advisable to make prints from the biopsy for cytological examination.

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Additional diagnostic tests

• If metastases to the lungs are suspected
• CT scan of the chest organs
• If there is a suspicion of involvement of bone structures in the process, radiography of the bones of this anatomical region in two projections (direct and lateral, including the joints located above and below)
• If metastases to other bones are detected according to the data
• RID-targeted radiography of the affected areas or CT of the specified areas
• If brain metastases are suspected - EchoEG and CT of the brain
• Ultrasound of regional lymph nodes if metastatic lesions are suspected
• Renal scintigraphy in cases of detected renal dysfunction
• If rhabdomyosarcoma is localized in the soft tissues of the limb - MRI of the affected limb
• Ultrasound color duplex angioscanning of the vessels of the affected limb
• Angiography of the limb (as indicated)
• When localized in the bladder:
  • cystoscopy with possible biopsy;
  • excretory urography;
  • uroflowmetry
• In parameningeal localizations:
  • ENT examination;
  • ophthalmological examination;
  • cytological examination of cerebrospinal fluid;
  • CT/MRI of the brain

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Treatment of rhabdomyosarcoma

Treatment of rhabdomyosarcoma is complex. It includes chemotherapy, radical surgery and radiation therapy. Modern chemotherapy programs include the use of cytostatics such as alkylating agents (ifosfamide, cyclophosphamide), vinca alkaloids (vincristine), anthranilline antibiotics (doxorubicin), actinomycin-D, topoisokerase inhibitors (etoposide), platinum preparations (carboplatin).

Surgical treatment of rhabdomyosarcoma should be carried out following the general principle of surgical radicality. In case of initially unresectable neoplasms, the first stage should be a biopsy. This allows subsequently to avoid repeated local growth of the tumor from its macro- or microscopic remnants, which is especially important for localizations in the head, neck, orbit. In some cases, even after effective polychemotherapy, rhabdomyosarcoma may remain unresectable (nasopharyngeal neoplasms, parameningeal localizations). In this case, surgical treatment is not indicated, local control is carried out by means of conservative chemoradiation therapy.

When the tumor is localized in the soft tissues of the extremities, a significant volume of damage and involvement of the vascular-nerve bundle in the neoplasm are possible. In such cases, despite the absence of signs of the spread of the malignant process to bone structures, the only radical option is an organ-sparing operation. Limb-preserving operations are carried out either after the tumor size has been reduced as a result of chemotherapy, or initially for small neoplasms that have clear boundaries in ultrasound and CT-MRI.

In case of isolated rhabdomyosarcoma lesion of the bladder fundus (other parts are free from the tumor) with a good response to chemotherapy, resection of the bladder wall is possible. In most cases, the bladder is either totally affected, or rhabdomyosarcoma is localized in the area of the vesical triangle, therefore, there is a need for extirpation of the bladder with subsequent surgical reconstruction of the urine outflow tract. The optimal tactics of one-stage surgical treatment in pediatric oncology practice should be considered ureterosigmoidostomy, as opposed to both ureterocutaneostomy and one-stage formation of complex artificial urinary reservoirs from different parts of the intestinal tube. Against the background of chemotherapy in the first case, there is a high risk of ascending urinary infection with the development of bilateral pyelonephritis, and in the second - failure of the formed reservoir due to a decrease in the regenerative capacity of tissues against the background of the action of cytostatic agents. As an alternative, a tactic with an initial ureterocutaneostomy and a subsequent (several months after the end of chemoradiation treatment) stage of formation of an artificial urinary reservoir is possible.

Paratesticular neoplasms are removed together with the testicle and spermatic cord from the inguinal access (orchofuniculectomy). In case of rhabdomyosarcoma of the uterus, its extirpation is indicated, in case of a vaginal tumor - removal of the vagina. In case of neoplasms affecting both of these organs, the uterus and vagina are removed as a single block with the tumor.

Lung metastases, if resectable, are subject to surgical removal. Bone metastases, due to their fatality, should not be removed for the prognosis.

Radiation therapy for rhabdomyosarcoma is performed according to the criteria defined by the specific treatment program. The radiation dose depends on the location or metastases.

High-dose chemotherapy with bone marrow transplantation is prescribed to patients with rhabdomyosarcomas from the high-risk group: at stage IV.

What is the prognosis for rhabdomyosarcoma?

Rhabdomyosarcoma is associated with a relatively favorable prognosis: at stage I, up to 80% of patients survive, at stage II - up to 65%, at stage III - up to 40%. Stage IV is associated, as a rule, with a fatal prognosis. The prognosis is better for the embryonic type (up to 70%) compared to the alveolar and other types (50-60%). The prognosis worsens with an increase in the size of the neoplasm at the time of diagnosis (usually taken into account: more or less than 5 cm is the tumor size in the largest dimension). Depending on the location of rhabdomyosarcoma, favorable and unfavorable localizations are distinguished. The prognosis for unfavorable localizations is worse than for favorable ones; however, it is not fatal. Favorable localizations include the orbit, paratesticular region, superficial areas of the head and neck, vulva, vagina, uterus. Unfavorable sites include the trunk, extremities, bladder, prostate, chest and abdominal cavity, deep areas of the head and neck. Better outcomes are observed in children under 7 years of age compared with older children. This is associated with both a decrease in the frequency of the embryonic type of rhabdomyosarcoma and an increase in the frequency of common forms with age of patients. The prognosis for local relapse after programmatic treatment, including after radical surgery, is usually fatal.