Rhabdomyosarcoma

RhabdomyosarcomaRhabdomyosarcoma is the most common aggressive soft tissue tumor, which affects children and adolescents.


Description

Rhabdomyosarcoma is a soft tissue tumor,which most often occur in children and adolescents. Rarely, it is seen in adults over 40. Common sites where rhabdomyosarcomama develops are head and neck (40%), genitourinary tract (20%), retroperitoneal cavity and the limbs. The tumor arises from mesenchymal cells (the precursors of skeletal muscles), that don’t differentiate normally.

There are several types of rhabdomyosarcoma distinguished – alveolar, embryonal, which comprises 60% of cases, and anaplastic rhabdomyosarcoma.

Related: Sarcomatoid carcinoma

Incidence

Annually occur 4.5 cases per million. The majority of the cases occur in children under 10 years, usually a person is at the age of 6-8 years when the diagnosis is made. The prevalence is a bit higher among males with a male to female ratio of 1.3:1.

 

Causes

Mutations in the RAS and FGFR4 genes, 11p15 are associated with embryonal rhabdomyosarcoma.

In alveolar rhabdomyosarcoma  the translocation between the FKHR/FOXO1 transcription factor gene (on chromosome 13) and either PAX3 transcription factor gene (on chromosome 2) or PAX7 gene (on chromosome 1) may be identified, mutations of NMYC, ALK and MET genes may also be present.

Alveolar and embryonal subtypes are characterized by the overexpression of insulin growth factor 2 (IGF2).

 

Risk factors

The tumor may be associated with other congenital disorders such as neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Li–Fraumeni syndrome, cardio-facio-cutaneous syndrome, Noonan syndrome, pleuropulmonary blastoma, and Costello syndrome.

Possible link to parental use of cocaine and marijuana was reported.

 

Symptoms

Common symptoms of rhabdomyosarcoma are the swelling/painful palpable mass at the site of origin along with other local symptoms – displacement of the eye, vaginal bleeding, dysuria, etc.

Rhabdomyosarcoma of the head and neck may be suspected when the following symptoms are present: diplopia (doubled vision), exophtalmos (bulging of the eyeball), headache, congestion, nasal discharge, cranial nerve palsy, obstruction, dysphagia, hearing or vision loss. Genitourinary rhabdomyosarcoma may cause urinary tract obstruction or constipation. Abdominal or pelvic manifestations include abdominal pain and abdominal mass, ascites, haematuria.

Cancer commonly disseminates to lungs, bones, bone marrow and brain.

Embryonal rhabdomyosarcoma usually develops in head, neck and genitourinary tract. Alveolar rhabdomyosarcoma typically arises in the trunk or extremities.

 

Stages

According to the estimated risk and possible outcomes the following risk groups are distinguished:

  • Low-risk – embryonal rhabdomyosarcoma without dissemination, which locates in the orbit, vagina and paratesticularly;
  • Intermediate-risk – alveolar rhabdomyosarcoma without metastases, parameningeal tumors or extremities tumors;
  • High-risk;

 

Based on the size of the tumor, its location and dissemination there are 4 stages of rhabdomyosarcoma:

  • Stage 1 – a tumor of any size, which grows in the favorable area (the orbit, the head and neck, genitourinary tract and bile ducts). It hasn’t spread to a distant areas of the body;
  • Stage 2 – a tumor about 5 cm in size originates from an unfavorable area (the bladder and prostate, limb, a parameningeal area). Lymph nodes or other body parts are unaffected;
  • Stage 3 – a tumor originates from an unfavorable area (the bladder and prostate, limb, a parameningeal area). This tumor may be 5 cm in size or even smaller with no signs of dissemination. If the neoplasm is bigger than 5 cm it may have disseminated or may not.
  • Stage 4 – a tumor has disseminated to the distant parts of the body;

 

Treatment

Treatment depends on the size of the tumor, its location and spread. Surgery solely is used when the tumor is localized. The combination of surgery, chemotherapy, radiotherapy and immunotherapy is usually used.

 

Applicable medicines

Chemotherapy agents which are used in the treatment of rhabdomyosarcoma include vincristine, actinomycin D, doxorubicin, cyclophosphamide, ifosfamide, etoposide, melphalan and cisplatin.

 

Prognosis

Prognostic factors in rhabdomyosarcoma include:

  • Poor prognostic factors, which are associated with worse outcomes, are parameningeal and retroperitoneal site, lymph nodes and metastatic dissemination, inability to resect the tumor completely, alveolar histology of the tumor, poor response to chemotherapy and adulthood.
  • Good prognostic factors, associated with favorable outcomes, are localized tumor, possible complete resection of the neoplasm, embryonal histology, response to chemotherapy, childhood and infancy.

In general the survival rate is 70-75%. The five-year survival rate for low-risk is 95%, intermediate-risk – 65% and high risk – 15%.