Nicholas G. Cost, MD
Paul H. Noh, MD, FACS, FAAP
BASICS
DESCRIPTION
• Rhabdomyosarcoma (RMS) (sarcoma botryoides) is a malignancy arising from embryonal mesenchyme that tends to occur mostlyin children (Sometimes also called Embryonal Rhabdomyosarcoma)
• Most common soft tissue sarcoma in children
• Sarcoma botryoides describes a polypoid variant of RMS originating in a hollow viscus (vagina, bladder)
• Of all types of pediatric RMS15–20% involve GU system:
– Paratesticular
– Bladder
– Prostate
– Uterus
– Vagina
EPIDEMIOLOGY
Incidence
• 0.5–0.7 cases per million children <15 yr
• Bimodal age distribution:
– 1st peak: 2–4 yr
– 2nd peak: 15–19 yr
• 3rd most common solid tumor in children (behind neuroblastoma and Wilms tumor)
Prevalence
N/A
RISK FACTORS
See genetics
Genetics
• Li–Fraumeni syndrome:
– Mutation of p53 tumor suppressor gene
– Higher incidence of RMS
• Neurofibromatosis:
– Higher incidence of RMS
• Cytogenetic abnormalities:
– Alveolar histology subtype:
1;13 translocation (favorable prognosis)
2;13 translocation (unfavorable prognosis)
– Embryonal histology subtype:
Loss of heterozygosity on chromosome 11
PATHOPHYSIOLOGY
• The Latin word “botryoides” refers to the polypoid or “grape-like lesion” appearance of the tumor beneath the mucosa
– Some sources refer to this as “embryonal RMS”
• Rapid growth with local invasion
• Can spread by lymphatic and hematogenous routes
• Thought to arise from immature cells that are destined to form striated skelet al muscle:
– However, may arise in locations where skelet al muscle is not typically found, such as the bladder
• Defect in regulatory mechanism that controls proliferation and differentiation of skelet al muscle
• Prognosis and pattern of spread depends on histologic subtype and clinical staging
• Lymph nodes (LNs) and lungs are the most common sites of distant metastasis
ASSOCIATED CONDITIONS
See Genetics
GENERAL PREVENTION
None
DIAGNOSIS
HISTORY
• Family history of malignancy or genetic syndromes (Li–Fraumeni, neurofibromatosis)
• Bladder/prostate:
– Urinary frequency
– Stranguria
– Urinary retention
– Hematuria
• Paratesticular:
– Scrotal swelling or pain
– Back pain
• Vaginal/uterine:
– Vaginal discharge/bleeding
PHYSICAL EXAM
• Bladder/prostate
– Abdominal mass
– Bladder distention
– Firm prostate or mass on rectal exam
• Paratesticular
– Scrotal mass
• Vagina/uterine
– Vaginal mass (may be prolapsing)
– Abdominal mass
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Basic metabolic panel: BUN/Cr may be elevated with ureteral obstruction
• Complete blood count: May see anemia due to vaginal bleeding or hematuria
• β-HCG or AFP: Evaluate for testicular tumors
Imaging
• CT/MRI of abdomen/pelvis: Evaluate local extent of tumor, pelvic or retroperitoneal LN involvement, distant metastasis
• Chest x-ray/CT: Evaluate for pulmonary metastases
• PET scan: Evaluate the metabolic activity of the primary for future comparison after therapy, as well as assess for metastasis
• Bone scan: Evaluate for osseous metastasis
• Scrotal US: Characterize paratesticular mass
Diagnostic Procedures/Surgery
• Bone marrow aspirate/biopsy: Evaluate for metastases for all primary sites of RMS
• Bladder/prostate
– Cystoscopy: Transurethral resection/biopsy for pathologic diagnosis
– Image-guided needle biopsy: Pathologic diagnosis
• Paratesticular
– Radical inguinal orchiectomy: Diagnostic and therapeutic
• Vagina/uterine
– Cystoscopy/vaginoscopy: Evaluate extent of tumor, biopsy for pathologic diagnosis
Pathologic Findings
• Embryonal:
– Most common subtype
– Accounts for majority of GU RMS
– Embryonal variants associated with excellent prognosis:
Sarcoma botryoides
Spindle cell/leiomyomatous
• Alveolar:
– Less common in GU RMS
– More common in trunk/extremity RMS
– Higher rates of local recurrence, LN spread, and distant metastasis
• Pleomorphic:
– Undifferentiated/anaplastic variant
– Poor prognosis
DIFFERENTIAL DIAGNOSIS
• Bladder/prostate
– TCC of bladder
– Inflammatory pseudotumor of bladder
– Nephrogenic adenoma of bladder
– Fibroepithelial polyps of prostatic urethra
• Testis
– Primary testicular tumor
– Benign adnexal mass
• Vagina/uterine
– Prolapse of ureterocele, urethra, vagina
TREATMENT
GENERAL MEASURES
• Pre- and post-op staging and risk classification are critical in evaluation and treatment planning
– Preoperative staging: Intergroup Rhabdomyosarcoma Study Group (IRSG) staging/classification system based on TNM and primary location
– Postoperative grouping: IRSG grouping based on primary resection
– Risk classification: Combines stage, group, and histology—helps determine therapy and prognosis
• Preoperative staging: TNM system
– T1: Confined to organ of origin
(a) ≤5 cm in diameter
(b) >5 cm in diameter
– T2: Extension or fixed to surrounding tissue
(a) ≤5 cm in diameter
(b) >5cm in diameter
– N0: Regional LNs clinically negative
– N1: Regional LNs clinically positive
– Nx: Unknown
– M0: No distant metastasis
– M1: Metastasis present
• Preoperative staging: IRSG
– Stage 1: Vaginal and paratesticular, any T, any N, M0
– Stage 2: Bladder/prostate, T1/T2a, N0/Nx, M0
– Stage 3 Bladder/prostate, T1/T2a and N1, OR T1b/T2b, any N, M0
– Stage 4: Any T, M1
• Postoperative grouping
– Group I: Localized disease, completely excised, no microscopic residual
(a) Confined to site of origin, completely resected
(b) Infiltrating beyond site of origin, completely resected
– Group II: Total gross resection
(a) Gross resection with microscopic local residual
(b) Regional disease with involved LNs, completely resected, no microscopic residual
(c) Microscopic local or nodal residual
– Group III: Incomplete resection with gross residual disease or biopsy only for diagnosis
– Group IV: Distant metastasis
• Risk grouping
– Low risk
Embryonal histology, Stage 1, all groups
Embryonal histology, Stage 2/3, Group I/II
– Intermediate risk
Embryonal histology, Stage 2/3, Group III
Alveolar histology, Stage 1/2/3, Group I/II/III
– High risk
Any histology, Stage 4, Group IV
• All sites of GU RMS require a multidisciplinary approach to curative therapy including appropriate surgical excision, chemotherapy, and radiation (1)
• For bladder/prostate and vaginal/uterine RMS, chemotherapy is 1st-line therapy after biopsy and before radiation or extirpative surgery in all cases except rare instances amenable to immediate partial cystectomy with negative margins
• For paratesticular RMS, retroperitoneal staging is critical. Any boys <10 yr with radiologic evidence of enlargedretroperitoneal LNs, and all patients >10 yr should have an ipsilateral retroperitoneal LN dissection (RPLND). Thisshould be done to complete staging and must be done before chemotherapy or radiation (1).
MEDICATION
First Line
• Bladder/prostate
– Low risk: Vincristine, actinomycin-D (VA)
– Low-risk N1, intermediate risk, high-risk: VA + Cyclophosphamide (VAC)
• Paratesticular
– VA: Stage 1, <10 yr, no evidence of LN involvement on imaging (1)
– VAC: Positive LNs on RPLND
• Vagina/uterine (1)
– VAC: Chemotherapy followed by repeat biopsy to assess residual disease
Second Line
• 2nd-line chemotherapy with addition of carboplatin, etoposide, irinotecan, or topotecan
• Phase I studies
SURGERY/OTHER PROCEDURES
• Bladder/prostate:
– Partial cystectomy: Primary treatment in rare cases at dome/lateral wall where adequate margins can be obtained
– Radical cystectomy: Performed after chemotherapy or chemoradiation if tumor not amenable to bladder-sparing options
– Urinary diversion: Both temporary and permanent reconstructive options
– Radical prostatectomy: Performed for isolated prostatic tumors after chemoradiotherapy
• Paratesticular:
– Radical inguinal orchiectomy: All cases should be approached inguinally with radical resection
– RPLND (2):
All >10 yr regardless of imaging
<10 yr if evidence of LN involvement on imaging, prior to chemotherapy
• Vagina/uterine:
– Vaginectomy: If evidence of residual disease on postchemotherapy biopsy
ADDITIONAL TREATMENT
Radiation Therapy
• Bladder/prostate:
– Postdiagnostic biopsy, in addition to chemotherapy: Most cases (Group III)
– Following initial attempted resection initial resection with residual margins, in addition to chemotherapy: Group II
• Paratesticular:
– Positive LNs on RPLND
• Vagina/uterus:
– After chemotherapy or surgical resection unless an initial upfront resection (Group I)
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Bladder/prostate:
– 3-yr disease-free survival (3)
Embryonal: 83% (Botryoid variant: 92%) (4)
Alveolar: 40%
• Paratesticular:
– 3-yr disease-free survival: 81% (3)
– Overall survival: 96%
• Vagina/uterine:
– 5-yr disease-free survival: 69% (3)
– Overall survival: 82% (94%in those <10 yr, 76% in those >10 yr) (5)
COMPLICATIONS
• Bladder/prostate
– Bladder dysfunction
– Hematuria/dysuria
– Secondary malignancy
– Incontinence
• Paratesticular
– Complications of RPLND
Bowel obstruction
Ejaculatory dysfunction
• Vaginal/uterine
– Infertility
– Sexual dysfunction
• Chemotherapy-related toxicity
– Neurotoxicity
– Secondary malignancy
FOLLOW-UP
Patient Monitoring
• Follow up imaging to assess for recurrent disease
• Assessment of residual bladder/vaginal function (exam, labs, urodynamics)
Patient Resources
http://www.curesearch.org/
REFERENCES
1. Wu HY, Snyder HM 3rd. Pediatric urologic oncology: Bladder, prostate, testis. Urol Clin North Am. 2004;31:619–627.
2. Wiener ES, Anderson JR, Ojimba JI, et al. Controversies in the management of paratesticular rhabdomyosarcoma: Is staging retroperitoneal lymph node dissection necessary for adolescents with resected paratesticular rhabdomyosarcoma? Semin Pediatr Surg. 2001;10:146–152.
3. Wu HY, Snyder HM 3rd, Womer RB. Genitourinary rhabdomyosarcoma: Which treatment, how much, and when? J Pediatr Urol. 2009;5:501–506.
4. Leuschner I, Harms D, Mattke A, et al. Rhabdomyosarcoma of the urinary bladder and vagina: A clinicopathologic study with emphasis on recurrent disease. A report from the Kiel Pediatric Tumor Registry and the German CWS Study. Am J Surg Pathol. 2001;25:856–864.
5. Arndt CA, Donaldson SS, Anderson JR, et al. What constitutes optimal therapy for patients with rhabdomyosarcoma of the female genital tract? Cancer. 2001;91:2454–2468.
ADDITIONAL READING
N/A
See Also (Topic, Algorithm, Media)
• Bladder Mass, Differential Diagnosis
• Bladder Tumors, Benign and Malignant, General Considerations
• IRS (Intergroup Rhabdomyosarcoma Study) Clinical Classification
• Rhabdomyosarcoma, Pediatric (Sarcoma Botryoides) Images 
• Testis, Tumor, and Mass, Pediatric, General
• Vaginal Mass, Newborn
CODES
ICD9
• 171.6 Malignant neoplasm of connective and other soft tissue of pelvis
• 171.9 Malignant neoplasm of connective and other soft tissue, site unspecified
• 184.9 Malignant neoplasm of female genital organ, site unspecified
ICD10
• C49.5 Malignant neoplasm of connective and soft tissue of pelvis
• C49.9 Malignant neoplasm of connective and soft tissue, unsp
• C57.9 Malignant neoplasm of female genital organ, unspecified
CLINICAL/SURGICAL PEARLS
• Radical upfront surgery should be avoided with the goal of organ preservation.
• Small residual masses may not require resection if such surgery would lead to morbidity.