Rhabdomyosarcoma

Steven H. Lin and Moody D. Wharam, Jr.

Background

What are the 3 most commonly tested rhabdomyosarcoma (RMS) cases on the radiation oncology oral boards?

Bladder (trigone), parameningeal (PM), and orbit

What are the 2 incidence age peaks of RMS and their associated histologies?

2–6 yo (embryonal) and 15–19 yo (alveolar)

What is the estimated overall annual incidence of RMS in the U.S.?

350 cases/yr of RMS in the U.S., 3% of all childhood cancers (#1 soft tissue sarcoma)

What are the most common sites of RMS? List them in order of approximate frequency in %.

Most common sites of RMS:

H&N 40% (PM 25%, orbit 9%, non-PM 6%)
GU 30%
Extremity 15%
Trunk 15%

What are the most common sites of mets?

Bone, BM, and lung

What % of pts present with mets? What types are prone to have hematogenous mets?

15% of pts present with mets. The prostate, trunk, and extremities are prone to hematogenous mets.

What is the most common origin of RMS?

Mesenchymal stem cells. Sporadic RMS is the most common.

What genetic syndromes and environmental risk factors are associated with RMS?

Genetic syndromes: Beckwith-Wiedemann syndrome (BWS), Li Fraumeni, and NF-1

Environmental risk factors: parental marijuana/cocaine use and prior RT

What are the 4 major histologies of RMS and their associated subtypes (if any)?

Major histologies of RMS and subtypes:

Embryonal (classic, spindle cell, and botryoid)
Alveolar
Pleomorphic
Undifferentiated

What genetic change is associated with embryonal RMS?

LOH 11p15.5 (embryonal) is associated with IGF2 gene deletion, seen in BWS; also abnormalities in chromosomes 2, 8, 12, and 13 are associated with MYCN, MDM2, CDK4, CDKN2A (p16), CDKN2B, and TP53 genes.

What translocations are associated with alveolar RMS? What are the genes involved in the fusion?

Alveolar RMS is associated with t(2:13) (70%) and t(1,13) (20%). Genes involved are PAX3 or PAX7 with FKHR.

Which is the most common histology of RMS in infants? Young children? Adolescents? Adults?

Most common RMS histology (by age group):

Infants: botryoid
Young children: embryonal
Adolescents: alveolar
Adults: pleomorphic

Which histologies are most commonly associated with each organ site (H&N, GU, extremities/trunk)?

Most common RMS histologies (by site):

Head & Neck: embryonal
Genitourinary: botryoid
Extremities/Trunk: alveolar

What is the most important cytogenetic tumor marker for RMS?

MyoD (and other myogenic proteins: actin, myosin, desmin, myoglobin)

List the histologies of RMS in terms of prognosis from best to worst.

RMS histologies (by prognosis best to worst):

Spindle cell and botryoid
Classic embryonal
Alveolar
Undifferentiated

What are the ~5-yr OS rates for each of the histologic subtypes?

~5-yr OS (by histology):

Botryoid: 95%
Spindle cell: 88%
Embryonal: 66%
Alveolar: 54%
Undifferentiated: 40%

Which sites require LND b/c of a high propensity for LN mets? What is the risk of LN mets for these sites?

The following sites are associated with > 20% LN mets rate and thus require LND

Paratesticular (PT): (only if >10 yo)
Bladder: pelvic
Head & Neck: nasopharynx (NPX), LND typically not done for NPX
Extremities: upper extremity (UE) (axillary) and lower extremity (LE) (inguinal/femoral)

Which International Rhabdomyosarcoma Study (IRS) called for routine LN sampling in RMS of the extremity?

IRS-IV (Neville HL et al., J Ped Surg 2000): 139 extremity pts, 10% cN+, 50% pN+; of those cN0, 17% were pN+.

What are considered nonregional mets/LNs for various sites (upper extremity [UE], lower extremity [LE], pelvic organs [PT, vagina, uterus])?

Nonregional LN stations by primary site:

UE: scalene node
Pelvic (PT/vagina/uterus): inguinal
Retroperitoneal (RP): para-aortic (P-A) (except if immediately adjacent)
LE: iliacs/P-A

What are the 4 favorable organ sites and their ~3-yr OS rate?

Favorable organ sites:

Orbit
Non-PM H&N
Non-prostate/bladder GU
Biliary

The ~3-yr OS is 94%.

What is the estimated 3-yr OS for RMS arising from unfavorable sites (PM H&N, prostate, bladder, extremities/trunk)?

For unfavorable sites, overall ~3-yr OS is 70%.

What are the PM H&N sites?

PM H&N sites:

Middle ear
Mastoid
Nasal cavity
Nasopharynx
Infratemporal fOssa
Pterygopalatine fOssa
Paranasal sinuses
Parapharyngeal space

(Mnemonic: MMNNOOPP)

What are the non-PM H&N sites?

Scalp, cheek, parotid, oral cavity, oropharynx, and larynx

Workup/Staging

List the general workup for RMS.

RMS workup: H&P, basic labs (CMP, CBC, LDH), EUA, CT/MRI primary, CT chest/abdomen, bone scan, BM Bx, and primary site core Bx/incisional Bx; PET/CT may be useful in determining extent of Dz

What specific workup studies are needed for PM RMS?

PM RMS workup: MRI head, CSF cytology (neuroaxial MRI if +)

What specific workup studies are needed for bladder RMS?

Bladder RMS workup: EUA and cystoscopy

Summarize the TNM criteria for RMS.