DEFINITION AND PATHOGENESIS
- Juvenile types
- Embryonal rhabdomyosarcoma (70-80%): mainly affects children < 15 years of age occurring in the head and neck, GU tract, retroperitoneum and extremities
- (Botryoid type: a variant of the embryonal type characterized by a grapelike growth pattern not occurring in the extremities, but in hollow visceral organs)
- Alveolar rhabdomyosarcoma (10-20%): usually occurs between ages 10-25, responsible for a second incidence peak
- Occurs with greater incidence in the extremities
- Adult type
- Pleomorphic rhabdomyosarcoma: peak incidence >45 years of age, occurring most commonly in the thigh
- Pretreatment staging system
- Stage Site* Invasiveness Size Nodes Metastases
- 1 favorable T1 or T2 a or b N0, N1 M0
- 2 unfavorable T1 or T2 a (<5cm) N0 M0
- 3 unfavorable T1 or T2 b (>5cm) N0, N1 M0
- 4 any site T1 or T2 a or b N0, N1 M1
* all extremity sites unfavorable
- Intergroup Rhabdomyosarcoma Study Clinical groups
- I Localized, complete resection, no LNs
- a) confined to nuscle/organ or origin
- b) tumor infiltration beyond muscle/organ of origin
- II Localized/regional disease, complete macroscopic resection
- a) resection with microscopic margin, no LNs
- b) complete resection of tumor and LNs
- c) tumor and LNs resected with microscopic margins
- III < wide resection with macroscopic residual
- IV Distant metastases at dx
- The most common soft tissue sarcoma of children, addolescents, and young adults, although only 14.6% occur in the extremities
- Accounts for 4-8% of all pediatric malignancies
- 20% involve the extremities
- Rare >45 years of age (except pleomorphic type which occurs 40-80 yrs of age)
- May present at birth
- M:F = 1.5:1
- Discovery frequently associated with a traumatic episode (falsely diagnosed as a hematoma or benign tumor)
- Most are deep-seated intramuscular masses
- Often asymptomatic
- Alveolar subtype reported in a neonate with Beckwith-Wiedemann Syndrome with multiple nodular and vesicular lesions on the face, limbs, and abdomen, resembling "blueberry muffin baby"
- Head/neck locations
- Unusual locations
- Erosion of bone in hand or foot lesions
- MRI: deep-seated intramuscular mass
- Poorly defined, infiltrating into surrounding structures in extremity lesions
- Firm, rubbery, and grayish-white in appearance ± necrosis or cystic degeneration
HISTOLOGIC AND MOLECULAR FEATURES
- Rhabdomyoblasts have eosinophilic cytoplasm that is filamentous and granular ± transverse striations, contractile elements
- Alveolar types: embryonal types = 4:3
- Embryonal types (46-60%)
- Poorly-differentiated to well-differentiated looking like fetal muscle tissue with variation in cellularity denseness and alternating cellular and myxoid areas
- Scant interstitial collagen
- Elongated and rounded rhabdomyoblasts with hyperchromatic nuclei, eosinophilic cytoplasm, and fibrillary material around the nucleus ± cross striations (50-60%)
- + PAS ± diastase for intracellular glycogen in well-differentiated tumors("spider-web" cells are rhabdomyoblasts with glycogen washed out by the fixative and strands extending to the cellular periphery)
- Iron hematoxylin, PTAH, Masson trichrome shows cross striations
- "Broken-straw" sign = angulation of narrow, ribbon-shaped muscle fibers
- Alveolar types (20-41%)(50% of extremity locations)
- Aggregates of tumor cells with "alveolar" spaces separated by loose fibrous septa are typical but areas may be solid cells, especially at the periphery of a tumor
- Rounded nuclei and indistinct cytoplasm
- Rhabdomyoblasts in only 30% ± cross striations (20-30%)
- Multinucleated giant cells are prominant
- Entrapment of normal muscle tissue
- Pleomorphic types (~13%)(adult-type)
- Difficult to distinguish from other pleomorphic sarcomas (eg, MFH)
- Rarely with cross striations
- Undifferentiated (15-20%)
- Spindle cell
- Rhabdomyosarcoma with rhabdoid features
- Immunohistochemistry and special stains
- Desmin and myoglobin (beware of false + in entrapped normal muscle)
- + PAS for glycogen
- Myogenic transcriptional regulatory proteins
- + myogenin
- + MyoD1
- Li-Fraumeni syndrome associated with rhabdomyosarcoma
- Reported in Noonan syndrome due to a SOS1 mutation
- Metastatic alveolar rhabdomyosarcoma reported in Multiple Endocrine Neoplasia Type 2A
- Expression of MyoD1 geneLoss of 11p15 heterozygosity in embryonal subtype
- Translocation t(2;13) or t(1;13) with fusion gene Pax 3-FKHR or Pax 7-FKHR fusion genes respectively in alveolar subtype
- Variable appearance resembling stages of embryonal muscle tissue development
- Myofilaments and polyribosomes
- Golgi apparatus is prominent
DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS
- Poorly differentiated round or spindle cell sarcomas
- Ewing’s sarcoma
- Poorly differentiated angiosarcoma
- Synovial sarcoma
- Malignant melanoma
- Granulocytic sarcoma
- Small cell carcinoma
- Benign lesions
DISEASE COURSE AND TREATMENT
- Alveolar subtype with more aggressive clinical behavior/worse outcome than embryonal subtype
- Chemotx + wide resection + chemotherapy ± XRT after careful staging
- Dictated by Intergroup Rhabdomyosarcoma Study (IRS) protocols
- Aggressive regional LN sampling, if +, further proximial node evaluation
- Response to chemotx overall is good; "second look" surgeries have been advocated
- Vincristine, actinomycin-D, cyclophosphamide, ± adriamycin, ifosfamide
- De novo multiple drug resistance has been reported
- Lung (67% when metastases are present)
- LNs(depends on location and type--alveolar > embryonal)
- Bone marrow (aspirate as part of staging work-up)
- Abdominal organs
- Prognosis depends on stage at time of diagnosis with up to 83% 5 year survival with localized disease and with histological type (alveolar type has a worse prognosis), and with ability to gain a wide margin and complete resection
- Unresectable lesions will have <10% long term survivors
- Embryonal histologic subtype has the most favorable prognosis
- More distally located tumors generally have a better prognosis
- Extemity lesions have a worse prognosis than orbital or GU lesions
- 12% 5-yr risk of regional failure
- Poor prognostic indicators
- Female gender
- LN involvement at dx
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