Rhabdomyosarcoma is the most common soft tissue sarcoma in children. It arises from skeletal muscle and can occur anywhere in the body. The two main histologic subtypes are embryonal and alveolar. Treatment involves chemotherapy, surgery if possible, and radiation therapy. The chemotherapy regimens most often used are VAC or IVA. Prognosis depends on factors like age, location, stage and histology. With multimodal treatment, the 5-year survival rate for localized disease is over 70% while metastatic disease has a lower survival rate of around 25%.

1. RHABDOMYOSARCOMA
Dr Sumit Agarwal
JR
RT & RM

2. Introduction
 Most common soft tissue sarcoma of childhood .
 4.4 per 1 million whites & 1.3 per 1 million black.
 Male : female – 1.5: 1 .
 Bimodal peak seen- peak at 2-6 years & in adolescence.
 Majority <10 year at diagnosis
 5% are < 1 year
 RMS arises from unsegmented ,undifferentiated mesoderm or
myotome derived skeletal muscle .

3.  Younger age has embryonal histology.
 Age is independent prognosis factor children <1 & > 10 year
has inferior survival
 Adults with RMS has poor prognosis
 RMS most seen in children with LI fraumani syndrome &
neurofifromatosis

4. Fig. (A) (B) In hematoxylin and eosin stain, there were many high
nuclear/cytoplasmic ratio small blue round cells along connective tissue
strands.
(C) Muscle-specific Actin stain and
(D) skeletal muscle specific MyoD1 stain were positive.

5. PATTERN OF SPREAD
 Locally invasive with spread along facia ,muscle, lymphatic and
hematogenous .
 Risk of lymphatic spread 15%, rare in orbital tumors and 25%
in children with paratesticular extremities , 50% in perineal and
perianal tumors .
 Hematogenous metastases detected 15 %of patients mainly in
truncal and extremity primary tumors .
 Hematogenous spread mostly lungs, bone marrow and bone .

6. Clinical presentation
 Asymptomatic mass ,symptoms are usually present as mass effect
on associated organs and tissues .
 Orbit may cause proptosis, optalmoplegia.
 Parameningeal present with nasal aural or sinus obstruction ,crnial
nerve palsy , headache.
 Genitourinary – hematuria , urinary obstruction or constipation .
 Trunk ,pelvis & abdomen- nerve root compression, palpable mass
or adenopathy ,& perirectal pain.

7. Diagnostic workup

8. Staging work up & follow up evaluation for patients with Rhabdomyosarcoma

9. Staging systems
 It reflects surgical procedure for patient and not reflect biology of
disease and useful in guiding decisions for radiotherapy .

10.  Three year failure free survival was –
 86% for stage 1 tumors
 80% for stage 2 tumors
 68% for stage 3 tumors
 25% for stage 4 tumors

11. International Classification of Rhabdomyosarcoma
1. Superior prognosis
(both are variants of embryonal rhabdomyosarcoma)
a. Botryoid
b. Spindle cell
2. Intermediate prognosis
a. Embryonal rhabdomyosarcoma
3. Poorer prognosis
a. Alveolar rhabdomyosarcoma
b. Undifferentiated sarcoma

12. WHO - four variants of rhabdomyosarcoma
– Embryonal (65%)
– Alveolar (25%)
– Pleomorphic, and
– Spindle cell/sclerosing rhabdomyosarcoma

13. EMBRYONAL
 Favourable clinical outcome
 Affect younger male patients
 Most commonly arise in the head, neck, and genitourinary
regions
 Loss of heterozygosity at the imprinted 11p15 locus
 Loss of the maternal allele and duplication of the paternal allele
 Encodes the IGF-2 growth factor
 Share features with other embryonal neoplasms of childhood,
such as Wilms tumours, hepatoblastomas, pancreatoblastomas,
and neuroblastomas.

14.  Zones of loose & dense cellularity
 Recapitulate normal embryonal
myogenesis, in which loose primitive
mesenchyme condenses to form nascent
muscle
 exhibit all cellular phases of myogenesis
dense condensations of rhabdomyoblast
foci with a loose myxoid stroma.
 variable cell population consisting of
small, round tumor cells with
hyperchromatic nuclei and of large,
polygonal-shaped tumor cells with
abundant eosinophilic cytoplasm, which
contains diagnostic cross striations
(arrow)
A B

15. ALVEOLAR
 20% of RMS
 < 1 Yr --- >10 Yr ( Adolescents)
 Extremities, trunk, perianal, perineal
 more aggressive
 metastatic disease

16.  Fibrous septa with loose
clusters of rounded cells in
center
- alveolar pattern
 uniform cell population consisting
of cells with a high nuclear-to-
cytoplasmic ratio.
The cells are arranged in variably
sized nests separated by fibrous
tissue septa.
 In places, the cells appear loosely
dispersed, mimicking a pulmonary
alveolar pattern
A B

17. BOTRYOID TYPE
 Subtype of Embryonal
 10% of all Childhood RMS
Mucosal Surface
Vagina
Billiary
Bladder
Nasopharynx
 Most common in hollow visceral organs - GU tract
 Superior Prognosis

18.  Polypoid, grape-like tumor
masses scattered malignant cells
in myxoid Stroma
 abut an epithelial surface, such
as that of the bladder, bile duct,
vagina, or conjunctiva, and
project into the lumen as
multinodular excrescences of
variable size.
 arises under the mucosal
surfaces of body orifices
 Fig B shows Botryoid
Rhabdomyosarcoma of
Rhinopharynx .
A B

19. SPINDLE CELL
 Subtype of Embryonal
 MC site is Paratesticular
 Superior Prognosis
 whorled spindly appearance smooth muscle tumours
 Marked collagen deposition and have a nested, storiform
growth pattern.
 Rare in the head and neck.

20. UNDIFFERENTIATED
 Diagnosis of exclusion
 aka Pleomorphic
 Rare in children
 More common in Adults ( 30-50 Yrs)
 In skeletal muscles of older people,
- Marked pleomorphism
- Irregularly arranged cells
- Multinucleated giant cells
- Hyperchromatic

21. Pathological classification

22. HEAD AND NECK : PARAMENINGEAL SITES
 Parameningeal sites are nasopharynx , nasal cavity, paranasal
sinuses, middle ear, pterygopalatine fossa & infratemporal
fossa
 They spread by invading the base of skull & direct extension
to CNS a pattern of spread seen in 41% patients.
 Patients with known meningeal dissemination should receive
CSI , dose of 50.4Gy in 28# .
 Surgery is rarely indicated because complete resection not
possible ,does not obviate need of high dose radiation
therapy
 5year survival 75% with adequate radiotherapy .

23. Coronal T1 contrast enhanced MRI obtained at presentation in a child with
Intracranial extension from a pterygoplatine fossa RMS.
A

24. Fig. 1. (A) Brain computed tomography demonstrated a large soft tissue mass lesion
involving the left paranasal sinus, nasal cavity, and orbital cavity with crossing of the
midline to the right paranasal sinus and nasal cavity.
(B) Brain magnetic resonance imaging axial view, coronal view, and sagittal view revealed
obvious intracranial extension with cribriform plate destruction to bilateral frontal base
regions.
B

25. C
MRI of right
masticator space
rhabdomyosarcoma

26. HEAD & NECK:NON PARAMENINGEAL SITE
 Children with these tumors have better outcome & 5 year
survival is 80 % in IRS4.
 Site are scalp, parotid, oral cavity ,larynx, oropharynx , cheek
and amenable for complete gross resection .
 15% patients have lymph node metastasis .
 Radiotherapy depend on amount of residual tumor.
 Draining lymph node are not routinely irradiated unless
involved clinically or pathologically.

27. BLADDER AND PROSTATE :
 75% Patients are of <5 years at presentation & more than 95%
are of embryonal histologic subtype botryoid .
 Patients with tumors arising from prostrate has inferior
outcome as compared to those arising from bladder.
 IRS 2 study treated these patients chemotherapy then by
delayed surgery or by RT.3yearsurvival s inferior that is 52%
compared to 80% those treated with primary radical surgery &
only 22% survived with intact bladder .

28.  IRS3 study intensify therapy by use of planned irradiation
6weeks after the start of treatment & added cisplatin &
doxorubicin
 5 year survival was 82% with locoregional disease & 64% have
retaining functional bladder.
 Demonstrating need of routine radiotherapy early in treatment.
 CWS-96 protocol treated these patients with multiagent
chemotherapy follow by response adapted RT & surgery.
 Children with complete resection did not receive RT ,whereas
others receive 32-44.8 Gy using 1.6 Gy twice daily .
 5 year EFS was 70%.

29. The MRI below shows an embryonal RMS which has
arisen from the dome of the bladder

30. Alveolar Rhabdomyosarcoma of Prostate

31. PARATESTICULAR TUMORS:
 At presentation usually painless inguinal or scrotal mass that
does not transilluminate .
 Mostly they present with early stage that is amenable for
complete resection & cure rate is 90%.
 IRS 3 study retroperitoneal lymph node sampling showing a
14% incidence of node involvement for <10 years age & 47% in
>10 year .
 IRS 4 a thin cut CT without surgical sampling was used for
staging and incidence of detected nodes dropped to 4% & 13%
fot the two age groups .

32. A) Macroscopic images of a paratesticular rhabdomyosarcoma from an 8-month-old infant.
The tumor appears as a pale pink and slightly myxoid lesion adjacent to the comparatively
smaller testis, showing a smooth and glistening tunica albuginea.
(B) Low-power view of a paratesticular rhabdomyosarcoma, spindle cell variant, arising
adjacent to the epididymis in an 8-year-old boy.
(C) Histological features the spindle cell appearance with multiple enlarged cells with
abundant, pink cytoplasm (H&E, 100). (D) High magnification from C, showing a “strap” cell
with abundant, “myogenic” cytoplasm featuring the classic striations of skeletal muscle (arrow)

33.  Surgical procedure is inguinal orchidectomy .
 In IRS study the high risk of nodal involvement led to
recommend for ipsilateral retroperitoneal nerve sparing node
dissection for staging of all >10 years .
 Patients with nodal disease 5 year survival is 69% & 96 % for
those without nodal involvement.
 Regional lymph node irradation is recommend in nodal
involvement .
 If scrotal irradiation is done then orchidopexy is considered
prior to treatment to protect remaining structures .

34. Gynecologic tumors
 Accounts for 4% of all RMS tumors & vagina is the most
common site .
 Mostly diagnosed at 3 years of age & present as vaginal mass .
 Botryoid is most common morphology .
 IRS4 & IRS 5 reveals high rate of local filure for vaginal tumors
when local control with surgery is omitted.
 COG STS committee call for radiotherapy in all patients with
post surgical micro or macro scopic tumor.
 Children 1 to 9 years has 95% 5 year survival .

35. Botryoid embryonal RMS of the female urogenital tract in an infant

36. EXTREMITY
 Alveolar or undifferentiated subtype usually.
 Large ,deeply invasive , & associated with high probability of
lymphatic and hematogenous spread .
 Complete surgical resection is difficult to achieve, so
chemotherapy and radiotherapy is recommended .
 Regional lymph node involvement is 24% & dissection is
performed for staging purpose not for treatment.

37.  Sentinel lymph node mapping & biopsy is being investigated
for their diagnosis & prognostic value.
 radiotherapy to involved regional lymphatics is mandatory ,
improve local control
 OS at 3 years is 70% & failure free survival is 55%.
.

38. (A) Coronal T2-weighted , (B) sagittal T2-weighted, (C) axial
T1-weighted and (D) T2-weighted TSE images with Dixon fat
suppression

39.  For metastasis
 Patients < 10 years of age & have 1 Or 2 metastatic site ,
long term survival is 55%.
 Intensive multiagent chemotherapy plays a major role in
these patients .
 Metastatic site should be treated with radiotherapy
wherever is possible

40. Treatment

42. SURGERY
 Only 20% patients have long term survival , except in orbit where
50 % those with localized disease.
 0nly 20 % tumors are located in sites where excision is possible.
 60% tumor is amenable for biopsy & complete resection is better
than subtotal resection or biopsy alone .
 TNM staging indicated prognosis is dictated by tumor size &
invasiveness not by initial surgical approach.
.

43.  Initially biopsy then surgical excision is indicated without any
compromise of function
 IRS 5 study evaluated whether delayed primary excision (DPE)
able to reduce dose of RT for local control but the results
similar after high dose RT for bladder RMS.

44. CHEMOTHERAPY
 Single agent activity is measured as age response rate
 Vincritine 59%,
 dactinomycin 24%,
 cyclophosphamide 54%,
 cisplatin 15 to 21 %,
 dacarbazine11%,
 mitomycin C 23%,
 ifosfamide 86%.
 Embryonal histology with no gross residual disease or lymph node
involve may treated with VA for 1 year with RT.

45.  IRS 5 study suggest omitting alkylating agents : local control is
compromised .
 Patients with unresectable pelvic tumors benefit with addition
of doxorubicin & cisplatin to VAC .
 Patients with metastatic RMS benefit with addition of
ifosfamide & etoposide to standard VAC regimen.

46. RADIOTHERAPY
 Treatment encompass the involved region before
chemotherapy with margins that encompass surgical sites &
biopsy tracts
 Prophylactic lymph node irradiation not done with clinically
node negative .
 Local control of gross tumor require dose of 50 to 55Gy.
 90% of patients with microscopic residual tumor achieve local
control with 41.4 Gy.

47.  Dose response with age suggests that lower doses given to
infants & children have high relapse rates .
 Local control is more for tumor <5cm in diameter than for
larger lesion .
 Radiotherapy avoided with dactinomycin & doxorubicin as
they causes radiation recall injury .
 In contrast cyclophosphamide & vincristine can be given with
radiotherapy.

49. General treatment paradigm

53. Standard regimen ( 0f equivqlent efficacy)
IVA REGIMEN : 9 CYCLES
Ifosfamide 3g/m2for two days
Vincristine 1.5mg/m2 (max2mg) for one day
Actinomycin D 1.5mg/m2(max2mg) for one day
VAC REGIMEN 9-15 CYCLES
Cyclofosfamide 1200 mg/m2 for one day
Vincristine 1.5mg/m2(max2mg ) one day
Actinomycin D 1.5mg/m2 (max2mg) for one day

54. IRS Study

57. IRS III
 5- year survival was 71% for IRSIII group which 8% improvement
over IRS II .
 5 year progression free survival was 65% a 10% improvement from
IRS II.
 Group I patient – 5year PFS – VA- 83%.
 5year PFS-VAC- 76%.
 Group II patient excluding orbit ,head & paratesticular were not
improved with addition of doxorubicin over VA chemotherapy * 1
year & radiation therapy.

58.  Patients with group III tumors ,excluding those in special pelvic,
orbit , far better for intensive regimen used in IRSIII than pulsed
therapy used in IRS II that is VAC or VAC vincristine & doxorubicin
VADR.
 5 year PFS were 62% & 52%
 Patients with tumors of bladder ,vagina & central pelvis in clinical
group III improved more than IRS II
 Patients with unfavorable histology group I & II receive VADR- VAC
+cisplatin & radiation improved over IRS II receive VA or VAC .
 Whole brain RT is omitted for patients with parameningeal primary
tumors.