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RHABDOMYOSARCOMA

OUTLINE

• Introduction• Epidemiology• Pattern of Spread• Associated Syndromes• Clinical Presentations• Pathological Classification• Diagnosis and DDx• Clinical Staging and prognosis• Treatment

INTRODUCTION

• Rhabdomyosarcoma (RMS)malignant mesenchymal tumor of

striated skeletal muscleMost common of the childhood soft

tissue sarcomasRhabdomyoblast is the characteristic cell• exhibits cytoplasmic cross-striations and

positive immunohistochemical staining for desmin and myogenin.

EPIDEMIOLOGY

• 65% of cases are diagnosed in children less than six Y.0. with the remaining in the 10-18 age group• 250 new cases are diagnosed in the U.S.A. each

year• Annual incidence of 4-7/million children 15 years of age

or younger

• 2/3 of cases diagnosed in the first years of life• Specific Risk factors• Unknown, most cases are usually sporadic

• 20% have lung metastases at time of presentation

PATTERN OF SPREAD

• locally invasive tumor often with a pseudocapsule, has the potential for local spread along fascial or muscle planes, lymphatic extension, and hematogenous dissemination• regional lymphatic spread-15%•Hematogenous metastases-15%

INHERITED SYNDROMES

• Li-Fraumeni Syndromes• Germ line mutations cause inactivation of tumor

suppressor gene (p53) Adenocortical carcinoma, Brain tumors (particularly Glioblastoma), lung cancer, breast cancer.

• Beckwith-Wiedemann Syndrome• Associate with overgrowth tumors

• NF-1 (Neurofibromatosis Type 1)• 30 fold risk to develop RMS

• Costello Syndrome• Aka FCS syndrome• Has growth and mental retardation

CLINICAL PRESENTATION

•Depends on (Site, age, Metastases is present)• Rapidly growing asymptomatic mass• Mass effects associated organs and

tissues

CLINICAL PRESENTATION…• Head and neck• Most Commonest site: Orbit• Parameningeal Sites

• Genitourinary Tract• 2nd common site• Presents with hematuria and S&S of obstruction• Bladder, Prostate, Paratesticular, Gynecologic

• Extremities• Mainly proximal lower limbs, and in adults Lymph

Nodes involved in 50% and have alveolar subtype

HEAD AND NECK: ORBIT

• favorable prognostic site• lymphatic extension/hematogenous

metastasis is rare• embryonal histology

HEAD AND NECK: PARAMENINGEAL SITES

•Nonorbital rhabdomyosarcomas of the head and neck are grouped into parameningeal sites• nasopharynx, nasal cavity, paranasal

sinuses, middle ear, pterygopalatine fossa, and infratemporal fossa

HEAD AND NECK: NON-PARAMENINGEAL SITES

• include the scalp, parotid, oral cavity, larynx, oropharynx, and cheek• complete gross surgical excision• Approximately 15% of these patients

present with regional lymph node metastases• Radiotherapeutic management is based

on the amount of residual tumor after surgery. • Draining regional lymph nodes are not

routinely irradiated unless they contain metastatic tumor

GENITOURINARY TRACT: BLADDER AND PROSTATE TUMORS

• half of all pelvic rhabdomyosarcomas• 75% of patients are age <5 years at presentation• male predominance

• More than 90% of these tumors are of the embryonal histologic subtype, • with approximately one-third having a botryoid

morphology

• anterior pelvic exenteration (or partial cystectomy for small tumors arising from the dome of the bladder) combined with chemotherapy and irradiation for microscopic or gross residual disease has been associated with a survival rate of approximately 70%

GENITOURINARY TRACT: PARATESTICULAR TUMORS

•Paratesticular Tumors• represent approximately 7% of all rhabdomyosarcomas and may arise anywhere along the spermatic cord• inguinal orchiectomy and no further local therapy is necessary.

GYNECOLOGIC TUMORS

• 4% of all rhabdomyosarcomas• vagina is the most common site of origin• before the age of 3 years• botryoid morphology• These tumors are often quite sensitive to

chemotherapy• Radiation therapy usually is reserved for

patients with residual disease after resection or as part of a preoperative treatment regimen to help limit the extent of surgery. • Intracavitary and interstitial brachytherapy are useful

irradiation techniques

E X T R E MIT Y

• alveolar or undifferentiated subtypes• Because radiation therapy and multi-

agent chemotherapy have been shown to provide excellent local control, it is advisable to avoid disfiguring and mutilating surgical procedures

• A) Biopsy revealed an alveolar RMS. • B) In this case, soft tissue

and lymph node metastases in the distal anterior thigh and inguinal and pelvic region are demonstrated. • C) Osseous metastases

involving numerous vertebral bodies are shown

PATHOLOGICAL CLASSIFICATION

I. Embryonic: Common in age less that 10 Y.O. (2/3)• Site: Head and neck > Genitourinary > Lower Extremities •Molecular Genetic: Loss of heterozygosity at 11p5(IGF-11)

• Subtypes:a. Spindle Cell Type

• Mainly Paratesticular• Good Prognosis

b. Botryoid Type • Grape like nodular tumor• Less common (10%)• Mainly submucosal in vagina and bladder• Good prognosis

c. Not-otherwise specific:• Intermediate Prognosis

II. Alveolar Type:• Adolescent type (10-25 Y.O)• M=F• Site: Trunk, extremities and paraspinal• Subtypes

a. Classic: has typical alveolar patternb. Solidc. Mixed

• Molecular genetic: t(2,13)(q35,q14)• Present in 60%• Prognosis poor

III.Pleomorphic = Undifferentiated• Adult type (50-70 Y.O)• Site: Proximal L.L• Poor Prognosis (25% 5 year

survival)

DIAGNOSIS

• Extend blood works• Bone Marrow Aspiration in children • Lymph Node Biopsy if RMS involve

extremities • CSF sampling in head and neck RMS• Radiographic evaluation• X-ray and C.T. scan:• Nothing suggestive about RMS (Soft Tissue)• Bone involvement rare

LOCAL AND SYSTEMIC STAGING

• Important to have biopsy by wither needle or incision biopsy • Apply different IHC (actin, desmin and myoglobin)•Determine the pretreatment stage and surgioco-pathological clinical group to know the prognosis and the treatment regimens

TREATMENT

• Need multidisciplinary team • Aim for local and systemic control1. Surgical Treatment: wide local resection 2. Chemotherapy:• Always respond to neoadjuvant and adjuvant

chemotherapy• 2-3 years duration of treatment • Common Regimen (VAC)• S/E: Myelosuppresion (90%)

3. Radio Therapy • If +ve margin, also helps decrease risk of

recurrence• S/E: either acute or chronic post radiation

sarcoma

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