JEREMY GEORGE ROLL # 1207 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 muscle Most common of the childhood soft tissue sarcomas Rhabdomyoblast 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 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 2 nd 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

EXTREMITY 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 pattern b.Solid c.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 control 1. 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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