RHADOMYOSARCOMA

• Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal

origin that shows skeletal muscle differentiation.
• It is the most common soft tissue sarcoma in children.
• Accounts for ~5% of childhood cancers
• Peak age:2–6 years (embryonal subtype)Adolescents (alveolar
subtype)
• Slight male predominance
• Can occur anywhere in the body, especially where skeletal muscle is
present or presumed to exist
Epidemiology- KENYA
• National Perspective: A retrospective histopathologic review from
Kijabe Hospital, analyzing 6,771 pathology reports between 1992 and
2006, identified 1,217 pediatric malignancies. Among these,
rhabdomyosarcoma accounted for 3.5% of cases, highlighting its
presence among the top ten pediatric cancers in Kenya
• Data from Moi Teaching and Referral Hospital in Eldoret, covering
2006 to 2010, reported 436 pediatric cancer cases.
Rhabdomyosarcoma constituted 7% of these cases, making it the fifth
most common pediatric malignancy in that region
RISK FACTORS
•Genetic syndromes:
•Li-Fraumeni syndrome (TP53 mutation)
•Neurofibromatosis type 1 (NF1)
•Beckwith-Wiedemann syndrome
•Noonan syndrome
•Parental exposure to drugs or chemicals (e.g., cocaine, marijuana, radiation)
•Prenatal X-ray exposure
•Advanced paternal age
•Male sex
•Caucasian ethnicity
•Radiation exposure in early childhood
•Previous chemotherapy for other cancers
•Family history of soft tissue sarcomas
•Congenital anomalies of the genitourinary tract
HISTOLOGIC SUBTYPES
Embryonal RMS (ERMS) – ~60–70%
• Younger children
• Better prognosis
• Often found in head/neck, genitourinary tract
• Alveolar RMS (ARMS) – ~20–30%
• Older children and adolescents
• Worse prognosis
• Typically in extremities, trunk
• Pleomorphic – Rare in children
• Spindle cell/sclerosing RMS – Rare, better prognosis
COMMON SITES
Head and Neck (orbital, parameningeal)
• Genitourinary Tract (bladder, prostate, vagina, paratesticular)
• Extremities
• Trunk/Chest wall
• Retroperitoneum
PIC-A
PIC-B
PIC-C
Symptoms depend on site

Site Features
Orbit Proptosis, eyelid swelling
Parameningeal Nasal obstruction, epistaxis, cranial nerve palsies
Bladder/Prostate Hematuria, urinary obstruction
Vagina Vaginal bleeding or mass ("grape-like" mass)
Paratesticular Painless scrotal mass
Extremities Painless, firm swelling
Metastatic disease Bone pain, cough, lymphadenopathy, weight loss
Investigations
• Laboratory
• CBC, renal/liver function, LDH (may be elevated)
• Urinalysis (for GU RMS)
• Imaging
• MRI of primary tumor site – to assess local extent
• CT scan of chest – to detect lung metastases
• Bone scan or PET-CT – for bone metastases
• Ultrasound – for superficial masses or testicular lesions
Investigations
• Tissue Diagnosis
• Core needle biopsy or excisional biopsy
• Histology: Small round blue cell tumor
• Immunohistochemistry:
• Positive for desmin, myogenin, MyoD1
• Cytogenetics:
• PAX3/7–FOXO1 fusion gene in alveolar RMS
• 🔬 Bone Marrow Biopsy + CSF Analysis
• If parameningeal or metastatic disease
TREATMENT
• Multimodal Approach: Chemotherapy + Surgery + Radiotherapy
• Chemotherapy (backbone of treatment)VAC regimen: Vincristine,
Actinomycin D (Dactinomycin), Cyclophosphamide Sometimes
ifosfamide and etoposide are added Duration: ~6 months to 1 year
depending on risk group
• Surgical Resection
• Preferred when tumor is resectable without major morbidity
• Aim: Maximal resection with negative margins
• Avoid mutilating surgery, especially in head/neck or GU RMS
TX
• Radiotherapy
• Used for:
• Incompletely resected tumors (Group II/III)
• Unresectable tumors
• Residual disease after surgery
• Brain/CNS involvement
• Doses adjusted by age and tumor site
COMPLICATIONS
A. Disease-related
• Local invasion → Obstruction, organ dysfunction
• Metastasis (lungs, bone, marrow)
B. Treatment-related
• Myelosuppression → infection, bleeding
• Infertility, growth retardation
• Secondary malignancies
• Organ toxicities:
• Cardiotoxicity (doxorubicin)
• Bladder toxicity (cyclophosphamide)
BONE TUMORS
OSTEOSARCOMA
• Osteosarcoma is a malignant bone tumor arising from primitive
bone-forming mesenchymal cells and characterized by production of
osteoid or immature bone by malignant cells.
• It is the most common primary malignant bone tumor in children
and adolescents.
EPIDEMIOLOGY
• Accounts for ~3–5% of all childhood cancers
• Peak incidence: 10–20 years (during adolescent growth spurts)
• Male predominance (male:female ratio ≈ 5:1)
• Common in African and Hispanic descent
• Metaphyseal regions of long bones are most affected:
• Distal femur
• Proximal tibia
• Proximal humerus
EXHIBIT-A
EXHIBIT-B
RISK FACTORS

•Genetic syndromes:
•Li-Fraumeni syndrome (TP53 mutation)
•Retinoblastoma (hereditary RB1 mutation)
•Bloom syndrome
•Diamond-Blackfan anemia
•Previous radiation therapy (especially at a young age)
•Paget’s disease of bone (mainly in older adults)
•Male sex
•Age 10–20 years (peak incidence in this age group)
•Bone infarction or chronic osteomyelitis
•Exposure to alkylating agents (chemotherapy)
•Implants or foreign bodies (e.g., orthopedic implants, especially metal)
•Family history of osteosarcoma or related cancer
COMMON SITES

Bone Site Frequency

Distal femur ~40%

Proximal tibia ~20%

Proximal humerus ~10%

Other long bones, pelvis, jaw Less common

CLINICAL FEATURES
- Progressive localized bone pain (worse at night or with activity)

- Swelling and tenderness over the affected area

•Decreased range of motion (if near joint)

| Constitutional symptoms | Usually absent, but may have low-grade fever, fatigue |

| Pathological fracture | Due to weakened bone structure |

| Metastasis | - Lungs (most common site)

•Bones (especially spine and pelvis)

INVESTIGATIONS
• Initial Labs
• CBC (anemia possible), ESR, CRP – nonspecific
• LDH and alkaline phosphatase – may be elevated and correlate with tumor burden
• Imaging - X-ray- Sunburst appearance (spiculated periosteal reaction)
• Codman's triangle (elevated periosteum)
• Lytic and sclerotic areas
• MRI of affected limb - Best for local extent, soft tissue involvement, neurovascular
structures
• CT chest - To detect lung metastases .
• Biopsy - Core needle biopsy or open biopsy Histology: Malignant osteoblasts producing
osteoid
• Bone scan or PET-CT - Evaluate for skip lesions and distant metastases |
SUNBUSRT APPEARANCE
TREATMENT
Multimodal Approach
• Neoadjuvant Chemotherapy
• Adjuvant Chemotherapy
• Surgery
• Performed after neoadjuvant chemo
• Options:
• Limb-sparing surgery (preferred)
• Amputation (if neurovascular involvement)
• Wide local excision with negative margins is the goal
ROLE OF RADIOTHERAPY?
Radiotherapy
• Generally not used because osteosarcoma is radioresistant
• Considered only in:
• Unresectable tumors
• Palliation
• Positive margins after surgery
SUPPORTIVE MX
• Pain management
• Nutritional support
• Physical and occupational therapy
• Psychosocial counseling
Ewing Sarcoma in Children
• Ewing sarcoma is a highly malignant, small round blue cell tumor that
arises from primitive neuroectodermal cells. It primarily affects bone
and soft tissue in children and adolescents.
• Affects diaphysis of long bones
• Second most common bone tumor in children (after osteosarcoma)
• Peak incidence: 10–20 years
• Male predominance (M:F ≈ .5:1)
• More common in Caucasians, rare in African and Asian descent~25–
30% present with metastases at diagnosis
COMMON SITES

Location Frequency

Pelvis Most common

Diaphysis of long bones (femur, tibia, humerus) Common

Ribs (Askin tumor) Chest wall

Spine, scapula, skull, hand, foot Less common

CLINICAL FEATURES
• Localized pain (often severe, progressive)
• Swelling or palpable mass Warmth, tenderness, erythema (resembles
infection)
• May cause limping or restricted joint movement
• Constitutional symptoms - Fever Fatigue, malaise Weight loss
• Neurological (if spinal/paraspinal) – back pain
• Limb weakness Bladder/bowel dysfunction
• Metastatic disease - Lungs (most common) Bone, bone marrow
microscopy
Pathology
• Small, round, blue cell tumor with scant cytoplasm
• Pseudorosette formation sometimes seen
INVESTIGATIONS

Test Purpose

CBC May show anemia or leukocytosis

ESR, CRP Often elevated

LDH Elevated, reflects tumor burden

INVESTIGATIONS
Biopsy
• Core needle or open biopsy
• Histology confirms small round blue cells
• Cytogenetics/molecular tests confirm EWSR1 fusion gene
IMAGING
• X-ray- Moth-eaten, lytic lesion in diaphysis
• Onion-skin periosteal reaction (laminated appearance)
• Codman’s triangle may be seen
• MRI - Defines local extent, soft tissue involvement
• CT chest - Detect lung metastases
• Bone scan or PET-CT | - Identify other skeletal metastases
Onion skin appearance
TREATMENT
Multimodal approach:
• Neoadjuvant chemotherapy
• Local control – surgery or radiotherapy
• Adjuvant chemotherapy
GERM CELL TUMORS
Germ cell tumors (GCTs) are a type of cancer that
develops from germ cells, which are the cells that
produce sperm (in males) or eggs (in females).
While they most commonly originate in the ovaries or
testes (gonads), they can also occur in other areas of the
body, such as the brain, mediastinum (area between the
lungs), or abdomen.
• GCTs can be either benign (non-cancerous) or
malignant (cancerous- Can be benign (mature teratoma)
or malignant (yolk sac tumor, etc.)
CLASSIFICATION
• Benign: Mature teratoma
• Malignant: Yolk sac tumor, embryonal carcinoma,
choriocarcinoma
• Sites: Gonadal & extragonadal (sacrococcygeal, mediastinal,
etc.)
EIDEMIOLOGY
• Account for ~3% of pediatric cancers
• Bimodal age distribution: infancy & adolescence
• Common in sacrococcygeal region, ovaries, testes,
mediastinum, CNS
CLINICAL FEATURES
• A. Sacrococcygeal Teratoma (SCT)
• Mass at the base of the spine (often visible externally)
• May be ulcerated or bleeding
• May cause bowel/bladder obstruction
• Large tumors may lead to high-output cardiac failure
• B. Testicular Tumors
• Painless testicular mass
• May cause scrotal swelling
• No transillumination (unlike hydrocele)
CLINICAL FEATURES
• C. Ovarian Tumors
• Abdominal distension or mass
• Pain, nausea, or vomiting due to torsion or hemorrhage
• Precocious puberty in hormone-secreting tumors
• D. Mediastinal Tumors
• Cough, chest pain, dyspnea
• SVC syndrome (facial swelling, distended neck veins)
• E. Intracranial Tumors
• Diabetes insipidus, visual disturbances
• Headache, vomiting (raised ICP from pineal tumors)
INVESTIGATIONS
• Tumor markers: AFP (yolk sac),
• Ultrasound, MRI, CT scan, Brain MRI
• Histopathology & Immunohistochemistry
TREATMENT
• Surgery: Site-specific (orchiectomy, oophorectomy,
resection)
• Chemotherapy: BEP (Bleomycin, Etoposide, Cisplatin)
• Radiotherapy for CNS GCTs
• Supportive care: pain, psychosocial support, side effect
management
EXHIBIT-A
LIVER TUMORS
HEPATOBLASTOMA
• Hepatoblastoma is the most common primary malignant liver tumor
in children, typically arising from immature liver precursor cells. It
represents a type of embryonal tumor.
• Incidence: Accounts for ~1% of pediatric cancers.
• Age group: Primarily affects children < 3 years old,
• peak incidence around 18 months.
• Sex: More common in males (M:F = 2:1).
• Geography: Higher incidence in Asian and Hispanic populations.
ASSOCIATIONS

• Very low birth weight infants (<1500 g).

• Genetic syndromes:
• Beckwith-Wiedemann syndrome
• Familial adenomatous polyposis (FAP)
• Trisomy 18
• Li-Fraumeni syndrome
RISK FACTORS
• Genetic mutations: APC, CTNNB1 (β-catenin)
• Congenital syndromes (as above).
• Prematurity and low birth weight.
• Parental exposure to toxins
PRESENTATIONS
• Abdominal distension or palpable abdominal mass (most common
presentation).
• Anorexia, weight loss.
• Vomiting or abdominal pain.
• Fever (occasionally).
• Signs of anemia.
• Jaundice (uncommon).
• Puberty-like changes due to β-hCG secretion (rare).
• Gross Appearance: Usually a solitary mass in the right lobe of the liver,
well-circumscribed.
• Laboratory Tests
• Serum Alpha-Fetoprotein (AFP):
• Elevated in >90% of cases.
• Useful for diagnosis, monitoring treatment response, and relapse.
• Liver function tests (LFTs).
• CBC: May show anemia or thrombocytosis.
• Imaging
• Ultrasound: Initial imaging; defines mass.
• CT scan/MRI:
• To define local extension, vascular involvement, calcifications.
• MRI is preferred for detailed soft tissue characterization.
• Biopsy- CORE BIOPSY
• Metastatic Work-up- CHEST CT, BONE SCAN
TREATMENT
• Multidisciplinary approach:
• Surgery
• Definitive treatment: Complete resection is curative
• Liver transplant: Indicated if unresectable after chemotherapy.

• Chemotherapy
• Neoadjuvant chemotherapy to shrink tumor (typically cisplatin-
based).
• Radiotherapy: Rarely used; mainly for metastasis or palliative care.
MX
• Supportive care:
• Transfusions for anemia
• Nutritional support
• Pain management
• Management of chemotherapy side effects
• Prognosis- Good prognosis if:
• Tumor is resectable
• AFP is elevated and decreases with treatment
Poor prognosis if:
• Metastasis at diagnosis
• AFP is not elevated (or very low)
• Unresectable tumor even after chemotherapy
COMPLICATIONS
• Tumor-related:
• Compression of adjacent organs
• Tumor rupture → hemorrhage
• Metastasis (especially to lungs)
• Treatment-related:
• Nephrotoxicity (cisplatin)
• Ototoxicity
• Cardiotoxicity (doxorubicin)
• Myelosuppression
• Risk of secondary malignancy