1. Soft tissue sarcomas

2. Heterogeneous group of neoplasms which stem from muscles, vessels, lymphatic tissue, connective tissue, synovial tissue or primitive mesenchymal cells
The most common – rhabdomyosarcoma (RMS) approximately 50% of all sarcomas in children and young adults
Incidence: in childhood 7.5% of all neoplasms annually new diagnosis in 8/1 million children <16years ratio of boys: girls 1.4 : 1

3. Subtypes Mesenchyma Myxoma, mesenchymoma Striated muscle RMS
Smooth muscle
Fatty tissue
Connective tissue
Synovial tissue
Lymphatic vessels
Nerve sheath
Blood vessels
Myxoma, mesenchymoma
RMS
Leiomyosarcoma
Liposarcoma
Fibrosarcoma
Synovial sarcoma
Lymphoangiosarcoma
Neurofibrosarcoma
Angiosarcoma, hemangiopericytoma

4. Rhabdomyosarcoma Age of distribution: Location: <1 year -7%
1 – %
5 – % %
> %
Location:
Head and neck %
Orbital %
Genitourinary %
Extremities %
Trunk %
Retroperitoneal %
Perineal and anal %
Others %

5. Histopathology
Embryonal : % of all RMS in childhood location: orbit, head and neck, abdomen, genitourinary tract subtype: sarcoma botryoides(6%) – in genitourinary tract
Alveolar: 21% location: mainly extremities
Pleomorphic : 1% mainly in adulthood
Undifferentiated: 8%

6. Clinical manifestation
Symptoms depend on tumor location
Head and neck -35% location : orbit and parameningeal – middle ear, mastoid, nasal, paranasal area, pharynx, fossa pterygopalatina, fossa infratemporalis, neck symptoms: orbit- proptosis middle ear: pain, chronic otitis media, polypoid mass obstructing the ear canal nasopharyngeal tract:obstruction of airways, sinusitis, pain, epistaxis, difficulty in swallowing, eventually polypoid tumor visible in the pharynx or in nasal area neck:hoarseness, difficulty in swallowing, visible tumor

7. RMS

8. Genitourinary tract: 22% location:urethra, vagina, uterus, prostate, bladder, testes, paratesticular area, spermatic cord symptoms: problems of urination, hematuria, vaginal bleeding, sarcoma botryoides
Extremities (18%) and trunk (7%): location: trunk, chest, abdomen, paraspinal area symptoms: indolent mass, symptoms of spinal compression, dyspnea
Retroperitoneal area:7%, symptoms: large tumor, abdominal pain, ascites

9. Extermity RMS

10. RMS of the bladder

11. Diagnosis Biopsy Radiology diagnosis: usg, CT, MRI Bone scan
Bone marrow aspiration and biopsy
Lumbar puncture

12. Staging
I A- localized tumor,confined to site origin, completely resected
I B - localized tumor infiltrating beyond site of origin, completely resected II A –localized tumor, gross total resection, but microscopic residual disease
II B –locally extensive tumor (spread to regional lymph nodes), completely resected
II C –extensive tumor (spread to lymph nodes, gross total resection, but with microscopic residual disease)
III A- localized or locally extensive tumor, gross residual disease after biopsy only
III B- localized or locally extensive tumor, gross residual disease after major resection (50% debulking)
IV any size of primary tumor with or without regional lymph node involvement, with distant metastases, irrespective of surgical approach to primary tumor

13. Metastatic spread
-metastases via lymphatic or/and hematogenous spread CNS, lung, lymph nodes, liver, bone, bone marrow
Treatment
Surgical procedure (total resection or biopsy)
Radiotherapy (II- IV)
Chemotherapy (CWS)

14. Prognosis Depend on: stage, tumor size, extension after surgery,
location (favorable: orbit or genitourinary tract),
histology (unfavorable: pleomorphic)
Age (more favorable in children < 7years old)
Survival:
EFS 20 – 80 % depending on stage

15. Bone tumors Osteosarcoma Ewing’s sarcoma
= 90% of primary bone tumors occuring in children and adolescents

16. Osteosarcoma
Primary malignant tumor of bone, originates from mesenchymal stem cell capable of differentiating toward bone
The most common bone tumor in children and adolescents
Rare in first decade of life
Most frequent in adolescent during growth spurt
Male : female 1.3 – 1.6 :1

17. Location Approximately 50% in knee region
Skeletal regions affected by greatest growth rate, i.e. distal femoral and proximal tibial metaphyses
humerus – third most frequently involved bone
Pelvis, i.e. ilium approximately 10%

18. Etiology/ genetics
Relation between rapid growth and development of osteosarcoma
Ionizing radiation
Alkylating agents and anthracyclines →secondary osteosarcoma
Association with Paget’s disease
Common second malignancy after inherited retinoblastoma –alteraltion in Rb common in sporadic osteosarcoma
Common association with a germline TP53 mutation (Li-Fraumeni syndrome)

19. Clinical presentation
Pain originating from involved region for weeks – months – even 1 –1.5 year!!! Delayed diagnosis !!!
Loss of function
10-15% of patients metastases when staged
Lung metastases predominate

20. Evaluation Radiology:
plain radiographs in two planes – characteristic radiological features: tumor matrix may be mineralized resulting in variable dense opacities of different sized and shapes tumor margins may be poorly defined Destructive growth pattern with lytic and sclerotic areas and normal bone tissue commonly observed
- cortex exhibits frequently destructive growth, the tumor is rarely limited to medullary space
-extension into soft tissue
-periosteal reaction often present, radiating striations called „sunburst signs” or open traingles overlying the diaphyseal side of lesion –Codman’s triangle or in the form of multiple layers – „onion skin”

21. Magnetic resonance imaging (MRI) of primary site of at least complete involved bone plus adjacent joints. MRI is more appropriate than CT scan
Open biopsy
Metastases: chest X-ray, CT scan of thorax, skeletal radionuclide scan

22. Treatment
Combined therapy : preoperative chemotherapy surgery (goal is a wide resection, limb –saving surgery with allograft or prosthesis ) postsurgical chemotherapy Osteosarcoma is relatively radioresistant
Prognosis:
5 -year overall survival –65% (without metastasis at diagnosis– 70%, with metastasis -30%

23. Ewing sarcoma family of tumors
Neuroectodermal histogenesis of tumors
Genetics: 95% of patients present translocation t(11;22) >translocation of the EWS gene on chromosome 22q12 with one of the genes of the FLI oncogene family = fusion transcript EWS - FLI
Histological subclassification: classic Ewing sarcoma (ES) extraskeletal or soft tissues ES Askin tumor (chest wall) peripheral primitive neuroectodermal tumor (PNET) of bone or/and soft tissue

24. Epidemiology Annual incidence 2.7/1million children < 15 years
Male : female 1.5 :1
80% of tumors in patient younger than 20 years of age
50% - in second decade of life
Mean age at diagnosis 15 years
More common in white than black population

25. Clinical presentation
Pain followed by swelling of the overlying affected bone
The duration from the onset of first symptoms to diagnosis - many months.Symptoms are frequently explained away as being a result of trauma or „growing pains”
Systemic symptoms: fever (20%)
Presence of nerve root pain or neuropathies from nerve compression
Anemia, leukocytosis, increased sedimentation rate
Pathological fracture – in 10% of cases

26. Location Almost 50% of ES – in the femur or pelvis
Mainly lower extremities involved, less frequently – upper extremities
Chest wall
Less common in the spine, paravertebral region, head and neck

27. Pathologic fracture mass of Ewing sarcoma

28. Metastases
Hematogenous route is most frequent pattern of spread: lungs, bone, bone marrow
Askin tumor may invade the adjacent pleural space with subsequent pleural effusion

29. Metastases Radionuclide scan of skeleton
X-rays or MRI scans of affected areas
Chest X-ray
Bone marrow aspiration

30. Evaluation
Laboratory findings: complete blood count blood sedimentation, C- reactive protein tumor lysis parameters, electrolites, kidney and liver parameters lactate dehydrogenase
Radiology : x-ray:periosteal reaction(onion-skin phenomenon) MRI (tumor volume)
Open biopsy

31. Treatment
Neoadjuvant chemotherapy surgery adjuvant chemotherapy radiotherapy
Prognosis
Depends on surgical resection, tumor localization, tumor volume, presence of macroscopic metastases, molecular/ biological aspects
5 year EFS approximately 70%

32. Retinoblastoma

33. Epidemiology 2% of all neoplasms in childhood
Annually 3/ 1 million children < 16 years old diagnosed,
1 in – births
Median age at diagnosis – 2 years
Boys : girls 1:1
Bilateral form 20-40% (more frequent in girls)

34. Etiology/ genetics/pathogenesis
Sporadic form –60%
Hereditary form 40%, two mutational event are required for tumor occurence: Mutation in germ cell Mutation in target cell (retina). Autosomal , dominant trait with high penetrance, i.e. nearly 50% of relatives develop a retinoblastoma, mostly bilateral.
Chromosomal alteration is located on chromosome 13q14 involving the RB1 retinoblastoma gene ( which is in the chromosomal region linked to the development of osteosarcoma – the most frequent secondary tumor)

35. Clinical manifestation
Leukokoria – „cat’s eye” – in the pupil of the eye is the first sign in majority of patients
Strabismus
Anisocoria
Loss of vision
Diagnosis is generally established on fundoscopy

36. Diagnosis
Fundoscopy – a white tumor accompanied by angiomatous dilatation of the vessels.
Radiological examinations: ultrasound CT magnetic resonance imaging (MRI)

37. Therapy Surgical management (enucleation)
The objective is to maintain vision without endangering the life of the child. In the advanced stages enucleation is necessary.
Chemotherapy
Radiotherapy
Laser photocoagulation
Cryotherapy
Brachytherapy
Prognosis: survival 80-90% of all patients