PEDIATRIC ONCOLOGY

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PEDIATRIC ONCOLOGY
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Leading causes of death of children between of 1
and 14
HIV infection 1 Homicide, 1
Suicide, 1
Pneumonia, 2
cerebral palsy 1
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Distribution of cancer in children younger than
15 years of age by diagnosis
Acute lynphoblastic leucemia 23.3
CNS tumors 20.7
Neuroblastoma 7.3
Non-Hodgkin's 6.3
Wilms' tumor 6.1
Hodgkin's disease 5
Acute myeloid leukemia 4.2
Rhabdomypsarcoma 3.4
Retinoblastoma 2.9
Osteosarcoma 2.6
Other 2.1
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Etiology and mechanisms of carcinogenesis.

• Endogenous factors constitutional chromosomal
  abnormality mendelian autosomal dominant,
  recessive, or X-linked patterns non-mendelian
  inheritance mutations in multiple genes or
  mitochondrial DNA or caused by mutations
  affecting imprinted genes.

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Etiology and mechanisms of carcinogenesis.

• Exogenous factors
• - physical agents most commonly studied are
  ultraviolet radiation, ionizing radiation, and
  extremely low-frequency (50-60 Hz) magnetic
  fields.
• - chemical factors are environmental pollutants,
  tobacco, aflatoxin, and androgenic steroids.
• - biologic agents.

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Prenatal diagnosis of tumors (sonographic
features)

• Absence or disruption of contour, shape,
  location, sonographic texture or size, of a
  normal anatomic structure
• Presence of an abnormal structure or abnormal
  biometry
• Abnormality in fetal movement
• Polyhydramnios
• Hydrops fetalis.

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Common chief complaints given by parents that
suggest a pediatric cancer
Chief complaints Suggested cancer
Chronic drainage from ear Rhabdomyosarcoma Langerrhans cell histiocytosis
Morning headache with vomiting Brain tumor
Lump in neck that that does not respond to antibiotics Hodgkins or non- Hodgkins lymphomas
Swollen face and neck Non-Hodgkins lymphoma, leukemia
Mass in abdomen Wilms tumor, neuroblastoma, hepatoma
Bleeding from vagina Yolk sack tumor, rhabdomyosarcoma
Weight loss Hodgkins lymphoma
Bone pain Leukemia, neuroblastoma
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Noninvasive imaging techniques

• Plain film chest radiography
• Plain films of the abdomen
• Barium studies
• Diagnostic ultrasound (US) examination
• Computed tomography (CT)
• Magnetic resonance imaging (MRI)
• Tumor markers
• Excisional and incisional biopsies

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TERATOMAS

• Teratomas are tumors comprising more than a
  single cell type derived from more than one germ
  layer. A significant degree of confusion has
  arisen regarding nomenclature for the various
  subtypes of teratomas. The word itself is derived
  from the Greek word teraton, meaning monster, and
  was used initially by Virchow in the first
  edition of his book on tumors, which was
  published in 1863. Teratomas range from benign,
  well-differentiated (mature) cystic lesions to
  those that are solid and malignant (immature).
  Besides being mature, with malignant
  transformation, teratomas also may be monodermal
  and highly specialized.

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The most common location

• sacrococcygeal (57)
• gonads (29)
• mediastinal (7)
• retroperitoneal (4)
• cervical (3)
• intracranial (3)

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Classification of the sacrococcygeal teratomas

• Type I tumors are predominantly external,
  attached to the coccyx, and may have a small
  presacral component (45.8). No metastases were
  associated with this group.
• Type II tumors have both an external mass and
  significant presacral pelvic extension (34) and
  have a 6 metastases rate.
• Type III tumors are visible externally, but the
  predominant mass is pelvic and intraabdominal
  (8.6). A 20 rate of metastases was found in
  this group.
• Type IV lesions are not visible externally but
  are entirely presacral (9.6) and have an 8
  metastases rate.

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Malignant sacrococcygeal teratoma
Sacrococcygeal teratoma
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Complications
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Complications of the sacrococcygeal teratomas

• associated congenital anomalies
• pre-term labor and delivery
• massive hemorrhage into the tumor with secondary
  fetal exsanguination
• dystocia, secondary to tumor bulk or tumor
  rupture
• placentomegaly and/or hydrops evolved, which, in
  turn, precipitated rapid fetal death

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Differential diagnosis

• ?eningomyelocele
• rectal abscess
• dermoid cyst
• angioma
• lipoma
• neurogenic tumor
• pilonidal cyst.

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Treatment

• Surgical, including removal of the coccyx.
• Malignant surgical excision chemotherapy
  radiation (metastases to lung, bone, liver).

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Prognosis of the sacrococcygeal teratomas

• Benign - disease free survival is greater than
  90 malignant - significant mortality, although
  good progress has been made recently in treatment
  of these tumors.
• Time of diagnoses is key
• lt 2 months of age, only 7-10 are malignant
• Age 1 year, 37 malignant
• Age 2 years, 50 malignant

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RHABDOMYOSARCOMA

• A malignant tumor of mesenchimal cell origin is
  called a sarcoma. Mesenchymal cells normaly
  mature into skeletal muscle, smooth muscle, fat,
  fibrous tissue, bone, and cartilage.
  Rhabdomyosarcoma is thought to arise from
  immature mesenchimal cells that are committed to
  skeletal muscle lineage, but these tumors can
  arise in tissues in which striated muscle is not
  normally found, such as urinary bladder.
• Rhabdomyosarcoma (RMS), the most common soft
  tissue sarcoma in infants and children,
  represents about 5-15 of all malignant solid
  lesions. RMS arises from a primitive cell type
  and occurs in mesenchymal tissue at almost any
  body site excluding brain and bone.

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The Intergroup Rhabdomyosarcoma Study divides
tumors into 5 types

• embryonal (57 ),
• alveolar (19 ),
• botryoid (6 ),
• undifferentiated (17 ),
• pleomorphic (1 ).

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embryonic rhabdomyosarcoma of the vesica urinaria
                                                
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20
Orbital embryonic rhabdomyo-sarcoma
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Alveolar rhabdomyosarcoma
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Diagnosis.

• Biopsy (open, percutaneous, or endoscopic) is
  required for diagnosis and histological typing,
  which directs therapy. The extent of the tumour
  is defined by imaging techniques such as
  ultrasound, computed tomography (CT), or magnetic
  resonance imaging (MRI).

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Treatment

• is determined on an individual basis, according
  to the site, stage, and histological type of the
  tumor. Treatment of rhabdomyosarcoma should be
  multimodal, consisting of chemotherapy, surgery,
  and radiotherapy.

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• Surgery is the most rapid way to ablate the
  disease, and it should always be used if
  subsequent function or cosmetic will not be
  greatly impaired. In sites such as vagina and
  urinary bladder and most head and neck sites,
  incisional biopsy (for diagnosis) may be the only
  feasible surgical procedure because of proximity
  to vital blood vessels and nerves, cosmetic
  consideration, or both. The second-look operation
  is used to resect residual tumor after the
  administration chemotherapy or local radiotherapy.

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• Radiation therapy can eradicate residual tumor
  cells from sites where surgical therapy alone
  cannot ablate the mass, especially in the head,
  neck, and pelvis.

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• Preoperative chemotherapy may reduce the extent
  of surgery required and should be considered.
  Postoperative chemotherapy is helpful in
  eradicating residual disease and micrometastases.
  Chemotherapy is the primary treatment for
  patients with metastatic disease at presentation.
  The commonly used drugs are a combination of
  cyclophosphamide, vincristine, actinomycin D, and
  Adriamycin. Doxorubicin, DTIC (ditriazoimidazole
  carboximide), cisplatin, and ifosfamide have also
  been known to be effective agents.

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Wilms tumor (nephroblastoma)
                                                
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• Wilms tumor is thought to be caused by
  alterations of genes responsible for normal
  genitourinary development. Examples of common
  congenital anomalies associated with Wilms tumor
  are cryptorchidism, double collecting system,
  horseshoe kidney, and hypospadias. Environmental
  exposures, although considered, seem less likely
  to play a role.

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Clinical

• History. The most common presentation is an
  asymptomatic abdominal mass discovered by the
  parent or physician. Occasionally the child
  presents with haematuria, but symptoms are often
  non-specific abdominal fullness, abdominal pain,
  gastrointestinal upset, fever, weight loss,
  malaise, and anaemia. Hypertension is sometimes
  detectable.
• A small number of patients who have hemorrhaged
  into their tumor may present with signs of
  hypotension, anemia, and fever. Rarely, patients
  with advanced-stage disease may present with
  respiratory symptoms related to the presence of
  lung metastases.

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Cytogenetics studies

• An 11p13 deletion as in the WAGR syndrome
  (Wilms, aniridia, genitourinary abnormalities,
  mental retardation)
• A duplication of the paternal allele 11p15 as in
  BWS
• Mutational analysis of the WT1 gene in cases
  where Denys-Drash syndrome (intersexual
  disorders, nephropathy, Wilms tumor) is suspected

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Imaging Studies

• Renal ultrasonography (with dynamic imaging of
  the renal vein and interior vena cava).
• CT scanning. Abdominal CT scanning helps
  determine the tumor's origin, lymph node
  involvement, bilateral kidney involvement, and
  invasion into major vessels (eg, inferior vena
  cava or liver metastases). If findings on chest
  CT scanning are positive while chest radiographic
  findings are negative, diagnostic biopsy of the
  lesions noted on the chest CT scan is
  recommended.
• Chest radiography (4-field) - Detects lung
  metastases (Patients with lung lesions on chest
  radiography receive whole lung radiotherapy.)

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Wilms tumor (nephroblas-toma)
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nephroblastoma angiograma
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Leftside nephroblastoma (CT-scan)
                                                
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Current approach to Wilms tumor by stage and
histology
Stage, Histology Surgery Chemotherapy Radiotherapy
Stage I or II with FHStage I with anaplasia Nephrectomy VincristineDactinomycin None
Stage III or IV with FHStage II, III, or IV with focal anaplasia Nephrectomy VincristineDactinomycinDoxorubicin Yes
Stage II, III, or IV with diffuse anaplasiaStage I, II, III, or IV CCSK Nephrectomy VincristineDoxorubicinCyclophosphamideEtoposide Yes
Stage I, II, III, or IV RTK Nephrectomy CyclophosphamideEtoposideCarboplatin Yes
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Complications.

• The primary treatment, nephrectomy, may damage
  kidney function. However, additional treatment
  modalities may cause damage to several organs
  such as the heart, lungs, liver, bones, and
  gonads. In addition, both chemotherapeutic agents
  and radiation therapy can induce second malignant
  neoplasms.

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NEUROBLASTOMA

• Neuroblastoma is a tumour of neural crest origin
  which may occur in the adrenal medulla or
  anywhere along the sympathetic ganglion chain,
  namely in the neck, thorax, abdomen, and pelvis.
  Seventy-five per cent of tumours occur in the
  abdomen (adrenal medulla 50 , paraspinal ganglia
  25 ), 20 occur in the thorax, and 5 occur in
  the neck and the pelvis.

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Localizations of the neuroblastoma

• 75 of tumours occur in the abdomen
• adrenal medulla 50 ,
• paraspinal ganglia 25
• 20 occur in the thorax,
• 5 occur in the neck and the pelvis

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The Evans classification for neuroblastoma

• Stage I tumor confined to an organ of origin.
• Stage II tumor extending beyond an organ of
  origin, but not crossing the midline. Ipsilateral
  lymph nodes may be involved.
• Stage III tumor extending beyond midline.
  Bilateral lymph nodes may be involved.
• Stage IV remote disease involving skeleton, bone
  marrow, soft tissue or distant lymph nodes.
• Stage IVS same as stage I or II with presence of
  disease in liver, skin or bone marrow.

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Diagnosis

• Ultrasonography distinguishes neuroblastoma
  (solid, extrarenal) from cystic lesions and renal
  tumours. The radiographic detection of
  calcification in the tumour is suggestive of
  neuroblastoma. In children with an abdominal
  neuroblastoma, intravenous urography shows
  displacement rather than distortion of the
  pelvicaliceal system. A skeletal survey and chest
  radiograph are mandatory to detect possible
  metastases. CT gives good anatomical data about
  the tumour. Recent studies suggest that magnetic
  resonance imaging (MRI) is useful both to
  delineate the primary tumor and to evaluate bone
  marrow metastasis, vessel involvement, and
  extension into spinal cord.

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Mediastinal neuroblastoma
                                                
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Treatment.

• The treatment modalities traditionally employed
  in the management of neuroblastoma are surgery,
  chemotherapy, and radiation therapy. The role of
  each method is determined by the natural history
  of individual cases considering stage, age, and
  histological features.

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Surgery

• plays the pivotal role in the management of
  neuroblastoma. Depending of the timing, operative
  procedures can have diagnostic as well as
  therapeutic functions. The goals of primary
  surgical procedures, performed before any other
  therapy, are to establish the diagnosis, to
  provide tissue for biological studies, to stage
  the tumor surgically, and to attempt to excise
  the tumor, if feasible. In delayed primary or
  second look surgery, the surgeon determines
  response to therapy and removes residual disease
  when possible.

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Chemotherapy

• is the predominant modality of management in
  management in neuroblastoma. Cyclophosphamide,
  vincristine, cisplatin, and doxorubicinare are
  the cornerstone of multiagent management. Drug
  combinations have been developed that take
  advantage of drug synergism, mechanism of
  cytotoxicity, and differences in side effects.

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Radiation therapy

• has been used in the multimodality management of
  residual neuroblastoma, bulky unresectable
  tumors, and disseminated disease. More recently,
  the role of radiation therapy in neuroblastoma
  continues to be refined with the improviment in
  multiagentchemotherapyand the increasing trend
  toward developing risk-related treatment groups
  based on age, stage, and biologic features.

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Classification of Vascular Lesions

• Vascular malformations (flat lesions)
• Salmon patch (also known as nevus simplex or
  nevus telangiectaticus)
• Port-wine stain (also known as nevus flammeus)

• Hemangiomas (raised lesions)
• Superficial hemangioma (Cherry, strawberry
  hemangioma)
• Deep hemangioma (also known as cavernous
  hemangioma)

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Strawberry haemangiomas
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Cherry haemangiomas
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Cavernous haemangiomas
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After treatment
Before treatment
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Port wine stains
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Treatment Indications for Hemangiomas

• Threat to life or function
• Kasabach-Merritt syndrome (coagulopathy)
• Anatomic site
• Vision impairment
• Respiratory impairment
• High-output cardiac failure (mortality up to 50
  )
• Internal lesions
• Location in scar-prone area
• Nose, Lip, Ear, Glabellar area
• Any large facial hemangiomas
• Pedunculated lesions
• Tendency to bleed or to become infected
• Rapid rate of growth (tripling in size within
  weeks)

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Cavernous lymphangioma
                                                
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melanoma
naevus
                                                
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melanoma
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