accidents; 44%

other; 22%

meningitis; 1%

heart disease; 4%

congenital anomalies; 8%

CANCER; 10%

Suicide, 1%

Pneumonia, 2%

cerebral palsy; 1%

HIV infection; 1%Homicide, 1%

Leading causes of death of children between of 1 and 14

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 %

Etiology and mechanisms of Etiology and mechanisms of carcinogenesis.carcinogenesis.

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

Etiology and mechanisms of Etiology and mechanisms of carcinogenesis.carcinogenesis.

Exogenous factorsExogenous factors:: - - physical agents most commonly studied are physical agents most commonly studied are

ultraviolet radiation, ionizing radiation, and ultraviolet radiation, ionizing radiation, and extremely low-frequency (50-60 Hz) magnetic extremely low-frequency (50-60 Hz) magnetic fields.fields.

- - chemical factors are environmental pollutants, chemical factors are environmental pollutants, tobacco, aflatoxin, and androgenic steroids.tobacco, aflatoxin, and androgenic steroids.

- - biologic agentsbiologic agents..

Prenatal diagnosis of Prenatal diagnosis of tumors (sonographic tumors (sonographic

features)features) • Absence or disruption of contour, Absence or disruption of contour,

shape, location, sonographic texture shape, location, sonographic texture or size, of a normal anatomic or size, of a normal anatomic structure; structure;

• Presence of an abnormal structure Presence of an abnormal structure or abnormal biometry; or abnormal biometry;

• Abnormality in fetal movement; Abnormality in fetal movement; • Polyhydramnios; Polyhydramnios; • Hydrops fetalis. Hydrops fetalis.

Common chief complaints given by parents that suggest a pediatric cancerChief complaints Suggested cancer

Chronic drainage from ear Rhabdomyosarcoma: Langerrhans cell histiocytosis

Morning headache with vomiting Brain tumorLump in neck that that does not respond to antibiotics

Hodgkin’s or non- Hodgkin’s lymphomas

Swollen face and neck Non-Hodgkin’s lymphoma, leukemia

Mass in abdomen Wilm’s tumor, neuroblastoma, hepatoma

Bleeding from vagina Yolk sack tumor, rhabdomyosarcoma

Weight loss Hodgkin’s lymphomaBone pain Leukemia, neuroblastoma

Noninvasive imaging Noninvasive imaging techniquestechniques

• Plain film chest radiographyPlain film chest radiography • Plain films of the abdomenPlain films of the abdomen • Barium studiesBarium studies • DiagnosticDiagnostic ultrasoundultrasound (US) (US)

examinationexamination • Computed tomographyComputed tomography (CT) (CT) • Magnetic resonance imagingMagnetic resonance imaging (MRI) (MRI) • Tumor markersTumor markers • Excisional and incisional biopsiesExcisional and incisional biopsies

TERATOMASTERATOMAS • Teratomas are tumors comprising more than a single cell Teratomas are tumors comprising more than a single cell

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

The most common The most common location location

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

Classification of the Classification of the sacrococcygeal teratomassacrococcygeal teratomas • Type I tumorsType I tumors are predominantly external, are predominantly external,

attached to the coccyx, and may have a small attached to the coccyx, and may have a small presacral component (45.8%). No metastases presacral component (45.8%). No metastases were associated with this group.were associated with this group.

• Type II tumorsType II tumors have both an external mass have both an external mass and significant presacral pelvic extension and significant presacral pelvic extension (34%) and have a 6% metastases rate.(34%) and have a 6% metastases rate.

• Type III tumorsType III tumors are visible externally, but the are visible externally, but the predominant mass is pelvic and predominant mass is pelvic and intraabdominal (8.6%). A 20% rate of intraabdominal (8.6%). A 20% rate of metastases was found in this group.metastases was found in this group.

• Type IV lesionsType IV lesions are not visible externally but are not visible externally but are entirely presacral (9.6%) and have an 8% are entirely presacral (9.6%) and have an 8% metastases rate.metastases rate.

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Sacrococcygeal teratoma

Malignant sacrococcygeal teratoma

Complications

ComplicationsComplications of the of the sacrococcygeal teratomassacrococcygeal teratomas

• associated congenital anomaliesassociated congenital anomalies • pre-term labor and deliverypre-term labor and delivery • massive hemorrhage into the tumor massive hemorrhage into the tumor

with secondary fetal exsanguinationwith secondary fetal exsanguination • dystocia, secondary to tumor bulk or dystocia, secondary to tumor bulk or

tumor rupturetumor rupture • placentomegaly and/or hydrops placentomegaly and/or hydrops

evolved, which, in turn, precipitated evolved, which, in turn, precipitated rapid fetal deathrapid fetal death

Differential diagnosis:Differential diagnosis:

• ммeningomyeloceleeningomyelocele• rectal abscess rectal abscess • dermoid cyst dermoid cyst • angioma angioma • lipomalipoma• neurogenic tumorneurogenic tumor• pilonidal cyst.pilonidal cyst.

TreatmentTreatment • Surgical, including removal of the Surgical, including removal of the

coccyxcoccyx..• Malignant = surgical excision + Malignant = surgical excision +

chemotherapy + radiation chemotherapy + radiation (metastases to lung, bone, liver). (metastases to lung, bone, liver).

Prognosis of the sacrococcygeal Prognosis of the sacrococcygeal teratomasteratomas

• Benign - disease free survival is greater Benign - disease free survival is greater than 90%; malignant - significant than 90%; malignant - significant mortality, although good progress has mortality, although good progress has been made recently in treatment of been made recently in treatment of these tumors. these tumors.

Time of diagnoses is key: Time of diagnoses is key: • < 2 months of age, only 7-10% are < 2 months of age, only 7-10% are

malignant malignant • Age 1 year, 37% malignant Age 1 year, 37% malignant • Age 2 years, 50% malignant Age 2 years, 50% malignant

RHABDOMYOSARCOMARHABDOMYOSARCOMAA malignant tumor of mesenchimal cell origin is A malignant tumor of mesenchimal cell origin is

called a sarcoma. Mesenchymal cells normaly mature called a sarcoma. Mesenchymal cells normaly mature into skeletal muscle, smooth muscle, fat, fibrous tissue, into skeletal muscle, smooth muscle, fat, fibrous tissue, bone, and cartilage. Rhabdomyosarcoma is thought to bone, and cartilage. Rhabdomyosarcoma is thought to arise from immature mesenchimal cells that are arise from immature mesenchimal cells that are committed to skeletal muscle lineage, but these tumors committed to skeletal muscle lineage, but these tumors can arise in tissues in which striated muscle is not can arise in tissues in which striated muscle is not normally found, such as urinary bladder. normally found, such as urinary bladder.

Rhabdomyosarcoma (RMS), the most common soft Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in infants and children, represents about tissue sarcoma in infants and children, represents about 5-15% of all malignant solid lesions. RMS arises from a 5-15% of all malignant solid lesions. RMS arises from a primitive cell type and occurs in mesenchymal tissue at primitive cell type and occurs in mesenchymal tissue at almost any body site excluding brain and bone. almost any body site excluding brain and bone.

The Intergroup The Intergroup Rhabdomyosarcoma Study Rhabdomyosarcoma Study

divides tumors into 5 types:divides tumors into 5 types:– embryonal (57 %), embryonal (57 %), – alveolar (19 %), alveolar (19 %), – botryoid (6 %), botryoid (6 %), – undifferentiated (17 %), undifferentiated (17 %), – pleomorphic (1 %). pleomorphic (1 %).

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embryonic rhabdomyosarcoma of the vesica urinaria

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Orbital embryonic rhabdomyo-sarcoma

Alveolar rhabdomyosarcoma

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DiagnosisDiagnosis..

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

TreatmentTreatment

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

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

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

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

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Wilms’ tumor (nephroblastoma)

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

ClinicalClinical History.History. The most common presentation is an The most common presentation is an

asymptomatic abdominal mass discovered by the asymptomatic abdominal mass discovered by the parent or physician. Occasionally the child presents parent or physician. Occasionally the child presents with haematuria, but symptoms are often non-with haematuria, but symptoms are often non-specific: abdominal fullness, abdominal pain, specific: abdominal fullness, abdominal pain, gastrointestinal upset, fever, weight loss, malaise, and gastrointestinal upset, fever, weight loss, malaise, and anaemia. Hypertension is sometimes detectable. anaemia. Hypertension is sometimes detectable.

A small number of patients who have hemorrhaged A small number of patients who have hemorrhaged into their tumor may present with signs of into their tumor may present with signs of hypotension, anemia, and fever. Rarely, patients with hypotension, anemia, and fever. Rarely, patients with advanced-stage disease may present with respiratory advanced-stage disease may present with respiratory symptoms related to the presence of lung metastases. symptoms related to the presence of lung metastases.

Cytogenetics studiesCytogenetics studies

• An 11p13 deletion as in the WAGR An 11p13 deletion as in the WAGR syndrome (Wilms’, aniridia, syndrome (Wilms’, aniridia, genitourinary abnormalities, mental genitourinary abnormalities, mental retardation)retardation)

• A duplication of the paternal allele A duplication of the paternal allele 11p15 as in BWS11p15 as in BWS

• Mutational analysis of the WT1 gene in Mutational analysis of the WT1 gene in cases where Denys-Drash syndrome cases where Denys-Drash syndrome (intersexual disorders, nephropathy, (intersexual disorders, nephropathy, Wilms’ tumor) is suspectedWilms’ tumor) is suspected

Imaging StudiesImaging Studies• Renal ultrasonographyRenal ultrasonography (with dynamic imaging of the (with dynamic imaging of the

renal vein and interior vena cava).renal vein and interior vena cava).• CT scanningCT scanning.. Abdominal CT scanning helps determine Abdominal CT scanning helps determine

the tumor's origin, lymph node involvement, bilateral the tumor's origin, lymph node involvement, bilateral kidney involvement, and invasion into major vessels (eg, kidney involvement, and invasion into major vessels (eg, inferior vena cava or liver metastases). If findings on inferior vena cava or liver metastases). If findings on chest CT scanning are positive while chest radiographic chest CT scanning are positive while chest radiographic findings are negative, diagnostic biopsy of the lesions findings are negative, diagnostic biopsy of the lesions noted on the chest CT scan is recommended.noted on the chest CT scan is recommended.

• Chest radiographyChest radiography (4-field) - Detects lung metastases (4-field) - Detects lung metastases (Patients with lung lesions on chest radiography receive (Patients with lung lesions on chest radiography receive whole lung radiotherapy.)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)

Current approach to Wilms’ tumor by stage and histologyCurrent 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

NephrectomyVincristine

DactinomycinDoxorubicin

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

Complications.Complications.• The primary treatment, nephrectomy, The primary treatment, nephrectomy,

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

NEUROBLASTOMANEUROBLASTOMANeuroblastoma is a tumour of neural Neuroblastoma is a tumour of neural

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

Localizations of the Localizations of the neuroblastoma

• 75 % of tumours occur in the 75 % of tumours occur in the abdomen: abdomen: – adrenal medulla 50 %, adrenal medulla 50 %, – paraspinal ganglia 25 %paraspinal ganglia 25 %

• 20 % occur in the thorax, 20 % occur in the thorax, • 5 % occur in the neck and the 5 % occur in the neck and the

pelvispelvis

The Evans classification for The Evans classification for neuroblastoma neuroblastoma

• Stage I:Stage I: tumor confined to an organ of origin. tumor confined to an organ of origin. • Stage II:Stage II: tumor extending beyond an organ of tumor extending beyond an organ of

origin, but not crossing the midline. origin, but not crossing the midline. Ipsilateral lymph nodes may be involved. Ipsilateral lymph nodes may be involved.

• Stage III:Stage III: tumor extending beyond midline. tumor extending beyond midline. Bilateral lymph nodes may be involved. Bilateral lymph nodes may be involved.

• Stage IV:Stage IV: remote disease involving skeleton, remote disease involving skeleton, bone marrow, soft tissue or distant lymph bone marrow, soft tissue or distant lymph nodes. nodes.

• Stage IVS:Stage IVS: same as stage I or II with presence same as stage I or II with presence of disease in liver, skin or bone marrow.of disease in liver, skin or bone marrow.

DiagnosisDiagnosisUltrasonographyUltrasonography distinguishes neuroblastoma (solid, distinguishes neuroblastoma (solid,

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

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Mediastinal neuroblastoma

Treatment.Treatment.The treatment modalities The treatment modalities

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

SurgerySurgeryplays the pivotal role in the management of plays the pivotal role in the management of

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

ChemotherapyChemotherapyis the predominant modality of management in is the predominant modality of management in

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

Radiation therapyRadiation therapy

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

Classification of Vascular Classification of Vascular Lesions Lesions Vascular Vascular

malformations malformations (flat lesions)(flat lesions)

• Salmon patch Salmon patch (also known as (also known as nevus simplex or nevus simplex or nevus nevus telangiectaticustelangiectaticus))

• Port-wine stain Port-wine stain (also known as (also known as nevus flammeus) nevus flammeus)

Hemangiomas Hemangiomas (raised lesions)(raised lesions)

• Superficial Superficial hemangioma hemangioma ((Cherry, Cherry, strawberrystrawberry hemangioma)hemangioma)

• Deep Deep hemangioma hemangioma (also known as (also known as cavernous cavernous hemangioma) hemangioma)

Strawberry Strawberry haemangiomashaemangiomas

Cherry haemangiomasCherry haemangiomas

Cavernous haemangiomas

Before treatment

After treatment

Port wine stains

Treatment Indications for HemangiomasTreatment Indications for Hemangiomas Threat to life or functionThreat to life or function

– Kasabach-Merritt syndrome (coagulopathy)Kasabach-Merritt syndrome (coagulopathy)– Anatomic siteAnatomic site– Vision impairment Vision impairment – Respiratory impairmentRespiratory impairment– High-output cardiac failure (mortality up to 50 %)High-output cardiac failure (mortality up to 50 %)– IInternal lesions nternal lesions

Location in scar-prone area Location in scar-prone area – NoseNose, , LipLip, , EarEar, , Glabellar area Glabellar area – Any large facial hemangiomasAny large facial hemangiomas– Pedunculated lesions Pedunculated lesions

Tendency to bleed or to become infectedTendency to bleed or to become infectedRapid rate of growth (tripling in size within weeks)Rapid rate of growth (tripling in size within weeks)

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Cavernous lymphangioma

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naevus melanoma

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melanoma