Overview of Pediatric Oncology

Question 1

• The most common cancer in children, accounting for 30% of all childhood malignancies
• Acute lymphoblastic leukemia (ALL) accounts for 80% of cases

Answer 1

Acute leukemia

Question 2

• second most common of all childhood malignancies
• the most common pediatric solid organ tumor

Answer 2

primary malignant CNS tumors

Question 3

Most prevelant solid tumor in children outside of the cranium

Answer 3

neuroblastoma

Question 4

Risk factors for cancer by age?

Answer 4

0-2 years: neuroblastoma
2-5 years: ALL
10-15 years: osteosarcoma, Ewing sarcoma
15-19 years: Hodgkin lymphoma

Question 5

what are some cancer predispositon disorders?

Answer 5

• Trisomy 21 (leukemia)
• Fanconi anemia (AML and solid tumors)
• Li fraumeni syndrome
• von Hippel- llindaue disease

Question 6

• the overall risk of malignancy is up to 4x higher than that of the general population
• common tumors: Neurofibromas (most common overall; most are benign); optic pathway gliomas (most common intracranial neoplasm; most are low grasde astrocytomas and occur in kids <6)

Answer 6

Neurofibromas type 1

Question 7

• vestibular schwannoma (typically bilateral and benign)
• meningioma
• spinal tumors

Answer 7

Neurofibromatsosis Type 2

Question 8

pathogenesis of ALL

Answer 8

• B cell (85%) > T cell (10-15%)
• consecutive genetic lesions (i.e a sentinel hit followed by a secondary hit, resulting in an arrest in development and abnormal proliferation
• aberrant lymphoblast cell proliferation and survival is the hallmark of ALL

Question 9

• slight predilection for boys than girls
• Age 2-5 years
• often nonspecific
• common presenting signs and symptoms: Fever, pallor, bruising and/or petechiae, lymphadenopathy, anorexia, weight loss, bone pain, abdominal pain and/or distention, hepatosplenomegaly

Answer 9

ALL

Question 10

What are some specific scenerios that can be seen in ALL?

Answer 10

CNS involvement

• Headache, vomiting, lethargy, cranial nerve palsies, and/or papilledmea

Testicular involvement

• Persistant, painless, unilateral testicular enlargement/solid mass
• more commonly seen at a time of relapse

Mediastinal mass (esp. T-Cell)

• Orthopnea, facial flushing and or swelling, chest pain and/or stridor

Question 11

• leukemia
• adrenocortical carcinoma
• CNS tumors
• rabdomyosarcoma
• osteosarcoma

SLAB

Answer 11

Li Fraumeni Syndrome

Question 12

• retinal and CNS hemangioblastoma
• clear cell renal cell carcinoma
• pheochromocytoma

Answer 12

Von Hippel-lindau disease

Question 13

Evaluation of ALL

Answer 13

Labs

• Thrombocytopenia and/or anemia
• WBC count can be decreased, increased, or normal (may or may not have circulating blasts, often have a low absolute neutrophil count (ANS)
• elevated LDH and uric acid

Lumbar puncture

• Evaluate for the presence of leukemic blasts in the CSF
• Administer the first dose of intrathecal (IT) chemotherapy

Bone marrow aspirate and biopsy

• Gold standard for diagnosis
• > 25% blasts in the bone marrow (if 25%–> lymphoma)
• perform flow cytometry, immunohistochemistry, and cytogenetics

Question 14

ALL management

Answer 14

• most protocols take 2.5 years to complete
• multi drug regimen
• includes CNS-direted therapy w/IT chemo for all patients

Question 15

• Fever, malaise, bone pain, lymphadenopathy, hepatosplenomegaly
• gingival hypertrophy, chloroma
• bleeding/DIC (especially common in acute promyelocytic leukemia)
• clinical signs: Bleeding or oozing from various sites, peripheral cyanosis of the fingers or toes (microvascular thrombosis) signs and symptoms of stroke, hemodynamic instability
• lab findings: thrombocytopenia, elevated D-dimer, and PT/INR, decreased fribrinogen

Answer 15

AML

Question 16

large nuclei, usually with prominent nucleoli; may have auer rods (caused by abnormal fusion of primary granules)

Answer 16

AML

Question 17

Scant amount of cytoplasm, absence of cytoplasmic granules

Answer 17

ALL

Question 18

AML managment

Answer 18

• induction: typically 2 cycles of intense chemo
• conslidation (post-remission therapy): more chemo, allogenic BMT is offered to children with high-risk cytogenetics in
• IT chemotherapy is given to all children with AML

Question 19

treatment of APML

Answer 19

ATRA (all trans retinoic acid) can reduce the risk of DIC and should be started quickly when APML is suspected even if the diagnosis is not confirmed

Question 20

• clonal transformation of cells of B-cell origin
• pathognomic bi-nucleated reed-sternberg cells
• bimodal age distribution, peaks in the AYA population
• females> males
• possible causes: Genetic susceptibility, history of radiation or chemotherapy, certain infections, immunosuppressive agents, congential immunodeficiency, autoimmune disorders

Answer 20

Hodgkins lymphoma

Question 21

hodgkins lymphoma clinical presentation

Answer 21

• 80% present with painless lymphadenopathy (usually cervical, supraclavicular or axillary)
• rubbery and more firm than inflammatory adenopathy
• fatigue, anorexia, pruritus
• B symptoms: night sweats, weight loss, persistent unexplaind fevers
• mediastinal mass- more common among > 12 yers old

Question 22

evaluation of HL?

Answer 22

Evaluation

• labs are non-specific
• imaging: CXR; CT neck , chest abdomen and pelvis; FDG-PET CT skull base to thigh

Tissue Biopsy

• excisional biopsy is the gold standard
• needle biopsy does not provide adequate tissue because malignant cells may represent < 1% of the cellular infiltrate
• bone marrow aspirates are recommended for select patients

Question 23

HL staging

Answer 23

• lugano classification
• each disease stage is further noted according the the presence or absence of B symptoms, bulky disease, extranodal involvement
• stage 1: localized disease, one region or single organ
• stage 2: two or more lymph node regions on the same side of diaphragm
• stage 3: two or more lymph node regions about and below diaphragm
• stage 4: widespread disease, multiple organs with or without lymph node involvment

Question 24

HL management

Answer 24

low risk: 2-4 cycles of chemotherapy +/- radiation
intermediate risk: 2-6 cycles of chemotherapy + response based radiation
high risk: 3-5 cycles of chemotherpay + response based radiation

Question 25

* 5th most common diagnosis of pediatric cancer in children < 15 years * pathogenesis similar to HL * Congenital and acquired immunodeficiency syndromes and DNA damage repair syndromes place affected pts at risk * Common varriable immunodeficiency (CVID), wiskott aldrich syndrome (WAS), Ataxia-telangiectasia, x-linked lymphoproliferative disease, HIV infection

Answer 25

Non-hodgkins lymphoma

Question 26

NHL clinical presentation

Answer 26

* painless lymphadenopathy is most common * mediastinal mass: dyspnea, wheezing, stridor, dysphagia * any organ, tissue, or anatomic area can be involved * **burkitt: abdominal pain that mimics appendicitis, intussuception, abdominal mass, sick!** * T- lymphoblastic leukemia: males > females, median age 12 years, 20% of pediatric NHL

Question 27

evaluation of NHL

Answer 27

* CT of the neck, chest, abdomen and pelvis * FDG-PET scan * skeletal scintigraphy can detect bone involvement * bone marrow biopsy for cytology, immunophenotyping, and genetic evaluation should be performed on all pts * lumbar puncture for examination of CHF

Question 28

NHL management

Answer 28

Burkitt lymphoma * multi-agent combination of chemotherapy with or without immunotherapy (2-4 cycles of chemotherapy) * **no role for surgical debulking or radiation** T-lymphoblastic leukemia * combination chemotherpay based on regimens used for ALL

Question 29

* Pilocytic astrocytoma (most common) * > 1000 diagnosed annually * median age: 8 years

Answer 29

low grade glioma (50%)

Question 30

DIPG * 300 diagnosed annually * mean age 5-9 years * median survival:10-11 months

Answer 30

high grade glioma (10-15%)

Question 31

Embyonal tumors

Answer 31

Medulloblastoma * 500 diagnosed annually * median age 5-9 Atypical tertoid rhabdoid tumor * < 100 diagnosed annually * median age < 3 years * median survival 12-24 months Cranial and pasaspinal nerve turmors: Neurofibroma * benign * usually present by age 3

Question 32

Clinical presentation of CNS tumors

Answer 32

* may be subtle or nonspecific and may vary with the childs age and tumor location common presenting signs and symptoms * headache (most common- **Early morning headache** relieved by vomiting) * nausea and vomiting * clumsiness, incoordination, worsening handwriting * speech changes: slurring, aphasia * cranial nerve palsies * vision changes: decreased visual acuity, squinting, head tilt * seizues * developmental delay and behavioral change

Question 33

how does age and location of the CNS tumor change clinical presentation?

Answer 33

Age * infants: macrocephaly is the most common * infants and young children are more irritable * older: headache, abnormal gait, poor coordination, papilledema, and seizures Location * supratentorial and central: generally nonspecific but most common is headache * posterior fossa: nausea/vomiting, headache, abnormal gait, and coordination * brainstem: abnormal gait and coordination, cranial nerve palsies * spinal cord: back pain and/or weakness and abnormal gait

Question 34

evaluation of CNS tumors

Answer 34

* **CT (preferred in emergent situations)** * **MRI with contrast (best modality for imaging CNS tumors)** * Biopsy and reduction of tumor done at the same time * long term prognosis of some types is dependent on degree of surgical resection

Question 35

management of CNS tumors

Answer 35

* Surgery (near total resection can be achieved in most cases) * Chemotherapy (routinely used in young children with specific tumor types with the goal of delaying or replacing radiation therapy

Question 36

* **usually avoided in children < 3 years due to risk of severe neurocognitive sequelae** * associated with several complication * acute: headache, nausea, drowsiness * somnolence syndrome (occurs anywhere from a few weeks to 3 months after treatment) * late: impaired neurocognitive funciton and social/behavioral deficits, hearing and or vision impairment

Answer 36

Radiation therapy | CNS tumor management

Question 37

NBL pathogenesis

Answer 37

* abnormal growth of embryonic neural crest cells that normally make up the sympathetic ganglia and adrenal medulla * **most common extracranial solid tumor in children** * genetic syndromes associated: Congenital hypoventilation syndrome, neurofibromatosi, costello syndrome, noon syndrome, li-fraumeni syndrome

Question 38

NBL clinical presentation

Answer 38

* metastatic disease to the bone marrow, liver and kin is seen in 50% of patients at presentation * constitutional symptoms (fever, malaise, pallor, fussiness) * **blueberry muffin rash** * spinal cord compression: pain, numbness, limb weakness * **hornor syndrome: suggests impingement of the oculosympathetic tract; ptosis, miosis, anhydrosis** * opsoclonus myoclonus syndrome: rapid multidirectional eye movements, involuntary muscle spasms, irritability * **raccoon eyes: periorbital ecchymosis represent metastatic spread to the retrobulbar region**

Question 39

NBL management

Answer 39

* **Half of all cases of neuroblastoma found in infants < 6 months spontaneously resolve** * most patients > 12 months of age are stage IV and require intense multimodal therapy * MIBG therapy

Question 40

* thought to arise from a mesenchymal stem cell that differentiates towards fibrous tissue, cartilage or bone * risk factors: genetic syndromes and germline conditions -Heredirtary RB, Li-fraumeni syndrome, round-Thomson syndrome * **prior cancer treatment, especially exposure to alkylating chemotherapy agents** * rapid bone growth (peak incidence during an adolescent growth spurt) * males > females * **African American race**

Answer 40

Osterosarcoma

Question 41

OSt: Clinical presentation

Answer 41

* but is the most common primary malignant bone tumor * **most common symptom is localized pain (frequently begins after injury)** * systemic symptoms: **(ex. fever, weight loss and malaise) are generally ABSENT** * most important physical finding is a **large soft tissue mass that is tender to palpation**

Question 42

Ost Evaluation

Answer 42

* plain film radiographs (sunburst: variable ossification of the soft tissue mass in a radial pattern, formation of codman's triangle ,pathlogic fracture) * MRI of the entire length of the involved long bone is superior to CT * CT is the best modality to evaluate the chest for metastatic disease * radionuclide bone scan and/or PET scan for whole body staging * **BIOPSY is required for definitive diagnosis**

Question 43

* increasing evidence supports a mesenchymal progenitor cell origin * nonrandom chromosomal translocations that involve breakpoints * **2nd most common primary bone malignancy** * 200 new diagnoses per year, peak incidence in children 10-15 years * males > females * **caucasian**

Answer 43

Ewing sarcoma

Question 44

EWS clinical presentation

Answer 44

* can develop in any bony or soft tissue but **tend to develop in the diaphysis of long bones and the axial skeleton** * **localized pain or swelling of varying duration: may be mild at first but intensifies rapidly, may be aggravated by exercise, and often worse at night** * minor trauma may be the initiating event that calls attention to the lesion * constitutional symptoms: seen in 10-20% of patients and often associated with advanced disease * **fever, fatigue, and weight loss**