Peds Oncology Flashcards
Cancer mortality rates in the US
Although cancer in children is rare it is the leading cause of death by disease past infancy among children in the United States
Care for children and adolescents after cancer diagnosis
Children and adolescents who have been treated for cancer need regular follow-up care for the rest of their lives because they are at risk of late side effects that can occur many years later including second cancers
Which cancer makes up the majority of childhood cancer?
Leukemia - MC**
Leukemia pathophysiology
- results from an event in a bone marrow precursor cell which gives rise to immature progeny that have lost the capacity to differentiate and proliferate in an uncontrolled manner
- immature progeny (blasts) expand in marrow and impair normal hematopoiesis
List the leukemia types that make up the majority of childhood cancer
- Acute Lymphoblastic Leukemia (ALL)
- Acute Myeloid Leukemia (AML)
Which population has higher risk of developing acute leukemia compared to other children?
Children with Down Syndrome have 20x greater risk
- ALL: 12x risk
- AML 46x risk
Which other groups have increased risk of developing acute leukemia?
- siblings of children with leukemia
- those with genetic disorders such as:
- -neurofibromatosis
- -Li-Fraumeni syndrome
- -Fanconi’s anemia
Leukemia - common presenting s/sx
- Expanding blast population in bone marrow causes bone and joint pain
- Pallor and fatigue due to anemia
- Bruising, petechiae and bleeding due to thrombocytopenia and coagulopathy
- Fever due to infection and cytokines from leukemia
- Adenopathy, hepatomegaly and splenomegaly due to blasts migrating out of marrow
- Gingivitis/gingival hyperplasia
Lab findings in acute leukemia
-CBC
- Leukocytosis or leukopenia with or without circulating blasts
- Anemia
- Thrombocytopenia
- CBC may also be completely normal
Lab findings in acute leukemia
Coagulopathy/DIC is common in AML
Lab findings in acute leukemia
-metabolic derangement
- due to rapid cell growth and turnover
- Elevated creatinine, potassium, phosphorus and uric acid
- Elevated lactate dehydrogenase
Approaching new leukemia cases
- Need to obtain diagnosis by flow cytometry on peripheral blood or marrow
- Need bone marrow samples for cytogenetics
- Need diagnostic LP to assess CNS status
Epidemiology of Childhood ALL
**MC pediatric cancer
-Peak age 2-5 years
>90% overall survival on modern therapy regimens
ALL morphology under the microscope
Blasts are much larger than regular lymphocytes and RBCs
ALL therapy
- Majority of therapy is outpatient
- IV chemotherapy given in clinic and oral chemotherapy given at home
- CNS directed chemotherapy via lumbar puncture**
- Therapy lasts 2.5 years for girls and 3.5 years for boys
- Bone marrow transplant (BMT) reserved only for certain very high risk patients and in relapse
Define B precursor ALL
MC subtype of acute lymphoblastic leukemia (ALL)
-has the highest cure rate
How does T cell ALL present?
- Patients frequently have WBC >100K, are male (4X more than female), and >10 years old
- Anterior mediastinal mass is often present at diagnosis and can cause severe cardio-respiratory compromise so often have to make diagnosis from peripheral blood or from biopsy done under minimal sedation
What patients should make you concerned for T cell ALL?
- adolescents who present with asthma-like symptoms/respiratory distress who have never had respiratory problems or been diagnosed with asthma as a child
- asthma does not typically appear in adolescence
Acute myeloid leukemia (AML) morphology
- 15-20% of childhood leukemia
- Malignant precursors of the myeloid, monocyte, erythroid and megakaryocytic cell lineages
- MC leukemia seen in children with bone marrow failure syndromes like Fanconi’s Anemia
- Can result from exposure to chemotherapy
Which kind of AML is MC in Down Syndrome?
M7 AML - acute megakaryoblastic leukemia
Pediatric AML Therapy
- 4-5 cycles of high-dose IV chemotherapy given inpatient every 4-5 weeks
- Associated with lengthy periods of severe neutropenia and mucositis
- Remain hospitalized for most of therapy due to high risk of life threatening bacterial infections
When is bone marrow transplant considered in
- Used frequently in kids who have a sibling match, have poor response to Induction or have unfavorable cytogenetics
- Almost always used in cases due to bone marrow failure syndromes or chemotherapy exposure
Relationship between AML and Trisomy 21
- 20-30% of neonates will have Transient Myeloproliferative Disorder (TMD) and may need low dose chemo if liver of pulm dysfunction
- these neonates have 20-30% chance of developing AML
What is the MC leukemia in children with trisomy 21?
AML is MC***
- majority are M7
- is associated with better outcomes than other children with less intensive therapy and without BMT**
Define Chronic myeloid leukemia (CML)
- accounts for 1-3% of childhood cancer (20% in adults)
- most peds cases occur after 4 years old
- Myeloproliferative disorder characterized by an increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate
What is the Philadelphia chromosome?
- associated with CML
- reciprocal translocation of the long arms of chromosomes 22 and 9
- produces tyrosine kinase
CML presentation
- Very high WBC (often >100K) with small percentages of circulating blasts, myelocytes, metamyelocytes and promyelocytes
- often otherwise well appearing
- tx now includes tyrosine kinase inhibitors
Define Juvenile Myelomonocytic Leukemia (JMML)
- Rare myeloproliferative syndrome in very young children
- Increased risk in certain inherited genetic disorders:
- Neurofibromatosis type 1
- Noonan’s syndrome
- Cardio-facio-cutaneous congenital disorders
JMML Prognosis
- typically runs an aggressive clinical course
- Allogeneic BMT is only curative option
- Median duration of survival without SCT is < 12 months from diagnosis
Define lymphomas
- malignant proliferation of white blood cells derived from peripheral lymphoid tissue
- make up 15% of childhood cancers
When to Worry About Lymphadenopathy
-History
- Rapidly growing
- Stay enlarged >2 months
- No response when treated with antibiotics
- Shrinks with steroids but then grows again
- Associated fever, weight loss, fatigue
- Causing respiratory distress bad enough to consider steroids
When to Worry About Lymphadenopathy
-Physical
- Supraclavicular nodes always require more evaluation
- > 3 cm is worrisome
- Hard, immobile, non-tender or irregular are worrisome
When to Worry About Lymphadenopathy
-Labs
High LDH and uric acid are worrisome (these are signs of high cell turnover)
Radiology imaging CT vs. PET CT
CT: Look at size, location and extent
PET CT: Looks at metabolic activity
Incidence of Lymphoma by Age
- Majority of lymphomas in younger children are NHL (non-Hodgkin’s lymphoma)
- Incidence of Hodgkin’s Lymphoma increases with age
Hodgkin’s Lymphoma Presentation
- Usually painless adenopathy (80%) commonly in the supraclavicular or cervical area
- The enlarged nodes are typically firmer than inflammatory nodes and have a rubbery texture.
- Many have some mediastinal involvement at presentation (silhouette present on CXR)
Etiology of Non-Hodgkin’s Lymphoma
- Incidence increases steadily with age
- Most commonly in the second decade of life
- Most frequent malignancy in children with AIDS
- Several subtypes in children:
- Lymphoblastic Lymphomas
- Burkitt’s Lymphomas
- Large Cell Lymphomas
- Tx: generally just chemo without radiation
Presentation of lymphoblastic lymphoma
- a subtype of non-Hodgkin’s lymphoma
- frequently initially presents with “asthma” (~75% present with anterior mediastinal mass)
- 85-90% are Precursor T-Cell Origin
Burkitt’s Lymphoma Endemic form
- primarily in Africa
- Associated with EBV infection
- Majority localized to Jaw or Head/Neck
Burkitt’s Lymphoma Sporadic Form
- MC in United States
- No clear association with EBV
- ~ 90% are intra-abdominal
Burkitt’s Lymphoma presentation
- Most rapidly growing lymphoma
- Frequently have electrolyte issues at presentation
Large Cell Lymphomas Etiology
B lineage LCL:
- Similar to Burkitt’s Lymphoma but more indolent (slower presenting)
- Most often localized, frequently involves the mediastinum
T-lineage LCL (rarer):
- Anaplastic LCL
- Peripheral T-cell lymphomas
Childhood brain tumors
- 2nd MC cancer in children
- Children have more low-grade gliomas and embryonal tumors while adults have more high-grade gliomas and meningiomas
- Nearly 2/3 of pediatric brain tumors are infraratentorial while the majority of adult brain tumors are supratentorial
Symptoms of Increased Intracranial Pressure
- Headache and vomiting
- -Mainly in the mornings and then improves**
- -No associated diarrhea
- Bulging fontanelle
Cushing’s Triad in increased intracranial pressure
*signals impending herniation Triad is: -Hypertension -Bradycardia -Abnormal Respirations
Imaging for CNS tumors
MRI is best tool for localization especially for cerebellum and brain stem tumors
Metastases in Solid Tumors
Lungs are the most frequent sight of metastatic disease
General Approach to Solid Tumor Therapy
Chemotherapy:
- Shrink primary tumor to make surgical resection more feasible
- Treat microscopic and radiographic metastatic disease
Surgery and/or radiation
-For local control of primary tumor site
Surgery and/or radiation to metastatic sites
Common types of abdominal tumors in children
- Neuroblastoma
- Wilms Tumor
- Hepatoblastoma
Common presenting symptoms in abdominal tumors
- Abdominal pain and distension
- Constipation
- Vomiting and weight loss
- Hematuria
- Jaundice
OR
asymptomatic with mass incidentally discovered by family member or PCP
Define Beckwith-Wiedeman Syndrome
- complex multi-genic disorder
- require screening as young children with abdominal ultrasound
- increased risk of abdominal tumors
Beckwith-Wiedeman Syndrome Clinical Features
- Macroglossia
- Macrosomia
- Hemihypertrophy
- Omphalocele
- Neonatal hypoglycemia
Neuroblastoma Etiology
1 extra cranial solid tumor in children**
- Median age at diagnosis is 22 months (MC cancer diagnosed in infancy)
- Primary tumors occur in abdomen (65%) and along thoracic or cervical spine (sympathetic chain)
Neuroblastoma Presentation
- S/sx depend on location
- Abdomen (fullness, fixed/hard mass)
- Cervical/high thoracic (Horner syndrome - ptosis, miosis, anhydrosis- SVC syndrome, spinal cord or nerve root compression)
- Orbital mets (proptosis and periorbital ecchymoses - Raccoon eyes)
- Bone and bone marrow (Pain and cytopenias)
Neuroblastoma Evaluation
Masses frequently have calcifications
Neuroblastoma Risk Factors
-Age
< 18 months age at diagnosis is favorable while > 18 months age at diagnosis is unfavorable
Wilms Tumor Etiology
- MC renal tumor in children
- most cases are unilateral, but some are bilateral
- 10-15% of cases are in children with congenital anomalies
Wilms Tumor Presentation
- Palpable abdominal mass
- Most common presentation
- Often asymptomatic and incidentally noted while bathing child
- Hematuria
- HTN
- Obstipation, weight loss (less common)
Wilms Tumor on CT
shows “claw sign”
Renal Cell Carcinoma (RCC) Etiology
- 5-6% of pediatric renal neoplasms
- Makes up 2/3 of renal tumors in 15-19 year olds
- MC adult renal cancer
Hepatoblastoma Etiology
- Third MC intra-abdominal neoplasm
- 66% of hepatic malignancies in age <20 years
- 91% of patients are < 5 years age at diagnosis
Hepatoblastoma risk factors
- Prematurity and low birth weight (<2500 grams) is associated with increased risk
- Elevated alpha-fetoprotein in >90% of cases
Hepatoblastoma Therapy
- Surgery alone is an option for resectable pure fetal histology tumors
- Majority require chemotherapy in addition to surgery
Hepatocellular Carcinoma Etiology
> 95% of liver tumors in age >15 years
-Elevated alpha-fetoprotein in 75-80% of cases
Soft Tissue Sarcomas in Children
-Presentation
- pain +/- associated soft tissue mass
- Pelvic tumors: Urinary and stool retention or incontinence
- Chest/rib tumors: respiratory distress
- Orbital tumors: Proptosis
- Biliary tract: Jaundice
- Can present with pathologic fracture due to minimal trauma
- Can have diffuse pain due to metastatic disease
Osteosarcoma Etiology
- MC malignant bone tumor
- Predilection for metaphyseal portion of growing bones:
- -Distal femur
- -Proximal tibia
- -Proximal humerus
Osteosarcoma Therapy
- Chemotherapy x10 weeks followed by resection of primary tumor
- Amputation vs limb salvage
- Try to remove metastatic disease as well if possible
- No role for radiation
Ewing Sarcoma Etiology
- Second MC malignant bone tumor
- MC sites:
- -Pelvic bones
- -Diaphysis of long bones of legs
- -Chest wall and rib
- Predilection for Caucasians (6x> African Americans)
Ewing Sarcoma Therapy
- Chemotherapy
- Local control to primary tumor site (surgery, radiation or both)
- Radiation to metastatic sites
- poor prognosis in metastatic disease
Rhabdomyosarcoma Etiology
- Malignant muscle tumor
- 3% of childhood cancer
- MC in Caucasians
- Most occur sporadically but may arise with NF1 and Li-Fraumeni
Rhabdomyosarcoma Therapy
- Chemotherapy
- Local Control
Germ Cell Tumors
- 3% of childhood cancer
- Arise from primordial cells involved in gametogenesis
- Increased risk with Turner’s and Klinefelter’s syndromes as well as cryptorchidism
Germ Cell Tumor Presentation
-Testicular
- Irregular, non-tender mass
- Often mistaken for epididymysis
Common Complications of Chemotherapy
- Bone marrow suppression
- -Require blood product transfusions
- -Increased risk of infection when neutrophil count is low
- GI symptoms
- -Nausea/Vomiting, Constipation, Mucositis
- Liver and renal toxicity
- Alopecia
- Myositis
- Neurotoxicity
Long Term Effects of Cancer Therapy
- Cardiac dysfunction
- Renal dysfunction
- Liver dysfunction
- Infertility
- Abnormal growth
- Osteoporosis
- Secondary malignancies
- Neurocognitive dysfunction
Define Tumor Lysis Syndrome
- Release of intracellular contents by rapid tumor cell death
- Hyperphosphatemia and hyperuricemia can lead to renal stones and renal insufficiency
- Hyperkalemia can result from cell death as well as renal insufficiency
- -Can cause cardiac arrhythmias which can be fatal
*Can be present at diagnosis or immediately after starting therapy
List the Mediastinal Masses That can Cause Cardio-Respiratory Compromise
-Superior Vena Cava Syndrome (SVCS): tumor can compress SVC resulting in impaired venous return and stasis
- Superior Mediastinal: syndrome (SMS)
SVCS with airway compromise
Presentation of mediastinal masses
- Swelling, plethora and cyanosis of face/upper extremities
- Cough, dyspnea, orthopnea, wheezing, and stridor worse when supine
Management of SVCS / SMS
- Avoid sedation and general anesthesia**
- Can cause decreased respiratory drive, increased peripheral vasodilation & decreased venous return
- Difficult to intubate past obstruction
Spinal Cord Compression Etiology
- Ewing Sarcoma
- Neuroblastoma
- Rhabdomyosarcoma
- Lymphoma/leukemia
- rare in kids, many aren’t picked up on xray
- any compromise of the spinal cord, conus medullaris, or cauda equina requires emergent attention
S/Sx of Spinal Cord Compression
- Local or radicular pain >80% of cases
- Weakness / Sensory loss / Paresis
Disseminated Intravascular Coagulation (DIC)
-Pathophysiology
- increased circulating thrombin and plasmin results in:
- -Consumption of platelets, clotting factors
- -Microangiopathy
- -Hyperfibrinolysis
- -Clinically, results in microthrombi and bleeding
Disseminated Intravascular Coagulation (DIC)
-Labs
- increased PT/INR
- increased PTT
- increased D-Dimer
- decreased Fibrinogen
- decreased Platelets
DIC Management
- Replace consumed factors
- Suppress / attenuate underlying cause:
- -Leukemia: start chemotherapy**
- -Sepsis: broad spectrum antibiotics
Platelet Transfusion Guidelines
Well appearing: transfuse if < 5K
Mucosal bleeding or Febrile: transfuse if < 20K
Extensive mucosal or internal bleeding: transfuse if < 50K
Fever During Treatment
ANC < 500: immediately give very broad spectrum antibiotics like Cefepime, Ceftazadime or Zosyn and
ANC >500: Can discharge home if looking well
Fever & Severe Neutropenia
Must be hospitalized***
Discharge criteria (before ANC >500/mm3):
-WBC and ANC rising to at least ANC 100
-Afebrile for >24 hours
-No significant or persistently positive cultures
-Well appearing with reliable follow-up
Define Typhlitis
- Necrotizing colitis of the cecum in neutropenic patients
- Bacterial / fungal invasion of cecal mucosa that can progress into full thickness infarction and perforation
- MC pathogens: Clostridium, Pseudomonas & E. Coli
Typhlitis on examination
- Abdominal pain is the most persistent sign on exam
- Fever, hypotension, tachycardia
- Hematochezia / hematemesis
- Abdominal distension, obstruction, ileus
Typhlitis on imaging
shows pneumotosis intestinalis (air bubbles in the bowel wall) or non-specific thickening of the bowel wall
Define Pneumocystis jiroveci/carinii
Ubiquitous fungus that causes interstitial pneumonia in immunocompromised patients
Pneumocystis jiroveci/carinii on physical exam
- Non-productive cough
- Hypoxia, Dyspnea, Tachypnea
Pneumocystis jiroveci/carinii imaging
- Bilateral reticular infiltrates
- “Angel Wings” appearance on CT
Define Varicella Zoster (Shingles)
Vesicular rash that follows a dermatome
Causes of Varicella Zoster
- Re-activation of past infection
- New exposure to Varicella
- Getting vaccine while immunocompromised
Live vaccines and chemotherapy
Avoid live vaccines until 1 year from the end of chemotherapy**
Vaccinations During Treatment
- Hold all vaccines during therapy except inactivated seasonal flu vaccine
- Continue to vaccinate family members*
- Safe to administer live vaccines to siblings but advise patient not to change diapers
- Resume vaccinations 6 months after therapy
