Heme onc Flashcards
fever of unknown origin (FUO)
-daily temp >100.4F (38C) lasting for > 14 days w/o obvious cause, or…
-Fever documented by HCP that cause could not be identified after > 8 days of work-up
-Must differentiate persistent fever from recurrent/periodic fevers (serial acute illnesses)
-Infections are MCC of FUO in children (40-50%) -> inflammatory ds (20%) -> malignancy (10%)
-Approx 15% of kids with FUO have no dx
-Fever eventually resolves in many cases w/o sequelae
FUO work up
-H&P with few screening lab tests
-labs/imaging guided by initial eval
-consult with ID, immunology, rheum, oncology etc
-strep/throat culture
-UA/culture
-TB skin test/HIV
-lumbar puncture
-CXR
-rheumatic ds work up
-blood work
-PET scan (head, chest, abdomen)
-stool culture
-bone marrow bx (cytology, culture)
anemia
-Nutritional causes: ask dietary intake
-Underlying illness: Eval growth and development, sx of chronic ds/malabsorption, or manifestations of blood loss
-Hemolytic ds: Hx of jaundice or family hx of anemia, jaundice, gallbladder ds, splenomegaly, or splenectomy
-Child’s ethnicity may suggest hemoglobinopathies or red cell enzyme deficiencies
-Poor growth- chronic ds/hypothyroidism
-Congenital anomalies- anemias
-Petechiae/purpura (leukemia, aplastic anemia, HUS), jaundice (hemolytic disease), generalized lymphadenopathy, splenomegaly (leukemia, sickle syndromes, hereditary spherocytosis, liver disease, hypersplenism), chronic/recurrent infections
anemia: lab workup
-CBC w/ diff and platelet count
-peripheral blood smear
-reticulocyte count
-MCV to determine micro/normo/macrocytic
-microcytic -> trial of iron -> if fails -> further workup
-normo/macrocytic -> reticulocyte count + peripheral smear
iron deficiency anemia
-ID- Insufficient iron to maintain normal functions such that iron stores are reduced
-IDA- Hemoglobin > 2 SDs below normal for age and gender, secondary to ID
-Normal term infants are born with sufficient iron stores to prevent ID x 4 months
-Premature infants, LBW, neonatal anemia, perinatal blood loss, hemorrhage – reduced iron stores
-Breast milk is low in iron relative to cow’s milk and fortified formulas
-Exclusively breast-fed children should receive 1 mg/kg/day of supplemental iron x 6 months of age
-Pallor, fatigue, irritability
-Hx of pica is common
-Assoc with increased lead absorption – neurotoxicity
IDA dx and tx
-According to AAP -> screening for anemia at 12 months with hemoglobin concentration and review of RF
-Risk factors: Low socioeconomic status, premature/LBW, exclusively breast-fed > 4 mo w/o iron supplementation, lead exposure, weaning to whole milk or complementary foods low in iron, feeding/growth problems, inadequate nutrition
-Hmg < 11 = high-risk ID –> iron eval performed (iron saturation, ferritin, CRP, reticulocyte hemoglobin concentration)
-Tx:
-Hmg 10-11 at screening: Closely monitored/empirical tx with iron supplementation and a re-check in 1 mo
-If ID/IDA: PO iron 3 mg/kg/day x 3 mo
-Iron supplementation results in an increased reticulocyte hemoglobin x 48 hrs; maximal between 5-7 days
-Rise in hemoglobin of 1 or more g/dL after 1 mo is a good response
-Therapy continued x 3 months to replenish stores of iron
-Parenteral iron for those with CKD and erythrocyte stimulants
-May be indicated for those with celiac or IBD as well
megaloblastic anemia
-Macrocytic anemia
-caused by low cobalamin (B12), red cell folic acid, or both
-Cobalamin deficiency
-MCC in kids is intestinal malabsorption (Crohn, chronic pancreatitis, bacterial overgrowth of small bowel, parasites)
-Inadequate dietary intake: Infants breast-fed by vegan moms or moms with pernicious anemia, or in kids fed diets with no to little animal foods
-older children- Parasthesias, weakness, unsteady gait, decreased vibratory/proprioception on neuro exam
-Folate deficiency
-Inadequate dietary intake, malabsorption (Celiac), increased folate requirements (times of rapid growth), or a combination
-Medications like anti-convulsants and cytotoxic drugs
-Pallor and mild jaundice
-Smooth, beefy red tongue
-Dx:
-high MCV and MCH, normal WBC and platelet count
-Blood smear: Macro-ovalocytes with anisocytosis and poikilocytosis
-CD: Low B12 level versus normal; elevated methylmalonic acid (MMA)
-FD: Red cell folate best reflection of folate stores; elevated MMA and homocysteine
-Tx: PO supplementation
thalassemia
-At birth, predominant hemoglobin is fetal (2 alpha/2 gamma chains)
-Gamma globin production decreases and B-globin increases (two alpha/two beta), so adult hemoglobin predominates after 2-4 months of age
-Alpha-thalassemia presents in newborn + later in life
-Beta-thalassemia/SCD asymptomatic during first 3-4 months
alpha thalassemia
-Deletion of 1 or more of the 4 alpha-globin genes
-African, Mediterranean, Middle Eastern, Chinese, Southeast Asian descent
-Sx depend on # of alpha-globin genes deleted
-Tx:
Silent carriers/trait: No treatment
Hemoglobin H disease: Supplemental folic acid and avoid same oxidant drugs that cause hemolysis in those with G6PD; possible transfusion of RBCs during period of infection
beta thalassemia
-Mutation of B-globin genes (2) resulting in damage to RBCs, causing ineffective erythropoiesis and hemolysis
-African, Mediterranean, Middle Eastern, Asian descent
-Classified into non-transfusion-dependent (used to be minor) or transfusion dependent (used to be major)
-NTD: Asymptomatic with normal PE versus mild-moderate anemia
-TD: Significant anemia during the 1st year of life
-If not identified early > poor growth, massive hepatosplenomegaly, enlargement of medullary space (facial deformities of forehead and maxilla), possible death from cardiac failure
beta thalassemia dx and tx
-DONT NEED TO KNOW DX except…
-NTD:
-Normal screening tests; subsequent decreased MCV with or without anemia of varying severity
-Blood smear: Hypochromia, target cells, basophilic stippling
-Hb electrophoresis diagnostic (6-12 months): Levels of hemoglobin A/F or both are elevated
-TD:
-Adult hemoglobin absent on neonatal screening
-Severe anemia after first few months of life -> transfusion dependent
-Blood smear: Severe hypochromic, microcytic anemia with marked anisocytosis and poikilocytosis; target cells
-!!Hb 5-6 g/dL or less (JUST KNOW THIS), reticulocyte count elevated, WBCs/platelets increased, unconjugated bilirubin elevated
-Tx:
-NTD: Supplemental folic acid
-TD:
-Temporary versus chronic transfusions to maintain Hb at 9.5-10.5 g/dL (with iron chelation)
-Hematopoietic stem cell transplant is curative and best performed < 14yo and development of hepatomegaly/portal fibrosis
sickle cell ds
-Sickle (S) hemoglobin is a consequence of a change in the sixth chain of the B-globin (valine substituted for glutamic acid)
-Polymerization of Hb S distorts erythrocyte morphology, decreases RBC deformability, causes hemolysis/marked reduction in RBC lifespan, increases blood viscosity, predisposes to inflammation/coagulation activation/episodes of vaso-occlusion
-Occurs in about 1/400 African American and 1/1200 Hispanic-American infants
-8% of African Americans are heterozygous carriers (trait)
-PE is normal at birth, sx unusual before 3-4 months
-Moderate-severe hemolytic anemia by age 1: Pallor, fatigue, jaundice, and predisposes to gallstones during childhood/adolescence
-Intense congestion of spleen with sickled cells > splenomegaly > functional asplenia > risk of infection with encapsulated bacteria (pneumococci)
-Acute exacerbations of anemia with aplastic crises from infection with human parvovirus B19 and other viruses
-Dactylitis is MC sx in 50% of children with sickle cell anemia prior to 3yo
-Recurrent episodes of abdominal/musculoskeletal pain
-Overt strokes in 11% of children (without transfusions)
-Acute chest syndrome: Respiratory symptoms, new pulmonary infiltrate caused by infection, infarction, or fat embolus from ischemic bone marrow
sickle cell disease dx and tx
-Most infants with sickle hemoglobinopathies born in U.S. are identified by universal neonatal screening
-Baseline Hb of 7-10 g/dL, elevated reticulocyte count
-Anemia is normocytic or macrocytic with sickle cells + target cells on peripheral blood smear
-Hemoglobin electrophoresis and HPLC and/or DNA analysis for def dx
-Tx:
-Daily prophylactic PCN: Initiated by 2 mo and continued to 5 years
-Pnuemococcal -> conjugate/polysaccharide vaccines to all children
H. influenzae and meningococcus as well
-Illnesses with fever > 38.5C: Prompt evaluation, bacterial cultures, parenteral broad-spectrum antibiotics, careful inpatient/outpatient observation
-Daily administration of oral hydroxyurea beginning at 9 months of age
-Other FDA-approved drugs: L-glutamine, crizanlizumab, voxeletor (dont need to know)
-Painful vaso-occlusive events: Fluids, correction of acidosis (if present), !analgesia, maintenance of normal oxygen sat!, tx of infections
-RBC transfusions for acute events: Stroke, ACS, multiorgan failure (pre-operative, as well)
-Human stem cell transplant can cure SCD
bleeding disorders: idiopathic thrombocytopenic purpura (ITP)
-MC bleeding disorder of childhood
-Often follows infection with viruses (rubella, varicella, measles, parvovirus, influenza, EBV, or HIV)
-Thrombocytopenia from clearance of circulating IgM/IgG-coated platelets by reticuloendothelial system
-Most patients recover spontaneously x several months
-Acute appearance of multiple petechiae and ecchymosis
-Epistaxis and gingival bleeding are common
idiopathic thrombocytopenic purpura (ITP) dx and tx
-Blood:
-Platelet count markedly reduced (< 50,000/uL and often < 10,000/uL)
-Large platelets in blood smear (accelerated new platelet production)
-WBC/differential and Hb usually normal
-PT and aPTT normal
-Bone marrow: Megakaryocyte hyperplasia with normal erythroid and myeloid cellularity
-Complications
-Severe hemorrhage and bleeding
-RF: Platelets < 10,000/uL and mean platelet volume < 8 fL
-Tx:
-Observation for most children in the absence of bleeding, regardless of platelet count
-Avoiding NSAIDs, physical activities
-Corticosteroids
-IVIG is treatment of choice for severe, acute bleeding (alternative or adjunct to corticosteroids)
-Anti-Rh(D) IG: Binds to D antigen on RBCs > spleen clears anti-D-coated RBCs versus platelets -> Only effective for Rh (+) patients
-Splenectomy:
-Considered after persistence x 12 months and failure of preferred/alternative second-line treatments
-Thrombopoietin receptor agonists (eltrombopag, romiplostim); FDA-approved for > 12 months
-Typically postponed to > 5 years of age if possible
-Complete response in 70%, partial in 20%
-Prognosis:
-80% remission
-Tx with combination steroid and IVIG better remission rates at 12 and 24 months than either alone
bleeding disorders: hemophilia A/factor V3 deficiency
-X-linked disorder, predominantly in males (1:5000 male births)
-Mild: Bleeding at times of trauma/surgery
-Moderate: Treated as severe
-Severe: Frequent, spontaneous bleeding episodes involving the skin, mucous membranes, joints, muscles, and viscera
Most significant: Recurrent hemarthroses that incites joint destruction and the sequelae of intracranial hemorrhage
Laboratory findings
-Prolonged aPTT, normal PT
-Dx confirmed by a decreased FVIII activity with normal vWF activity
-Complications:
-Intracranial hemorrhage is the leading disease-related cause of death
-Most are spontaneous, not assoc with trauma
-Hemarthroses > joint destruction
-Muscular hematomas > compartment syndrome
-Tx:
-Goal is to increase FVIII activity and prevent/stop bleeding
-Administration of exogenous FVIII
-Prophylactic infusions prevent development of arthropathy in severe/moderate hemophilia (standard of care in pediatric hemophilia)
hemophilia B/Christmas ds/Factor 9 deficiency
-Same inheritance pattern as A, 15-20% as prevalent
-Laboratory findings: Prolonged aPTT, normal PT and thrombin time; diagnosis confirmed by assaying FIX activity
-Treatment: Exogenous FIX
Von Willebrand ds
-MC inherited bleeding disorder among Caucasians (prevalence 1%)
-Can also be acquired: Hypothyroidism, Wilms tumor, cardiac/renal disease or SLE, valproic acid therapy
-Sx- Mucocutaneous bleeding, bruising, epistaxis
-Dx- Prolonged aPTT (decreased FVIII), normal PT with confirmatory lab testing
-Tx: Desmopressin acetate IV/SC (releases vWF from endothelial stores)
Bleeding disorders: Vitamin K deficiency
-Newborn period characterized by physiologically depressed activity of the vitamin K-dependent factors (II, VII, IX, and X)
-If vitamin K not administered at birth, bleeding diathesis, called vitamin K deficiency bleeding (VKDB) may develop
-1/3 patterns:
-1. Early (within 24 hours of birth):
-Cephalohematoma, IC hemorrhage, intra-abdominal bleeding
-Commonly associated with maternal ingestion of drugs that interfere with vitamin K metabolism (warfarin, phenytoin, isoniazid, and rifampin)
-2. Classic (24 hours to 7 days):
-GI, skin, or mucosal bleeding
-No vitamin K at birth, solely breast-fed
-3. Late (> 8 days):
-IC, GI, or skin bleeding
-Fat malabsorption or alterations in intestinal flora
-Breast-fed infants
vitamin K deficiency dx and tx
-Diagnosis:
-Prolonged PT out of proportion to aPTT (also prolonged), prolonged thrombin time (over time), normal platelets
-Confirmed by demonstration of noncarboxylation of specific clotting factors in absence of vitamin K/clinical and lab responses to vitamin K
-Treatment:
-IV or subcutaneous vitamin K
-Severe bleeding may require FFP or PCCs (prothrombin complex concentrates)
immunoglobulin A vasculitis/Henoch Schonlein Purpura (HSP)
-MC type of small vessel vasculitis in children; boys 2-7 years of age
-URI precedes diagnosis in 2/3 of children
-Antigens from GABHS, viruses, drugs, foods, and insect bites have been proposed as inciting factors
-Small vessels of skin, GI tract, and kidneys MC affected
-Skin: Urticarial > maculopapular > symmetrical, palpable, purpuric rash on legs, buttocks, and elbows
-Migratory polyarthralgia or polyarthritis (ankles/knees)
-Intermittent, sharp abdominal pain (50% of patients)
-Renal involvement in 2nd-3rd weeks with nephritic or nephrotic picture, often with high BP (25-50% of patients)
-Intussusception, hemorrhage/edema of small intestine, testicular torsion, neurologic symptoms also associated
immunoglobulin A vasculitis/Henoch Schonlein Purpura (HSP)
-Dx:
-Platelets normal/elevated, other screening tests of hemostasis and platelet function are normal
-UA with hematuria, sometimes proteinuria
-Stool with occult blood possible
-ASO titer elevated and throat culture positive for group A B-hemolytic streptococci
-Serum IgA may be elevated
-Treatment/Prognosis:
-Supportive, NSAIDs, corticosteroids
-If ASO titer elevated or + strep culture – PCN
-Good prognosis: Recurrence of symptoms in 25-50%, progressive renal failure in < 5%
bone marrow hematopoiesis review
neutropenia
-Absolute neutrophil count of < 1500/uL in childhood, or < 1100/uL between 1 mo - 2 years
-Results from absent/defective myeloid stem cells, ineffective/suppressed myeloid maturation, altered production of hematopoietic cytokines or chemokines/abnormalities in their receptors, decreased marrow release, increased neutrophil apoptosis, or destruction/consumption
-Diminished delivery of cells to areas where balance favors bacterial proliferation/invasion
-Severity characterized by level of peripheral neutrophils, number/severity of infections, production of mature neutrophils
-Associated with storage/metabolic diseases, immunodeficient states, and other disorders
-MCC include viral infection or drugs (decreased neutrophil production in marrow), increased peripheral turnover, or both
neutropenia
-Acute bacterial or fungal infection is the most significant complication of neutropenia
-MC infections: Septicemia, cellulitis, skin abscesses, PNA, and perirectal abscesses
-S. aureus and gram-negative bacteria MC pathogens
-Other significant problems (chronic neutropenia): Sinusitis, aphthous ulcers, gingivitis, and periodontal disease
-Sx: Chills, fever, malaise
-Dx:
-Neutrophils are absent or markedly reduced in the peripheral blood
-Monocytes and lymphocytes normal, RBCs/platelets not affected
-Bone marrow with normal erythroid series, adequate megakaryocytes, but marked reduction in myeloid stem cells
-If acquired cause (viral/drug) is not obvious:
-WBC counts/differential, platelet, reticulocytes twice weekly x 6 weeks
-BM bx with cytogenetic analysis
-Other tests: Neutrophil Ab, Ig levels, ANA, lymphocyte phenotyping (to detect immunodeficiency states); genetic analysis
-Tx:
-Underlying disorders should be identified and treated or associated agents should be eliminated
-Infections assessed/treated
-Prophylactic antimicrobial therapy is not indicated for afebrile, asymptomatic patients
Recombinant granulocyte-colony-stimulating factor (G-CSF) SC/IV QD -> Pts with neutrophil counts of 500 uL or less
-Immunization
-Hematopoietic stem cell transplant
Acute lymphoblastic Leukemia (ALL)
-MC malignancy of childhood (25% of all cancer diagnoses in patients < 15 years)
-Peak age of onset is 4 years; 85% of pts dx between 2-10 years
-Trisomy 21 – 10-20x increase in overall rate of leukemia
-Uncontrolled proliferation of immature lymphocytes -> Unknown cause, genetic factors may play a role
-Presence of > 25% malignant hematopoietic cells (blasts) in bone marrow aspirate
-> 70% of children receiving aggressive combination chemotherapy and early pre-symptomatic treatment to CNS are cured of ALL
ALL sx
-Complaints related to decreased production of RBCs, WBCs, or platelets and to leukemic infiltration of extramedullary sites
-Intermittent fevers, bruising/pallor, bone pain (pelvis, back, legs)
-Physical ranges from normal to highly abnormal
-Pallor, petechiae, purpura
-Hepatomegaly/splenomegaly in > 60% of patients
-Lymphadenopathy, testicular enlargement, SVC syndrome (mediastinal adenopathy), tachypnea/orthopnea/respiratory distress (mediastinal mass), CN palsies (leukemic infiltration), leukemic infiltration/hemorrhages of optic fundi, flow murmur/tachycardia (anemia)
ALL: work up
-Labs:
-CBC w/ diff is most useful
-95% of patients have a decrease in at least one cell type (neutropenia, thrombocytopenia, or anemia)
-WBC count is low or normal (50% of patients), with neutropenia (< 1000 uL)
-Peripheral smear: RBC abnormalities (teardrop shapes)
-Uric acid/LDH elevated as a result of cell breakdown
-Bone marrow bx: Infiltration of leukemic blasts replacing normal marrow
-Imaging
-CXR: Mediastinal widening/mass, tracheal compression due to lymphadenopathy or thymic infiltration
-AUS: Kidney enlargement, intra-abdominal adenopathy
-Plain films of long bones/spine: Demineralization, periosteal elevation, growth arrest lines, compression of vertebral bodies
ALL: tx/prognosis - DONT NEED TO KNOW ANY MEDS
-Induction (1st month) – > 95% of pts exhibit remission (on BM aspirates by morphology)
-PO prednisone/dexamethasone, IV vincristine, with or without daunorubicin, asparaginase, and intrathecal methotrexate
-Consolidation:
-Intrathecal CTX with continued systemic therapy and sometimes cranial radiation therapy
-Several months of intensive CTX follows consolidation (intensification)
-Maintenance:
-QD, PO mercaptopurine, weekly PO methotrexate, pulses of IV vincristine and PO prednisone or dexamethasone
-Intrathecal methotrexate with or without cytarabine/hydrocortisone q 2-3 months
-Tumor lysis syndrome should be anticipated when treatment is started
-Hyperkalemia, hyperuricemia, and hyperphosphotemia
-Maintaining UOP with IV fluids treating with PO allopurinol
-Hyperleukocytosis (with hyperviscosity and respiratory distress, AMS): Leukopheresis
-During tx, fever/neutropenia requires prompt assessment – blood cultures/treatment with empiric broad-spectrum abx
-Prophylaxis for Pneumocystis jirovecii (trimethoprim-sulfamethaxzole)
-Cure rates depend on specific prognostic features present at diagnosis, biologic features of leukemic blast, and response to therapy
-Most important features: WBC count and age
-Ages 1-9 with WBC count < 50,000 uL – survival rate > 90% range
-Ages > 10 - ~ 88%
acute myeloid leukemia (AML)
-Accounts for 25% of all leukemias in children/adolescents, but is responsible for 1/3 of deaths in same age groups
-RF: Congenital, acquired (ionizing radiation, cytotoxic CTX agents, benzenes)
-Aggressive induction therapy results in 75-85% remission rate
-Anemia (44%), thrombocytopenia (33%), and neutropenia (69%)
-Hyperleukocytosis: Venous stasis, sludging of blasts in small vessels (hypoxia, hemorrhage, infarction)
-CNS leukemia present in 5-15% of patients at diagnosis (higher than ALL)
lymphomas
-Malignant proliferation of lymphoid cells, usually arising from lymphoid tissues (lymph nodes, thymus, spleen)
-Accounts for 10-15% of all childhood malignancies
-MC form is Hodgkin disease (50% of all cases)
-Remaining subtypes referred to collectively as non-Hodgkin lymphoma (NHL)
hodgkin lymphoma sx and labs
-Better response to treatment than adults, 5- to 10-year overall survival rate of > 90%
-15% of cases occur in children < 16 years (3% < 5 years)
-4:1 male to female predominance in first decade
-Painless cervical lymphadenopathy
-Firm, rubbery texture; not fixed to surrounding tissues; variable growth rate
-Bx: Lack of identifiable infection in region drained by the enlarged node, > 2 cm in size, supraclavicular/abnormal CXR, lymphadenopathy increasing in size after 2 weeks or failing to resolve within 4-8 weeks
-Constitutional symptoms (33%): Fever, weight loss of 10% in prior 6 months, drenching night sweats (Ann Arbor staging)
-Asymptomatic mediastinal disease (adenopathy, mass) in 50% of patients: Symptoms with compression of vital structures
-Labs: CBC usually normal (although anemia, neutrophilia, eosinophilia, and thrombocytosis many be present), ESR and other acute phase reactants often elevated
hodgkin lymphoma: staging, pathologic findings, tx
-Staging:
-Ann Arbor classification utilized for staging (determines tx and prognosis)
-Search for ds w/ CT scan of neck, chest, abdomen, and pelvis, as well as PET scan (with or w/o bone marrow bx)
-Pathologic Findings:
-Histologic findings of Reed-Sternberg cell (germinal-center B cells with malignant transformation)
-Nearly 20% tumors in developed countries are positive for EBV
-Treatment/Prognosis:
-Based on stage, presence of B symptoms, tumor bulk, and number of involved nodal regions
-Chemotherapy and/or immunotherapy alone – less often by radiation therapy
-Overall 5-year survival rate of 90-95% in children with Stages I and II (slightly lower in Stages III and IV)
-2/3rds of all relapses within 2 years after diagnosis, relapse rarely beyond 4 years
non-hodgkin lymphoma
-Diverse group of cancers accounting for 5-10% of malignancies in children < 15 years of age
-Incidence increases with age, 3:1 male predominance
-In equatorial Africa, NHLs cause ~50% of pediatric malignancies due to EBV and associated Burkitt lymphoma
-Children with congenital or acquired immune deficiencies have 100-10K x greater risk than that of age-matched controls
-Virtually all childhood NHLs are rapidly proliferating, high-grade, diffuse malignancies; very responsive to tx though
-Arise at any site of lymphoid tissue as well as extra-lymphatic sites (bone, bone marrow, CNS, skin, and testes)
-S&S determined by location of lesions and degree of dissemination
-Syndromes correlate to cell type: (dont need to know)
-Lymphoblastic lymphoma (LL): Airway compression symptoms, SVC syndrome
-Small noncleaved cell lymphoma (BL/BLL): Abdominal distention, RLQ mass, intussusception at age > 5 years; bone marrow involvement common; TLS
-Large B-cell lymphoma (LBCL): Similar to BL/BLL
-Anaplastic large cell lymphoma (ALCL): Skin lesions, focal neurologic deficits, and pleural/peritoneal effusions without obvious mass
non-hodgkin lymphoma dx and tx
-Dx:
-Bx of involved tissue with histology immunophenotyping, and cytogenetic studies
-CBC, LFTs, and biochemical profile -> Elevated LDH reflects tumor burden
-CXR, CT scan of neck/abdomen/pelvis, PET scan
-Bone marrow and CSF exams
-Treatment/Prognosis
-Management of life-threatening problems at presentation is critical -> Acute TLS, SVC syndrome, airway compromise, cardiac tamponade
-Systemic CTX
-Intensive intrathecal CTX for CNS prophylaxis x 3-9 months
-LL: Treatment protocols for ALL x 2 years
-BL/BLL, LCBL, ALCL: Alkylating agents/methotrexate
-Prognosis based on extent of disease at diagnosis
-90% of pts with localized disease – long-term, disease-free survival
-Disease on both sides of diaphragm, CNS involvement, or BM involvement (in addition to primary site) – 70-80% failure-free survival rate
-Relapses early – may have chance for cure with HSCT
brain tumors
-MC solid tumors of childhood, often misdiagnosed or diagnosed late
-Range from low-grade lesions to high-grade tumors with dissemination
-Cause unknown: Genetic predisposition; children who received cranial irradiation for treatment of meningeal leukemia
-Infratentorial tumors (typically younger than 2):
-Symptoms: Vomiting, unsteadiness, lethargy, irritability
-Signs: Macrocephaly, ataxia, hyperreflexia, cranial nerve palsies
-Supratentorial tumors (older children):
-Headache, visual symptoms, seizures, and focal neurologic deficits (personality changes)
-Cerebellar/posterior fossa tumors: Morning vomiting
-Brainstem tumors: Facial and extraocular muscle palsies, ataxia, hemiparesis, hydrocephalus
brain tumors: imaging/staging
-MRI is imaging study of choice (with and without contrast)
-Imaging of entire neuraxis and CSF cytologic examination should be part of evaluation for those with medulloblastoma, ependymoma, and pineal region tumors
-MRI of spine for midline tumors of fourth ventricle/cerebellum
-Lumbar CSF preferred over ventricular CSF
-Biomarkers (human chorionic gonadotropin and a-fetoprotein) helpful in diagnosis and follow-up
brain tumors: classification
-2 categories (based on cell origin):
-Glial tumors: Astrocytomas, ependymomas
-Embryonal tumors: Medulloblastomas, atypical teratoid/rhabdoid (AT/RT) tumors
-Astrocytoma !!!
-MC brain tumor of childhood
-Low-grade may be curable by complete surgical excision alone
-CTX effective alone in 40-50% of low-grade cases (multiple courses often needed)
-Medulloblastoma
-MC high-grade brain tumors in children with four subgroups
-Usually occur in first decade of life (peak incidence between 5 and 10 years)
-Typically midline cerebellum with extension into fourth ventricle
-Neuraxis dissemination at diagnosis in 10-46% of patients
-Molecular classification increasingly used to determine therapy
-Brainstem tumors
-Frequently astrocytic in origin and high grade
-Long term survival rate of < 5% (with tumors that infiltrate brainstem and pons)
-Treated without tissue diagnosis (risk with bx of brainstem)
-Other brain tumors: Ependymomas, germ cell tumors, choroid plexus tumors, and craniopharyngiomas less common
brain tumors
-Tx:
-Supportive care: Dexamethasone, anti-convulsants (levetiracetam)
-Specific therapy
-Maximal safe surgical resection is preferred initial approach
-Radiation use varies/still in evolution
-Chemotherapy effective in treating low-grade and malignant astrocytomas and medulloblastomas
-Older children with malignant gliomas: Combination of above
-Prognosis:
-Low-grade astrocytomas: Five and 10-year survival rates for childhood is 60-90%
-Low-stage medulloblastoma: 10-year survival rate ~ 40-60%
-High-risk: Five-year survival rate ~ 25-40%
-Glioblastoma: Cure rates poor (survival rates < 10%)
neuroblastoma
-Arises from neural crest tissue of the sympathetic ganglia or adrenal medulla
-Small cells with scant cytoplasm and hyperchromatic nuclei (rosette pattern) -> differentiate from other “small, round, blue cell” malignancies
-7-10% of pediatric malignancies and is MC solid neoplasm outside the CNS
-50% dx < 2yo and 90% < 5yo
-Constitutional: Fever, wt loss, irritability
-PE: Firm, fixed, irregularly shaped, midline abdominal mass
-Can arise wherever there is sympathetic nervous tissue (location determines varied exam findings)
-Common metastatic sites: Bone, bone marrow, lymph nodes, liver, and subcutaneous tissue
-Skull/retrobulbar area: Periorbital ecchymosis, proptosis
-Liver: Massive hepatomegaly
-Skin: Bluish/purplish subcutaneous nodules (“blueberry muffin baby”)
-Paraneoplastic: Opsoclonus-myoclonus ataxia (“dancing eyes/dancing feet”)
-Rapid, chaotic eye movements, myoclonic jerking of limbs and trunk, ataxia, and behavioral disturbances
neuroblastoma dx, staging
-Labs: Anemia in 60%, urinary catecholamines (VMA/HVA) elevated in 90% of pts
-Imaging:
-X-rays of primary tumor may show stippled calcifications
-CT scan shows extent of primary tumor, effects on surrounding structures, and presence of metastatic ds
-MRI for determining spinal cord involvement
-PET scan for eval of bone metastases
-Staging:
-International Neuroblastoma Staging System/Risk Group
-Bx of tumor and bone marrow
-Tumors classified as favorable or unfavorable based on histologic characteristics and pt of dx (younger age -> more favorable dx)
neuroblastoma tx
-Tx based on classification of low-, intermediate-, or high-risk ds
-Low-risk: Surgical resection of more than 50% of tumor is usually sufficient for cure; survival rates 98%
-Intermediate-risk: Surgery + chemotherapy (carboplatin, etoposide, cyclophosphamide, vincristine, doxorubicin); survival rates 90-95%
-High-risk: Intensive, multimodal therapy including CTX, surgery, HSCT, irradiation, biologic therapy, and immunotherapy; 5-year overall survival rate 73%
nephroblastoma (wilms tumor)
-2nd MC abdominal tumor in children (after neuroblastoma
-5-6% of cancers in children < 15yo
-Typically sporadic; may occur in setting of other malformations/syndromes
-MC between 2-5yo, unusual after 6 yo, mean age 4
-Increasing size of abdomen or an asymptomatic abdominal mass incidentally discovered on exam/by parent
-Mass typically smooth, firm, well-demarcated, rarely crossing midline
nephroblastoma (wilms tumor) dx and tx
-Labs- CBC usually normal, possible anemia; UA with some blood/leukocytes
-Imaging/Staging
-US/CT of abdomen establishes presence of mass -> Liver, chest for metastases
-IVC evaluated via Doppler flow
-Staging at time of surgery
-Tx:
-Surgical exploration of abdomen
-Following excision, stage assigned, which defines further therapy (CTX)
-Higher stages require irradiation to tumor bed/sites of metastases
-Overall cure rate of 90% (varies based on stage)
bone tumors: osteosarcoma!!!
-6th MC malignancy in childhood -> 3rd in adolescents and young adults
-shows relationship between rapid bone growth and malignant transformation
-Metaphyses of long, tubular bones primarily affected
-Distal femur > 40% of cases; proximal tibia, proximal humerus, and mid-proximal femur following in frequency
-Pain with or w/o assoc soft tissue mass; systemic sx rare
-Labs: Possible elevation in serum alk phosphatase or LDH levels
-Imaging:
-Permeative (“moth-eaten”) destruction of normal bony trabecular pattern with indistinct margins
-Periosteal new bone formation and lifting of bony cortex may create a Codman triangle
-Soft tissue mass + calcifications in radial/sunburst pattern
-MRI > CT scan in defining primary tumor
-CT scan chest/bone scan for metastases
-MC sites of metastases: Lungs and other bony sites
-Bx of tissue for def dx
-Tx:
-Surgery + CTX (doxorubicin, cisplatin, high-dose methotrexate, ifosfamide, etoposide; prior to definitive surgery)
-Resection of tumor
-Postsurgical CTX x 1 year -> Highly radioresistant
-Localized ds – 70-75% long term survival rate
bone tumors: ewing sarcoma
-Typically in 2nd decade of life
-white males
-Small, round, blue cell malignancy
-Pain with or w/o swelling and erythema
-Fevers, wt loss
-Elevated LDH possible
-Imaging/Staging
-Similar to osteosarcoma, but involves diaphyses of long bones
-MRI of primary lesion
-CT scan essential for staging (chest) -> MC sites of metastases: Lung, bone, BM
-Bone scan, BM biopsy also essential
-Further electron microscopy, immunocytochemistry, and/or cytogenetic analysis may be necessary
-tx:
-CTX followed by local control measures (surgery, radiation)
-CTX continued x 6 months following local control (dactinomycin, vincristine, doxorubicin, cyclophosphamide, etoposide, and ifosfamide)
-Localized ds – 70-75% long-term survival rate
rhabdomyosarcoma
-MC soft tissue sarcoma of childhood (10% of childhood solid tumors)
-Peak incidence 2-5 years, M > F, 70% dx < 10yo
-anywhere in body
-Classified into subtypes based on features: embryonal RMS and alveolar RMS
-Embryonal RMS (70%): GU tract, head/neck; young children
-Alveolar RMS: Trunk and extremities; older children/adolescents
-Sx- Vary based on site affected
-Staging:
-CT and/or MRI scan
-CT of chest as well – Lungs MC site of metastasis
-Bone scan and bone marrow bx
-Treatment: (dont need to know)
-Tumor excised if feasible (CTX prior if not)
-Radiation for localized tumor control
-CTX for all patients following resection (VAC – vincristine, dactinomycin, cyclophosphamide)
-Regimen, duration determined by histology, age of patient, primary site, TNM staging, grouping classification
-Low-risk – FFS 90%, intermediate-risk – FFS 60-70%, high-risk – FFS < 20%
TEST
-growth and development -> milestones, immunization, recommended screening (lead tx/monitor), anticipatory guidance (car, sleep)
-common parental concerns- colic, teething, sleeping
-adolescence- tanner (FEMALE), anorexia/bulimia complications
-neonatal- birth injuries (cephalohematoma, caput, brachial plexus), jaundice (normal vs abnormal), respiratory distress syndrome, neck?, TORCH
-genetics- male conditions, now the big ones
-skin- VIRAL exanthems, lab findings, causes
-eyes- causes of conjunctivitis (viral, bacterial, allergic), eye injuries
-ENT- ear infections (other than OTM), pharyngitis (other than strep), rheumatic fever
-respiratory- croup tx, barking cough -> give dex, stridor at rest -> racemic epinephrine + dex, asthma (intermittent, persistent, step up?, what do we add), imaging for epiglottitis (thumb print), imaging for croup (steeple sign- narrowing of supraglottal airway), MCC for epiglottitis, croup, pertussis, MC tx for all
-cardio- MC defects, cyanotic vs acyanotic, classic CXR findings (boot shape heart- RV hypertrophy, egg on string), HTN -> lifestyle, syncope -> HX and PE
-heme onc- iron deficiency anemia, bleeding disorders (ITP, HSP), ALL, AML, lymphomas, surgical resection with chemo for solid tumors, MC solid tumors
