exam 1 - heme Flashcards

Question

neutropenia

Answer 1

-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

Answer 2

-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

Answer 3

-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

Answer 4

-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)

Answer 5

-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

Answer 6

-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%

Answer 7

-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)

Answer 8

-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)

Answer 9

-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

Answer 10

-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

Answer 11

-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

Answer 12

-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

Answer 13

-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

Answer 14

-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

Answer 15

-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

Answer 16

-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%)

Answer 17

-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

Answer 18

-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)

Answer 19

-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%

Answer 20

-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

Answer 21

-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)

Answer 22

-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

Answer 23

-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

Answer 24

-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%

Answer 25

-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