Hematology/Oncology Flashcards
Sites of RBC formation during prenatal life
2-8 weeks–yolk sac
8 weeks to 5 months–liver
5 months on–bone marrow
Causes of physiologic anemia of infancy
- Decrease in EPO production due to increase arterial oxygen content
- Shorted RBC lifespan in first 6-8 weeks (90 days vs 120 days)
Physiologic nadir–time and level
About 8-12 weeks of life, and about Hgb 9-11 (3-6 weeks and 7-9 in preterm infants)
Composition of hemoglobin types
Embryo: Gower 1--zeta and epsilon Gower 2--alpha and epsilon Portland--zeta and gamma Fetus: HbF--alpha and gamma (90% of Hb in 6 month fetus, 70% at birth, <2% in 1 year and older) Adult: HbA--alpha and beta HbA2--alpha and delta(2-3% of adult Hb)
Composition of Hb Barts
4 gamma chains–shows up on NBS, suggesting alpha thalassemia
Composition of HbH
4 beta chains–present in alpha thalassemia
Grouping of anemia mechanisms
1) Production defects (decreased EPO or bone marrow failure)
2) Maturation defects–cytoplasmic or nuclear
- Cytoplasmic with microcytic, hypochromic anemia–impaired Hgb synthesis, protoporphyrin deficiency (sideroblastic anemia), globin synthesis deficiency
- Nuclear with microcytic anemia–DNA synthesis defects (folate or B12 deficiency)
3) Survival defects–inherited or acquired
- Inherited–membrane cytoskeleton protein problems, metabolic enzyme problems, hemoglobinopathies
- Acquired–autoimmune, malaria, DIC, intravascular hemolysis
Anemia of chronic disease vs iron deficiency anemia
Anemia of chronic disease–low iron, low TIBC, low-normal transferring saturation, normal-high ferritin
Iron deficiency anemia–low iron, high TIBC, low transferrin saturation, low ferritin
What is the most common hypoproliferative anemia?
Anemia of chronic disease (impair iron utilization due to inflammatory mediators and decrease EPO)
What infants need iron supplementation and when?
- Breast-fed infants after 4 months of age (1mg/kg of elemental iron daily)
- Premature infants
What is the most common congenital GI cause of chronic blood loss?
Meckel diverticulum
What is the most common worldwide cause of chronic GI blood loss?
Hookworm infection (Necator americanus or Ancylostoma duodenale)
RDW in thalassemia trait vs iron deficiency anemia?
RDW is normal in thal trait, increased in iron deficiency anemia
Menzter Index–what is it? what is it used for?
MCV/RBC; >12 in iron deficiency (RBC count usually low); <11 in thal (RBC count normal or increased)
Treatment of iron deficiency anemia
1) PO iron–3-6 mg/kg/day of elemental iron
2) Correct underlying cause
Changes after starting iron therapy for iron deficiency?
1) Reticulocytosis starting in 3-5 days, peaking in 7-10 days.
2) Hgb increase 1-2 g/dL in 1st month
Syndromes with increased ALL risk (4)?
1) Down syndrome
2) Ataxia-telangiectasia
3) Bloom syndrome–short stature and increased homologous recombination
4) Fanconi anemia (more commonly AML)
Percentage of bone marrow blasts to diagnose acute leukemia?
> /= 25%
Breakdown of ALL lineage.
85% pre-B; 14% T-cell; 1% mature B-cell
Good prognostic indicators for ALL (4)?
1) Rapid responder
2) Hyperdiploidy (>50 chromosomes or DNA index >1.16)
3) t(12;21) (TEL-AML)
4) Female
Poor prognostic indicators for ALL (8)?
1) Age 10 years
2) Ph+ [t(9;22)]
3) t(4;11) (MLL gene)
4) WBC >50,000 at presentation
5) Mature B-cell lineage
6) T-cell lineage
7) Hypodiploidy
8) AA or hispanic ethnicity
Percentage of standard-risk ALL entering remission after induction?
> 95%
Predictive factor for 2nd remission in ALL?
Length of time of 1st remission
Conditions with increased AML risk (8)?
1) Down syndrome
2) Diamond-Blackfan syndrome
3) Fanconi anemia
4) Bloom syndrome
5) Kostmann syndrome (severe congenital neutropenia)
6) PNH
7) Neurofibromatosis
8) Exposure to ionizing radiation or etoposide
Chromosomal abnormality in APL (M3)?
t(15;17)
Chromosomal abnormality in AML-M2?
t(8;21)
Chromosomal abnormality in AML-M4?
Inv 16
Chromosomal abnormality in AML-M5?
11q
Classic histological finding in Hodgkin lymphoma?
Reed-Sternberg cell (large cell with multiple or multilobulated nuclei)–“owl’s eye”
Lineage of most Hodgkin’s?
B-cell
4 Rye Classifications of Hodgkin’s?
1) Lymphocyte predominance (10-15%)
2) Mixed cellularity (30%)
3) Lymphocytic depletion (rare in children, more common in HIV)
4) Nodular sclerosing (most common)
Most common presentation of Hodgkin disease?
Asymptomatic cervical or supraclavicular adenopathy (must get CXR if supraclavicular LAD is present)
Hodgkin disease “B” symptoms?
Fever, drenching night sweats, or unexplained weight loss >10%(+ in 1/3 of children)
Pel-Ebstein fevers in Hodgkin’s?
Periodic fevers–febrile for several days, then afebrile
Infections predisposed to in Hodgkin’s?
TB and fungal disease, as well as VZV (cellular immunity is impaired)
Ann Arbor Staging of Hodgkin’s
I–single LN region, or single extralymphatic site or organ
II–one or more LN regions on same side of diaphragm
III–LN regions on both sides of diaphragm
IV–disseminated disease with one or more extralymphatic organs or tissues
How to diagnose and stage Hodgkin’s
Excisional biopsy of LN (staged with CBC, ESR, ferritin, copper level, LFTs, CXR, chest CT with contrast, abd CT with contrast, gallium scan)
-Do BM bx if suspected II or IV disease or if + B symptoms
Chemo regimens for Hodgkin’s?
1) ABVE-PC–Adriamycin (doxorubicin), Bleomycin, Vinblastine, Etoposide, Prednisone, Cyclophosphamide
2) MOPP–nitrogen Mustard, vincristine [Oncovin], Procarbazine, Prednisone; old, rarely used
Long-term effects of XRT in Hodgkin’s?
Growth retardation, early CAD, thyroid failure/cancer, pulmonary fibrosis, increased risk of breast CA
Most common lymphoma?
Non-Hodgkin’s lymphoma (NHL)–60%
Conditions predisposing to NHL (4)?
1) Ataxia-telangiectasia
2) Wiskott-Aldrich syndrome
3) HIV
4) Other immunosuppressive diseases
Most common location for origination of Burkitt-type lymphomas?
- B-cells in Peyer’s patches of GI tract (usually ileocecal junction)–90%
- Only 10% present in Waldeyer ring (tonsils/adenoids)
Most common presentation of Burkitt lymphoma?
Abdominal mass or pain with nausea/vomiting (jaw involvement common in African form, but only ~15% in U.S.)
Fastest growing malignant tumor?
Burkitt lymphoma (can double in 2-3 days!)–high risk for TLS
3 histologic subtypes of NHL?
1) Lymphoblastic (cells are identical to ALL)–80% are T-cell
2) Large cell (can be T-cell, B-cell, or indeterminate)
3) Small, noncleaved-cell lymphoma (Burkitt and non-Burkitt subtypes, B-cell oritin)
Most common NHL in U.S.?
Burkitt (~50%)
Most common presentation for lymphoblastic lymphoma?
Anterior mediastinal mass with associated symptoms (mostly T-cell origin)
-B-cell lymphoblastic lymphomas can present in skin or bone
What is unique about LAD in large cell NHL?
LAD is tender!
-Can present as abdominal mass or as mediastinal disease or in unusual sites (bone, skin, lung)
How is NHL diagnosed and staged?
- Dx by biopsy
- Staging by volume of tumor
St. Jude/Murphy staging system for NHL
I–single tumor or anatomic note except mediastinum or abdomen
II–2 or more nodal areas on same side of diaphragm; 2 extranodal tumors on same side of diaphragm; or resectable primary GI tumor
III–both sides of diaphragm; all mediastinal or intrathoracic tumors; all unresectable abdominal disease; all paraspinal or epidural tumors
IV–any CNS or bone marrow disease
Most common malignancy in infants (+3 epidemiology facts)?
Neuroblastoma (8-10% of childhood cancers, boys>girls, median age 22 months)
Prognostic factors in neuroblastoma (5)?
1) Age (<1 year = good)
2) Extent of tumor
3) N-MYC amplification (more copies = bad)
4) Ploidy (more ploidy = good)
5) Chromosome 1p deletion (bad)
Presentation of neuroblastoma?
Non-tender abdominal mass (40% are from adrenal gland, 40% are in non-adrenal abdominal tissue, 20% in sympathetic chain of thorax and neck)
Metastatic sites of neuroblastoma?
Distant LN, bone, bone marrow, liver, skin
Paraneoplastic issues with neuroblastoma (3)?
1) Horner syndrome (esp. with cervical tumors)
2) Opsoclonus-myoclonus (myoclonic jerks and random eye movement, +/- ataxia)
3) Intractable diarrhea and abdominal distension (VIP secretion)
Uses of urine HVA/VMA in neuroblastoma?
Screening, diagnosis, and off-therapy follow-up
What is stage 4S in neuroblastoma?
Infant (<1 year of age) with stage 1 or 2 primary tumor and dissemination limited to liver, skin, and/or bone marrow (good prognosis)
How is treatment for neuroblastoma determines?
Combination of staging and biologic factors (“risk”–very low, low, intermediate, high)
Most common primary kidney tumor of childhood?
Wilms tumor (mean age 3.5-4 years for unilateral, 2.5-3 years for bilateral)
Wilms tumor association with syndromes (3)?
1) WAGR (Wilms, Aniridia, GU abnormalities, MR)
2) Beckwith-Wiedemann (organomegaly, hemihypertrophy, omphalocele, macroglossia)
3) Denys-Drash syndrome (Wilms, mesangial renal sclerosis, pseudohermaphroditism)
Staging of Wilms tumor?
Stage 1–limited to kidney, completely excisable
Stage 2–beyond kidney, but completely excisable
Stage 3–residual tumor in abdomen after surgery
Stage 4–hematagenous spread, usually to lungs
Stage 5–bilateral disease (5-10% of cases)
Importance of histology in Wilms tumor?
Favorable histology ("triphasic"--epithelial, blastemal, and stromal elements)-->90% survival at 2 years regardless of stage!
Poor histology ("anaplastic") beyond stage 1--<60% survival at 2 yearsPresentation of Wilms tumor?
Asymptomatic abdominal or flank mass (~50% with N/V or pain, 25% with HTN, less commonly gross hematuria)
Treatment of Wilms tumor?
Surgical removal is mainstay (don’t spill!!); chemo and radiation based on staging and histology
Other kidney tumors (4)?
1) Nephroblastomatosis (precursor to Wilms tumor–occurs in all bilateral tumors and 1/3 of unilateral)
2) Mesoblastic nephroma–most common congenital renal disorder; benign mass of kidney
3) Renal cell carcinoma–very rare, but poor prognosis
4) Rhabdoid tumor
Most common soft tissue tumor of childhood?
Rhabdomyosarcoma (arises from embryonic mesenchyme, 5% of childhood cancers, majority dx at <10 years old)
4 histologic types of RMS?
1) Embryonal–60% of cases, t(2,13)
2) Botryoid–6% of cases, grape-like projections, found in vagina, bladder, nasopharynx, middle ear
3) Alveolar–15% of cases, trunk and extremities, worst prognosis
4) Pleomorphic–1% of cases, “adult” type
Presentation of RMS?
Mass lesion +/- pain
Locations of RMS?
Head and neck (including orbit and parameningeal), GU, extremities, trunk
Other soft tissue sarcomas (3)?
1) Fibrosarcoma (most common soft tissue sarcoma in children <1 year old)
2) Synovial sarcoma [t(X;18)]
3) Leiomyosarcoma (most common retroperitoneal soft tissue tumor in children; seen in AIDS and immunosuppression after renal transplant)
Most common primary malignant bone tumor in children/adolescents?
Osteosarcoma (Ewing’s most common in kids <10 years); osteosarcoma presents most commonly during adolescent growth spurt
Diseases with increased risk of osteosarcoma (4)?
1) Hereditary retinoblastoma (Rb gene)
2) Li-Fraumeni syndrome (also rhabdomyosarcoma)
3) Rothmund-Thomson syndrome (short stature, skin teleangiectasias, hypoplastic/absent thumbs, small hands/feet)
4) XRT for malignancies (esp. Ewing’s)
Benign disease that can transform to osteosarcoma (3)?
1) Paget disease
2) Endochondromatosis
3) Multiple hereditary exostoses
4 pathologic types of osteosarcoma?
1) Osteoblastic (~50%)
2) Fibroblastic (~22%)
3) Chondroblastic (~25%)
4) Telangiectatic (~3%)
(No prognostic difference!)
Osteosarcoma vs Ewing’s: Race?
Osteo: All
EWS: Caucasian
Osteosarcoma vs Ewing’s: Cell type?
Osteo: Spindle cell-producing osteoid
EWS: Undifferentiated small round cells, probably neural crest
Osteosarcoma vs Ewing’s: Site?
Osteo: Metaphyses of long bones (invades medullary cavity)
EWS: Diaphyses of long bones; flat bones; paraspinal and vertebral
Osteosarcoma vs Ewing’s: Presentation?
Osteo: Hx of injury; local pain/swelling
EWS: Fever; local pain/swelling
Osteosarcoma vs Ewing’s: XR findings?
Osteo: “Sunburst pattern;” less commonly lytic
EWS: “Onion skinning;” lytic
Presentation of osteosarcoma?
Deep bone pain, nighttime awakening, palpable mass
Ewing’s translocations?
t(11;22); t(21;22)
More likely to be associated with systemic findings (fever, weight loss, etc)–osteosarcoma or Ewing’s?
Ewing’s
What is osteochondroma?
Benign bone tumor; metaphyses of long bones; have cartilage cap; on XR appear as stalks or projectiosn from surface of bone; malignant transformation rare in children; remove if symptomatic (usually asymptomatic)
What is enchondroma?
Solitary benign tumor of hyaline cartilage; hands affected most often
What is chondroblastoma?
Rare lesion of epiphysis of long bones; will destroy joint so curretage and graft
What is osteoid osteoma?
Benign tumors; usually in males; unremitting and worsening pain, mostly at night; XR shows round or oval lucency with surrounding sclerotic bone; remove lesion surgically
What is osteoblastoma?
Destructive tumor, usually in vertebrae; remove and graft +/- spinal stablization
Most common solid neoplasm of childhood?
CNS tumors (15-20% of childhood cancer)
CNS tumor associations: NF 1
Optic gliomas (also meningiomas, optic astrocytomas, ependymomas, neurosarcomas of cranial nerves, spinal cord astrocytoma)
CNS tumor associations: NF 2
Vestibular schwannomas (also retinal gliomas, meningiomas, , gliomas, cranial and peripheral nerve schwannomas)
CNS tumor associations: Tuberous sclerosis?
Subependymal giant cell tumor (benign, but can grow very large)
CNS tumor associations: Li-Fraumeni syndrome?
Gliomas, ependymomas, and choroid plexus carcinomas
CNS tumor associations: Turcot syndrome?
GBM, medulloblastoma
CNS tumor associations: Nevoid basal cell carcinoma syndrome?
Medulloblastomas
CNS tumor associations: von Hippel-Lindau disease?
Hemangiomas of cerebellum, medulla, and spinal cord
Signs of increased ICP?
Headache (pain on awakening, relieved by vomiting, better throughout day), vomiting, irritability
Common visual finding with CNS tumors?
Diplopia (due to 6th nerve palsy)
What is “sun-setting?”
Impaired upward gaze and downward deviation of eyes (early sign of increase ICP)
Signs of leptomeningeal dissemination of CNS tumors?
MS changes, neck/back/radicular pain, weakness, bowel/bladder dysfunction
3 types of primitive neuroectodermal tumors (PNET)?
1) Medulloblastoma (in posterior fossa)
2) Pineoblastoma (in pineal gland)
3) Central neuroblastoma or supratentorial PNET (cerebral cortex)
* Medulloblastoma has best prognosis
Most common type of malignant CNS tumor in childhood?
PNET (medulloblastoma is most common–33% of infratentorial tumors)
Common signs of medulloblastoma?
AM headache, vomiting, lethargy, ataxia, head-tilt (head tilted forward due to 4th nerve palsy), hydrocephalus (75%)
What is the source of ependymomas?
Ependymal lining of ventricular system (75% in posterior fossa); hydrocephalus almost always present
Most common overall (benign and malignant) CNS tumors in childhood?
Gliomas
Most common posterior fossa tumor?
Cerebellar astrocytoma (>90% 5-year survival)
4 important types of gliomas?
1) Cerebellar astrocytoma
2) Brainstem glioma
3) Diencephalic glioma
4) High-grade astrocytomas (including GBM)
What are craniopharyngiomas?
Benign tumors of squamous epithelial cell origin that arise in suprasellar region; can invade optic chiasm, carotic arteries, 3rd cranial nerve, and pituitary stalk
Presenting signs of craniopharyngiomas?
Endocrinopathies from pituitary invasion (short stature, growth failure, DI); personality changes, altered sleep pattern (hypothalamic dysfunction)
Common complication of craniopharyngioma surgery?
Diabetes insipidus
Causes of hydrocephalus in choroid plexus tumors?
CSF obstruction or CSF overproduction
Retinoblastoma: laterality and hereditary percentages?
60%–UNI-lateral and NON-hereditary
15%–UNI-lateral and hereditary
25%–BI-lateral and hereditary
Presentation of retinoblastoma?
White pupillary reflex (leukocoria), strabismus, pain only if secondary glaucoma occurs
Work-up for retinoblastoma?
EUA, US/CT/MRI, LP (look for optic nerve invasion)
Treatment of retinoblastoma?
Unilateral disease–enucleation if no chance for vision; otherwise, laser or cryotherapy, chemo
Bilateral disease–chemo, laser or cryotherapy
How do pineal gland tumors present?
Parinaud syndrome: triad of impaired upward gaze, dilated pupils (react better to accomodation than light), convergence-retraction nystagmus with upward gaze
What fraction of germ cell tumors are extragonadal?
2/3
Common sites for teratomas?
Sacrococcyx, ovaries, testes, and anterior mediastinum (with sacrococcygeal teratoma, risk of malignant transformation is 50% if infant is >2 months old)
Germinomas: malignant or benign?
Malignant (though often tumor marker negative)
Common extragonadal site for germinomas?
Intracranial (respond well to radiation and chemo)
Common site for embryonal carcinoma?
Testes (surgical resection usually sufficient)
Most common malignant childhoold germ cell tumor?
Endodermal sinus (yolk sac) tumor
Fraction of germ cell tumors that are malignant?
1/3 (mainly older children and adolescents; nearly all neonatal germ cell tumors are benign)
Tumor marker for endodermal sinus tumor?
AFP
Tissue type characteristically seen in choriocarcinoma?
Syncytiothrophoblast (malignant tumor that is usually mixed with other germ cell tumor histologies)
Tumor marker for choriocarcinoma?
B-HCG
When does gonadoblastoma occur?
Dysgenetic gonads (46XY or 46XY/45XO karyotype); 80% have female phenotype
Common associations with nasopharyngeal carcinomas?
EBV or prior radiation exposure
Paraneoplastic syndromes with nasopharyngeal carcinomas?
SIADH, digital clubbing, FUO
Most common pancreatic endocrine tumors?
Insulinoma and gastrinoma (Z-E syndrome); occur with autosoma dominant MEN-1 syndrome (pituitary, pancreatic, parathyroid)
Risk of colon cancer in familial adenomatous polyposis (autosomal dominant)?
100%–colectomy!
Tumors in Gardner syndrome?
Multiple intestinal polyps (precancerous) and tumors of mandible and soft tissue/bone
Tumors in Turcot syndrome?
Multiple colorectal polyposis (precancerous)and primary brain tumor (medulloblastoma)
Child <6 months old, multiple liver lesions, normal AFP–dx?
Hemangioendothelioma (most common benign liver tumor of childhood–no treatment needed if asymptomatic)
8yo child with solitary liver mass and elevated AFP–dx?
Hepatocellular carcinoma (associated with Hep B infection, 1/2 have elevated AFP, 1/3 have cirrhosis)
2yo child with solitary liver mass and elevated AFP–dx?
Hepatoblastoma (complete surgical resection, even transplant, follow AFP levels)
Adolescent female on OCP’s with liver mass?
Liver adenoma
Metastatic liver disease?
2yo–Wilms, sarcoma, lymphoma
What is histiocytosis?
Abnormal proliferation of histiocytes (dendritic cells or macrophages)
Which cell type is Langerhans cell histiocytosis (LCH) due to?
Dendritic cells
3 classifications of LCH?
1) Unifocal (formerly eosinophilic granuloma of bone)
2) Multifocal (formerly Hand-Schuller-Christian disease)
3) Systemic (formerly Letterer-Siwe disease)
Peak age for LCH?
1 year (males>females)
Dx of LCH?
Finding CD1a by immunophenotyping or birbeck granules on elctron microscopy
Presentation of unifocal LCH?
Solitary bone lesion (calvaria, vertebrae, mandible, ribs, ilia, scapula, femur), +/-pain, XR–punched-out lytic lesions
Presentaiton of multifocal LCH?
Skull lesions, DI, exophthalmos (in infants–erosion of lamina dura of teeth, gingival hemorrhage, premature tooth eruption, oral mucosal irritation)
-Can also have seborrheic rashes and chronic otitis externa
Presentation of systemic LCH?
Persistent fever, FTT, pupuric eroding rashes with lung, bone marrow, and liver involvement (can occur at birth)
What cell type is responsible for hemophagocytic lymphohistiocytosis (HLH?
Macrophages
How is HLH classified?
Primary (formerly familial erythrophagocytic lymphohistiocytosis, autosoma recessive) and secondary (includes infection-associated hemophgocytic syndrome and malignancy-associated hemophagocytic syndrome)
Location of HLH lesions?
Liver, spleen, lymph nodes, bone marrow, and CNS (lesions contain macrophages and lymphocytes)
What cells are in LCH lesions?
Dendritic cells (Langerhans cells), lymphocytes, macrophages, granulocytes, eosinophils, amd multinucleated giant cells
Presentation of HLH?
Fever, HSM, LAD, and rashes (seizures in infants); lab work shows pancytopenia, hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia
Dx criteria of HLH (6)?
Requires all:
1) Fever
2) Splenomegaly
3) 2 or more cytopenias
4) Hypertriglyceridemia OR hypofibrinogenemia
5) Hemophagocytosis without evidence of malignancy in bone marrow, spleen, or LN
6) Hyperferritinemia (massive!)
Treatment of HLH?
Chemo in both primary and secondary (BMT after remission only in primary HLH)
