Leukemias in general:
● Sx: lethargy, malaise, anorexia days / wks before dx; bone pain / arthralgias (leukemia in marrow cavity), pallor (normocrhomic, normocytic anemia with low retic count), ecchymoses / petechiae (thrombocytopenia), hepatosplenomegaly / cervical LAD at Dx.
● Get CBC with dif & blood smear, flow cytometry to type. Bone marrow bx is gold standard.
Acute leukemias: 97% of all childhood leukemias. rapidly fatal if untreated, but curable.
● Acute lymphoblastic leukemia (ALL):
○ More common (75%), increased risk with ataxia-telangiectasia, XLA, SCID, L3 ALL a/w EBV.
○ Hyperleukocytosis (WBC > 200,000) = vascular stasis (esp if > 300k) - bad!
Mental status changes, H/A, stroke, hypoxemia, etc. Can use hyperhydration, leukophoresis to tx
○ Treatment of ALL: induction of remission,consolidation to kill more cells (incl intrathecal methotrexate), interim maintenence (less intense), delayed intesification (another intense round), maintenence (ongoing, to maintain remission)
■ High risk of tumor lysis syndrome (hyperUricemia, hyperPhos,
hyperK) - give fluids, alkalanize urine, give allopurinol for high uric acid, aid elimination of K/phos
○ Worse prognosis if >10y, <1yr, WBC > 50k @ dx, philadelphia chromosome, hyperploidy
● Acute myeloid leukemia (AML):
○ Less common (25%) than ALL, peak in adolescence, white=AA
○ May develop chloroma (soft tissue tumor) in spinal cord, skin
○ Can also have hyperleukocytosis as above. Keep Hb < 10g/dL, plt > 20,000
○ Treatment is more intensive than ALL
○ Increased risk with congenital bone marrow failure states like Shwachman-Diamond (exocrine pancreatic insufficiency and neutropenia) and Shwachman- Diamond-Blackfan (congenital RBC aplasia), exposure to benezene, alkylating agents
○ Acute promyelocytic leukemia = M3 subtype; higher survival rate, retinoid gene translocation (retinoic acid part of tx), higher in latinos, better prognosis overall.
Chronic leukemias: only 3%, more indolent but can develop to blast crisis. CML in adolescents, but rare
Increased leukemia risk: Trisomy 21, fanconi anemia, Bloom syndrome, twin with leukemia, chemo / ionizing radiation for 1st malignancy.
Lymphomas
Non-Hodgkin:
● T-cell: a/w mediastinal mass, can have SVC syndrome as a result
○ lymphoblastic (pre-B), anaplastic types
● B-cell: often involves bone, isolated LNs, skin
○ lymphoblastic (pre-B)
○ Burkitt lymphoma: rapid growth, can have tumor lysis syndrome even before chemo!
■ Sporadic: abd tumora/w nausea, emesis, intussusception
■ Epidemic: jaw, orbit, maxilla, more definitely EBV associated
■ C-myc translocation
Hodgkin: childhood, young adult, older adult form; biomodal epidemiology (15-30, then >50)
● Painless, rubbery cervical lymphadenopathy in 80%, ⅔ also have mediastinal LAD
● B symptoms: unexplained fever, drenching night sweats, unintentional wt loss (>
10%/6mo)
● Diagnosis:
○ Get a chest radiograph to look for mediastinal mass; will guide how bx done (anesthesia? need to protect airway if impinged upon?)
○ Biopsy next: look for Reed-sternberg cells. Fewer is better for prognosis (lymphocyte predominance has best prognosis).
● Staging: depends on where involvement is (single LN, more, both sides of diaphragm, disseminated, B-sx?)
● Treatment: can be chemo combos +/- XRT depending on stage, other factors.
Chemo drugs and their side efects
● Alkylating agents / cross linkers
○ Cyclophosphamide - hemorrhagic cystitis, SIADH, cardiac toxicity, infertility
○ Iphosphamide - hemorrhagic cystitis, also renal / ototoxicity, infertility
○ Cisplatinum (platinates, doesn’t alkylate, but cross-links) - ototoxicity, renal toxicity, late nausea
● Antimetabolites
○ Methotrexate (dihydrofolate reductase inhibitor) - mucositis, hepatic/renal tox, neurotoxic
○ Mercaptopurine, thioguanine (block purine synthesis) - mucositis, hepatic toxicity
○ Cytarabine (inhibits DNApol): mucositis, flu-like sx, ocular toxicity
● Plant products
○ Vincristine (microtubule inhibitor) - SIADH, neurotoxicity, constipation
○ Etoposide (DNA strand breaks) - mucositis, infusion rxn, secondary leukemias
○ Asparaginase (asparagine depletion) - coagulopathy, pancreatitis, anaphylaxis
Retinoblastoma: malignant tumor of embryonic neural retina. Chr 13q14 mutation (RB1)
● 60% sporadic, rest hereditary (high but incomplete penetrance). Bilat (25%) = hereditary.
○ If parent has unilateral rb & known mutation or bilat rb, screen at birth (ophtho) &
reg intervals until 4-5 y/o
● ⅔ in < 2 year olds, 95% before age 5.
● Dx: leukocoria (absent red reflex). Get ophtho eval; may need MRI, etc.
○ DDx of leukocoria includes congenital cataract, medulloepithelioma, Toxocara
endopthalmitis, persistent hyperplastic primary vitreous, Coats disease = abnl development of blood vessels behind retina)
● Tx: varies: enucleation, chemo, local therapy (laser/cryo), radiation. depends on extent of disease.
● If heriditary form, higher risk for soft tissue sarcomas
Neuroblastoma: postganglionic sympathetic nervous system malignancy; childhood, embryonal
● Location: abdomen (70% - most often adrenal medulla; also retroperitoneal sympathetic ganglia), thoracic cavity (posterior mediastinal ganglia), head/neck (cervical sympathetic ganglia)
● 8% all childhood cancers < 15yrs; mean age @ dx 17-22 months
● Etiology unknown, may be related to other neural crest cell disorders (Hirschprung, NF-1, pheo)
● Presentation: Abd: smooth, hard, nontender abdominal mass; displace kidney forward/down. Can get abd pain, HTN if compressing renal vasculature. Chest:
respiratory distress. Neck: Horner’s syndrome, palpable mass. MULTIQUADRANT abdominal mass
● Mets: lymphatic, hematogenous. Wt, loss, fever, bone marrow failure (pancytopenia), cortical bone pain -> limp (Hutchinson syndrome), liver infiltrate -> hepatomeg (pepper syndrome), periorbital infiltration (proptossis, ecchymoses = “racoon eyes”), LN enlargement, skin infiltration (palpable nontender subcutaneous blue nodules).
● Paraneoplastic: can see watery diarrhea (VIP secreting), opsoclonus-myoclonus too
● Dx: Send urinary VMA, homovanillic acid (catechols), get bx
● Prognosis: stage with INSS (international neuroblastoma staging system - I=localized &
excised ; I = localized, not excised, III = tumor beyond midline (incl. contralateral LN
involvement), IV = distant mets, IVS = age < 1 + mets, with primary tumor that would otherwise be I or II. I, II, IVS have better prog than III/IV. Best prog for infants < 1. N-myc has worse prognosis. Tx with chemo, surgery, radiation, biotherapy, etc. as needed.
Wilms tumor: #1 renal tumor in kids, neoplastic embryonal renal cells from metanephros proliferate
● 11p13 (WT1) and 11p15 (WT2) are most common genes.
● most unilateral; 7% bilateral; most < 5 years old @ dx
● Associations: sporadic aniridia, hemihypertrophy, cryptorchidism, hypospadius, other GU abnormalities. Beckwith-Wiedemann (hemihypertrophy, macroglossia, omcephalocele, GU abnormalities), Denys Drash (congenital nephropathy, Wilms, intersex d/o), WAGR (Wilms, aniridia, GU abnormalities, mental Retardation), and
Perlman syndrome (unusual facies, islet cell hypertrophy, macrosmia, hamartomas) are related.
● Features: asx abd mass, usually found by parents. Abd pain / fever = may have hemorrhaged into tumor. Microscopic or gross hematuria in 33%, HTN in 25% (renin secretion by tumor or compression of renal artery). Can get varicocoele (if spermatic vein cord compression) too. vWD also 8%.
● Management: Get abd ultrasound, then CT, then bx (usually at time of removal). Treat with surgical removal of kidney; assess contralat idney for spread. Chemo and/or radiation depending on staging
● Good prognosis if small tumor, patient > 2 y/o, good histology, no LN mets / capsular invasion
● Anaplastic, clear cell, rhabdoid histology may necessitate diferent treatment Soft tissue sarcomas:
● Rhabdomyosarcomas = 50%. Associated with NF, Li-Fraumeni syndromes. #1 STS in kids < 10 yrs)
○ t(2;13), t(1;13) translocations.
○ Can be embryonal or alveolar subtype. 35% in head/neck, 22$ in GU sites, 20%
in extremities.
● Non-rhabdomyosarcomas: heterogenous group. fibrosarcoma is #1 STS in kids > 10 yrs.
○ Include nerve sheath tumors (malignant, congenital with NF-1) but also fibrous histiocytomas, leiomyosarcomas (after radiation for prior tumor)