Oncology

Oncology
Patrick T. McGann
Kevin R. Schwartz
Howard J. Weinstein
Lymphadenopathy in the Pediatric Patient
Definition
(Pediatr Rev 2008;29:53)
  • Axillary or cervical lymph node >1 cm in size; inguinal lymph node >1.5 cm; epitrochlear lymph node >0.5 cm; supraclavicular—any palpable lymph node
  • Note: Risk of underlying malignancy increases w/ increasing size, esp >2 cm
  • Localized lymphadenopathy: Involving one nodal group
  • Generalized lymphadenopathy: Involving ≥2 nodal groups or sites (i.e., spleen/liver)
Differential Diagnosis of Lymphadenopathy
(Pediatr Rev 2008;29:53; Pediatr Rev 2000;21:399)
Infections
  • Bacterial:
    • Localized: Lymphadenitis (tender, suppurative node, often unilateral cervical): Staph, GAS, anaerobes (periodontal disease). Cat-scratch dz, tularemia, bubonic plague, scrofula (TB) diphtheria, chancroid(inguinal)
    • Generalized: Brucellosis, leptospirosis, lymphogranuloma venereum, typhoid
  • Viral: Adenovirus, Influenza, RSV, EBV, CMV, HSV, HIV, HBV, mumps, measles, rubella, dengue fever
  • Fungal: Coccidiomycosis, cryptococcosis, histoplasmosis
  • Protozoal: Toxoplasmosis, leishmaniasis
  • Spirochetal: Lyme disease, syphilis
Malignancy: Leukemia, lymphoma, metastasis from solid tumorImmunologic: Angioimmunoblastic LAD w/dysproteinemia, autoimmune lympho-proliferative dz, chronic granulomatous dz, dermatomyositis, drug rxn, RA, hemophagocytic lymphohistiocytosis, Langerhans cell histiocytosis serum sickness, SLEEndocrine: Addison disease, hypothyroidismMisc: Amyloidosis, Castleman dz, Churg-Strauss, inflammatory pseudotumor Kawasaki dz, Kikuchi dz, lipid storage dz Sarcoidosis
Clinical Manifestations
(Pediatr Clin North Am 2002;49:1009)
  • Hx: Duration LAD, assoc sx, recent localized infxn’s (esp in drainage territory of nodes), skin lesions, trauma, animal scratches/bites, meds, ingestion of unpasteurized milk/undercooked meats, dental problems (cervical LAD), tick bites, travel Hx, sexual Hx.
  • Exam: Size, location (supraclavicular always concerning), tender/nontender, mobile/fixed, soft/hard, warm or erythematous, HSM, bruises or petechiae, signs of systemic dz.
Diagnostic Evaluation and Management
(Pediatr Rev 2008;29:53; Pediatr Clin North Am 2002;49:1009)
  • see table on next page
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Pediatric Oncologic Emergencies
(Principles & practice of pediatric oncology. 5th ed. Philadelphia. LWW 2006;12224)
Superior Vena Cava (SVC) Syndrome
(Pediatr Clin North Am 1997;44:809)
  • Definition: Signs and sx’s from compression &/or obstruction of SVC
  • Etiology: Often a presenting feature of intrathoracic malignancies
    • Malignancies p/w mediastinal mass most commonly include NHL, ALL, and Hodgkin dz. Less common: Sarcoma (Ewing, rhabdo), neuroblastoma, thymoma, and teratoma.
  • Pathophysiology: Mediastinal mass compresses SVC causing venous stasis
    • Compression, clotting, and edema of SVC lead to ↓ in tracheal airflow, and ↓venous return from head, neck, and upper thorax
  • Clinical manifestations: Cough, dyspnea, dysphagia, orthopnea, and hoarseness
    • Later sx’s of anxiety, confusion, lethargy, HA, Δ vision, and syncope may = CO2 retention; can also see facial +/- UE swelling, chest pain, pleural effusions
    • Sx’s worse when patient is supine; should raise suspicion for mediastinal mass
  • Diagnostic studies: CXR; typically will show anter mediastinal mass; trach deviation
    • CBC, Chem10, LDH, and uric acid; Obtain dx tissue sample before Rx if possible
  • Treatment: Depends on underlying malignancy
  • If significant CV or resp compromise, emergent XRT and/or IV methylprednisolone/dexamethasone treatment may be indicated
Tumor Lysis Syndrome (TLS)
(Nat Clin Pract Oncol 2006;3:438)
  • Definition: Metabolic abn 2/2 cell death and subsequent release cell contents into circ.
    • Metabolic disturbances can result in severe end organ impairment
  • Etiology/risk factors
    • Occurs in tumors w/ ↑ growth fraction and large tumor burden/volume.
    • Malignancies most commonly assoc w/ TLS include Burkitt lymphoma, ALL (particularly T-cell variant), lymphoblastic lymphoma; TLS rare in AML
    • Can occur before onset of Rx but typically occurs w/i 12–72 hr of initiation of Rx
    • Risk factors: WBC >50,000, ↑ LDH, ↑ uric acid on admit, Cr >1.6 or ↓ GFR
  • Diagnostic studies: Elevated uric acid (>10) – caused by breakdown of nucleic acids
    • Hyperphosphatemia and secondary hypocalcemia; hyperkalemia
  • Consequences of TLS
    • Hyperuricemia → precipitation of uric acid in collecting ducts of renal tubules, causing resultant nephropathy and acute renal failure
    • Hyperkalemia → cardiac arrhythmias and sudden death
    • Hypocalcemia → hypotension, EKG changes, tetany, and seizures
    • Hyperphosphatemia → renal precipitation; exacerbate nephropathy and renal failure
  • Management/prevention of TLS: Electrolyte abn managed acutely as indicated
    • Upon dx of malignancy and before starting Rx, aggressive mgmt to prevent TLS
      • Aggressive hydration (2–4× maintenance) to ↑ GFR and ↑ urinary outflow
      • Urinary alkalization w/ NaHCO3(40–80 mEq/m2/hr) to urine pH >7 to prevent uric acid precipitation
      • Allopurinol (250–500 mg/m2/d) inhibits xanthine oxidase; ↓ uric acid formation
      • Alternatively, rasburicase (recombinant urate oxidase) in place of allopurinol
      • Close observation of electrolytes, Ca, Mg, Ph, LDH, and uric acid (q6–8h upon initiation of Rx) essential to monitor for development of TLS
Spinal Cord Compression (SCC)
(Pediatr Clin North Am 1997;44:809)
  • Definition/etiology: Occurs in 2.7%–5% of children w/ cancer
    • Most cases 2/2 epidural compression from extension of paravertebral tumor
    • ↑ risk w/ neuroblastoma, Ewing sarcoma, non-Hodgkin lymphoma, and Hodgkin.
    • Osteosarcoma and rhabdomyosarcoma typically cause SCC only w/ recurrence
  • Clinical manifestations: Back pain present in 80% pedi pts w/ cord compression
    • Sx’s typically present for an avg of 2 wk before dx made
    • Weakness, sensory loss, and incontinence are later and more concerning findings
  • Evaluation/treatment
    • Detailed neuro exam in any pt p/w suspected malign; rectal exam for sphincter tone
    • Plain radiographs often performed but only show findings in ½ affected patients
    • MRI w/ contrast is study of choice to assess presence and extent of SCC
    • Children w/ neuro findings and/or rapidly progression spinal cord dysfxn should receive dexamethasone 1 mg/kg IV and have emergent spinal MRI
    • Children w/o neuro sx’s →MRI w/i 24 hr; low-dose dexamethasone PO (0.25–0.5 mg/kg)
    • Surgery, XRT, and chemo are other emergent Rx options depending on tumor type
Hyperleukocytosis
(Pediatr Clin North Am 1997;44:809)
  • Definition/etiology: WBC >100,000; Presence high # of circ leukemic blast cells
    • Clinically signif hyperleukocytosis >200,000 in AML, >300,000 in ALL and CML
    • Occurs in 9%–13% of patients with ALL and 5%–22% of patients with AML
  • Pathogenesis: Excessive leukocytes obstruct circulation in brain, lung, and other organs forming aggregates and white thrombi in small veins
    • Excessive leukocytes also compete for oxygen and damage vessel walls
    • Morbidity is directly related to blood viscosity
    • Myeloblasts and monoblasts are larger and more likely to cause obstruction
  • Clinical manifestations
    • Pulmonary leukostasis→ dyspnea, hypoxia, and right ventricular failure
    • Intracerebral leukostasis→ Δ mental status, frontal HA, szr’s, and papilledema
    • Other possible complications include priapism, renal failure, and dactylitis
    • Major complications of hyperleukocytosis in ALL usually result of TLS
    • Complications of hyperleukocytosis in AML usually are result of intracerebral leukostasis and include stroke and hemorrhage
  • Treatment: Aggressive hydration, alkalization, and allopurinol to minimize risk of TLS
  • Maintain platelet count >20,000 because of risk of intracranial hemorrhage
  • Maintain Hgb level <10 and minimize RBC xfusion to prevent further ↑ in viscosity
  • Correct coagulopathy w/ FFP and vitamin K as indicated
  • Exchange xfusion and leukophoresis also used to help rapidly ↓ leukocyte count
Neutropenia in the Pediatric Patient
(Pediatr Rev 2008;29:12)
Definition
  • Absolute neutrophil count (ANC) = WBC (cells/μL) × %(PMNs + bands) ÷ 100
  • Mild Neutropenia: ANC 1000–1500/μL; moderate neutropenia: ANC 500–1000/μL; severe neutropenia: ANC <500/μL
  • Note: Lower limit nml ANC = 1500 for pts >1 yo. For pts 2 wk–6 mo, nml ANC >1000. Pts <2 wk nml ANC variable. 3%–5% of African Americans have ANCs <1500 normally.
Differential Diagnosis
(Pediatr Rev 2008;29:12)
  • Acquired causes:
    • Infection:
      • Viral (most common cause neutropenia, 2/2 BM suppression, lasts 3–8 d): EBV, CMV, parvo, RSV, flu A/B, hepatitis, HHV6, VZV, rubella, rubeola, HIV
      • Bacterial: Typhoid fever, Shigella, brucellosis, tularemia, TB, malaria, RMSF
    • Drug-induced: PCNs, sulfonamides, chloramphenicol, phenytoin, ibuprofen, ranitidine, hydralazine, carbamazepine, cimetidine, chlorpromazine, indomethacin, quinidine, propylthiouracil, procainamide, chlorpropamide, phenothiazines.
    • Immune:
      • Neonatal alloimmune neutropenia (maternal antineutrophil IgG xfer across placenta, dx. w/ antineutrophil Ab in infant and maternal serum; self-resolves by 2–3 mo)
      • Primary autoimmune neutropenia (neutropenia may be severe, typically presents btw 5–15 mo, dx by detecting antineutrophil Ab in pt.)
      • Secondary autoimmune neutropenia (e.g., SLE, Evans syndrome)
    • Sequestration (typically mild neutropenia w/ splenomegaly of any cause)
    • Nutritional def (typically p/w anemia, hypersegmented PMNs): B12 or folate def
    • Chronic idiopathic
  • Inherited causes:
    • Severe congenital neutropenia (early infancy w/ severe neutropenia and infxns, may be AR = Kostmann syndrome (HAX1 gene mut) or AD (ELA2 and GFII mut’s. High risk of later developing MDS and/or AML)
    • Cyclic neutropenia (characterized by 21-d cycles w/ neutropenia lasting 3–6 d in a cycle, sometimes severe. Dx w/ serial CBCs 2–3×/wk × 4–6 wk.)
    • Shwachman-Diamond syndrome (mild-mod neutropenia + exocrine pancreatic insuff, short stature, metaphyseal dysplasia. ↑ risk for MDS/AML)
    • Marrow failure syndromes: Fanconi anemia(pancytopenia usually in 5–10 yo), dyskeratosis congenita (neutropenia, abn skin pigmentation, dystrophic nails, leukoplakia), Diamond-Blackfan syndrome (anemia, thumb, and craniofacial anom)
  • Syndromes w/ associated immunodeficiencies:
    • Hyper-IgM syndrome, dys-γ-globulinemia, myelokathexis, Chediak-Higashi (albinism, perph neuropathies), cartilage hair syndrome (fine hair, short-limbed, dwarfism, lymphopenia), Wiskott-Aldrich (eczema, neutropenia, thrombocytopenia), selective IgA def, reticular dysgenesis (SCID w/ neutropenia)
Initial Evaluation
(Pediatr Rev 2008;29:12)
  • Hx: Hx of infxn’s (esp mouth ulceration), cong anomalies, med exposures, recent illnesses. FHx for neutropenias or serious infxn’s, hospitalizations, blood dz’s
  • Exam: Physical feature c/w immunodeficiency syndrome (see earlier discussion).
  • Laboratory eval: CBC w/ diff & retic count. Consider rpt CBC to verify.
  • Further eval: Per suspected cause: observation (if mild/mod neutropenia and suspected viral cause, rpt CBC 1–2 wk), viral titers/tests, antineutrophil Ab (if AI suspected), serial CBCs (if cyclic suspected), DNA analysis for HAX1, ELA2, GFII (if severe congenital suspected), quant Igs w/ B and T cell subsets (if evidence of immunodef), ANA/anti-dsDNA (if SLE suspected), BM biopsy/aspirate (if multiple lines affected or dx unclear)
Acute Lymphoblastic Leukemia
Definition:
Clonal proliferation of either pre-B, mature B or T lymphocyte cell lines.
Epidemiology
(Pediatr Rev 2005;26:96)
  • ∼2500–3500 new pedi cases/yr; most common pedi cancer (25% all pedi cancer)
  • May occur at any age with peak incidence 2–5 yo; Males > Females, whites > blacks.
  • Risk factors: Down syndrome, neurofibromatosis type 1, ataxia telangiectasia, Fanconi, other syndromes.
Clinical Presentation
(Pediatr Rev 2005;26:96)
  • Fever (55%), bleeding +/- petechiae/purpura (45%), malaise (40%), bone pain (30%), hepatomegaly (70%), splenomegaly (50%), LAD (50%), abd pain (10%).
  • CBC: Leukocytosis or leukopenia and anemia (88%) and/or thrombocytopenia (80%)
  • Blasts may be visible on peripheral blood smear, but are not always present.
Prognostic Factors and Overall Prognosis
(N Engl J Med 2006;354:166)
  • Overall survival: ∼80 %
  • Favorable prognostic features: Age at presentation 1–9 yo, presenting WBC <50,000; favorable cytogenetics include: Hyperdiploidy (>50 chromo) w/ trisomies of 4, 10, and 17, t(12;21)/TEL-AML1 fusion gene.
  • Unfavorable prognostic features: Age <1 yo, presenting WBC >50,000, highly unfavorable cytogenetics: Hypoploidy (33–39 chromo) or near haploploidy (23 to 29 chromosomes), t(4;11)/MLL-AF4 fusion gene in infants (present in 80% of infant ALL), and t(9;22)/BCR-ABL protein/Philadelphia chromosome.
  • Other unfavorable features; fail to achieve morph remission after induction or >1% blasts detectable by PCR or flow cytometry (min residual dz) at the end of induction
Treatment
(Pediatr Clin North Am 2008;55:1; N Engl J Med 2006;354:166)
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Aug 18, 2016 | Posted by in PEDIATRICS | Comments Off on Oncology

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