Review – Kaplan Pediatrics: Oncology

LEUKEMIA AND LYMPHOMA

 

Acute Lymphoblastic Leukemia

A 5-year-old patient is brought to the physician’s office with the chief complaint of a limp. The patient on physical examination has a low-grade fever, URI symptoms, hepatosplenomegaly, and petechiae.

 

• 77% of all childhood leukemias
• Onset brief and nonspecific (poor prognosis age <1 or >10 years at diagnosis)

−   Common—bone and joint pain, especially lower extremities

• Then signs and symptoms of bone marrow failure—pallor, bruising, epistaxis, petechiae, purpura, mucous membrane bleeding, lymphadenopathy, hepato- splenomegaly, joint swelling

• Diagnosis
  • Peripheral blood:

°      Anemia

• Thrombocytopenia
• Leukemic cells not often seen early

• WBC mostly <10,000/mm3 (atypical lymphocytes); poor prognosis if >100,000

−   Best test is bone marrow aspirate → lymphoblasts

• If chromosomal abnormalities, poor prognosis

• Treatment
  • Remission induction (98% remission in 4–5 weeks; slow response = poor prog- nosis) with combination drugs
  • Second phase = central nervous system (CNS) treatment
• Intensive systemic plus intrathecal chemotherapy
  • Maintenance phase 2–3 years
• Complications
  • Majority is relapse (15–20%):

°      Increased intracranial pressure (ICP) or isolated cranial nerve palsies

• Testicular relapse in 1–2% of boys

• Pneumocystis pneumonia
• Other infections because of immunosuppression

Note

ALL is both CALLA (common acute lymphoblastic leukemia antigen) and TdT-positive.

 

 

• Tumor lysis syndrome—result of initial chemotherapy (cell lysis): hyperurice- mia, hyperkalemia, hypophosphatemia → hypocalcemia (tetany, arrhythmias, renal calcinosis)
  • Treat with hydration and alkalinization of urine; prevent uric acid formation (allopurinol)
• Prognosis: >80% 5-year survival

 

Hodgkin Lymphoma

A 16-year-old boy presents with complaints of weight loss, fever, and night sweats. On physical examination, he is noted to have a nontender cervical lymph node that is 4–5 cm.

 

• Most in 15- to 19-year-olds
• Ebstein-Barr virus may play a role; immunodeficiencies may predispose
• Diagnostic hallmark—Reed-Sternberg cell (large cell with multiple or multilobu- lated nuclei)
• Four major histologic subtypes
  • Lymphocytic predominant
  • Nodular sclerosing
  • Mixed cellularity
  • Lymphocyte depleted; now considered to be a high-grade non-Hodgkin lymphoma
• Clinical presentation depends on location

−   Painless, firm cervical or supraclavicular nodes (most common presenting sign)

• Anterior mediastinal mass
• Night sweats, fever, weight loss, lethargy, anorexia, pruritus

• Diagnosis

−   Excisional biopsy of node (preferred)

• Staging from I to IV (single node or site to diffuse disease; multiple tests)

• Treatment
  • Determined by disease stage, large masses, hilar nodes
  • Chemotherapy
  • Radiation
• Prognosis—overall cure of 90% with early stages and >70% with more advanced

 

 

Non-Hodgkin Lymphoma

A 6-year-old boy presents to his primary care provider (PCP) with a nonproductive cough. The PCP makes the diagnosis of an upper respiratory infection. However, the patient’s symptoms persist, and he returns to his PCP. At this visit the patient is wheezing, and the PCP makes the diagnosis of reactive airway disease and prescribes an inhaled b2-agonist. The medication does not improve the symptoms; and the patient returns to the PCP for a third time. The patient is now complaining of cough and has a low-grade fever. The patient is diagnosed with clinical pneumonia; and an antibiotic is prescribed. Two days later the patient presents to the emergency center in respiratory distress. A chest roentgenogram shows a large mediastinal mass.

• Malignant proliferation of lymphocytes of T-cell, B-cell, or intermediate-cell origin

•      Epstein-Barr virus—major role in Burkitt lymphoma

• Predisposition with congenital or acquired immunodeficiencies
• Three histologic subtypes
  • Lymphoblastic usually T cell, mostly mediastinal masses

−   Small, noncleaved cell lymphoma—B cell

• Large cell—T cell, B cell, or indeterminate

• Presentation—depends on location
  • Anterior mediastinal mass (respiratory symptoms)
  • Abdominal pain, mass

– Hematogenous spread

• Diagnosis—prompt because it is a very aggressive
  • Biopsy
  • Any noninvasive tests to determine extent of disease: staging I to IV (localized to disseminated; CNS and/or bone marrow)
• Treatment
  • Surgical excision of abdominal tumors, chemotherapy, and monoclonal anti- bodies ± radiation
  • 90% cure rate for stages I and II

 

 

BRAIN TUMORS

Introduction

•      Second most frequent malignancy in children; mortality 45%

• More common <7 years of age
• Most are infratentorial (age 2–10 years, g., juvenile pilocytic astrocytoma, medul- loblastoma)
• Symptoms depend on location
• Head CT scan best initial test for all (MRI best imaging test overall)

 

 

Some findings of brain tumors in general:

• Severe persistent headaches
• Onset recurrent seizures
• New onset neurological abnormalities, g., ataxia
• Behavioral, personality changes
• Deterioration of school performance
• Visual changes III and VI nerve palsies
• Abnormal endocrine findings/new onset
• Papilledema

 

Infratentorial Tumors

•      Most common

• Low-grade, rarely invasive
• Most common—juvenile pilocytic astrocytoma
  • Classic site—cerebellum
  • Surgery, radiation, and/or chemotherapy
  • With complete resection, 80–100% survival

 

Others

• Malignant astrocytoma (includes glioblastoma multiforme)
• Medulloblastoma (midline cerebellar)
• Brain stem tumors (diffuse intrinsic with very poor outcome low-grade gliomas)
• Ependymoma (most posterior fossa)

 

Supratentorial Tumors

Craniopharyngioma

A 14-year-old girl presents to the physician because of short stature. On physical examination, the patient is found to have bitemporal visual field defects. A head CT scan shows calcification at the sella turcica.

• Most common; 7–10% of all
• Minimal invasiveness; calcification on x-ray
• Major morbidity—panhypopituitarism, growth failure, visual loss
• Surgery and radiation; no role for chemotherapy

 

Optic nerve glioma

A 4-year-old boy with neurofibromatosis presents to the ophthalmologist with complaints of decreased visual acuity according to his parents. On physical examination, the patient has proptosis and papilledema.

• Most frequent tumor of the optic nerve; benign, slowly progressive

 

 

•      Unilateral visual loss, proptosis, eye deviation, optic atrophy, strabismus, nystagmus

• Increased incidence in neurofibromatosis
• Treatment—observation:
  • If chiasm is involved—radiation/chemotherapy
  • Surgery if proptosis with visual loss

 

OTHER MALIGNANCIES

Wilms Tumor

A mother brings her 3-year-old child to the physician because she found an abdominal mass while bathing the child. The child has been in her usual state of health according to the mother. However, on review of the vital signs, the patient is noted to have an elevated blood pressure.

 

 

• Nephroblastoma (Wilm’s tumor)

•      Second most common malignant abdominal tumor

• Usual age 2–5 years
• One or both kidneys (bilateral in 7%)

−   Associations:

• Hemihypertrophy
• Aniridia
• Genitourinary anomalies
• WAGR

• Clinical presentation—most are asymptomatic abdominal mass (unless invasive, at diagnosis some with ­ BP it renal ischemia)
• Diagnosis
  • Best initial test–ultrasound

−   Abdominal CT scan confirmatory test

• Treatment
  • Surgery
  • Then chemotherapy and radiation
  • Bilateral renal—unilateral nephrectomy and partial contralateral nephrectomy
• Prognosis—54 to 97% have 4-year survival

 

Neuroblastoma

A 2-year-old child is brought to the physician because of bluish skin nodules, periorbital proptosis, and periorbital ecchymosis that have developed over the last few days. On physical examination, a hard smooth abdominal mass is palpated.

•      From neural crest cells, due to N-myconcogene; can occur at any site

• 8% of childhood malignancies
• Most are
  • Adrenal

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Note

Patients with neuroblastoma can present with ataxia or opsomyoclonus (“dancing eyes and dancing feet”). These patients may also have Horner syndrome.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Note

Children with pheochromocytoma excrete predominantly

norepinephrine-increased VMA and metanephrine. Children with neuroblastoma usually

do not have hypertension, and major metabolites are dopamine and HVA.

• Retroperitoneal sympathetic ganglia
• Cervical, thoracic, or pelvic ganglia
• Firm, palpable mass in flank or midline; painful; with calcification and hemor- rhage
• Initial presentation often as metastasis—long bones and skull, orbital, bone mar- row, lymph nodes, liver, skin
• Diagnosis
  • Plain x-ray, CT scan, MRI (overall best)
  • Elevated urine homovanillic acid (HVA) and vanillylmandelic acid (VMA) in 95% of cases
  • Evaluate for spread—bone scan, bone marrow (neuroblasts) → staging from I (organ of origin) to IV (disseminated)
• Treatment
  • Surgery
  • Chemotherapy and radiation
  • Stem cell transplant (definitive)

 

Pheochromocytoma

• Catecholamine-secreting tumor from chromaffin cells
• Most common site—adrenal medulla, but can occur anywhere along abdominal sympathetic chain
• Children age 6–14 years; 20% are bilateral, and some with multiple tumors
• Autosomal dominant; associated with neurofibromatosis, MEN-2A and MEN2B, tuberous sclerosis, Sturge-Weber syndrome, and ataxia-telangiectasia
• Clinical presentation
  • Episodic severe hypertension, palpitations and diaphoresis, headache, abdomi- nal pain, dizziness, pallor, vomiting, sweating, encephalopathy
  • Retinal examination—papilledema, hemorrhages, exudate
• Labs—significant increase in blood or urinary levels of catecholamines and metabolites
• Diagnosis
  • Most tumors can be localized by CT scan (best initial test) and MRI, but extra- adrenal masses are more
  • Can use I131 metaiodobenzylguanidine (MBIG) scan → taken up by chromaf- fin tissue anywhere in body
• Treatment—removal, but high-risk
  • Preoperative alpha and beta blockade and fluid administration
  • Need prolonged follow up; may manifest later with new tumors

 

 

 

Rhabdomyosarcoma

A mother brings her 3-year-old daughter to the physician for evaluation because the young girl has “grapes” growing out of her vagina.

• Almost any site, which determines presentation; determination of specific histo- logic type needed for assessment and prognosis

−   Head and neck—40%

• Genitourinary tract—20%
• Extremities—20%
• Trunk—10%
• Retroperitoneal and other—10%

• Increased frequency in neurofibromatosis
• Types
  • Embryonal—60%
    • Intermediate prognosis
  • Botryoid (projects; grapelike)—vagina, uterus, bladder, nasopharynx, middle ear
  • Alveolar—15%
    • Very poor prognosis
    • Trunk and extremities
  • Pleomorphic—adult form; very rare in children
• Clinical presentation
  • Mass that may or may not be painful
  • Displacement or destruction of normal tissue
  • Easily disseminates to lung and bone
• Diagnosis—depends on site of presentation
  • Biopsy, CT, MRI, U ¹ S, bone scan
• Treatment—best prognosis with completely resected tumors (but most are not completely resectable)
  • Chemotherapy pre- and postoperatively; radiation