Chapter 14 - Oncology

Question 1

What are the most common childhood cancers?

Answer 1

1) leukemia
2) brain tumors
3) lymphoma
4) neuroblastoma
5) soft tissue sarcoma
6) Wilm’s tumor

Question 2

What are the typical presenting signs of a childhood cancer?

Answer 2

• persistent fever, especially that associated with weight loss or night sweats
• palpable or visible mass
• bone pain, reflecting metastatic cancer, primary bone tumors, or leukemic infiltration of bone marrow
• supraclavicular lymphadenopathy
• early morning headache and vomiting if CNS tumor
• bruising, petechiae, and pallor
• hypertension may be caused by neuroblastoma, Wilms’ tumor, or pheochromocytoma

Question 3

Acute Lymphoblastic Leukemia (ALL)

Answer 3

• the most common childhood cancer
• peak incidence is 2-6 years old in males
• most often of pre-B-cell origin, but occasionally of T-cell origin
• fever and bone/joint pain are most common, but other symptoms include pallor, bruising, hepatosplenomegaly, and lymphadenopathy
• diagnosis supported by anemia and thrombocytopenia but the white count is often variable
• lymphoblasts are often seen and stain positive for TdT
• age 1-9, female gender, caucasian, WBC less than 50K, hyperploidy, and no Ph- are all favorable prognostic factors
• treatment includes systemic and CNS chemotherapy, prophylaxis with TMP-SMX for opportunistic infections associated with chemo, and management of tumor lysis syndrome

Question 4

What is the difference between induction, consolidation, and maintenance therapy?

Answer 4

• induction: aims to destroy cancer cells and induce remission
• consolidation involves continuation of systemic chemo to prevent CNS involvement since systemic chemo penetrates the BBB poorly
• maintenance involves periodic chemo during remission

Question 5

What are the possible complications of tumor lysis syndrome?

Answer 5

• hyperuricemia, leading to renal insufficiency
• hyperkalemia, leading to cardiac dysrhythmias
• hyperphosphatemia, leading to hypocalcemia and tetany

Question 6

Acute Myelogenous Leukemia

Answer 6

• a leukemia of myeloid origin, which is less common than ALL in childhood
• presents with fever, hepatosplenomegaly, bruising and bleeding, bone pain, and gingival hypertrophy
• more likely than ALL to have CNS involvement and may contribute to DIC given the presence of Auer rods
• labs may find pancytopenia or leukocytosis
• managed with bone marrow transplant
• acute promyelocytic leukemia is the most important subtype but there is also acute monocytes leukemia (a proliferation of monoblasts, typically lacking MPO and characteristically infiltrating the gums) and acute megakaryoblastic leukemia (also lacking MPO and associated with Down syndrome, presenting before age 5).

Question 7

Acute Promyelocytic Leukemia

Answer 7

• a subtype of AML characterized by a t(15;17) translocation which disrupts the retinoic acid receptor (RAR)
• a risk for DIC given the presence of Auer rods
• treat with ATRA which causes the blasts to mature and die off

Question 8

Chronic Myelogenous Leukemia

Answer 8

• the least common type of leukemia in childhood
• the adult-type is more common than the juvenile and affects older children and adolescents whereas the juvenile type affects children younger than 2 years old
• the adult-type is defined by a BCR-ABL fusion protein due to a t(9;22) Philidelphia chromosome; the juvenile form is more associated with abnormalities of chromosomes 7 and 8
• the adult type presents with fatigue, weight loss, pain, massive splenomegaly, and an extremely high WBC (>100K)
• the juvenile type presents with fever, eczema-like facial rash, suppurative lymphadenopathy, petechiae and purpura, and moderate leukocytosis (<100K)
• the adult type has a biphasic course, responding to chemotherapy initially before relapsing and become unresponsive; the juvenile form is often fatal
• treat with imatinib, which binds and blocks the ATP-binding domain of the fusion protein

Question 9

What clinical features distinguish Hodgkin lymphoma from NHL?

Answer 9

• HL has a slower, indolent symptom onset
• HL is often accompanied by systemic symptoms whereas NHL is not
• HL most often localized to a single group of nodes, usually the cervical and supraclavicular nodes
• HL spreads contiguously and rarely affects the mesenteric nodes
• HL is characterized by the presence of Reed-Sternberg cells
• has a bimodal age distribution
• associated with EBV

Question 10

Describe Reed-Sternberg cells.

Answer 10

• markers of Hodgkin lymphoma
• binucleate
• CD15 and CD30 positive
• of B cell origin

Question 11

Hodgkin’s Disease

Answer 11

• a form of lymphoma associated with EBV infection
• presents with painless lymphadenopathy, most commonly in the supraclavicular or cervical regions
• treatment may lead to growth retardation, secondary malignancies, hypothyroidism, or male sterility
• distinguished from NHL on the basis that HL has a slower onset, rarely affects mesenteric nodes, is often accompanied by systemic symptoms, and Reed-Sternberg cells can usually be found
• staged according to the Ann Arbor system

Question 12

Describe the Ann Arbor System.

Answer 12

a method for staging hodgkin’s lymphoma
- I: involvement of a single lymph node or site
- II: involvement of two nodes on the same side of the diaphragm
- III: involvement of two nodes on different sides of the diaphragm
- IV: disseminated involvement
each stage is divided into A and B with A indicating a lack of systemic symptoms and B indicating systemic symptoms

Question 13

Burkitt’s Lymphoma

Answer 13

• a neoplastic proliferation of intermediate-sized B cells
• the fastest growing human tumor and therefore it may cause tumor lysis syndrome
• the sporadic form is strongly associated with EBV and classically presents with a mandibular mass
• the African form classically presents with an abdominal mass
• the HIV-related form presents with a nodal mass
• all are drive by t(8;14), which over expresses c-Myc, an oncogene
• characterized on histology by high mitotic index and a “starry-sky” appearance made by tingible macrophages

Question 14

Pilocytic Astrocytoma

Answer 14

• a benign tumor of astrocytes
• this is the most common CNS tumor in children and is typically located in the cerebellum
• arises as a cystic lesion with a mural nodule, which is easily identifiable on imaging
• histology shows Rosenthal fibers and eosinophilic granular bodies
• the section will be GFAP positive

Question 15

Medulloblastoma

Answer 15

• a malignant tumor derived from the granular cells of the cerebellum, which are neuroectoderm
• usually arises in children
• histology reveals small, round but cells forming Homer-Wright rosettes
• the tumor grows rapidly and spreads via the CSF; therefore it has a poor prognosis
• a metastasis to the cauda equina is known as a “drop metastasis”

Question 16

Ependymoma

Answer 16

• a malignant tumor of the ependymal cells lining the ventricles
• most often in the fourth ventricle of children
• may present with hydrocephalus if the tumor forms an obstruction
• histology reveals perivascular pseudorosettes

Question 17

Craniopharyngioma

Answer 17

• a tumor arising from the epithelial remnants of Rathke’s pouch (oral ectoderm) left behind on it’s way to form the anterior pituitary
• presents as a supratentorial mass in a child or young adult and may compress the optic chasm leading to a bitemporal hemianopsia
• associated with growth retardation, delayed puberty, visual changes, diabetes insidious, and other hormonal problems
• calcifications can be seen on imaging and cholesterol crystals are found in “motor oil-like” fluid within the tumor
• most common childhood supratentorial tumor
• although benign, it tends to recur

Question 18

What is the difference between a high-grade and a low-grade tumor?

Answer 18

• high grade are poorly differentiated and aggressive

- low grade are better differentiated and less aggressive

Question 19

What signs and symptoms are suggestive of a CNS tumor in children?

Answer 19

many nonspecific symptoms, which are caused by increased ICP and worse during sleep or on awakening since laying down reduces venous return from the head
- headache
- vomiting
- drowsiness, irritability, or abnormal behavior
- ataxia or head tilt
- seizure
PE findings
- enlarged or bulging fontanelle
- nystagmus
- papilledema
- cranial nerve abnormalities, most often CN VI palsy

Question 20

Under what circumstances is CNS radiation used in children?

Answer 20

• severe leukemia
• those with CNS tumor
• but usually avoided in those under the age of 5 because fo the risk of mental retardation, learning problems, stroke, hormonal problems, and secondary malignancy

Question 21

Wilms’ Tumor

Answer 21

• a malignant tumor comprised of blastema, primitive glomeruli and tubules, and stormal cells
• the most common malignant renal tumor in children, typically presenting before age 5
• presents as a large, unilateral flank mass with hematuria and hypertension
• usually sporadic but may be seen as part of WAGR, Denys-Drash, and Beckwiith-Weidemann syndromes
• in which case it may be accompanied by GU malformations, hemihypertrophy, or aniridia

Question 22

WAGR Syndrome

Answer 22

• a syndrome associated with deletion of the WT1 tumor suppressor gene
• presents with Wilms tumor, Aniridia, Genital abnormalities, and mental/motor Retardation

Question 23

Denys-Drash Syndrome

Answer 23

• a syndrome association with mutations of WT1

- presents with Wilms tumor, progressive renal disease, and male pseudohermaphroditism

Question 24

Beckwith-Wiedemann Syndrome

Answer 24

• a syndrome associated with mutations in the WT2 gene cluster, particularly IGF-2
• presents with Wilms tumor, neonatal hypoglycemia, muscular hemihypertrophy, and organomegaly including the tongue
• associated with hepatoblastoma

Question 25

Neuroblastoma

Answer 25

• a neuroendocrine tumor that can occur anywhere along the sympathetic chain but is the most common adrenal medullary tumor in children
• originates from neural crest cells and associated with N-myc oncogene over expression
• presents in children under 4 with abdominal distension and a firm, irregular mass that can cross the midline
• this distinguishes it from a Wilms tumor which is smooth and unilateral
• less likely to develop hypertension than with a pheochromocytoma but may present with opsoclonus-myoclonus syndrome (“dancing eyes and dancing feet”)
• may also present with flushing, hypertension, headache, sweating, weight loss, tracheal compression if cervical, or respiratory distress if mediastinal
• histology reveals prominent rosettes
• the catecholamine metabolites HVA and VMA are elevated in urine, the tumor is bombesin and neuron-specific enclave positive in addition to containing amine precursor uptake decarboxylase

Question 26

Rhabdomyosarcoma

Answer 26

• a malignant tumor of the embryonic mesenchyme that gives rise to skeletal muscle
• the most common malignant soft tissue tumor in children, usually occurring in those under 10yo
• the head, neck, and orbit are most commonly affected potentially causing proptosis, eyelid swelling, cranial nerve palsies, airway obstruction, or hoarseness
• the GU tract is also common as a “grape-like” mass with hematuria or vaginal bleeding
• characteristic cells are desmin-positive

Question 27

Osteoid Osteoma

Answer 27

• a benign tumor of osteoblasts, which produce osteoid, surrounded by a rim of reactive bone
• occurs mostly in males under the age of 25 in the cortex of long bones (most often the diaphysis)
• classically presents as bone pain that resolves with aspirin
• imaging will reveal a bony mass < 2 cm with a radiolucent core of osteoid

Question 28

Osteosarcoma

Answer 28

• a malignant proliferation of osteoblasts
• greatest incidence in males during the adolescent growth spurt, with another rise in prevalence in the elderly
• risk factors include familial retinoblastoma, Paget disease, radiation exposure, and Li Fraumeni syndrome
• arises in the metaphysis of long bones, most often around the region of the knee
• presents with bone pain, swelling, and pathologic fractures
• imaging reveals a destructive mass with a sunburst appearance that lifts the periosteum off the edge of the bone, creating Codman’s triangle
• histology reveals pleomorphic cells that produce osteoid

Question 29

Ewing’s Sarcoma

Answer 29

• a malignant proliferation of poorly-differentiated cells derived from neuroectoderm
• arises in the diaphysis of long bones, typically in males less than 15 years of age
• characteristic (11;22) translocation causing fusion protein EWS-FLI 1
• has an “onion-skin” appearance on x-ray since tumor grows in the medullary cavity, pushing on the surface and triggering the periosteum to produce layers of new bone
• biopsy reveals small, round blue cells that resemble lymphocytes; as such it may be confused with lymphoma or osteomyelitis since it may present with fever
• often presents with metastasis but is responsive to chemotherapy
• management should include chemo and surgery given the high risk for metastases

Question 30

Hepatoblastoma

Answer 30

• the most common liver tumor in childhood, presenting before age 3
• associated with Beckwith-Wiedemann syndrome
• presents as a right upper abdominal mass, loss of appetite, and weight loss; jaundice is usually not present
• diagnosed with CT or MRI and evaluation of AFP

Question 31

Hepatocellular Carcinoma

Answer 31

• occurs in young children and adolescents
• associated with chronic active hepatitis B infection, biliary atresia, glycogen storage disease type I, a1AT deficiency, and hereditary tyrosinemia
• presents as a right upper abdominal mass, loss of appetite, and weight loss; jaundice is usually not present
• diagnosed with CT or MRI and evaluation of AFP

Question 32

Langerhans Cell Histiocytosis

Answer 32

• a proliferation of langerhans cells, specialized dendritic cells found predominately in the skin
• Birbeck granules and CD1a+ S-100+ cells are classic findings
• the skull is most commonly affected by skeletal lesions and chronic draining ears may indicate involvement of the mastoid
• skin involvement often manifests as seborrheic dermatitis of the diaper area or scalp
• Letterer-Siwe disease is a malignant proliferation that presents with skin rash and cystic skeletal defects (more diffuse disease, common in those < 2 y.o.)
• Hand-Schuller-Christian disease is a malignant proliferation that affects bone and endocrine systems of those 2-5
• Eosinophilic Granuloma is a benign variant with bone and lung nodules, most common in those over the age of five

Question 33

Teratoma

Answer 33

• a cystic tumor composed of fetal tissue derived from two or three embryologic layers
• sacrococcygeal is the most common form in the first year of life and presents as a soft tissue mass; treat with removal of the tumor and coccyx
• anterior mediastinal teratomas may cause airway obstruction
• ovarian teratomas are bilateral in 10% of cases
• typically benign; however, the presence of immature tissue or somatic malignancy within the teratoma indicates malignant potential
• may present in females with pain secondary to torsion or enlargement of the ovary
• struma ovarii is a special teratoma that is composed mostly of thyroid tissue and may induce hyperthyroidism

Question 34

Endodermal Sinus Tumor

Answer 34

• a malignant germ cell tumor seen in men (as a nonseminoma) and women that mimics the yolk sac
• the most common germ cell tumor in children
• serum AFP is often elevated
• histology is likely to reveal Schiller-Duval bodies (glomeruloid-like structures)

Question 35

Seminoma

Answer 35

• a malignant testicular germ cell tumor and the most common testicular tumor
• comprised of large cells with clear cytoplasm and central nuclei, resembling an ovarian dysgerminoma
• grossly, it form s homogenous was without hemorrhage or necrosis
• it has the potential but rarely produces B-hCG
• responds well to radiotherapy

Question 36

Embryonal Carcinoma of the Testicle

Answer 36

• a malignant nonseminoma (testicular germ cell tumor)
• comprised of immature, primitive cells that may produce glands
• in contrast to a seminoma, it forms a hemorrhagic mass with necrosis
• it is aggressive with early hematogenous spread
• may see increases in AFP or B-hCG
• chemotherapy may result in differentiation into another type of germ cell tumor

Question 37

How do ovarian and testicular tumors differ in children compared to adults?

Answer 37

• ovarian are more likely malignant the young the patient

- testicular tumors are more likely benign in children than in adults