Module 8:PEDS: Neoplasms

Question 1

What are the common malignant neoplasms in 0-4 yr olds?

Answer 1

Leukemia 
Retinoblastoma 
Neuroblastoma 
Wilm's Tumor 
Hepatoblastoma 
Soft Tissue Sarcoma 
Teratoma 
CNS tumor

Question 2

What are the common malignant neoplasms in 5-9 yr olds?

Answer 2

Leukemia 
Retinoblastoma 
Neuroblastoma 
Hepatocellular carcinoma 
Soft tissue sarcoma 
Ewing tumor 
CNS tumor 
Lymphoma

Question 3

What are the common malignant neoplasms in 10-14 yr olds?

Answer 3

Heptocellular Carcinoma 
Soft tissue sarcoma 
Osteogenic sarcome 
Thyroid carcinoma 
Hodgkin disease

Question 4

What are some general features of pediatric neoplasms?

Answer 4

Magnitude of pediatric malignancy is much lower than in adult

• most pediatric tumors are embryonal, not carcinomas
• -pediatric tumors dont occur in the same location as adult tumors
• -pediatric tumors are more responsive to therapy
• -better prognosis and survival rate than adults

Question 5

What are the predisposing factors for pediatric neoplasms?

Answer 5

Down syndrome and agammaglobulinemia
Deletion 13q (retinoblastoma)
Wiskott Aldrich Syndrome (lymphoma)

Question 6

What are the tumors of embryonal origin?

Answer 6

Small, round, blue cell tumors

• lymphoma/leukemia
• medulloblastoma
• -neuroblastoma
• -rhabdomyosarcoma (embryonal and alveolar)
• wilms tumor
• bone tumors (ewings sarcoma and small cell osteosarcoma)

Question 7

What is the origin of neuroblastoma?

Answer 7

Poorly differentiated tumor of NCC that normally give rise to the adrenal medulla and sympathetic due to germline mutation in ALK gene
–second most common malignant tumor in kids

Question 8

What is the presentation for neuroblastoma?

Answer 8

less than 2 years old: mass in abdomen or mediastinum, fever or weight loss
Older children: signs of metastatic disease (bone pain, resp and GI symptoms)
Blueberry Muffin baby: disseminated neuroblastoma

Question 9

What investigations are done for neuroblastoma?

Answer 9

Gross: calcification in 40-50%
Microscopy: neurophil (eosinophilic fibrillary material) and Homer-Wright Pseudorosettes (tumor cells arrange around neurophil without a lumen)
EM: neurosecretory granules
IHC: neuron-specific enolase and synaptophysin

Question 10

What confirms diagnosis of neuroblastoma?

Answer 10

Increased blood catecholamines
Increased urine levels of catecholamines (VMA and HVA)
MIBG scintigraphy: concentrates over 90% of tumors – used for assessment of spread and response to therapy

Question 11

What are the good and poor prognostic factors for neuroblastoma?

Answer 11

Good: stage 4S and increased expression of tyrosine kinase receptor A
Poor: deletion distal 1p and gain of distal 17q; n-myc amplification and telomerase overexpression

Question 12

Moving on to nephroblastoma (Wilm’s Tumor), what is this?

Answer 12

Malignant embryonal neoplasm from nephrogenic blastemal cells
–most common primary renal tumor of childhood

Question 13

What are the various etiologies for Wilm’s Tumor?

Answer 13

Most cases are sporadic 
10% are associated with:
--WAGR syndrome: WT-1 gene mutation 
--Denys-Drash syndrome: WT-1 gene mutation 
-Beckwith-Wiedemann syndrome 
-Mutations of Beta-Catenin Gene

Question 14

What is the precursor lesion for Wilm’s Tumor?

Answer 14

Nephrogenic rests

Question 15

What is presentation for Wilm’s Tumor?

Answer 15

Detection of abdominal mass by parent while bathing the child

Question 16

What is seen on histology for Wilm’s Tumor?

Answer 16

Triphasic pattern due to divergent differentiation

• -blastema: sheets of small round blue cells
• stroma: myxoid
• epithelium: abortive tubules and glomeruli

Question 17

What are complications of Wilm’s Tumor?

Answer 17

Restricted pattern of metastasis = regional LNs, lungs and liver

Question 18

What is the anaplastic subtype of Wilm’s Tumor?

Answer 18

5% of cases: characterized by hyperchromatic nuclei with greater than 3 times larger than those in adjacent cells
–correlates with acquired TP53 mutations

Question 19

Next is retinoblastoma, what is the etiology?

Answer 19

Malignant neoplasm arising from retina
–40% congenital: RB1 gene: multiple, bilateral tumors
(increased susceptibility to other malignant tumors: osteogenic sarcoma, Ewing’s sarcoma, pinealoblastoma)
–60% sporadic: unifocal and unilateral tumors

Question 20

What is the presentation for retinoblastoma?

Answer 20

Leukocoria 
Strabismus
Poor Vision 
Spontaneous Hyphema 
Red and Painful eye

Question 21

What is found on histology for retinoblastoma?

Answer 21

Flexner-Wintersteiner Rosettes: clusters of cuboidal cells arranged around a central lumen

Question 22

What are complications of retinoblastoma?

Answer 22

Extension into optic nerve and/or subarachnoid space with intracranial spread
Invasion of blood vessels
Secondary Glaucoma

Question 23

Finally where do teratomas arise from?

Answer 23

Most arise in the sacro-coccygeal region

–other sites = testes and ovaries

Question 24

What is the prognosis for teratomas?

Answer 24

Less than 4 months = benign
1 year = 50% malignant
5 years = 100% malignant
–proportion of immature elements is important in gauging degree of malignant potential