PEDIATRIC NEOPLASIA

Philip R. Faught, M.D.

MALIGNANT PEDIATRIC TUMORS

• The leading natural cause of death

under age 14 (accidents are #1)
• Brain tumors and leukemia/lymphoma
account for about two-thirds
• Pediatric and adult cancers are
different
 Other
8%
Soft-Tissue Sarcoma
7%
Leukemia
Bone
30%
5%
Liver
1%
Kidney
6%

Retinoblastom
3%

Neuroblastoma
8% Lymphoma
13%

CNS
19%
Table 10-6. Common Malignant Neoplasms
of Infancy and Childhood
0-4 Years 5 to 9 Years 10 to 14 Years
Leukemia Leukemia
Retinoblastoma Retinoblastoma
Wilms Tumor
Hepatoblastoma Hepatoblastoma Hepatoblastoma
Soft tissue sarcoma Soft tissue sarcoma Soft tissue sarcoma
(especially
rhabdomyosarcoma)
Teratomas
CNS tumors CNS tumors
Neuroblastoma Ewing’s tumor
Lymphoma Osteogenic sarcoma
Thyroid carcinoma
Hodgkin’s disease
 DIFFERENCES
IN PEDIATRIC CANCER
1. Site of origin different
2. Type – sarcomas, “blastomas,” small
round blue cell tumors
3. Bulk typically greater but no cachexia
4. Prognosis often better
5. Neonatal tumors – tend to be less
aggressive
6. Usually no precursor lesions in ped
cancer (exception – some Wilms tumors)
Congenital Sacrococcygeal
Teratoma – 1415 g Tumor
Preterm female with large sacrococcygeal
teratoma, died at 7 days of age due to
high output cardiac failure
Congenital Cervical
Teratoma – One day
Old Female
Newborn with maxillofacial teratoma;
survival was about 15 minutes
BLASTOMA – A neoplasm composed
of embryonic cells derived from the
blastema of an organ or tissue [Gr.
BLASTOS = germ]

BLASTEMA – A primitive group of

cells that give rise to an organ or part
in development or regeneration.
 The Important Blastomas
Nephroblastoma (Wilms Tumor) – Kidney
Neuroblastoma – adrenal medulla and
sympathetic nervous system
Hepatoblastoma – liver
Pleuropulmonary blastoma – lung/pleura
Pancreatoblastoma – pancreas
Retinoblastoma – neural retina
Medulloblastoma - cerebellum
 Small Round Blue Cell Tumors
• So-called because they consist of primitive
blastema-like cells

• Some adult tumors also have this appearance

(oat cell carcinoma of lung)

• Important to classify since treatment varies

widely
 Important Pediatric Cancers Not
Named as Blastomas
Primitive neuroectodermal tumor (PNET)
– Central (medulloblastoma)
– Peripheral (bone and soft tissue)
Rhabdomyosarcoma
Ewing’s Sarcoma
Lymphoma/leukemic infiltrates
Osteogenic Sarcoma
Other soft tissue sarcomas
 Neuroblastoma
• The most common malignant solid tumor of
childhood (after CNS)

• Most patients <5 years old, half <2 years old,

may be congenital

• Arise in the adrenal medulla, but also along the

sympathetic chain ganglia (or dorsal root
ganglia) anywhere from the base of the skull to
the pelvis
 Neuroblastoma
• Usually sporadic, seen with increased incidence
in VRD, tuberous sclerosis, Hirschsprung’s
disease, others

• May present with mass only or constitutional

symptoms

• Commonly metastatic at presentation – may

involve bizarre sites (orbits, skin)

• 90% secrete catecholamines but HTN rare

 Clinical Manifestations of Neuroblastoma

Multiple bluish
subcutaneous
Large abdominal mass
Metastases
(blueberry muffin)

Metastases to
Horner’s syndrome periorbital bones of
on the left both eyes
Neuroblastoma Stage IV S (Special)
• Metastases limited to liver, skin, bone
marrow

• Patients usually <1 year old and with small

primaries

• Have an unusually good prognosis

compared with stage IV
 Neuroblast
Cells
From Neural Crest

Adrenal Medulla
Peripheral N.S. Neurons
And
(ganglion cells)
Paraganglia

Nerve Sheath Cells

(Schwann cells)
 PRIMITIVE NEUROBLASTOMA

RECOGNIZABLE NEUROBLASTOMA

DIFFERENTIATING NEUROBLATOMA

GANGLIONEUROBLASTOMA

GANGLIONEUROMA (Benign)
Common Chromosomal Abnormalities in Neuroblastoma
Differentiating Neuroblastoma,
Posterior Mediastinal, 3 year old
Ganglioneuroma,
Posterior Mediastinal,
Neuroblastoma – Poorly Differentiated Area
Neuroblastoma – Area with Septation and Neuropil
Neuroblastoma – Homer-Wright Rosettes
Neuroblastoma Electron Microscopy
Neuroblastoma Electron Microscopy
Differentiating Neuroblastoma
Differentiating Neuroblastoma,
>5% ganglion cells but still with
Immature neuroblasts
Ganglioneuroma – mature ganglion
Cells within a schwannian stroma,
no immature neuroblasts
 NEUROBLATOMA
PROGNOSTIC FACTORS
1. Age and histology (Shimada scheme)

2. Stage

3. Location – abdominal worse than mediastinum, neck

pelvis; adrenal primary worse than other sites (except
IV S)

4. N-myc oncogene – aggressive tumors show

amplification

5. Many others – see handout and Robbins text

Wilms Tumor (Nephroblastoma)
• Most common malignant kidney tumor in
children

• About 500 new cases per year in U.S.

• Peak age 2-4 years, rarely congenital

• Most are sporadic but also occurs in hereditary

forms
 Conditions Associated with
Wilms Tumor
• Aniridia (up to 33% will develop Wilms tumor) – see
discussion of WT1 and WT2 genes in Robbins text

• WAGR syndrome (Wilms tumor , aniridia, GU anom.,

retardation)

• Drash syndrome (Wilms tumor, pseudohermaphroditism,

nephrotic synd)

• Beckwith-Weidemann syndrome (Exomphalos,

macroglossia, gigantism) and Perlman’s syndrome
(Wilms tumor, renal dysplasia, fetal gigantism,
pancreatic endocrine hyperplasia, MCA, MR)
 Conditions Associated with
Wilms Tumor
• Hemihypertrophy

• GU anomalies, skin hamartoma,

hemangiomas, malformed ears

• Increased incidence in VRD, Bloom’s

syndrome, trisomy 13 & 18, intersex
anomalies
 Wilms Tumor Clinical
Presentation
• Typical history is abdominal mass noted by mother

• Hematuria 5-10%

• Sudden hemorrhage into Wilms tumor may cause

anemia, HTN, rapidly increasing abdominal mass
(Ramsey’s Triad)

• Metastases to nodes, liver, lungs; bone metastases

extremely rare
Neglected Wilms tumor in a young
girl. The child had marked hypertension
Wilms tumor
757 g
22 month old
female
Wilms Tumor with Invasion
Of the Renal Pelvis, 900 g,
13 Month Old Female
Wilms Tumor with Hemorrhage
3 Year Old Female
Wilms Tumor Microscopic from Robbins 4th Edition
Wilms Tumor – Triphasic Pattern
Wilms Tumor – Blastema and Stroma
Wilms Tumor – Blastema and Epithelium
Wilms Tumor – with Fetal Skeletal Muscle
Anaplasia in a Wilms’ tumor
with a bizarre mitotic figure
 Unfavorable Histology in Wilms’
Tumors
• About 5% of WT are unfavorable histology
• Characterized histologically by increased
nuclear anaplasia/hyperchromasia and by
bizarre mitotic figures
• UH tumors are more resistant to chemoTx,
and have a worse prognosis if beyond
stage 1
• Anaplasia correlates with p53 mutations
 Wilms Tumor Prognosis
• Survival of low stage favorable histology
>90%

• Prognosis not as strikingly related to age

as with neuroblastoma

• Worse prognosis with extensive lung

metastases or with UH beyond stage 1