CHILDHOOD TUMORS

SGT
Tumorlike lesions of childhood
Heterotopia (choristoma)

• Microscopically normal cells present in abnormal locations

• Eg: pancreatic tissue in wall of stomach

• Small mass of adrenal cells in kidneys, lungs or ovaries

Hamartoma

• Excessive, focal overgrowth of cells native to organ in which it occurs

• Mature elements but do not show normal architecture of surrounding tissue

• Eg: hemangiomas, lymphangiomas, rhabdomyomas of heart

Benign tumors
Hemangioma
• Most common tumors of infancy

• Occurs in the skin, particularly on the face and scalp,

• Gross appearance: flat to elevated, irregular, red-blue masses

• flat, larger lesions - port-wine stains

• May enlarge along with the growth of the child, but in many instances, they
spontaneously regress

• Types- Capillary and Cavernous

• Occurs in von Hippel-Lindau disease

• CNS cavernous hemangiomas can occur in familial setting – mutations

in KRIT1, CCM2 or PDCD10
 Fibrous tumors
• Sparsely cellular proliferations of spindle-shaped cells (fibromatosis)

• Richly cellular lesions indistinguishable from fibrosarcomas occurring in adults

(designated as congenital-infantile fibrosarcomas)

• The congenital-infantile variants - excellent prognosis

• Chromosomal translocation t(12;15)(p13;q25) generation of ETV6-NTRK3

fusion transcript
Teratomas
• Teratomas may occur as:

• Benign, well-differentiated cystic lesions (mature teratomas)

• Lesions of indeterminate potential (immature teratomas)

• Unequivocally malignant teratomas (usually admixed with another germ cell

tumor component such as yolk sac tumor)

• 2 peaks in incidence: the first at 2 years of age and the second in late
adolescence or early adulthood

• Benign teratomas – young infants (<4 months)

• Sacrococcygeal teratomas - most common teratomas
of childhood

• 4 times more common in girls than in boys

• 10% of sacrococcygeal teratomas - associated with

congenital anomalies, primarily defects of the hindgut
and cloacal region and other midline defects
(meningocele, spina bifida)

• 75% - mature teratomas

• Other sites: testis, ovary, midline locations

(mediastinum, retroperitoneum, head and neck)
Malignant tumors
Common sites:
• Hematopoietic system
• Nervous system (including the
central and sympathetic
nervous system, adrenal
medulla, and retina)
• Soft tissue
• Bone
• Kidney
• Malignant nonhematopietic pediatric neoplasms - primitive (embryonal)
undifferentiated appearance

• Sheets of cells with small round nuclei with features of organogenesis

specific to the site of tumor origin

• Designated by the suffix -blastoma, for example, nephroblastoma (Wilms

tumor), hepatoblastoma, and neuroblastoma

• Because of their primitive histologic appearance, many childhood tumors

have been collectively referred to as small round blue cell tumors
 Neuroblastoma
• Neuroblastic tumour – tumours of sympathetic ganglia and adrenal medulla,
derived from primordial neural crest cells

• Most common extracranial solid tumour of childhood

• Median age at diagnosis - 18 months

• Usually sporadic

• 1% to 2% are familial involving both adrenals or multiple primary autonomic

sites

• Germline mutations in ALK gene

Site:

• 40% in adrenal medulla

• Paravertebral region of abdomen, posterior mediastinum, pelvis,

neck and brain

Gross appearance:

• Size ranges from minute nodules (insitu lesions) to large masses

• Sharp demarcation by a fibrous pseudocapsule

• Infiltrative with invasion into adjacent structures

• C/S – soft, gray-tan tissue

• Areas of necrosis, cystic softening and hemorrhage, punctate

intratumoral calcification
Microscopy:

• Arranged in solid sheets

• Small, primitive-appearing cells with dark nuclei,

scant cytoplasm and poorly defined borders

• Mitotic activity, nuclear breakdown (karyorrhexis)

and pleomorphism

• Eosinophilic fibrillary material – neuropil

• Homer-Wright pseudorosettes – tumour cells

concentrically arranged about a central space filled
with neuropil
• Larger cells with abundant cytoplasm, large vesicular
nuclei and prominent nucleolus – ganglion cells

• Admixed with primitive neuroblasts –

ganglioneuroblastoma

• Mature ganglion cells with few residual neuroblasts

– ganglioneuroma

• Maturation of ganglion cells accompanied by

appearance of Schwann cells

• Metastases – local infiltration, lymph node spread,

distant metastases
Clinical features:

• Young children – large abdominal masses, fever, weight

loss

• Older children – bone pain, respiratory symptoms, GI

symptoms (manifestations of metastases)

• Neonates – multiple cutaneous metastases “blueberry

muffin baby”

• Elevated blood levels of catecholamines

• Elevated urine levels of the metabolites vanillylmandelic

acid [VMA] and homovanillic acid [HVA]).
Wilms tumor
• Most common primary renal tumour of childhood

• Peak incidence – between 2 and 5 years of age

• 5 to 10% of Wilms tumors involve both kidneys, simultaneously

(synchronous) or one after the other (metachronous)
 Pathogenesis and genetics:
• Risk of Wilms tumour increased with atleast 3 recognized groups of
congenital malformations
WAGR syndrome
• Wilms tumour, Aniridia,
Genitourinary anomalies
and Intellectual disability
• Constitutional germline
deletions of 11p13
• Identification of WT1 –
“first hit”
Denys-Drash syndrome
• Gonadal dysgenesis (male
pseudohermaphroditism)
and early-onset nephropathy
• Germline abnormalities in
WT1
• Increased risk for
developing
gonadoblastomas
Beckwith-Wiedemann
syndrome
• Organomegaly,
macroglossia,
hemihypertrophy,
omphalocele and adrenal
cytomegaly
• Genomic imprinting
• Band 11p15.5 (WT2 locus)
• Overexpression of IGF2
protein
• Sporadic Wilms tumors:

• Gain-of-function mutations of gene encoding ß-catenin,

• recurrent mutations in genes encoding proteins involved

in miRNA processing (DROSHA, DGCR8 and DICER1)

• TP53 mutations

• Gross appearance:

• Large, solitary, well-circumscribed mass

• C/S – soft, homogenous, tan to grey with occasional foci

of hemorrhage, cyst formation and necrosis
Microscopy:

Blastemal • Sheets of small blue cells

Stromal • Fibroblastic or myxoid nature

Epithelial • Abortive tubules or glomeruli

Other heterologous elements –

squamous or mucinous epithelium,
smooth muscle, adipose tissue, cartilage
• Anaplasia – cells with large, hyperchromatic, pleomorphic nuclei and abnormal
mitoses

• Nephrogenic rests – putative precursor lesions of Wilms tumors, seen in adjacent

renal parenchyma

• Clinical features: large abdominal mass, hematuria, pain abdomen, intestinal

obstruction and hypertension

• Prognosis: Anaplasia, loss of heterozygosity of chr 1p and 16q, gain of

chromosome 1q

• Increased risk of developing second primary tumours – bone and soft tissue
sarcoma, leukemia and lymphomas
 QUIZ
The mother of a 6-month-old boy notices that he has a palpable abdominal mass. On physical examination, the
infant has a temperature of 37.8° C, and he is at the 33rd percentile for weight. An abdominal CT scan shows
a solid 5.5-cm mass involving the right adrenal gland. Laboratory studies show that 24-hour urine levels of
homovanillic acid (HVA) and vanillylmandelic acid (VMA) are increased. The adrenal gland is excised
surgically; the histologic appearance of the mass is shown in the figure. Which of the following features of
this lesion is most likely associated with a poor prognosis?

A) Age younger than 1 year

B) Hyperdiploidy

C) MYCN gene amplification

D) Presence of many ganglion cells

A 3-year-old child’s mother notes that a large stain on the left side of the
child’s face has not diminished in size since birth. This irregular, slightly
raised, red-blue area is not painful, but is very disfiguring. Histologically, this
lesion is most likely composed of a proliferation of which of the following
tissue components?

A) Capillaries

B) Fibroblasts

C) Lymphatics

D) Neuroblasts
Thank you