3. Tumors and Tumor-like Conditions
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MC neoplasms of childhood = soft-tissue tumors (mesenchymal) - ? adults
Benign tumors more common than cancers
2% of all malignant tumors occur in infancy and childhood
Tumor-like conditions
1. Heterotopia (or Choristoma )
– Normal cells or tissues that are present in abnormal locations
– pancreatic tissue in stomach or small intestinal wall
– adrenal cells found in the kidney
2. Hamartoma
– Excessive, focal overgrowth of cells / tissues native to the organ but not having normal
architecture
– Examples = Adenomas of the liver, Hemangiomas, lymphangiomas, rhabdomyomas
Benign Tumors
1. Hemangioma = MC tumors of infancy
– Cavernous and capillary types
– Common on face and scalp
– Flat , larger lesions = port-wine stains
– Hereditary disorder:- von Hippel – Lindau (VHL) disease
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4. Benign Tumors contd….
• 2. Lymphatic tumors
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Lymphangiomas (hamartomatous or neoplastic)
– increase in size after birth
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Encroach on vital structures in mediastinum or nerve trunks of axilla
Lymphangiectasis = not progressive,
• 3. Fibrous tumors
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More common =Fibromatosis, sparsely cellular (multiple fibromas)
Congenital - infantile Fibrosarcomas {t (12:15)}
– ETV6-NTRK3 fusion transcript = diagnostic marker
– ETV6 (transcription factor) and NTRK3 gene is tyrosine kinase
• 4. Teratomas
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Histological maturity correlates with biologic behavior
well-differentiated cystic lesions (mature teratomas),
Age = two peaks ( 2 years of age & late adolescence or early adulthood)
Sacrococcygeal teratomas = MC ( more common in girls (M:F::4:1)
75% are mature and benign teratomas
Other sites of teratomas =testis, ovaries, midline
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5. • Malignant
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– Incidence and types (next slide)
– Neuroblastic tumors
– Wilm’s tumor
Neuroblastic tumors
Tumors of the sympathetic ganglia and adrenal medulla
Derived from neural crest cells
Neuroblastoma
– MC extra cranial solid tumor of childhood
– median age at diagnosis = 18 months
– MC diagnosed tumor of infancy
– Most of them are sporadic
Most characteristic features
– spontaneous or therapy-induced differentiation of primitive neuroblasts into
mature elements
– spontaneous tumor regression
– wide range of clinical behavior and prognosis,
Children younger than 18 months of age have better prognosis
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5-year survival is generally 40%
6. Malignant = Incidence and types
0 to 4 Years
Leukemia
5 to 9 Years
Leukemia
Retinoblastoma
Retinoblastoma
Neuroblastoma
10 to 14 Years
Neuroblastoma
Wilms tumor
Hepatoblastoma
Hepatocelluar carcinoma
Hepatocellular carcinoma
Soft-tissue sarcoma
(Rhabdomyosarcoma)
Soft-tissue sarcoma
Soft-tissue sarcoma
Teratomas
Central nervous system tumors Central nervous system tumors
Osteogenic sarcoma
Ewing sarcoma
Thyroid carcinoma
Lymphoma
Hodgkin disease
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7. • Malignant = Neuroblastic tumors contd..
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Morphology
Site = 40%arise in the adrenal medulla (MC site) followed by paravertebral region
of abdomen (25%), posterior mediastinum (15%) and other sites (pelvis, Neck,
brain (cerebral neuroblastomas)
Size = minute nodules (in situ lesions) to 1 kg in weight
– Larger tumors have necrosis, cystic softening, and hemorrhage
– In situ ones are more frequent and spontaneously regress
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Histologically
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LM= Made of small, primitive cells with dark nuclei, scant cytoplasm, and poorly defined
cell borders ; Karyorrhexis and pleomorphism are prominent; rosettes (Homer-Wright
pseudorosettes)
IHC =positive immuno –markers ( neuron-specific enolase (NSE), Synaptophysin,
Chromogranin A, S100 protein etc.,)
EM =cytoplasmic catecholamine-containing secretory granules with peripheral halo (dense
core granules)
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– Some show signs of maturation into ganglioneuroblastoma and ganglioneuroma
– Maturation is spontaneous or therapy-induced
– Differentiated lesions are accompanied by Schwann cells (this is prerequisite )
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Metastases to lymph node or/and liver, lungs, bone marrow, and bones
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8. • Malignant = Neuroblastic tumors contd..
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Staging.
Stage 1: Localized with complete gross excision
Stage 2: Localized with incomplete gross resection
Stage 3: Unresectable unilateral, across the midline
Stage 4: distant metastasis
Stage 4S ("S" = special): infants younger than 1 year & dissemination limited to
skin, liver, and/or bone marrow
Clinical Course and Prognostic Features
Under age 2 years= present with large abdominal masses, fever, weight loss
Older children = insignificant until metastases; present proptosis (common metastatic site)
and ecchymoses
– multiple cutaneous metastases ="blueberry muffin baby"
– 90% of neuroblastomas =produce catecholamines, helps in diagnosis
(hypertension is less frequent ) vanillylmandelic acid [VMA] and
homovanillic acid [HVA]) in urine or blood
• Prognosis
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"core" criteria used for risk stratification and therapeutic decision =age, stage, N8
MYC status, histology, and DNA ploidy
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9. Table 10-9. Prognostic Factors in Neuroblastomas
Table 10-9. Prognostic Factors in Neuroblastomas
Variable
Stage*
Favorable
Stage 1, 2A, 2B, 4S
Unfavorable
Stage 3, 4
Age*
<18 months
>18 months
Present
Absent
<200/5000 cells
>200/5000 cells
Histology*
Evidence of schwannian stroma and
gangliocytic differentiation†
Mitosis-karyorrhexis index‡
DNA ploidy*
Hyper diploid or near- Near-diploid
triploid
N-MYC*
Not amplified
Amplified
Chromosome 17q gain
Absent
Present
Chromosome 1p loss
Absent
Present
Chromosome 11q loss
Absent
Present
TRKA expression
Present
Absent
TRKB expression
Absent
Present
Telomerase expression
Low or absent
Highly expressed
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11. •
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Malignant= Wilm’s tumor
MC primary renal tumor of childhood
Peak age =between 2 and 5 years
Improvements in the cure rates
Pathogenesis and Genetics
Increased association with four syndromes
– 1. WAGR syndrome =aniridia, genital anomalies, mental retardation; deletions
of 11p13 (WT1 gene)
– 2. Denys-Drash syndrome= higher risk for Wilm's tumor (∼90%); gonadal
dysgenesis (male pseudohermaphroditism) and early-onset nephropathy;
dominant-negative missense mutation in the zinc-finger region of the WT1 gene
and increased risk for gonadoblastomas (WT1=critical for normal renal and
gonadal development)
– 3. Beckwith-Wiedemann syndrome (BWS) ="WT2”gene genomic
imprinting ; overexpression of IGF-2 (embryonal growth factor) is critical ;
Organomegaly, macroglossia, hemi-hypertrophy, omphalocele, adrenal
cytomegaly;
– 4. β-catenin associated Wilms tumors ; belong to WNT (wingless) signaling
pathway; 10% of sporadic cases, gain-of-function mutations
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Nephrogenic rests =precursor lesions of Wilms tumors
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12. • Malignant= Wilm’s tumor
• Clinical Features =large abdominal mass with hematuria,
abdominal pain, intestinal obstruction and HTN
• Pulmonary metastases
• Prognosis depends on (poor prognostic features)
– Anaplasia,
– loss of genetic material on chromosomes 11q and 16q,
– gain of chromosome 1q
• Risk of Second malignancies
– soft-tissue sarcomas,
– leukemia and lymphomas,
– breast cancers
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14. WILM’S TUMOR
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1stromal -Usually fibrotic or
myxoid in nature with Paler
type of cells
2blastemal - Bunch of less
undifferentiated
Dark cells Less differentiated
therefore worse prognosis
3Epithelial -Form of abortive
tubules or glomeruli as
epithelial rosettes
Better differentiated,
therefore better prognosis
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