Rotor syndrome path
low-grade pigment deposition, dissociation of liver cells, occasional necrotic foci, and fibrin precipitation.
Common Malignant Neoplasms of Infancy and Childhood
Special Predisposing Factors child cancers
Chromosomal and genetic syndromes.
• Congenital immunodeficiency syndromes.
• >200 genetic syndromes are associated with an increased susceptibility to cancer.
– Down syndrome (Trisomy 21) - Acute leukemia.
– Deletion 13q - Retinoblastoma.
– Wiskott Aldrich syndrome - Lymphoma.
– Agammaglobulinemia - Acute lymphoblastic leukemia (= ALL).
Common “Small, Round, Blue Cell” Tumors of Childhood
• Rhabdomyosarcoma (Sarcoma) – Embryonal
– Ewing‟s sarcoma/PNET – Small cell osteosarcoma
Neuroblastoma general characterisitcs
poorly differentiated tumor arising from primitive neural crest cells
normally give rise to the adrenal medulla and sympathetic ganglia.
Second most common solid malignant tumor in children.
Before age of 5
Germline mutation in ALK gene – familial predisposition to neuroblastoma.
Neuroblastoma clinical features
• < 2 years - Mass in abdomen, mediastinum, or other sites, fever, weight loss
• Older children – Signs of metastatic disease – bone pain, respiratory or gastrointestinal symptoms.
• Blueberry muffin baby – disseminated neuroblastoma – multiple cutaneous metastasis with deep blue discoloration of the skin
Neuroblastoma gross pathology
• 40 % arise in adrenal medulla.
• Remainder arise anywhere along the sympathetic chain
– paravertebral region of the
– posterior mediastinum (15%). .
• Size varies from minute nodules to tumors weighing >1 kg in weight
• With increasing size, areas of: – Necrosis.
– Cyst formation.
• Gross calcification in 40-50%.
Homer-Wright Pseudo rosette
the tumor cells are concentrically arranged about a central space filled with neuropil. No lumen.
Found in neuroblastomas
Small, round, blue cell tumor with sheets of small, primitive-appearing cells with dark nuclei, scant cytoplasm, and poorly defined cell borders
a faintly eosinophilic fibrillary material that corresponds to neuritic processes of the primitive neuroblasts.
Neuroblastoma spreads to
• Lymph nodes.
• Bone marrow.
• Subcutaneous tissue.
• Elevated blood levels of catecholamines
• Elevated urine levels of catecholamine metabolites
– Vanillylmandelic acid (VMA)
– Homovanillic acid (HVA)
• X –ray abdomen – calcification in tumor can be picked up
Neuroblastoma Prognostic factors
• Age of the patient
– < 1 year excellent prognosis – 1-5 years – intermediate
– > 5 years – poor prognosis
• Deletion distal 1p and gain of distal 17q - poor prognosis
• N-myc amplification – extrachromosomal double minute chromatin bodies or homogenously staining regions (HSR) on other chromosomes – poor prognosis
• Telomerase overexpression - poor prognosis
• Tyrosine kinase receptor A (Trk-A) – increased expression indicates good prognosis
Nephroblastoma (Wilms Tumor)
malignant embryonal neoplasm derived from nephrogenic blastemal cells
• Most common primary renal tumor of childhood
• Peak incidence – 2-5 years of age
• 10% cases associated with
– WAGR syndrome – deletion of WT1 gene
– Denys-Drash syndrome –dominant, negative inactivating mutation of WT1 gene
– Beckwith-Wiedemann syndrome – mutation of putative WT2 gene – overexpression of IGF2 protein
– Mutations of β-catenin gene (10% of sporadic
• Adrenal cortical cytomegaly
• Islet cell hypertrophy
• Renal medullary dysplasia
• Gonadal dysgenesis
• Renal abnormalities
• WT-1 gene mutation
• 90% chance of Wilms‟ tumor
ANIRIDIA (WAGR S.)
• Genitalabnormalities • Mentalretardation
Nephrogenic rests- precursor lesion
Seenintherenal parenchyma adjacent to approximately 40% of unilateral tumors and nearly 100% of bilateral tumors
Triphasic pattern: Embryonal tumor – recapitulates the normal development of the kidney.
• Blastema – sheets of small round blue cells
• Stroma – fibrocytic or myxoid in nature. May have striated muscle.
• Epithelium - abortive tubules and glomeruli
Anaplastic Subtype (5% of WT)
• Cells with hyperchromatic nuclei, >3 times larger than those in adjacent cells of similar type.
• Enlarged, bizarre, multipolar mitoses.
Correlates with acquired TP53 mutations
• Usually comes to clinical attention due to the detection of an abdominal mass by a parent when bathing or clothing a child.
• Other common presentations:
– Abdominal pain.
– Acute abdominal crisis secondary to traumatic rupture.
– Regional lymph nodes.
• Metastatic sites other than these three sites are unusual and should suggest other diagnoses
Most common intraocular malignant neoplasm of childhood.
• 40% congenital - RB1 gene - multiple tumors – bilateral
• 60% sporadic-unifocal, unilateral.
Within first 2 years
– White pupil (= leukocoria).
– Squint (= strabismus).
– Poor vision.
– Spontaneous hyphema (= hemorrhage into the anterior portion of the eye).
– Red, painful eye.
• Composed of small round cells with large hyperchromatic nuclei and scant cytoplasm.
• Flexner-Wintersteiner rosettes- Clusters of cuboidal tumor cells arranged around a central lumen
• Extension into optic nerve and/or subarachnoid space (CSF) with intracranial spread.
• Invasion of blood vessels, especially in the highly vascular choroid, with subsequent hematogeneous metastases.
• Frequent complication is secondary glaucoma
• Always fatal if untreated.
• 90% survival with early diagnosis and modern therapy.