7. Pediatric Tumors

1. 7. Pediatric Tumors

2. Tumors and Tumor-like Conditions 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 disease

3. Benign Tumors contd�. 2. Lymphatic tumors Lymphangiomas (hamartomatous or neoplastic) increase in size after birth Encroach on vital structures in mediastinum or nerve trunks of axilla Lymphangiectasis = not progressive, 3. Fibrous tumors 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 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

4. Malignant 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 most common extra cranial solid tumor of childhood median age at diagnosis = 18 months most frequently 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 5-year survival is generally 40%

5. Malignant = Incidence and types

6. Malignant = Neuroblastic tumors contd.. 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 Histologically 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) Some show signs of maturation ganglioneuroblastoma and ganglioneuroma Maturation is spontaneous or therapy-induced Differentiated lesions are accompanied by Schwann cells (this is prerequisite ) Metastases to lymph node or/and liver, lungs, bone marrow, and bones

7. Malignant = Neuroblastic tumors contd.. 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 Histologically 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) Some show signs of maturation ganglioneuroblastoma and ganglioneuroma Maturation is spontaneous or therapy-induced Differentiated lesions are accompanied by Schwann cells (this is prerequisite ) Metastases to lymph node or/and liver, lungs, bone marrow, and bones

9. Malignant = Neuroblastic tumors contd.. 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 "core" criteria used for risk stratification and therapeutic decision =age, stage, N-MYC status, histology, and DNA ploidy

11. 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, emihypertrophy, omphalocele, adrenal cytomegaly; 4. �-catenin associated Wilms tumors ; belong to WNT (wingless) signaling pathway; 10% of sporadic cases, gain-of-function mutations Nephrogenic rests =precursor lesions of Wilms tumors

12. Malignant= Wilm�s tumor Clinical Features =large abdominal mass with hematuria, abdominal pain, intestinal obstruction and HTN soft-tissue sarcomas, leukemia and lymphomas, and breast cancers 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

14. WILM�S TUMOR 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