Upload
krishna-tadepalli
View
313
Download
3
Tags:
Embed Size (px)
DESCRIPTION
Citation preview
Pediatric PathologyPediatric Pathology
1
Dr. Krishna Tadepalli, MD, www.mletips.com
7. Pediatric Tumors7. Pediatric Tumors
2
Dr. Krishna Tadepalli, MD, www.mletips.com
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 (VHL) disease 3
Dr. Krishna Tadepalli, MD, www.mletips.com
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
Dr. Krishna Tadepalli, MD, www.mletips.com
• 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
– 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
• 5-year survival is generally 40%5
Dr. Krishna Tadepalli, MD, www.mletips.com
Malignant = Incidence and types
0 to 4 Years 5 to 9 Years 10 to 14 Years
Leukemia Leukemia
Retinoblastoma Retinoblastoma
Neuroblastoma 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 6
Dr. Krishna Tadepalli, MD, www.mletips.com
• 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 into 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 bones7
Dr. Krishna Tadepalli, MD, www.mletips.com
• 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 8
Dr. Krishna Tadepalli, MD, www.mletips.com
Variable Favorable Unfavorable
Stage* Stage 1, 2A, 2B, 4S Stage 3, 4
Age* <18 months >18 months
Histology*
Evidence of schwannian stroma and gangliocytic differentiation†
Present Absent
Mitosis-karyorrhexis index‡ <200/5000 cells >200/5000 cells
DNA ploidy* Hyper diploid or near-triploid
Near-diploid
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
Table 10-9. Prognostic Factors in NeuroblastomasTable 10-9. Prognostic Factors in Neuroblastomas
9
Dr. Krishna Tadepalli, MD, www.mletips.com
NeuroblastomasNeuroblastomas
10
Dr. Krishna Tadepalli, MD, www.mletips.com
• 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
• Nephrogenic rests =precursor lesions of Wilms tumors 11
Dr. Krishna Tadepalli, MD, www.mletips.com
• 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
12
Dr. Krishna Tadepalli, MD, www.mletips.com
Wilms TumorWilms Tumor
13
Dr. Krishna Tadepalli, MD, www.mletips.com
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
14
Dr. Krishna Tadepalli, MD, www.mletips.com
15