7. tumors; pediatric pathology

Pediatric PathologyPediatric Pathology

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Dr. Krishna Tadepalli, MD, www.mletips.com

7. Pediatric Tumors7. Pediatric Tumors

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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


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

– 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


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


• 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


• 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


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

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NeuroblastomasNeuroblastomas

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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

• Nephrogenic rests =precursor lesions of Wilms tumors 11


• 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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Wilms TumorWilms Tumor

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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

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7. tumors; pediatric pathology

Health & Medicine

malignant tumors

fibrous tumors

krishna tadepalli

rhabdomyomas benign

adults benign tumors

weight larger tumors

mc tumors of infancy

softtissue tumors mesenchymal