Chapter 10 Part 3 Flashcards
Sudden Infant Death Syndrome definition
sudden death of an infant under 1 yr of age which remains unexplained after a thorough case investigation including performance of a complete autopsy, examination of the death scene, and review of the clinical history; diagnosis of EXCLUSION
Examples of SIDS risk factors
young maternal age, drug use, low socioeconomic group, male sex, SIDS in prior sibling, prematurity, hyperthermia, co-sleeping, child abuse, long QT syndrome, etc.
Common postmortem morphological findings
petechiae, congested lungs, vascular engorgement, astrogliosis of brainstem, hypoplasia of dentate nucleus
Key risk factors for SIDS
vulnerable infant, critical developmental period in homeostatic control, exogenous stressor
Leading hypothesis for SIDS pathogenesis
delayed development of “arousal” and cardioresp control (medulla oblongata), defective serotonin pathway
Function of laryngeal chemoreceptors as they relate to SIDS
Typically elicit a cardiorespiratory inhibitory effect, stimulation augmented by resp infection and prone position
Common environmental stressors that are associated with SIDS
maternal smoking, thermal stress, sleeping on soft surfaces, prone or side sleeping
Definition of benign tumor
gross and microscopic appearances considered innocent, meaning it will remain localized, not spread, and is amenable to surgical removal
Definition of heterotopia
microscopically normal cells or tissues that are present in abnormal locations
Definition of hamartoma
excessive focal overgrowth of cells and tissues native to the organ (ex. hemangioma, lymphangioma, adenoma of the liver)
Hemangioma
most common tumor of infancy, cavernous or capillary, most will spontaneously regress; can be indicative of von Hippel-Lindau disease
Sturge-Weber Syndrome
sporadic congenital neurocutaneous disorder characterized by port-wine stain affecting skin in ophthalmic branch of CNV, abnormal capillary venous vessels in leptomeninges of brain and choroid, glaucoma, seizures, stroke, intellectual disability
Lymphatic tumors
lymphangiomas (hamartomatous) or lymphangiectasis; often occurs in neck, axilla, mediastinum
Fibrous tumor genetic anomaly
can look like adult fibrosarcomas; chromosomal translocation t(12;15)(p13;q25) resulting in ETV6-NTRK3 transcript causing stimulation of oncogenic RAS and PI3K/AKT pathway
Teratoma
can be benign or malignant, peak incidence at 2 yrs of age or late adolescence/early adulthood; more mature=better prognosis
Sacrococcygeal teratoma
congenital anomalies in hindgut, cloacal region and midline defects
Characteristics of pediatric neoplasms
histologically unique, primitive, sheets of cells with small, round nuclei, organogenesis specific to site of tumor
In what tissues do most pediatric cancers arise?
hematopoietic system, soft tissues, nervous system, bone, kidney
Most common neoplasms in children under 10
leukemia, neuroblastoma, wilms tumor, hepatoblastoma, retinoblastoma, rhabdomyosarcoma, teratoma, ewing sarcoma, astrocytoma, medulloblastoma, ependymoma
Neuroblastic tumors
most common extracranial solid tumor of childhood, occur sporadically but 1-2% are familial (ALK gene), tumors of sympathetic ganglia and adrenal medulla arising from neural crest population
Key characteristics of neuroblastomas
spontaneous or therapy-induced differentiation of primitive neuroblasts into mature elements, spontaneous regression, wide range of clinical behavior and prognosis
Clinical presentation of neuroblastoma
<2 yo with large abdominal mass, fever, with or without weight loss, cutaneous metastases; >2yo presents with mets (periorbital region, lungs, blood, liver, bones)
Key diagnostic feature of neuroblastoma
catecholamines increased in blood, VMA and HVA increase in urine
Gross appearance of neuroblastoma
soft, gray-tan tissue, areas of necrosis, cystic softening, hemorrhage, calcification
Histological appearance of neuroblastoma
primitive cells with dark nuclei, mitotic activity, muclear breakdown, neuropil that corresponds to neuritic processes of neuroblasts, Homer-Wright pseudorosettes,
Stage I neuroblastoma
localized tumor with complete gross excision, ipsilateral lymphnodes negative for tumor
Stage IIa neuroblastoma
Localized tumor with incomplete gross resection
Stage IIb neuroblastoma
localized tumor with or without excision, ipsilateral lymph nodes positive for tumor, enlarged contralateral lymph nodes negative for tumor
Stage III neuroblastoma
unresectable unilateral tumor infiltrating across midline with or with out regional lymph node involvement
Stage IV neuroblastoma
any primary tumor with dissemination to lymph nodes, bone, bone marrow, other organs
Stage IVs neuroblastoma
localized tumor with dissemination to skin, liver, bone marrow; limited to infants < 1 year
Most important determinant of neuroblastoma outcome
age and stage
Favorable: Stage 1, 2A, 2B, 4S; <18 mo
Unfavorable: Stage 3, 4; >18 mo
Most important molecular determinant of neuroblastoma outcome
MYCN amplification
Favorable: not amplified
Unfavorable: amplified
Chromothripsis
extensive genomic rearrangement and oscillating DNA pattern in one or two chromosomes
Ploidy variable, neuroblastoma
Favorable: Hyperdiploid (whole chromosome gains)
Unfavorable: near-diploid (segmental losses)
Prevalence of neuroblastoma
1/7000 live births
Prevalence of Wilms tumor
1/10000 children in US, most primary renal tumor of childhood with peak incidence between 2-5 years
Synchronous
simultaneously
metachronus
one after the other
Common presentation of wilms tumor
large abdominal mass, hematuria, pain in abdomen, intestinal obstruction ,appearance of hypertension
Gross appearance of wilms tumor
large solitary well circumscribed mass, soft, homogenous, tan-grey, necrosis, cyst formation, hemorrhage
What combination of cell types are typically seen in a Wilms tumor
blastemal, stromal, epithelial; may also contain some cell types not normal to this organ
Definition of anaplasia
lack of differentiation, hallmark of malignancy, TP53 mutation, correlates with chemo resistance
Risk of wilms tumor is increased with what 3 groups of chromosomal malformations?
WAGR/WAGI syndrome, Denys-Drash syndrome, Beckwith-Weidman syndrome
WAGR syndrome
Wilms tumor, aniridia, genital anomalies, mental retardation
WAGR syndrome genetic anomaly
deletion of 11p13 - WT1 (wilms tumor) and PAX6 (aniridia/eye development); germline WT1 deletion is “first hit”, frameshift or nonsense mutation is second hit
Risk for wilms tumor of WAGR patients
33%
Risk for wilms tumor of Denys-Drash syndrome
90%
Clinical characteristics of Denys-Drash syndrome
gonadal dysgenesis, early onset nephropathy, increased risk of gonadoblastoma
Genetic anomaly in Denys-Drash syndrome
dominant negative missense mutation in WT1 that effects DNA binding properties, interferes with function of wild-type allele resulting in genital anomalies; bi-allelic inactivation of WT1 results in tumorigenesis
Normal function of WT1
oncogene, DNA transcription factor involved in kidney and gonad development expressed during embryogenesis
Clinical characteristics of Beckwith-Wiedemann syndrome
organomegaly, macroglossia, hemihypertrophy, omphalocele, adrenal cytomegaly
Gene/chromosomal region in BWS
WT2, 11p15.5 - coding IGF2, if genetic imprinting is lost IGF will be over expressed
CDKN1C mutation
BWS mutation, normally acts as a cell cycle regulator that inhibits multiple CDKs
Increased tumor risks associated with BWS
hepatoblastoma, pancreatoblastoma, adrenal cortical tumors, rhabdomyosarcoma
Definition of nephrogenic rests
precursor lesions of Wilms tumors seen in renal parenchyma adjacent to unilateral tumors, increased risk for developing wilms tumor in contralateral kidney and requires regular surveillance
