13_Peds II Flashcards
define: sudden infant death syndrome (SIDS)
- sudden death of infant under 1 years old; usually dying while asleep
- remains unexplained after investigation incl
- complete autopsy
- examination of death scene
- review of clinical hx
sudden infant death syndrome:
epidemiology
- A leading cause of death in US infants ages 1 mo- 1 year
- 90% of cases are <6 months (most 2-4 months)
- 3rd cause of death overall in this age group (after congenital anomalies, disease of prematurity and low birth weight)
sudden infant death syndrome:
pathogenesis (“triple risk” model)
- multifactorial condition; triple risk model:
- vulnerable infant: delayed development of arousal and cardiorespiratory control; ? genetic factors
- critical developmental period in homeostatic control (1 mo- 1 year)
-
one or more exogenous stressors:
- prone (face-down) sleeping
- sleeping on soft surfaces
- thermal stress
how does the prone position cause Sudden Infant Death Syndrome?
- increases infant’s vulnerability to noxious stimuli during sleep
- assoc w/ decreased arousal responsiveness compared to supine
what campaign decreased SIDS incidence?
- Recommendation is to have healthy infants on their back;
- “back to sleep” campaign –> substantial decrease in SIDS-related deaths since 1994
- (studies from europe, australia, new zealand, and US
gross morphology of Sudden Infant Death Syndrome?
-
multiple petechiae:
- most common finding in typical SIDS autopsy (80%)
- usually present on thymus, visceral and parietal pleura, and epicardium
- congested lungs
microscopic morphology of Sudden Infant Death Syndrome?
- inconsistent histologic findings, but:
- vascular engorgement w/ or w/out pulmonary edema
- sophisticated morphometric studies: hypoplasia of arcuate nucleus;
- or subtle decrease in brain stem neuronal populations
factors associated w/ SIDS?
some are related to environment (prone sleeping position, soft surface, hyperthermia, co-sleeping with parents);
some related to birth order
what is: accumulation of edema fluid in the fetus during intrauterine growth?
fetal hydrops
what are causes of fetal hydrops?
(2 major types)
- immune hydrops: hemolytic anemia caused by Rh blood group incompatibility b/w mother and fetus
- nonimmune hydrops: due to successful pregnancy prophylaxis
how does severity of fetal hydrops vary?
- RANGE OF INTRAUTERINE FLUID ACCUMULATION
-
Usually lethal:
- progressive, generalized edema of the fetus (hydrops fetalis)
-
Compatible with life:
- more localized and less marked edema, (isolated pleural & peritoneal effusions or postnuchal fluid collections (cystic hygroma)
what type of immune hydrops results from antibody-induced hemolytic disease in the newborn caused by blood group incompatibilty b/w mother and fetus (ABO & Rh)?
Immune hydrops
- Immune hemolysis
- progressive anemia
- tissue ischemia
- intrauterine cardiac failure
- peripheral pooling of fluid edema
what is most common cause of immune hydrops (immune hemolytic disease of newborn)?
- fetomaternal ABO incompatibility currently is the most common cause of immune hemolytic disease (no effective method of ABO incompatibility prevention, but milder than Rh)
- DUE TO REMARKABLE SUCCESS IN PREVENTION OF Rh hemolysis
- Tx is Rh-negative mothers are given anti-D globulin soon after delivery of Rh-positive baby
causes of Nonimmune hydrops?
- cardiovascular defects (structural and functional)
- chromosomal anomalies (45,X karyotype/Turner syndrome, Trisomy 21, Trisomy 18)
- fetal anemia
how does fetal anemia cause nonimmune hydrops?
- homozygous alpha-thalassemia
- causes
- tissue ischemia
- secondary myocardial dysfunction
- circulatory failure
- secondary liver failure
- hypoalbuminemia
- reduced plasma osmotic pressure
- edema
gross morphology of hydrops fetalis?
- generalized accumulation of fluid in fetus
- fluid accumulation particularly prominent in soft tissues of the neck; (cystic hygroma)
which virus is thought to be associated w/ fetal hydrops?
transplancental infxn by parvovirus B19 –> increasingly recognized as important cause
- virus gains entry into erythroid precursors (normoblasts) –> replicates
- cellular injury –> death of normoblasts –> aplastic anemia
HISTO: parvoviral intranuclear inclusions can be seen w/in circulating and marrow erythroid precurosrs (arrows)
what is / cause of erythroblastosis fetalis?
- large number of normoblasts and erythroblasts in peripheral circulation
- caused by increased hematopoeitic activity
define: extramedullary hematopoiesis
- hematopoiesis occurring outside of the medulla of the bone (bone marrow); physiologic or pathologic
- occurs in any solid organ: liver, spleen, kidneys, lungs, lymph nodes, heart
In bone marrow, there is compensatory hyperplasia of erythroid precursors
kernicterus:
pathophysiology
- hemolysis in Rh or ABO incompatibility –> increased circulating bilirubin from RBC breakdown –>
- circulating unconjucated bilirubin is taken up by brain tissue –> toxic effect
- basal ganglia and brain stem are prone to deposition of bilirubin pigement –> characteristic yellow hue to parenchyma
at what point of kernicterus may the CNS be damaged?
when hyperbilirubinemia is markedly elevated
(above 20 mg/dL in full-term infants, lower threshold in premature infants)
terms for: microscopically normal cells or tissues that are present in abnormal locations
heterotopia or choristoma
(eg. pancreatic tissue “Rest” in stomach or small intestine, or adrenal rest in kidneys, lungs, ovaries, etc)
usually of little clinical significance
define: hamartoma
-
tissue is normal, but pattern of growth is not normal
- focal overgrowth of cells and tissues native to the organ in which it occurs
- cellular elements are mature and identical to those found in the remainder of the organ,
- but they do not reproduce the normal architecture of the surrounding tissue
define: hemangioma
- produce flat to elevated, irregular, red-blue masses; flat, larger lesions called “port wine stains”
- mostly in skin, (face and scalp)
- types
- cavernous hemangioma
- capillary hemangioma
what are the most common tumors of infancy?
hemagioma;
may enlarge at child gets older, or spontaneously regress
clinical significance of hemangiomas?
- majority of superficial hemangiomas: cosmetic significance
- rarely - can be manifestation of hereditary disorder assoc w/ disease of internal organs
- von Hippel-Lindau & Sturge-Weber syndromes
- some CNS cavernous hemangiomas can occur in familial setting
- have mutations in one of 3 cerebral cavernous malformation genes
define: lymphangioma
- lymphatic counterpart of hemangiomas
- may occur on skin or deeper regions of neck, axilla, mediastinum, retroperitoneum
- HISTOLOGICALLY BENIGN, but may encroach on mediastinal structures or nerve trunks in axilla
- (tend to increase in size after birth)
histo features of lymphangioma
- cystic and cavernous spaces lined by endothelial cells and surrounded by lymphoid aggregates
- spaces usually contain pale fluid
what is most common germ cell tumor of childhood (accounting for 40% of cases)?
sacrococcygeal teratoma
- 10% of associated with congenital anomalies
- 75% of tumors are histologically mature with a benign course
- 12% are malignant and lethal
- remainder are immature teratomas
are immature teratomas benign or malignant?
malignant potential correlates w/ amount of immature tissue elements present;
most benign teratomas seen in young infants; children w/ malignant lesiosn are usually older
what type of tumors are collectively referred to as small, round, blue cell tumors, even if they’re histologically unique?
many malignant tumors have sheets of cells w/ small round nuclei, incl:
- neuroblastoma
- lymphoma
- rhabdomyosarcoma
- ewing sarcoma (peripheral neuroectodermal tumor)
- some wilms tumor
malignant tumors:
microscopic appearance
- primitive (embryonal) microscopic appearance)
- exhibit features of organogenesis specific to site of origin
most common malignant neoplasm in ages 0-9 y/o?
leukemia
neuroblastoma:
define, and unique features
- def: tumors of sympathetic ganglia & adrenal medulla derived from primordial neural crest cells
- unique features:
- spontaneous regression
- spontaneous or therapy-induced maturation
neuroblastoma:
epidemiology
- second most common solid malignancy of childhood after brain tumors
- 7-10% of all pediatric neoplasms & 50% of infancy malignancies
neuroblastoma:
etiology
more are sporadic, but 1-2% are familial, with autosomal
- germ line mutations in anaplastic lymphoma kinase gene; major cause of familial disposition
- somatic gain of function ALK mutations are observed in subset of sporadic neuroblastomas
Tumors harboring ALK germline or somatic mutations will be amenable to treatment using drugs that target activity of this kinase
neuroblastoma:
location
- 40% arise in the adrenal medulla
- remainder anywhere along sympathetic chain
- paravertebral region of the abdomen (25%)
- posterior mediastinum (15%)
neuroblastoma:
macroscopic morphology
- range in size from minute nodules (the in situ lesions) to large masses weighing more than 1 kg
- cut surface: soft, gray-tan, brain-like tissue
- larger tumors have areas of necrosis, cystic softening, and hemorrhage
neuroblastoma:
histo morphology
- small cells embedded in a finely fibrillar matrix (neuropil)
- a homer-wright pseudorosette (tumor cells arranged concentrically around a central core of neuropil)
ganglioneuroma:
etiology, and microscopic morphology
- arises from spontaneous or therapy-induced maturation
- histo:
- clusters of large cells w/ vesicular nuclei and abundant eosinophilic cytoplasm, representing neoplastic ganglion cells
- spindle-shaped schwann cells are present in background stroma
neuroblastoma:
clinical course and prognosis
- most important prognostic factors
- stage of the tumor*
- age of the patient*
- morphology
- amplification of the NMYC oncogene
- currently most important genetic abnormality for risk stratification
- automatically renders a tumor as “high risk”, irrespective of stage or age
what is the most common primary intraocular malignancy of children?
retinoblastoma;
- 40% of tumors are assoc w/ germline mutation in the RB1 gene (heritable)
- 60% of tumors develop sporadically, and these have somatic RB1 gene mutations
why is retinoblastoma a misnomer?
name suggests that it’s from primitive retinal cell;
cell of origin is neuronal
retinoblastoma:
etiology
-
familial cases: typically multiple bilateral tumors
- these pts are at inc risk of developing osteosarcoma and other soft tissue tumors
- sporadic, nonheritable tumors: unilateral and unifocal
what is this gross morphology?
retinoblastoma:
a poorly cohesive tumor in retina abutting the optic nerve
retinoblastoma:
microscopic morphology
small, round cells w/ large hyperchromatic nuclei and scant cytoplasm;
resembling undifferentiated retinoblasts; Flexner-Wintersteiner rosettes: clusters of cuboidal or short columnar cells arranged around a central lumen
retinoblastoma:
presentation, course
- presentation: ~2 y/o, but tumor may be present at birth
- poor vision, strabismus
- whitish hue to the pupil (“cat’s eye reflex”), and pain and tenderness
- course: usually fatal if untreated; after early tx w/ enucleation, chemo, radiotherapy; survival is the rule
- some tumors spontaneously regress
- OR disseminate beyond eye –> metastasize to CNS, skull, distal bones, lymph nodes
what is most common tumor of the kidney in children?
Wilms tumor, aka nephroblastoma;
most in children 2-5 years
microscopic appearance of:
wilms tumor
- recgonizable attempts to recapitulate diff’t stages of nephrogenesis
-
triphasic combination of blastemal, stromal, and epithelial cell types
- Blastemal component: sheets of small blue cells, w/ few distinctive features
- Epithlial differentiation: abortive tubules or glomeruli
-
Stromal cells: fibrocytic, myxoid or skeletal muscle differentiation
- rarely other heterologous elements are identified, incl squamous or mucinous epithelium, smooth muscle, adipose tissue, cartilage, and osteoid & neurogenic tissue
gross anatomy:
wilms tumor
tumor in the lower pole of the kidney w/ the characteristic tan to gray color and well-circumscribed margins
wilms tumor:
microscopic morphology
- wilms tumor w/ tightly packed blue cells consistent w/ the blastemal component and interspersed primitive tubules, representing the epithelial component
- focal anaplasia in other areas othe same tumor; cells have hyperchromatic, pleomorphic nuclei, and abnormal mitoses
wilms tumor:
clinical course
- complaints related to tumor’s enormous size –> palpable abdominal mass; may extend across the midline and down into the pelvis
- less often, fever and abdominal pain, w/ hematuria or intestinal obstruction
- (due to pressure from the tumor)
wilm’s tumor:
prognosis
- prognosis generally very good; excellent results obtained w/ nephrectomy adn chemotherapy
- anaplasia –> adverse prognosis
- national wilm’s tumor study group in US:
- focal and confined anasplasia: outcome is similar to tumors w/o anaplasia
- diffuse extrarenal spread anaplasia: lease favorable outcome
