13_Peds II

Question 1

define: sudden infant death syndrome (SIDS)

Answer 1

• 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

Question 2

sudden infant death syndrome:

epidemiology

Answer 2

• 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)

Question 3

sudden infant death syndrome:

pathogenesis (“triple risk” model)

Answer 3

• multifactorial condition; triple risk model:
  
  1. vulnerable infant: delayed development of arousal and cardiorespiratory control; ? genetic factors
  2. critical developmental period in homeostatic control (1 mo- 1 year)
  3. one or more exogenous stressors:
     
     • prone (face-down) sleeping
     • sleeping on soft surfaces
     • thermal stress

Question 4

how does the prone position cause Sudden Infant Death Syndrome?

Answer 4

• increases infant’s vulnerability to noxious stimuli during sleep
• assoc w/ decreased arousal responsiveness compared to supine

Question 5

what campaign decreased SIDS incidence?

Answer 5

• 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

Question 6

gross morphology of Sudden Infant Death Syndrome?

Answer 6

• multiple petechiae:
  
  • most common finding in typical SIDS autopsy (80%)
  • usually present on thymus, visceral and parietal pleura, and epicardium
• congested lungs

Question 7

microscopic morphology of Sudden Infant Death Syndrome?

Answer 7

• 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

Question 8

factors associated w/ SIDS?

Answer 8

some are related to environment (prone sleeping position, soft surface, hyperthermia, co-sleeping with parents);

some related to birth order

Question 9

what is: accumulation of edema fluid in the fetus during intrauterine growth?

Answer 9

fetal hydrops

Question 10

what are causes of fetal hydrops?

(2 major types)

Answer 10

• immune hydrops: hemolytic anemia caused by Rh blood group incompatibility b/w mother and fetus
• nonimmune hydrops: due to successful pregnancy prophylaxis

Question 11

how does severity of fetal hydrops vary?

Answer 11

• 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)

Question 12

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)?

Answer 12

Immune hydrops

• Immune hemolysis
• progressive anemia
• tissue ischemia
• intrauterine cardiac failure
• peripheral pooling of fluid edema

Question 13

what is most common cause of immune hydrops (immune hemolytic disease of newborn)?

Answer 13

• 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

Question 14

causes of Nonimmune hydrops?

Answer 14

• cardiovascular defects (structural and functional)
• chromosomal anomalies (45,X karyotype/Turner syndrome, Trisomy 21, Trisomy 18)
• fetal anemia

Question 15

how does fetal anemia cause nonimmune hydrops?

Answer 15

• homozygous alpha-thalassemia
• causes
  
  • tissue ischemia
  • secondary myocardial dysfunction
  • circulatory failure
  • secondary liver failure
  • hypoalbuminemia
  • reduced plasma osmotic pressure
  • edema

Question 16

gross morphology of hydrops fetalis?

Answer 16

• generalized accumulation of fluid in fetus
• fluid accumulation particularly prominent in soft tissues of the neck; (cystic hygroma)

Question 17

which virus is thought to be associated w/ fetal hydrops?

Answer 17

transplancental infxn by parvovirus B19 –> increasingly recognized as important cause

1. virus gains entry into erythroid precursors (normoblasts) –> replicates
2. cellular injury –> death of normoblasts –> aplastic anemia

HISTO: parvoviral intranuclear inclusions can be seen w/in circulating and marrow erythroid precurosrs (arrows)

Question 18

what is / cause of erythroblastosis fetalis?

Answer 18

• large number of normoblasts and erythroblasts in peripheral circulation
• caused by increased hematopoeitic activity

Question 19

define: extramedullary hematopoiesis

Answer 19

• 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

Question 20

kernicterus:

pathophysiology

Answer 20

1. hemolysis in Rh or ABO incompatibility –> increased circulating bilirubin from RBC breakdown –>
2. circulating unconjucated bilirubin is taken up by brain tissue –> toxic effect
3. basal ganglia and brain stem are prone to deposition of bilirubin pigement –> characteristic yellow hue to parenchyma

Question 21

at what point of kernicterus may the CNS be damaged?

Answer 21

when hyperbilirubinemia is markedly elevated

(above 20 mg/dL in full-term infants, lower threshold in premature infants)

Question 22

terms for: microscopically normal cells or tissues that are present in abnormal locations

Answer 22

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

Question 23

define: hamartoma

Answer 23

• 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

Question 24

define: hemangioma

Answer 24

• 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

Question 25

what are the most common tumors of infancy?

Answer 25

hemagioma; may enlarge at child gets older, or spontaneously regress

Question 26

clinical significance of hemangiomas?

Answer 26

* 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

Question 27

define: lymphangioma

Answer 27

* 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)

Question 28

histo features of **lymphangioma**

Answer 28

* cystic and cavernous spaces lined by endothelial cells and surrounded by lymphoid aggregates * spaces usually contain pale fluid

Question 29

what is most common **germ cell tumor** of childhood (accounting for 40% of cases)?

Answer 29

**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

Question 30

are **immature** teratomas benign or malignant?

Answer 30

**malignant potential correlates w/ amount of immature tissue elements present;** most benign teratomas seen in young infants; children w/ malignant lesiosn are usually older

Question 31

what type of tumors are collectively referred to as **small, round, blue cell tumors,** even if they're histologically unique?

Answer 31

many malignant tumors have sheets of cells w/ small round nuclei, incl: * neuroblastoma * lymphoma * rhabdomyosarcoma * ewing sarcoma (peripheral neuroectodermal tumor) * some wilms tumor

Question 32

**malignant tumors:** microscopic appearance

Answer 32

* primitive (embryonal) microscopic appearance) * exhibit features of organogenesis specific to site of origin

Question 33

most common malignant neoplasm in ages 0-9 y/o?

Answer 33

leukemia

Question 34

**neuroblastoma**: define, and unique features

Answer 34

* def: **tumors of sympathetic ganglia & adrenal medulla derived from primordial neural crest cells** * unique features: * spontaneous regression * spontaneous or therapy-induced maturation

Question 35

**neuroblastoma**: epidemiology

Answer 35

* **_second most_ common solid malignancy of childhood** after brain tumors * 7-10% of all pediatric neoplasms & 50% of infancy malignancies

Question 36

**neuroblastoma**: etiology

Answer 36

**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

Question 37

**neuroblastoma:** location

Answer 37

* 40% arise in the **adrenal medulla** * remainder anywhere **along sympathetic chain** * paravertebral region of the abdomen (25%) * posterior mediastinum (15%)

Question 38

**neuroblastoma**: macroscopic morphology

Answer 38

* range in size from **minute nodules (the in situ lesions) to large masses w**eighing more than 1 kg * cut surface: **soft, gray-tan, brain-like tissue** * larger tumors have **areas of necrosis, cystic softening, and hemorrhage**

Question 39

**neuroblastoma**: histo morphology

Answer 39

* small cells embedded in a finely fibrillar matrix (neuropil) * a **homer-wright pseudorosette** (tumor cells arranged concentrically around a central core of neuropil)

Question 40

**ganglioneuroma**: etiology, and microscopic morphology

Answer 40

* 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

Question 41

**neuroblastoma:** clinical course and prognosis

Answer 41

* 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

Question 42

what is the most common **primary intraocular malignancy of children?**

Answer 42

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**

Question 43

why is **retinoblastoma** a misnomer?

Answer 43

name suggests that it's from primitive retinal cell; ## Footnote **cell of origin is _neuronal_**

Question 44

**retinoblastoma**: etiology

Answer 44

* **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**

Question 45

what is this gross morphology?

Answer 45

retinoblastoma: a poorly cohesive tumor in retina abutting the optic nerve

Question 46

**retinoblastoma**: microscopic morphology

Answer 46

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

Question 47

retinoblastoma: presentation, course

Answer 47

* 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

Question 48

what is most common tumor of the kidney in children?

Answer 48

Wilms tumor, aka **nephroblastoma**; most in children 2-5 years

Question 49

microscopic appearance of: wilms tumor

Answer 49

* 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*

Question 50

gross anatomy: ## Footnote **wilms tumor**

Answer 50

tumor in the lower pole of the kidney w/ the characteristic tan to gray color and well-circumscribed margins

Question 51

wilms tumor: microscopic morphology

Answer 51

* 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

Question 52

**wilms tumor:** clinical course

Answer 52

* 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)

Question 53

wilm's tumor: prognosis

Answer 53

* 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