Pathology

Lecture 20 Diseases of Infancy and Childhood

1)To learn why the causes of death differ in infancy and childhood in each cohort age group.Each stage of development of the infant and child is prey to a somewhat different group of disorders. Four time spans are apparent: 1) the neonatal period, 2) infancy, 3) ages 1-4, and 4) ages 5-14 (see table). The first month and the first year of life carry greater risks for congenital abnormalities, disorders relating to short gestation, low birth weight, and SIDS. These risks lessen as the child gets older and accidents and neoplasms take the fore.

Under 1 year / 1-4 years / 5-14 years / 15-24 years
Congenital malformations/anomalies
Premature gestation/delivery/low birth weight/respiratory distress syndrome
SIDS/accidents
Perinatal conditions: maternal disease, placental/membranes or cord conditions, birth hypoxia and sepsis / Accidents
Congenital malformations/ anomalies
Malignant neoplasms
Homicide
Heart diseases
Pneumonia / Accidents
Malignant neoplasms
Homicide & suicide
Congenital malformations/ anomalies / Accidents/homicide
Suicide
Malignant neoplasms
Diseases of the heart

2)To learn the basic types and causes of congenital malformations.

Types of congenital malformations include:

  1. Malformation – an intrinsically abnormal development process, usually multiple factors and variety of patterns. Ex: congenital heart defects and anencephaly.
  2. Disruptions – result from secondary destruction of normally developing tissue from an extrinsic disturbance in morphogenesis. Ex: Amniotic bands.
  3. Deformations – an extrinsic force on development, such as uterine constraint, places abnormal biomechanical forces on the fetus. Ex: Clubfeet.
  4. Sequence – a pattern of cascading or secondary anomalous changes. Ex: Potter Sequence (Oligohydraminos – decreased amniotic fluid due to varying factors) causes compression of the fetus’ hands, feet, face, and chest, may be fatal.
  5. Syndrome – a constellation of pathologically related changes simultaneously affecting multiple tissues which cannot be explained on the basis of a single, localized initiating defect. Ex: Down syndrome (trisomy 21).

Causes of congenital malformations:

  1. Unknown etiology – at least 50% of cases.
  2. Genetic – chromosomal aberrations (10-15%) and Mendelian inheritance (2-10%)
  3. Environmental – maternal/placental infections: rubella, toxoplasmosis, syphilis, CMV, and HIV (2-3%). Maternal disease states: diabetes, phenylketonuria, and endocrinopathies (6-8%). Drugs and chemicals: EtOH, folic acid antagonists, androgens, phenytoin, thalidomide, warfarin, 13-cis-retinoic acid, and others (1%). Irradiations (1%).
  4. Multifactoral – a combination of genetic and environmental (20-25%).
  5. Timing – In the first part of the embryonic stage (0-3 weeks) damage results in death or total recovery. In the second part, organogeneisis (4-9 weeks), damage results in malformations of organs, teratogenesis. In the fetal stage (10 weeks to birth) damage can cause neural problems and injury to existing organs.

3)To learn the risks of and diseases associated with prematurity.Prematurity is defined as less than 37 weeks gestation and infants are usually less than 2500 grams. Risks of prematurity include: intrauterine infections (ascending or hematogenous), premature rupture of membranes, maternal diseases, multiple gestation, and uterine, cervical or placental structure abnormalities. Diseases associated with prematurity include: immature organ functions: lungs –hyaline membrane disease (respiratory distress syndrome),GI – necrotizing enterocolitis and Heart – intraventricular hemorrhage, sepsis with (bleeding) coagulopathy, cervicovaginal source (bacteria and herpes), group B streptococcus, hematogenous (Toxoplasmosis, Rubella, CMV, Herpes, Parvovirus B19, Listeria, Syphilis, HIV and Hepatitis B).

4)To learn the relationship of histologic maturity to the behavior of the teratoma and neuroblastoma.

  1. Teratoma–histologically mature tumors are well differentiated, often cystic and benign (75%) presenting at 4 months. Histologically immature tumors are indeterminate in their biologic potential. Solid teratomatous tumors (12%) are malignant when mixed with another germ layer. Sacrococcygeal teratomas account for 40% of teratomas and usually present ~age 2 with 4x greater frequency in girls.
  2. Neuroblastoma – histologically immature neural crest cells can become malignant. Neuroblastomas are the most common malignancy of infants and account for half of all cancers in infancy. Mature neural crest cells are ganglion cells. Neuroblastomas can arise in different locations: the adrenal medulla (40%), the sympathetic chain – paravertebral region (25%) and posterior mediastinum (15%).

5)To learn some of the differences between pediatric and adult malignant tumors.Malignant tumors commonly occurring in adulthood are epithelial in origin including: lung, colon, breast, prostate, and skin. Many tumors are unique to infancy and childhood due to the relationship between teratogenesis and oncogenesis and are mesenchymal in origin. Fetal and neonatal malignancies tend to regress spontaneously or cytodifferentiate. The most frequent childhood cancers arise in the hematopoitic system, nervous tissue, soft tissues, bone, and kidney.

6)To learn what are the most common pediatric malignancies.

0 to 4 years / 5 to 9 years / 10 to 14 years
Leukemia
Retinoblastoma
Neuroblastoma
Wilms tumor
Hepatoblastoma
Soft tissue sarcoma (especially rhabdomyocarcoma)
Teratomas
Central Nervous system tumors / Leukemia
Retinoblastoma
Neuroblastoma
Hepatocarcinoma
Soft tissue sarcoma
Central nervous system tumors
Ewing sarcoma
Lymphoma / Hepatocarcinoma
Soft tissue sarcoma
Ostogenic sarcoma
Thyroid carcinoma
Hodgkin disease

7)To learn some of the favorable/unfavorable features of neuroblastoma.

Variable / Favorable / Unfavorable
Stage / Stage 1, 2A, 2B, 4S / Stage 3, 4
Age / ≤ 1 year / > 1 year
Histology
Evidence of schwannian stroma and gangliocytic differentiation
Mitotic rate
Mitosis-keryorrhexis index
Intratumoral calcification / Present
Low
≤200/5000 cells
Present / Absent
High
>200/5000 cells
Absent
DNA ploidy / Hyperdiploid or near triploid / Diploid, near-diploid, or near-triploid
Telomerase expression / Low or absent / Highly expressed

8)To learn why Wilms’ tumor is thought of as a “pathogenic model” of malignancy.Wilms’ tumor shows a relationship between chromosomal-related malformations and neoplasia (10% of cases), the histologic overlap of organogenesis and neoplasia, the role of precursor lesions and reflects the potential for therapy modification to vastly improve prognosis.