Pediatric pathology principles

Congenital Anomalies - Womb Worries

• Malformation: Primary, intrinsic error in morphogenesis; multifactorial.
  • Examples: Congenital heart disease, neural tube defects.
• Disruption: Secondary destruction of a previously normal organ/part.
  • Examples: Amniotic bands, vascular accidents.
• Deformation: Extrinsic mechanical forces on the fetus.
  • Examples: Clubfeet, hip dislocation due to uterine constraint.
• Sequence: A single primary defect leads to a cascade of anomalies.
  • Example: Potter sequence (oligohydramnios → fetal compression).

⭐ The embryonic period (weeks 3-8) is the most vulnerable to teratogens, causing major malformations. Before week 3 is often an "all-or-none" effect.

Perinatal Infections - TORCH Terror

📌 TORCH: Toxoplasmosis, Other (Syphilis, VZV, Parvovirus B19), Rubella, CMV, HSV. Infections acquired in utero (transplacental) or during birth. Common findings: IUGR, hepatosplenomegaly, jaundice, rash.

• Toxoplasmosis: Classic triad of chorioretinitis, hydrocephalus, and diffuse intracranial calcifications.
• Rubella: Triad of cataracts, sensorineural deafness, and patent ductus arteriosus (PDA).
• CMV: Blueberry muffin rash (extramedullary hematopoiesis), microcephaly, and periventricular calcifications.
• HSV: Usually perinatal. Vesicular skin lesions, encephalitis.
• Syphilis: Early signs non-specific; late signs include saber shins, saddle nose.

⭐ Cytomegalovirus (CMV) is the most common congenital infection in the United States.

Pediatric Neoplasia - Tiny Tumors

• Origin: Arise from embryonal tissues (blastomas); often termed "small, round, blue cell tumors" on histology.
• Genetics: Strong association with congenital malformations & genetic syndromes (e.g., Down syndrome, Neurofibromatosis, Beckwith-Wiedemann).
• Prognosis: Generally more responsive to chemotherapy and have a better prognosis than adult cancers.

• Key Examples (Small, Round, Blue Cell Tumors):
  • Neuroblastoma: Most common extracranial solid tumor.
  • Wilms Tumor: Kidney tumor, associated with WAGR syndrome.
  • Retinoblastoma: Eye tumor, associated with RB1 gene mutation.
  • Hepatoblastoma: Most common pediatric liver tumor.
  • Ewing Sarcoma: Bone tumor, t(11;22) translocation.
  • Rhabdomyosarcoma: Soft tissue sarcoma of skeletal muscle origin.

⭐ Neuroblastoma often presents as an abdominal mass crossing the midline. It can spontaneously regress, especially in infants < 1 year old. Look for elevated urinary catecholamines (VMA, HVA).

Metabolic & Genetic - Inborn Issues

• Inborn Errors of Metabolism (IEMs): Mostly autosomal recessive single-gene defects blocking metabolic pathways, leading to substrate accumulation or product deficiency.
• Phenylketonuria (PKU):
  • Deficiency: Phenylalanine hydroxylase (PAH).
  • Features: Intellectual disability, seizures, musty/mousy odor, fair skin.
  • Tx: Lifelong dietary restriction of phenylalanine.
• Galactosemia (Classic):
  • Deficiency: Galactose-1-phosphate uridyltransferase (GALT).
  • Features: Jaundice, hepatomegaly, infantile cataracts, vomiting.

⭐ Neonates with galactosemia are at markedly increased risk for E. coli sepsis.

• Lysosomal Storage Diseases:
  • Tay-Sachs: Hexosaminidase A deficiency; GM2 ganglioside accumulates. Cherry-red macula, neurodegeneration.
  • Gaucher: Glucocerebrosidase deficiency. Hepatosplenomegaly, pancytopenia, bone crises.

High‑Yield Points - ⚡ Biggest Takeaways

• Congenital anomalies are the leading cause of infant mortality.
• Pediatric tumors are typically embryonal (neuroblastoma, Wilms tumor) and involve soft tissue, CNS, or marrow.
• Teratogen effects depend on the timing of exposure (weeks 3-9 are critical).
• Perinatal TORCH infections cause chorioretinitis, intracranial calcifications, and hydrocephalus.
• Fetal hydrops is a severe, generalized edema, often a final pathway for many fetal diseases.
• Sudden Infant Death Syndrome (SIDS) is a diagnosis of exclusion in infants <1 year.