1. Pediatric-Perinatal Pathology
Tutorials
Malformations and Deformations:
1. Cleft lip, gross
2. Lateral cleft lip, gross
3. Facial abnormalities, gross
4. Hands with abnormal crease, gross
5. Omphalocele, gross
6. Gastroschisis, gross
7. Limb-body wall complex, gross
8. Limb-body wall complex, gross
9. Alobar holoprosencephaly, gross
10. Semilobar holoprosencephaly, gross
11. Holoprosencephaly, gross
12. Hydranencephaly, gross
13. Syndactyly, hand and foot, gross
14. Syndactyly, hand, gross
15. Bowel atresia, gross
16. Duodenal atresia, gross
17. Colonic atresia, gross
18. Tracheo-esophageal fistula and atresia, gross
19. Sirenomelia, gross
20. Intrauterine fetal demise, external features, gross
21. Recessive polycystic kidney disease, gross
22. Diaphragmatic hernia, gross
23. Diaphragmatic hernia, gross
24. Renal agenesis, gross
25. 'Potter facies' from oligohydramnios, gross
26. 'Potter facies' and 'glove-like' hand from oligohydramnios, gross

2. 27. Normal chest cavity, gross
28. Pulmonary hypoplasia, gross
29. Pulmonary hypoplasia, microscopic
30. Varus deformities, feet, gross
31. 'Rocker bottom' foot, gross
32. Clenched hand, gross
33. Hydrops fetalis, gross
Abnormalities of Twinning:
34. Siamese twins (craniothoracopagus), gross
35. Siamese twins (thoracopagus ), gross
36. Acardius acephalus (chorangiopagus parasiticus), gross
37. Acardius anceps (chorangiopagus parasiticus), gross
38. Twin-twin transfusion syndrome, gross
Neural Tube Defects:
39. Meningomyelocele, gross
40. Meningomyelocele, gross
41. Anencephaly, gross
42. Anencephaly, gross
43. Anencephaly, gross
44. Iniencephaly, gross
45. Rachischisis, gross
46. Iniencephaly, encephalocele, rachischisis, gross
47. Exencephaly, gross
Pediatric Neoplasia:
48. Nasopharyngeal teratoma, congenital, gross
49. Teratoma, congenital, low power microscopic
50. Lymphangioma, congenital, gross
51. Lymphangioma, congenital, medium power microscopic
52. Lymphangioma, congenital, medium power microscopic
53. Hemangioma, congenital, gross
54. Wilms tumor, gross

3. 55. Wilms tumor, medium power microscopic
56. Neuroblastoma, gross
57. Neuroblastoma, medium power microscopic
58. Rhabdomyosarcoma, low power microscopic
59. Rhabdomyosarcoma, medium power microscopic
Congenital Infections:
60. Congenital syphilis, gumma in heart, gross
61. Spirochetes (Treponema pallidum), microscopic
62. Cytomegalovirus, congenital, kidney, microscopic
63. Parvovirus, congenital, spleen, microscopic
64. Congenital pneumonia, microscopic
Complications of Prematurity:
65. Hyaline membrane disease, lung, microscopic
66. Bronchopulmonary dysplasia, lung, microscopic
67. Germinal matrix, brain, normal and with hemorrhage, low power
microscopic
68. Intraventricular hemorrhage, gross
69. Intraventricular hemorrhage, severe, gross
70. Kernicterus, brain, gross
71. Neonatal necrotizing enterocolitis (NEC), gross
72. Neonatal necrotizing enterocolitis (NEC) and normal bowel, low
power microscopic
Miscellaneous Conditions:
73. Pyloric stenosis, gross
74. Meconium ileus, gross
75. Meconium ileus with peritonitis, gross
76. Hirschsprung disease, gross
77. Pneumatosis intestinalis, microscopic
78. Normal skin with hair, gross
79. Accessory spleens, gross
80. Postmaturity with prominent fingernails, gross

4. 81. Maceration, gross
82. Fetal chest with thymus, gross
83. Thymus with macrophages, low power microscopic
84. Subgaleal hemorrhage, gross
85. Meconium aspiration, medium power microscopic
86. Meconium aspiration, high power microscopic

5. Examination of a stillborn fetus or neonate should consist of a
careful and detailed physical examination. You must note the
presence of any anomalies, as well as detail size and gestational
age. The anomaly seen in this photograph, a large bilateral cleft lip,
is not so subtle, but some anomalies are. Call a clinical geneticist for
consultation. The presence of one anomaly suggests that additional
anomalies may be present, including internal anomalies such as
congenital cardiac defects that may be life-threatening.

6. Here is a lateral cleft in a child with multiple congenital anomalies. In
this case, the constellation of anomalies suggested a possible
chromosomal anomaly, and a karyotype revealed 47, XY, +18
(trisomy 18).

7. The facial features shown in the 3rd trimester
fetus above and the 2nd trimester fetus below
are typical for trisomy 18 (e.g., 47, XY, +18).
The face is small in proportion to the head, with
micrognathia.

9. There is an abnormal transverse crease across the palm of each
hand seen here. Together with the single flexion crease on the 5th
digit, this is quite typical for trisomy 21 (e.g., 47, XX, +21).

10. Here is a ventral abdominal wall defect. This defect involves the
region of the umbilical cord, so this is an omphalocele. Note that
there is a thin membrane covering the herniated abdominal contents
(loops of bowel can be seen under the membrane). This defect
would have to be repaired over a period of time. Since the bowel has
mainly developed outside of the abdominal cavity, it is malrotated
and the cavity is not properly formed (too small).

11. This is large lateral abdominal wall defect does not involve the umbilical
cord and is not covered by a membrane. This is a gastroschisis. Much
of the bowel, stomach, and liver are herniated outside the abdominal
cavity.

12. This is a gastroschisis in association with a limb-body wall (LBW)
complex. This complex is sometimes called "amnionic band syndrome"
but such bands may only be present in half of cases of LBW complex.
Seen here in association with LBW complex are reductions of the
extremities, particularly the left upper extremity, and scoliosis. Not seen
here are craniofacial clefts and defects that can also occur with LBW
complex.

13. This is limb-body wall (LBW) complex with constricting amnionic
bands. The bands, as well as the other defects, may arise from early
embryonic disruption with formation of adhesions and subsequent
abnormal formation and loss of structures such as extremities and
abdominal wall.

14. This is holoprosencephaly, often accompanied by the failure of fetal
facial midline structures to form properly. Hence, there are usually
midline facial defects (cleft lip, cleft palate, cyclopia, etc) accompanying
this condition. The "alobar" form of holoprosencephaly is shown here in
which there a single large ventricle, because there is no attempt to
form separate cerebral hemispheres. This condition may be associated
with trisomy 13. It may rarely occur in association with maternal
diabetes mellitus.

15. The skull is opened here to reveal the "semilobar" form of
holoprosencephaly, because there is a small cleft representing an
attempt to separate the hemispheres. There is no gyral pattern here
because this stillborn fetus was under 20 weeks gestation.
Holoprosencephaly is a grave condition with little or no brain
function. Holoprosencephaly can be associated with chromosomal
anomalies (such as trisomy 13), with maternal diabetes mellitus, and
can be seen sporadically.

16. Here is a cross section though a brain with holoprosencephaly,
revealing a single ventricle. Toward the base of the brain are the fused
thalami typical of this process.

17. This is hydranencephaly. The brain is essentially a bag of water,
because an intrauterine vascular accident involving the brain led to
lack of blood flow and subsequent loss of cerebral tissue.

18. Syndactyly represents fusion of two or more digits. It can be an
isolated finding or part of syndromes that define patterns of
anomalies. Most of these syndromes do not have a specific genetic
defect yet defined, though some do. Seen above are the digits of the
hand fused together. Below, the foot has rudimentary, partially fused
digits.

20. Here is an example of syndactyly in which the 3rd and 4th fingers
are fused into one large digit. This particular pattern can be seen
with triploidy (69 chromosomes).

21. The meconium-filled bowel ends in a blind pouch. This is atresia of
the bowel. Such a defect, like many anomalies, often happens along
with other anomalies. Bowel atresias are accompanied by
polyhydramnios, since the swallowing and absorption of amniotic
fluid by the fetus is impaired.

22. There is a point of marked narrowing indicative of congenital duodenal
atresia depicted here. Interestingly, half of all duodenal atresias occur
with Down syndrome, although conversely, few cases of Down
syndrome have duodenal atresia. By ultrasound, there is a "double
bubble" sign from duodenal enlargement proximal to the atresia
accompanying the normal stomach bubble. The normal esophagus,
liver, and gallbladder are seen here as well.

23. This is a colonic atresia accompanied by additional anomalies,
including a persistent cloaca that resulted from failure of the urogenital
septum to form. The right testis and the left testis are cryptorchid, and
there is absence of the penis. The presence of one anomaly suggests
that others are present as well, and the term "multiple congenital
anomalies" applies.

24. This is a tracheo-esophageal fistula with esophageal atresia. The
esophageal atresia is present in the mid-esophagus. The
tracheoesophageal fistula is located below the carina.

25. This is sirenomelia. The term comes from "siren" or "mermaid"
because of the characteristic fusion of the lower extremities that
results from a failure in the development of a normal vascular supply
to lower extremities from the lower aorta in utero.

26. The first thing to notice is the features of intrauterine fetal demise:
skin slippage and reddening. These features are those of
maceration and not trauma or birth defect. Note the shortened lower
extremities, known as phocomelia. It was idiopathic in this case, but
in the 1950's the drug thalidomide was responsible for many cases
when pregnant women took it. Thus, it is very important that
pregnant mothers be advised that drugs (including cigarette smoking
and alcohol consumption) may have profound effects on the fetus.

27. The two enormous masses beneath the liver are cystic kidneys.
This is an example of autosomal recessive polycystic kidney disease
(ARPKD).

28. In this case, the diaphragmatic dome is missing on the left, allowing
herniation of the abdominal contents into the chest cavity. The metal
probe in the photograph is behind the left lung, which has been
displaced by the stomach. Below the stomach is a dark spleen (at
the white arrow). The white arrow overlies the left lobe of liver which
is extending upward.

29. A diaphragmatic hernia on the left allows herniation of bowel into the left
chest cavity. The herniating liver has become tilted vertically. Incursion
of abdominal contents into the chest cavity will result in pulmonary
hypoplasia. Though diaphragmatic hernia may occur as an isolated
defect that is potentially repairable, most are associated with multiple
anomalies, and often with chromosomal abnormalities.

30. Agenesis refers to the absence of formation of a body part in
embryogenesis. Here the kidneys are absent from the
retroperitoneum, and this renal agenesis will result in
oligohydramnios, because amniotic fluid is mainly derived from fetal
urine. The oligohydramnios leads to deformations such as a
constricted chest, diminished lung development, and pulmonary
hypoplasia.

31. This baby demonstrates the typical "Potter's facies" with prominent
infraorbital folds resulting from oligohydramnios in utero. This is an
example of a deformation sequence in which an anomaly (here the
lack of normal kidneys) leads to lack of fetal urine output with
resultant oligohydramnios that causes deformation through
constraint.

32. Seen in the right panel is the characteristic facial appearance with
oligohydramnios, with prominent infraorbital creases and a flattened
nose. In the left panel the hand appears to have excessive skin
folds, like a loose glove. Oligohydramnios restricts fetal movement.
The umbilical cord may be short.

33. This is the normal appearance of the chest cavity in a neonate. Note
the prominent pink thymus above the heart in the mediastinum.
Note the size of the heart in relation to the lungs and chest cavity.
The diaphragmatic leaves are intact. The liver is normally quite
large in neonates in relation to other organs.

34. The most serious consequence of oligohydramnios is pulmonary
hypoplasia. Note the extremely small lungs in this case on each
side of the heart in the middle of the chest. The chest cavity is
opened here at autopsy and the lung appear small in comparison to
chest size, but in utero the constriction from diminished amnionic
fluid would have decreased the chest cavity size.

35. Microscopic examination of the lung reveals no alveolar
development, only tubular bronchioles incapable of significant gas
exchange, in this premature baby with pulmonary hypoplasia from
oligohydramnios. This results in insufficient gas exchange from
respiration following birth.

36. Deformation from constraint with oligohydramnios in utero can result
in the appearance of the club feet (varus deformity) seen here. The
feet are turned inward.

37. This is the appearance of a "rocker bottom" foot with a prominent
calcaneus and rounded bottom. Such an anomaly may suggest a
chromosomal abnormality such as trisomy 18.

38. These are clenched hands resulting from camptodactyly (fingers
bent over) and clinodactyly (fingers inclined to one side or the other).
This particular appearance is very suggestive of trisomy 18.

39. Generalized edema from fluid collection in the soft tissues results in
hydrops fetalis. There are many causes for fetal hydrops. The most
common are "non-immune" types that include infections, congestive
failure (from anemia or cardiac abnormalities), and congenital
anomalies. Immune hydrops, from maternal antibody formed against
fetal red blood cells, is not common when Rh immune globulin is
employed in cases of potential Rh incompatibility.

40. This is an uncommon complication of monozygous twinning in which
there is fusion of the twins. The popular term is "siamese" twins. The
scientific term applicable in the case shown here is
craniothoracopagus, or twins joined at the head and chest. There is
only one brain, and the hearts and gastrointestinal tracts are fused
as well. The location and amount of fusion can vary.

41. This is an example of thoracopagus. Note the large omphalocele in
the lower abdomen shared by these monozygous twins. These twins
shared a heart and liver and several other organs were partially
fused. Attempts at separation of such twins can either be viewed as
heroic new technology or expensive futility. The survival rate with
significant fusion of organs is essentially nil.

42. This is another abnormality of twinning in which one fetus is
essentially a poorly formed blob attached to, or separate from, a
complete fetus. This condition is called acardius-acephalus because
there is typically no heart or brain in the "blob" twin. The photograph
here reveals an acardiac twin that consists mainly of just lower
extremities. Such a non-viable twin can be surgically removed.

43. This is a more complete acardiac twin in which actual body regions
are present. There were few poorly formed internal organs present.
Nonetheless, it is non-viable.

44. If there is a vascular connection across a monochorionic twin
placenta, then a twin-twin transfusion syndrome can develop. In this
condition, there is diminished blood flow to one twin (the "donor")
and increased blood flow to the other twin (the "recipient"). The pale
appearing donor is smaller and may die for lack of sufficient blood
flow. More commonly, the larger plethoric recipient may die from
congestive heart failure.

45. Neural tube defects are are one of the more common congenital
anomalies to occur. Such defects result from improper embryonic
neural tube closure. The most minimal defect is called spina bifida, with
failure of the vertebral body to completely form, but the defect is not
open. Open neural tube defects with lack of a skin covering, can include
a meningocele, in which meninges protrude through the defect. Here is
a large meningomyelocele in which the defect is large enough to allow
meninges and a portion of spinal cord to protrude through the defect.
Such defects can be suggested by an elevated maternal serum alpha-
fetoprotein (MSAFP).

46. This is a fetus from a termination of pregnancy via dilation and
extraction, which is done in the second trimester. Note the large
neural tube defect in the lower back.

47. This is anencephaly. This condition occurs when there is failure of
formation of the fetal cranial vault. The brain cannot form properly
when exposed to amniotic fluid. Note that this fetus died in utero--
there are signs of maceration, with skin slippage and reddening.

48. Note the absence of the cranial vault in this fetus with anencephaly.
Supplementing the maternal diet with folate prior to and during
pregnancy can reduce the incidence of neural tube defects.

49. The eyes appear proptotic with anencephaly because of the lack of
the skull. Note the low set external ear.

50. This is a slight variation of a neural tube defect known as
iniencephaly in which there is lack of proper formation of occipital
bones with a short neck and defect of the upper cord. The head is
tilted back.

51. A severe rachischisis is shown here in a fetus that also has
iniencephaly.

52. Seen protruding from the back of the head is a large encephalocele
that merges with the scalp above. The encephalocele extends down
to partially cover a rachischisis on the back. This fetus also has a
retroflexed head from iniencephaly.

53. This form of neural tube defect is known as exencephaly. The
cranial vault is not completely present, but a brain is present,
because it was not completely exposed to amniotic fluid. Such an
event is very rare. It may be part of craniofacial clefts associated
with the limb-body wall complex, which results from early amnion
disruption.

54. Congenital and pediatric neoplasms are uncommon. One type that
can occur is a teratoma. Shown here is a large nasopharyngeal
teratoma that is protruding from the oral cavity.

55. The microscopic appearance of a teratoma is seen here. This
neoplasm, though benign from a microscopic standpoint, can
become a large mass that has severe consequences for a small
fetus, infant, or child. The three embryologic germ layers are
represented by skin (ectoderm) at the top, cartilage (mesoderm) at
the bottom left center, and a colonic gland (endoderm) at the right.

56. There is a large mass involving the left upper arm and left chest of
this fetus. This congenital neoplasm turned out to be a
lymphangioma.

57. Here is the microscopic appearance of the lymphangioma at
medium power, with large lymphatic spaces lined by a thin
endothelium. The adjacent stroma has lymphoid nodules.
Lymphangiomas in the pediatric age range tend to involve head,
neck, and chest.

58. At high magnification, the histologically benign nature of the
lymphangioma is apparent. There are enlarged lymphatic spaces
lined by a thin endothelium. However, such lesions tend to be poorly
circumscribed and extend widely into surrounding soft tissues,
making their surgical removal difficult.

59. Beneath the skin surface at the left are many dilated vascular
channels filled with many red blood cells. This is a neoplasm known
as a hemangioma.

60. This lobulated tan-white mass involving the kidney of a child is a
Wilms tumor. It manifests most often as an abdominal mass. Over
90% of Wilms tumors are diagnosed during the first 6 years of life.
About a fourth of cases are associated with hypertension.

61. Wilms tumor microscopically resembles the primitive nephrogenic
zone of the fetal kidney, with primitive glomeruloid structures and a
cellular stroma. Wilms tumor is associated with mutations involving
the WT1 tumor suppressor gene on chromosome 11. This neoplasm
is very treatable with an excellent prognosis and >80% cure rate
overall.

62. This is the gross appearance of a neuroblastoma arising in the right
adrenal gland. It is the most common pediatric malignancy in
infancy, and 75% of cases are diagnosed in children less than 4
years old. These tumors most often present as an abdominal or
mediastinal mass.

63. Microscopically, neuroblastoma is a "small round blue cell" tumor.
Histologic variations, as well as staging and cytogenetic
characteristics help to determine the prognosis.

64. A rare neoplasm that appears most commonly in the first decade of
life is the rhabdomyosarcoma. This malignant neoplasm has skeletal
muscle derivation. The alveolar variant is shown here. These
neoplasms occur most frequently in the head and neck area, as well
as the genitourinary tract.

65. This alveolar rhabdomyosarcoma is composed of primitive round
blue cells (rhabdomyoblasts) arranged in nests with spaces and
surrounded by a fibrous stroma. A variant of this neoplasm seen in
the genital tract is the sarcoma botryoides.

66. This is an example of a granulomatous process known as a
"gumma" in a case of congenital syphilis. The gumma shown here is
located in the heart of a fetus. Syphilis can be acquired in utero in
the third trimester. Congenital syphilis is increasing in incidence in
the U.S.

67. Spirochetes are seen here. These are Treponema pallidum
organisms and are the causative agents for syphilis.

68. Here within the tubular epithelium of a fetal kidney can be seen
many large violet intranuclear inclusions characteristic cof congenital
cytomegalovirus (CMV) infection. The inclusions may appear in the
urine of a liveborn infant with CMV.

69. The large pink inclusion in the erythroid precursor seen here in fetal
spleen is evidence for parvovirus infection. Parvovirus, or "fifth"
disease, produces a mild illness in children, marked by a "slapped
cheek" facial rash. In adults, the illness often goes unnoticed, but
pregnant women can pass the virus to the fetus, where it may
produce marked fetal anemia and hydrops in some cases.

70. One of the most common forms of perinatal congenital infection
arises from bacterial agents that ascend the birth canal and may be
seen in association with premature rupture of membranes (PROM)
and acute chorioamnionitis. Seen here is a congenital pneumonia
with many neutrophils filling immature bronchioles.

71. This is hyaline membrane disease due to prematurity and lack of
surfactant production from type II pneumonocytes within the
immature lung. Note the thick pink membranes lining the alveolar
spaces.

72. A later complication of prematurity should the baby survive the
immediate neonatal period, during which time mechanical ventilation
was necessary, is bronchopulmonary dysplasia (BPD). With BPD,
there is interstitial fibrosis and inadequate alveolar development
for good pulmonary function. Respiratory distress can continue for
months to years.

73. The dense layer of small dark blue cells seen here below the
ependyma of the lateral ventricle is the germinal matrix. The
germinal matrix is a highly cellular and highly vascularized region
from which cells migrate out during brain development, mainly
between 22 and 30 weeks gestation. This area is highly vulnerable
to birth injury and changes in blood pressure following birth. If
severe and if survival occurs, the hemorrhage may organize and
lead to obstructive hydrocephalus. A germinal matrix hemorrhage
is shown below.

74. This coronal section of a premature neonatal brain shows
intraventricular hemorrhage (IVH) extending from a germinal
matrix hemorrhage. Such hemorrhages occur from a variety of
factors that afflict neonates, including difficulty regulating blood
pressure. Such hemorrhages can be devastating.

75. Intraventricular hemorrhage (IVH) can be minimal, but can also be
severe as shown here with blood filling and distending all of the
lateral ventricles, extending into brain parenchyma, and extending
down the third ventricle and out into the subarachnoid space. The
prognosis is grim.

76. The yellow staining in the brain of a neonate is known as
kernicterus. There is a coronal section of medulla on the left and
cerebral hemisphere on the right demonstrating kernicterus in deep
grey matter of hemisphere and brain stem. Increased unconjugated
bilirubin, which accounts for the kernicterus, is toxic to the brain
tissue. Kernicterus is more likely to occur with prematurity, low birth
weight, and increased bilirubin levels. [Image contributed by
Jeannette J. Townsend, MD, University of Utah]

77. A complication of prematurity and low birth weight is neonatal
necrotizing enterocolitis (NEC) in which ischemia results in focal to
confluent areas of bowel necrosis, most often in the terminal ileum.
Seen at autopsy here is a dark red appearance to the small intestine
of a premature neonate. [Image contributed by Ted Pysher, MD,
University of Utah]

78. The clinical manifestations of neonatal necrotizing enterocolitis (NEC) in
premature neonates include abdominal distension, ileus, and bloody
stool at several days of age. Compared to normal bowel at the left,
bowel involved by NEC at the right shows hemorrhagic necrosis,
beginning in the mucosa and extending to involve the muscular wall,
with the potential for perforation.

79. This is pyloric stenosis. Note the prominent hypertrophied muscle
with elongation and narrowing of the pylorus at the gastric outlet on
the left. Pyloric stenosis is uncommon, but is a cause for "projectile"
vomiting in an infant about 3 to 6 weeks of age. Males are affected
more than females. The overall incidence is approximately 3 per
1000 livebirths.
The "pacemaker" interstitial cells of Cajal (ICC) regulate motility, and
contain the enzyme heme oxygenase-2 which generates carbon
monoxide (CO) as a neurotransmitter to cause relaxation in adjacent
smooth muscle cells. The lack of ICCs in pyloric stenosis results in
deficient CO production leading to motility dysfunction.

80. Meconium ileus is most often seen in the first few days of life in
neonates with cystic fibrosis, but can rarely occur in infants with a
normal pancreas. In cystic fibrosis, the abnormal pancreatic
secretions lead to inspissated meconium that produces intestinal
obstruction. The dilated coils of ileum are opened here to reveal the
inspissated green meconium (which may also be tarry or gritty),
while the unopened colon at the upper left and the appendix at the
lower left beyond the ileocecal valve are not dilated, and little or no
meconium is passed per rectum. [Image contributed by Ted Pysher,
MD, University of Utah]

81. Meconium peritonitis shown here as a greenish exudate overlying
the serosal surfaces of the peritoneal cavity can complicate
meconium ileus in utero, particularly in fetuses with cystic fibrosis.
The bowel ruptures and leaks meconium, which produces a
chemical peritonitis. Calcifications in the spilled meconium may be
seen radiographically. Another complication of meconium ileus is
volvulus. [Image contributed by Ted Pysher, MD, University of Utah]

82. Shown here is dilation of bowel (megacolon) proximal to the affected
region of narrowing at the lower left center in sigmoid colon. Mucosal
damage and secondary infection may follow.
Hirschsprung disease results from an absence of ganglion cells in
both submucosal and myenteric plexuses and can occur in either a
segment of colon (short segment disease) or the entire colon (long
segment disease). The aganglionic segment becomes narrowed,
causing obstruction, with proximal dilation. Affected newborns may
develop focal inflammation at the point of obstruction, with fever and
diarrhea. Colonic perforation may occur. Infants with the disease
may have alternating diarrhea and constipation, while children
mainly have constipation. Treatment consists of surgical correction
with resection of the aganglionic segment.
Hirschsprung disease is thought to result from mutation of
susceptible genes interacting with environmental and other factors,
resulting in variable penetrance. Multiple genetic mutations have
been found, but about half of familial cases and 15% of sporadic
cases are associated with RET gene mutations that inactivate RET
receptor kinase activity. RET promotes survival and growth of
neurites and provides direction to migrating neural crest cells. The
incidence of Hirschsprung disease is 1 in 5000 livebirths. It has a 4:1

83. male to female predominance. Short segment disease is more
common in males, while the rarer long segment disease
predominates in females.

84. Pneumatosis intestinalis is a rare finding in which gas-filled cysts
appear in submucosa. It may complicate necrotizing enterocolitis, as
in this case. The gas may dissect into submucosa or may be
generated by bacteria.

85. The skin is soft and the hair is fine in a normal newborn, as seen
here.

86. The accessory spleens seen here at the hilum of the normal-sized
spleen are not uncommon and by themselves have no significance.

87. There are few changes indicative of postmaturity (gestation beyond
42 weeks). Here are long fingernails that can be seen with
postmaturity.

88. Death of the fetus in utero is accompanied by changes of
maceration. Seen here is one of the earliest changes (within half a
day) which is slippage of the skin. As this process advances, the
skin becomes reddened.

89. The normal fetal chest at term is shown here. The thymus is a large
structure with the important job of developing the cell-mediated
immune system with T-cells. The right lung, heart, diaphragm, and
liver are seen here as well.

90. Stress from a variety of illnesses in the fetus and neonate may be
manifested with thymic involution. One of the earliest changes seen
is an increase in cortical macrophages, typical in 1 to 2 days
following the onset of illness. Note the "starry sky" appearances here
from increased macrophages.

91. The neonatal scalp is reflected at autopsy to reveal dark red blood
beneath the galea aponeurotica (dense connective tissue of scalp)
and over the cranium. This is subgaleal hemorrhage and it is fairly
common during the birth process.

92. Meconium spillage is a complication seen at or near term, typically
when there is fetal distress with loss of anal sphincter tone and
passage of meconium into amniotic fluid. A clue to this occurrence is
greenish staining of fetal skin or fetal surface of the placenta. The
worst consequence of meconium spillage is meconium aspiration
into the lungs. Fetal distress also leads to reflex gasping efforts by
the baby, with the result that the meconium in the amniotic cavity is
aspirated into the lungs. Rugby ball shaped balls of meconium as
well as numerous "squames" from fetal skin are seen here.

93. In this case of meconium aspiration, small rounded balls of
meconium are seen in an alveolus, along with flattened "squames"
or desquamated fetal skin cells that are found in the amnionic fluid.
Meconium is an irritant that leads to respiratory distress. At birth,
tracheal suction and lung lavage may be useful to help remove the
meconium.