PMC9036388_01
Gross internal photographs of the decedent demonstrating thoracic and abdominal adhesions and a dilated transverse colon. (A) Posterior view of the thoracic and upper abdominal structures demonstrating patent thoracic duct and right-sided aorta. (B) Internal organs of the chest and abdomen demonstrated significant adhesions and a distended transverse colon.
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The esophagus traversed the thorax just left of midline and behind the trachea and left bronchus (Figure 1A). The stomach was increased in size but was normally formed and free of ulcers (Figure 1B). The ascending and the transverse colon were significantly enlarged and distended (Figure 1B). The right pleura and lung tissue were extensively adherent to the anterior chest wall (Figure 1B). The pericardial sack was surgically resected from over the entire anterior surface of the heat and was present only over the lateral-most and inferior borders of the heart (Figure 1B). The ascending aorta was noted to be right-sided, rather than in its normal left-sided orientation (Figures 1A, 3A, and B).
Adhesions and stenosis of the transverse colon with unusually enlarged villi were identified microscopically within the small and large bowel. (A) The transverse colon that has been removed and opened. The proximal portion of the transverse colon was significantly dilated and thinned with an area of stenosis (blue arrow) within the distal transverse colon. (B) H&E section of the grossly stenotic bowel demonstrated fibrotic adhesions on the antimesenteric side (left image) with scattered chronic inflammatory cells permeating through the fibrotic areas around the serosa. The muscular wall was significantly thickened (right image). The mucosa was roughly intact with minimal autolysis. (H&E, 40x) (C). H&E section of the transverse colon just proximal to the area of stenosis. It was relatively well-preserved with mucosa demonstrating eosinophilia on the distal aspect of the mucosa suggestive, but not definitive for ischemia versus autolysis. The muscular wall was significantly thinned, especially compared to the adjacent grossly stenosed bowel (seen in part B) (H&E, 40x). (D) Photograph of a single polyp (blue arrow) that was identified within the small intestine (left). An H&E section of the polyp (right) demonstrates that the polyp had a stalk composed of normal appearing muscularis tissue that was covered with normal small intestinal mucosa. There was an abnormal amount of submucosa and possibly muscularis associated with the polyp. Adjacent to the polyp there are distinct, elongated villi were present. (H&E, 40x) (E). The representative samples of the small intestine demonstrated significantly elongated villi with minimal autolysis. (H&E, 20x and 100x; as labeled) (F) The rectal tissue demonstrated long villi that are not typically seen in the rectum with well-preserved rectal mucosa, patent, with bits of stool. (H&E, 20x, 40x, and 100x; as labeled).
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An area of non-occlusive stenosis was identified within the distal transverse colon (Figure 2A). The muscular wall was significantly thickened in the area just before and after the area of stenosis (Figure 2B). Conversely, the distended and thin transverse colon proximal to the area of stenosis (Figure 2C) was relatively well preserved with mucosa demonstrating eosinophilia on the distal aspect of the mucosa suggestive, but not definitive, for ischemia. The muscular wall was significantly thinned, especially compared to the adjacent grossly stenosed bowel (Figure 2B vs Figure 2C). The polyp had a small stalk and was composed of normal appearing muscularis tissue that was covered with normal small intestinal mucosa (Figure 2D). A sample of the rectum also demonstrated significantly elongated villi (Figure 2E).
The decedent's heart demonstrating a right-sided aorta with mirror image branching, patent mBTT-shunt and significant pulmonary artery stenosis immediately distal to the shunt. (A) Anterior view of the decedent's heart demonstrating a right-sided aorta and mirror image branching of the arteries. All major structures are labeled. (B) Posterior view of the decedent's heart demonstrating a right-sided aorta and mirror image branching. The 3.5 mm PTFE shunt is clearly visible. All major structures are labeled. (C) Close up view of the pulmonary artery after longitudinal sectioning of the artery and opening of the PTFE shunt. There was a patent shunt with no thrombosis or stenosis at the distal end of the shunt (left); however, there is significant stenosis of the pulmonary artery that is just distal to the distal opening of the PTFE shunt (right; labeled in blue). All major structures are labeled.
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The ascending aorta was noted to be right-sided, rather than in its normal left-sided orientation (Figures 1A, 3A, and B). There was mirror image branching, with the left carotid and left subclavian arteries arising from a small left brachiocephalic artery (Figure 3A and B). The right subclavian and right carotid artery arose independently from the aorta (Figure 3A and B). A 3.5 mm polytetrafluoroethylene (PTFE) modified Blalock-Taussig-Thomas shunt (mBTTS) was noted to run from the right carotid artery to the right pulmonary artery (Figure 3B and C). However, just distal to the mBTT shunt was an area of significant stenosis within the pulmonary artery (Figure 3C). The heart weighed 49 g and was larger than normal for the decedent's weight and age (Figure 3A and B; expected weight, 21-35 g).
Sectioning of the heart demonstrates a large atrial-ventricular defect and pulmonary valve that was significantly decreased in size. (A) Multiple views of the Rastelli Type C atrial-ventricular septal defect. The picture on the left is of the opened right atrium and right ventricle demonstrating an atrial-ventricular septal defect (*). The middle picture is of the interior of the left atrium and left ventricle demonstrating the other side of the atrial-ventricular septal defect (*). Both views demonstrate the tricuspid valve connecting with mitral valve through the ventral defect and attaching to the anterior papillary muscle of the right ventricle (Rastelli Type C; arrow). Finally, the picture on the far right is looking up through the left ventricle demonstrating the atrial-ventricular septal defect (blue arrow) and the tricuspid valve connecting with mitral valve through the ventral defect (red arrow), crossing through the path of the aortic outflow tract (metal probe is traversing the aortic outflow tract). (B) Opened left aorta and ventricle demonstrating atrial-ventricular septal defect (ASVD) and the pulmonary valve within the pulmonary artery (PA). The picture on the right is heart rotated 90 degrees and showing the small (2 mm) pulmonary valve. (C) A representative section of the left ventricle demonstrates elongated myocytes with eosinophilic cytoplasm, appropriate for gestational age. There was minimal vascular congestion of the tissues. No leukocyte infiltrate or coagulative necrosis was identified. Overall, no microscopic abnormalities were identified. (H&E, 400x.).
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There was a moderate-size atrial component and a large ventricular component of the atrioventricular canal defect (Figure 4A). The pulmonary outflow tract was very stenotic (Figure 4B). The pulmonic valve was normal in shape but exceedingly small (2 mm; Figure 4B). The histologic appearance of the heart was normal with no indication of infarct or necrosis (Figure 4C).
Abnormally shaped right tracheal bronchus with heavy, immature, edematous lungs, and severe pulmonary stenosis. (A) Photographs of the anterior surface of the decedent's lungs both uncut (left) and coronally sectioned (right). There was an abnormally shaped right bronchus, with a large upper right bronchus going into the upper lobe and a second large lower right bronchus going into the middle lobe that has a branch within the middle lobe supplying right lower lobe. The left bronchus was singular and of normal configuration. The right lung has 3 lobes. The left lung has 2 lobes. The pleura and parenchyma of both lungs were roughened and somewhat fibrotic. The pulmonary arteries and veins were patent and have a grossly normal configuration. On cut surface, the lungs were firm and not well aerated. (B) Representative H&E stained lung tissue at indicated magnifications. At 20x, there was increased fibrin deposition on the surface of the lung consistent with the significant adhesions seen grossly. At 100x and 200x, most of the lung parenchyma was nearly filled with macrophages (many of which are hemosiderin-laden), indicative of severe congestion and significantly decreased elasticity of the lung. There was moderate vascular congestion as well, with both nucleated and non-nucleated RBCs visualized. There was significant loss of the overall structure of the alveoli with very immature alveoli seen in areas with less infiltration of macrophages and RBCs. (H&E, 20x, 100x, 200x; as labeled) (C) A representative H&E section demonstrating severe features of pulmonary hypertension, with severe calcification more than would be expected for the age of this patient, with marked medial thickening and intimal fibrosis. There was interstitial fibrosis, a feature of pediatric pulmonary hypertension, and seen in patients with hypoxia. There was extensive calcification of the vessels, which is a secondary phenomenon related to arterial damage and/or metabolic derangements. (H&E,100x). (D) The lung tissue was stained with smooth muscle actin and demonstrates there is no extension the smooth muscle layer into the distal acinar vessel (the normally non-muscularized intra-acinar arteries) indicating there was no medial hypertrophy. (E) This section of the lung demonstrates one of the focal areas of extramedullary hematopoiesis, which is indicative of profound hypoxia.
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There was an abnormally-shaped right bronchus, with a large bronchus going into the right upper lobe and a second large bronchus going into the right middle lobe that had a branch within the right middle lobe supplying the right lower lobe (Figure 5A). Both the upper lobes and the right lower lobe, and to a lesser degree, the left lower lung parenchyma was nearly filled with macrophages (Figure 5B). The radial alveolar count was not diminished, which is not typically seen in neonates with trisomy 21.   In addition, there were prominent intrapulmonary bronchopulmonary vascular anastomoses.   There were distinct histologic changes related to pulmonary hypertension with marked thickening of the media of the muscular pulmonary arteries. The muscular pulmonary arteries also displayed intimal fibrosis with extensive calcification of the pulmonary vessels, typically a secondary phenomenon related to arterial damage and metabolic disorders (Figure 5C). However, there was no evidence of extension of a complete smooth muscle layer into distal acinar vessels (Figure 5D). There was also scattered, focal areas of extramedullary hematopoiesis, indicative of profound hypoxia (Figure 5E).
No anatomic abnormalities of the thoracic duct or hematologic malignancies were identified to account for the decedent's chylothorax. (A) Additional views from the posterior surface of the thoracic cavity demonstrating an intact and patent thoracic duct (blue arrows). (B) The H&E section of the vertebral body demonstrated cartilage surrounding pink bone with bone marrow spaces that contain normal trilineage hematopoiesis occupying nearly 100% of the bone marrow. A Kappa and Lambda ISH stain were performed that showed appropriate 2:1 Kappa to Lambda staining, further ruling out the possibility of leukemia or lymphoma. (H&E 400x; Kappa and Lambda ISH, 200x).
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A single thoracic duct arose from the cisterna chyli (Figure 6A). A Kappa and Lambda ISH stain was performed that showed appropriate 2:1 Kappa to Lambda staining (Figure 6B).
No anatomic abnormalities in the kidneys or urinary tract were identified to account for the decedent's severe, medically refractive anasarca. (A) Representative image of the kidneys demonstrating fetal lobulation but otherwise normal in gross appearance. (B) A representative H&E micrograph of the kidney that demonstrated the appropriate maturity for the age of the decedent. There were mature glomeruli from the capsule downwards with mild autolysis present. There was also mild vascular congestion present. No atrophic tubules or chronic inflammatory infiltrate or sclerosis of the glomeruli were seen. Overall, no pathological abnormalities were identified. (H&E, 20x, 200x, as labeled) (C). A representative H&E cross section of the proximal ureter within the renal pelvis with no pathologic abnormalities or obstruction demonstrated. (H&E, 40x) (D). An H&E cross-section of the distal ureter demonstrating normal histological architecture and intact mucosa. The lumen is fully patent. (H&E, 100x).
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However, we did note that both kidneys had fetal lobulation (Figure 7A). However, on microscopic evaluation, the kidneys had appropriate maturity for the age of the decedent, with mature glomeruli (Figure 7B). The ureters were straight, thin, tubular structures without focal lesions or evidence of obstruction (Figure 7C). No obstructions or stenosis were identified (Figure 7D).