A preterm baby passed away and these are his lungs on gross specimen. What might a chest x-ray have looked like if taken before the infant died?
Note the firm lungs with focal hemorrhage almost look more like liver. This is RDS (Hyaline Membrane disease). You would see the “ground-glass” white-out appearance from alveolar edema and pulmonary collapse.
A preterm baby passed away and these are his lungs on gross specimen. What might a chest x-ray have looked like if taken before the infant died?
Hyaline membranes, hemorrhage, fibrin, necrosis of pneumocytes, squames and atelectasis are histological characteristics of hyaline membrane disease.
How does surfactant replacement therapy save a preterm baby with RDS?
It induces pneumocyte growth over the hyaline membrane and the hyaline membranes are replaced.
How can you as the physician cause permanent damage to a neonate’s lungs?
High O2 and ventilation used to treat hyaline membrane disease can cause permanent fibrosis in the alveolar walls and very stiff lungs = bronchopulmonary dysplasia (BPD).
A child has difficulty exchanging oxygen after a preterm delivery. He was put on high flow O2 for a number of days. What might you expect histology of his lungs to look like?
Bronchopulmonary dysplasia is characterized by necrotizing bronchiolitis and fibrosis of the lung parenchyma and alveolar septal fibrosis in addition to hyaline membrane disease.
When do alveoli stop developing? What does this mean for BPD?
18 months old. Patients with BPD just don’t develop enough alveoli due to septal fibrosis and they cannot adequately peruse blood on their own.
A premature baby left the hospital doing just fine, but presents with asphyxia, abdominal distention, vomiting, pallor, thermal instability, apnea and shock after oral feedings began. Radiographs are shown below. What is causing this child’s condition?
Neonatal necrotizing enterocolitis. Note the air in the bowel (pneumatosis intestinalis), pneumoperitoneum and portal tract due to dissection of GI mucosa. All of these things put the child at risk for intestinal perforation (shown below) and hemorrhage.
Mortality rate for babies that need surgery to correct neonatal necrotizing enterocolitis?
A premature baby left the hospital doing just fine, but presents with asphyxia, abdominal distention, vomiting, pallor, thermal instability, apnea, DIC, thrombocytopenia and shock after oral feedings began. Radiographs show pneumoperitoneum. What would you expect histology of this child’s bowel to look like?
Neonatal Necrotizing Enterocolitis would have mucosal necrosis that extends into the submucosa and mucosal layers. You would also see small air-filled cysts beneath the mucosa (pneumatosis intestinalis).
How do you treat neonatal necrotizing enterocolitis?
Stop oral feeding, give IV fluids and decompress all air out of the abdomen to reduce mucosal ischemia.
If a child survives neonatal necrotizing enterocolitis, what complications may they suffer from later on in life?
Short gut syndrome if they had bowel surgically resected. This can cause malabsorption, strictures, atresia, obstruction and fistulas.
A newborn child presents with coughing, choking and cyanosis with feeding. What congenital abnormality may be causing his condition?
Tracheoesophageal atresia or fistula. The most common presentation is esophageal atresia with TEF in the distal esophagus (shown below).
When can people get TEF not due to congenital infection?
Swallowing batteries, the acid erodes through the esophagus and causes fistula formation to the trachea.
What other anomalies are associated with a congenital TEF?
“VATER”: Vertebral defects, Anal atresia, TEF and Renal anomalies. CV anomalies and limb defects are also seen.
A pregnant mother goes in for an ultrasound and the physician sees oligohydramnios. The urinary bladder, ureters and kidneys were all dilated. The kidneys were noted to be sac-like. What is causing this child’s condition and how would you expect the child to appear out of the womb?
Potter Sequence (flat facies, swooping ears, sloped forehead, epicanthal folds). This is a result of oligohydramnios because the fetus is squished against the uterine wall. This can be caused by bilateral renal agenesis, bilateral renal dysplasia, obstructive uropathy (unilateral or bilateral) or polycystic renal disease.
Serious postpartum complications in babies with Potter sequence?
Pulmonary hypoplasia from lung compression.
A child is born with pulmonary hypoplasia but oligohydramnios was not noted in utero. What could cause this?
Diaphragmatic hernia, intrathoracic masses and skeletal abnormalities (dwarfism) that compress the lungs during development.
A newborn presents with respiratory distress. Imaging of the child’s lung is shown below. How do you treat this child?
This child has congenital pulmonary airway malformation (CPAM). This is a result of abnormal formation of the bronchial tree that produces abnormal spaces of lung tissue that form collapsed cysts. Taking this out of the affected lobe provides more room for the rest of the lungs to expand and respiratory distress will be relived.
A newborn presents with respiratory distress. Gross image of the child’s lungs is shown below. What would this look like histologically?
Congenital pulmonary airway malformation (CPAM) forms larger cysts made up of hamartoma (normal tissue that is malformed with epithelium and muscle)
What tumors can arise from this section of a newborn’s lung?
Pleural pulmonary blastomas (type of rhabdomyosarcoma) can arise from congenital pulmonary airway malformation.
A child presents with respiratory distress at birth. Gross specimen is shown below. What caused this child’s RDS? What would you expect to see on histology?
Extralobar sequestration. This is an abnormal outpouching of the foregut that can fill with air and compress the lungs. On histology you would see expanded alveolar ducts and bronchioles because there is no place for lung fluid to drain.
Anomalies associated with extralobar sequestration
Congenital heart malformation, pulmonary hypoplasia, diaphragmatic hernia and renal ectopia.
A mother brings in her infant who has had slowly progressive respiratory distress. CXR is shown below. What is your diagnosis? What would you expect lung biopsy to look like?
Infantile lobar emphysema. Note the hyper lucent lobe, mediastinal shift and compression of the uninvolved lobes. On biopsy you would see one of two patterns: normal alveoli that are hyperinflated/hyperexpanded and hyper plastic alveoli.
A 3 week old boy presents with progressive nonbilious vomiting. On physical exam you see peristaltic waves and and almond like abdominal mass. What is your diagnosis and how do you treat?
Hypertrophic pyloric stenosis presents with non-bilious vomiting because food has not yet reached the duodenum. You treat with a longitudinal incision of hypertrophied muscle down the gastric mucosa.
An infant was born to a women who had a cytogenetic study of amniotic fluid that showed trisomy 21. After the 3rd feeding the infant’s abdomen became distended and vomited bilious fluid. What is likely causing this child’s condition?
Intestinal atresia beyond ampulla of Vater, which is associated with Down syndrome and cystic fibrosis. Note that 10% of cases are multiple and rarely found in the colon.
A 2 day old infant has not passed any meconium and has a slowly distended bowel. Abdominal x-ray is shown below. What is causing this child’s condition?
Note the enlarging sigmoid colon ending in a funnel-shape above the anus. This is typical of Hirschsprung disease. This is a result of congenital absence of parasympathetic ganglion cells in the distal GI tract. Note that this is common in males and common with trisomy 21.
What does the pathologist look for on diagnosis of Hirchsprung’s disease?
A 12 year old boy presents with lower abdominal pain and rectal bleeding. Image of the surgery is shown below. What causes this condition? What is the rule of 2’s associated with this condition?
A Meckel diverticulum is a remnant of the vitelline duct. Note that it occurs 2% of the time, 2 feet from ileocecal valve, 2 cm long and 2% have ectopic pancreatic tissue.
When is the only time you really see carcinomas in children?
Familial Adenomatous Polyposis yields adenocarcinoma in the intestine. 100% will have carcinoma by age 50.
What are the two types of sarcomas you see in children? Which has the worse prognosis?
Embryonal (small round blue cells that are precursors to skeletal muscle) and alveolar (worse prognosis) rhabdomyosarcoma.
A 7 year old boy complains of diplopia. He has fallen a couple of times in the past week, but has not had any injuries. Physical exam reveals uneven gait and can’t walk in a straight line, MRI shows a 2.5cm lesion in his cerebellum. What is the most likely cause of his symptoms?
Astrocytomas are the most common CNS tumors in kids.
Most frequently occurring solid tumors in children?
CNS tumors: astrocytoma (most frequent), primitive neuroectodermal tumor, ependymoma and craniopharyngioma.
A 7 year old boy complains of diplopia. He has fallen a couple of times in the past week, but has not had any injuries. Physical exam reveals uneven gait and can’t walk in a straight line, MRI shows a 2.5cm lesion in his cerebellum. The tumor is excised and shown below. What grade tumor is this?
This is a low-grade astrocytoma. Note the firm, white, enlarged structure with indistinct margins and cysts. A high-grade “glioblastoma multiforme” would have necrosis and hemorrhage.
A 7 year old boy complains of diplopia. He has fallen a couple of times in the past week, but has not had any injuries. Physical exam reveals uneven gait and can’t walk in a straight line, MRI shows a 2.5cm lesion in his cerebellum. What are the histological categories of this tumor?
1) Pilocytic astrocytoma: loose spongy and compact areas, microcysts, Rosenthal fibers, lower cellularity and focal calcifications. 2) GBM: lots of anaplastic cells, giant cells, necrosis, endothelial proliferation, mitoses and increased cellularity.
A 2 year old has watery diarrhea for 2 weeks with no fever or any other symptoms. Abdominal CT shows focal calcification in a mass just above the left kidney. What is the likely diagnosis and prognosis? How do you confirm your diagnosis?
Calcification is related to areas of necrosis. Neuroblastomas are the most common malignant tumor in the 1st year of life and they often occur in the adrenal gland. The prognosis is not great because 50% have already metastasized at the time of diagnosis. You confirm by testing urine for VMA and HVA.
Aside from the adrenal, where else do neuroblastomas like to pop up at in children under 4?
Posterior mediastinum, cervical sympathetic ganglion, retroperitoneum and spinal cord.
Diseases associated with neuroblastomas
von Recklinghausen’s, neurofibromatosis and Hirschsprung’s disease.
Paraneoplastic syndromes associated with neuroblastomas
Watery diarrhea (vasoactive peptide production), raccoon eyes (orbital metastases) and blueberry muffin skin (skin metastases)
How do you stage neuroblastoma?
1) Confined to organ of origin 2) Extending to adjacent structures 3) Extending across midline 4) Metastatic 4S) Stage I or II patients with remote disease confined only to liver (may cause RDS), skin and/or bone marrow (this has a good prognosis)
Gene associated with a poor prognosis in neuroblastomas
N-myc (poor response to chemo), 1p deletion and 17q21 gain.
Histologic characteristics of a neuroblastoma
Small round blue cells, Homer Wright rosettes (central neural fibrils), necrosis, calcification and stroma separates clusters of neuroblasts. Some neuroblasts may be hyperchromatic and others may look like ganglion cells.
How do you grade a neuroblastoma?
1) Calcification + low mitoses 2) Calcification or low mitoses 3) No calcification and high mitoses
What is your diagnosis of these tumors that began as small, round, blue cell neuroblastomas?
Top - ganglioneuroblastoma. Bottom - ganglioneuroma. Note the differentiation of tumor cells into ganglion cells.
Good prognostic factors for neuroblastoma
< 1.5 years old, not in adrenal, paraneoplastic (opsoclonus-myoclonus), stages I, II, IVS, calcification + low mitotic rate and no N-myc or Ha-ras amplification.
A 3 year old presents with a very large mass in the LUQ of his abdomen. His mother says that he has been nauseated over the past two weeks. Physical exam reveals a BP of 145/90. What is the most likely malignant tumor presenting in this child?
Wilms tumor (a nephroblastoma) is the most common malignant renal tumor in children.
A 3 year old presents with a mass in the LUQ of his abdomen. His mother says that he has been nauseated over the past two weeks. Physical exam reveals a BP of 145/90. He also has gigantism, macroglossia, visceromegaly, omphalocele and umbilical hernia. What is your diagnosis?
Wilms tumor + the other conditions = Beckwith -Weidemann Syndrome.
What optic effects are associated with Wilms tumors?
Aniridia. It is associated With WAGR syndrome (Wilms tumor, Aniridia, GU anomalies and Retardation).
Wilms tumor staging
1) Limited to kidney 2) Adjacent structures 3) Across midline but confined to abdomen 4) Metastatic 5) WIlm’s in both kidneys.
What would you see on histologic analysis of a Wilms tumor?
Small, round, blue cells, epithelial gland formation and fibromyxoid stroma (w/cartilage, bone and muscle)
What is the prognosis of this Wilms tumor?
Note the anaplasia: nuclear enlargement, hyperchromasia and mitoses. This is a worse prognosis. Note that regardless of the stage, absence of anaplasia = good prognosis.
A 14 year old boy notes a tender bump on the lateral side of his left knee where he was kicked playing soccer. His bone is shown below. If this is a tumor, what is your differential?
Osteosarcoma is most likely. Note cortical bone destruction, lifting of the periosteum, soft tissue extension and sclerosis of bone. Ewing sarcoma or chondrosarcoma can also happen.
What syndromes and diseases should you check for if a kid presents with osteosarcoma?
Ollier disease, Maffucci syndrome, Osteogenesis imperfecta and Paget disease.
Most common site of osteosarcoma
Distal femur and proximal tibia
Histological pattern of osteogenic sarcoma.
Osteoid epithelium being formed by osteoblasts
Common site of metastasis of osteosarcoma? Prognosis?
Lung. These have a good prognosis because they are very radiosensitive. Prognosis is great if pre-operative chemotherapy produced 95% of tumor necrosis. Poor prognosis if < 50% of tumor is necrosed after chemo.