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Pediatric Pathology
Sunday, February 12, 2006 - 7:30 PM
Centennial II
Pediatric Potpourri
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Moderator:
Deborah Perry
Children's Pathology
Omaha, NE
Disclosure: The speakers have indicated they have nothing to disclose.
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Clinical histories are printed below.
Click on the case numbers for text and references of each case.
Click on each slide thumbnail image for an enlarged view
Submitted by:
Sara O. Vargas
Children's Hospital
Boston, MA
This 7-year-old girl presented with a painless nontender swelling of the left labium majus that had been apparent for one year. The area was soft without overlying skin discoloration, and although no distinct mass was palpable, the left labium majus was clearly larger than the right. Breasts were Tanner stage 1, and there were no early pubertal signs. Serum FSH, LH, and estradiol levels were within normal limits. The abnormality was followed for 6 months and appeared to enlarge. Ultrasound examination failed to reveal a discrete mass, and the sonographic changes were described as "extra soft tissue." MRI showed a somewhat circumscribed area (low in signal intensity on T1-weighted images, high in signal intensity on T2-weighted images, and enhancing fairly homogeneously with gadolinium) measuring approximately 4 x 2 x 2 cm. Given the concern for possible malignancy, surgical excision was performed. In the operative report the surgeon stated, "There was no clear definable mass." The tissue was described as fatty and likened to a lipoma. There was no inguinal hernia.
Case 1 - Figure 1 -
Gross examination showed fibrofatty tissue without discrete lesional boundaries.
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Case 1 - Figure 2 -
A sparsely cellular collection of round, oval, and spindled fibroblasts expanded fibrous septa and surrounded fat lobules, individual adipocytes, and blood vessels (original magnification, 10x).
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Case 1 - Figure 3 -
Here, the fibroblasts were surrounded by an abundant pale matrix containing thin and thick collagen and elastic fibers (original magnification, 20x).
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Case 1 - Figure 4 -
Many fibroblasts were slightly plump and showed amphophilic cytoplasm, often with bipolar cytoplasmic extensions (original magnification, 40x).
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Case 1 - Figure 5 -
Nerves characteristically showed thick perineuria and myxoid change (original magnification, 20x).
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Case 1 - Figure 6 -
More heavily collagenized areas alternated with less heavily collagenized areas. Defining any boundary of the abnormality was difficult (original magnification, 4x).
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Case 1 - Figure 7 -
An elastic tissue stain highlighted numerous elastic fibers (original magnification, 40x).
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Case 1 - Figure 8 -
Immunostaining for estrogen receptor highlighted a subset of the plump fibroblast nuclei (original magnification, 40x).
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Submitted by:
David Witte
Children's Hospital Medical Center
Cincinnati, OH
A 2665-gram female infant was delivered vaginally at 36 weeks of gestation to a 24 year-old gravida IV para II Caucasian mother and her 41 year-old African American father. Prenatal care had been sporadic, but maternal laboratory values were normal. The family history was negative for any inheritable disorders and there was no history of renal or ophthalmologic problems. The pregnancy was remarkable for an abnormal fetal ultrasound at 28 weeks which revealed large, hyperechoic kidneys. At the 36 week visit, another ultrasound showed a decreased bio-physical profile (5/10) and a decreased amniotic fluid index, prompting induction of labor. Delivery was uneventful with Apgar scores of 7 and 8 at one and five minutes, respectively. On initial newborn exam, the patient had slightly decreased muscle tone but intact reflexes. Moreover, she was found to have bilateral microcoria, ie.- pinpoint pupils, prompting a maternal drug screen which was positive only for caffeine. No other dysmorphology was noted.
On day of life 3, the patient was noted to have slight edema of her legs and left eyelid. After initially doing well, she started to feed poorly, taking only 10 milliliters per feeding. Meconium drug screen was also negative.After further inquiry revealed the abnormal prenatal ultrasound findings, a renal profile was obtained, showing hyponatremia (129 mmol/dL) and renal insufficiency (creatinine of 2.7 mg/dL). A follow-up renal ultrasound was obtained which confirmed bilaterally enlarged hyperechoic kidneys. Because of the patient's renal failure, she was transferred with a suspected diagnosis of autosomal recessive polycystic kidney disease.
Laboratory evaluation after transfer showed significant proteinuria (>300 mg/dL on dipstick), hypoalbuminemia (1.5 gm/dL) and persistent renal dysfunction (creatinine of 2.9 mg/dL), leading to the diagnosis of Congenital Nephrotic Syndrome with renal failure. Abdominal and pelvic ultrasound revealed a normal liver and spleen, the aforementioned enlarged hyperechoic kidneys with loss of corticomedullary differentiation, and normal ovaries and uterus. A head ultrasound was normal, as well. CMV antigen was undetectable, and there was no other evidence of TORCH infections. High resolution chromosomal analysis showed a normal XX karyotype. Pediatric ophthalmology consultants found continued pupillary constriction despite dilating drops and persistent hyperplastic primary vitreous of the right eye. The patient was noted to be moderately hypertensive with blood pressures >120/ 80 in all four extremities, requiring multiple anti-hypertensive medications to control. She was also dependent on intravenous albumin and furosemide for edema management. An open renal biopsy was performed at 3 weeks of life.
Case 2 - Figure 1 -
Closeup photograph of the patients eye with microcoria (pinpoint pupil).
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Case 2 - Figure 2 -
Photomicrograph of kidney showing extensive tubular atrophy and cystic dilatation of tubules. There is a wide range of glomerular lesions including crescent formation, sclerosis, and some immature glomeruli.
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Case 2 - Figure 3 -
Higher magnification photomicrograph of the kidney showing hypercellular glomerulus and tubular atrophy.
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Case 2 - Figure 4 -
Higher magnification of kidney section shown in Figure 2 showing details of glomerulus with crescent formation and a sclerotic glomerulus.
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Case 2 - Figure 5 -
Photomicrograph of kidney section stained with Jones stain. There is one collapsed glomerulus with increased matrix surrounded by a crescent.
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Case 2 - Figure 6 -
Electron photomicrograph of kidney which shows microvillous change, foot process effacement with patent capillary loops.
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Case 2 - Figure 7 -
High magnification electronphotomicrograph of the kidney showing a very thin lamina densa (< 50 nm) and foot process effacement.
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Case 2 - Figure 8 -
Electron photomicrograph of kidney showing an immature glomerulus with a capillary loop surrounded by a "corona" of prominent podocytes.
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Submitted by:
Megan K. Dishop
Texas Children's Hospital
Houston, TX
3 month old full term Hispanic infant girl with severe interstitial lung disease. She was delivered by Cesarean section after an uneventful pregnancy and had no perinatal complications, discharged on the fourth day of life. She presented initially at 10 weeks of age with respiratory distress including nasal flaring, retractions, tachypnea, and hypoxia. She was afebrile without cough and there were no concurrent illnesses in family members. Chest x-ray showed bilateral interstitial infiltrates with consideration of bronchiolitis versus bilateral pneumonia. Chest CT showed diffuse ground-glass appearance consistent with interstitial infiltrates or alveolitis. She received a two-week course of antibiotics and also steroids, bronchodilators, and supplemental oxygen during her course, but her respiratory status continued to deteriorate. Other evaluation included an esophagram showing frequent episodes of gastroesophageal reflux, normal echocardiogram, negative HIV serology, negative cystic fibrosis mutation analysis, and a bronchoalveolar lavage with increased lipid-laden macrophages and negative cultures. One month after initial presentation, she underwent an open lung biopsy (see images).
Case 3 - Figure 6 -
Bronchoalveolar lavage (Wright-Giemsa). Amorphous proteinosis material appears basophilic on Giemsa stain.
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Case 3 - Figure 7 -
Bronchoalveolar lavage (Wright-Giemsa). The cellular components included many alveolar macrophages including some with orangophilic droplets, as well as occasional reactive alveolar epithelial cells. Increased lipid-laden macrophages and occasional hemosiderin-laden macrophages were noted.
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Case 3 - Figure 1 -
Lung biopsy (H&E). The alveolar architecture is altered with mild lobular remodeling and airspace enlargement.
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Case 3 - Figure 2 -
Lung biopsy (H&E). Patchy areas of eosinophilic globular and granular proteinosis material fill the airspaces.
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Case 3 - Figure 3 -
Lung biopsy (H&E). The alveolar proteinosis is accompanied by diffuse type II alveolar epithelial cell hyperplasia.
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Case 3 - Figure 4 -
Lung biopsy (H&E). Scattered alveolar macrophages and occasional cholesterol clefts are present within areas of granular proteinosis material.
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Case 3 - Figure 5 -
Lung biopsy (PAS). The alveolar material is PAS-positive, typical of alveolar proteinosis.
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Case 3 - Figure 8 -
Lungs (Gross). At autopsy, the lungs showed subpleural stippled yellow material corresponding to alveolar lipoproteinosis material seen histologically.
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Case 3 - Figure 9 -
Non-specific interstitial pneumonia pattern. Lung biopsy in 6 year old with chronic lung disease and ABCA3 mutations (H&E). Mild interstitial lymphocyte infiltrates with reactive alveolar epithelial hyperplasia, clusters of alveolar macrophages, and extension of airway smooth muscle into the lobular interstitium.
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Case 3 - Figure 10 -
Non-specific interstitial pneumonia pattern. Lung biopsy in 6 year old with chronic lung disease and ABCA3 mutations (H&E). Subpleural cholesterol clefts and clusters of foamy macrophages associated with lobular remodeling, similar to endogenous lipoid pneumonia.
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Case 3 - Figure 11 -
Non-specific interstitial pneumonia pattern. Lung biopsy in 6 year old with chronic lung disease and ABCA3 mutations (PAS). Rare PAS-positive alveolar material.
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Case 3 - Figure 12 -
Chronic pneumonitis of infancy pattern. Lung biopsy in 3 month old infant with SP-C mutation (H&E). Infants with SP-C mutations tend to have more prominent lobular remodeling and extension of airway smooth muscle into the lobular interstitium. Cholesterol cleft formation may be prominent.
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Case 3 - Figure 13 -
Chronic pneumonitis of infancy pattern. Lung biopsy in 3 month old infant with SP-C mutation (H&E). Alveolar proteinosis material is inconspicuous relative to SP-B or ABCA3 mutations.
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Submitted by:
Theodore J. Pysher
Primary Children's Medical Center
Salt Lake City, UT
A percutaneous renal biopsy was performed in an adolescent female with nephrotic range proteinuria.
A 19 year old Caucasian female was referred for evaluation of proteinuria that was discovered in the course of a routine physical examination. She had not noticed facial or extremity edema, skin rash, joint pain or swelling, or discolored urine. She was overweight, complained of intermittent heartburn, and was being treated for obstructive sleep apnea. Neither the patient nor her family members had hearing problems, and there was no family history of renal disease, but both parents were on antihypertensives. Physical examinations on several occassions were remarkable only for pulse rates that ranged from 100-108/minute, blood pressures that ranged from 126/65-150/90 Torr, and height at the 50th percentile for age but weight greater than the 95th percentile with a body mass index of 40 kg/M2.
Urinalyses showed 3+-4+ protein and negative or trace blood, the protein:creatinine ratio ranged from 0.49-1.67 (expected <0.2), and a timed urine collection revealed 2.3 grams of protein/24 h and a creatinine clearance of 85 mL/min/1.73 M2. Abnormal laboratory studies included cholesterol 233 mg/dL, triglycerides 246 mg/dL, LDL cholesterol 141 mg/dL, non-fasting glucose levels that ranged from 87-136 mg/dL, and alanine aminotransferase 58 IU. Normal studies included blood urea nitrogen, creatinine, total protein, albumin, sodium, potassium, chloride, total bicarbonate, calcium, inorganic phosphate, complete blood count, C3 and C4 complement levels, anti-nuclear, anti-smooth muscle and anti-neutrophil cytoplasmic antibodies, hemoglobin A1C, thyroid stimulating hormone, and serologic studies for hepatitis A, B and C.
Case 4 - Figure 1 -
This low magnification photomicrograph shows five glomeruli. The glomeruli at the left and top are large and the other three show segmentally increased mesangial matrix. PAS
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Case 4 - Figure 2 -
At higher magnification the increased mesangial matrix in the three smaller glomeruli and the large glomerulus at the top is more evident. The glomerulus at the lower right also shows segmental proliferation of visceral epithelial cells (between 6 and 9 o’clock). Jones
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Case 4 - Figure 3 -
The glomerulus in the center is enlarged, the glomerulus at the left shows segmental tuft sclerosis, and the intervening parenchyma shows tubular atrophy and interstitial fibrosis. PAS
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Case 4 - Figure 4 -
This glomerulus shows segmental sclerosis (6 to 9 o’clock) and increased mesangial matrix and cellularity in the remaining tufts. Hyaline material can be seen at the interface of the sclerotic tuft and Bowman’s capsule. PAS
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Case 4 - Figure 5 -
Beginning at the upper left there is an area of tubular atrophy and interstitial fibrosis, then a globally sclerotic glomerulus, and then a glomerulus that shows extensive segmental sclerosis involving at least 50% of the glomerular area. PAS
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Case 4 - Figure 6 -
This glomerulus shows several features of diabetic nephropathy – a capsular drop at 11 o’clock, a hyaline cap at 12 o’clock, and an area of mesangial expansion near 7 o’clock. PAS
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Case 4 - Figure 7 -
This arteriole shows eccentric sub-intimal hyalinosis. PAS
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Case 4 - Figure 8 -
Approximately 15% of the cortical area showed interstitial fibrosis. Trichrome
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Case 4 - Figure 9 -
Immunofluorescent microscopy showed only non-specific staining for IgG (shown here), IgM and C3. Fluoresceinated anti-IgG
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Case 4 - Figure 10 -
This electron micrograph shows a widely patent capillary loop at the upper left and a collapsed tuft at the lower right with electron dense material of uncertain significance in the sclerotic area at the upper right. No deposits consistent with immune complexes, or alterations of the capillary basement membrane are evident.
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