We reviewed clinical data and quantitative muscle biopsy data from infants with hypotonia and developmental delay who had relatively small type 1 muscle fibers (fiber size disproportion; FSD). Study material consisted of 49 thigh muscle specimens from 37 patients, 1 week to 11.5 years old, who had FSD diagnosed between 1971 and 1985. Beyond 2 months of age, FSD was greater than 12% in at least one biopsy from all but 2 patients. In sequential specimens obtained from 11 patients, we observed that FSD may resolve, persist unchanged, or intensify with age. In 6 patients, hypotonia regressed, and development tended to normalize during 1-4 years of observation; FSD resolved in 4 cases, but numerical predominance of type 1 fibers persisted in 3 of them. In a small group designated congenital myopathy with FSD only, the disproportion in fiber diameter persisted unchanged or intensified with time and was more severe after the age of 6 months than in the other subgroups. We classified FSD as definitely or probably myopathic (15 cases), definitely or probably neuropathic (17 cases), and benign maturation delay (5 cases). Six of 17 neuropathic cases had a history of perinatal asphyxia. In most cases, type 1 fibers were absolutely small and type 2 fibers were hypertrophied, independent of classification. FSD is a manifestation of muscle maturation delay of variable etiology. The prevalence of nervous system disorders in our series suggests that neuronal dysfunction plays an important role in pathogenesis. We were unable to define morphometric criteria that consistently distinguished congenital myopathy with FSD from definable neuropathic FSD or from benign maturation delay.
A fatal case of diphtheria occurred in a nonimmunized child. The child died because of the late diagnosis of the disease, which is now extremely rare.
This review discusses the neuropathological issues pertaining to temporal lobectomies and neocortical resections for medically refractory seizures of childhood. Most cases in our pediatric series are ''lesional'' and have CT/MRI abnormalities that contribute to a higher incidence of ''dual pathology'' lesions rather than pure mesial temporal sclerosis. Almost up to two thirds of our cases are represented by neuronal migration disorders and low grade gliomas. We have also encountered lesions that have both neoplastic and malformative foci, some of which behave more like tumors, while others defy precise classification as tumor or malformation. Our preliminary data indicate a role for cytomegalovirus in some cases of Rasmussen's encephalitis.
We report the necropsy findings for three infants with the unusual combination of proximal renal tubular dysgenesis and severe congenital liver disease with excessive iron in several organs resembling neonatal hemochromatosis. Two of the infants were caucasian siblings and one was an Australian aborigine. One died in utero at 35 weeks of gestation and two died at 7 days. The liveborn infants presented with anuria and liver failure. The livers all showed marked loss of hepatocytes and replacement by pseudotubules in the collapsed lobules. The liveborn infants also showed giant cell transformation ofhepatocytes, small regenerative nodules, cholestasis, and normal bile ducts. Absence of proximal renal convolutions was confirmed by epithelial membrane antigen positivity in nearly all tubules. In each family there was another sibling with congenital liver disease, fatal in one case, but no renal tubular dysgenesis. No infection or metabolic disease was uncovered in any of our patients, and the cause of the hepatocyte destruction was not determined. The combination in three infants of two rare congenital diseases could be genetic or acquired in utero from the same etiological agent. Alternatively, the absence of proximal convolutions could be secondary to hypoperfusion, perhaps because of shock due to extensive necrosis of hepatocytes.
Late infantile neuronal lipfuscinosis was confirmed by electron microscopy in this case, At magnifications above 100,000 a particular alternating linear pattern of the curvilinear bodies was found.
We report a 23-month-old girl and a 9-month-old boy who presented with autoimmune hemolytic anemia followed by recurrent episodes of severe hepatitis. The first episode of hepatitis occurred 1 week and 15 months after presentation, respectively. Histologically, the livers showed loss of lobular architecture with diffuse giant cell transformation of hepatocytes and portal and pericellular fibrosis. The first patient died at 4 1/2 months after her initial presentation with a well-established micronodular cirrhosis. The second patient responded to steroid therapy and the hepatitis recurred when steroids were tapered. Postinfantile giant cell hepatitis may occur in association with Coombs-positive hemolytic anemia, it is thought to have an autoimmune mechanism, and early and sustained immunosuppression may control the progressive hepatocellular damage and prevent cirrhosis.
Sixty-seven childhood tumors were studied immunohistochemically for the extracellular matrix element type IV collagen, laminin, and fibronectin. Tumors included Ewing's sarcoma, primitive neuroectodermal tumor, small cell osteosarcoma, neuroblastoma or ganglioneuroblastoma, rhabdomyosarcoma, and lymphoma. It was found that small cell osteosarcoma was often positive for fibronectin but not type IV collagen or laminin, a new observation. In the lymphomas, matrix proteins were rarely found. Ewing's sarcoma was variably positive for type IV collagen and laminin, but fibronectin was absent. Extracellular laminin and fibronectin were found in one of two cases of primitive neuroectodermal tumor. In neuroblastoma and ganglioneuroblastoma, the matrix components were rarely found. These results, discrepant with findings in cultured cells, may reflect the altered capacity of tumors to produce these proteins in vitro, which suggests that caution should be exercised in drawing conclusions regarding the nature or histogenesis of tumors from data obtained with cultured tumor cells. Embryonal rhabdomyosarcoma frequently contained all matrix elements in the extracellular space and in a dotlike pattern in the cytoplasm; alveolar rhabdomyosarcoma rarely contained these proteins and never exhibited the dotlike pattern. The frequent finding of matrix proteins in embryonal rhabdomyosarcoma but only rarely in alveolar rhabdomyosarcoma and the unique immunostaining pattern in embryonal rhabdomyosarcoma may prove to be a useful adjunct in the diagnosis of childhood tumors.
Necrotizing funisitis is associated with an increased rate of stillbirth, perinatal infection, and preterm delivery. No one organism has been associated with necrotizing funisitis, although this condition has been linked with congenital syphilis in some studies. We report a case of necrotizing funisitis in a 24-year-old G2P0A2 woman who experienced preterm labor at 31 weeks of gestation. Examination of the placenta revealed severe chorioamnionitis and necrotizing funisitis; large numbers of gram-positive filamentous branching organisms could be seen on the surface of the cord and within Wharton jelly. Initial cultures of the placenta, which had not been maintained under anaerobic conditions after delivery, were negative. A fragment of the cord was then homogenized; anaerobic culture on brain-heart infusion agar yielded Actinomyces meyeri. This organism usually resides in the periodontal sulcus and has not been previously reported in the female genital tract. The mother gave a history of a dental abscess that flared up and drained with each of her three pregnancies; the pain was particularly severe during the last 2 months of this pregnancy, so she had the tooth removed after delivery. The infant was treated for prematurity and presumed sepsis and did well.
Respiratory distress syndrome (RDS) is associated with prematurity-related deficiency of surfactant. Surfactant replacement therapy has been used in premature infants to prevent RDS or reduce its severity. In this study we describe the pathology of the lungs after surfactant replacement therapy. All the neonatal autopsies during the years 1989 and 1990 (n = 235) were examined. Infants > or = 31 weeks gestation, with congenital anomalies or who lived more than 2 weeks were excluded from the study. Infants who had received intratracheal Survanta, a modified surfactant extracted from cow lung (n = 14), were compared with infants who did not receive exogenous surfactant (n = 20). The two groups were statistically comparable in terms of weight, gestational and postnatal age, gender, and clinical management. H&E-stained lung sections were examined independently by two pathologists without knowledge of surfactant treatment status; any discrepancies in histological evaluation were resolved by joint review. Nine histological features were evaluated including hyaline membranes, necrosis of the epithelium, hemorrhage, edema, inflammation, metaplasia, arteriolar muscular hyperplasia, interstitial fibrosis, and pulmonary interstitial emphysema (PIE). Histological changes were graded from 0 to 3+. When it was present, cerebral periventricular-intraventricular hemorrhage (PVH-IVH) was graded 1-4. The presence or absence of sepsis and necrotizing enterocolitis (NEC) were also determined. Comparisons between patient groups were performed using the Mann-Whitney U, Student's t and chi 2 tests. The severity of hyaline membrane disease, PIE, and epithelial necrosis was less severe in the surfactant-treated group than in the untreated group. There were no differences between the two groups in the degree of pulmonary hemorrhage or in the incidence of PVH-IVH, sepsis, or NEC.
The combination of renal tubular dysgenesis (RTD) and meconium ileus in a native Israeli is presented for the first time. The clinical diagnosis was oligohydramnios and abruptio placentae, respiratory failure, and anuria refractory to treatment. The autopsy revealed meconium ileus and meconium peritonitis. RTD was established by the detection of a monomorphous undifferentiated population of tubules, absence of proximal tubules, and dense epithelial membrane antigen immunoreactivity of all tubules. The lack of alpha 1-antitrypsin- and lysozyme-immunoreactive tubules was first revealed in the kidney with RTD. These findings extend the possibilities of RTD detection.
We describe immunohistochemical studies of the expression of alpha and pi class glutathione S-transferases (GSTs) in normal fetal kidneys. These define, in greater detail, changes in expression of alpha isoforms in the proximal tubule. At about 36 weeks of gestation expression of alpha isoforms was down-regulated in the distal tubules and collecting ducts while pi was expressed throughout the nephron. Tubular expression of alpha isoforms was restricted to the part adjacent to the glomerulus; cells farthest from the glomerulus were negative. After 40 weeks of gestation, alpha isoforms were expressed along the entire proximal tubule, while pi was restricted to the distal tubule and collecting ducts. GST expression was also studied in multicystic renal dysplasia, autosomal recessive polycystic kidney disease, and autosomal dominant polycystic kidney disease to determine whether the patterns of expression of alpha and pi isoforms allow identification of the origin of the cysts that characterize these diseases. Cysts were lined by epithelia that were strongly positive for alpha and pi isoforms. The epithelia of noncystic nephrons in renal cystic dysplasia demonstrated delayed maturity, suggesting that GST expression was dependent on the stage of development and not length of gestation.
To investigate if fetuses with cystic hygroma colli have ear article dysmorphism, we studied 16 fetuses with cystic hygroma colli, all of which had 45,X karyotype, and 107 normal fetuses. All the specimens were second-trimester formalin-preserved human fetuses. The ear lengths and widths were measured and ear indices (length/width) calculated. There were no significant differences in the ear measurements of age-matched normal male and female fetuses (P > .05). Ear growth was less linear in the cystic hygroma colli group than in the normal fetuses; Pearson's coefficient .45 vs. .87 for ear length, and r = .77 vs. .88 for ear width. The mean (+/- SD) ear index of the normal fetuses was 1.56 +/- 0.22 compared to 2.10 +/- 0.36 of the cystic hygroma colli fetuses, P < .001. The ear dysmorphism (> 2 SD of gestational age norm) was observed in 6.3% (1/16) of the ear widths, 56.3% (9/16) of the ear lengths, and 62.5% (10/16) of the ear indices. We conclude that cystic hygroma colli fetuses with 45,X have unique ear auricle morphology.
A 27-month-old boy of Hispanic background developed multiple cranial nerve palsies, difficulty swallowing, bloody nasal discharge, and irritability. Radiographic evaluations showed extensive destruction of the clivus by a large tumor that invaded the sphenoid bone, left cavernous sinus, ethmoid sinus, nasal cavity, and left orbit. Multiple pulmonary nodules were also noted. The bone marrow and spinal fluid showed no evident tumor cells. Transnasal biopsy revealed a chordoma. Treatment was initiated with a combination of ifosfamide, mesna, and etoposide along with radiation therapy to the cranial tumor. Shifting pulmonary densities were noted on serial films. Despite some clinical improvement, the child developed rapidly progressive hypoxemia 3 weeks after admission and died. Autopsy showed persistent viable tumor in the primary site and massive pulmonary arteriolar tumor emboli, infarcts, and widespread lung parenchymal metastases. No other sites of tumor involvement were discovered. This is the second child reported with intracranial chordoma, pulmonary metastases at diagnosis, and early death attributed to pulmonary tumor emboli.
Late onset of symptoms in a 12 1/2-year-old male with ornithine transcarbamylase (OTC) deficiency were associated with unusual histological features in the liver. The patient presented with an acute onset of hyperammonemia and altered mental status after a 2-day prodrome of vomiting and lethargy. Physical examination showed a combative and disoriented male with icteric sclerae but with no fever or hepatomegaly. The plasma ammonia level was 282 microM. Enzyme assays of liver tissue obtained by percutaneous needle biopsy showed OTC activity of approximately 3% of normal; carbamyl phosphate synthetase was normal. Histopathological findings included severe microvesicular centrilobular steatosis. Hepatic architecture and reticulin framework were well preserved. Many hepatocyte nuclei were filled with glycogen. Electron microscopy showed mitochondria that were rounded and expanded with cristae at the edge of the mitochondrial membrane. In contrast to other reports, only slight variations in size and shape were seen. Megamitochondria and intramatrical paracrystalline inclusions were not identified. The cytoplasm contained scattered fat globules, peroxisomes, and dilated smooth endoplasmic reticulum. The prominent mitochondrial abnormalities commonly found in OTC deficiency were notably absent.
Anomalous coronary arteries (ACAs) are a potential cause of myocardial ischemia resulting in arrhythmias, angina, infarction, and sudden death. We analyzed 7857 pediatric autopsy cases from four tertiary centers to gain an overall picture of the range and significance of ACAs within this pediatric autopsy population. The incidence of ACAs was 0.5%, with ectopic origin from the aorta (43%) being most frequent, followed by ACA arising from the pulmonary trunk (40%). The mean age at death was 2.2 years (4 h-14 years). ACAs were associated with other anomalies in 57% of cases, 43% of these being cardiac defects. Growth retardation was noted in 50% of the cases. Examination of the heart showed cardiomegaly in 92% of cases, which was marked (> 95 percentile) in 63%, but histologically apparent ischemic damage was seen in only 50% of cases. ACAs arising from the pulmonary trunk were associated with earlier death (1.4 years), more frequent cardiomegaly (100%), and more frequent myocardial scarring (92%) than other types of anomalies. Although the terminal presentation was sudden death in 45% of cases, ACAs associated with other cardiac defects presented mainly with problems related to the latter anomalies. The results highlight the need to examine coronary arteries carefully during the pediatric autopsy. Not only are the positions of the coronary artery ostia important, but also the variations in the angles of arterial take-off, initial courses through the aortic adventitia, subsequent courses, and presence of ostial ridges or membranes that may result in significant compromise of blood flow.
Renal agenesis and dysplasia are frequently regarded by pathologists, even pediatric pathologists, as sporadic malformations. We report six fetal autopsy cases of hereditary renal adysplasia (HRA): two pairs of siblings, one case with paternal unilateral renal agenesis, and one case with an autosomal balanced 6p/19q translocation. The main purpose of this paper is to emphasize that nonsyndromal renal agenesis and dysplasia are pathogenetically related and often inherited as an autosomal dominant trait with incomplete penetrance and variable expression. A subsidiary purpose is to present a case of bilateral multicystic dysplasia with a balanced 6p/19q translocation. This observation further supports the assignment of one of the loci for HRA to chromosome 6p.
A newborn with hypoalbuminemia, hematochezia, and hypertrophic gastropathy is described. These features are similar to those reported in association with prostaglandin therapy in newborns, as well as those described in so-called Menetrier's disease. Very few cases of hypertrophic gastropathy have been reported in children and fewer still verified histologically; only three other cases have been reported in newborns. The clinical and pathologic features of hypertrophic gastropathy in children, as well as its close association with eosinophilic gastroenteritis and with prostaglandin therapy, are discussed.
The term congenital soft tissue dysplasias (CSTDs) regroups some localized malformations of covering soft tissues in children, presenting as various clinical entities, either recognized as particular syndromes (e.g., Parkes-Weber, Klippel-Trenaunay, Proteus) or, most often, appearing less stereotyped (e.g., segmental hypertrophy or gigantism, lymphedema, angiodysplasia, phakomatosis), with a common histopathological lesion, the hamartoma. The aim of this paper is to report a morphological and biochemical study of the extracellular matrix of skin and subcutaneous tissue in children with CSTD. For every patient, pathological tissues were compared with contralateral, symmetrical tissues, taken as controls. In all CSTDs, pathological samples were characterized by an increase in water and total glycosaminoglycan (GAG) content with a decrease in collagen content. Other results lead the authors to distinguish two main entities, segmental dysplasia (SeD) and neuroectodermal dysplasia (NeD). Elastic fiber content was increased in SeD and decreased in NeD. Hyaluronic acid (HA) and dermatan sulfate (DS) were increased in NeD, whereas in SeD, HA was decreased with an increase in the DS/HA ratio. Cultured fibroblasts from dysplastic skin had slower proliferation in vitro than fibroblasts from control skin, whereas their biosynthetic activity concerning collagen and GAGs was greater. The difference in the composition of extracellular matrix supports the clinical classification of CSTDs in two main groups: segmental dysplasia with or without gigantism and neuroectodermal dysplasia (in von Recklinghausen's disease and nevi).
A 7-year-old boy had undergone kidney transplantation for chronic renal failure secondary to bilateral renal hypoplasia. HE developed acute and chronic rejection and received inmunosuppressive therapy. A year later he died with EBV-associated hemophagocytic syndrome. The main pathologic findings disclosed visceral (lung and stomach) and abdominal lymph node involvement of Kaposi's sarcoma and EBV-positive immunoblasts in several organs. In the lungs and lymph nodes these had the features of polymorphous lymphoimmunoblastic lesions. Because of the peculiar distribution of Kaposi's sarcoma lesions a pathogenetic hypothesis is proposed based on the site of entry of the virus. This case contributes to expanding the relationship between Kaposi's sarcoma and kidney transplantation in the pediatric population.
