Pathology reports on neonatal necrotizing enterocolitis (NNEC) rarely consider its effects on the enteric nervous system (ENS). Thus, the aim of this study has been to perform a two-dimensional assessment of neuropathologic lesions within the three ganglionated plexuses of the intestinal wall by means of whole-mount immunohistochemistry. Resected segments of ileum and colon affected by acute NNEC were submitted to immunohistochemical procedures using antibodies against neuronal (protein gene product 9.5) and glial (protein S-100, glial fibrillary acidic protein) Proteins. Examination of the myenteric plexus and external submucosal plexus revealed a noticeable reduction in glial cells concomitant with the gradual deterioration of nerve cells, both findings predominating in the antimesenteric intestinal circumference, where ischemic lesions tend to appear first. The most severe damage of nervous tissue was observed in the plexus submucosus internus dependent on the depth of mucosal injury. The destroyed ganglia appeared like "empty baskets" (residual tangles) and housed deteriorated nerve and glial cells. Taking the anatomy of the intestinal vascular blood supply into consideration, the characteristic topography of neuropathologic lesions gives further support to an ischemic event within the cascade of different pathogenetic factors culminating in NNEC. Moreover, the demonstrated alterations of the ENS and their potential adverse effects on intestinal motility and neuroimmunologic interactions may contribute to the complex pathogenesis of NNEC, which remains a field of further investigation.
Disseminated Acanthamoeba infection has been described in immunocompromised or debilitated patients. The usual sites of involvement are skin, sinus, and brain. Sporadic reports of Acanthamoeba infection in patients infected with the human immunodeficiency virus are present in recent literature, predominantly in adults, and one case involving an 8-year-old child. We describe a case of amebic osteomyelitis, seen in a 6-year-old child with vertically acquired human immunodeficiency virus and a 6-month history of cutaneous Acanthamoeba infection.
We investigated the intra-acinar pulmonary vascular muscularization in the developing human fetal lung between the 17th and 24th gestational weeks, that is, during the canalicular phase of lung development. Fifteen hypoplastic and 25 normal developed lungs were included in this study using monoclonal alpha-smooth muscle (sm) actin antibodies for smooth muscle detection. Computer-aided image analysis was performed for morphometrical measurements and statistical evaluation. Alpha-sm-actin-immunoreactive intra-acinar vessels down to a luminal diameter of less than 10 microns were detected in hypoplastic as well as in normally developed lungs. Crucial differences presented as follows: significantly higher density of intra-acinar vessels, especially due to alpha-sm-actin-negative vessels less than 30 microns in luminal diameter, in the control group; significantly higher alpha-sm-actin immunore-activity per section unit as well as per vessel in the hypoplastic lung group. As suggested by others, alpha-sm-actin-positive cells of the intra-acinar vessel wall in the developing human lung were demonstrated to be smooth muscle cells, their immediate precursors, and pericytes. We conclude that the increased alpha-sm-actin immunoreactivity represents muscularization of the vessel wall in functional terms and may be regarded as one structural cause among others for the establishment of persistent fetal circulation in hypoplastic lungs.
Children with hyper-immunoglobulin M (hyper-IgM) syndrome are at increased risk for Pneumocystis carinii pneumonia (PCP), an opportunistic infection often found in immunodeficient hosts. PCP can present with increasing hypoxia, fever, cough, and respiratory distress. We describe a child with hyper-IgM syndrome in whom bronchoalveolar washings were negative for PCP. However, there was an atypical lung response in which caseating granulomas predominated. The histopathology, resembling that found in tuberculosis, stresses the importance of a high index of clinical suspicion and histologic confirmation for early intervention and treatment. Immunocompromised children with rapidly progressive pulmonary disease may require lung biopsy and stains such as GMS to identify PCP.
Triploidy is a common chromosomal aberration seen in 1% of clinically recognized human pregnancies. Development beyond 10 weeks is unusual. Occasionally fetuses survive past 20 weeks; however, they usually present as a stillbirth with only a few managing some hours of independent life. The clinical features of these infants cover a wide spectrum, but a consistent feature is organ hypoplasia and hypotonia. We observed marked enlargement of somatostatin-producing cells (D cells) in the pancreata of triploid fetuses. Somatostatin-producing cells are widely distributed in normal mammals although concentrated in the pancreas and gastrointestinal tract, generally being antiproliferative and having an inhibitory effect on various functions. The control of fetal growth is not well understood. There is, however, some evidence that somatostatin does play a significant part and our consistent observation of cytomegaly of the pancreatic D cells in growth-retarded triploid fetuses provides more support for this contention.
An extremely aggressive malignant epithelial neoplasm of the kidney has recently been described and named renal medullary carcinoma. The finding of this tumor is highly predictive of drepanocytes (sickle cells) in tissue sections and thus the presence of sickle hemoglobin, specifically sickle cell trait, in the patient. We present a case report of this rare tumor in a 10-year-old male. The tumor displayed a variable histologic architecture including gland-like areas with intra- and extracytoplasmic material resembling mucin with hematoxylin and eosin stain. This material was negative with periodic acid-Schiff and mucicarmine stains, stained only weakly with Alcian Blue, and was positive using antibodies against peanut agglutinin. Tumor cells stained positively with antibodies to epithelial membrane antigen, cytokeratin, vimentin, and Ulex europaeus lectin. The luminal face of tumor cells stained with peanut agglutinin. Stains using antibodies against carcinoembryonic antigen and alpha-fetoprotein were negative. Ultrastructurally, the tumor cells were characterized by short microvilli lining the luminal surface and lateral complex infoldings of adjacent plasma membranes. We discuss the relationship of this neoplasm to another renal pelvic neoplasm, collecting duct carcinoma, which may rarely occur in children. Renal medullary carcinoma should be included in the differential diagnosis of gross hematuria, which is most commonly benign self-limited hematuria, in young patients with sickle cell trait.
Four portable analyzers, HemoCue B-Glucose (I), Accu-Check III (II), One-touch II (III), and Glucometer Elite (IV), with different measuring principles were tested for their suitability for measuring blood glucose in neonates. Precision of all instruments is satisfactory. In the analysis of capillary blood from newborns, two instruments show an excellent accuracy; however, the scatter of the results for instrument (II) is about 1.6 times greater than for instrument (I). The inaccuracy of instruments (III) and (IV) is not acceptable from a clinical point of view. All devices show an influence of hematocrit, the magnitude of which varies between 5% (I) and 12% (III) for every 10% change of hematocrit. Instruments II and IV show that temperature has a marked influence on the readings; the same is true for oxygen in instrument IV. In conclusion, only instrument (I) has met the requirements of accurate and precise blood glucose determinations in neonates.
Fetal and placental tissues and maternal sera from a series of 273 cases of first and second trimester fetal loss were collected to detect the frequency of parvovirus B19 infection. In addition, fetal tissues were studied for the presence of congenital anomalies. Serology of maternal sera, histology of fetal tissues and placenta, polymerase chain reaction (PCR), in situ hybridization (ISH), and immunohistochemistry (IHC) were used for the detection of parvovirus B19 infection. Sera were tested for B19-specific immunoglobulin M (IgM) and/or IgG using an enzyme-linked immunosorbent assay technique. Based on serology, 149 cases not related to B19 infection were excluded from further analysis. Two of the remaining 124 cases (0.7% of all 273 cases) had parvovirus B19-specific IgM and IgG at the time of abortion, indicating a recent maternal parvovirus B19 infection. In our histological examination, 10 cases contained nuclear vacuolization in fetal erythroid progenitor cells, either in fetal tissues (n = 2) or in placental tissue (n = 8). However, this vacuolization was considered a fixation artifact and not identical to parvovirus B19-specific nuclear inclusions described in previous reports. Only 1 of these 10 cases had parvovirus B19 DNA detectable in placental tissue by PCR analysis. Neither in this case nor in any of the other cases tested was parvovirus B19 DNA or protein detectable by ISH or IHC, respectively. In none of 41 cases in which fetal tissues were available were congenital anomalies found. In conclusion, the frequency of maternal parvovirus B19 infection in this series of fetal losses is low (0.8%). This low frequency does not allow any conclusions with regard to the occurrence of congenital anomalies resulting from parvovirus B19 infection and the usage of nuclear histology for the detection of fetal parvovirus B19 infection is considered a nonspecific parameter that requires confirmation by PCR.
Clinicopathologic details of an atypical Spitz nevus are reported. A metastasis to a single ipsilateral lymph node is documented. Cytogenetic analysis of the metastatic lesion revealed a clonal chromosomal abnormality, add(6)(q12-13), previously noted in cases of malignant melanoma.
Diagnosis in certain metabolic diseases or the establishment of long-term reservoirs of cytogenetic material requires tissue culture of fibroblasts obtained by skin snip or punch biopsy. Fine needle aspiration biopsy (FNAB) was investigated as an alternative method of fibroblast collection with advantages of minimal morbidity and the potential of better patient acceptance. After flank FNAB, culture, and incubation, confluent fibroblast growth was achieved within 19 days. The number of cells produced was sufficient for potential cytogenetic or metabolic studies. Cultured fibroblasts obtained via FNAB proved to be a successful alternative to skin biopsy, with reduced trauma and better cosmetic results.
We report a case of histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi-Fujimoto disease), diagnosed at necropsy in a 19-month-old child dying unexpectedly after a febrile illness. This is the youngest case with this disease that has been thus far reported. It is one of only two reported cases in which the patient died during the acute phase of the illness. Histological findings not unlike those seen in the lymph nodes were present at extranodal sites; this is the first case in which this feature has been described. In keeping with many other reported cases, it was not possible to identify an underlying etiology that might explain the morphologic changes.
Analysis of the prognostic importance of various clinicopathological parameters in 17 hepatoblastomas (HBs) confirmed the utility of preoperative chemotherapy to convert inoperable to resectable tumors. There was no significant survival advantage for patients who underwent initial tumor resection compared with those resected following chemotherapy, although complete resection, with or without prior chemotherapy, was critical for cure. Young age was associated with better survival but did not correlate with histologic subtype or clinical stage. A relationship between low initial alpha-fetoprotein (AFP) level and tumor resectability was noted, perhaps related to tumor size, but tumor location was of greater importance than size in determining resectability. Neither the mean proportions of fetal and embryonal epithelium, nor their mitotic activity, nor the presence of vascular invasion in the prechemotherapy biopsy specimens was predictive of outcome, but the low mitotic activity of the fetal component correlated with ultimate resectability. On the other hand, although complete resection was necessary for survival, histologic examination of postchemotherapy specimens had additional predictive value; the presence of vascular invasion, the amount of viable mesenchyme, the extent of tumor necrosis, the proportion of embryonal epithelium, and the mitotic activity of the epithelial component in postchemotherapy resection specimens were each predictive of outcome. Although the presence of osteoid was not predictive, both the proportion of HBs that contained osteoid and the extent of mature mesenchymal tissues within individual HBs were increased by chemotherapy, suggesting that maturation of previously immature clones had been induced. We conclude that although complete resectability remains the fundamental goal of therapy, evaluation of the clinicopathologic characteristics that we have found to be predictive of outcome may permit tailoring of therapeutic regimens to individual patients; those whose tumors are deemed likely to respond well may require less toxic preoperative chemotherapy, and those deemed likely to progress in spite of complete resection may be considered for more aggressive postoperative regimens.
Archival lung tissue from 99 cases of sudden infant death syndrome (SIDS) and from 58 matched comparison cases with known causes of death was studied. Sections were examined by in situ hybridization (ISH) using a cocktail of three synthetic oligonucleotides with sequences chosen from the published sequence of the nucleoprotein gene of respiratory syncytial virus (RS virus). The oligonucleotides were end-labelled with dinitrophenyl (DNP) or digoxigenin (DIG) and hybrids were detected immunocytochemically. RS virus nucleic acid was detected in 24 cases of SIDS (24%) and in 11 (19%) of the comparison group. Specificity was confirmed using a DIG-labeled cloned probe covering the whole of the nucleoprotein gene sequence. With one exception, the same results were obtained. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to confirm the specificity of these results. When matched for age and month and year of death, 76 SIDS cases and 38 controls could be compared. Twenty-one SIDS cases (27.6%) and seven comparison cases (18.4%) contained detectable RS virus sequences by ISH, with a higher detection rate in winter in both groups. The differences were not significant and reflected the seasonal pattern of RS virus infection in the community rather than a causal relationship of RS virus with SIDS. Detection of RS viral mRNA through the summer months suggests that persistence is possible.
The present report describes opportunistic infections found at 74 autopsies of pediatric HIV/AIDS patients performed at several hospitals in Latin American countries. Fungal infections were the most common (53 cases), Candida sp. (39.18%) and Pneumocystis carinii (20.27%) being the most frequently recognized. Other fungal diseases included histoplasmosis, aspergillosis, and cryptococcosis. Viral infections were present in 31 cases, 38.7% being due to cytomegalovirus. Other viruses recognized included herpes simplex and adenovirus. Additional opportunistic infections were due to Mycobacterium avium-intracellulare, toxoplasmosis, and tuberculosis. Nonspecific bacterial bronchopneumonia was present in 11 cases. Cytomegalovirus and P. carinii coinfection was the most common association found. In this series patients died at a younger age (72% at or younger than 1 year old) and there was a slightly higher number of cases of histoplasmosis and brain toxoplasmosis than in other previously published series of infants and children.
The pathologic changes in the gastrointestinal tract of children with AIDS are variable, clinically significant, and reflect multisystemic disease processes. Inflammation, changes in the lymphoid tissue, miscellaneous lesions, and tumors are documented in 58 patients in addition to cases reported in the literature. Cytomegalovirus infection of the gastrointestinal tract, associated with ulcerations, hemorrhage, perforations, and intestinal obstruction, carries a high morbidity and mortality, whereas the remaining infections are not life threatening. Special stains and electron micrographic examination are important to identify correctly certain microorganisms such as mycobacterium avium intracellulare, cryptosporidia, and microsporidia. Lymphoproliferative changes of the gastrointestinal tract, a component of the generalized lymphoproliferative process, need to be characterized by tumor markers and cytogenetic studies. Within the miscellaneous lesions, AIDS associated arteriopathy can be complicated by intestinal ulceration and perforation. Both lymphomas and smooth muscle tumor in children with AIDS are related to Epstein-Barr virus infection. The smooth muscle tumors are frequently malignant and multiple.
We report on a rare case of fatal congenital alveolar capillary dysplasia. The newborn boy of a 37 weeks' normal gestation suffered from persistent pulmonary hypertension without any cardiovascular malformation and died at the age of 4 weeks despite intensive treatment. The autopsy tissue was examined histologically, immunohistochemically, and ultrastructurally. Moreover, a three-dimensional tissue reconstruction based on serial sections was performed comparing the affected lung with normal lung tissue. We observed a unique pattern of pulmonary dysplasia: An extreme decrease of capillaries was localized centrally within thickened intra-acinar septa instead of capillaries intensely neighboring pneumocytes; ectatic veins normally running in the interlobular septa were found to accompany intralobular bronchovascular bundles, denying a clear distinction between pulmonary and bronchial veins; small muscular pulmonary arteries extended to the precapillary level and type 2 pneumocytes exceeded by far the type 1 pneumocytes, inverting the normal ratio. In summary, alveolar capillary dysplasia is assumed to be a primary capillary disorder of unknown origin, which possibly involves the regular differentiation of pneumocytes, according to the close alveolocapillary relationship during pulmonary ontogenesis. We consider the venous alterations as being part of the dysplasia, whereas the arterial phenomena might occur secondarily. Recent reports on affected siblings suggest a genetic component of pathogenesis.
Parental smoking is considered to be an important risk factor for the sudden infant death syndrome (SIDS). We studied the concentrations of nicotine and cotinine in the pericardial fluid of SIDS and non-SIDS victims, with particular emphasis on the relationship to body position at the time of death and organ pathology. Pericardial fluid was collected during a forensic postmortem examination of 85 nonselected infants, under the age of 1 year, who died from SIDS (n = 67) and non-SIDS (n = 18) in the period from 1988 to 1994. There was no significant difference in the pericardial concentration of nicotine and cotinine between SIDS and non-SIDS victims. However, in contrast to non-SIDS victims, about 25% of the infants in the SIDS group had cotinine concentrations exceeding 30 ng/mL, indicating tobacco exposure prior to death. High concentrations of cotinine were found in infants with focal necrosis and inflammatory changes in the myocardium and the liver. Further, a relationship was found between high nicotine concentration and otitis media and also with death while cosleeping.
(1997). Editorial: Point-of-Care Testing—The Cost of Convenience. Pediatric Pathology & Laboratory Medicine: Vol. 17, No. 4, pp. v-vi.
