Pediatric and Developmental Pathology

In fetuses and neonates hepatic subcapsular hematomas are relatively common lesions and may be life-threatening. Conditions previously associated with these hematomas include trauma, coagulopathies, hypoxia, sepsis, pneumothorax, maternal diseases, and placental lesions. In this study of 755 perinatal autopsies, hepatic subcapsular hematomas were found in 52 (6.9%) cases, including 31 stillborn fetuses and 21 liveborn infants. The average body weight was 690 g. A comparison group consisted of 52 temporally proximal autopsies of fetuses and neonates without hematomas. Body weights, gender, maternal age, and stillbirth or postnatal survival were matched as closely as possible while evaluating the presence or absence of sepsis, pneumothorax, cerebral germinal matrix hemorrhage, trauma, coagulopathy, placental lesions, and maternal diseases.

Sepsis was associated with 62% of the cases with hepatic subcapsular hematomas and with 25% of the comparison group (P = .0001). Group B streptococcus infection was the most common cause of sepsis, but many different organisms were isolated. Cerebral germinal matrix hemorrhages were present in 35% of the cases with hematomas and in 14% of the comparison group (P = .0001). No other lesions or conditions were statistically different in the study group versus the comparison group. The delicacy of the hepatic capsule and its connections to the collagen along the sinusoids provide insight for the pathogenesis of hematomas in premature fetuses and neonates. We conclude that sepsis is present in most perinatal cases of hepatic subcapsular hematomas and that such patients also frequently have cerebral germinal matrix hemorrhages. Each of these lesions is a greater hazard among very small premature fetuses or neonates than among older fetuses and neonates.

Celiac disease (CD) may cause changes throughout the gastrointestinal tract. The pathology is best described in the distal duodenum and jejunum. It is also associated with lymphocytic gastritis (LG) and varioliform gastritis in adults and children, but the histologic spectrum in the gastric biopsy and the clinical implications are undefined. In this report we relate our experience with the clinical, endoscopic, and histologic changes in gastric biopsies in CD in childhood.

Slides (hematoxylin and eosin stained) were reviewed from 33 celiac children, 5 having had more than 1 gastric biopsy during a 7-year period. Gastric intraepithelial lymphocyte (IEL) counts were compared with those of 10 histologically normal controls (normal range, 1–7 IEL/100 antral or body epithelial cells) and 10 nonceliac chronic gastritis (CG) biopsies without H. pylori (normal range, 1–19 IEL/100 antral cells), noting changes in the epithelium and lamina propria (LP). LG was present in 29/33 initial biopsy sets. Fifteen of 29 showed LG/CG. The IEL number was greater in LG/CG than in LG only (27.2 ± 9.3, n = 14 vs. 18.6 ± 13.4, n = 15 in the antrum; 23.5 ± 2.8, n = 4 vs. 13.0 ± 8.4 in the body). In CD the difference between these mean values and those of normal and nonceliac CG controls was statistically significant. In CG/LG the inflammatory infiltrate was predominantly diffuse/superficial in the LP; mucin depletion was noted in 11/15. The IELs were in the LG/CG range in two CG controls. The IELs were normal at follow-up in five cases. There were no statistically significant differences between the groups with respect to clinical parameters or gastric endoscopic findings. No child had varioliform gastritis.

We conclude that in CD children, the stomach is endoscopically unremarkable but may show LG, or LG/CG with or without mucin depletion, or occasionally appear normal. Gastric histology returned to normal with gluten withdrawal. Normal gastric histology is not typical, but does not exclude CD.

We evaluated renal biopsies from 34 children with IgA nephropathy or Henoch Schönlein purpura to further characterize the ultrastructural features of the glomerular membranopathy that occurs in these disorders. Focal glomerular basement membrane damage was identified in 29 children and was severe in 4 of the children. Alterations included focal and segmental attenuation, splitting, duplications, and spike-like subepithelial protrusions of the lamina densa, along with saccular glomerular microaneurysms arising at the paramesangium. Those cases with extensive glomerular basement membrane lesions had either moderate or severe glomerular alterations apparent by light microscopy. Over half of the cases with glomerular membranopathy had immunohistological or ultrastructural evidence of focal peripheral glomerular capillary wall immune deposits and electron-dense deposits occurred at sites of glomerular basement membrane splitting. Despite the focal attenuation of the glomerular basement membrane, we did not identify any biopsy with findings of thin basement membrane disease. The glomerular basement membrane ultrastructural findings we describe are characteristic of IgA nephropathy and Henoch Schönlein purpura, are common in children with these disorders, and are similar to the ultrastructural alterations of the basement membrane that occur in other glomerulonephritides. These basement membrane injuries may be inflammatory cell or immune mediated but their pathogenesis requires further study.

This review examines 197 cases of fibrous hamartoma of infancy (FHI) described in the literature and provides a detailed clinicopathologic analysis of what is known to date of this peculiar lesion of the subcutis and lower dermis. The vast majority of these cases occurred within the first year of life (91%). Twenty-three percent were congenital. There was a predilection for boys with a male/female ratio of 2.4. Males and females had similar anatomic distribution with the most common locations being the axillary region, upper arm, upper trunk, inguinal region, and external genital area. Most cases presented as solitary masses, but four cases of multiple separate synchronous lesions have been reported.

Most lesions presented as a painless nodule, sometimes with rapid growth. A few cases had overlying skin changes, including alteration in pigmentation, eccrine gland hyperplasia, and increased hair. No lesions were reported to have familial or syndromic association, or to occur in combination with other hamartomas. Spontaneous regression has not been reported. The treatment of choice is local excision. Even with incomplete excision, FHI has a low recurrence rate. Criteria for histologic diagnosis include the presence of well-defined bundles of dense, uniform, fibrous connective tissue projecting into fat, primitive mesenchyme arranged in nests, concentric whorls or bands, and mature adipose tissue intimately admixed with the other components.

Flow-cytometric and conventional cytogenetic studies have not been reported; these may clarify any relationship to other fibroblastic/myofibroblastic proliferations in children, resulting in better classification and terminology of this unique lesion.

From 1939 to 1967, J.L. Conel quantitatively studied the microscopic features of the developing human cerebral cortex and published the findings in eight volumes. We have constructed a database using his neuroanatomical measurements (neuronal packing density, myelinated large fiber density, large proximal dendrite density, somal breadth and height, and total cortical and cortical layer thickness) at the eight age periods (0 [term birth], 1, 3, 6, 15, 24, 48, and 72 postnatal months) he studied. In this report, we examine changes in neuron numbers over the eight age-points for 35 von Economo areas for which Conel gave appropriate data. From birth to 3 months postnatal age, total cortical neuron number increases 23–30%, then falls to within 3.5% of the birth value at 24 months, supporting our previous work showing that the observed decrease in the number of neurons per column of cortex under a 1-mm² cortical surface from birth to 15 months is almost entirely due to cortical surface expansion. The present study also shows a 60–78% increase in total cortical neuron number above the birth value from postnatal ages 24 to 72 months. The generalization, to humans at least, of the finding of no postnatal neurogenesis in rhesus macaques, a species belonging to a super-family that diverged from that of Homo sapiens more than 25 million years ago, is not warranted until explicitly proven for humans. The data of the present study support the existence of substantial postnatal neurogenesis in humans for the 35 cortical areas studied.

The nomenclature and occurrence of chorangioma of the placenta are reviewed here. Recurrence of multiple chorangiomas has been described, but it is apparently an uncommon or underreported event. There is a strong relationship between placental chorangiomas and gestation at high altitude, suggesting the occurrence of vascular growth factors induced by hypoxia. Fluid transitions may exist between chorangioma, chorangiomatosis, and chorangiosis, although the latter is common in diabetic pregnancies, whereas chorangiomas are not so correlated.

We report the clinical, pathologic, and genetic features of renal malignancy in two children with diffuse cystic hyperplasia. Both presented with massive bilateral nephromegaly. Neither had a family history or clinical findings suggestive of tuberous sclerosis or von Hippel–Lindau disease. The kidneys of both children were extensively replaced by tubulocystic hyperplasia with large eosinophilic epithelial cells. The masses of hyper-plastic tissue were nodular, compressing remnants of uninvolved renal parenchyma. Tubulopapillary carcinoma was present in both children, one of whom had bilateral multicentric carcinoma. No loss of heterozygosity was detected in the tumors at the TSC1, TSC2, or VHL gene regions, and no alterations in the VHL gene were detected using single-strand conformation polymorphism analysis. These cases of bilateral renal enlargement with diffuse cystic hyperplasia appear to represent a new clinical syndrome that may warrant bilateral nephrectomy because of the risk of malignancy.

This review chronicles the series of publications that were the result of the willingness of pathologists and clinicians in the United States to share their pathologic materials and clinical data on patients who were placed on treatment protocols for rhabdomyosarcoma and related tumors over an extended period of time. The availability of this database enabled pathologists and clinicians to study a tumor type that is rare in individual institutions, but occurs in large enough numbers to produce valid conclusions not otherwise possible. Furthermore, young investigators were challenged by this opportunity and were able to spend the necessary time to make new observations that, in retrospect, helped direct protocol designs that produced significant improvement in patient survival. The key factor in this process is the surrender of individual scientific prerogatives to a small number of investigators. It is also important to recognize that the pathologist component of these series of contributions is only a part of the entire effort. It takes an organization of gifted, dedicated experts in many disciplines working together. The investigators who served on the Intergroup Rhabdomyosarcoma Group over a 25-year period eminently fulfilled this.

Isovaleric acidemia, an autosomal recessive disorder, is due to isovaleryl-coenzyme A dehydrogenase deficiency and is one of the branched-chain aminoacidopathies. Isovaleric acidemia may present in the neonatal period with an acute episode of severe metabolic acidosis, ketosis, and vomiting and may lead to coma and death in the first 2 months of life. This report concerns an infant who presented at 10 days of age because of lethargy, poor feeding, hypothermia, cholestasis, and thrombocytopenia, leukopenia, and profound pancytopenia. Death occurred at 19 days of age. Autopsy showed mild fatty change in the liver and extramedullary hematopoiesis, generalized Escherichia coli sepsis, and myelodysplasia of the bone marrow with arrest of the myeloid series at the promyelocytic stage. The appearance resembled promyelocytic leukemia, but the diagnostic 15:17 translocation was not present. The maturation arrest in granulopoiesis in isovaleric acidemia appears to be most likely due to a direct metabolic effect on granulocyte precursor cells.