Hepatic Hilar Lymph Node Reactivity at Kasai Portoenterostomy for Biliary Atresia: Correlations With Age, Outcome, and Histology of Proximal Biliary Remnant.

We hypothesized that if infection is the proximate cause of congenital biliary atresia, an appropriate response to antigen would occur in lymph nodes contiguous with the biliary remnant. We compared the number of follicular germinal centers (GC) in 79 surgically excised hilar lymph nodes (LN) and 27 incidentally discovered cystic duct LNs in 84 subjects at the time of hepatic portoenterostomy (HPE) for biliary atresia (BA) to autopsy controls from the pancreaticobiliary region of non-septic infants >3 months old at death. All 27 control LN lacked GC, a sign in infants of a primary response to antigenic stimulation. GC were found in 53% of 106 LN in 56 of 84 subjects. Visible surgically excised LN contiguous with the most proximal biliary remnants had 1 or more well-formed reactive GC in only 26/51 subjects. Presence of GC and number of GC/LN was unrelated to age at onset of jaundice or to active fibroplasia in the biliary remnant but was related to older age at HPE. Absent GC in visible and incidentally removed cystic duct LNs predicted survival with the native liver at 2 and 3 years after HPE, P = .03, but significance was lost at longer intervals. The uncommon inflammatory lesions occasionally found in remnants could be secondary either to bile-induced injury or secondary infection established as obstruction evolves. The absence of consistent evidence of antigenic stimulation in LN contiguous with the biliary remnant supports existence of at least 1 major alternative to infection in the etiology of biliary atresia.

Treatment of presumed arrhythmogenic right ventricular dysplasia in an adolescent.

Familial arrhythmogenic right ventricular dysplasia is a rare cardiomyopathy that is usually diagnosed on postmortem examination or on presentation with progressive congestive heart failure. We present a patient in whom an automatic implantable cardioverter-defibrillator was inserted prophylactically. A review of the condition and possible therapies is included.

Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell tumor.

We report two cases of desmoplastic small round cell tumor (DSRCT) with novel molecular variants of the specific EWS-WT1 gene fusion. This fusion usually encodes a chimeric RNA with an in-frame junction of exon 7 of EWS to exon 8 of WT1. In one variant patient, the EWS-WT1 fusion transcript contained an in-frame junction of exon 9 of EWS to exon 8 of WT1. Moreover, in this patient the tumor arose in the hand, an extremely unusual site for DSRCT. In the second patient, an in-frame junction of exon 10 of EWS to exon 8 of WT1 was present. These two cases of DSRCT show that the molecular variability in the EWS breakpoint observed in the EWS-FLI1 fusion of Ewing's sarcoma can occur in DSRCT as well. This type of heterogeneity is relevant to the interpretation of molecular diagnostic assays and could also affect the functional properties of the encoded chimeric transcription factors.

Thoracolumbar accessory penis: etiology, diagnosis, and management.

Human sacral appendages have rarely been reported. We present a neonate with a thoracolumbar appendage resembling a penis, and discuss the nature of the anomaly and its diagnosis and management.

Disseminated candidiasis. Newer approaches to early recognition and treatment.

The clinical triad of fever, erythematous papular rash, and diffuse muscle tenderness has recently been reported to be presumptive evidence for disseminated candidiasis in the immunocompromised host who is receiving broad-spectrum antibiotics. This case report further explores this clinical association and demonstrates that the immediate institution of antifungal therapy before laboratory test results are known may favorably alter the outcome of this frequently fatal condition. In view of the low positive yield of blood cultures, skin biopsy may represent an effective method for achieving rapid laboratory confirmation of the diagnosis.

The acid-fast stain is a superior stain for use in the mean mature spermatid count for testicular biopsies.

The mean mature spermatid count (MMSC) provides a useful, simplified quantitative evaluation of human spermatogenesis that is based on the number of mature spermatids in histological sections of testicular biopsies. Here, the activity of the acid-fast (AF) stain was compared to that of the usual hematoxylin and eosin (H&E) stain in performing the MMSC. Thirty bilateral testicular biopsies showing normal spermatogenesis were chosen retrospectively from 15 subfertile patients with obstructive azoospermia or severe oligospermia. The MMSC was determined on each biopsy by utilizing both H&E and AF stains. The AF stain proved to be specific for the mature spermatids normally counted for the MMSC. It simplified recognition of mature spermatids, thereby shortening the overall time required for the procedure. The mean AF MMSC was lower than the mean H&E MMSC, and the mean interobserver differences were decreased. The AF stain is a superior stain for the MMSC when used in conjunction with the H&E stain for descriptive histology.

Motile sperm in human testis biopsy specimens.

We prospectively studied 62 consecutive infertile men who underwent 100 intraoperative wet prep cytological examinations of testis biopsy material obtained simultaneously with permanently fixed specimens. Wet preps were performed by placing a small sample of fresh testicular tissue on a slide, adding a drop of Ringer's lactate, and compressing the specimen under a glass coverslip. Among these 100 wet preps, complete sperm with tails were identified in 62 specimens, of which 44 contained nonmotile sperm and 18 contained motile sperm. Reproductive tract obstruction was documented in 65 testes (65%) on subsequent reconstructive surgery and/or inferred from histological evaluation, including mean mature spermatid counts on the permanent sections fixed in Bouin's solution. Obstruction was absent in the remaining testes (35%). All 18 testes with motile sperm found on wet prep were obstructed. These testes were also found to have complete spermatogenesis, a category selected to include normal spermatogenesis and slight hypospermatogenesis, determined by examination of the permanently fixed sections. The finding of motile vs. nonmotile sperm on a wet prep has positive predictive values of 100% vs. 81% for the presence of reproductive tract obstruction and 94% vs. 86% for complete spermatogenesis, respectively. The presence of motile sperm in human testis biopsy specimens is a novel finding. When any complete sperm with tail is found in a testis biopsy wet prep, obstruction is likely. When motile sperm are present, obstruction is almost certain, and immediate exploration and reconstructive surgery can be justified.(ABSTRACT TRUNCATED AT 250 WORDS)

Histological criteria for the identification of acute cellular rejection in human small bowel allografts: results of the pathology workshop at the VIII International Small Bowel Transplant Symposium.

Acute cellular rejection remains a serious and frequent complication during the posttransplant course of small bowel allograft recipients. Currently, small bowel biopsies are the optimal method to identify this form of rejection. The morphological criteria for this diagnosis have been known for some time; however, no consensus study has classified these changes. To address issues in bowel transplant pathology, several pathologists experienced in this particular subdiscipline participated in a Pathology Workshop preceding the VIIIth International Small Bowel Transplant Symposium in Miami, Florida. Among the results of this workshop was the development a standardized grading scheme for acute cellular rejection in small bowel transplants.

Increased erythrocyte osmotic fragility in pregnancy.

An unexpected increase in erythrocyte osmotic fragility during pregnancy in two healthy women prompted a study of the effects of pregnancy on osmotic fragility. The incubated glycerol lysis time, a rapid, sensitive measure of osmotic fragility, was determined in 100 pregnant women and 50 nonpregnant control subjects. Twenty-two of the pregnant women (22%) showed abnormal results when compared to normal nonpregnant women (p less than 0.0005). Increased erythrocyte fragility was observed primarily in the last trimester of pregnancy. Twenty-one of 65 women in the last trimester (32.3%) had abnormal incubated glycerol lysis time values, but only one of 34 (2.9%) showed increased fragility during early pregnancy. Physiologic shifts in erythrocyte osmotic fragility may create a problem in the diagnosis of hereditary spherocytosis during the last trimester of pregnancy.

Hepatic heterotopias in the jejunum: a case study over time showing progressive degenerative changes.

Multiple foci of heterotopic liver in the jejunum were sequentially discovered in an infant boy at the ages of 1 day, 2 months, and 4 months. This is the second reported case of jejunal heterotopic liver, a rare entity in any site. Progressive histological changes indicative of biliary duct obstruction were observed in the hepatic heterotopias, which demonstrated no connections to the main body of the liver or biliary tree.

Follicle-stimulating hormone receptor is expressed in human ovarian surface epithelium and fallopian tube.

The cellular expression of pituitary gonadotropin receptors in gonadal tissues is poorly defined because of the lack of suitable reagents. In this study, we developed in situ hybridization and reverse transcription polymerase chain reaction techniques for the evaluation of follicle-stimulating hormone receptor (FSHR) expression in the ovary and fallopian tube. Using a single-strand RNA probe, we demonstrated that FSHR mRNA expression is strongest in Graafian follicles. Within these developing follicles, granulosa cells showed the greatest expression, although both theca interna and theca externa were also positive, interna greater than externa. Granulosa cells in both primary and primordial follicles were positive, with primordial follicles showing only weak focal positivity. Ovarian surface epithelium and fallopian tube epithelium, not previously recognized to express FSHR, were both strongly positive. The FSHR expression in the ovary and fallopian tube was confirmed by reverse transcription polymerase chain reaction. Our results indicated that the FSHR is expressed in a cell-specific fashion at different stages of follicular development and is also expressed in ovarian surface and fallopian tube epithelia. The presence of FSHR in ovarian surface epithelium and of gonadotropin-binding sites in ovarian neoplasms provide additional evidence supporting the derivation of epithelial ovarian tumors from the surface epithelium and should promote heightened interest in the gonadotropin theory of ovarian tumorigenesis. More importantly, this study shows the feasibility of evaluating FSHR expression by both in situ hybridization and reverse transcription polymerase chain reaction. Application of these techniques to tumor specimens will help to elucidate the role of gonadotropins and their receptors in the carcinogenesis of gynecological tumors.

Enhanced endothelial cell apoptosis in splenic tissues of patients with thrombotic thrombocytopenic purpura.

Idiopathic thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy of obscure etiology. The fundamental pathologic lesion is a hyaline thrombus composed of platelets and some fibrin accompanied by endothelial cell proliferation and detachment, in the absence of an inflammatory response. We have previously demonstrated that plasmas from patients with both idiopathic TTP and a related disorder, sporadic hemolytic-uremic syndrome (HUS), induce apoptosis and expression of the apoptosis-associated molecule Fas (CD95) in vitro in those lineages of microvascular endothelial cells (MVECs) that are affected pathologically. We now demonstrate the presence of enhanced MVEC apoptosis in splenic tissues from patients with TTP, documented by terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) and morphology. This is accompanied by elevated Fas expression. It contrasts with the absence of apoptosis in splenic tissues obtained after splenectomy for trauma or immune thrombocytopenic purpura. TUNEL-positive cells, identified by immunohistochemistry as MVECs or macrophages, presumably engulfing apoptotic ECs, are noted in numerous areas, including those apart from microthrombi. Thus, it is unlikely that EC apoptosis is simply a sequela of thrombus formation. Based on these data, we propose that MVEC apoptosis is of pathophysiologic significance in idiopathic TTP/sporadic HUS.

Immunohistochemical localization of endothelial nitric oxide synthase in human testis, epididymis, and vas deferens suggests a possible role for nitric oxide in spermatogenesis, sperm maturation, and programmed cell death.

Recent work has implicated nitric oxide (NO) in several aspects of male genital physiology including erectile function and androgen secretion, as well as in vitro effects on sperm motility and capacitation. The objectives of this study were to characterize the distribution of endothelial nitric oxide synthase (eNOS) in "normal" human testis, epididymis, and vas deferens and in testis pathology. Nitric oxide synthase protein was localized immunohistochemically using an eNOS monoclonal antibody. Endothelial NOS protein co-localized to areas that showed positive NADPH diaphorase activity. Within the testis, eNOS protein was localized to the cytoplasm of Leydig cells and Sertoli cells at all stages of spermatogenesis. Within the epididymis and vas deferens, eNOS was localized to the epithelium. Endothelial NOS was also localized to endothelial cells in all tissues; it was not detectable in normal germ cells. Endothelial NOS and diaphorase activity were, however, detected in degenerating or apoptotic intraepithelial germ cells. In addition, prematurely shed spermatocytes and spermatids had intense eNOS expression. Previous studies have suggested a role for NOS in the contractile, hemodynamic, and hormonal aspects of testicular function as well as in epididymal secretion. The studies reported herein suggest a role for eNOS in spermatogenesis and germ cell degeneration.

Death as a complication of peripherally inserted central catheters in neonates.

We report 2 neonatal deaths caused by cardiac tamponade related to peripherally inserted central catheters (PICCs). A total of 3 deaths were noted for 390 PICCs placed, giving an incidence of 0.76%. To determine the magnitude of neonatal death related to PICCs, directors of neonatal intensive care units in the United States were surveyed by means of a questionnaire. Myocardial perforation and pericardial effusion were reported by 29% and 43%, respectively. Deaths were attributed to PICCs by 24% of the respondents. Uniform guidelines need to be formulated to avoid this complication.

Infantile myofibromatosis with hemangiopericytoma-like features of the tongue: a case study including ultrastructure.

We report a case of an infantile myofibromatosis with hemangiopericytoma-like features arising in the tongue of a 5-month-old female infant. Many authors now classify neoplasms as infantile myofibromatosis that were previously called infantile hemangiopericytoma. The ultrastructural features of our tumor illustrate its biphasic nature and provide a possible explanation for its histogenesis. Infantile myofibromatosis, including those diagnosed as infantile hemangiopericytomas, rarely arise in any intraoral location. Despite the generally good prognosis associated with these neoplasms, complete surgical excision is recommended to avoid recurrences.

Parathyroid gland hemorrhage in perinatally lethal osteogenesis imperfecta.

In four neonates with perinatally lethal osteogenesis imperfecta (OI) who survived for more than 9 days after birth, vascular congestion and acute hemorrhage were found in 10 of 11 parathyroid glands; in one neonate, all four parathyroid glands, including the only gland without acute hemorrhage, contained abundant deposits of stainable iron. One neonate had hypocalcemia, and one had both hyperphosphatemia and hypocalcemia. In four neonates with OI who died within 72 minutes of birth, all 10 parathyroid glands demonstrated were free of hemorrhage and hemosiderin deposition. Only minor foci of acute hemorrhage were seen in three of 170 glands in 113 comparison neonates and infants. We conclude that parathyroid gland hemorrhage is common in perinatally lethal OI with survival beyond the immediate period of birth, and is otherwise rare. We speculate that parathyroid hemorrhage may be related to difficulty in maintaining postnatal calcium homeostasis in the absence of adequate calcium reserves in bone. Acute parathyroid gland hemorrhage causes fluctuations in serum calcium levels that have on occasion proved fatal, and parathyroid hemorrhage may be a proximate cause of death in some neonates with OI.

A cross between truncus arteriosus communis and aortopulmonary septal defect: a hitherto undescribed entity.

Case history and necropsy findings of a 5-month-old infant with a unique heart defect with features of truncus arteriosus communis and aortopulmonary defect in combination with severe tricuspid stenosis are presented. There is a wide spectrum of remarkable heart defects between truncus arteriosus communis and aortopulmonary septal defect.

Acute hypoxemic respiratory failure in children following bone marrow transplantation: an outcome and pathologic study.

OBJECTIVES: To describe the pulmonary pathology and clinical outcome in children with acute hypoxemic respiratory failure after bone marrow transplantation. DESIGN: Review of medical records and pathologic material of patients diagnosed with acute hypoxemic respiratory failure after bone marrow transplantation. SETTING: Pediatric intensive care unit (ICU) of a teaching hospital. PATIENTS AND METHODS: Retrospective review of a consecutive cohort of children, with a history of bone marrow transplantation admitted to the pediatric ICU during a 7-yr study period, and who met a published definition of acute hypoxemic respiratory failure. For each admission, the pediatric ICU course and outcome were reviewed. Pathologic material that was obtained from the patients was reexamined and assigned to one of the following categories: acute or organizing diffuse alveolar damage, pulmonary hemorrhage, nonspecific interstitial pneumonitis, or infectious pneumonia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-three patients satisfied criteria for inclusion in the study group. Indications for bone marrow transplantation were: solid tumor (30%), leukemia (44%), congenital immunodeficiency (19%), and aplastic anemia (7%). Patients were admitted to the pediatric ICU a median of 1 month (range 0 to 126) after bone marrow transplantation. Thirty-eight (88%) patients died in the pediatric ICU. Tissue histologic material was available from 21 (49%) patients. Six (29%) of 21 patients had acute diffuse alveolar damage; one (5%) had organizing diffuse alveolar damage; three (14%) had nonspecific interstitial pneumonitis; and two (10%) had pulmonary hemorrhage. Infectious pneumonia occurred in nine (43%) cases (five fungal; four viral). CONCLUSIONS: The acute mortality rate (88%) for children with acute hypoxemic respiratory failure after bone marrow transplantation is similar to that reported for adults with this combination of conditions. Diffuse alveolar damage, the histologic hallmark of adult respiratory distress syndrome, was present in a minority (33%) of patients. Infectious pneumonia was the most frequent cause of acute hypoxemic respiratory failure in patients who had pathologic tissue available, emphasizing the need for aggressive diagnostic studies and early institution of antifungal and antiviral therapy.

Placental pathology in systemic lupus erythematosus: a prospective study.

OBJECTIVES: Systemic lupus erythematosus and antiphospholipid antibody, often identified in patients with systemic lupus erythematosus, are associated with poor pregnancy outcome. This study distinguishes between the effect of each of these factors on gestational outcome and placental pathologic conditions in pregnant patients with systemic lupus erythematosus. STUDY DESIGN: Thirty-seven pregnancies and 40 placentas from 33 women with systemic lupus erythematosus were studied prospectively. RESULTS: Systemic lupus erythematosus alone, but not systemic lupus erythematosus activity, was associated with increased spontaneous abortions, preterm gestations, and fetal growth restriction. Placental correlates were ischemic-hypoxic change, decidual vasculopathy, decidual and fetal thrombi, chronic villitis, and decreased placental weight. Extensive infarction and fetal death were important antiphospholipid antibody-related findings. CONCLUSIONS: Decidual vasculopathy/coagulopathy appears to mediate the antiphospholipid antibody-related and much of the systemic lupus erythematosus-related deleterious effect on the placenta and gestational outcome. The presence of antiphospholipid antibody largely, but not invariably, predicts fetal death. Antiphospholipid antibody-independent chronic villitis may represent a second mechanism of systemic lupus erythematosus-related change.