Bartonella henselae-mediated disease in solid organ transplant recipients: two pediatric cases and a literature review.

Bartonella henselae, the etiologic agent of cat-scratch disease, causes a well-defined, self-limited syndrome of fever and regional lymphadenopathy in immunocompetent hosts. In immunocompromised hosts, however, B. henselae can cause severe disseminated disease and pathologic vasoproliferation known as bacillary angiomatosis (BA) or bacillary peliosis. BA was first recognized in patients infected with human immunodeficiency virus. It has become more frequently recognized in solid organ transplant (SOT) recipients, but reports of pediatric cases remain rare. Our review of the literature revealed only one previously reported case of BA in a pediatric SOT recipient. We herein present 2 pediatric cases, one of which is the first reported case of BA in a pediatric cardiac transplant recipient, to our knowledge. In addition, we review and summarize the literature pertaining to all cases of B. henselae-mediated disease in SOT recipients.

Proteus syndrome: three case reports with a review of the literature.

Proteus syndrome (PS) is a rare, progressive disorder that manifests as asymmetric, disproportionate overgrowth affecting tissues derived from any germline layer. Cases of PS from 2005-2010 were retrieved from the pathology files at our institution. Two confirmed cases and one possible case of PS were identified. All patients came from different ethnic backgrounds. Patient 1 displayed classic skin and overgrowth lesions. Patient 2 displayed various features, particularly vascular malformations. Patient 3 demonstrated a cerebriform connective tissue nevus alone. These patients demonstrate the spectrum of presentations of PS. Much is left to learn about this disfiguring disease.

Splenic cysts in the pediatric population: a report of 21 cases with review of the literature.

Splenic cysts are rare lesions that can occur in parasitic and non-parasitic forms. Because they are uncommon, the classification, pathogenesis, and management techniques are still debated. The continual review of splenic cyst cases in the pediatric population is essential for establishing a clear diagnosis and course of treatment. This report presents 21 cases of pediatric splenic cysts observed at Children's Healthcare of Atlanta over an 18 year period (1993-2011). The cases include both parasitic and and nonparasitic cysts. The current splenic cyst classification and treatment methods are analyzed through a review of the current theories and based on our experiences.

Inflammatory pseudotumor of the spleen in a young child.

We describe a case of an inflammatory pseudotumor of the spleen in a 5-year-old boy, found incidentally during a physical examination. The boy underwent a hemisplenectomy. The problems in differentiating this disease from lymphoma of the spleen before surgery and the advantages of hemisplenectomy are discussed. This rare disease has previously been described in the spleen in only 28 cases, the youngest being a 16-year-old patient.

The normal pediatric larynx on CT and MR.

PURPOSE: To determine the MR and CT appearance of the normal pediatric larynx. METHODS: Fifteen CT scans and 15 MR examinations of children with normal larynges and airways were reviewed retrospectively. Characteristics that were noted included the level of the hyoid bone, calcification and signal intensity within separate laryngeal components, amount of paraglottic fat, anteroposterior airway diameters, and airway contours. Two cadaveric larynges were imaged by CT and MR and were then sectioned at corresponding levels and section thicknesses. RESULTS: The larynx is higher in children than in adults, with the hyoid bone found at the C2-3 level in the youngest children (newborn to 2 years). The subglottic airway was narrowest in the youngest children. The hyoid bone was the only laryngeal structure ossified in any of the children. A thin line of high density was seen in the expected location of the thyroid cartilage in some children. The featureless circumferential soft tissue seen around the airway represented the uncalcified laryngeal cartilaginous structures. This was confirmed on gross sectioning of cadaveric larynges. The supraglottic airway contour was triangular or oval, the glottis was shaped like a teardrop, and the subglottic contour was oval. Contours were confirmed on histologic examination of necropsy specimens. CONCLUSIONS: This preliminary study suggests that the pediatric larynx differs from the adult larynx with respect to size, position, consistency, and shape, and these differences are reflected on CT and MR studies.

Fetus-in-fetu with malignant recurrence.

Fetus-in-fetu is an unusual condition in which a vertebrate fetus is enclosed within the abdomen of another fetus. These occurrences are usually benign. This report describes an instance of malignant recurrence after resection of a fetus-in-fetu.

Long-term dual perfusion of isolated human placental lobules with improved oxygenation for infectious diseases research.

An improved method for long-term perfusion of the isolated human term placental lobule has been developed to investigate the maternofetal transfer of infectious agents, in particular the human immunodeficiency virus (HIV). The purpose of this paper is to describe those modifications that allow for substantially prolonged perfusions in in a biohazard environment. The method described has been adapted from previous models. The perfusion apparatus has been modified for use within a biohazard hood, and, intravenous bags contain the medium for circulation of perfusates in closed circuits. A Mera Silox-S 0.3 membrane oxygenator delivers more oxygen to the tissue, and, Electromedic Cardioplegia heat exchangers warm the perfusate prior to oxygenation. Viability criteria (glucose consumption, lactate production, de novo production of human placental lactogen (hPL), volume loss, flow, temperature, pressure, oxygen transfer, carbon dioxide production, absence of IgM transfer and light and electron microscopy) demonstrate that the placental tissue remains in a functional state throughout the perfusion. Oxygen and glucose consumption are both stable over time; lactate levels remain constant; and hPL continues to be produced. These significant modifications of the perfusion system have permitted the investigators to increase the duration of perfusion to 48 h while preserving normal metabolic function of ultrastructurally intact tissue as demonstrated by ultra structural observations. This perfusion model device provides biohazard precautions and may be applied to other studies of placental physiology.

Immunofluorescence studies of lung tissue in cystic fibrosis.

Previous studies have suggested that immune mechanisms contribute to lung injury in cystic fibrosis (CF); however, there have been no comprehensive studies of immunofluorescent staining patterns in CF lung tissue. We performed immunofluorescence (IF) studies for immunoglobulins, C3, and fibrinogen on autopsy frozen lung tissue from 21 CF patients. Results were compared with lung findings in patients without CF. In CF-derived lung tissue fibrinogen was ubiquitous along the alveolar wall, alveolar space, and interstitium. Free immunoglobulin G (IgG) and IgA coated the alveolar surface segmentally in 14 and 6 cases, respectively. Unequivocal interstitial deposits were infrequent and IgM was present in blood vessels in one patient only. Intra-alveolar and interstitial inflammatory cells demonstrated cytoplasmic IgG, IgA, and IgM, respectively, in 18, 14, and 6 patients. C3 was seen only segmentally along the alveolar wall in two patients and in blood vessels in one. Antinuclear antibody (ANA) staining of interstitial cells for C3 and immunoglobulins was seen in five patients, four of whom had interstitial pneumonitis. Insignificant amounts of alveolar or interstitial fibrinogen and immunoglobulins in inflammatory cells were seen in controls in the absence of lung inflammation. The IF patterns were similar in the inflammatory lesions of CF and control specimens. The IF patterns observed in CF lung tissue are consistent with nonspecific vascular leakage and chronic inflammation with little evidence of immune complex deposition in the interstitium or blood vessels. This study confirms previous reports of ANA activity in CF patients, although the significance of this finding is unknown.

The pathology of fungal infection and colonization in patients with cystic fibrosis.

We used methenamine silver stains to retrospectively evaluate the prevalence of fungi and their associated inflammatory reactions in 63 patients with cystic fibrosis (CF) autopsied between 1982 and 1987. Fungi were detected in 13 patients (21%) who fell into three groups: respiratory tract colonization (five patients); localized infection (five patients); and disseminated infection (three patients). Hyphae consistent with Aspergillus sp were present in five patients; yeast-like cells and/or pseudohyphae consistent with Candida sp occurred in eight patients; and Histoplasma capsulatum produced fibrocaseous lymph node and splenic granulomas in one patient. Acute inflammation typified most fungal lesions, while bronchocentric granulomatosis affected one patient. Compared with patients with no fungi, those with fungi were more frequently treated with indwelling central venous catheters (P less than .05). Autopsy reports on 156 CF patients from 1964 to 1982 disclosed only one with disseminated mycosis (P less than .05). We conclude that stainable fungi can be found in CF patients at autopsy more frequently than previously realized. Fungi usually represent respiratory tract colonization or minimal localized infection, but the prevalence of fatal disseminated infection (4.8%) has also increased. Fungal infection in CF appears to be most closely associated with aggressive therapeutic intervention.

Cryptococcosis of the placenta in a woman with acquired immunodeficiency syndrome.

Multiple microscopic colonies of encapsulated budding yeasts morphologically consistent with Cryptococcus sp were found in the maternal (intervillous) space of the placenta from a woman with AIDS. The patient contracted acquired immunodeficiency syndrome from her affected husband, who had died of the disease 3 years previously. The woman, who was in her sixth pregnancy at term, became symptomatic 1 month before delivery with malaise, oral thrush, and cervical lymphadenopathy. Tests for human immunodeficiency virus and serum hepatitis were negative. Cryptococcus neoformans was cultured in the blood and herpes simplex virus type II was isolated from the cervix. On the second postpartum day, the patient had difficulty breathing and died suddenly. Post-mortem examination disclosed a massive pulmonary embolus and disseminated infection with Cryptococcus organisms.

Flow cytometry DNA ploidy analysis and catecholamine secretion profiles in neuroblastoma.

Previous studies have shown that catecholamine secretion patterns have been imperfect predictors of clinical behavior of neuroblastomas. Recently, studies of nuclear DNA content in neuroblastoma have shown that an aneuploid DNA content predicts favorable clinical behavior. To determine if a correlation exists between these tumor biologic indicators, the authors analyzed both in a series of 39 patients with neuroblastoma. Flow cytometric DNA analysis performed on paraffin blocks determined that 23 patients had tumors with aneuploid DNA content (aneuploid tumors) and 16 patients showed no demonstrable anomalies of tumor DNA content (nonaneuploid tumors). Comparison of catecholamine levels in urine and tumor homogenates with DNA content data indicate that nonaneuploid neuroblastomas include a significant number (P less than 0.02) of biochemically primitive tumors which secrete high levels of 3,4 dihydroxyphenylalanine (DOPA), dopamine and homovanillic acid (HVA). This suggests a dopamine-norepinephrine pathway block, which supports previous reports of deficiency of dopamine beta-hydroxylase activity in some neuroblastomas. The study shows that in contrast to aneuploid tumors, nonaneuploid neuroblastomas secrete higher levels of early pathway catecholamine metabolites and are more likely to present in higher (unfavorable) clinical stages of disease.

The pathologic characteristics of interstitial pneumonia cystic fibrosis. A retrospective autopsy study.

Interstitial pneumonia is a poorly understood variant of lung injury in patients with cystic fibrosis (CF). The authors identified prominent interstitial pneumonia (defined as an inflammatory reaction predominantly involving alveolar septa) in 9 of 43 autopsied patients with CF. Lungs from these nine were studied by light microscopy to determine the histopathologic features, clinicopathologic correlates, and potential causes of CF-associated interstitial pneumonia. Two histologic variants were identified, alveoloseptal (in which the inflammatory reaction was confined to the alveolar wall) and organizing (in which intraalveolar granulation tissue was present in addition to septal inflammation), which respectively affected four and five patients. Cholesterol deposits and capillary proliferation were prominent associated features in some patients. Interstitial pneumonia was not diagnosed antemortem and was identified on chest roentgenogram in only two patients. There were no distinctive clinical features associated with different histologic subtypes, nor did histologic or clinical data identify a specific cause(s) of interstitial pneumonia. The authors conclude that CF-associated interstitial pneumonia, although usually an incidental finding at autopsy, may potentially contribute to respiratory impairment and death. Although there are multiple possible causes of interstitial lung injury associated with CF, the authors were unable to identify, with certainty, the pathogenesis of interstitial pneumonia in any patient in this study.

Regional enteritis-like enteropathy in a patient with agammaglobulinemia: histologic and immunocytologic studies.

A 24-year-old man with agammaglobulinemia developed a form of chronic inflammatory bowel disease over the past 18 years characterized by recurrent diarrhea, malabsorption, and protein-losing enteropathy. In the most recent admission he presented with abdominal cramps and active intestinal bleeding. Radiologic studies showed distal ileal irregularities and strictures that led to two distal intestinal and ileocecal resections. The gross pathologic appearance of these specimens was consistent with regional enteritis. Microscopically, healing ulcers, mucosal irregularities, and a prominent lymphocytic infiltrate without plasma cells or granulomas were observed. Immunocytochemical studies revealed a prominent T-helper cell and a modest T-suppressor/cytotoxic lymphocyte population in the lamina propria. Early and late B-cell differentiation markers were not detected in any of the cells. The immunocytologic findings suggest that T-helper lymphocytes proliferated without inhibition to stimulate non-existent B cells. The study confirms the occurrence of a regional enteropathy-like lesion in the total absence of B-cell function.

The causes of morbidity and mortality among infants born at term.

Previous studies have reported on the pathologic spectrum of perinatal mortality; however, in our opinion, the problems pertaining to the term newborn have not been emphasized sufficiently. We reviewed the autopsies of all term infants up to 2 months of age in a ten-year period (July 1975 to July 1985). These 342 patients comprised 20% of all pediatric autopsies. The patients were grouped according to cause of death in the following categories: congenital anomalies (59%); infection (10%); perinatal injury, including meconium aspiration (9%); maternal-placental problems (11%); and miscellaneous (5%). In 4% of the cases, mainly stillbirths, the cause of death was unclear. Of the congenital anomalies, the cardiovascular system was most affected (57%). Hyaline membrane disease and intraventricular hemorrhage, usually frequent in series involving many preterm patients, were seldom seen. This study emphasizes the different pathologic spectrum of mortality between premature and term newborns.

Secretory immunoglobulin deposits in renal glomeruli of children with extrahepatic biliary atresia: studies in a human counterpart of experimental ligation of the bile ducts.

Experimental ligation of the biliary tract often results in glomerular deposits of polymeric IgA commonly associated with secretory component. These studies offer evidence that, in animals, hepatobiliary transport of polymeric IgA, which is of mucosal origin, is crucial for its clearance from the serum. We studied a human counterpart of bile duct ligation--extrahepatic biliary atresia--for the presence of secretory or polymeric immunoglobulins in renal glomeruli. Kidney was available at autopsy as paraffin or frozen blocks from 24 patients with biliary atresia and age-matched controls (5 weeks to 5 years old). Several of the patients had undergone portoenterostomy (Kasai procedure) or liver transplantation. Immunohistologic studies showed glomerular (often mesangial) deposits of IgA in 10 of 24 and IgM in 16 of 24 specimens. The differences with controls were highly significant for IgA but not for IgM. In frozen sections, secretory component was positive in glomeruli in seven of 12 specimens. In vitro glomerular binding of purified secretory component to glomeruli was shown in four of 12 samples, including three with IgM only. This last observation suggests that IgM in some of these patients was polymeric and thus derived from a mucosal source. Our study shows that in humans with biliary atresia, secretory IgA, polymeric IgA, and possibly polymeric IgM are deposited in glomeruli. The study confirms the occurrence of renal immunopathologic findings in liver disease and supports the existence of an active hepatobiliary immunosecretory transport mechanism even at the early age of these patients.