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Recurrent autoimmune hepatitis (rAIH) occurs in patients who undergo liver transplantation (LT) for AIH and de novo AIH (dAIH) is seen in patients who are transplanted for etiologies other than AIH. Whether these are distinct diseases with a similar phenotype remains understudied. The aim of this study was to identify clinical and immunologic factors affecting outcome in patients with dAIH and rAIH. A retrospective review of 387 LT patients from 1997 to 2014 was carried out, and they were followed until 2018. Patients with rAIH or dAIH were identified based on the pre-transplant diagnosis of AIH (or not) and characteristic histology. Liver biopsies were stained with H&E, B-cell marker CD20, and plasma cell marker CD138. Out of 387 patients, 31 were transplanted for AIH, and 8/31 developed rAIH. Of the remaining 356 patients, eight developed dAIH. Compared to the dAIH group, rAIH occurred in older patients, had an earlier onset in the allograft, and had higher IgG and serum ALT levels. It was most commonly seen in African American (AA) patients (87%). rAIH patients had significantly higher CD20 and CD138 positivity in liver biopsies. In addition, they had increased rejection episodes prior to the onset of recurrence, increased graft loss, and mortality. rAIH is a more aggressive disease, and has a preponderance of B cells and plasma cells in the liver tissue as compared to dAIH. The concurrent association with increased graft loss and patient mortality in rAIH warrants further investigations into B cell-targeted therapies.

Background: Right ventricular myocardial fatty infiltration has been observed in pediatric cardiac allografts with an associated decrease in graft life expectancy. A possible explanation included a...

Leydig cell nodular hyperplasia (LCNH) is a lesion that is less characterized than the familiar Leydig cell tumors. The paracrine effects of these lesions on adjacent gonadal stroma have not been widely documented. We present two cases of precocious puberty in pre-pubertal boys found to have a single LCNH with adjacent focal maturation of the seminiferous tubules. Blood tests showed elevated serum testosterone and dehydroepiandrosterone (DHEAS). Ultrasound revealed unilateral testicular enlargement with irregular echogenicity. Radical orchiectomy was performed. Histologically Leydig cell nodular proliferation without destruction of surrounding tubules was seen. Mature seminiferous tubules undergoing spermatogenesis were noted adjacent to the lesion, while away from the lesion seminiferous tubules were as expected in pre-pubescent boys. These cases emphasize the potential presence of both paracrine and endocrine effects in Leydig cell nodular hyperplasia. However, instances of the endocrine effects of hyperplastic Leydig cell lesions are more widely reported than the paracrine effects.

During the age of enlightenment in the 18th century, radical changes were occurring in the Western world in science, medicine, philosophy, religion, and socioeconomic concepts. In medicine, major advances had already been underway since the days of Vesalius.

Malakoplakia, a rare granulomatous disease caused by impaired macrophage response, has been reported only rarely in children. We report 3 unique cases, with lesions occurring in unusual locations in children with primary immune deficiencies.

Intrathecal and systemic methotrexate (MTX), as well as cranial radiation, are effective modalities to prevent central nervous system relapse in childhood acute lymphoblastic leukemia. Leukoencephalopathy is a well-described adverse effect of MTX therapy and is associated with a wide range of neurological sequelae. Most recent studies of MTX-induced leukoencephalopathy have focused exclusively on imaging findings, particularly magnetic resonance imaging. Here we report a case of severe MTX-induced leukoencephalopathy with unique magnetic resonance imaging findings and pathologic correlation from a brain biopsy taken during a period of active neurological symptomatology.

Noniatrogenic neonatal gastric perforation is a rare and life-threatening condition whose etiology is often unclear. Interstitial cells of Cajal act as gastrointestinal pacemaker cells and express the proto-oncogene c-Kit. Six new cases were identified at our institution which presented with no mechanical, pharmacologic, or otherwise medical-related intervention prior to rupture. The number of interstitial cells of Cajal in nonnecrotic muscularis propria from five random high-power fields per specimen was compared using immunohistochemical stains for c-Kit. The authors show that a lack of interstitial cells of Cajal in the stomach musculature may be implicated in the development of noniatrogenic gastric perforation (p = 0.008). Further large-scale studies, including molecular and genetic analysis, may help to better understand this phenomenon.

Epstein-Barr virus (EBV) may present few or no symptoms in immunocompetent individuals; however, in immunocompromised patients as in the case of AIDS and post-transplant patients, the virus occasionally stimulates neoplastic transformations. Epstein-Barr virus may play a role in the development of smooth muscle tumors (SMT). In the case of Epstein-Barr associated smooth muscle tumors (EBV+SMT), the virus is thought to be the leading factor to the tumorigenic pathway. We report two pediatric patients (6 and 13 years old) who underwent liver transplantation and developed EBV+SMT in the colon and orbit. These two cases represent rare locations for this kind of lesion.

Bacterial infection of Salmonella enterica serotype Typhi is rare in the United States but endemic in many developing countries. Approximately 3-5% of patients become chronic asymptomatic carriers. We describe an atypical presentation of S. enterica serotype Typhi infection in a 10-year-old male, whose cholecystechtomy and bile culture revealed chronic carrier status despite negative stool tests and the absence of gallstones. The gallbladder showed marked thickening of the wall with an intense suppurative granulomatous reaction.

Colorectal adenocarcinoma (CRAC) is exceedingly rare in the pediatric population (fewer than 2 cases per 1 million children). There are 2 major categories of pediatric colorectal adenocarcinoma syndromes: polyposis-related and hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome. Germ line mutations in DNA mismatch repair (MMR) genes (eg, MLH1, MSH2, PMS2, MSH6) have been established as the molecular genetic basis of Lynch syndrome. Another prognostic factor in adult CRAC is the reduced expression of epithelial cadherin (E-cadherin), which has been associated with poor outcome in some adult CRAC cases; however, its role in predicting prognoses in pediatric cases remains unclear. Seven pediatric patients with primary CRAC were reviewed. Available molecular genetic test results were evaluated, and immunohistochemical labeling for MMR proteins and E-cadherin were performed on 5 patients. Four of the 5 patients in our study with available paraffin blocks showed loss of MMR protein expression, consistent with Lynch syndrome. In cases stained for E-cadherin, 3 were strongly positive and 2 were weakly positive; however, with the small sample size and the relatively short follow-up period, an accurate correlation between E-cadherin and prognosis cannot be reached with any degree of certainty. Our findings highlight the importance of genetic testing for MMR gene mutations in children with colorectal cancer and suggest further investigation into the prognostic role of E-cadherin in pediatric CRAC.

Hepatic pulmonary fusion (HPF) is characterized by a fibrous connection between the liver and lung tissue. We present two cases of hepatic pulmonary fusion diagnosed with right diaphragmatic hernia and a third case with Pentalogy of Cantrell exhibiting complete agenesis of the diaphragm and finger-like projections of liver adhered to the right lung. It has been proposed that this anomaly is secondary to developmental failure of the mesoderm between days 14-18 after conception and is attributed to diaphragmatic maldevelopment. Understanding the molecular-genetic basis of diaphragmatic hernias may shed light on this unusual presentation and explain why other cases show no fusion.

Parasitic infections of the central nervous system (CNS) occur mostly in underdeveloped regions of the world. Neurocysticercosis (NC) occurs when the larval form of the T. solium tapeworm invades the CNS. Spinal cysticercosis is an extremely rare type of NC and occurs when the cyst occupies the subarachnoid space of the spinal column. Previous cases have been successfully treated through both surgical and medical means. The current case describes the symptoms, diagnosis, and treatment of a patient with this extremely uncommon manifestation of neurocysticercosis.

Rosai-Dorfman disease (RDD), or sinus histiocytosis with massive lymphadenopathy (SHML), is a rare idiopathic histiocytic disorder. The usual presentation of RDD is painless bilateral cervical lymphadenopathy. Extranodal RDD with lymphadenopathy occurs in almost 50% of patients but extranodal RDD, without lymphadenopathy, is very rare. Isolated RDD in the bone occurs in only 2% of patients but it is histologically similar to its nodal counterpart. There are only 14 previously reported cases of RDD in the bone without lymph node involvement in children. Here we describe two new patients--one with rib and lung involvement and the other with multi-osseous involvement.

Congenital infantile fibrosarcoma (CIFS) is a rare mesenchymal tumor that primarily presents in the soft tissue of the distal extremities and occasionally in unusual locations such as the lung and retroperitoneum. Herein, we report seven cases of unusual presentations of CIFS. These cases include three in the lungs, one in the retroperitoneum with cord compression, one in the posterior trunk, one in the heart, and one infratemporal involving the sphenoid bone. All tumors demonstrated CIFS's characteristic t(12;15)(p13;q25) and associated ETV6-NTRK3 gene fusion. One of the three lung cases was previously reported as primary bronchopulmonary fibrosarcoma (PBPF), but molecular analysis of the paraffin embedded tissue revealed the ETV6-NTRK3 gene fusion consistent with CIFS. We show that CIFS may occur in unusual sites including visceral locations, and we propose that neoplasms displaying the ETV6-NTRK3 gene fusion represent the visceral components of CIFS.

A balance has evolved over deep time between the various immune systems of the "triad" that is linked together for a short period: the pregnant woman, the fetus, and the placenta. This balance is a ...

The pathogenesis of right ventricular fibrofatty changes can be broadly divided into genetic or acquired. The genetic cause is termed arrhythmogenic right ventricular dysplasia, an inherited cardiomyopathy characterized by fibrofatty replacement of the right ventricular myocardium, and represents an underdiagnosed cardiac entity leading to syncope, recurrent ventricular tachycardias, heart failure, and sudden death. Our study demonstrates that fibrofatty changes can also be seen in pediatric cardiac allografts. Conversely, fat replacement without fibrosis may be seen secondary to infectious myocarditis, chronic inflammation, and ischemia and as part of the aging process. We examined 29 failed cardiac allografts to identify the etiology of graft failure. In this study, 4 patients (13%) had severe right ventricular fibrofatty changes, and when compared with control patients, those with fibrofatty changes had a shorter interval from transplant to graft failure, 2.75 years vs 5.45 years ( P = 0.029). Neither body mass index nor other physiologic parameters found on electrocardiography, echocardiography, or cardiac catherization were different between groups. Furthermore, arrhythmias indicative of arrhythmogenic right ventricular dysplasia were not observed in the study group. This study suggests the fibrofatty infiltration in cardiac allografts is a clinically different entity from arrhythmogenic right ventricular dysplasia and has an unknown etiology. Our study findings suggest that identifying fibrofatty infiltrates in cardiac transplant patients during routine right ventricular biopsy can be a predictive factor for shortened life of the pediatric cardiac allograft.

Although Kawasaki disease (KD) was first discovered and identified in Japan by Kawasaki in the 1960s, fatal KD cases resulting from coronary artery aneurysms had been identified retrospectively in the West as early as 1871. Kawasaki initially postulated that this disease was a new, as yet unidentified, self-limiting illness with no fatal coronary sequelae. The connection between fatal cases, then diagnosed as infantile polyarteritis nodosa, was not made until the late 1970s. Kawasaki's thoughts were reinforced by an apparent absence of nonfatal cases in the West before 1967. Close examination of a 1948 autopsy report suggests that nonfatal cases of KD did indeed exist, at least in the United States, before its emergence in Japan in the early 1950s. These nonfatal cases of KD were misdiagnosed as Stevens-Johnson syndrome. The autopsy report reviewed in this article reinforces the likelihood that KD did occur in the United States before it was identified as Kawasaki disease in Japan.

Three cases of congenital immature intracranial teratomas were examined by autopsy. The fetuses were diagnosed prenatally as macrocephalic and hydrocephalic due to skull-occupying lesions. These fetuses were born alive at 32, 31, and 36 weeks gestation, respectively, via Cesarean section. Intracranial teratoma in the first case was diagnosed by MRI and in the second and third cases by ultrasound. All tumors were deemed to be unresectable. Congenital CNS teratoma should be considered in the differential diagnosis of fetuses diagnosed with macrocephaly or hydrocephaly.

Thoracoschisis is an extremely rare congenital birth defect in which intra-abdominal organs eviscerate through a defect in the thoracic wall(1). There are only seven previously reported pediatric cases and in each case, there is some diaphragmatic anomaly, suggesting that the defect took place before complete formation of the diaphragm. Our patient was referred to us from a local hospital immediately after delivery. The patient was born with a thoracoschisis of the left side below the 8(th) intercostal space. The thoracoschisis was repaired. Although there is a high prevalence of cardiac defects among thoracoschisis patients, this patient shows only small atrial septal defects.

Anti- N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a potentially fatal neurologic syndrome in which patients present with a spectrum of central nervous system deficits. Sixty percent of the cases can be attributed to the presence of tumors, most often ovarian teratomas. This report examines 6 pediatric patients who presented with neurologic deficits associated with the presence of such tumors. These cases illustrate a perplexing phenomenon, where benign teratomas could have a possible association with anti-NMDAR encephalitis. The purpose of this study was to compare the histology and immunohistochemistry of tumors associated with this syndrome to ovarian teratomas found in patients presenting with no neurologic symptoms. After obtaining institutional review board approval, 57 cases of ovarian teratomas were identified at our institution over 12 years. Six patients were identified with anti-NMDAR encephalitis. A panel of immunostains, including S100, GFAP, MAP2, and NeuN was applied to patients' tumor sections as well as the 6 controls from age-matched patients. No qualitative histologic or immunohistochemical differences were seen between the study cases and control group. Because no qualitative differences were identified between the study cases and the control group, testing of paired serum and cerebrospinal fluid remains the best method for diagnosis of anti-NMDAR encephalitis. Tumor banking with molecular analysis of ovarian teratomas, including whole-genome sequencing and comparative genomic hybridization between ovarian tissue saved from patients with and without anti-NMDAR encephalitis, is necessary to fully understand the etiopathogenesis of anti-NMDAR encephalitis.

Reports indicate peripheral eosinophilia (PE) and gastrointestinal eosinophilic inflammation can occur after pediatric liver transplantation. The incidence of these conditions, potential risk factors, and the impact of PE and gastrointestinal eosinophilic inflammation on liver transplant outcome were determined in this pediatric liver transplant program. Medical records of liver transplant recipients from 1 to 97 and from 12 to 99 were reviewed. Fifty-seven transplants on 54 patients were performed during the study period. Fifty-three patients were evaluated; all had normal pre-transplantation peripheral eosinophil counts. PE of > 10% developed in 28% of patients. Using this definition, all such identified patients had absolute eosinophil counts of > 350/mm3. History of immediate hypersensitivity did not differ between patients with or without eosinophilia. Gastrointestinal endoscopy and biopsy was performed in 23 patients with gastrointestinal complaints. Of those, six had eosinophilic gastroenteritis and all six had PE. Compared with patients without eosinophilia, those with PE were younger at the time of transplantation (p < 0.05), had more frequent rejection (p < 0.01), were more commonly managed with tacrolimus-based immunosuppression (p < 0.001), and experienced more frequent episodes of detectable EBV viral load (p < 0.04). Patients with eosinophilic gastroenteritis were more frequently retransplanted (p < 0.006). PE associated with symptomatic eosinophilic gastroenteritis is common after pediatric liver transplantation. Age at transplant, frequency of rejection episodes, tacrolimus-based immunosuppression, and EBV viral load may be associated with the development of this condition. There may be higher rates of graft loss in such patients. Whether innate immune responsiveness or an acquired immune dysregulation accounts for these findings merits further evaluation.

Giant cell myocarditis is a rare but often fatal form of myocarditis that often requires cardiac transplantation and has been associated with autoimmune diseases. We describe a 14-year-old female who developed painful proptosis and was diagnosed clinically and histologically with orbital myositis that improved with corticosteroid therapy. Approximately 2 months later, she developed abdominal pain, vomiting, weight gain, and fatigue. She was diagnosed with congestive heart failure and cardiomyopathy, and endomyocardial biopsy revealed giant cell myocarditis. She was treated with immunosuppressive agents and has responded well, without the need for cardiac transplantation. Three previous case reports have described an association between giant cell myocarditis and orbital myositis, but we present the first pediatric case report. We conclude that if orbital myositis is diagnosed in a patient, regardless of age, cardiac function should be closely monitored to detect myocarditis, which may affect the overall outcome.

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.

Studies indicate a close relationship between Yersinia and Crohn's disease in adults. Our study tested 77 colonic specimens from children with Crohn's disease for the presence of Yersinia DNA using a validated polymerase chain reaction (PCR) assay. Control cases included specimens from 45 ulcerative colitis patients and 10 appendicitis patients. The presence of Yersinia in Crohn's specimens was significant compared to the control specimens (9% vs. 0%; p = 0.0055). While our study supports the medical literature, future studies are needed to determine if the relationship between Crohn's disease and Yersinia is an initiating or mediating factor in the pathogenesis of pediatric Crohn's disease.

We examined the association of placental malaria and mother-to-child transmission (MTCT) of HIV in a prospective community-randomized trial in Rakai District, Uganda. In the 746 HIV-positive mother-infant pairs, the MTCT rate was 20.4%. Placental malaria was more common in HIV-positive than HIV-negative women. After multivariate adjustment for HIV viral load, the risk of MTCT associated with placental malaria was 2.89 and with HIV viral load the risk was 2.85. Interventions to prevent malaria during pregnancy could potentially reduce MTCT.

Hepatopulmonary syndrome (HPS) is infrequently reported in children. Clinical-pathological findings in 10 HPS children were compared with non-HPS controls. Six patients had cirrhosis and four had noncirrhotic portal hypertension (NCPH) 40%. Polysplenia and abnormal venous malformations were exclusive to this group. This prevalence of NCPH with systemic venous anomalies suggests that HPS is associated with pulmonary vasoactive factors not cleared by the liver. Hepatopulmonary syndrome should be considered in any patient with hypoxemia and intrapulmonary shunting whether there is overt clinical liver disease or not.

Anita K. McElroy, Joseph A. Hilinski, Carlos R. Abramowsky, Ronald Jaffe, Sunita I. Park, Bahig M. Shehata, and ToddM. Cooper Divisions of Infectious Diseases and Hematology/Oncology, Department of Pediatrics, and Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia;, and Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania

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.

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.

NUT midline carcinoma is a rare and aggressive tumor that has primarily been reported in children and young adults. The tumor is characterized by a rearrangement on the nuclear protein in testis (NUT) gene, located on chromosome 15q14, resulting in the BRD4-NUT fusion oncogene. This carcinoma most commonly presents in the midline and displays an invariably lethal clinical course. To highlight the imaging features of NUT midline carcinoma. IRB approval was obtained for chart review. We retrospectively reviewed the chart and imaging studies of three children. All three cases were diagnosed by karyotyping and confirmed by fluorescence in situ hybridization (FISH). Cross-sectional imaging including CT, MRI and, in one patient, PET was available for review. Two out of three children presented with midline and multifocal disease. The third case had a medial left thigh mass and no metastatic disease at initial presentation. The common imaging features include heterogeneous low density on CT and T1 hypointensity and low-level T2 hyperintensity on MRI with heterogeneous enhancement. All cases were confirmed pathologically and by molecular studies. NUT midline carcinoma usually presents in the midline, either in the head, neck or chest. We present three cases with the bulk of the tumor below the diaphragm, which is seen in the minority of patients with NUT midline carcinoma, according to the available literature. Metastatic disease is common at initial presentation and can be quite extensive. The most striking feature of this disease is its aggressive nature with exponential interval growth of tumor.

Mesenteric cysts, seen in all age groups, represent a rare cause of benign abdominal masses in children. We reviewed 21 patients with mesenteric/omental cysts. Gross and radiologic images, along with histologic sections, were reviewed to categorize the structures and determine the relationship to the mesentery and intestines. The cysts were composed of multi-loculated dilated channels at the serosal surface consistent with lymphangioma. Most treatment was simple excision, infrequently with intestinal resection. Nineteen patients did well after surgery. One patient developed short-gut syndrome after massive bowel resection, and one patient died immediately after birth due to massive fetal hydrops and heart failure.

Congenital diaphragmatic hernia (CDH) is a defect seen in approximately 1 in 3500 live births. A complication of CDH is the herniation of abdominal contents into the chest cavity through the defect, which may prevent normal intrauterine development of the lungs. The resultant pulmonary hypoplasia and pulmonary hypertension causes respiratory distress in the newborn, usually requiring some form of intervention before the defect is surgically corrected (Embryology for Surgeons. Baltimore, MD: Williams & Wilkins; 1994:491-539). Extracorporeal membrane oxygenation, which involves cannulation of the superior vena cava (SVC), is often used to manage these infants. However, the mediastinal shift that often occurs with CDH can cause an abnormal acute angulation of the SVC, which during cannulation can result in trauma and possible perforation of the SVC. We present 2 autopsy cases where the infants accidentally died as a result of extracorporeal membrane oxygenation cannulation.

Hepatopulmonary syndrome (HPS) is a triad of liver dysfunction, hypoxemia, and intrapulmonary vascular dilatation. We describe the prevalence and clinical features of HPS at a pediatric liver transplant center. Patients referred to Children's Healthcare of Atlanta/Emory University transplant program from February 1999 to May 2005 were reviewed. Oxygen saturation in room air was screened by percutaneous pulse oximetry. HPS cases were compared with similar age non-HPS recipients (n = 38) to determine differences in clinical characteristics, Pediatric End-Stage Liver Disease (PELD) scores, and posttransplantation survival. Of 211 patients referred and 114 patients transplanted, 7 met criteria for HPS (3.3% and 6.1%, respectively). Patients with HPS had lower PELD score (-0.4 +/- 5.9 vs. 11 +/- 11; P = 0.01) and total bilirubin (1.7 +/- 1.1 vs. 11.2 +/- 10.1; P = 0.02) at the time of transplantation. Four of 7 patients with HPS had polysplenia/interrupted inferior vena cava (PS/IVC) compared with 0 of 38 age-matched controls (P = 0.0002). Three patients with HPS did not have cirrhosis; 2 of these 3 had PS/IVC. All HPS cases normalized room air oxygen saturation by 6 months, and survival after transplantation in HPS cases was 100%. Marked hepatic synthetic or biochemical dysfunction may not be present, and cirrhosis is not a requirement for the development of HPS in children. HPS in children is frequently associated with PS/IVC. Histologic evidence of abnormal intrahepatic portal vein flow and the demonstration of portosystemic communications at any level should be sought in children presenting with unexplained intrapulmonary vascular dilatation. Liver transplantation for HPS in childhood may be appropriate even in the absence of cirrhosis.

BACKGROUND: Bilateral microtia with aural atresia is rare. Rhabdomyomatous hamartomata containing salivary tissue, situated bilaterally and symmetrically simulating the palatine (faucial) tonsils, has apparently not been reported. We present the combination of these findings in two unrelated patients. CASES: In the first case, the patient was exposed prenatally to 13-cis-retinoic acid (isotretinoin) and has typical features of this exposure, including bilateral microtia with aural atresia and bilateral 7th nerve palsies. Due to symptoms of obstructive sleep apnea, patient 1 had a “tonsillectomy” and adenoidectomy. Histopathologic studies demonstrated rhabdomyomatous hamartomata containing salivary and striated muscle tissue in place of the palatine tonsils. In the second case, the patient had been prenatally exposed to alcohol, cocaine, and marijuana. He has been noted to have developmental delay and behavioral issues in addition to bilateral microtia with aural atresia. “Tonsillectomy” and adenoidectomy were performed to alleviate chronic upper respiratory infections and snoring. Again, histopathologic studies of the tissue submitted as “tonsil” demonstrated rhabdomyomatous hamartomata containing salivary and muscle tissue. Although an extended banded karyotype and subtelomere panel were normal, a genetic etiology for the second patient's features cannot be excluded. CONCLUSIONS: We hypothesize that the findings of bilateral microtia with aural atresia and rhabdomyomatous hamartomata containing salivary and muscle tissue in the area of the palatine tonsils may represent a newly recognized association, which may have a teratogenic and/or genetic etiology. Birth Defects Research (Part A), 2007. © 2006 Wiley-Liss, Inc.

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.

1but the biological basis for this link is unknown. We report two cases of Langerhans-cell histiocytosis arising in the context of precursor T-lymphoblastic leukaemia/lymphoma. The Langerhans-cell histiocytosis cells and the precursor T-lymphoblastic leukaemia/lymphoma cells had identical rearrangements of the gene for T-cell receptor � , confirming a clonal relation between the two neoplastic diseases. In April, 1996, a 5-year-old boy presented with a mediastinal mass and a white-cell count of 2·9� 10 9 /L. Bone-marrow aspiration showed precursor T-cell acute lymphoblastic leukaemia; cerebrospinal fluid was negative. He had a complete response to the BerlinFrankfurt-Munster middle-risk schedule. However, from August, 1998, to October, 1998, he developed multiple penile lesions and a biopsy sample showed Langerhans-cell histiocytosis. Between 1998 and 2002 he received several chemotherapeutic regimens and radiotherapy (total dose 44·8 Gy), without a sustained complete response. Regimens included: etoposide and prednisolone; combinations of topical chlormethine, indometacin, betamethasone-depot, vinblastine, thalidomide, etanercept, and intralesional methylprednisolone; mercaptopurine, vinblastine, and 500 mg/m 2 metho

We present a case of an infant with Down syndrome (trisomy 21) who was affected by alveolar capillary dysplasia and other complications including endocardial cushion defect, hypothyroidism, and intrauterine growth restriction. The patient was the product of a third pregnancy to a 33-year-old woman with no significant risk factors. The child lived for 3 months, during which he developed intractable dyspnea, hypoxemia, and cardiac dysfunction and he eventually died from septicemia and multiorgan failure. In addition to the facial phenotypic features and cardiac anomalies, the autopsy revealed the characteristic microscopic pulmonary findings of alveolar capillary dysplasia with misalignment of pulmonary veins. This appears to be the first reported case of this anomaly associated with trisomy 21. In addition to the many reasons for pulmonary hypertension that occur in children with trisomy 21, alveolar capillary dysplasia may have to be included in the differential diagnosis although it appears to be a rare association.

From 1995–2002, 14 patients with predominantly prehepatic, noncirrhotic portal hypertension were evaluated. At presentation, the eight females and six males had a mean age of 9 years (range 2–18). Seven were admitted with gastrointestinal, mostly esophageal bleeding, three with splenomegaly, three with hepato-pulmonary syndrome, and one with hyperammonemia. Imaging studies showed portal vein obstruction in six patients and non-obstructed but frequently anomalous vascular patterns, including hypoplasia of the portal vein, in the remaining eight patients. At the onset, liver function was marginally abnormal in all patients, but thrombocytopenia of approximately 100 × 109/L was consistently observed, probably reflecting chronic mild consumption coagulopathy and hypersplenism. The most striking and frequent histopathologic finding in 25 liver samples, was the presence of hypoplastic portal triads with collapsed portal vein radicles. In contrast, other triads showed markedly distended and misshapen portal vein radicles and likely lymphatics. These two patterns of collapse and distention presumably reflect areas of impaired versus overloaded intrahepatic portal venous flow. Some of the biopsies showed variable portal/sinusoidal fibrosis. Four patients (two with intestinal bleeding, two with hepatopulmonary syndrome) required liver transplants and are doing well. Eight patients are doing well clinically after surgical or spontaneous vascular shunting. Two patients with intestinal bleeding and hepato-pulmonary syndrome, respectively) who had congenital dyskeratosis, underwent bone marrow transplantation and died of nonhepatic-related complications. It is possible to suggest prehepatic causes of portal hypertension even in needle biopsies when collapsed portal vein radicles are present in portal triads, but more than one biopsy sample with larger bore bioptomes may be required to see the changes. Conversely, identifying these changes may suggest to the clinicians the need to work-up a patient for portal hypertension.

Hamartomas of the spleen or splenomas, are uncommon benign tumorous growths in this organ which have not been well characterized in children. We report four patients, 4 to 11 years old, who had splenomegaly and splenic “hamartomas” associated with different hematologic conditions (refractory microcytic anemia, sickle cell anemia, hereditary spherocytosis, and dyserythropoietic hemolytic anemia). All patients had total splenectomy as a primary therapeutic approach or to lessen their transfusion requirements. In only one patient was a focal splenic mass identified preoperatively with contrasted computed tomography (CT) scans and magnetic resonance imaging (MRI). None of the patients showed a mass by ultrasonography. Gross examination showed enlarged spleens (315–724 g) which on cut surface revealed a single nodule in one and multiple bulging nodules in three specimens. The nodules varied from 1.3 to 7 cm and were indistinct from the surrounding nonlymphoid splenic (i.e., red pulp) parenchyma. Histology of the nodules showed red splenic pulp with variable histiocytic proliferation, focal extramedullary hematopoiesis, lympho-plasmacytosis, fibrosis, and siderotic-calcific deposits. Intranodular small T- and B-cell lymphoid aggregates but no organized secondary follicles or periarteriolar sheaths were seen. Proliferation antigen Ki-67 (Mib-1) immunostains showed a low (< 5%) proliferation index in the nodules and surrounding tissue. Reticulin stains did not show a capsule or border between the normal spleen and the nodules. The critical histologic differential diagnosis for these lesions is with benign vascular tumors. These can be identified by their more disorderly pattern, by immunohistochemistry and by their higher proliferation index. It is our contention that these splenic nodules are not true hamartomas, as they seem to result from remote ischemic or infectious/ inflammatory insults, leading to the fibro-inflammatory reaction and deposition of calcium and hemosiderin that is better designated with the descriptive term of splenoma. Review of the literature and our own experience indicates that most children with splenic hamartomas or splenomas as we prefer to call them, have an underlying hematologic disorder likely made worse by a state of hypersplenism that explains the consistent improvement in the blood values after splenectomy.

Esophageal leiomyomas are rare in the pediatric population. They frequently occur in association with other anomalies, such as Alport's syndrome, osteoarthropathy, and leiomyomas elsewhere in the body. The authors describe the case of a focal esophageal leiomyoma in a 12-month-old girl with a history of long-gap esophageal atresia. The patient initially underwent bouginage of the proximal pouch while awaiting definitive repair. After esophageal repair, the patient required multiple dilatations for anastomotic strictures. A segmental resection of the esophagus was performed because of recurrent strictures. A leiomyoma, arising from the site of the previous esophageal atresia repair, was noted on histologic evaluation. Esophageal leiomyomas have not been reported previously in a child with esophageal atresia. J Pediatr Surg 36:1832-1833. Copyright © 2001 by W.B. Saunders Company.

Objective: The purpose of this study was to assess presumptive sexually transmitted disease treatment on pregnancy outcome and HIV transmission. Study Design: In a randomized trial in Rakai District, Uganda, 2070 pregnant women received presumptive sexually transmitted disease treatment 1 time during pregnancy at varying gestations, and 1963 control mothers received iron/folate and referral for syphilis. Maternal-infant sexually transmitted disease/HIV and infant outcomes were assessed. Intent-to-treat analyses estimated adjusted rate ratios and 95% confidence intervals. Results: Sexually transmitted diseases were reduced: Trichomonas vaginalis (rate ratio, 0.28; 95% CI, 0.18%-0.49%), bacterial vaginosis (rate ratio, 0.78; 95% CI, 0.69-0.87), Neisseria gonorrhoeae / Chlamydia trachomatis (rate ratio, 0.43; 95% CI, 0.27-0.68), and infant ophthalmia (rate ratio, 0.37; 95% CI, 0.20-0.70). There were reduced rates of neonatal death (rate ratio, 0.83; 95% CI, 0.71-0.97), low birth weight (rate ratio, 0.68; 95% CI, 0.53-0.86), and preterm delivery (rate ratio, 0.77; 95% CI, 0.56-1.05); but there were no effects on maternal HIV acquisition or perinatal HIV transmission. Conclusion: Reductions of maternal sexually transmitted disease improved pregnancy outcome but not maternal HIV acquisition or perinatal HIV transmission. (Am J Obstet Gynecol 2001;185:1209-17.)

Figure. A, Coronal images of noncontrast computed tomography of the brain showing extensive pneumocephalus (white arrows) involving the brain parenchyma, the extra-axial subarachnoid space, and the intracranial vessels, primarily the cortical venous structures and superior sagittal dural sinus.B, Placental histology (hematoxylin and eosin staining) showing severe chorioamnionitis, as evidenced by massive neutrophil infiltration and umbilical vessel thrombosis (white arrow).

The pathologic findings from biopsy or autopsy material in four patients, who were vaccinated with bacillus Calmette-Guerin (BCG) at birth in Chile, are presented. Two patients had severe combined immunodeficiency, and two had more restricted cellular (T-cell) immunodeficiency with no evidence of human immunodeficiency virus infection. The patients had distinct skin nodules and nodular lesions in systemic organs and bone marrow. Three patients had regional BCG lymphadenitis. One patient with severe combined immunodeficiency, however, had disseminated BCG without any local reaction. In all cases BCG strains of Mycobacterium were identified in a reference mycobacteriology laboratory. The histologic lesions in most patients usually consisted of diffuse histiocytic infiltrates with poorly formed granulomas and variable or no necrosis. Histiocytes were plump and engorged with numerous acid-fast bacilli (AFB). In some areas the massive histiocytosis resembled a spindle cell neoplasm. Other histologic findings supported the underlying immunodeficiency. The pattern of histiocytic response and degree of microbial killing depend on the host's immunocompetence. In the later stages of disease or in severe immunodeficiency, there is a lack of granuloma formation and unimpeded proliferation of AFB. These findings are reminiscent of nontuberculous mycobacterial infections in AIDS patients. Bacillus Calmette-Guerin dissemination has to be considered in immunocompromised individuals when the patient comes from other countries in which such vaccinations are practiced.

Disseminated intravascular coagulation (DIC) and other clotting abnormalities are common in sick newborn infants who have a variety of conditions. To document evidence of DIC at autopsy, immunoperoxidase staining of fibrin-related antigens (FRA) was used to detect intravascular microthrombi in liver, kidney, and lung from 127 newborns. Patients were selected from seven major disease groups: hyaline membrane disease/bronchopulmonary dysplasia, infection, meconium aspiration, necrotizing enterocolitis, congenital heart disease, other congenital anomalies, and extreme prematurity. Staining for FRA in intravascular microthrombi was seen in 40% of cases studied. The liver showed the highest frequency of intravascular microthrombi, located predominantly in the sinusoids. Unlike the adult kidney, the newborn kidney seldom had evidence of intravascular coagulation. Extravascular staining of FRA was observed in the renal distal tubular epithelium in 48 cases, many of which also had evidence of intravascular FRA staining. No significant differences in FRA staining patterns were seen among the disease groups except for cases of extreme prematurity in which all tissues showed minimal staining. Control tissues from SIDS patients also showed minimal FRA staining. Hepatic sinusoidal staining was the only tissue finding that correlated with thrombocytopenia, a clinical indicator of DIC. Despite the use of this immunohistochemical staining method, discrepancies between the clinical and autopsy diagnosis of DIC remain.