Yolk sac tumor of the ovary in a young girl with tuberous sclerosis: A case report and review of the literature.

•We reported the first tuberous sclerosis patient with an ovarian yolk sac tumor.•Although angiomyolipoma is a common benign tumor in TS patients, abdominal malignancies must be considered.

Eculizumab induces long-term remission in recurrent post-transplant HUS associated with C3 gene mutation.

A 15-year-old male patient developed atypical hemolytic uremic syndrome (aHUS) at 16 months of age leading to end-stage renal disease. The family history was suggestive of autosomal dominant aHUS, and he was more recently found to have a C3 heterozygous gene mutation (1835C>T mutation in exon 14, which determines the amino-acidic substitution R570W) with no other complement abnormalities. He had two renal transplants, the first at 2.5 years, and the second at 8 years of age, but allograft dysfunction developed in both transplants leading to graft failure due to recurrent HUS at 5 years and 18 months post-transplantation respectively. At 15 years of age he received a third transplant from a deceased donor with pre-emptive plasmapheresis. He had immediate graft function and nadir serum creatinine was 1.3-1.4 mg/dl. Severe allograft dysfunction and hypertension developed 2 months after transplantation following influenza infection. Renal allograft biopsy showed thrombotic microangiopathy. He received plasmapheresis followed by eculizumab therapy. Allograft function returned to baseline 3 weeks after starting therapy, and post-treatment allograft biopsies showed improvement in thrombotic microangiopathy. He continues to receive eculizumab every 2 weeks with stable graft function 13 months after transplantation.

Distinguishing undifferentiated embryonal sarcoma of the liver from biliary tract rhabdomyosarcoma: a Children's Oncology Group study.

Morphologically, the distinction between undifferentiated embryonal sarcoma of the liver (UESL) and biliary tract rhabdomyosarcoma (RMS) can be uncertain because of some shared pathologic similarities. Patients with UESL have been consistently but erroneously enrolled in Children's Oncology Group (COG) treatment protocols because UESL was equated with RMS, despite the differing primary treatment modalities of these entities. Review of COG pathology files yielded 20 cases of UESL that were compared to 25 cases of biliary tract RMS. Clinicopathologic features including immunohistochemical staining were examined. In the UESL cases, the male:female ratio was 1:1 and the median age was 10.5 years. Histologically, hyaline globules and diffuse anaplasia were consistently present. The cases of RMS had a male:female ratio of 1.8:1 with a median age of 3.4 years and routinely lacked diffuse anaplasia and hyaline globules. Polyclonal desmin and muscle-specific actin were variably immunoreactive in UESL and RMS; however, myogenin and myogenic regulatory protein D1 (MyoD1) were uniformly negative in UESL and routinely positive in the majority of biliary tract RMS. Myogenin, in particular, was highly significant (P = 0.0003) in distinguishing RMS from UESL. With a median follow-up of 8 months, 11 of 18 patients with UESL were still alive. The estimated 5-year survival for biliary tract RMS was 66%. Establishing the correct diagnosis of these distinct clinical and pathologic entities is important, as surgery alone may be curative in UESL, whereas initial chemotherapy is often recommended for the treatment of biliary tract RMS.

Fatal cephalosporin-induced acute hypersensitivity myocarditis.

A frequently fatal, although rare, side effect of cephalosporin antibiotics is noninfectious myocarditis. We report two cases of hypersensitivity myocarditis secondary to administration of cephalosporin antibiotics. In both cases, acute hypersensitivity myocarditis was not suspected clinically, and the diagnosis was made postmortem. Histology revealed intense eosinophilic infiltration of the endomyocardium with eosinophil degranulation and myocyte damage, Clinically, death in both cases was due to cardiac failure. When suspected early, appropriate management may be lifesaving.

Maternal use of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), and muscular ventricular septal defects.

BACKGROUND: Muscular ventricular septal defects (mVSDs) are the most common congenital heart defects. Previous studies have suggested maternal use of acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), and/or fever as risk factors. We evaluated the association between mVSDs and maternal use of acetaminophen or NSAIDs adjusting for fever. METHODS: Infants with nonsyndromic mVSDs (cases) and without birth defects (controls), with gestational age > or =37 weeks and their mothers were enrolled in the National Birth Defects Prevention Study. Two exposure periods were defined: the first trimester of pregnancy, and one month before pregnancy through delivery. Mothers reporting fever or medication use at least once during either period were considered exposed. Adjusted odds ratios and 95% confidence intervals were estimated independently for each exposure period. RESULTS: The analysis included 168 cases and 692 controls. Two case groups were evaluated: all mVSD infants (n = 168) (including those with associated minor cardiac defects or noncardiac defects), and infants with isolated mVSDs (n = 133). Mothers of cases were less likely to be African-American than Caucasian (OR, 0.36; 95% CI, 0.18, 0.73). Approximately equal numbers of case mothers and control mothers (10.4 versus 9.7%, respectively) reported at least one febrile episode during the first trimester. Neither acetaminophen nor NSAID exposure was significantly associated with mVSDs. This was true for both case groups and both exposure periods. CONCLUSIONS: Significant associations were not detected between the occurrence of mVSDs and maternal use of NSAIDs or acetaminophen adjusting for maternal fever, nor were they detected between maternal fever and mVSDs.

Incidence of autopsy findings in unexpected deaths of children and adolescents.

Studies in various settings reveal that a significant percentage of autopsies demonstrate findings that were not previously clinically diagnosed. In the pediatric and adolescent age group, forensic examinations comprise a large percentage of total autopsies performed. We hypothesized that a similar number of previously undiagnosed findings would be present in this population and thus reviewed a series of autopsy reports from the Medical Examiners Office in the Arkansas Crime Laboratory. During 1997 through 1999, we performed 439 complete forensic autopsies on children and adolescents (age range 1 day to 19 years; median 18 months). Previously undiagnosed lesions were found in 173 (39%). Of these subjects, 68 (39%) had clinically significant pathology, 60 (35%) had insignificant pathology, and 45 (26%) had pathology of undetermined significance. Thirty-six subjects had lesions expected from a previously diagnosed condition. Of the total number of lesions found, 168 were inflammatory, 58 were congenital anomalies (48 unexpected), and 88 comprised miscellaneous other conditions. Infants <6 months of age were significantly more likely to have a previously undiagnosed lesson than children > 6 months (P <0.0001). Previously undiagnosed findings, mostly inflammatory, occur relatively frequently in pediatric and adolescent forensic autopsies and are more likely to occur in infants.

Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns.

Clinically responsive placental examination seeks to provide useful information regarding the etiology, prognosis, and recurrence risk of pregnancy disorders. The purpose of this study was to assemble and validate a complete set of the placental reaction patterns seen with amniotic fluid infection in the hope that this might provide a standardized diagnostic framework useful for practicing pathologists. Study cases (14 with amniotic fluid infection, 6 controls) were reviewed blindly by six pathologists after agreement on a standard set of diagnostic criteria. After analysis of initial results, criteria were refined and a second, overlapping set of cases were reviewed. Majority vote served as the gold standard. Grading and staging of maternal and fetal inflammatory responses was found to be more reproducible using a two- versus three-tiered grading system than a three- versus five-tiered staging system (overall agreement 81% vs. 71%). Sensitivity, specificity, and efficiency for individual observations ranged from 67-100% (24/30 > 90%). Reproducibility was measured by unweighted kappa values and interpreted as follows: < 0.2, poor; 0.2-0.6, fair/moderate; > 0.6, substantial. Kappa values for the 12 lesions evaluated in 20 cases by the six pathologists were: acute chorioamnionitis/maternal inflammatory response (any, 0.93; severe 0.76; advanced stage, 0.49); chronic (subacute) chorioamnionitis (0.25); acute chorioamnionitis/fetal inflammatory response (any, 0.90; severe, 0.55; advanced stage, 0.52); chorionic vessel thrombi (0.37); peripheral funisitis (0.84); acute villitis (0.90); acute intervillositis/intervillous abscesses (0.65), and decidual plasma cells (0.30). Adoption of this clearly defined, clinically relevant, and pathologically reproducible terminology could enhance clinicopathologic correlation and provide a framework for future clinical research.