Persistence of parenchymal and perivascular T-cells in treatment-refractory anti-N-methyl-D-aspartate receptor encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease mediated by IgG1 or IgG3 antibodies to the GluN1 subunit of the NMDAR, resulting in downregulation of NMDARs. Early diagnosis, prompt reduction of anti-NMDAR antibodies, and removal of associated ovarian tumors when identified are important drivers of prognosis. Immunohistochemical studies were carried out to evaluate B cell, plasma cell, and T-cell infiltrates in the brain of a 3-year-old patient with anti-NMDAR encephalitis who failed to show improvement after plasma exchange and Rituximab treatment. Complement activation was evaluated by C4d staining. Plasma cells and B-cells were rarely detected in the brain. In contrast, persistent intraparenchymal infiltrates and perivascular CD3+ T cells and evidence of complement activation were detected. Activated microglia and microglial nodules were also detected in the frontal lobes and the basal ganglia. The role of T cells and complement activation should be investigated in patients who do not respond to plasma exchange and Rituximab treatment.

Placental pathology is associated with severity of neonatal encephalopathy and adverse developmental outcomes following hypothermia.

OBJECTIVE: Although neonatal encephalopathy (NE) due to perinatal asphyxia accounts for a notable proportion of brain injury, the causal pathway remains largely unexplained. We sought to determine the association of placental pathology with: (1) severity of NE in the first 6 hours postnatal, and (2) abnormal neurodevelopmental outcomes (NDO) in neonates requiring hypothermia therapy. STUDY DESIGN: This is a retrospective cohort study of neonates ≥36 weeks' gestation born at Parkland Hospital, Dallas, TX, from January 2006 through November 2011 with NE. Placental histology was reviewed and validated by a pediatric pathologist blinded to outcomes. Abnormal NDO was defined as death or Bayley-III score of <85 at 18-24 months of age. RESULTS: Of 86,274 neonates ≥36 weeks' gestation, 120 had evidence of a combination of perinatal acidosis and NE. In all, 47 had mild NE and received no treatment, while 73 had moderate (n = 70) or severe (n = 3) NE and received systemic hypothermia. Nine neonates died and all survivors receiving hypothermia had a Bayley-III assessment at 22 ± 7 (SD) months of age. Chorioamnionitis with or without fetal response and patchy/diffuse chronic villitis were found to be independently associated with severity of NE (P < .001). Univariate logistic regression revealed an association with a diagnosis of major placental pathology (odds ratio, 3.5; 95% confidence interval, 1.1-11.4) and abnormal outcomes following cooling. Specifically, diffuse chronic villitis (odds ratio, 9.29; 95% confidence interval, 1.11-77.73) was the only individual predictor of abnormal NDO following hypothermia therapy. CONCLUSION: Placental inflammatory villitis appears to be a harbinger of abnormal outcomes in neonates with NE, spanning to the 18-24 month NDO.

Intraventricular rituximab and systemic chemotherapy for treatment of central nervous system post-transplant lymphoproliferative disorder after kidney transplantation.

PTLD of the CNS is a rare complication of solid organ transplantation, and there are only case reports/series available in the literature. Current literature suggests that CNS PTLD carries a worse prognosis than PTLD outside the CNS, and most are of B-cell lineage, predominantly monomorphic, and are associated with EBV infection. Because this disorder is so rare, there is no standard chemotherapy for pediatric patients with CNS PTLD and reported therapies for EBV-associated CNS PTLD are heterogeneous with mixed results. Since outcomes of CNS PTLD are historically poor, we attempted to develop a novel therapeutic treatment regimen. Based on a review of the literature and with the help of a multidisciplinary team, we created a regimen of chemotherapy that included dexamethasone and high-dose methotrexate in addition to intravenous and intraventricular Rituximab in two pediatric patients. The intraventricular chemotherapy succeeded in shrinking the tumor in both of our patients; however, as shown in the second case, the clinical outcome depends on the location of the tumor. Systemic and intraventricular therapies hold promise in the management of EBV-associated CNS PTLD; however the rarity of this entity prevents the development of well-designed studies necessary for the establishment of an evidence-based treatment standard.

Sclerosing lobular hyperplasia of breast: cytomorphologic and histomorphologic features: a case report.

BACKGROUND: Mammary sclerosing lobular hyperplasia is an uncommon benign lesion of adolescent and young women. Fine-needle aspiration cytology of mammary sclerosing lobular hyperplasia is said to show characteristic features that include an absence of stromal fragments. CASE PRESENTATION: In this article, we describe a case of sclerosing lobular hyperplasia that occurred in the right breast of a 12-year-old girl. Fine-needle aspiration cytology showed some fibroadenoma-like features including the presence of stromal fragments, while branched tubular fragments were not seen. The diagnosis of sclerosing lobular hyperplasia was made on histologic examination that showed preserved acinar architecture with lobular hyperplasia and sclerosis of intralobular and interlobular stroma. CONCLUSION: Fine-needle aspiration cytology features of mammary sclerosing lobular hyperplasia are not diagnostic and overlap with those of fibroadenoma; however, a distinction between the two benign entities is of no clinical significance. The definitive diagnosis of sclerosing lobular hyperplasia requires histopathologic evaluation.