No abstract

No abstract

No abstract

Eosinophilic/T-cell chorionic vasculitis (ETCV) is an idiopathic placental lesion characterized by chorionic vasculitis composed predominantly of eosinophils and CD3+ T lymphocytes. It usually presents as a unifocal lesion, but a subset have multifocal involvement. We report 4 Di-Di and 2 Di-Mo twins sharing fused placental discs with discordant circulatory involvement by multifocal ETCV. The findings are difficult to explain by sampling alone. The limitation of ETCV to 1 fetus's vascular territory in monozygotic twin pregnancies is difficult to explain but could provide insights into the fetal immune system and the etiology of ETCV.

Neuroblastoma is the most common cancer in infants younger than 12 months of age, occurring with an incidence of 1 in 100,000 children. The clinical outcome of neuroblastoma ranges from spontaneous regression to treatment-resistant progression and/or metastasis, and accounts for 8–10% of childhood cancer deaths. Segmental chromosomal aberrations, as well as <i>MYCN</i> and <i>ALK</i> amplification, are among factors contributing to an unfavorable genomic profile and high-risk disease classification. Here, we describe a 5-year-old male who presented with a large right renal neuroblastoma tumor having lung and liver metastases. Fluorescence in situ hybridization analysis indicated the presence of &#x3e;20 copies of the 5′ region of the <i>ALK</i> gene in 26% of cells examined. Subsequent copy number assessment did not confirm <i>ALK</i> amplification, but revealed a gain of exons 2–5 of <i>ALK</i>, consistent with increased copy number for the 5′ region of the <i>ALK</i> gene. Subsequent array analysis showed the presence of other unfavorable prognostic genomic features, including segmental gain of the 17q region and amplification of the long arm of chromosome 12 harboring <i>CDK4</i> and <i>MDM2,</i> both reported to be poor prognostic indicators in patients with atypical clinical features in neuroblastoma. Taken together, this report illustrates the importance of careful interpretation of aberrant FISH findings and subsequent use of orthogonal methods to clarify the presence of genomic alterations to successfully determine potential treatment targets.

We report varicella-zoster virus (VZV) gastritis in a 70-year-old woman postchemotherapy for lymphoma, presenting with abdominal pain, vomiting, and delirium without rash. A gastric biopsy demonstrated viral inclusions but posed a diagnostic challenge as immunohistochemistry for cytomegalovirus and herpes simplex virus were negative, and VZV immunohistochemistry was not available. The patient developed a vesicular rash 7 days after her symptoms began. Molecular testing of the gastric biopsy and a skin swab both confirmed VZV infection. She also had probable involvement of her liver and pancreas based on imaging and serum chemistry, and possible central nervous system involvement. She recovered with appropriate antiviral therapy but later developed a postherpetic neuralgia, and chronic intrahepatic biliary strictures; liver biopsy demonstrated a cholangiopathy of uncertain etiology. A literature review of the pathogenesis, epidemiology and sequelae of VZV infection is included.

35RNA sequencing is emerging as a powerful technique to detect a diverse array of fusions in 36 human neoplasia, but few clinically validated assays have been described to date. We designed 37 and validated a hybrid-capture RNAseq assay for FFPE tissue (Fusion-STAMP). It fully targets 38 the transcript isoforms of 43 genes selected for their known impact as actionable targets of 39 existing and emerging anti-cancer therapies (especially in lung adenocarcinomas), prognostic 40 features, and/or utility as diagnostic cancer biomarkers (especially in sarcomas). 57 fusion results 41 across 34 samples were evaluated. Fusion-STAMP demonstrated high overall accuracy with 98% 42 sensitivity and 94% specificity for fusion detection. There was high intra-and inter-run 43 reproducibility. Detection was sensitive to approximately 10% tumor, though this is expected to 44 be impacted by fusion transcript expression levels, hybrid capture efficiency, and RNA quality. 45Challenges of clinically validating RNA sequencing for fusion detection include a low average 46 RNA quality in FFPE specimens, and variable RNA total content and expression profile per cell. 47These challenges contribute to highly variable on-target rates, total read pairs, and total mapped 48 read pairs. False positive results may be caused by intergenic splicing, barcode hopping / index 49 hopping, or misalignment. Despite this, Fusion-STAMP demonstrates high overall performance 50 metrics for qualitative fusion detection and is expected to provide clinical utility in identifying 51 actionable fusions. 52 54 55 56 57 Introduction: 58In human neoplasia, numerous clinically relevant translocations have been described, and 59 more continue to be identified. Many are specific to one or several diagnoses, especially among 60 soft tissue neoplasms.In conjunction with clinical history and 61 histomorphologic/immunohistochemical findings, the detection of one of these translocations is a 62 valuable diagnostic adjunct 1 . For example, in the setting of a small round blue cell tumor, 63 translocation testing can help distinguish among differential diagnoses that include Ewing 64 sarcoma, Ewing-like sarcomas, desmoplastic small round cell tumor, alveolar 65 rhabdomyosarcoma, and synovial sarcoma, all of which are associated with distinct 66 translocations or sets of translocations. 67Other translocations may guide therapeutic decision making to optimally utilize targeted 68 therapies, particularly in the setting of non-small cell lung carcinoma (NSCLC) 2 . For example, 69 ALK, ROS1, and RET rearrangements are standard-of-care biomarkers predictive of a response 70 to an FDA-approved medication in the setting of NSCLC. In addition, evidence is accumulating 71for clinical actionability of many other structural rearrangements in NSCLC and other tumors 3-5 . 72Numerous techniques have been employed to detect fusions 3 . Traditional methods that do 73 not employ next generation sequencing (NGS) include karyotyping, reverse transcriptase 74 polymerase chain reaction (RT-PCR), ...

Two primary patterns of placental calcification have been described, each with distinctive pathophysiology and clinical relevance. We report a novel pattern of diffuse subamniotic calcification. It occurred in a 25-week placenta involved by recurrent chronic histiocytic intervillositis (CHI) associated with severe intrauterine growth restriction (IUGR) and intrauterine fetal demise (IUFD). This was the mother’s third stillbirth related to CHI, despite treatment with intravenous immunoglobulin (IVIG), prednisone, low-molecular-weight heparin, and acetylsalicylic acid (ASA). On placental examination, the majority of the fetal surface was calcified. This variably formed a continuous band or dispersed calcium microparticles. Electron microscopy demonstrated associated electron dense deposits highly suggestive of immune complex deposition. CHI explains recurrent IUGR and stillbirth, but has not been associated with calcification or immune complex deposition. We hypothesize IVIG therapy may have caused immune complex deposition and subsequent dystrophic calcification, supported by its rare association with immune complex deposition disorders in the kidney. Identification of additional cases with this pattern of calcification, with additional studies on fresh tissue including immunofluorescence, electron microscopy and mass spectrometry, may aid in elucidating the underlying pathophysiology and clinical significance of this unusual lesion.