No abstract

Glomus tumors (GT) have been classified among tumors of perivascular smooth muscle differentiation, together with myopericytoma, myofibroma/tosis, and angioleiomyoma, based on their morphologic overlap. However, no molecular studies have been carried out to date to investigate their genetic phenotype and to confirm their shared pathogenesis. RNA sequencing was performed in three index cases (GT1, malignant GT; GT2, benign GT and M1, multifocal myopericytoma), followed by FusionSeq data analysis, a modular computational tool developed to discover gene fusions from paired-end RNA-seq data. A gene fusion involving MIR143 in band 5q32 was identified in both GTs with either NOTCH2 in 1p13 in GT1 or NOTCH1 in 9q34 in GT2, but none in M1. After being validated by FISH and RT-PCR, these abnormalities were screened on 33 GTs, 6 myopericytomas, 9 myofibroma/toses, 18 angioleiomyomas and in a control group of 5 sino-nasal hemangiopericytomas. Overall NOTCH2 gene rearrangements were identified in 52% of GT, including all malignant cases and one NF1-related GT. No additional cases showed NOTCH1 rearrangement. As NOTCH3 shares similar functions with NOTCH2 in regulating vascular smooth muscle development, the study group was also investigated for abnormalities in this gene by FISH. Indeed, NOTCH3 rearrangements were identified in 9% of GTs, all present in benign soft tissue GT, one case being fused to MIR143. Only 1/18 angioleiomyomas showed NOTCH2 gene rearrangement, while all the myopericytomas and myofibroma/toses were negative. In summary we describe novel NOTCH1-3 rearrangements in benign and malignant, visceral and soft tissue GTs.

The vascular complications of diabetes mellitus impose a huge burden on the management of this disease. The higher incidence of cardiovascular complications and the unfavorable prognosis among diabetic individuals who develop such complications have been correlated to the hyperglycemia-induced oxidative stress and associated endothelial dysfunction. Although antioxidants may be considered as effective therapeutic agents to relieve oxidative stress and protect the endothelium, recent clinical trials involving these agents have shown limited therapeutic efficacy in this regard. In the recent past experimental evidence suggest that endoplasmic reticulum (ER) stress in the endothelial cells might be an important contributor to diabetes-related vascular complications. The current paper contemplates the possibility of the involvement of ER stress in endothelial dysfunction and diabetes-associated vascular complications.

No abstract

The 2017 World Health Organization update introduced a new category of nodal peripheral T-cell lymphoma with T-follicular helper phenotype (PTCL-TFH) defined by expression of at least 2 or 3 TFH markers. Our study assesses the utility of an immunohistochemical panel of 5 TFH markers (CD10, BCL6, PD-1, CXCL13, and ICOS) for identification of TFH phenotype in angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS). Immunohistochemical for the 5 markers was performed on 22 cases of AITL and 29 cases of PTCL-NOS. Cases were reviewed for morphologic features characteristic of AITL. All AITL cases showed expression of ≥2 TFH markers. This panel resulted in reclassification of 41% PTCL-NOS cases to PTCL-TFH. Positive percent agreement for the TFH phenotype is 97% for PD1, 94% for ICOS, 44% for CD10 and CXCL13, and 29% for BCL6. Negative percent agreement for TFH phenotype is 100% for CD10, BCL6, and CXCL13, 82% for ICOS and 71% for PD1. AITL cases were more likely than PTCL-TFH cases to contain expanded CD21-positive follicular dendritic cell meshworks, clear cell cytology and polymorphous inflammatory background; however, there was a significant (P<0.005) Kruskal-Wallis trend in all morphologic variables between the 3 groups suggesting a continuum from PTCL-NOS to PTCL-TFH to AITL. The median number of morphologic features of AITL also correlated significantly with number of TFH markers positive (Spearman coefficient ρ=0.759). In summary, the stain panel chosen will have an impact on cases classified as PTCL-TFH. This entity may exist along a spectrum between PTCL-NOS and AITL.