Thyroid Carcinoma With NSD3::NUTM1 Fusion and Secondary TERT Promoter Mutation: A Case Report and Literature Review.

Nuclear protein in testis (NUT) carcinoma is a rare but highly aggressive tumor characterized by translocation of the NUTM1 gene. To date, only about 20 NUT carcinomas arising from the thyroid have been reported in the literature, with the majority showing immunohistochemical markers indicative of squamous differentiation. We present a 29-year-old man with NUT carcinoma arising from thyroid follicular cells. Notably, the tumor cells expressed markers characteristic of thyroid follicular cells such as thyroglobulin, TTF1 and PAX8, without obvious histological and immunohistochemical features of squamous differentiation. Molecular analysis revealed a concurrent TERT promoter mutation (C228T) together with the NSD3::NUTM1 fusion, a combination not previously documented in NUT carcinoma. The tumor highlights the need to include NUT carcinoma in the differential diagnosis of thyroid cancer, especially when it presents with unconventional histopathological features, even in the absence of signs of squamous differentiation.

MYB/MYBL1::QKI fusion-positive diffuse glioma.

The MYB/MYBL1::QKI fusion induces the protooncogene, MYB, and deletes the tumor suppressor gene, QKI. MYB/MYBL1::QKI rearrangement was previously reported only in angiocentric glioma (AG) and diffuse low-grade glioma. This report compares 2 tumors containing the MYB/MYBL1::QKI fusion: a diffuse pediatric-type high-grade glioma (DPedHGG) in an 11-year-old boy and an AG in a 46-year-old woman. We used immunohistochemistry, next-generation sequencing, and methylation profiling to characterize each tumor and compare our findings to the literature on AG and tumors with the MYB/MYBL1::QKI rearrangement. Both tumors were astrocytic with angiocentric patterns. The MYB::QKI fusion-positive DPedHGG, which recurred once, was accompanied by TP53 mutation and amplification of CDK6 and KRAS, suggesting malignant transformation secondary to additional genetic aberrations. The second case was the adult AG with MYBL1::QKI fusion, which mimicked ependymoma based on histopathology and its dot- and ring-like epithelial membrane antigen positivity. Combined with a literature review, our results suggest that MYB/MYBL1 alterations are not limited to low-grade gliomas, including AG. AG is most common in the cerebra of children and adolescents but exceptional cases occur in adults and the acquisition of additional genetic mutations may contribute to high-grade glioma. These cases further demonstrate that molecular characteristics, morphologic features, and clinical context are essential for diagnosis.

Topical application of zwitterionic chitosan suppresses neutrophil-mediated acute skin inflammation.

Zwitterionic chitosan (ZWC), a water-soluble succinylated chitosan derivative, has anti-inflammatory activities with therapeutic effects on sepsis and colitis. However, it remains unknown whether ZWC has any influence on skin inflammation. Here, we investigated the role of ZWC in the tape-stripping-induced acute skin inflammation model. Topical application of ZWC to the wounded area significantly reduced skin lesion compared with PBS controls. Since tape-stripping-induced skin inflammation is mediated by neutrophils, we examined if ZWC has any suppressive effects on neutrophil's function. ZWC treatment downregulated the skin recruitment of neutrophils, subsequently reducing inflammatory responses by keratinocytes. ZWC also suppressed LPS-induced inflammatory responses of neutrophils in vitro, indicating the direct effect of ZWC on neutrophils. Moreover, such anti-inflammatory effects of ZWC extended to other immune cells such as basophils in the spleen. Overall, our results support that ZWC may be used as a therapeutic material to control acute skin inflammation.