Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive TFE3 fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required TFE3 FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods.
Oxidative stress and chronic inflammation play critical roles in the pathogenesis of ulcerative colitis (UC) and inflammatory bowel diseases (IBD). A previous study has demonstrated that dimethyl fumarate (DMF) protects mice from dextran sulfate sodium (DSS)-induced colitis via its potential antioxidant capacity, and by inhibiting the activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. This study aims to clarify the nuclear factor erythroid 2-related factor 2/antioxidant responsive element (Nrf2/ARE) pathway pharmacological activation and anti-inflammatory effect by DMF, through focusing on other crucial antioxidant enzymes and inflammatory mediator, including glutamate-cysteine ligase catalytic subunit (GCLC), glutathione peroxidase (GPX) and cyclooxygenase-2 (COX-2), in a DSS-induced colitis mouse model. The oral administration of DMF attenuated the shortening of colons and alleviated colonic inflammation. Furthermore, the expression of key antioxidant enzymes, including GCLC and GPX, in the colonic tissue were significantly increased by DMF administration. In addition, protein expression of the inflammatory mediator, COX-2, was reduced by DMF administration. Our results suggest that DMF alleviates DSS-induced colonic inflammatory damage, likely via up-regulating GCLC and GPX and down-regulating COX-2 protein expression in colonic tissue.
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