High-grade transformation of head and neck adenoid cystic carcinoma demonstrates distinctive clinicopathological features and an unfavorable prognosis: a matched case-control study of the largest series in China.

PURPOSE: Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications. METHODS: A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes. RESULTS: The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group. CONCLUSION: This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.

Clinicopathological and molecular study of 10 salivary gland clear cell carcinomas, with emphasis on rare cases with high grade transformation and occurring in uncommon sites.

BACKGROUND: As a rare salivary gland malignancy, clear cell carcinoma (CCC) is easily misdiagnosed. This study identified the features that allow better recognition of the clinicopathological and molecular characteristics and the prognosis of CCC, focusing on high-grade transformation (HGT) in this tumor and cases arising in uncommon sites. METHODS: Clinicopathological and follow-up data for 10 CCC samples were retrieved. Immunohistochemical (IHC) staining was performed, and fluorescence in situ hybridization (FISH) was used to detect EWSR1 gene rearrangements, EWSR1-ATF1 gene fusions, and MAML2 gene rearrangements. RESULTS: Histologically, typical CCCs comprised bland polygonal or round cells with clear cytoplasm. In contrast with typical CCCs, HGT tumor cells exhibited nuclear pleomorphism, high nuclear-to-cytoplasmic ratios, high mitotic activity, and necrosis. Rare morphologic features such as pseudopapillae, gland-like spaces, and entrapped ducts were also observed. Occasionally, tumors involving the oral cavity might arise from the overlying epithelium of the mucosal surface. Immunohistochemically, all the cases expressed p63, p40, and CK5/6, while myoepithelial-related markers were uniformly negative in all cases. HGT exhibited a wild type p53 expression pattern. FISH demonstrated EWSR1 rearrangement (10/10) and EWSR1-ATF1 fusion (4/5); however, MAML2 remained intact (0/3). CONCLUSIONS: CCCs with HGT or occurring in uncommon sites are extremely rare. Combining morphology based IHC and molecular detection provided reliable evidence that the HGT component represented a transformation of CCC rather than the coexistence of another tumor and helped differentiating CCCs in uncommon sites from their mimics, avoiding potential misdiagnosis and inappropriate therapy. The overall prognosis for CCCs is good, except for the HGT cases, which needed continued treatment.

Dominant cell type analysis predicts head and neck adenoid cystic carcinoma outcomes.

Traditional histological grading for predicting adenoid cystic carcinoma (ACC) outcomes is challenging and unreliable. We explored the relationship between dominant cell type (DCT) and outcomes for ACC of the head and neck to develop a new approach to predicting prognosis. Clinicopathological data were obtained from a retrospective cohort of 167 patients with primary ACC of the head and neck. Using immunohistochemistry markers to determine DCT, tumors were subclassified into three distinct subtypes, epithelial-predominant (E-ACC), myoepithelial-predominant (M-ACC), and conventional (C-ACC). Differences in clinicopathological parameters and clinical outcomes among these subtypes were then analyzed. Compared to that of M-ACC and C-ACC, E-ACC exhibited more aggressive clinicopathological features with predominantly solid components, high-grade transformation, lymphovascular invasion, tumor necrosis (TN), Ki-67 ≥ 30%, and advanced stage of disease. Both E-ACC and M-ACC could present as solid morphological forms, but E-ACC had a significantly worse prognosis than M-ACC. DCT, TN, and disease stage were independent predictors of recurrence-free survival. DCT, TN, age ≥ 50 years, and disease stage were independent predictors for overall survival. In conclusion, DCT was an independent prognostic indicator for both recurrence-free and overall survival for ACC. Our results provide a new approach to predicting prognosis in ACC and a strong pathological basis for clinically optimizing treatment.

Identification of Carotid Artery Microstructure and Plaque Rupture Using C-Arm Cone-Beam CT: A Case Report.

C-arm cone-beam computed tomography (CBCT) offers a high imaging resolution with a wide range of contrast to visualize vessels, soft tissue, and bone. We report the usefulness of CBCT in observing neovascularization, microcalcification, and plaque rupture. A 56-year-old man presented with vertigo and complain of an unsteady gait for 5 months. Catheter angiography demonstrated right severe carotid stenosis with irregular filling defect, which on high-resolution MRI showed vessel wall enhancement. The CBCT showed high density structures and linear contrast enhancement from the vascular lumen to the plaque, related to microstructure and plaque rupture. Carotid endarterectomy was performed, and histopathology confirmed that the high-density areas represented neovascularization and microcalcification, with linear enhancement representing plaque rupture. This is the first report showing that microcalcifications and plaque rupture can be identified by CBCT. Thus, CBCT can be used as a promising supplement to current imaging modalities to evaluate plaque components more accurately.

RNF8 induces autophagy and reduces inflammation by promoting AKT degradation via ubiquitination in ulcerative colitis mice.

RING finger protein 8 (RNF8) is an E3 ligase that is pivotal for DNA repair. However, the role of RNF8 in ulcerative colitis (UC) remains unclear. The aim of this study is to investigate the effect and the mechanism of RNF8 on UC model induced by trinitrobenzene sulfonic acid (TNBS) in mice. Lentiviruses overexpressing RNF8 were injected into mice after the induction of UC. The histopathological changes in colon tissues were assessed by haematoxylin and eosin staining. The mRNA level of RNF8 was detected by real-time quantitative polymerase chain reaction. The protein levels of RNF8, autophagy-related proteins (LC3 and P62) and AKT/mammalian target of rapamycin (mTOR) signalling-related proteins were measured by Western blot. The pro-inflammatory cytokines (tumour necrosis factor-α and interleukin-1ß) were examined by immunohistochemical analysis. Immunoprecipitation was performed to analyse the interaction between RNF8 and AKT1. The TNBS-induced UC mice exhibited colonic damage and inflammation, accompanied by decreased RNF8 expression, impaired autophagy and increased phosphorylation levels of AKT and mTOR in the colon. However, these alterations were reversed by RNF8 overexpression. Furthermore, RNF8 bound to AKT1 and mediated its ubiquitination. Collectively, RNF8 overexpression protects against TNBS-induced UC, which might be due to its enhancement of autophagy by suppressing the AKT/mTOR signalling via AKT1 ubiquitination.