IDH2 Mutation Analysis in Undifferentiated and Poorly Differentiated Sinonasal Carcinomas for Diagnosis and Clinical Management.


  • 影响因子:6.06
  • DOI:10.1097/PAS.0000000000001420
  • 作者列表:"Riobello C","López-Hernández A","Cabal VN","García-Marín R","Suárez-Fernández L","Sánchez-Fernández P","Vivanco B","Blanco V","López F","Franchi A","Llorente JL","Hermsen MA
  • 发表时间:2020-03-01

:A large number of tumor types arise from the mucosa of the sinonasal cavities. Although presenting clinically distinct behavior, due to poorly differentiated histologic features, they can be difficult to classify correctly. Our aim was to investigate whether IDH2 and IDH1 mutations may be specific to a subset of undifferentiated and poorly differentiated sinonasal carcinomas. A total of 125 tumor samples of 7 different histologic subtypes were analyzed for IDH mutations by sequencing and mutant-specific immunohistochemistry, and the results were correlated to clinical and follow-up data. The highest incidence of IDH2 mutations occurred in sinonasal undifferentiated carcinoma, with 11/36 (31%) cases affected. However, also, 1/9 neuroendocrine carcinomas, 2/4 high-grade non-intestinal-type adenocarcinomas, and 1/8 poorly differentiated squamous cell carcinomas carried the IDH2 mutation, whereas 1/48 intestinal-type adenocarcinomas harbored an IDH1 mutation. Immunohistochemical analysis of mutant IDH1/2 produced a number of false-negative results, but also 1 false-positive tumor was found. Disease-specific survival was more favorable in IDH2-mutant versus wild-type cases. Our data suggest that IDH-mutant sinonasal cancers, independent of their histologic subtype, may represent a distinct tumor entity with less aggressive clinical behavior. Clinically, patients with these mutations may benefit from specific IDH-guided therapies.


: 大量肿瘤类型来自鼻腔鼻窦粘膜。虽然呈现临床上不同的行为,但由于分化不良的组织学特征,它们可能难以正确分类。我们的目的是研究IDH2和IDH1突变是否对未分化和低分化鼻腔鼻窦癌的一个亚组具有特异性。通过测序和突变特异性免疫组织化学分析了7种不同组织学亚型的总共125个肿瘤样本的IDH突变,并将结果与临床和随访数据相关联。IDH2突变的最高发生率发生在鼻腔鼻窦未分化癌,11/36 (31%) 例受影响。然而,1/9的神经内分泌癌、2/4的高级别非肠型腺癌和1/8的低分化鳞状细胞癌携带IDH2突变,而1/48的肠型腺癌携带IDH1突变。突变体IDH1/2的免疫组织化学分析产生了许多假阴性结果,但也发现了1个假阳性肿瘤。与野生型病例相比,IDH2-mutant病例的疾病特异性生存期更有利。我们的数据表明,独立于其组织学亚型的IDH突变型鼻腔鼻窦肿瘤可能代表了一种侵袭性较小的临床行为的独特肿瘤实体。临床上,具有这些突变的患者可能受益于特定的IDH指导疗法。



来源期刊:The Laryngoscope
作者列表:["Tyler MA","Mohamed ASR","Smith JB","Aymard JM","Fuller CD","Phan J","Frank SJ","Ferrarotto R","Kupferman ME","Hanna EY","Gunn GB","Su SY"]

METHODS:OBJECTIVE:To evaluate long-term global and site-specific health-related quality of life (HRQoL) in patients treated for sinonasal and nasopharyngeal malignancies. STUDY DESIGN:Cross-sectional. METHODS:One hundred fourteen patients with sinonasal and nasopharyngeal malignancies received surgery, radiation, systemic chemotherapy, or a combination thereof, with curative intent. Validated global ([EuroQol-5D] Visual Analogue Scale [EQ-5D VAS]) and disease-specific instruments (MD Anderson Symptom Inventory-Head and Neck [MDASI-HN], Anterior Skull Base Questionnaire [ASBQ]) were administered to patients who were both free of disease and had completed treatment at least 12 months previously. Associations between instruments, instrument domains, and specific clinical parameters were analyzed. RESULTS:The median age was 55 years. The mean EQ-5D VAS, MDASI-22 composite score, and ASBQ score were 74 (standard deviation [SD] 21), 48 (SD 36), and 130 (SD 27), respectively. The most frequently reported high-severity items in MDASI-HN were dry mouth and difficulty tasting food. The most frequently reported high-severity items in ASBQ were difficulty with smell and nasal secretions. Advanced Tumor (T) classification was associated with worse overall ASBQ sum score (P = 0.02). ASBQ performance at home and MDASI-HN drowsy symptom items independently predicted worse global HRQoL as measured by the EQ-5D VAS (P < 0.001). CONCLUSION:Global HRQoL for survivors of sinonasal and nasopharyngeal malignancies after multimodality treatment approximates that of the U.S. population for the same age group. ASBQ and MDASI-HN correlate well with global HRQoL outcomes as measured by EQ-5D VAS. MDASI-HN and ASBQ elicited unique symptoms, highlighting the complex symptom burden experienced by these patients. Further studies should identify patients predisposed to reduced long-term QOL. LEVEL OF EVIDENCE:3 Laryngoscope, 130:86-93, 2020.

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作者列表:["Todo-Bom A","Braido F","Molinengo G","Loureiro C","Canonica GW","Baiardini I"]

METHODS:BACKGROUND:Allergic rhinitis (AR) and asthma are two common chronic diseases that often coexist. There is a need for a validated tool to evaluate HRQoL of Portuguese speakers with asthma and/or rhinitis patients in clinical practice. OBJECTIVES:To adapt and validate RhinAsthma Patient Perspective (RAPP) in Portuguese. METHODS:The RAPP questionnaire was translated into Portuguese. Asthmatics with comorbidities and rhinitis attending the allergy department of Coimbra University Hospital were asked to complete the Portuguese translation of RAPP, in addition to the SF-12, ACT, and a Symptomatologic VAS twice, with a 4-week interval between visits. During Visit 2, a Global Rating Scale (GRS) was completed to assess any change in health status. Scale dimensions, internal consistency and convergent validity, reliability, discriminant ability and responsiveness to change, as well as Minimal Clinical Difference were assessed. RESULTS:Factor and confirmatory analysis confirm the unidimensional structure of the questionnaire. Internal consistency has been shown to be satisfactory (0.82 visit 1 and 0.86 at visit 2). The tool is able to discriminate between patients on the basis of asthma severity, asthma control level, and rhinitis severity; convergent validity showed a significant correlation with SF-2 Physical component (r=-0.46 and 0.42, p at Visits 1 and 2). An ICC of 0.97 and a CCC=0.94 indicate that the tool is highly reliable. Responsiveness was shown in detecting a significant association with GRS changes (r=0.41, p<0.01) and ACT (r=-0.47, p<0.01) but not with VAS. (r=.14, n.s.). MID value was 2 points. CONCLUSIONS:The Portuguese version of RAPP has been demonstrated to have good measurement properties and sensitivity to health changes, which will provide a valid, reliable and standardized HRQoL measurement in patients with asthma and comorbid allergic rhinitis in clinical practice.

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来源期刊:The Laryngoscope
作者列表:["Goel AN","Lee JT","Wang MB","Suh JD"]

METHODS:OBJECTIVE:To characterize treatment delays in sinonasal cancer managed with surgery and adjuvant radiation and determine the associated impact on survival. STUDY DESIGN:Retrospective cohort study. METHODS:We identified adults in the National Cancer Database treated for sinonasal squamous cell carcinoma with definitive surgery followed by adjuvant radiation from 2004 to 2014. We then examined intervals of diagnosis to surgery (DTS), surgery to radiation (SRT), and radiation duration (RTD). Next, we performed recursive partitioning analysis (RPA) to identify thresholds for these treatment intervals that estimated the greatest differences in survival. We determined the association of treatment delay with overall survival using Cox proportional hazards regression. RESULTS:Among 2,267 patients included, median durations of DTS, SRT, and RTD were 32, 49, and 47 days, respectively. Predictors of treatment delay included care transitions, black race, and Medicare insurance. We identified thresholds of 26, 64, and 51 days for DTS, SRT, and RTD, respectively, as estimating the largest survival differences. Delays in SRT (hazard ratio [HR] 1.20; 95% confidence interval [CI], 1.03-1.40), and RTD (HR, 1.27; 95% CI, 1.10-1.46) beyond these thresholds independently predicted mortality. Delay in DTS beyond the RPA-derived threshold was not significantly associated with mortality after adjusting for other covariates. CONCLUSION:Delays in SRT and RTD intervals are associated with decreased overall survival. Median durations may serve as national benchmarks. Treatment delays could be considered quality indicators for sinonasal cancer treated with surgery and adjuvant radiation. LEVEL OF EVIDENCE:NA Laryngoscope, 130:2-11, 2020.

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