Analysis For Pre-operation Diagnostic Clues Of Diffuse Sclerosing Variant Of Papillary Thyroid Carcinoma

Diffuse sclerosing variant(DSV)papillary thyroid carcinoma is an uncommon and aggressive subtype of papillary thyroid carcinoma(PTC).The rates of lymph node metastasis,extrathyroidal extension,distant metastasis,recurrence and mortality in DSV are significantly higher than classical PTC.Since the prognosis of DSV is less favorable,this subtype needs to be treated more aggressively.However,DSV still needed to be diagnosed by the histological examination post-operation until now,pre-operation diagnosis of DSV still full of challenges.Understanding the clinical features of DSV and analyze its diagnosis clues will be helpful for the surgeon to assess the illness and make a more comprehensive and appropriate strategy of surgery.Objective 1.Comparing differences between DSV and Non-DSV,and we analyze the clinical features of DSV.2.To increase the diagnostic rates of DSV pre-operation,we establish logistic regression model and explore pre-operation diagnostic clues of DSV.3.To find the specific genetics of DSV,we performed the whole genome sequencing for some of the patients.Materials and methods 1.We searched the cases of DSV and Non-DSV treated in Guangzhou First people’s Hospital between 2012-2017.Cases meet the criteria we made would be included in the further analysis.2.We analyzed the difference of gender and age between DSV and Non-DSV.3.We analyzed differences in symptoms between DSV and Non-DSV 4.We analyzed differences in image between DSV and Non-DSV.5.We analyzed differences in the check of thyroid function and the level of thyroid antibody(TPOAb and Tg Ab).6.We analyzed differences of the result of fine needle aspiration between DSV and Non-DSV.7.We analyzed the difference in the condition of BRAFV600 E mutation between DSV and Non-DSV.8.We established the logistic regression model and explored the pre-operation diagnostic clues of DSV.Then we calculated the accuracy,sensitivity and specificity of the model,and we drew the receiver operating characteristic curve(ROC).9.To explore if there are any specific alterations of genetics of DSV,we performed the Whole Genome Sequencing(WGS)for some of patients with DSV.Results 1.The female rates in DSV group were 76.2%,and it was 78.0% in Non-DSV group.There was no significant difference between two groups(P>0.05).The mean age of DSV group was 28.38±11.1 years(age range:12-55 years),and the mean age of Non-DSV group was 45.07±14.5 years(age range: 10-84 years);patients in the group of DSV is significantly younger than the group of Non-DSV(P<0.05).2.The swelling of the neck was the main symptom in the group of DSV(85.7%),and this rate of were significantly higher than Non-DSV group(42.9%,P<0.05).3.There was a significant difference between DSV and Non-DSV in the comparison of the check of TPOAb and Tg Ab(P<0.05).However,there was no significant difference between DSV and Non-DSV in the comparison of the check of thyroid function(P>0.05).4.The diffusely enlarged thyroid gland,heterogeneous echoic,ill-defined tumor margin,the high longer than the wide and diffuse microcalcification were the main differences of the ultrasonography between DSV and Non-DSV(all p-value <0.05).Additionally,the rate of lymph node metastasis was higher in the group of DSV(DSV: 76.2%,Non-DSV: 31.2%;P<0.05).5.The rate of BRAFV600 E mutation in the group of DSV was lower than Non-DSV(DSV: 37.5%,Non-DSV: 79.2%;P<0.05).6.Establishing the logistic regression model;the diffusely enlarged thyroid gland,heterogeneous echoic,ill-defined tumor margin,and diffuse microcalcification were the pre-operation independent predictive factors of DSV(all p-value <0.05).The accuracy,sensitivity,specificity of the regression model were 99.5%,89.5%,and 99.0%.We drew the ROC,the area under the curve was 0.97,P<0.01,95% confidence interval(0.92,1.00)7.Two patients have performed the test of WGS,and MTND5P3、MUC3A and FAM86B2 mutation were found to be related to tumor genesis.Conclusion There are some differences in the comparison of features of age at presentation,the symptom,ultrasonography and the rates of positive thyroid antibody between DSV and Non-DSV.The diffusely enlarged thyroid gland,heterogeneous echoic,ill-defined tumor margin,and scattered microcalcification are the independent predictive factors of DSV,and they are the important pre-operation diagnostic clues of DSV.We should be vigilant if we encounter patients with these clues above,especially for the young.Understanding the pre-operation diagnostic clues of DSV will contribute to the surgeon to make a more appropriate strategy of surgery.Exploring the specific genetic alteration of DSV will contribute to the precise diagnosis and apprppriate treatment.