Relationship between recurrence and age in the diffuse sclerosing variant of papillary thyroid carcinoma: clinical significance in pediatric patients.

Background: The diffuse sclerosing variant (DSV) is among the aggressive variants of papillary thyroid carcinoma (PTC) and is more prevalent in pediatric patients than in adult patients. Few studies have assessed its characteristics owing to its low incidence. We aimed to evaluate the relationship between recurrence and age in the DSV of PTC. Methods: We retrospectively reviewed patients diagnosed with the DSV or conventional PTC (cPTC) after surgery at a medical center between May 1988 and January 2019. We compared the clinico-pathological characteristics and surgical outcomes of the DSV and cPTC groups and between adult and pediatric patients with DSV. Results: Among the 24,626 patients, 202 had the DSV, and 24,424 were diagnosed with cPTC. The recurrence rate was significantly higher in the DSV group than in the cPTC group. In the DSV group, the recurrence rate was significantly higher in the pediatric patient group than in the adult patient group. Moreover, the association between recurrence and age group showed different patterns between the DSV and cPTC groups with restricted cubic splines (RCS). While both RCS curves showed a U-shaped distribution, the RCS curve tended to be located within the younger age group. Conclusions: This study demonstrated that pediatric patients with DSV are at a greater risk for recurrence compared with adult patients; moreover, the pattern of recurrence risk according to age is different from that of cPTC.

Sonographic characteristics of diffuse sclerosing variant of papillary thyroid carcinoma with histopathological correlation: a preliminary study.

BACKGROUND: Diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) is a rare but high invasive subtype of papillary thyroid carcinoma, which mandates an aggressive clinical strategy. Few studies have focused on the sonographic characteristics of DSVPTC and the role of ultrasound in diagnosis and treatment of this variant remains unknown. This study aimed to identify and understand DSVPTC more accurately under ultrasound in correlation with pathology. METHODS: The ultrasound characteristics and histopathologic sections of 10 lesions in 10 DSVPTC patients who underwent thyroid surgery at our center between 2014 and 2020 were reviewed and compared with 184 lesions in 168 classic variant of papillary thyroid carcinoma (cPTC) patients. RESULTS: 6 DSVPTC cases (60%) showed the "snowstorm" pattern on sonogram and 4 cases (40%) presented hypoechoic solid nodules only. Vague borders (100.0% vs. 18.5%, P = 0.019) and abundant microcalcifications (66.7% vs. 10.9%, P = 0.037) were more common in DSVPTC nodules than in cPTC nodules, corresponding to the infiltrating boundaries and numerous psammoma bodies under the microscope respectively. Most of the DSVPTC cases had a heterogeneous background (80%) and suspicious metastatic cervical lymph nodes (80%) on sonograms. All DSVPTC cases had histopathological metastatic cervical lymph nodes. CONCLUSION: The sonographic "snowstorm" pattern indicated DSVPTC with whole-lobe occupation. Hypoechoic solid nodules with vague borders and abundant microcalcifications on sonogram suggested DSVPTC lesion with an ongoing invasion. Regardless of which of the two sonograms was shown, the corresponding DSVPTC lesions were aggressive and required the same attention from the surgeons.

Construction and validation of a nomogram for predicting cervical lymph node metastasis in diffuse sclerosing variant of papillary thyroid carcinoma.

OBJECTIVE: To analyze the risk factors associated with the occurrence of cervical lymph node metastasis (LNM) in patients with diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) and to establish a nomogram model. METHODS: Clinical data of 199 DSV-PTC patients from SEER database were obtained, and they were randomly divided into training group (n=139) and validation group (n=60). The clinicopathological characteristics were analyzed by logistic regression, including age, marital status, race, gender, tumor size(cm), T stage, M stage, bilaterality, capsular invasion, extrathyroidal extension (ETE), and multifocality. The Validation was carried out using C-index, calibration curves, and Decision Curve Analysis (DCA) in terms of differentiation and calibration of the nomogram model, respectively. RESULTS: Age, tumor size(cm), capsular invasion, and multifocality were independent risk factors for the development of LNM in patients with DSV-PTC (P<0.05). In the training and validation groups, the C-index of internal validation of the nomogram was 0.808 (95%CI: 0.733-0.755) and 0.813 (95% CI: 0.591-0.868), the calibration curves showed that the model was in good agreement, and the decision curve (DCA) indicated that the nomogram model had good clinical utility.  CONCLUSION: Age, tumor size(cm), capsular invasion, and multifocality are independent risk factors for the development of LNM in DSV-PTC. The nomogram model can predict the risk of developing LNM in DSV-PTC patients and provide clinical guidance.

Clinicopathological and Genetic Characteristics of Patients of Different Ages with Diffuse Sclerosing Variant Papillary Thyroid Carcinoma.

Diffuse sclerosing variant papillary thyroid carcinoma (DSVPTC) is commonly observed in young patients, with a median age at diagnosis in the third decade of life. Further, the risk of recurrence is higher for DSVPTC than for classical PTC. Therefore, this study aimed to describe the clinicopathological and genetic characteristics of patients of different ages with DSVPTC. We retrospectively reviewed 397 patients who underwent thyroidectomy for DSVPTC at Gangnam Severance Hospital, Yonsei University, from January 2005 to December 2017. The mean age at diagnosis was 36.7 ± 11.6 years, with most patients (163, 41.1%) aged 31-40 years. DSVPTC was predominant in women (276, 69.5%). We observed recurrence in 46 (11.6%) patients, with regional nodal recurrence being the most common type of recurrence (32 patients, 69.6%). The mean tumour size was larger in younger patients than in older patients. DSVPTC was more aggressive in paediatric patients with a larger-sized tumour, more common multiplicity, and lateral neck metastasis. Through random sampling, we selected 41 patients by age group and examined the mutations in 119 genes using next-generation sequencing. BRAF, KRAS, and TERT displayed relatively higher mutation rates than other genes. DSVPTC displays different clinical, pathological, and molecular profiles than classical PTC. The BRAF, KRAS, and TERT mutations are the most important, with age-specific differences.

Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma Is Related to a Poor Outcome: A Comparison Study Using Propensity Score Matching.

OBJECTIVE: The clinical outcome of diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) remains controversial. We aimed to determine whether DSV-PTC is associated with an increased risk of persistent/recurrent disease. METHODS: We performed a retrospective cohort study of DSV-PTC and classic variant of papillary thyroid carcinoma (CV-PTC) after postoperative radioactive iodine therapy. We used propensity score matching (1:3 matching ratio) to account for differences between the recipients of DSV-PTC and CV-PTC. Univariate and multivariate analyses were performed to assess the independent factors for persistent/recurrent disease. The Kaplan-Meier curve analyses were used to compare disease-free survival (DFS). RESULTS: In total, 35 (12.7%) patients with DSV-PTC and 240 (87.3%) patients with CV-PTC were included. After propensity score matching, 35 pairs of patients were selected (DSV-PTC, n = 35; CV-PTC, n = 105). In the matched analysis, a higher proportion of patients with DSV-PTC experienced persistent/recurrent disease than that of those with CV-PTC (25.7% vs 5.7%, P = .003). In the multivariate analyses of clinical and tumor characteristics, only the histologic type of DSV-PTC (odds ratio, 6.288; 95% confidence interval, 1.900-20.811; P = .003) was associated with an increased risk of persistent/recurrent disease. The 5-year DFS rates for the DSV-PTC and CV-PTC groups were 69.2% and 93.6%, respectively. The Kaplan-Meier analysis indicated that the DSV-PTC group (P= .001) had shorter DFS. CONCLUSION: This propensity score-matched analysis found that the histologic type of DSV-PTC may increase the risk of persistent/recurrent disease.

Diffuse sclerosing variant papillary thyroid carcinoma has worse survival than classic papillary thyroid carcinoma: a meta-analysis.

Diffuse sclerosing variant (DSV) of papillary thyroid carcinomais a rare form of thyroid cancer that demonstrates more aggressive histopathology than classical papillary thyroid carcinoma (c-PTC); however, if this leads to worse survival is debated. Many DSVs are driven by fusion events which are of recent clinical importance due to the advent of targeted RET inhibitors. A systematic search and meta-analysis of the literature was performed to compare outcomes of disease-specific mortality (DSM), metastatic and recurrent disease and the incidence of fusion events between DSV and c-PTC to July 2022. The Newcastle-Ottawa Quality Assessment studies was used to assess quality. An odds ratio (OR) was utilised to measure outcomes with 95% CIs. The Preferred Reporting Items for Systematic Reviews and Meta-analysis guideline was followed. Seventeen studies were included with 874 DSV patients compared to 76,013 c-PTC patients. DSV patients had worse DSM (OR=2.50, 95% CI 1.39-4.51) and presented with a higher rate of metastatic lymph nodes (OR = 5.85, 95% CI 2.73-12.53) and more distant metastases (OR = 3.83, 95% CI 2.17-6.77). DSV patients had higher odds of recurrent disease (OR = 3.23, 95% CI 2.00-5.23) and overall distant metastasis (OR = 2.70, 95% CI 1.74-4.17). Rates of RET fusion alterations for DSV ranged from 25 to 83%. DSV has a worse prognosis than c-PTC with higher rates of recurrent disease and distant metastasis. The high prevalence of RET fusions offers the potential to improve outcomes for patients with DSV.

Differential diagnosis of diffuse sclerotic thyroid papillary carcinoma and Hashimoto's thyroiditis using fine-needle aspiration cytology, BRAFV600E , and ultrasound elastography.

BACKGROUND: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) has ultrasound findings that are similar to Hashimoto's thyroiditis (HT), resulting in under-diagnosis. DSV-PTC combined with HT is also common, so early and accurate diagnosis of DSV-PTC using a variety of diagnostic techniques, including FNAC, BRAFV600E mutation detection, and ultrasound elastography, is critical. OBJECTIVE: To assess the diagnostic value of fine-needle aspiration cytology (FNAC) and BRAFV600E detection in combination with ultrasound elastography in the diagnosis of DSV-PTC. METHODS: We performed a retrospective analysis of 40 patients with pathologically confirmed DSV-PTC and 43 patients with HT admitted to our hospital's ultrasound department between January 2015 and December 2020. Preoperative FNAC, BRAFV600E mutation detection, and ultrasound elastography imaging were all performed on all patients. For a definitive diagnosis, the results of these tests were compared to postoperative pathological findings. The diagnostic value of FNAC, BRAFV600E mutation detection, ultrasound elasticity imaging, and their combination for DSV-PTC diagnosis was assessed. RESULTS: The mean elastic strain rate ratio (E1/E2) of the 40 DSV-PTC cases was 5.75 ± 2.14, while that of the 43 HT cases was 2.81 ± 1.20. The receiver operating characteristic (ROC) curve was generated using the average value of E2/E1. The area under the ROC curve was 0.910, and the optimal E2/E1 cut-off value was 4.500. When FNAC, BRAFV600E mutation detection, and ultrasound elasticity imaging detection were combined, the diagnostic sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of DSV-PTC diagnosis were 92.5%, 95.3%, 93.2%, 94.9%, and 94.0%, respectively, which were significantly higher than the single technique (p < 0.05). CONCLUSIONS: The use of FNAC, BRAFV600E mutation detection, and ultrasound elastography in combination is more helpful in establishing an accurate diagnosis of DSV-PTC than using a single diagnostic technique alone.

Diffuse sclerosing variant of papillary thyroid carcinoma: outcomes of 33 cases.

Introduction: Diffuse sclerosing variant of PTC (DSV-PTC) is an uncommon subtype of thyroid cancer. Although an aggressive behavior is often recognized, prognostic significance is still under debate. Objectives: To describe the clinicopathological features and outcomes of a series of DSV-PTC patients. Methods: Retrospective data collection involving 33 patients diagnosed with DSV-PTC followed at the Endocrine Department of the Portuguese Institute of Oncology in Lisbon between 1981 and 2020. Results: Twenty-six patients (78.8%) were females with a mean age at presentation of 29.4 ± 11.7 years old. Mean time of follow-up was 19.5 ± 10.6 years (range 0.5-39). Histologically, bilateral tumors were present in 72.7% patients (n = 24), thyroid capsular invasion was documented in 57.6% (n = 19), 45.4% (n = 15) had extrathyroidal extension, and 42.4% (n = 14) had lymphovascular invasion. Most patients were staged pT3 (42.4%, n = 14) and pN1 (81.8%, n = 27). Median lymph nodes resected were 16. None of the patients showed distant metastases at presentation. All patients were treated at least once with 131I. During follow-up, four patients (14.8%), with persistent neck disease, were diagnosed with distant metastases, all of them in the lung. Two patients (1.8%) presented recurrent disease in the neck after being considered with no evidence of disease. At the last appointment, 18 patients (54.5%) were in remission, 4 (12.1%) had biochemical evidence of disease, 6 had structural disease, and for 5 patients disease status was considered as undetermined. There was no disease related mortality. Discussion/conclusion: Our study confirms that DSV-PTC is diagnosed more often in young patients and exhibits a local extensive disease at presentation. On the other hand, even in the presence of distant metastases, no patient died during follow-up.

Clinical Outcomes of Diffuse Sclerosing Variant Papillary Thyroid Carcinoma in Pediatric Patients.

OBJECTIVES/HYPOTHESIS: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV) may be more aggressive than conventional well-differentiated non-DSV related papillary thyroid carcinomas (N-PTC). STUDY DESIGN: Retrospective chart review. METHODS: Retrospective review of clinical outcomes for patients 21 years of age or younger who underwent initial surgery for PTC at a single institution from January 1, 2005 to April 1, 2020. Genomic analysis was performed using targeted next-generation sequencing. Data were analyzed using Fischer's exact test and Kaplan-Meier curve log-rank test. RESULTS: Our cohort consisted of 72 patients, nine with DSV and 63 with N-PTC. Age at diagnosis was comparable (15.4 vs. 16.2 years, respectively, P = .46). DSV were more likely to be in the high-risk American Thyroid Academy pediatric risk group (100% vs. 41.3%, P = .004), to present with regional cervical lymph node metastases (100% vs. 60.3%, P = .036), and to present with distant metastases (67% vs. 22%, P = .005). No mortality seen in either group over 27.5 (interquartile range 14.8, 46.00) months average follow-up. Throughout the follow-up period, DSV were more likely to experience progression than N-PTC (hazard ratio = 5.7 [95% confidence interval 1.7-20.0; P = .0056]). In a subset of 19 patients with aggressive disease who had molecular testing as part of clinical care we detected RET fusions in nearly all DSV compared to a minority of N-PTC (83% vs. 15.4%, P = .0095). CONCLUSIONS: Pediatric patients with DSV have more advanced disease at diagnosis and are more likely to experience progression of disease compared to patients with N-PTC. The prevalence of RET fusions in our cohort recapitulates the frequency of this alteration described in prior studies. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1132-1138, 2022.

Comparison of the clinical characteristics of primary thyroid lymphoma and diffuse sclerosing variant of papillary thyroid carcinoma.

Objective: Both primary thyroid lymphoma (PTL) and diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) are two rare malignant tumours with different therapies and prognoses. This study compared their clinical features. Methods: From a retrospective review of the pathologic database at our institute between January 2015 and August 2020, 52 PTL patients and 40 DSVPTC patients were included. Demographic, clinical, laboratory and ultrasound data were extracted from electronic medical records. Statistical analyses were performed using GraphPad Prism 5.0. Results: Both PTL and DSVPTC were more likely to occur in women (83.7 and 67.5%, respectively), but DSVPTC patients were younger (median age: 36 vs 64.5), had fewer compressive symptoms, and more frequently had neck lymph node metastasis than PTL patients. The prevalence of Hashimoto's thyroiditis (HT) and hypothyroidism was significantly higher in PTL patients than in DSVPTC patients (31% vs 17.5%). Hyperthyroidism could only be found in DSVPTC patients, which accounted for 7.5%. Heterogeneous echogenicity and irregular edges were frequently observed in both PTL and DSVPTC. However, compared with PTL, DSVPTC exhibited smaller lesion sizes, higher frequencies of diffuse sonographic patterns and calcification and lower frequencies of hypoechoic features and internal blood flow signal. The overall survival rate with PTL was 77.23%, which was lower than that with DSVPTC (90.91%), but this difference was not significant (P = 0.096). Conclusion: Clinical characteristics such as age, compression symptoms, and sonographic features such as a large mass with heterogeneous echogenicity, hypoechoic, irregular edges, and calcification are helpful for impression diagnosis of PTL and DSVPTC before surgery.

Diffuse intrathyroidal dissemination of papillary thyroid carcinoma with no stromal fibrosis at presentation: A pattern of aggressive differentiated thyroid carcinoma.

BACKGROUND: Multifocal Papillary thyroid carcinoma (PTC) is a very common condition. In certain cases, it is possible to find tens to hundreds of foci with a diffuse intrathyroidal spread in the whole thyroid with no stromal fibrosis. Herein, PTC with such features was nominated as diffuse disseminate variant (DDV) PTC. The aim of the present study was to investigate the histopathological characteristics, molecular features, and biological behavior of DDV and compare the characteristics of DDV to diffuse sclerosing variant (DSV) PTC. MATERIALS AND METHODS: Thirty-four DDV and 23 DSV cases were identified from consecutive surgical specimens diagnosed with PTC between 2014 and 2019. Targeted next-generation sequencing (NGS) was applied to investigate the mutation spectrum of DDV and DSV. RESULTS: DDV was commonly diagnosed in young patients and exhibited high rates of LNM (100 %), ETE (61.8 %), and LVI (44.1 %); however, they did not differ from DSV (P > 0.05). Male patients were more frequently diagnosed with DDV than with DSV (P < 0.001). The size of the largest tumor was significantly greater in DDV than in DSV patients (P = 0.008). In addition, BRAFV600E mutation was significantly higher in the DDV than in the DSV group (P < 0.001). The RET/PTC rearrangement was more frequent in DSV than in DDV patients; however, the difference was not statistically significant (P = 0.106). Moreover, DDV had a higher rate of recurrence compared to DSV treated with the same protocol (total thyroidectomy followed by radioactive iodine (RAI) treatment) (47.1 % and 8.7 %, P = 0.002). CONCLUSIONS: DDV should be regarded as a novel aggressive variant of PTC with distinct clinicopathological characteristics, aggressive biological behaviors, and a high recurrence.

Axillary lymph node metastasis from papillary thyroid carcinoma with elevated CA 19-9 and CA 242 levels: a case report and literature review.

Axillary lymph node metastasis is a rare event in thyroid carcinoma. The simultaneous expression of carbohydrate antigens 19-9 (CA 19-9) and 242 (CA 242) in thyroid tumors is also extremely rare. Herein, we report a case of axillary lymph node metastasis with elevated serum CA 19-9 and CA 242 in papillary thyroid carcinoma. In a 47-year-old woman with thyroid carcinoma, masses developed in the neck and axilla over a two-month period, which were surgically treated using total thyroidectomy, with neck and axillary lymph node dissection. Histopathological examination confirmed a diffuse sclerosing variant-papillary thyroid carcinoma, with 52 of 63 axillary lymph node metastases. Notably, serum CA 19-9 and CA 242 levels decreased from the initial values of 1,110 and 50 kU/L, respectively, to normal levels one month postoperatively and have remained stable for two years since. The aggressive biological behavior of diffuse sclerosing variant-papillary thyroid carcinoma and the abnormal anatomical distortion caused by tumors in this case most likely reflect the mechanisms underlying retrograde dissemination in lymphatic tubes. However, the mechanism leading to a simultaneous elevation of CA 19-9 and CA 242 secreted by the diffuse sclerosing variant-papillary thyroid carcinoma has not been elucidated. The patient has survived for two years suggesting that timely surgery can help such patients achieve a better prognosis.

Consensus Statement by the American Association of Clinical Endocrinology (AACE) and the American Head and Neck Society Endocrine Surgery Section (AHNS) on Pediatric Benign and Malignant Thyroid Surgery.

OBJECTIVES: To provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children. METHODS: A literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.). RESULTS: Twenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus. CONCLUSION: Pediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons.

Consensus statement by the American Association of Clinical Endocrinology (AACE) and the American Head and Neck Society Endocrine Surgery Section (AHNS-ES) on Pediatric Benign and Malignant Thyroid Surgery.

OBJECTIVES: To provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children. METHODS: A literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.). RESULTS: Twenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus. CONCLUSION: Pediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons.

Occult carcinoma confirmed to be a diffuse sclerosing variant of papillary thyroid carcinoma with unusual immunohistochemical features: A pitfall of clinicopathological diagnosis.

Immunocytochemistry in a 78-year-old man diagnosed as having systemic metastatic cancer of unknown primary origin revealed atypical cells positive for napsin A and TTF-1, suggesting adenocarcinoma of the lung. However, there was no evidence of a primary lesion in the lung on positron emission tomography/computed tomography or at autopsy. Meanwhile, both the left and right thyroid lobes were firm and grayish white with marked fibrosis. Histology identified a diffuse sclerosing variant of papillary thyroid carcinoma that was positive for TTF-1 and napsin A but negative for PAX8. This disease entity is often misdiagnosed clinically as chronic thyroiditis. This is the first report of napsin A-positive and PAX8-negative thyroid carcinoma and highlights the pitfalls of clinicopathological diagnosis.

Survival of aggressive variants of papillary thyroid carcinoma in patients under 55 years old: a SEER population-based retrospective analysis.

BACKGROUND: Patients younger than 55 years of age with papillary thyroid carcinoma (PTC) have excellent survival. Diffuse sclerosing variant (DSV) and tall cell variant (TCV) of PTC are associated with aggressiveness; the survival of patients <55 years of age with these variants is still unclear. We aim to investigate the clinicopathological features and survival of these variants in the age group <55 years. METHODS: All adult patients (<55 years old) with DSV, TCV and conventional PTC (CPTC) came from the Surveillance, Epidemiology, and End Results program (1988-2013). Kaplan-Meier method and log-rank test were used to analyze the survival. Prognostic factors associated with survival were analyzed by Cox multivariate regression. RESULTS: There were 280 DSV, 615 TCV, and 56287 CPTC in the age group <55 years. DSV and TCV were associated with multifocality, extrathyroidal extension, lymph node and distant metastasis (all p < 0.05). The 10-year disease-specific survival (DSS) of TCV was worse than CPTC (96.3 vs. 99.4%, p < 0.01), but there was no significant difference between DSV and CPTC (99.5 vs. 99.4%, p > 0.05). Cox multivariate regression showed TCV was the independent predictor of DSS (HR: 5.39, p < 0.01). CONCLUSION: In the age group <55 years, DSV and TCV are more likely to exhibit aggressive characteristics than CPTC. Patient <55 years of age with DSV have excellent survival likewise, while patients <55 years of age with TCV carry worse survival. Further investigation for the recurrence risk of patients <55 years with these variants would contribute to optimal clinical management making.

Tall cell and diffuse sclerosing variants of papillary thyroid cancer: outcome and predicting value of risk stratification methods.

PURPOSE: Tall cell (TCV) and diffuse sclerosing (DSV) variants are aggressive variants of papillary thyroid cancer (PTC). We compared the risk of recurrent/persistent disease in patients with TCV, DSV and classical PTC (cPTC) and evaluated the prognostic accuracy of initial vs. ongoing risk stratification. METHODS: A consecutive series of DSV (n = 54), TCV (n = 72) and cPTC (n = 184) patients was retrospectively analyzed. TCV and DSV patients were first risk stratified for recurrent/persistent disease without considering the histotype as a risk factor and subsequently, 6-24 months after initial treatment, re-classified on the basis of the response to therapy (ongoing risk stratification). RESULTS: Extrathyroidal extension was more frequent in DSV than in TCV and cPTC patients (p < 0.05); moreover, only DSV tumors had a higher rate of recurrent/persistent disease when compared to cPTC treated with the same protocol (total thyroidectomy followed by 131I treatment) (p < 0.01). After initial treatment, 54.2% of TCV and 20.4% of DSV patients were classified at low risk, while at ongoing risk stratification, the excellent response (low risk) was higher for both TCV (77.8%) and DSV (50.0%) patients relative to initial stratification (both p < 0.01). Using ongoing risk classification, positive predictive value (PPV) for persistent/recurrent disease was higher relative to initial risk stratification for both TCV (PPV = 93.8 vs. 39.4%) and DSV (PPV = 63.0 vs. 34.9%), p < 0.05 for both. CONCLUSIONS: In our series DSV, but not TCV patients, had poorer outcome than cPTC treated with the same protocol. Moreover, the ongoing risk stratification predicted outcome better than the initial classification in both TCV and DSV patients.

Bethesda classification is a valuable guide for fine needle aspiration reports and highly predictive especially for diagnosing aggressive variants of papillary thyroid carcinoma.

BACKGROUND: A fine needle aspiration biopsy (FNAB) is the most valuable diagnostic procedure for pre-operative discrimination of benign and malignant nodules. The Bethesda System for Reporting Thyroid Cytopathology provides standardised reporting and cytomorphological criteria in aspiration smears. The aim of the present study was to determine malignancy rates in nodules with different cytology results and evaluate the diagnostic value of Bethesda for variants of papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: A retrospective analysis of 2534 cases with 5784 thyroid nodules, who underwent FNAB followed by surgery, were included in this study. FNAB was performed with ultrasonography guidance. Cytological diagnoses were classified as: non-diagnostic (ND), benign, atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy (SUS) and malignant. Histopathological diagnoses were classified into four groups: benign, PTC, follicular thyroid cancer and other types of thyroid cancer (including medullary thyroid cancer, undifferentiated thyroid cancer and thyroid tumours of uncertain malignant potential). Cases with PTC were further divided into four categories: conventional variant, follicular variant, aggressive variants (tall cell, diffuse sclerosing and columnar variant) and other variants (oncocytic, solid/trabecular and warthin-like variants). FNAB results were compared with histopathological results. RESULTS: Malignancy rates were 6.3%, 3.2%, 20.7%, 33.3%, 74.2% and 95.6% in the nodules with ND, benign, AUS/FLUS, FN/SFN, SUS and malignant cytology results, respectively. Pre-operative cytology was malignant or SUS in 56.6% of conventional, 24.3% of follicular, 92% of aggressive and 41.7% of other variants of histopathologically confirmed PTC. The difference between the groups was significant (P < 0.001). CONCLUSION: The Bethesda classification is a reliable indicator of malignancy in nodules with different cytology results and seems to be very effective in predicting the malignancy for the nodules diagnosed with aggressive variant PTC on the final histological examination.

Research progress of diffuse sclerosing variant papillary thyroid carcinoma / 国际外科学杂志

Diffuse sclerosing variant papillary thyroid carcinoma,one of the variants of papillary thyroid carcinoma,nearly account for 0.7％ to 6.6％ of papillary thyroid carcinoma.It is an aggressive tumor that shows higher rates of recurrence,metastasis and persistent disease compares to classic papillary thyroid carcinoma,thus diffuse sclerosing variant papillary thyroid carcinoma needs stricter and more exhaustive operation.Since the incidence of diffuse sclerosing variant papillary thyroid carcinoma is low,many physicians lack of understanding of the disease,it's often missed diagnosis or misdiagnosed.Consequently.In order to let physicians understand more about diffuse sclerosing variant papillary thyroid carcinoma,this paper will elaborate the epidemiology,clinic and pathology features of it.

High endothelial venule-like vessels and lymphocyte recruitment in diffuse sclerosing variant of papillary thyroid carcinoma.

Diffuse sclerosing variant of papillary thyroid carcinoma (DSPTC) is a rare subtype of papillary thyroid carcinoma with a high incidence of lymph node metastasis. One of its characteristic histological features is the presence of dense lymphocyte infiltrates; however, how these lymphocytes are recruited in this pathological setting remains unclear. Here, we analysed 17 DSPTC cases immunohistologically for cell adhesion molecules expressed on endothelial cells. We found that venules morphologically similar to high endothelial venules (HEVs) in secondary lymphoid organs were induced in lymphoid aggregates in DSPTC, and such HEV-like vessels expressed 6-sulfo sialyl Lewis X (sLeX) glycans as well as intercellular adhesion molecule 1 (ICAM-1). Triple immunohistochemistry revealed that CD8+ cytotoxic T cells were the major lymphocyte subset attached to the luminal surface of HEV-like vessels. sLeX-type glycans were also expressed on DSPTC carcinoma cells, which in binding assays were decorated with E-selectin•IgM chimaeras calcium-dependently. These findings collectively suggest that 6-sulfo sLeX glycans, together with ICAM-1, on HEV-like vessels may function to recruit CD8+ cytotoxic T cells in DSPTC. Additionally, sLeX-type glycans on carcinoma cells might partly contribute to highly metastatic properties of DSPTC through interaction with E-selectin expressed on endothelial cells.