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Background: Papillary thyroid cancer, comprising 80% of thyroid malignancies in iodine-sufficient areas, can be effectively treated if detected early before metastasis. Cervical lymph nodes are a common site of metastasis, prompting some surgeons to suggest prophylactic dissection in all patients. To minimize potential side effects, this study aims to identify patients benefiting from this procedure by assessing risk factors for central lymph node metastasis. Methods and materials: This descriptive-analytical study was conducted on 150 patients with papillary thyroid cancer. The samples included cases in which central lymph node involvement was ruled out clinically and radiologically. After proving papillary cancer in the pathology sample, the variables of age, sex, frequency of central lymph node involvement, tumor size, location of thyroid involvement, multi-centric involvement, multi-focal involvement, presence of microcalcification, capsular invasion, lymphovascular invasion, and pathology were analyzed. The results were presented with descriptive statistics. Results: The percentage of central lymph node involvement in this study was reported as 9.3%. In the analysis, capsular invasion (P=0.01), lymphovascular invasion (P=0.0001) and involvement of the upper thyroid pole (P=0.001) were identified as risk factors for central lymph node involvement. There was no significant relationship between the variables of age, sex, tumor size, pathology, multi-centricity and multifocality and central lymph node involvement. Conclusion: Involvement of central lymph nodes in patients with capsular invasion, lymphovascular invasion, and involvement of the upper thyroid bridge is far more common than in other patients, and central lymph node dissection is recommended in patients with several of the above risk factors.

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BACKGROUND: Follicular tumors include follicular thyroid adenomas and carcinomas; however, it is difficult to distinguish between the two when the cytology or biopsy material is obtained from a portion of the tumor. The presence or absence of invasion in the resected material is used to differentiate between adenomas and carcinomas, which often results in the unnecessary removal of the adenomas. If nodules that may be follicular thyroid carcinomas are identified preoperatively, active surveillance of other nodules as adenomas is possible, which reduces the risk of surgical complications and the expenses incurred during medical treatment. Therefore, we aimed to identify biomarkers in the invasive subpopulation of follicular tumor cells. METHODS: We performed a spatial transcriptome analysis of a case of follicular thyroid carcinoma and examined the dynamics of CD74 expression in 36 cases. RESULTS: We identified a subpopulation in a region close to the invasive area, and this subpopulation expressed high levels of CD74. Immunohistochemically, CD74 was highly expressed in the invasive and peripheral areas of the tumor. CONCLUSIONS: Although high CD74 expression has been reported in papillary and anaplastic thyroid carcinomas, it has not been analyzed in follicular thyroid carcinomas. Furthermore, the heterogeneity of CD74 expression in thyroid tumors has not yet been reported. The CD74-positive subpopulation identified in this study may be useful in predicting invasion of follicular thyroid carcinomas.

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Introduction: Papillary thyroid microcarcinoma has provoked discussion among the endocrinological community due to the extremely diverse therapeutic methods adopted in international guidelines. From the radical approach of total thyroidectomy with prophylactic central lymphatic dissection to "active monitoring" and opinions such as "papillary microcarcinoma is not carcinoma". Aim: To investigate the factors of invasiveness in papillary microcarcinoma. Material and methods: We included 184 patients with thyroid microcarcinoma, operated in the Department of General Surgery "Kaspela",Plovdiv, for a period of five years. Results: Intra-organ metastases or multifocal growth was identified in 38 of the patients. Positive for micro and macro metastases lymph nodes in the central lymphatic basin are found in 54. In 46 of them we identified metastases in the ipsilateral, and in 21 in the contralateral central neck nodes. The analysis of patients with lateral metastases found 7 unilaterally and 3 bilaterally. Skip metastases were registered in 4 of these 10 patients. Conclusions: The results of our study show that despite the favorable prognosis and non-aggressive behavior of papillary microcarcinoma, factors attesting to the invasive nature of the tumor occur in 44.5% or almost half of patients. This requires careful and individual approach constructing therapeutic strategy for the treatment of patients with papillary microcarcinoma.

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We collected all cases of poorly differentiated thyroid carcinoma at our institution diagnosed between 2007 and 2022 to investigate the role of tumor capsule in these neoplasms along with other histologic factors that may lead to adverse patient outcomes. After the exclusion of those meeting criteria for differentiated high-grade thyroid carcinoma or anaplastic carcinoma, we were left with 65 cases with a poorly differentiated component. Four of those cases (6.2%) were entirely encapsulated with no invasion of the tumor capsule. Unencapsulated tumors showed significantly greater rates of extrathyroidal extension (75.0% versus 41.5%) and death from disease (45.5% versus 12.5%) than encapsulated tumors, regardless of capsular invasion, with no differences in sex, tumor size, angioinvasion, local recurrence, or metastasis. Compared with encapsulated tumors with invasion, encapsulated tumors without capsular invasion showed a strong male predominance (100% versus 38.8%). No encapsulated tumors without capsular invasion demonstrated local recurrence, metastasis, or death from disease. No differences in the percentage of poorly differentiated components were noted among the 3 groups, although there was a trend for encapsulated tumors to have a higher percentage of poorly differentiated components than unencapsulated tumors. We conclude that invasive tumors lacking a capsule demonstrate greater rates of disease-related death despite showing similar adverse histologic features to invasive encapsulated tumors. Moreover, we confirm that encapsulated tumors without capsular invasion have excellent long-term outcomes in terms of recurrences, metastases, and survival.

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Purposes: To quantitatively predict the probability of cervical lymph node metastasis for papillary thyroid carcinomas (PTC) patients with or without thyroid capsular invasion (TCI), to guide the decision-making of management strategies for neck regions. Methods: A total of 998 PTC patients from three medical centers were retrospectively analyzed. Results: Patients with positive TCI (TCI group) exhibited higher risks for both CLNM and LLNM than those with negative TCI (no-TCI group). Patients receiving lateral lymph node dissection showed significantly higher incidence of relatively severe postoperative complications. For no-TCI group, factors including age less than 55 years old, male, the presence of bilateral disease and multifocality, and maximum tumor diameter (MTD)>=0.5cm were confirmed to be independent risk factors for CLNM, while the presence of bilateral disease and ipsilateral nodular goiter (iNG), and maximum positive CLN diameter (MCLND)>1.0cm independent factors for LLNM. Independent risk factors of LLNM for patients within the TCI group included MCLND>1.0cm, positive CLN number>=3, and the presence of iNG. Predictive models of CLNM and LLNM were established based on the aforementioned risk factors for patients within no-TCI and TCI groups. A meticulous and comprehensive risk stratification flow chart was established for a more accurate evaluation of central neck involvement including both CLNM and LLNM risk in PTC patients. Conclusions: A meticulous and comprehensive stratification flow chart for PTC patients for quantitatively evaluating both CLNM and LLNM was constructed.

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Background: Thyroid carcinoma >4 cm in size is staged as T3a. The current American Thyroid Association guidelines recommend subtotal/total thyroidectomy and consideration for postoperative radioactive iodine (RAI) treatment for these tumors. In this retrospective cohort study, we aimed to explore the clinical course of large encapsulated thyroid carcinoma without other risk factors. Methods: Eighty-eight patients with large (>4 cm) encapsulated well-differentiated thyroid carcinoma resected between 1995 and 2021 were included in this retrospective cohort study. Exclusion criteria were tall cell variant, any extent of vascular invasion, extrathyroidal extension (microscopic or gross), high-grade histology, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), infiltrative tumors, positive resection margin, and cases with follow-up <1 year. The primary outcomes are risk of nodal metastasis at the initial resection, disease-free survival (DFS), and disease-specific survival (DSS). Results: The tumor histotype was follicular carcinoma (n = 18, 21%), oncocytic (Hurthle cell) carcinoma (n = 8, 9%), and papillary thyroid carcinoma (PTC; n = 62, 70%). Among PTC, 38 were encapsulated follicular variant, 20 classic type, and 4 solid variant. Four cases had extensive capsular invasion (CI), 61 (69%) had focal CI, whereas 23 did not have CI. Thirty-two cases (36%) were treated with lobectomy/hemithyroidectomy alone, and 55 patients (62%) did not receive RAI. Five patients had nodal metastasis at the time of primary resection, all of whom had classic-type PTC. The median follow-up period was 4.8 years (interquartile range: 3.2-9.7 years). No recurrence, being local, regional, or distant, was observed in the entire cohort, including those patients treated with lobectomy alone without RAI. The 10-year DFS and DSS were 100%, respectively. Conclusion: Large intrathyroidal encapsulated well-differentiated thyroid carcinoma without vascular invasion follow an extremely indolent clinical course with negligible risk of recurrence. Lobectomy alone without RAI may be the appropriate treatment strategy for this selected group of patients.

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Non-invasive biomarkers for the diagnosis and prognosis of papillary thyroid microcarcinoma (PTMC) are still urgently needed. We aimed to characterize the N-glycome of PTMC, and establish nomograms for the diagnosis of PTMC and the prediction of lymph node metastasis (LNM). N-glycome of PTMC (LNM vs. non-LNM, capsular invasion (CI) vs. non-CI (NCI)) and matched healthy controls (HC) were quantitatively analyzed based on mass spectrometry. N-glycan traits associated with PTMC/LNM were used to create binomial logistic regression models and were visualized as nomograms. We found serum N-glycome differed between PTMC and HC in high-mannose, complexity, fucosylation, and bisection, of which, four N-glycan traits (TM, CA1, CA4, and A2Fa) were significantly associated with PTMC. The nomogram based on four traits achieved good performance for the identification of PTMC. Two N-glycan traits (CA4 and A2F0S0G) showed strong associations with LNM. The nomogram based on two traits showed relatively good performance in predicting LNM. We also found differences between CI and NCI in several N-glycan traits, which were not the same as that associated with LNM. This study reported serum N-glycosylation signatures of PTMC for the first time. Nomograms constructed from aberrant glycans could be useful tools for PTMC diagnosis and stratification.

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Background: Radioiodine (RAI) therapy plays a vital role in the postoperative treatment of differentiated thyroid cancer (DTC) patients underwent total thyroidectomy (TT). However, even in the presence of capsular invasion and lymph node metastasis prognosis can be excellent and a postoperative RAI treatment might not be necessary for all patients. Therefore, this study explored the criteria for avoiding unnecessary RAI therapy in these patients. Method: We applied response to therapy assessment immediately after surgery and prospectively recruited 179 excellent or indeterminate response DTC patients with capsular invasion and/or LNM who underwent TT without RAI therapy. During the follow-up, thyroglobulin (Tg), thyroglobulin antibody (TgAb) levels, and cervical ultrasonography were collected and analyzed. Disease-free survival (DFS) was calculated using the Kaplan-Meier method. In addition, response to therapy assessments was performed on patients during each follow-up. Results: The mean follow-up period was 29.85 ± 17.44 months, and the 3- and 5-year DFS for all the patients was 99.3% in each. At the last follow-up, 165 (92.2%) patients had excellent responses, while 12 (6.7%) had an indeterminate response, and one (0.6%) each had biochemical and incomplete responses. No significant difference was observed in response to therapy between the subgroups of LNM and tumor invasion (P>0.05). For patients with capsular invasion and a number of metastatic lymph nodes ≤5 and >5, the proportions of recorded excellent responses were 95.9%, 91.0%, and 85.7%, respectively. Better responses were observed in females (excellent response: 95.5%, P=0.023), patients with stimulated Tg (s-Tg) ≤1ng/ml (excellent response: 100%, P<0.001), s-Tg ≤ 2ng/ml (excellent response: 98.4%, P<0.001), and excellent response for the immediate postoperative assessment (excellent response: 98.5%, P=0.004). Conclusions: The current study suggested that the response to therapy assessment immediately applied postoperatively could help avoid unnecessary RAI therapy among DTC patients with capsular invasion and/or LNM. Moreover, excellent response patients and patients with indeterminate response and s-Tg ≤ 2ng/ml could be managed without RAI therapy.

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Introducción: El cáncer diferenciado de tiroides (CDT) se encuentra representado por el carcinoma papilar y el carcinoma folicular. Comprende la gran mayoría (>90%) de todos los cánceres de tiroides. Objetivos: Estratificar el riesgo de recurrencia inicial de los pacientes con CDT. Relacionar la edad, sexo y tamaño tumoral con el riesgo de recurrencia, invasión capsular, ganglionar, vascular y de tejido peritiroideo. Materiales y métodos: Estratificar el riesgo de recurrencia inicial de los pacientes con CDT. Relacionar la edad, sexo y tamaño tumoral con el riesgo de recurrencia, invasión capsular, ganglionar, vascular y de tejido peritiroideo. Resultados: El 87% fueron del sexo femenino. La edad media fue de 43±14 años. Predominó el riesgo de recurrencia bajo en el 49% de los pacientes, seguido del riesgo intermedio (33%) y riesgo alto (18%). El tamaño tumoral ˃1cm confiere mayor riesgo de ser estratificado como riesgo de recurrencia intermedio/alto (OR 5,7 IC 95% 3,6-9). El sexo masculino representó mayor riesgo de invasión ganglionar (OR 2,8 IC 95% 1,2-6,6); la edad ≥55 años lo fue en la invasión vascular (OR 2,1 IC 95% 1,1-4,1); el tamaño >1cm constituyó un mayor riesgo de manera significativa de invasión capsular (OR 10,5 IC 95% 6,5-17), invasión ganglionar (OR 10,2 IC 95% 3,8-26,9), invasión vascular (OR 30,7 IC 95% 4,2-224) e invasión de tejido peritiroideo (OR 5,2 IC 95% 3,3-8,2). Conclusión: El riesgo de recurrencia inicial más frecuente fue el riesgo bajo. El sexo masculino, la edad ≥55años y el tamaño >1cm constituyen factores de riesgo de invasión a estructuras vecinas.

Introduction: Differentiated thyroid cancer (DTC) is represented by papillary carcinoma and follicular carcinoma. It comprises the vast majority (> 90%) of all thyroid cancers. Objectives: Stratify the risk of initial recurrence of patients with DTC. Relate age, sex, and tumor size to the risk of recurrence, capsular, nodal, vascular, and perithyroid tissue invasion. Materials and methods: Observational, descriptive, retrospective, cross-sectional study with an analytical component. A total of 432 patients with a diagnosis of DTC from Hospital de Clínicas, Instituto de Previsión Social and Instituto Nacional del Cáncer between 2011 and 2015 were included. Results: 87% were female. The mean age was 43 ± 14 years. Low recurrence risk predominated in 49% of patients, followed by intermediate risk (33%) and high risk (18%). Male sex, age ≥55 years and tumor size ˃1cm confer a higher risk of being stratified as intermediate / high recurrence risk, but only size> 1cm was significantly (OR 5.7 95% CI 3.6-9). Male sex represented a higher risk of lymph node invasion (OR 3.1 95% CI 1.4-2.8) and vascular invasion (OR 2.3 95% CI 1.1-4.8); age ≥55 years was in the vascular invasion (OR 2.6 95% CI 1.4-4.9); size> 1cm constituted a significantly higher risk of capsular invasion (OR 10.7 95% CI 6.7-17.3), nodal invasion (OR 10.5 95% CI 4-27.7), vascular invasion (OR 33 95% CI 4.5-244) and invasion of perithyroid tissue (OR 5.1 95% CI 3.2-8.1). Conclusion: The most frequent initial recurrence risk was low risk. Male sex, age ≥55 years, and size> 1cm are risk factors for invasion of neighboring structures.

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Context: Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine neoplasm that may spread to lymph nodes before the primary tumor is diagnosed; moreover, distant metastases are already present in about 10% of patients at diagnosis. Serum calcitonin (Ctn) usually reflects the spread of disease, thus orienting the extent of surgery and predicting the possibility of biochemical remission. Tumor size and vascular invasion are important prognostic factors, but little is known on the relationship between other histopathological features, such as the presence of a tumor capsule, and long term outcome of MTC. Purpose: To evaluate the prevalence of encapsulated tumors among MTCs and the association of tumor capsule with a favorable outcome after surgery. Methods: A retrospective observational single-center study was conducted together with a narrative review of the available literature. Results: Among 44 patients (27 female, 17 male; median age: 56 years) with MTC (6 hereditary, 37 sporadic) followed up at our center in the last four years (median follow-up: 29.2 months), seven (15.9%) showed an encapsulated tumor at histology and a clinical remission after surgery. None of them had nodal metastases and median preoperative Ctn (398 pg/mL, IQR 126.5-7336) did not differ significantly from that of the 14 patients (31.8%) with persistent disease after surgery (787 pg/mL, IQR 340.5-2905.5; p=0.633), although their tumor size was significantly higher (median 33 mm versus 16 mm respectively, p=0.036). Among patients with preoperative Ctn levels above 500 pg/mL (n=11), only two (18.2%) showed undetectable Ctn levels during follow-up, both having an encapsulated MTC (OR 0.000, p=0.02). Notably, they were two similar cases of large MTC (> 3 cm) with extensive hyalinization and calcification, associated with very high Ctn levels (> 13'500 and 1'100 pg/mL, respectively) but no nodal nor distant metastases, in complete remission after surgery although one of them carried the aggressive M918T somatic RET mutation. Conclusion: MTC rarely shows a tumor capsule, which seems to correlate with a better prognosis and absence of nodal metastases, regardless of RET or RAS mutational status. Among encapsulated MTCs (E-MTC), Ctn levels and tumor size are not predictive of persistence of disease after surgery.

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The World Health Organization (WHO) classifies follicular thyroid carcinoma (FTC) into three categories: minimally invasive (mFTC), encapsulated angioinvasive (eaFTC), and widely invasive (wFTC). This study investigated whether this classification is appropriate. We enrolled 523 patients who underwent initial surgery at Kuma Hospital between 1998 and 2015 and were diagnosed with FTC. Capsular invasion (CI) was classified as none, minimal (microscopic), or wide (macroscopic) invasion. Vascular invasion (VI) was divided according to the number of invasive foci into three degrees: VI(-), VI(1+), and VI(2+). For 507 M0 patients, age ≥55 years (p = 0.004), non-oxyphilic histology (p = 0.043), and male sex (p < 0.001) predicted poor distant recurrence-free survival (DR-FS) on univariate analysis; however, tumor size >4 cm and wide CI did not. The DR-FS rates significantly decreased from VI(-) to VI(2+) in a step-by-step fashion, including VI(-) vs. VI(1+) (p = 0.011) and VI(1+) vs. VI(2+) (p = 0.014). Multivariate analysis revealed that older age (p = 0.0004), non-oxyphilic histology (p = 0.041), male sex (p = 0.0052), VI(1+) (p = 0.017), and VI(2+) (p < 0.001) independently predicted distant recurrence. The DR-FS rates did not significantly differ among mFTC, wFTC/VI(-), and eaFTC/VI(1+). The DR-FS rate of eaFTC/VI(2+) was worse than that of eaFTC/VI(1+) (p = 0.042), but did not differ from that of wFTC/VI(1+/2+). Our findings suggest that subclassifying eaFTC according to the degree of VI and restricting wFTC to VI-positive cases would be better in the WHO classification. Revising the definition for wide CI is recommended.

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Breast implant augmentation is a low-risk procedure with few life-threatening complications. Capsular contracture and rupture/leakage of the implant are the most common complications encountered. Malignant breast implant augmentation-associated lesions are rare, with anaplastic large cell lymphoma being the most common. Squamous cell carcinomas associated with breast implant augmentation are exceedingly rare, with only eight patients reported. Breast implant capsule-associated squamous cell carcinoma occurs in patients with long standing breast implant augmentations (>11 years). We report two additional patients with breast implant capsule-associated squamous cell carcinoma. Review of the literature reveals that invasion beyond the breast implant capsule into the adjacent tissue by the squamous cell carcinoma appears to have negative prognostic implications, and possibly warrants close clinical follow-up.

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OBJECTIVE: To evaluate the feasibility, efficiency, and safety of microwave ablation (MWA) for T1N0M0 papillary thyroid carcinoma (PTC) with capsular invasion (CI). METHODS: The data of 69 T1N0M0 PTC with CI underwent MWA from August 2015 to January 2020 were retrospectively analyzed. All PTC nodules were pathologically confirmed by fine needle aspiration (FNA). The extended ablation was performed in all cases, that is, the ablation zone completely covered the tumor and extended the tumor edge by at least 2 mm. The strategy of fluid isolation was successfully applied before and during ablation. The strategy of multiple point ablation was applied. After ablation, the changes in tumor size at different time points, local recurrence, new lesions, lymph node metastasis (LNM), and complications were evaluated and recorded. The technical feasibility, technical success rate, and safety were analyzed. RESULTS: Based on the contrast-enhanced ultrasound results, complete ablation has been achieved in all enrolled cases after ablation. The mean maximum tumor diameter and the mean volume of PTC nodules before ablation were 0.84 ± 0.39 cm (range, 0.3-2 cm) and 0.26 ± 0.35 ml (range, 0.01-1.72 ml) respectively. The mean follow-up time was 26 ± 10 months (range, 9-48 months). Nodules in 47 cases (68.1%) completely disappeared in the follow-up period. No local recurrence was detected. The incidence of new lesions and LNM was 4.3% (3/69) and 4.3% (3/69) respectively. Further ablations have been successfully employed for all of the new lesions and LMN. Light voice changes (2.9%, 2/69) were the only major complication, which was relieved within 6 months after MWA. The sizes of the ablation zone increased firstly within 6 months after MWA compared with the pretreatment tumor size (p < 0.05). Twelve months later, the sizes were smaller than those before MWA (p < 0.05 for all). CONCLUSIONS: MWA is an effective, safe, and feasible method in treating T1N0M0 PTC with CI.

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BACKGROUND: Accumulating evidence shows that pleomorphic adenoma (PA) exhibits a unique capsular invasion and with a crucial role in recurrence. This study was designed to explore RNA expression profiles in salivary gland PA in an attempt to further analyse genes associate with capsule invasion. METHODS: We evaluated the expression profiles of 4 salivary gland PA patients by RNA-sequencing. The principal functions of the differentially expressed mRNAs (DEGs) were explored using GO and KEGG analysis. Then, RT-qPCR and correlation analyses were performed to verify the candidate DEGs in 59 PA patients, and immunohistochemical examinations were conducted to validate candidate DEGs. Finally, the COMP-related genes were screened using correlation and biological pathway enrichment analysis, and further validated by RT-qPCR. RESULTS: A total of 974 DEGs were significantly upregulated, and 1464 were downregulated (fold change ≥2.0; p < 0.05). Based on GO and KEGG analyses, extracellular matrix organization and the PI3K-Akt signalling pathway might play pivotal roles in the tumorigenesis of PA. 40 DEGs were screened and validated by RT-qPCR, 11 upregulated and 5 downregulated DEGs were consistent with the sequencing results. Cartilage oligomeric matrix protein (COMP) was identified to have a significant correlation with the capsular invasion of PA and expression of COMP in patients with invasive capsular PA was significantly stronger than PA. Finally, further results could reveal that 5 highest scoring genes were screened as hub genes for COMP. CONCLUSIONS: These findings suggested that COMP may be a prognostic target for PA and might contribute to its capsular invasion.

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This study aimed to determine whether additional tissue sampling of encapsulated thyroid nodules would increase the frequency of follicular thyroid carcinoma (FTC) diagnoses. We examined thyroid tissue specimens from 86 patients suspected of FTC (84.9% female; mean age, 49.0 ± 17.8 years). The number of tissue blocks created for pathological assessments ranged from 3 to 20 (mean, 9.1 ± 4.1); the numbers in the previous method recommended by the Japanese General Rules for the Description of Thyroid Cancer and additional blocks ranged from 1 to 12 (mean, 6.0 ± 2.8) and from 1 to 8 (mean, 3.1 ± 2.0), respectively. The additional blocks were subsequently examined to determine whether any diagnoses changed from those based on the previous method. Five patients were diagnosed with FTC using the previous method; however, additional tissue blocks led to the diagnosis of FTC in 6 patients, as 1 diagnosis was revised from follicular adenoma to FTC. It has been reported that increasing the number of tissue blocks used for pathological assessments can increase the frequency of FTC diagnoses; however, this was not clinically significant in thyroid carcinoma, which requires completion thyroidectomy and radioactive iodine treatment. It resulted in no benefits to the patient because all minimally invasive FTCs, follicular tumors of uncertain malignant potential (FT-UMP), and follicular adenomas are treated with lobectomy alone in Japan. Additional tissue sampling only had a slight impact on our thyroid practice; therefore, we decided to cease it.

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Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. Some PTCs with classical papillae can be totally or partially encapsulated, and these tumors are called "encapsulated" (conventional) variant of papillary thyroid carcinoma. We aimed to investigate the clinicopathological features of this variant, comparing with non-encapsulated conventional type PTC. Among 823 thyroidectomy specimens with PTC diagnosed between 2015 and 2018, 121 tumors from 105 patients (12.75%) were reclassified as encapsulated conventional PTC. In 76 patients, tumors were unifocal. Size, cystic changes, background thyroiditis, psammoma bodies, cervical lymph node metastasis at presentation, capsular/vascular invasion, and immunohistochemical BRAF-V600E expression were evaluated. Ninety-two non-encapsulated conventional PTCs served as control group. Encapsulated cases were predominantly women (73.3%), 56.4% were microcarcinomas, 97.5% had cystic changes, 81.4% were BRAF-V600E positive, and 36.8% of unifocal encapsulated tumors had cervical lymph node metastasis. Thyroiditis and psammoma bodies were detected in nearly half of the encapsulated PTCs. Fourteen percent of the unifocal tumors showed total encapsulation, whereas capsular and vascular invasion was detected in 85.5% and 5.8%, respectively. Encapsulated cases did not show any significant difference from the control group, except for prominent cystic changes (p < 0.001). Relationship between lymph node metastasis at presentation and capsular invasion was statistically significant (p = 0.001), and metastasis was more frequent in cases with extensive capsular invasion (no/minimal invasion versus extensive invasion, p < 0.001). Cystic changes are very common, and this feature deserves mentioning as a morphological characteristic of encapsulated conventional PTCs. As in encapsulated "follicular" variant of PTC, capsular invasion status is important in evaluating papillary patterned encapsulated PTC for predicting lymph node metastasis. Total examination of the tumor capsule and inclusion of capsular invasion status in pathology reports are recommended.

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Parathyroid carcinoma (PC) is a rare malignancy that poses a diagnostic challenge on histologic examination. We analyzed various clinicopathologic features of PC. Pathology reports and slides were reviewed to evaluate the diagnostic histopathologic features of archived cases of PC from the years of 2004-2018. The study cohort comprised twenty cases of PC. The median age was 49 years (range 21-73 years) with equal gender distribution (M:F = 1:1). Most patients presented with symptoms of hypercalcemia (n = 7, 54%). Serum calcium and serum parathyroid hormone were elevated in all but one patient. The right inferior parathyroid was commonly involved (n = 8/14, 57%). The mean tumor size was 2.4 cm (range 0.8-3.5 cm). On frozen section examination, PC was diagnosed in 8 out of 9 cases. Vascular (n = 19/20, 95%) and soft tissue invasion (n = 10/20, 50%) were the most common characteristic histologic findings. Capsular invasion was identified in all cases. Perineural invasion or metastasis at presentation was absent in all cases. Other histological features noted were intratumoral fibrous bands (70%), nodular growth pattern (70%), moderate nuclear atypia (30%), prominent nucleoli (20%), and necrosis (20%). Regional lymph nodes were negative for metastatic disease in all cases (n = 10). Eight out of 16 patients received adjuvant radiotherapy. Follow-up was available in 16 cases (median 21.5 months). Two patients died of disease. Vascular and soft tissue invasion are the most common diagnostic histologic features of PC. Capsular invasion is important to distinguish PC from its benign counterparts. Intraoperative frozen section examination can be used for accurate diagnosis and surgical management.

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Objective:To investigate the value of CT tumor-thyroid marginal contact range (MCR) for predicting capsular invasion and cervical lymph node metastasis in papillary thyroid carcinoma (PTC) with a diameter>1.0 cm and papillary thyroid microcarcinomas (PTMC) with a diameter ≤ 1.0 cm, and to evaluate the diagnostic efficacy of direct CT signs for lymph node metastasis.Methods:The CT data of 148 patients with PTC (>1.0 cm) and 193 patients with PTMC confirmed by surgery and pathology were retrospectively analyzed from January 2017 to April 2020 at Hangzhou First People′s Hospital. MCR was evaluated based on CT images and classified as<1/4 tumor circumference or ≥1/4 tumor circumference. Direct CT signs of cervical lymph nodes were observed, including cystic change, microcalcification, hyperenhancement, short/long diameter≥0.5, clustered lymph nodes or central area turbidity. The difference in the distribution of MCR between PTC (>1.0 cm) and PTMC was compared using the χ 2 test, and the efficiency of MCR and direct CT signs for diagnosing capsular invasion and lymph node metastasis was calculated using the pathological results as the gold standard. Results:In 148 PTC (>1.0 cm) and 193 PTMC patients, the pathological results showed capsular invasion in 88.5% (131/148) and 57.0% (110/193), and lymph node metastasis in 71.6% (106/148) and 44.0% (85/193), respectively. In PTC (>1.0 cm) patients, MCR≥1/4 tumor circumference was more common in patients with capsular invasion (χ2=22.211, P<0.001) and lymph node metastasis (χ2=4.746, P=0.029), and the corresponding sensitivity and specificity for predicting capsular invasion and lymph node metastasis were 84.7% (111/131) and 64.7% (11/17), 83.0% (88/106) and 33.3% (14/42), respectively. In PTMC patients, MCR≥1/4 tumor circumference was more common in patients with capsular invasion (χ2=66.066, P<0.001) and lymph node metastasis (χ2=5.343, P=0.021), and its sensitivity and specificity for predicting capsular invasion and lymph node metastasis were 87.3% (96/110) and 69.9% (58/83), 71.8% (61/85) and 44.4% (48/108), respectively. The sensitivity and specificity of direct CT signs for diagnosing lymph node metastasis in PTC (>1.0 cm) and PTMC were 89.6% and 73.8%, 69.4% and 76.9%, respectively. Conclusions:Both direct CT signs and MCR ≥ 1/4 tumor circumference can predict cervical lymph node metastasis in PTC patients, and the former had higher sensitivity and specificity. MCR≥1/4 tumor circumference has high efficiency for predicting capsular invasion in PTC patients.

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Objective: This retrospective study aimed to analyze the ultrasound (US) imaging features of solitary papillary thyroid carcinoma (PTC) located in the isthmus and to assess the risk factors for lymph node metastasis (LNM) and tumor capsular invasion. Methods: We included a total of 135 patients with solitary PTC located in the isthmus. All the cases underwent US, total thyroidectomy, and prophylactic central lymph node dissection. Patients' demographic and thyroid isthmus nodules' US characteristics, as well as risk factors associated with LNM and tumor capsular invasion, were analyzed. Results: It was revealed that the occurrence of LNM was higher in male patients than in female patients (P < 0.001). As risk factors, the size of PTC in the isthmus was found to be associated with LNM and tumor capsular invasion (P = 0.005 and 0.000, respectively). The area under the receiver operating characteristic curve (AUC) of the size of the isthmus PTC was 0.64 [95% confidence interval (CI) = 0.55-0.72], indicating a probability for LNM. The AUC value for tumor capsular invasion was 0.77 (95% CI: 0.68-0.83). When the threshold was set to 1.1 cm, the larger size indicated that there was a probability of occurrence of LNM with sensitivity and specificity of 47.4 and 73.7%, respectively. When the threshold was set to 0.7 cm, the larger size indicated that there was potentially a tumor capsular invasion, with sensitivity and specificity of 80.6 and 56.3%, respectively. Wider-than-tall nodules were found to be significantly different from those in LNM and tumor capsular invasion (P = 0.038 and 0.030, respectively). There were significant differences in tumor capsular invasion in extrathyroidal extension (ETE) compared with smooth or ill-defined and lobulated or irregular nodules (P = 0.017). Conclusions: This study showed that the incidence of LNM in male patients was higher than that in female ones. When a US image shows a thyroid isthmus nodule with a wider-than-tall shape, LNM and tumor capsular invasion were likely to occur. When a US image shows a thyroid isthmus nodule with an ETE, tumor capsular invasion was likely to occur. ETE and wider-than-tall may be indicators of FNA under US guidance, even though the size of thyroid isthmus nodule may be <1 cm.

RESUMEN

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and invasive encapsulated follicular variant of papillary thyroid carcinoma (EFV-PTC) are indistinguishable preoperatively. CD26 expression in follicular tumor-uncertain malignant potential (FT-UMP) is reported to be clearly higher than in that without capsular invasion. To verify the diagnostic significance of CD26 immunostaining in EFV-PTC, we examined the expression pattern of CD26 in non-invasive EFV-PTC (NIFTP) and invasive EFV-PTC. We performed immunohistochemical analysis using CD26 antibody for 37 NIFTPs and 54 EFV-PTCs (34 minimally invasive EFV-PTCs and 20 widely invasive EFV-PTCs). Most NIFTP samples showed an apical membranous pattern or a cytoplasmic diffuse pattern of expression. Invasive EFV-PTCs more frequently showed a cytoplasmic dot-like pattern, and the labeling indices of tumor cells with cytoplasmic dot-like patterns were significantly higher than those in NIFTPs. The sizes of dots seen in NIFTPs (mean: 1.12 µm) were significantly smaller than in invasive EFV-PTCs (1.33 µm), minimally invasive EFV-PTC (1.27 µm), and widely invasive EFV-PTC (1.38 µm). We, therefore, conclude that cytoplasmic diffuse and/or cytoplasmic dot-like CD26 expression, particularly the larger CD26-positive dots, could be useful markers for capsular invasion in EFV-PTC. CD26 immunostaining, using cell blocks or cytological specimens, may preoperatively distinguish between NIFTP and invasive EFV-PTC.

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