A Comprehensive Approach to the Thyroid Bethesda Category III (AUS) in the Transition Zone Between 2nd Edition and 3rd Edition of The Bethesda System for Reporting Thyroid Cytopathology: Subcategorization, Nuclear Scoring, and More.

Significant interobserver variabilities exist for Bethesda category III: atypia of undetermined significance (AUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Thus, subcategorization of AUS including AUS "nuclear" and AUS "other" is proposed in the recent 3rd edition of TBSRTC. This study investigated the impact of the nuclear features/architectural features/nuclear score (NS) (3-tiered)/subcategories and subgroups on risk of malignancy (ROM) in thyroid fine-needle aspirations (FNA). 6940 FNAs were evaluated. 1224 (17.6%) cases diagnosed as AUS were reviewed, and 240 patients (initial FNAs of 260 nodules and 240 thyroidectomies) were included. Subcategories and subgroups were defined according to TBSRTC 2nd and 3rd editions. Histological diagnostic groups included nonneoplastic disease, benign neoplasm, low-risk neoplasm, and malignant neoplasm. Overall, ROM was 30.7%. ROM was significantly higher in FNAs with nuclear overlapping (35.5%), nuclear molding (56.9%), irregular contours (42.1%), nuclear grooves (74.1%), chromatin clearing (49.4%), and chromatin margination (57.7%), and these features were independent significant predictors for malignancy. FNAs with NS3 had significantly higher ROM (64.2%). Three-dimensional groups were significantly more frequent in malignant neoplasms (35.7%). ROM was significantly higher in AUS-nuclear subcategory (48.2%) and in AUS-nuclear and architectural subcategory (38.3%). The highest ROM was detected in AUS-nuclear1 subgroup (65.2%). ROM was significantly higher in the group including AUS-nuclear and AUS-nuclear and architectural subcategories, namely "high-risk group" than the group including other subcategories, namely "low-risk group" (42.0%vs 13.9%). In conclusion, subcategorization may not be the end point, and nuclear scoring and evaluation of architectural patterns according to strict criteria may provide data for remodeling of TBSRTC categories.

The Impact of Total Tumor Diameter on Lymph Node Metastasis and Tumor Recurrence in Papillary Thyroid Carcinomas.

(1) Introduction: The impact of multifocality/bilaterality on the prognosis of papillary thyroid carcinoma (PTC) is a matter of debate. In order to clarify this debate, several studies have attempted to identify additional parameters associated with poor prognosis, including total tumor diameter (TTD), in the context of multifocal PTCs. In this context, this study was carried out to investigate the impact of TTD on tumor recurrence and lymph node metastasis (LNM) in PTCs. (2) Materials and Methods: The sample of this single-center retrospective study consisted of 706 patients diagnosed with PTC. TTD was calculated as the sum of the largest diameters of tumor foci in multifocal tumors. The resulting TTDs were grouped into TTDs ≤ 10 mm, TTDs > 10 mm, TTDs ≤ 20 mm, and TTDs > 20 mm, using 10 mm and 20 mm as cutoff values. (3) Results: There was no significant difference between multifocal papillary microcarcinomas (PTMCs) with a TTD of >10 mm and unifocal PTCs with a primary tumor diameter (PTD) of >10 mm except for advanced age and lymphovascular invasion (LVI). In addition, perineural invasion (PNI) and TTD > 10 mm were found to be significant risk factors for LNM, and PNI, TTD > 10 mm, TTD > 20 mm, and bilaterality were found to be significant risk factors for recurrence. LVI, and TTD > 10 mm were found to be independent significant predictors for recurrence, and LVI and extrathyroidal extension (ETE) were found to be independent significant predictors for LNM. (4) Conclusions: Considering TTD > 10 mm in recurrence risk categorization models and adopting a clinical approach that takes into account multifocal PTMCs with TTD > 10 mm along with unifocal PTCs with PTD > 10 mm may be more useful in terms of clinical management of the disease.

Assessing the correlation between FDG PET findings of IDC breast carcinoma and histopathology of coexisting ductal carcinoma in-situ.

BACKGROUND: Ductal carcinoma in-situ (DCIS) often coexists with invasive ductal carcinoma (IDC) of the breast. DCIS is considered as a non-obligate precursor of IDC when both coexist. 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) imaging is commonly used in the staging and follow-up assessment of breast cancer. In this study, we aimed to assess if there is any correlation between primary tumor PET and histopathology findings and histopathological features of the coexisting DCIS. MATERIAL AND METHODS: FDG PET/CT images and histopathology results of the patients with newly diagnosed breast cancer (IDC) with coexisting DCIS were analyzed in this retrospective study. The grade and size of the primary tumor and histopathological features of the coexisting DCIS (nuclear grade and architectural pattern) were obtained from the postoperative histopathology results. Maximum standardized uptake values (SUV: SUVmax and SULmax) of the primary tumor normalized by weight and lean body mass were measured. Statistical analysis was performed to assess the correlation between various parameters of IDC and DCIS. RESULTS: This study included sixty-two (62) patients with IDC-DCIS. Primary tumor grade was significantly correlated and associated with the nuclear grade of the coexisting DCIS (polychoric correlation r = 0.736, and Fisher exact test, PV < 0.001, respectively). Primary tumor SUV was not correlated with the nuclear grade and architectural pattern of the coexisting DCIS (polyserial correlation r = 0.172, PV = 0.155, and Point Bi-Serial correlation r = -0.009, PV = 0.955, respectively). Median primary tumor size was marginally significantly different among DCIS nuclear grades but it was not significantly different in comedo and non-comedo cases (Kruskal-Wallis test PV = 0.053, and Mann-Whitney U test PV = 0.890, respectively). CONCLUSIONS: Primary tumor grade is correlated with the nuclear grade of the coexisting DCIS. SUV of primary tumor does not seem to be correlated with the histopathological features of coexisting DCIS (nuclear grade and architectural pattern) but this may be further studied in a larger number of patients.

Is there a difference in FDG PET findings of invasive ductal carcinoma of the breast with and without coexisting DCIS?

OBJECTIVES: Studies have reported that invasive ductal carcinoma (IDC) with coexisting ductal carcinoma in situ (DCIS) show lower metastatic potential and recurrence and better overall survival than pure IDC. In this study, we assessed F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images of patients with newly diagnosed IDC to determine if there is any difference in PET findings in IDC-DCIS and pure IDC cases. METHODS: FDG PET/CT images of patients with newly diagnosed IDC of the breast who subsequently underwent breast surgery and had histopathology result in our records were further evaluated. Tumor grade, pathological staging, and presence of DCIS were noted from the histopathology results. Standardized uptake value (SUV) of the primary tumor (SUVmax and SULmax), other hypermetabolic foci in the breast, and ipsilateral normal breast were measured. Presence of axillary and distant metastases was noted. RESULTS: Fifty seven (57) patients with IDC were included. Coexisting DCIS was present in 44 (IDC-DCIS) and not present in 13 (pure IDC) cases. Per histopathology, the primary tumor was unifocal in 33 IDC-DCIS (75%) and 12 pure IDC (92.3%) cases, and multifocal in 11 IDC-DCIS cases (25%), and 1 pure IDC case (7.7%). FDG uptake was multifocal in 20 IDC-DCIS cases (45.5%) and 1 pure IDC case (7.7%), and unifocal in 24 IDC-DCIS (54.5%), and 12 pure IDC (92.3%) cases. There was no significant difference in patient age, size of the primary tumor, SUVmax and SULmax of the primary tumor and SUVmax of the normal breast in IDC-DCIS and pure IDC cases (p>0.05). Pathology showed axillary metastasis in all 13 pure IDC (100%), and 27 IDC-DCIS (61.4%) cases. PET showed axillary uptake in 25 IDC-DCIS (56.8%), and 8 pure IDC (61.5%) cases, and abnormal/questionable distant uptake in 12 IDC-DCIS cases and 1 pure IDC case. CONCLUSION: In our preliminary findings, multifocal breast FDG uptake and multifocal tumor appear to be more common in IDC-DCIS than pure IDC. There is no significant difference in SUV and size of the primary tumor in IDC-DCIS and pure IDC cases. Axillary metastases appear to be more common in pure IDC than IDC-DCIS cases.

Follicular morphological characteristics may be associated with invasion in follicular thyroid neoplasms with papillary-like nuclear features.

The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors. In this study, we examined the predictive value and association of follicular morphological characteristics with the tumor invasion. In addition, we analyzed the association between tumor encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases of FVPTC were included in the study. The tumors were grouped based on the presence of tumor capsule and characteristics of tumor border, as 1) completely encapsulated tumors without invasion, 2) encapsulated tumors with invasion, 3) infiltrative tumors without a capsule. Clinicopathological features, histomorphological features [nuclear criteria, minor diagnostic features, follicles oriented perpendicular to tumor border/capsule (FOPBC)] and molecular alterations in BRAF, NRAS, and KRAS genes were evaluated. FOPBC were significantly more frequently seen in encapsulated tumors with invasion (p = 0.008). The nuclear features were not associated with the presence of encapsulation and characteristics of tumor border. BRAF mutation was more frequent in infiltrative tumors, while NRAS mutation was more frequent in encapsulated tumors, but the results were not statistically significant (p = 0.917). In conclusion, FOPBC histomorphological feature may be associated with tumor invasion in EFVPTC/NIFTP. Additionally, BRAF/KRAS/NRAS mutation analysis may prevent inadequate treatment in these patients.

Histopathological Evidence of Lymph Node Metastasis in Papillary Thyroid Carcinoma.

Prophylactic lymph node dissection is still controversial due to the potentially surgery-related morbidity in management of papillary thyroid carcinomas. So, some histopathological predictors for lymph node metastasis in thyroidectomy specimens may reveal importance. The objective of this study was to define histomorphological indicators of lymph node metastasis in the patients who had been performed thyroidectomy without lymph node dissection. Clinicopathological features of patients archived in Department of Pathology at Trakya University Medical Faculty were reviewed. A total of 211 patients who had been diagnosed as papillary carcinoma and had been performed total thyroidectomy/lobectomy with central/cervical lymph node dissection were included in the study. Clinical features (age, gender, preoperative/postoperative clinical, and laboratory findings) and histopathological features (histological variant, tumor size, focality, extrathyroidal extension, tumor border, lateral tubular growth, intraglandular dissemination, stromal and lymphocytic tumor response, lymphocytic thyroiditis, lymphovascular invasion, lymph node metastasis, number of metastatic lymph nodes, extranodal extension, size of the metastatic foci) were evaluated. Male gender, conventional variant, tumor size greater than 10 mm, multifocality, extrathyroidal extension, lateral tubular growth, intraglandular dissemination, lymphocytic and stromal tumor response, and absence of lymphocytic thyroiditis were predictive, and older age (≥45 years) and follicular variant PTC were protective for lymph node metastasis. In order to optimize the management of papillary thyroid carcinomas, pathologists should search for the clues of lymph node metastasis particularly intraglandular dissemination, lateral tubular growth, tumor border and lymphocytic/stromal tumor response, multifocality, concomitant lymphocytic thyroiditis besides the actual prognostic criteria especially in younger aged male patients.

Combined effects of tauroursodeoxycholic Acid and glutamine on bacterial translocation in obstructive jaundiced rats:.

BACKGROUND: Bacterial Translocation is believed to be an important factor on mortality and morbidity in Obstructive Jaundiced. AIMS: We investigated the probable or estimated positive effects of tauroursodeoxycholic acid, which has antibacterial and regulatory effects on intestinal flora, together with glutamine on BT in an experimental obstructive jaundiced rat model. STUDY DESIGN: Animal experimentation. METHODS: Forty adult, male, Sprague Dawley rats were used in this study. Animals were randomised and divided into five groups of eight each: sham (Sh); control (common bile duct ligation, CBDL); and supplementation groups administered tauroursodeoxycholic acid (CBDL+T), glutamine (CBDL+G), or tauroursodeoxycholic acid plus glutamine (CBDL+TG). Blood and liver, spleen, MLN, and ileal samples were taken via laparotomy under sterile conditions for investigation of bacterial translocation and intestinal mucosal integrity and hepatic function tests on the tenth postoperative day. RESULTS: There were statistically significant differences in BT rates in all samples except the spleen of the CBDL+TG group compared with the CBDL group (p=0.041, p=0.026, and p=0.041, respectively). CONCLUSION: It is essential to protect hepatic functions besides maintaining intestinal mucosal integrity in the active struggle against BT occurring in obstructive jaundice. The positive effect on intestinal mucosal integrity can be increased if glutamine is used with tauroursodeoxycholic acid, which also has hepatoprotective and immunomodulatory features.