Buket Yilmaz Bulbul

Tert expression in pituitary adenomas

OBJECTIVE Although pituitary adenomas have benign histomorphological features, some of them may present in an aggressive manner. To predict the behaviour of these tumours, telomerase reverse transcriptase (TERT) activity in pituitary adenomas has been the subject of a few studies with contradictory results. This study aims to investigate whether immunohistochemical expression of TERT differs in neoplastic and nonneoplastic pituitary tissues and aims to investigate whether TERT expression is related to clinicopathological features of pituitary adenomas. MATERIAL AND METHOD The study included 48 patients who had been diagnosed with pituitary adenomas and had clinical follow-ups. Nonneoplastic pituitary tissues were obtained from autopsy specimens (n=20). Immunohistochemistry for TERT antibody was performed. Both the nuclear and cytoplasmic expression of TERT antibody was noted, and total combined TERT staining was evaluated according to nuclear and cytoplasmic stainings. RESULTS TERT expression did not differ between neoplastic and nonneoplastic pituitary tissues. Neither total (combined nuclear and cytoplasmic) TERT nor nuclear TERT expression revealed any statistically significant relationship with any of the clinicopathological features. Higher cytoplasmic TERT expression was observed in adenomas with recurrence than adenomas without recurrence (p=0.035). CONCLUSION This study introduces the notion that immunohistochemical expression of TERT does not differ in neoplastic and nonneoplastic pituitary tissues. Pituitary adenomas with cytoplasmic immunohistochemical expression of TERT have significantly higher rates of recurrence. Further studies, including combined methods of immunohistochemistry and molecular analyses in larger groups, may reveal applicable results for the clinical significance of TERT in pituitary adenomas.

Histological perspective on the effects of tumor-associated macrophages in the tumor microenvironment surrounding papillary thyroid carcinoma

Tumor-associated macrophages (TAMs) are one of the most noticeable elements of the tumor microenvironment. The present study investigated the relationships between the density of CD163 immunolabeled M2-like TAMs with other histological properties of the tumor microenvironment and clinipathological features in 90 patients with papillary thyroid carcinomas (PTC). The percentage of TAMs was higher in tumors with significant lymphocytic tumor response (p = 0.020), in tumors with a significant degree of stromal tumor response (p = 0.014), those with infiltrative tumor borders (p = 0.029), in conventional variant papillary carcinoma (p = 0.032), and in patients with autoantibodies for thyroid peroxidase (p = 0.014). The tumors associated with lymphocytic thyroiditis had lower numbers of TAMs (p = 0.027). In conclusion, for the first time, the present study attempts to establish a full assessment of interactions of CD163 expressing M2-like TAMs with the triad of primary tumor- tumor microenvironment- tumor behavior and above all, with markers of autoimmunity. Thus, these alternatively polarized macrophages may act in tumor progression and dissemination according to their various products, which may be ordered by tumor cells or neighboring immune cells. The molecular studies may reveal their roles in various tumors and may improve the therapy strategies targeting TAMs in various malignant tumors, including PTCs.

Comparison of clinicopathological features in incidental and nonincidental papillary thyroid carcinomas in 308 patients

Incidental papillary thyroid carcinomas (IPTCs) consist of a significant portion of increasing incidence in papillary thyroid carcinomas. This study investigated the clinicopathological features of IPTCs from different perspectives and by comparing nonincidental PTCs (NIPTCs) in patients who underwent total thyroidectomy and lymph node dissection. Basic results were as follows. IPTC was present in 27.9% of 308 patients. IPTCs were significantly accompanied by lymphocytic thyroiditis (LT), particularly, multinodular hyperplasia (MNH). IPTCs were more common in older patients (51.3 years vs. 47.2 years) and in female patients. IPTCs significantly differed from NIPTCs in terms of smaller tumour size, lymphatic vessel invasion (2.6% vs. 97.4%), extrathyroidal extension (4.3% vs. 95.7%), lymph node metastasis (3.6% vs. 96.4%), multifocality (21.2% vs. 78.8%), bilaterality (5.3% vs. 94.7%), and BRAFV600 mutation (6.7% vs. 93.3%). Older age, bilaterality, encapsulation, and radioactive iodine (RAI) were significantly more common in IPTCs > 5 mm than in those ≤ 5 mm. In conclusion, IPTCs are more commonly associated with LT and MNH. IPTCs may have a more favourable prognosis than NIPTCs, and tumour size > 5 mm may predict bilaterality and need for RAI. Nevertheless, the patient-based clinical approach in IPTCs may have benefits in the management of IPTCs.

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.

Relationship between lymphovascular invasion and clinicopathological features of papillary thyroid carcinoma

Lymphovascular invasion (LVI) is an important prognostic factor in various solid tumors, however, data on the association between LVI and thyroid carcinomas are limited. In this study, we evaluated the relationship between LVI and clinicopathological features of papillary thyroid carcinoma (PTC). Six hundred seventy-eight patients diagnosed with PTC between 2012 and 2015 were included into the study. Patients were classified based on the presence or absence of LVI. Gender, age, ultrasonography (US), tumor size and multifocality, BRAFV600E mutation, perineural and capsular invasion, extrathyroid extension (ETE), nodal metastasis, and recurrences were evaluated, and risk analysis was performed for each parameter. The number of patients with LVI [LVI (+)] was 63, while the number of patients without LVI [LVI (-)] was 615. The female/male ratio was 564/114. LVI was present in 18.4% of male patients and in 7.4 % of female patients. In the age group between 17-25 years LVI was detected in 6/13 patients, and this result was statistically significant compared to other age groups (p = 0.004). Suspicious lymph nodes upon US, perineural or capsular invasion, ETE, tumor size, and nodal metastasis were significantly more frequent in LVI (+) group (p < 0.001). The frequency of BRAFV600E mutation was also significantly higher in LVI (+) group (p < 0.001). Overall, the presence of LVI was associated with gender, tumor size, age, lymph node metastasis, pathological lymph nodes, perineural and capsular invasion, ETE, and BRAFV600E mutation. These results suggest that in PTC patients undergoing thyroidectomy, the presence of LVI should be considered as an indicator of aggressive clinicopathological features and those patients should be followed up carefully for recurrences and metastasis.