Anna Krzentowska

Background: Indeterminate thyroid cytology remains a major diagnostic challenge. Thyroid nodules classified as Bethesda category (BC) III and IV carry an intermediate risk of malignancy, and their management often involves a choice between active surveillance and diagnostic surgery. This study aimed to assess the prevalence of benign, low-risk, and malignant lesions in surgically treated patients with these nodules, and to identify factors associated with malignancy. Methods: We retrospectively analyzed 618 patients with BC III or IV thyroid nodules, selected from 2,239 patients who underwent thyroid surgery between October 2022 and December 2025 at a Tertiary Referral Endocrine Surgery Centre in Krakow. Histopathology followed the 2022 WHO Classification of Thyroid Tumors. Results: The distribution of tumor types differed significantly in both BCs III (n=365) and IV (n=253) nodules (both p<0.001), with benign lesions predominating (62.5% in BC III and 55.7% in BC IV), followed by malignant (30.4% and 32.8%) and low-risk lesions (7.1% and 11.5%), respectively. Younger age was associated with a higher risk of malignancy in both BC III (p=0.03) and BC IV (p=0.02). Sex was associated with lesion distribution in BC III (p = 0.016) but not BC IV (p = 0.06), and was not an independent predictor of malignancy. Tumor size ≥1 cm was associated with malignancy in BC IV (p=0.005), but not in BC III (p=0.35). Although age alone showed limited discriminative ability, multivariable analysis identified age <50 years as the only independent predictor of malignancy (adjusted OR 1.74; 95% CI 1.23–2.47; p=0.002) and lymph node metastasis (adjusted OR 4.56; 95% CI 1.19–17.53; p=0.03), while sex, chronic lymphocytic thyroiditis (CLT), and BC were not significant. Conclusions: In this surgical cohort of BC III and IV thyroid nodules, approximately one-third of lesions were malignant. Younger age was independently associated with malignancy, but its value as an isolated predictor was limited, and the overall discriminative performance of the multivariable model was modest. These findings may support individualized preoperative risk stratification; however, given the retrospective design and the selection of patients for surgery, they do not justify firm conclusions regarding the optimal extent of surgery.

Pituitary neuroendocrine tumors (PitNETs) are usually benign intracranial neoplasms that may exhibit invasion of the cavernous sinus, complicating surgery and increasing the risk of recurrence. This study aimed to investigate membranous E-cadherin (mE-cad) expression across PitNET subtypes and transcription factor (TF) lineages, including Pit-1 (pituitary-specific positive transcription factor 1), SF-1 (Steroidogenic Factor 1), and TPIT (T-box pituitary transcription factor), and its association with tumor invasiveness in sixty-nine patients. mE-cad expression was evaluated as the percentage of positive cells (0%, 1–10%, >10%) and by immunoreactive score (IRS). Staining intensity was scored as: 0, no staining; 1, weak; 2, moderate; 3, strong. The proportion of positive cells was scored as: 0, none; 1, 80%. Mean mE-cad expression was 5.2% in gonadotroph, 3.2% in corticotroph, 0.5% in lactotroph, and 17.5% in plurihormonal PitNETs. By TF lineage, the mean expression was 5.3% for Pit-1, 3.2% for TPIT, and 5.1% for SF-1. Low mE-cad expression (IRS 1–2) was associated with higher odds of cavernous sinus invasion compared with IRS 3–6 (adjusted OR = 6.0, 95% CI 1.08–33.4, p = 0.04), independent of tumor volume (adjusted OR = 4.0, 95% CI 1.50–10.7, p = 0.01). After restricting the analysis to the gonadotroph PitNET group, tumors with an IRS of 1–2 showed significantly higher invasiveness compared with those with an IRS of 3–6 (p = 0.012). These findings suggest that mE-cad may serve as a biomarker of PitNET invasiveness, with expression varying according to TF lineage and tumor subtype.

Objective: This study assessed the relationship between serum calcium (Ca) and parathyroid hormone (PTH) levels, the size and weight of the enlarged parathyroid gland (PG), and the results of technetium-99m-metoxyisobutylisonitrile (MIBI) parathyroid scintigraphy with single-photon emission computed tomography/computed tomography. Methods: Among 252 patients who underwent surgery for hyperparathyroidism between October 2022 and March 2025 at the Department of Endocrine Surgery of the University Hospital in Krakow, 212 patients with primary hyperparathyroidism (PHPT) were selected and divided into the MIBI(−) (n = 49) and MIBI(+) (n = 163) groups. Results: MIBI was positive in 76.9% and negative in 23.1% patients with PHPT. Mean PTH in the MIBI(+) and MIBI(−) groups was 177.3 ± 144.7 and 127.7 ± 59.4 pg/mL, respectively. Significant differences were found in PTH (p < 0.01), maximum excised PG size (p < 0.01), and weight (p < 0.01). PTH predicted positive scintigraphy in univariate analysis (OR = 2.65; 95% CI: 1.19–5.89; p = 0.02) and showed a borderline association in the multivariate model (OR = 2.47; 95% CI: 0.95–6.41; p = 0.06). Optimal cut-offs for predicting MIBI positivity were 135.0 pg/mL for PTH (AUC = 0.64), 0.73 g for PG weight (AUC = 0.81), and 18.0 mm for PG maximum size (AUC = 0.78). The Wisconsin index (Ca × PTH) was associated with positive MIBI (OR = 2.58; 95% CI: 1.15–5.78; p = 0.02), with an optimal cut-off of 256.0. Serum total Ca levels showed no significant association with positive MIBI (p = 0.60). Conclusions: Serum PTH levels, Wisconsin index, and enlarged PG size and weight may help predict parathyroid scintigraphy outcomes.

Addison’s disease (AD) is a relatively uncommon illness presented by decreased adrenal production of adrenocortical hormones - mainly glucocorticoids. We present a case of a patient who had symptoms of chronic fatigue, depression that made it difficult for her to carry out everyday household activities. In basic laboratory tests, they mainly noted low sodium (Na), increased potassium (K) and low fasting glucose concentration. The patient’s informed consent was obtained for the presentation of anonymised laboratory, clinical and imaging data. On the basis of the clinical picture and hormonal tests, Addison’s disease was confirmed. Significant clinical improvement was observed following the addition of hydrocortisone to the treatment regimen. Advances in optimizingtreatment for patients with Addison’s disease have enabled them to lead normal lives. However, it is important to continuously educate patients and healthcare professionals about the ever-present threat of adrenal crisis.

Pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, are rare tumors that are usually benign. At present, the WHO PitNET classification based on transcription factors is in force. A problem is caused by invasive tumors and silent tumors which, despite a lack of obvious clinical symptoms, tend to behave aggressively. Factors influencing the clinical course of these tumors are currently being sought. The aim of our study was to assess the expression of programmed death-ligand 1 (PD-L1) and proliferation biomarkers (Ki-67, cyclin D1, and P53) in PitNETs depending on the transcription factor and adenoma subtype. The analysis was performed in seventy-four patients operated on in a single neurosurgical center for pituitary tumors. Immunohistochemistry was performed for transcription factors and biomarkers—PD-L1, Ki-67, P53, and cyclin D1—in tissue microarray format. Membranous expression of PD-L1 was scored as 0 (no expression) and ≥1%. Nuclear expression of Ki-67 was scored at p = 0.03). All tumors (100%) with a combination of cyclin D1 ≥ 10% and P53 < 10% were invasive on the Hardy scale. Of the four factors, PD-L1 increased the odds of invasiveness the most (adjusted OR = 2.35; 95% CI: 0.56–9.90). PD-L1 expression was present in some types of PitNETs. PD-L1 expression may help in identifying null cell adenomas. High cyclin D1 with low P53 may indicate greater tumor invasiveness.

Objective: The aim of our study was to assess the expression of Programmed death-ligand 1 (PD-L1) and proliferation biomarkers (Ki-67, cyclin D1 and P53) in Pituitary Neuroendocrine Tumors (PitNETs) depending on the transcription factor and adenoma subtype. Material and methods: The analysis was performed in seventy-four patients operated on in a single neurosurgical centre for pituitary tumor. Immunohistochemistry was performed for transcription factors and biomarkers: PD-L, Ki-67, P53 and cyclin D1 in tissue microarray format. Membranous expression of PD-L1 was scored as 0 (no expression) and ≥1%. Nuclear expression of Ki-67 was scored at <3% and ≥3%, expression of P53 and Cyclin D1 were scored at <10% and ≥10%. Results: The following tumors expressed PD-L1≥1%: gonadotroph - 21 (28.4%), corticotroph - 5 (6.7%), gonadotroph/lactotroph - 2 (2.7%), null cell adenoma - 3 (4.0%), multiple synchronous PitNET - 2 (2.7%); immature PIT-1 tumour – 1 (1.3%); mature PIT-1 tumor -1 (1.5%). KI≥3% was found in the following types of PITNETs: gonadotroph – 3 (4.0%), corticotroph - 2 (2.7%), lactotroph – 1 (1.3%), multiple synchronous PitNET – 1 (1.3%), immature PIT-1 tumor -1 (1.3%), mature PIT-1 tumor -1 (1.3%). Of the four factors, PD-L1 increased the odds of invasiveness the most (adjusted OR = 2.35; 95% CI: 0.56–9.90). Patients with K≥3% were statistically significantly younger (p=0.03). All tumors (100%) with a combination of Cyclin D1≥10% & P5310% may affect the invasiveness of PitNETs. Further studies are needed in a larger group of patients to determine the importance of this factor, as well as studies on the role of cyclin D1 in PitNETs.

Background: Our study investigated the association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer (TC). Methods: A retrospective review of 1670 patients who underwent thyroid surgery between October 2022 to February 2025 was performed. The clinicopathological characteristics of patients with TC and CLT were collected. CLT was diagnosed histopathologically. Results: Patients with a positive CLT result (60.39%) compared to a negative CLT result (34.12%) had more frequently TC (p < 0.001), predominantly PTC. In univariate analysis, patients with malignancy + CLT-positive compared to malignancy + CLT-negative were found to be younger in age (p < 0.001), female gender (p < 0.001), smaller tumours focus (p = 0. 013), smaller mass of thyroid removed (p < 0.001) and more often Bethesda category V and VI (p = 0.019), true positive fine needle aspiration biopsy (FNAB) for PTC (p = 0.009), and microcarcinoma (p = 0.021). There were no differences in multifocality, the presence of LNM, or the number of LNMs. The location of metastases at neck lymph nodes was at the borderline of significance (p = 0.065). In multivariate analysis, after accounting for Bethesda and age, CLT+ was found to increase the risk of TC by 73% (OR = 1.73; 95%CI, 1.15-2.29), while the risk of PTC increased more than 2-fold (OR = 2.12; 95% CI, 1.45–3.11). CLT had no statistically significant effect on the presence of LNM. Conclusions: We found that CLT is a risk factor for TC. One should be vigilant concerning the coexistence of these two diseases. We suggest that total thyroidectomy should be considered in patients referred for thyroid nodules and suspected CLT. However, this issue requires further research.

Background/Objective: Pituitary neuroendocrine tumors (PITNETs) often show a tendency towards invasive behavior, i.e., an invasion towards the cavernous sinuses or destruction of the sella turcica. In the present study, we analyzed whether a transcriptionally active HPV infection affects the invasiveness of pituitary tumors. Methods: Sixty patients with different phenotypes of PITNETs who underwent neurosurgery were studied. The obtained postoperative material was analyzed histopathologically. For each patient, formalin-fixed paraffin-embedded blocks were cut into ultra-thin slices and two to three of them were designated for DNA extraction, while one was used for histological slides. Based on the isolated DNA, the presence of DNA from individual HPV types was determined by the real-time detection polymerase chain reaction using the REALQUALITY RQ-Multi HPV Detection reagent kit (AB ANALITICA, Italy). P16 protein expression was assessed by immunohistochemical staining on the histological slides. A transcriptionally active infection with individual HPV types was distinguished when HPV DNA and P16 protein overexpression were detected simultaneously for a given tumor. Results: In the group of the 60 analyzed PITNETs, a transcriptionally active high-risk HPV infection was detected in a subset of 11 tumors (18.3%). This infection was associated with a significantly lower probability of tumor invasiveness, measured on both the Knosp (OR = 0.11, 95% CI: 0.02–0.58) and Hardy scales (OR = 0.12 95% CI: 0.024–0.56). Conclusions: Further studies are needed to confirm the prevalence of transcriptionally active HPV infections in pituitary adenomas and the role of these infections in the invasiveness of pituitary tumors.

The human pituitary is a gland located within a small bony box, the sella turcica, under the base of the brain

Objective: The objective of the study was to provide radiological and immunohistochemical evaluation of pituitary neuroendocrine tumors (PitNETs) concentrating on their invasiveness, endocrine function and expression of transcription factors. Methods: 79 cases of PitNETs were analyzed. The analysis included their MRI features, invasiveness and immunophenotype (immunoexpression of transcription factors Pit-1, SF1, TPit and the hormones). Results: Tumors from the SF1 line were statistically significantly more likely to show a tendency to invade the sella turcica (p<0.0001), while tumors from the Pit-1 and TPit factor lines were demonstrated to be both invasive and non-invasive, and the difference was not statistically significant. No statistically significant difference was found in the invasion of the cavernous sinuses by the pituitary tumors regardless of the transcription factor from which they originated. No statistically significant differences were observed between hormonally active and inactive tumors in terms of gender, age, invasiveness, size, or volume. Conclusions: PitNETs, also known as pituitary adenomas, continue to represent a significant challenge for clinicians. Tumors from the SF1 factor line are characterized by a statistically significantly more frequent invasion directed towards the sella turcica, while tumors from the Pit-1 and TPit lines do not show such a relationship. Patients with corticotroph PitNETs need to be controlled due to the proclivity of the tumors for aggressive behavior. Other types of PitNETs are less common. Tumors that express multiple transcription factors necessitate the patient to be subjected to further diagnostic and investigative procedures.