Background: Prophylactic central lymph node dissection (pCND) in papillary thyroid carcinoma (PTC) is still a matter of debate. Therefore, we aimed to identify the factors affecting central lymph node metastasis (CLNM) in patients with clinically node-negative (cN0) PTC. Methods: This retrospective study included 248 patients with cN0 PTC who underwent total thyroidectomy (TT) or TT + pCND. Clinicopathological associations among CLNM, complication rates and the effect of pCND on staging were assessed. Risk factors (RFs) and the pattern of lymph node metastasis (LNM) in PTC patients were studied via multivariate analysis. Results: A total of 216 patients underwent pCND, and 58.8% (127/216) had positive CLNM. Male patients, aged < 41 years, and those with lymphatic invasion were identified as RFs for CLNM, with odds ratios of 2.59, 2.26, and 4.09, respectively. Among the 216 patients, 65 (30%) had transient hypoparathyroidism (HPT), and 20 (9.3%) had permanent HPT. Transient recurrent laryngeal nerve (RLN) palsy occurred in 15 (6.9%) patients, and permanent RLN palsy occurred in 3 (1.4%) patients. Over 55 years of age, 46.7% of patients were upstaged according to the American Joint Committee on Cancer (AJCC) TNM staging system, and 14.2% (n = 18) of the 127 patients with CLNM were upgraded according to the American Thyroid Association (ATA) risk stratification system (RSS). Conclusion: Taken together, in terms of the high incidence rate of CLNM in cN0 PTC patients; We believe that routine pCND, which can be performed with low morbidity rates, is optimal for cN0 PTC patients during their first treatment, especially for those with RFs for CLNM. Clinical trials number: NCT05873283.

Background/Objectives: Advances in the genetic understanding of pheochromocytoma–paraganglioma (PPGL) have considerably refined personalized approaches to diagnosis and management. This study aims to present our institutional experience on the diagnostic characteristics, clinical course, and genetic background of patients with PPGL, in the context of the current literature. Methods: This retrospective analysis included 35 patients diagnosed with PPGL between years 2020 and 2024, all of whom underwent surgical resection and next-generation sequencing for germline mutations in major PPGL susceptibility genes. Clinical presentation, biochemical profile, pathological findings, and follow-up outcomes were compared between mutation-positive and mutation-negative cases. Results: Of the 35 patients with PPGL, germline mutations were identified in 6 patients (17%): 2 in Cluster 1A genes (SDHA, SDHB), 2 in Cluster 1B (VHL), and 2 in Cluster 2 (NF1). Consistent with existing literature, pathogenic germline variants—particularly SDHB and VHL—were identified in our cohort exclusively in patients younger than 30 years (ages 17, 20, and 25). Mutation-positive patients more frequently exhibited noradrenergic or non-secretory profiles (p = 0.01). Among the three non-secretory tumors in the cohort, two harbored genetic mutations (SDHA, NF1). Interestingly, both NF1-positive patients were normotensive—one (c.3496G > A) with a non-secretory tumor and the other (c.2329T > A) presenting at an unusually late age (63 years)—a strikingly atypical spectrum that underscores the phenotypic variability of NF1-associated PPGL. Bilateral disease was observed exclusively in VHL carriers (p = 0.03). Importantly, we identified a rare VHL c.369delG frameshift variant, not previously reported in association with PPGLs, in a patient with PPGL. No significant difference was observed between SDHB loss (p = 0.1) and proliferative indices (mitotic count, Ki-67) (p = 0.07, p = 0.6) between the two groups. During a median follow-up of 24 months (IQR: 18–36), one SDHB-positive patient had a recurrence, while no distant metastases were detected in the remaining mutation carriers. Conclusions: These findings support characteristic clinical patterns among mutation-positive PPGL and underscore the importance of systematic germline testing in all cases—irrespective of age, family history, or biochemical profile—to guide individualized management and enable cascade screening. The identification of a rare VHL c.369delG variant, previously unreported in association with PPGL, within a characteristic VHL-related clinical phenotype highlights the importance of this association. Similarly, atypical NF1 cases emphasize phenotypic variability and reinforce the importance of germline testing even in clinically silent presentations.

Background: We aim to investigate any possible associations between chemokine receptor expression and responses to neoadjuvant chemotherapy (NAC) along with outcomes in patients with triple-negative breast cancer (TNBC) with locally advanced disease. Method: Expressions of chemokine receptors were examined immunohistochemically after staining archival tissue of surgical specimens (n = 63) using specific antibodies for CCR5, CCR7, CXCR4, and CXCR5. Results: Patients with high CCR5, CCR7, CXCR4, and CXCR5 expression on tumors and high CXCR4 expression on tumor-infiltrating lymphocytes (TILs) were less likely to have a pathological complete response (pCR) or Class 0-I RCB-Index compared to others. Patients with residual lymph node metastases (ypN-positive), high CCR5_TM(tumor), and high CXCR4_TM expressions had an increased hazard ratio (HR) compared to others (DFS: HR = 2.655 [1.029–6.852]; DSS: HR = 2.763 [1.008–7.574]), (DFS: HR = 2.036 [0.805–5.148]; DSS: HR = 2.689 [1.020–7.090]), and (DFS: HR = 2.908 [1.080–7.829]; DSS: HR = 2.132 (0.778–5.846)), respectively. However, patients without CXCR5_TIL expression had an increased HR compared to those with CXCR5_TIL (DFS: 2.838 [1.266–6.362]; DSS: 4.211 [1.770–10.016]). Conclusions: High expression of CXCR4_TM and CCR5_TM was found to be associated with poor prognosis, and CXCR5_TM was associated with poor chemotherapy response in the present cohort with locally advanced TNBC. Our results suggest that patients with TNBC could benefit from a chemokine receptor inhibitor therapy containing neoadjuvant chemotherapy protocols.

Amyloid spherule-containing prolactinomas are rare entities associated with dopamine agonist (DA) resistance and aggressive behaviour. We report a giant amyloid spherule-containing prolactinoma with a substantial tumour burden and markedly elevated prolactin levels, highlighting novel multimodal therapeutic strategies. A 49-year-old man presented with headache and visual disturbance. Imaging revealed a giant pituitary macroadenoma (63 × 84 × 46 mm) with Knosp grade 4 cavernous sinus invasion and clivus erosion. Laboratory investigations revealed marked hyperprolactinemia (prolactin (PRL): 30,969 ng/mL) and autonomous growth hormone (GH) hypersecretion. Histopathology confirmed a sparsely granulated lactotroph tumour with extensive amyloid spherules and dystrophic calcifications (Ki-67: 8%). Notably, immunohistochemistry demonstrated PRL positivity without GH immunoreactivity, suggesting tumour heterogeneity with sampling limitations. Comprehensive systemic amyloidosis screening, the first systematic evaluation reported for this entity, excluded systemic disease. Following surgical debulking with extensive residual disease, postoperative cabergoline treatment resulted in a reduction in the PRL (4,700→927 ng/mL). Given the presence of amyloid-associated dopamine resistance, cabergoline was discontinued, and radiotherapy (RT) (45 Gy) was initiated to control the amyloid burden, followed by temozolomide. Based on evidence from other malignancies suggesting RT-mediated amyloid reduction, cabergoline was reintroduced postradiotherapy without paradoxical tumour growth. Concurrent cabergoline-temozolomide therapy, a novel approach that differs from conventional sequential protocols, achieved a dramatic response: 93.4% prolactin reduction (10,320→677 ng/mL) and 52.4% tumour volume reduction. This superior outcome far exceeded that of initial postsurgical cabergoline monotherapy (80% reduction), suggesting that RT successfully modulated the amyloid burden and restored dopamine sensitivity. This case suggests that RT may restore dopamine agonist sensitivity in patients with amyloid-containing prolactinomas, potentially enabling concurrent dopamine agonist-temozolomide therapy in refractory cases, warranting further validation.