Nil Comunoglu

Objective: Chondroblastoma (CB) is a benign but locally aggressive bone tumor that may present histopathologic diagnostic challenges, particularly in atypical locations and limited biopsy specimens. Recent studies have identified recurrent mutations in the H3F3B and, less frequently, H3F3A genes, suggesting their potential diagnostic value. This study aimed to evaluate the prevalence and diagnostic utility of H3F3A and H3F3B mutations in a multicenter cohort of CB patients. Methods: Forty-three patients with histopathologically confirmed CB were included in a retrospective analysis. All cases were re-evaluated by 2 pathologists, and mutation analysis of H3F3A and H3F3B genes was performed using polymerase chain reaction–based Sanger sequencing. Results: H3F3B mutations were detected in 41 cases (95.3%), all corresponding to the Lys36Met substitution. One case (2.3%) harbored an H3F3A Gly34Trp mutation, whereas 1 case (2.3%) showed no detectable mutation. No significant histopathological differences were observed between mutation-positive and mutation-negative cases. A notable case involved a 72-year-old patient with frontal bone involvement, highlighting the diagnostic difficulty in unusual locations and older age groups. Conclusion: The findings demonstrate that H3F3B mutation analysis is an extremely sensitive and reliable molecular tool for confirming the diagnosis of CB. It is particularly valuable in challenging cases and especially in small biopsy samples where pathognomonic findings, such as chicken-wire calcification and chondroid matrix are not visible. Incorporation of molecular testing into targeted diagnostic workflows may improve diagnostic accuracy and assist in distinguishing CB from its histological mimics. Cite this article as: Tosun I, Yilmaz I, Cakir A, et al. H3F3B gene mutation in chondroblastomas: a multicenter study. Acta Orthop Traumatol Turc.,2026; 60(4), 0277, doi: 10.5152/j.aott.2026.25277.

Introduction: Research on immune checkpoint molecules is increasing, reflecting their critical role in cancer pathogenesis. While PD‐1, PD‐L1, and CTLA‐4 have been widely studied in head and neck cancers, outcomes remain unsatisfactory, highlighting the need for novel prognostic markers and therapeutic targets. This study evaluated the prognostic significance of TIM‐3 and LAG‐3 expressions in laryngeal squamous cell carcinoma. Methods: Fifty patients who underwent open partial or total laryngectomy for laryngeal squamous cell carcinoma (2016–2018) were retrospectively analyzed. Tumor specimens were assessed by immunohistochemistry for TIM‐3 and LAG‐3 expressions, as well as overall immune infiltration. Survival analyzes were performed using Kaplan–Meier and multivariable Cox regression models. Results: TIM‐3 expression showed no significant prognostic impact in the overall cohort but was associated with worse overall survival in the low‐to‐moderate immune infiltration subgroup ( p = 0.045). LAG‐3 positivity correlated with reduced recurrence‐free survival in the full cohort ( p = 0.015) and with both overall and recurrence‐free survival in the low/moderate infiltration subgroup ( p = 0.029 and p = 0.016, respectively). Multivariable Cox regression suggested LAG‐3 as an independent predictor of recurrence, while TIM‐3 showed an effect on overall survival only in the low/moderate immune infiltration subgroup. Conclusion: TIM‐3 and LAG‐3 expressions are associated with adverse outcomes in laryngeal cancer, particularly in tumors with limited immune infiltration. These findings are exploratory and support further multicenter studies to validate their prognostic and potential immunotherapeutic relevance. Level of Evidence: 3.

Objective: Crooke cell adenomas (CCAs) are considered rare and potentially aggressive variants of corticotroph adenomas. However, data on their clinical behaviour remain limited. This study aimed to compare the clinical, biochemical, radiological, and surgical outcomes of patients with CCAs and non‐CCA Cushing's disease (CD). Material and Methods: We retrospectively analyzed patients diagnosed with CD at our tertiary Pituitary Centre. Clinical presentation, baseline biochemical characteristics, tumour size, Ki‐67 index, remission rates, recurrence, and presence of residual tumour on follow‐up MRI were compared between CCA and non‐CCA groups. Results: At baseline, patients with CCAs ( n = 21) and non‐CCAs ( n = 60) demonstrated comparable biochemical profiles, except for ACTH levels, which were higher in the CCA group compared with the non‐CCA group ( p = 0.007). Remission and recurrence rates at 3, 6, and 12 months did not differ significantly between the two groups ( p > 0.05 for all). However, CCAs tended to present with larger tumour sizes and higher Ki‐67 proliferation indices than non‐CCAs ( p = 0.055 and p = 0.05, respectively). Moreover, residual pituitary lesions were more frequently detected on follow‐up MRI among patients with CCA ( p = 0.005). Conclusion: Our findings suggest that CCAs may not be as aggressive as previously assumed with respect to biochemical remission and recurrence rates. Nonetheless, their larger tumour size, higher proliferative index, and increased likelihood of residual disease underscore the importance of careful long‐term follow‐up. Further multicenter studies are warranted to better characterize the clinical course of CCAs.

Aim. Granular cell tumors (GCTs) are mostly benign. Malignant GCTs are extremely rare. Although the criteria proposed by Fanburg-Smith et al are widely used, some authors do not find them especially useful. We aimed to present our GCT case series consisting of 54 patients from 2 institutions during a 22-year period and evaluate these tumors according to these criteria of malignancy. Materials and Methods . Fifty-four patients with GCT diagnosed between 2000 and 2024 were retrospectively reviewed. All hematoxylin/eosin-stained slides were evaluated for spindling pattern, nucleolar prominence, pleomorphism, geographical necrosis, increase in nuclear/cytoplasmic ratio, and mitotic index. Results . Overall, 7 tumors were classified as “Malignant GCT.” Histopathologically all malignant tumors showed nucleolar prominence and pleomorphism. Ki-67 proliferation index was 3% or higher in 6 tumors. In 4 of the malignant GCTs, lymph node metastasis was present at the time of diagnosis. In 2 of these patients, lung metastasis and in 1 patient liver metastasis were also found. Another malignant tumor showed bone invasion. In one of the malignant tumors, local recurrence, lymph node metastasis, and lung metastasis occurred 1 year after excision. Conclusions . Malignant GCTs had behaved as frequently metastasizing high-grade sarcomas.

Purpose: In the 2021 World Health Organization (WHO) classification, ependymomas were classified according to their anatomical localization and molecular features. The “RELA fusion‐positive ependymoma” group, which was the first defined molecular subtype in the previous (2016) classification, was included as “ZFTA fusion‐positive ependymoma” in the final classification. We aimed to determine ZFTA fusion‐positivity in supratentorial (ST) and posterior fossa (PF) ependymomas and to investigate the correlation with both L1CAM and p65 immunoreactivity. Methods: The study included 17 ST and 9 PF cases with Grades 1, 2, and 3 ependymomas. The presence of the ZFTA fusion was evaluated using the fluorescence in situ hybridization (FISH) technique. L1CAM and p65 antibodies were applied for immunohistochemical analysis. The immunoreactivity for L1CAM and p65 was correlated with ZFTA fusion as assessed by FISH. Prognostic significance of the same was evaluated using the Kaplan–Meier survival analysis. Results: ZFTA fusion‐positivity was detected in 7 of 12 (58%) ST‐localized Grade 3 ependymoma cases; however, it was not observed in PF‐localized cases or in ST‐localized Grade 1 subependymoma (SE) and Grade 2 ependymoma cases. Six of the seven ZFTA fusion‐positive cases exhibited clear cell morphology. All ZFTA fusion‐positive cases showed L1CAM immunohistochemical positivity, and six of them also demonstrated nuclear p65 positivity. Moreover, we identified a new FISH pattern, which we termed the “short break‐apart.” Conclusion: Together, these data indicate a strong correlation between FISH and immunohistochemistry results. However, a more reliable assessment on this matter could be accomplished through a multicentric study involving a larger number of cases.

Aims: Epilepsy, particularly drug-resistant epilepsy in adults, is often caused by Mesial Temporal Sclerosis (MTS), which can develop after brain injury from febrile illnesses or trauma. Magnetic Resonance Imaging (MRI) is crucial for diagnosing MTS, although challenges such as patient movement and mild or bilateral hippocampal atrophy can complicate the diagnosis. T1-weighted hippocampal volume measurements are effective in detecting MTS, with recent software advancements enabling automatic hippocampal segmentation. This study compared the hippocampal volumes and indices between adults with MTS and a control group of similar age and sex in the Turkish population. This study aimed to highlight structural differences in the hippocampus associated with MTS. Methods: This study involved a retrospective review of cranial MRIs scans from patients with MTS, confirmed through histopathological examination after epilepsy surgery. To ensure unbiased comparisons, a control group was selected using propensity score matching by age and gender. Two experienced neuroradiologists independently assessed the MRIs findings for MTS without knowledge of hippocampal volumetric data. Hippocampal volumes were measured using FreeSurfer software and standardized using the hippocampal volume index (HVI) and hippocampal asymmetry index (HAI). Results: In our study of 38 patients, MTS was found in 55.2% of patients on the right side and in 44.8% of patients on the left side, with no bilateral cases. Visual MRI analysis identified MTS in 84.2% of patients, with an area under of curve (AUC) of 0.921. Automatic volumetry detected MTS in 23 patients with an AUC of 0.791. Combining both methods, MTS was diagnosed in 33 patients, with an AUC of 0.922. Conclusion: Automated volumetric analyses have been shown to enhance the detection of hippocampal volume loss in patients with MTS.

Introduction: We examined the relationship between proinflammatory cytokines that occur in the inflammatory reaction in the intestine in Hirschsprung disease (HD) and Hirschsprung-associated enterocolitis (HAEC). Methods: Thirty cases (M:27, F:3) operated on due to HD. The cases were divided into three groups: group 1 with pre and post operative EC, group 2 with post-operative, and group 3 with pre-operative EC. The intestinal segments were evaluated by immunohistochemistry for interleukin 1 beta (IL-1ss), tumor necrosis factor-alpha (TNF-alpha), and interleukin 6 (IL-6). Results: IL-1 beta staining was significantly higher in the ganglionic zone of groups with enterocolitis compared to the control group (p = 0.012). TNF-alpha staining in the transitional zone of Group 3 and IL-1 beta staining in the ganglionic zone of Group 1 was significantly higher than the control group (p = 0.030, p = 0.020). Conclusion: In our study, older age at diagnosis and more than 20% IL-1ss staining in the ganglionic segment were found to be risk factors for HAEC. It is noteworthy that the increase in IL-1ss can be associated with HAEC.

Objective: Localized type tenosynovial giant cell tumor is a rare, benign tumor that originates from synovial joints, tendon sheaths, and bursae. It has two forms: diffuse and localized. The localized form is most commonly found in hand and knee joints. The aim of this study is to present and evaluate the behavior of the tumor, its recurrence rates, its distribution by gender and localization, and the demographic features of affected individuals. Methods: In this study, charts of patients operated on localized type tenosynovial giant cell tumors located at the upper extremity between 2000-2020 were retrospectively evaluated. Results: A total of 139 patients underwent surgery for localized type tenosynovial giant cell tumor of the upper extremity, with 99 of them being female and 40 being male. The average age of the patients was 45.9 years. Among these cases, 114 (82%) were localized in the fingers, 13 (9.8%) were in the palmar and dorsal region, 6 (4.3%) were in the wrists, 4 (1.88%) were in the elbows, and 1 (0.7%) was in the shoulder. The first finger was the most frequently affected location, accounting for 24.5% of cases, and the tumor was more commonly seen on the right hand. This study provides information on the tumor's location, its correlation with relapse, and any comorbidities that may be present. Conclusion: Localized-type tenosynovial giant cell tumors are rare neoplasms. This study concludes that overuse of the extremity and female sex may be risk factors for developing the tumor.