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.

ABSTRACT 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.

This study aimed to assess the diagnostic accuracy of three large language models (LLMs)—ChatGPT-4o, Grok-3, and Claude 3.7 Sonnet—in differentiating cerebellopontine angle (CPA) schwannomas and meningiomas using clinical data combined with either raw images or structured imaging features. This retrospective pilot study included 53 patients with pathologically confirmed CPA tumors (28 meningiomas, 25 schwannomas). Each case was submitted to LLMs with clinical data and either raw imaging slices (clinical + images), expert-derived structured imaging features (clinical + expert prompt), or resident-derived structured features (clinical + resident prompt). To establish task difficulty and provide performance context, traditional machine learning algorithms were trained via nested cross-validation. Two board-certified neuroradiologists (each with 10 years of experience) and two third-year radiology residents independently contributed: one pair (B.K. and B.Y.) generated structured imaging features, while the other pair (S.A. and K.H.O.) independently evaluated all cases for performance comparison. Diagnostic performance was compared using McNemar’s and Cochran’s Q tests with 95

To evaluate predictors of mortality in acromegaly using machine learning (ML) models. We analyzed 607 patients with acromegaly. A grid search was applied to compare five types of prediction models in 1,200 configurations. Each model predicted mortality based on 40 disease characteristics, assessed using the Matthews’ correlation coefficient (MCC) and the area under the curve (AUC) metrics. To ensure robust and reliable predictions, we constructed a virtual ensemble model by generating 100 Explainable Boosting Machine (EBM) variants and evaluating their performance across 50 random train–test splits. The single EBM model fitted to all data achieved an MCC of 0.88 and an AUC of 0.99. Feature importance analysis identified hypertension, first-line transsphenoidal surgery (TSS), disease duration, baseline insulin-like growth factor 1 levels, hypopituitarism, and repeat TSS as key predictors of mortality. A virtual ensemble prediction model showed good generalization performance, with an MCC of 0.64 ± 0.08 and an AUC of 0.96 ± 0.015 across 50 random data splits. 58

Cushing's disease is a rare endocrine disorder characterized by excessive endogenous glucocorticoid production, primarily resulting from adrenocorticotropic hormone-secreting pituitary neuroendocrine tumors (ACTH-PitNETs). This study investigated the expression of several genes implicated in the development of ACTH-PitNETs, including EGFR, USP8, CABLES1, USP2, STAM2, VPS28, HDAC2, IL-6, SMARCA4, WEE1, CDKN2A, CCND1, NR4A1, NEUROD1, and RIPK1. The methylation levels of the USP8 and CDKN2A genes were also assessed for insights into their regulatory mechanisms.Formalin-fixed paraffin-embedded pituitary tumor tissue samples from 32 patients diagnosed with ACTH-PitNET and 15 anterior pituitary tissue samples were analyzed. Gene expression was analyzed through quantitative reverse transcription polymerase chain reaction, while methylation was examined through methylation-specific polymerase chain reaction. All data were analyzed with IBM SPSS Statistics 21. The relationships among gene expressions were assessed using principal component analysis.The expression of CABLES1, NR4A1, CCND1, NEUROD1, USP2, and WEE1 differed significantly between the patient and control groups. Additionally, significant correlations were observed between the levels of RIPK1, SMARCA4, and USP2 and pre-operative cortisol levels; WEE1 expression and pre-operative ACTH levels; CDKN2A expression and urinary cortisol levels; CABLES1, NEUROD1, SMARCA4, and STAM2 expression and post-operative cortisol levels at 48 h. CCND1 expression was correlated with adenoma size, while WEE1 expression was linked to remission status. Notably, the CDKN2A gene displayed partial methylation, whereas the USP8 gene was fully unmethylated.The altered expression levels of the USP2, CABLES1, CDKN2A, and WEE1 may be closely associated with the development of ACTH-PitNETs. Notably, WEE1 emerged as a target gene for predicting clinical remission in patients with Cushing's disease.

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.

To investigate the protein expression levels of circadian clock genes in pituitary adenomas (PAs) using the immunohistochemical staining method. Patients who had regular follow-up at the pituitary center, underwent transsphenoidal surgery (TSS) for PA between 8:00 AM and 2:00 PM, and had sufficient clinical data were enrolled. Patients with a known diagnosis of depression, those receiving psychiatric medication or melatonin agonists that may affect the protein expression of circadian clock genes, or those working night shifts during the preoperative period were excluded. Formalin-fixed paraffin-embedded tissue samples from patients with somatotroph, gonadotroph, lactotroph, and corticotroph adenomas were immunohistochemically stained for BMAL1, CLOCK, CRY1, CRY2, and PER2. Non-neoplastic adenohypophysis tissue adjacent to the adenoma in surgical specimens underwent the same staining procedure and served as the control group. Protein expression levels were then evaluated. A total of 86 PAs and 17 non-neoplastic adenohypophysis tissue samples were evaluated. Total BMAL1 scores tended to be higher in PAs than in control tissues (170.93 ± 59.81 vs. 142.06 ± 47.40; p = 0.064), whereas total CRY2 scores tended to be lower (12.5 [0-59.25] vs. 35 [10–60]; p = 0.053). Total CLOCK scores were lower in patients with recurrent disease compared to those without recurrence (225 [165–270] vs. 250 [212.5–280]; p = 0.038), and preoperative maximum tumor size was negatively correlated with total CRY2 scores (r=-0.463, p < 0.001). Among PA subtypes, CRY2 was the circadian clock gene showing the most prominent differences. Alterations in the protein expression levels of circadian clock genes may contribute to the development and behavior of PAs.

Kaposi sarcoma (KS) is a rare, human herpesvirus-8 (HHV-8)-associated vascular tumor that primarily affects the skin but can involve visceral organs, particularly in immunosuppressed patients. While iatrogenic KS is well-documented in adults, isolated gastrointestinal involvement in pediatric cases remains unreported. We describe a 16-year-old HIV-negative male with chronic granulomatous disease (CGD) who initially presented with inflammatory bowel disease-like symptoms and was treated with immunosuppressive therapy. Over 17 months, he developed recurrent infections, hepatosplenomegaly, and ultimately intestinal perforation, necessitating emergency colectomy. Histopathology confirmed iatrogenic KS, highlighting the need for increased awareness of this rare malignancy in immunocompromised pediatric patients and carefully balancing the risks of long-term immunosuppressive therapy.

Melorheostosis is a rare sclerosing bone dysplasia that can clinically and radiologically mimic common bone disorders, particularly in atypical presentations. Its heterogeneous manifestations and limited awareness among clinicians frequently contribute to diagnostic delays or misdiagnosis. We report the case of a 34-year-old woman with chronic forearm pain and a longstanding subcutaneous mass. She was initially misdiagnosed as having a metabolic bone disorder based on imaging and histopathology. However, subsequent evaluation with MRI and bone scintigraphy demonstrated eccentric cortical thickening and longitudinal sclerotic lesions involving the radius, olecranon, and first metacarpal. Normal biochemical markers and the absence of systemic involvement further supported a diagnosis of melorheostosis. Histopathological re-examination confirmed lamellar cortical bone with osteoblastic rimming but remained nonspecific. This case underscores the importance of considering melorheostosis in the differential diagnosis of sclerosing bone disorders, especially when radiographic features are ambiguous. It highlights the critical role of multimodal imaging in establishing an accurate diagnosis, while histopathology provides complementary but not definitive evidence. Importantly, melorheostosis may also serve as a window into bone physiology, illustrating aberrant osteogenesis and dysregulated cortical remodeling. A better understanding of its molecular basis, particularly MAPK pathway alterations, may ultimately facilitate more targeted and effective treatments.

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.

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-α), and interleukin 6 (IL-6). RESULTS:IL-1β staining was significantly higher in the ganglionic zone of groups with enterocolitis compared to the control group (p = 0.012). TNF-α staining in the transitional zone of Group 3 and IL-1β 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.

Background Differential diagnosis of hypothalamic-optic chiasmatic gliomas (HOCGs) and craniopharyngiomas on magnetic resonance imaging (MRI) can be quite challenging. Purpose To compare the MRI features of HOCGs and cranipharyngiomas. Material and Methods Patients diagnosed with HOCG or craniopharyngioma in histopathological evaluation between 2012 and 2022 and who underwent preoperative contrast-enhanced brain MRI were included. Various MRI features were retrospectively evaluated for each lesion: T2-weighted imaging and fluid attenuation inversion recovery hyperintensity, calcification, cystic change, T1-weighted (T1W) imaging hyperintensity of the cystic component, hemorrhage, involvement of sellar, suprasellar or other adjacent structures, lobulated appearance, presence of hydrocephalus, and contrast enhancement pattern. Apparent diffusion coefficient (ADC) values were also evaluated and compared. Results Among 38 patients included, 13 (34%) had HOCG and 25 (66%) had craniopharyngioma. Craniopharyngiomas had a significantly higher rate of cystic changes, calcification, and T1W imaging hyperintensity of the cystic component than HOCGs ( P <0.05). Of HOCGs, 92% had chiasm involvement, 23% had optic nerve involvement, and 31% had brain stem involvement. On the other hand, chiasm involvement was observed in 8% of craniopharyngiomas, but none had optic nerve and/or brain stem involvement ( P <0.05). While 62% (8/13) of HOCGs had diffuse homogeneous enhancement, 80% (20/25) of craniopharyngiomas had a diffuse heterogeneous enhancement pattern. Mean ADC values were significantly higher in craniopharyngiomas compared to HOCGs (2.1 vs. 1.6 ×10 −3 mm 2 /s, P <0.05). Conclusion Although some neuroimaging findings may overlap, features such as presence of cyst and calcification, brain stem and optic pathway involvement, different enhancement patterns, and ADC values may be helpful in the differential diagnosis of HOCGs and craniopharyngiomas.

The absence of improvement in survival rates across various cancers, including laryngeal cancer, has led to an increasing interest in understanding the immune response to cancer. In head and neck cancers, immune modulatory mechanisms such as immune microenvironment and immune infiltration are important in cancer pathogenesis. This study aims to explore the distribution of tumor-infiltrating lymphocyte (TIL) subgroups in the immune microenvironment and evaluate their impact on tumor histopathological characteristics and prognosis. The study included 50 patients who underwent laryngectomy for laryngeal squamous cell carcinoma, in Istanbul University - Cerrahpaşa, Faculty of Medicine Department of Otorhinolaryngology, between January 2016 and January 2018. Pathology specimens were evaluated using immunohistochemistry to assess the expressions of the CD3, CD20, CD8, CD4, CD25, and FoxP3 markers, identifying subgroups of TILs. The investigation aimed to uncover how these subgroups influence tumor histopathological features and survival outcomes. The high infiltration of CD3, CD20, and CD4 had a positive impact on disease-specific survival, disease-free survival, and recurrence-free survival. In addition, overall survival was positively affected by high CD3 and CD4 infiltrations. However, no significant relationship was observed between the expressions of CD8, FoxP3, and CD25 and any of the survival parameters. The infiltration of CD3, CD20, and CD4 positive cells indicative of a robust antitumoral immune response—emerged as favorable prognostic factors in laryngeal cancer. These findings suggest that enhancing the infiltration of CD3, CD20, and CD4 lymphocytes could be a therapeutic strategy worth exploring in clinical trials.

Background/aim:To compare the MRI findings and clinical features of multinodular and vacuolating neuronal tumor (MVNT) and dysembryoplastic neuroepithelial tumor (DNET), and reveal the distinguishing features of these tumors from each other. Materials and methods:Patients with a suspected magnetic resonance imaging (MRI)-based diagnosis of MVNT between 2018 and 2022 were collected from the hospital database. In addition, patients diagnosed with DNET on histopathological examination and who had MRIs in the same time period were included in the study. The MRI findings and clinical features were evaluated for each patient. Results:There were 21 patients in the MVNT group and 20 patients in the DNET group. Headache was the most common symptom in patients with MVNTs (61.9%), whereas seizures were more prevalent in those with DNETs (70%). The most frequent locations for the MVNTs were the frontal and parietal lobes (66.6%), while DNETs were most commonly located in the temporal lobe (60%). All the MVNTs were hyperintense in both fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging (T2WI). All the DNETs were hyperintense on T2WI. However, on FLAIR, seven (35%) of the DNET lesions were hyperintense, while the remaining 13 lesions showed mixed signal intensity forming a bubbly appearance. Moreover, 20 of 21 (95.23%) MVNTs were hyperintense on diffusion-weighted imaging (DWI) (b800), with no apparent diffusion coefficient hypointensity in the lesions. None of the DNETs showed hyperintensity on DWI. Conclusion:MRI findings, particularly those observed on FLAIR and DWI, may be helpful for distinguishing between MVNTs and DNETs, especially in cases where the differential diagnosis is challenging.