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Introduction: Salivary gland malignancies account for 2 to 4% of head and neck cancers. Fine needle aspiration cytology (FNAC) is used in preoperative diagnosis of salivary gland lesions. Although FNAC is a highly reliable technique for preoperative diagnosis, there were no consensus on salivary gland cytopathology reporting. Recently, an international group has recommended a classification system for salivary gland FNAC reporting titled \"Milan System for Reporting Salivary Gland Cytopathology\" (MSRSGC). In this study, we aimed to evaluate the usability of the Milan System, its ability to determine the risk of malignancy for each category, with comparisons of inital cytologic and final histopathological diagnosis. Materials and Methods: We performed a retrospective analysis of salivary gland lesion FNAC in our department from 2013 to 2019. A total of 578 FNACs were performed in 514 patients. Of these, 85 cases had surgical follow-up (parotid gland, n = 73, submandibular gland, n = 12). The cytological samples were categorized according to the MSRSGC into six categories by two pathologists. The risk of malignancy (ROM) and diagnostic accuracy values were calculated for each diagnostic categories. Results: A total of 85 aspirates of the patients with follow-up, the MSRSGC diagnostic categories were as follows: non-diagnostic in 7 aspirates (8.2%), non-neoplastic in 3 (3.5%), atypia of undetermined significance (AUS) in 9 (10.5%), benign neoplasm in 43 (50.5%), salivary gland neoplasm of undetermined malignant potential in 7 (8.2%), suspicious for malignancy in 10 (11.7%), and malignant in 6 (7%). The ROM for each category was 28, 5%, 0%, 33%, 0%, 28.5%, 90%, and 100%, respectively. Conclusion: FNAC plays a critical role in the evaluation of patients with salivary gland lesions. The MSRSGC helps in the standardization of the process of diagnosis and clinical management of salivary gland lesions, especially of AUS and SUMP categories that are indeterminate categories in nature.

Accurate diagnosis of hematologic malignancies from peripheral blood smears (PBSs) requires integrating cellular morphology and composition across numerous white blood cells. Existing computational approaches predominantly automate single-cell classifications and do not provide holistic, slide-level diagnostic predictions. We present a framework that employs a high-performance cell-based encoder (DeepHeme) for feature extraction, integrated with our weakly supervised, attention-based multiple instance learning (MIL) model, termed CAREMIL (Cell AggRegation, Explainable, Multiple Instance Learning). Through comprehensive evaluations of leading image encoders and MIL architectures, the combination of DeepHeme and CAREMIL demonstrated superior performance on disease classification tasks. CAREMIL functions as a robust aggregation mechanism, consistently outperforming established slide-level MIL methods (gated MIL and Dual-stream MIL Network) across multiple encoder types. The most pronounced performance gains were observed with out-of-domain encoders, including ImageNet-pretrained and open-source pathology foundation models (UNI2 and Virchow2). CAREMIL combined with DeepHeme achieves the highest diagnostic accuracy across acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and hairy cell leukemia (HCL), with AUROCs of 0.999, 0.891, and 0.945, respectively, and successfully identifies AML even in cases with minimal or absent circulating blasts. Attention values assigned by CAREMIL highlight diagnostically relevant cells and reveal disease-specific morphometric patterns, enabling biological interpretability and case-level insights. The framework remains resilient to individual cell misclassifications and does not require explicit cell-level supervision. These findings establish CAREMIL as an effective and interpretable MIL framework for hematologic slide diagnosis, extendable to bone marrow aspirates, cytology, and other liquid biopsy specimens, supporting a shift toward quantitative, morphology-informed hematologic diagnostics.

Objective: Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM, are plasma cell neoplasms. The evolution of the treatment of MM in recent years has dramatically improved the outcome for these patients. Currently, multidisciplinary studies are being conducted to elucidate the etiopathogenesis of the disease and develop specific treatment agents and prognostic markers. The present study investigates the relationships between immunoexpression of CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 and disease progression in cases of MM and MGUS. Materials and Methods: Immunohistochemical staining for CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 were performed on bone marrow biopsy samples from 94 MM and 20 MGUS patients diagnosed between 2011 and 2018. Immunohistochemical results were examined semiquantitatively, and the associations between the immunohistochemical, clinical, and biochemical markers utilized for MM and MGUS patient staging were analyzed. Results: Pan-Ras, DKK-1, and MUM-1 staining results were significantly higher in MM compared to MGUS (p=0.005, 0.001, and 0.001, respectively). The mean CCL-3 expression in patients with MGUS was 23.15%, while it was 18.68% in cases of MM (p=0.413). CCL-3 expression was significantly higher in high-risk MGUS cases compared to other risk groups according to the Mayo Clinic Risk Stratification for MGUS. According to the International Staging System and the Revised International Staging System, CD138 expression was higher among stage II and stage III patients than stage I patients. Conclusion: Differences in Pan-Ras, MUM-1, DKK-1, and CCL-3 expressions between MM and MGUS suggest that these molecules may play a role in the progression of MGUS to MM. CCL-3, an immunohistochemical marker, may be predictive of MGUS progression, while CD138 is associated with more advanced stages of MM. Keywords: Multiple myeloma, Monoclonal gammopathy of undetermined significance, DKK-1, Pan-Ras, CCL-3, MUM-1 Amac: Multipl myelom (MM) ve MM'nin prekursoru olan onemi belirsiz monoklonal gamopati (MGUS), plazma hucreli neoplazilerdir. Guncel calicmalarda bu hastaliklarin etiyopatogenezini aydinlatmak, spesifik tedavi ajanlari ve prognostik belirtecler gelictirmek icin multidisipliner calicmalar yurutulmektedir. Calicmamizda MM ve MGUS'lerde CD138, Pan-Ras, CCL-3, DKK-1 ve MUM1 immunoekspresyonun hastalik evreleriyle olan ilickisini aractirmayi hedefledik. Gerec ve Yontemler: 2011-2018 yillari arasinda tani alan 94 MM ve 20 MGUS olgusuna ait kemik iligi biyopsilerine, CD138, Pan-Ras, CCL-3, DKK-1, MUM-1 immunohistokimyasal (IHK) boyamasi yapildi. IHK sonuclari semi kantitatif olarak degerlendirildi ve MM ve MGUS olgularinin hastalik evreleriyle olan ilickileri degerlendirildi. Bulgular: Pan-Ras, DKK-1 ve MUM-1 immunoekspresyonu, MM'li olgularda MGUS'li olgulara gore anlamli olarak daha yuksek saptandi (p=0,005, 0,001, ve 0,001, sirasiyla). MGUS olgularinda ortalama CCL-3 immunoekspresyonu %23,15 iken, MM olgularinda %18,68 idi (p=0,413). MGUS olgularinda Mayo Klinik risk siniflandirmasi (MCRS) modeline gore, yuksek riskli MGUS olgularinda diger risk gruplarina kiyasla CCL-3 ekspresyonu onemli olcude artmic olarak saptandi. CD138 ekspresyonu, ISS ve R-ISS siniflama sistemlerine gore, evre 2 ve evre 3 hastalarda evre 1 hastalara gore artmic olarak tespit edildi. Sonuc: MM ve MGUS olgularinda Pan-Ras, MUM-1, DKK-1 ve CCL-3 ekspresyonlarindaki farkliliklar, bu belirteclerin MGUS-MM progresyonunda onemli roller ustlendigini gostermektedir. Kemik iligi biyopsilerinde, kolay ve pratik bir cekilde, CCL-3 immun belirteci MGUS progresyonunda prediktif; CD138 ise MM olgularinda ileri evre tayininde kullanilabilir. Anahtar Sozcukler: Multipl myelom, Onemi belirsiz monoklonal gammopati, DKK-1, Pan-Ras, CCL-3, MUM-1

Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM, are plasma cell neoplasms. The evolution of the treatment of MM in recent years has dramatically improved the outcome for these patients. Currently, multidisciplinary studies are being conducted to elucidate the etiopathogenesis of the disease and develop specific treatment agents and prognostic markers. The present study investigates the relationships between immunoexpression of CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 and disease progression in cases of MM and MGUS. Immunohistochemical staining for CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 were performed on bone marrow biopsy samples from 94 MM and 20 MGUS patients diagnosed between 2011 and 2018. Immunohistochemical results were examined semiquantitatively, and the associations between the immunohistochemical, clinical, and biochemical markers utilized for MM and MGUS patient staging were analyzed. Pan-Ras, DKK-1, and MUM-1 staining results were significantly higher in MM compared to MGUS (p=0.005, 0.001, and 0.001, respectively). The mean CCL-3 expression in patients with MGUS was 23.15%, while it was 18.68% in cases of MM (p=0.413). CCL-3 expression was significantly higher in high-risk MGUS cases compared to other risk groups according to the Mayo Clinic Risk Stratification for MGUS. According to the International Staging System and the Revised International Staging System, CD138 expression was higher among stage II and stage III patients than stage I patients. Differences in Pan-Ras, MUM-1, DKK-1, and CCL-3 expressions between MM and MGUS suggest that these molecules may play a role in the progression of MGUS to MM. CCL-3, an immunohistochemical marker, may be predictive of MGUS progression, while CD138 is associated with more advanced stages of MM.