Rituximab and lenalidomide for the treatment of relapsed or refractory indolent non-Hodgkin lymphoma: real-life experience.

The combination of rituximab and lenalidomide (R-len) stands as an established treatment for relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). However, the reproducibility of clinical trial results in routine clinical practice is unknown. To address this gap in knowledge, we reviewed our experience with patients diagnosed with R/R follicular lymphoma (FL) or marginal zone lymphoma (MZL) treated with this combination. Eighty-four patients underwent treatment with R-len, 69 (82%) affected by FL and 15 (18%) by MZL. The median age at the time of treatment initiation was 65 years (range, 39-94), 38 patients (45%) had a pre-treatment FLIPI score of 3-5, 19 (23%) had a bulky disease, 29 (37%) had a lymphoma refractory to the last treatment line, while in 20 (24%) cases the disease was refractory to rituximab. The best overall response rate (ORR) was 82%, and 52% achieved a complete response (CR). The best CR rates for FL and MZL patients were 55% and 40%, respectively. With a median follow-up of 22 months, the median progression-free survival (mPFS) was 22 months (95% CI 19-36) and the 2-year overall survival (OS) was 83% (95% CI 74-93). The median duration of CR (DoCR) was 46 months (95% CI 22-NR). Factors associated with shorter PFS in multivariate analysis were bulky disease and rituximab refractoriness. The most common adverse events (AE) included hematologic toxicity, fatigue and gastrointestinal disorders, such as diarrhea and constipation. Neutropenia and thrombocytopenia were the most common severe toxicities (grade ≥3 in 25% and 4%, respectively). No new safety signals were reported. Real-life results of R-len in patients with R/R iNHL appear consistent with those reported in prospective studies, and further support its use as comparator arm in controlled clinical trials.

Prognostic impact of mitosis and necrosis in non-mucinous lung adenocarcinomas and correlation with IASLC grading system.

BACKGROUND: In 2020, the International Lung Cancer Study Group (IASLC) Pathology Committee established a grading system for non-mucinous primary lung adenocarcinomas. This grading system is based on whether areas of high-grade patterns are present in more than 20% of the tumor. Parameters, such as necrosis, mitotic activity, lymphovascular invasion (LVI) and spread through air spaces (STAS), are excluded from evaluating the grading system. METHODS: A total of 217 patients' lung resection materials for primary lung adenocarcinoma were re-reviewed using the IASLC grading system. Necrosis, mitotic activity, LVI status and STAS were also evaluated in the resection materials, aiming to demonstrate the relationship between these histopathological features and clinical outcome data. RESULTS: At all stages, overall survival (OS) and recurrence-free survival (RFS) were related to grade (p=0.011 and 0.024, respectively). Additionally, patients with necrosis were associated with worse OS and RFS (p=0.002 and 0.048, respectively). When grade 2 and 3 tumors were analyzed individually, a significant relationship was found between necrosis and OS in grade 3 tumors (p=0.002). Patients with a high mitotic count (≥10/10 high-power fields) had significantly worse OS (p=0.046). The prevalence of LVI and STAS increased with grade; however, their prognostic significance has not been demonstrated. CONCLUSIONS: The new grading system provides a highly efficient prognostic classification for survival. Necrosis and high mitotic count are important prognostic parameters for survival. Additionally, necrosis is a stage-independent prognostic factor for OS in grade 3 tumors, although no effect on prognosis can be demonstrated in grade 2 tumors.

Predictive Immune Markers for Disease Progression in Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

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.

Histopathological Review of Diagnostic Categories of the Milan System for Reporting Salivary Gland Cytopathology - An Institutional Experience of 6 Years.

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.