Available epidemiological reports on follicular lymphoma (FL) often highlight a significant discrepancy between its high and low incidence rates in Western and Eastern Europe, respectively. The reasons behind that difference are not fully understood, but underreporting is typically presumed as one of the main factors. This study aimed to assess FL epidemiology in Poland based on 2000-2014 data from the Polish National Cancer Registry, which has 100% population coverage and over 90% completeness of the registration. All cases were coded according to ICD-10 and ICD-O-3 recommendations. The total number of registered FL cases was 3,928 with crude (CR) and standardized (SR) incidence rates of 0.72/10 5 and 0.87/10 5 , respectively. The median age of FL diagnosis was 61 years, with the male to female incidence ratio of 1.06. The distribution of morphological types of FL: not otherwise specified (NOS), grades 1, 2, or 3 were 72.58, 4.81, 12.88, and 9.73%, respectively. Among all reported mature B-cell non-Hodgkin lymphomas, FL was ranked the fourth in incidence, just after chronic lymphocytic leukemia/small lymphocytic lymphoma (CR 3.62/10 5 , SR 4.99/10 5), plasma cell neoplasms (CR 3.78/10 5 , SR 4.97/10 5) and diffuse B-cell lymphoma, NOS (CR 2.13/10 5 , SR 2.65/10 5). The systematic increase in FL incidence among females was observed. Our study confirms a lower FL incidence rate in Poland as compared to other European countries. Moreover, as our analysis was based on a registry with high data completeness, it provides evidence that reasons other than underreporting are responsible for FL incidence discrepancies between Eastern and Western Europe. Follicular lymphoma (FL) is one of the most common non-Hodgkin's lymphomas (NHLs) and its incidence varies between geographical regions. In Western Europe and US FL accounts for 20-40% of all NHLs, whereas in Eastern Europe, Asia, and developing countries, its prevalence is about threefold lower. FL affects mostly white adults of a median age of sixty, with a slightly higher incidence rate in females 1. There is an upward trend in the incidence of NHLs in Western countries, which can be attributed mainly to the increased incidence of FL 2. According to data from the Polish histopathological registry of lymphomas, FL accounted for less than 5% of all diagnoses reported in the 2007-2012 period 3. One of the main risk factors predisposing to FL is exposition to high doses of pesticides and herbicides, which may induce BCL2 gene translocation t(14;18)(q32;q21) 4. FL heterogeneity poses a diagnostic and therapeutical challenge, from early indolent lymphoma to aggressive transformation into therapy-resistant diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). FL is composed of germinal follicle center B-cells containing centrocytes and centroblasts that almost always present focal follicular growth pattern 4,5. An absolute number of centroblasts per high-power microscopic field should be evaluated by a pathologist to classify FL into the histological grading sys...

Background: The presence of tumor-infiltrating lymphocytes (TILs) in many studies is associated with a better prognosis in melanoma patients. Programmed death-ligand 1 (PD-L1) expression has a significant value in predicting several cancers, but its role in melanoma remains ambiguous. The study aims to report a comprehensive analysis of TILs characteristics and their impact on survival in primary acral melanoma (AM). Methods: Clinical and pathological features and survival outcomes were investigated in 70 patients with AM. Immunohistochemical quantitative analysis of TILs, including expression of CD4, CD8, FOXP3, PD-1, and PD-L1, on melanoma cells was performed. Results: Kaplan-Meier analysis showed significant differences in overall survival (OS) for CD4+ (p = 0.021), CD8+ (p = 0.037), FOXP3+ (p = 0.007), and TILs density (p = 0.043). In univariate analysis of immunohistochemical features, FOXP3, CD4, CD8, PD-1, and Melanoma Institute of Australia (MIA) grading TILs (grade, density, and distribution) were correlated with survival. The higher density of FOXP3-positive cells was an independent factor associated with better survival. Conclusions: High TILs content (classed as brisk Clark scale and marked/diffuse TILs MIA grade) regardless of its immunophenotype was associated with better survival outcomes in AM. PD-L1 expression on tumor cells did not influence OS and was independent of clinical and pathological characteristics. We demonstrated that TILs are significant biomarkers in sentinel lymph node status prediction.

IntroductionHistopathological examination and immunohistochemistry (IHC) with a crucial role of CD10 expression remain a standard diagnostic tool in follicular lymphoma (FL). The results of IHC CD10 detection with different primary antibodies are not fully reproducible, but some reports show that flow cytometry (FCM) can be a reliable method of CD10 identification.MethodsThe aim of the study was to compare results of CD10 expression in FL by IHC and FCM including immunophenotypic features in the context of the BCL2 and BCL6 alterations.ResultsOut of 76 histopathologically diagnosed FL, a group of 25 cases had simultaneously FCM. Immunohistochemically 77.6% of cases were CD10‐positive with comparable and reproducible results to FCM. Differences between the FCM expression of CD5/CD10/CD11c/CD25/CD43 and BCL2 overexpression (BCL2(+)higher) correlated with the BCL2 and BCL6 rearrangements (R) status. Lack of CD10 expression corresponded with the absence of BCL2R and higher MUM1 expression by IHC results but had no clinical impact on the long‐time outcomes.ConclusionsImmunohistochemistry staining is a comparable method to FCM assessment in the evaluation of CD10 expression and diagnosis of FL. Fine‐needle aspiration biopsy/FCM (FNAB/FCM) could be a useful tool for verifying FL diagnosis and CD10 detection. Despite its heterogeneity, FL has a characteristic immunophenotype. BCL2R and BCL6R FL cases differ mainly in levels of BCL2 and CD10 with CD43 co‐expression; BCL2(+)higher by FCM correlates with BCL2R. Moreover, FNAB plays an important role in material provision for supportive karyotyping and BCL2R, BCL6R assessed by FISH.

▶ Fig. 3 EUS image of a tumor of the right parapharyngeal space located between the pharyngeal wall, the medial pterygoid muscle (mpm), and the ramus of the mandible. The tumor (TU) is 34 mm × 28 mm in size, has well-delineated borders and a hypoechoic, homogeneous echo pattern. A needle passing through the pharyngeal wall into the tumor is visible. ▶ Fig. 4 Specimen obtained by EUS-guided fine-needle biopsy under 100 × magnification. Typical appearance of a pleomorphic adenoma of the parotid gland with epithelial, myoepithelial, and stromal components. Hematoxylin and eosin stain. ▶ Fig. 2 Schematic drawing of the anatomy of the mouth and throat (midsagittal plane), showing the position of the echoendoscope during endoscopic ultrasound (EUS) examination and fine-needle biopsy of the tumor. Polkowski Marcin et al. Transoral endoscopic ultrasound-guided fine-needle biopsy of a tumor of the parapharyngeal space … Endoscopy

Background/Aim: Follicular lymphoma (FL) relapse within 24 months of the first immunochemotherapy (POD24) indicates more precisely poor overall survival and high risk of death. The aim of the study was to assess the potential value of POD24 in FL and describe the enhancer of zeste homolog 2 (EZH2) expression profile, in correlation with clinical/ histopathological/immunophenotypical characteristics. Materials and Methods: This retrospective single-center study included 75 patients with FL treated under watch and wait (W&W) and immunochemotherapy regimens. All cases were immunohistochemically assessed: assays were performed for EZH2, CD10, BCL6, BCL2, MUM1, MYC and p53. Results: POD24 was independent of clinical/histopathological/ immunohistochemical features and separated patients with inferior outcomes. EZH2 high expression was observed in high/low grade and follicular/diffuse FL patterns. BCL2negative (p=0.042) and MUM1 (p=0.039), MYC (p<0.001), p53 (p<0.001) -positive cases had significantly higher EZH2 expression. Conclusion: POD24 is currently the most useful tool for the identification of poor outlook patients. EZH2 is crucial in FL biology, but the value of its protein expression is limited as a prognostic factor. Follicular lymphoma (FL) is an indolent B-cell lymphoma, but early relapse after first-line therapy occurs in up to 20% of patients (1-3). Different prognostic markers have been evaluated; however, the follicular International Prognostic Index (FLIPI) is still the only reproducible tool (4, 5). Its molecular modifications have not been yet widely accessible, while the next-generation sequencing-based genetic evaluation of FL is not a routine part of a diagnostic examination (6-8). Recently, the progression of disease within 24 months of first treatment (POD24) was applied for the identification of FL high-risk patients (3, 9). Early treatment failure is predictive of poor overall survival (10) and seems to be independent of initial treatment modality (11). Available results indicating the association of POD24 with prognostic markers, i.e., reduced intratumoral immune infiltration, pre-treatment positronemission tomography-based staging, and molecular status, are still inconsistent and unsatisfactory (12,13).Enhancer of zeste homolog 2 (EZH2) is a histone-lysine Nmethyltransferase enzyme encoded by the EZH2 gene. It is a functional component of polycomb repressive complex 2 (PRC2) and catalyzes the methylation of histone H3 lysine 27 6685

Immune checkpoint inhibitors, including those concerning programmed cell death 1 (PD-1) and its ligand (PD-L1), have revolutionised the cancer therapy approach in the past decade. However, not all patients benefit from immunotherapy equally. The prediction of patient response to this type of therapy is mainly based on conventional immunohistochemistry, which is limited by intraobserver variability, semiquantitative assessment, or single-marker-per-slide evaluation. Multiplex imaging techniques and digital image analysis are powerful tools that could overcome some issues concerning tumour-microenvironment studies. This novel approach to biomarker assessment offers a better understanding of the complicated interactions between tumour cells and their environment. Multiplex labelling enables the detection of multiple markers simultaneously and the exploration of their spatial organisation. Evaluating a variety of immune cell phenotypes and differentiating their subpopulations is possible while preserving tissue histology in most cases. Multiplexing supported by digital pathology could allow pathologists to visualise and understand every cell in a single tissue slide and provide meaning in a complex tumour-microenvironment contexture. This review aims to provide an overview of the different multiplex imaging methods and their application in PD-L1 biomarker assessment. Moreover, we discuss digital imaging techniques, with a focus on slide scanners and software.

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that is associated with a variety of underlying diseases. We report a case of AVWS associated with plasma cell myeloma. The patient was a 57-year-old male with recurrent bleeding symptoms for a few months. Physical examination was normal. Laboratory studies revealed isolated prolongation of the activated partial thromboplastin time. His factor VIII activity, von Willebrand factor (VWF) Ag, and VWF activity were low. Bone marrow aspirate showed diffuse infiltration of atypical plasma cells and erythroid line hyperplasia.

Background: Marginally resectable and unresectable soft tissue sarcomas (STS) remain a therapy challenge due to the lack of highly active treatment. The aim of the study was to identify a biomarker to predict the pathological response (PR) to preplanned treatment of these STSs. Methods: In the phase II clinical trial (NCT03651375), locally advanced STS patients received preoperative treatment with a combination of doxorubicin-ifosfamide chemotherapy and 5 × 5 Gy radiotherapy. PR to the treatment was classified using the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group recommendations. We have chosen HIF-1α, CD163, CD68, CD34, CD105, and γH2AFX proteins, rendering different biological phenomena, for biomarker study. Results: Nineteen patients were enrolled and in four cases a good PR was reported. The high expression of HIF-1α before surgery showed a negative correlation with PR, which means a poor response to therapy. Furthermore, the samples after surgery had decreased expression of HIF-1α, which confirmed the correlation with PR. However, high expression of γH2AFX positively correlated with PR, which provides better PR. The high number of positive-staining TAMs and the high IMVD did not correlate with PR. Conclusions: HIF1α and γH2AFX could be potential biomarkers for PR prediction after neoadjuvant treatment in STS.