Classical Hodgkin Lymphoma Cases Research Articles

Proteomic Profiling of Lymph Nodes Differentiates Classic Hodgkin Lymphoma With and Without Skeletal Involvement.

Classic Hodgkin lymphoma (CHL) is a highly curable disease, even in advanced stages. Controversy remains over whether bone involvement negatively affects overall and progression-free survival in patients treated with intensive chemotherapy regimens. Whether cases that present with bone lesions harbor specific tumor microenvironmental features is unknown. We investigated protein expression in diagnostic lymph node biopsies from CHL patients with and without skeletal involvement at diagnosis to identify potential markers of skeletal disease. Protein expression patterns in diagnostic formalin-fixed paraffin-embedded lymphoma lymph node samples from CHL patients were analyzed by nano-liquid chromatography-tandem mass spectrometry. Patients were grouped according to skeletal involvement, which was defined as the presence of one or more FDG-avid lesions on a diagnostic FDG-PET/CT scan. Protein profiles identified patients with skeletal disease at diagnosis and showed disrupted cellular pathways, including immune system processes, cell adhesion, and cell growth/survival. Immunohistochemical evaluation also demonstrated differential expressions of angiotensin-converting enzyme (ACE), intercellular adhesion molecule 3 (ICAM3), integrin alpha-X (ITGAX), and calreticulin (CALR). In conclusion, proteomics identified altered protein expression profiles in lymph nodes among CHL cases presenting with disease disseminated to the skeletal system, which implies altered disease pathogenesis for these patients.

Utility of CCR7 to differentiate classic Hodgkin lymphoma and other B-cell lymphomas by flow cytometry and immunohistochemistry.

Classic Hodgkin lymphoma (CHL) is characterized by infrequent neoplastic Hodgkin and Reed-Sternberg (HRS) cells in an inflammatory background. The diagnostic utility of CC-chemokine receptor 7 (CCR7) in CHL was explored using flow cytometry and immunohistochemistry (IHC). Neoplastic specimens and non-neoplastic lymph nodes were immunophenotyped and CCR7 expression was measured semiquantitatively by flow cytometry (clone 3D12) and IHC (clone 150503). Our results showed that CCR7 was expressed on HRS cells in the vast majority of CHL cases (45/48 by flow cytometry, 57/59 by IHC) but rarely expressed in neoplastic cells in diffuse large B-cell lymphoma, not otherwise specified (1/25 by flow cytometry, 2/40 by IHC) and nodular lymphocyte predominant Hodgkin lymphoma (0/4 by flow cytometry, 1/13 by IHC). Primary mediastinal large B-cell lymphoma (PMLBCL) revealed weak CCR7 expression by flow cytometry in most cases (8/10) but only occasionally by IHC (2/12). Both cases (2/2) of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) also showed CCR7 expression detected by flow cytometry compared with IHC (0/7). The HRS cells demonstrated a greater percentage of positive cells and greater antigen intensity than the other B-cell lymphomas by IHC. The expression identified by flow cytometry in PMLBCL and THRLBCL but not by IHC suggests that there may be differences in the detection capabilities of the 2 techniques or the2 CCR7 clones used. The expression of CCR7 in HRS cells suggests its potential utility in differentiating CHL from other B-cell lymphomas. Incorporating CCR7 into flow cytometry and IHC panels may further enhance the diagnostic sensitivity of CHL.

Association of both BCL2 positive and negative follicular lymphoma to clasical Hodgkin lymphoma and/or gray zone lymphoma

We present a series of 9 follicular lymphomas that progressed/transformed into classical Hodgkin lymphoma (CHL). Three cases of CHL showed a syncytial pattern (SCHL) making the differential diagnosis to Gray zone lymphoma (GZL) challenging. None of these three cases presented in the mediastinum. Based in all molecular data analyzed (BCL2/BCL6 FISH studies, IgH PCR and TNGS with a customized gene panel) we did find clonal relationship between the BCL2-positive FL cases and their CHL components in all cases. The three SCHL/GZL cases showed an activated phenotype according to Hans algorithm, presented the t(14; 18)(q32; q21), two out of three showed B cell markers and all expressed CD30 and p53. Interestingly, we identified three BCL2-negative FL cases with a further diagnosis of CHL expanding the spectrum of these association. In one of these three cases a different mutational profile was found in both the FL and the CHL components. All this data together suggests that CHL associated to BCL2-positive FL could be originated in a common progenitor cell (CPC) that give rise to both FL and CHL, acquiring this last component further genetic events in a linear fashion. On the other hand, no clonal relationship between CHL and BCL2-negative FL could be found, suggesting a fortuity association. Nevertheless, ample series of cases studied with more sensitive techniques are needed to confirm our hypothesis.

Optimizing assessment of CD30 expression in Hodgkin lymphoma by controlling for low expression.

Since the approval of brentuximab vedotin (BV), assessment of CD30 status by immunohistochemistry gained increasing importance in the clinical management of patients diagnosed with CD30-expressing lymphomas, including classical Hodgkin lymphoma (CHL). Paradoxically, patients with low or no CD30 expression respond to BV. This discrepancy may be due to lack of standardization in CD30 staining methods. In this study, we examined 29 cases of CHL and 4 cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) for CD30 expression using a staining protocol that was designed to detect low CD30 expression levels, and an evaluation system similar to the Allred scoring system used for breast cancer evaluation. For CHL, 10% of cases had low scores and 3% were CD30 negative, with 3 cases in which the majority of tumor cells showed very weak staining. Unexpectedly, one of four cases of NLPHL was positive. We demonstrate intra-patient heterogeneity in CD30 expression levels and staining patterns in tumor cells. Three CHL cases with weak staining may have been missed without the use of control tissue for low expression. Thus, standardization of CD30 immunohistochemical staining with use of known low-expressing controls may aid in proper CD30 assessment and subsequent therapeutic stratification of patients.

TMTV-Net: fully automated total metabolic tumor volume segmentation in lymphoma PET/CT images - a multi-center generalizability analysis.

Total metabolic tumor volume (TMTV) segmentation has significant value enabling quantitative imaging biomarkers for lymphoma management. In this work, we tackle the challenging task of automated tumor delineation in lymphoma from PET/CT scans using a cascaded approach. Our study included 1418 2-[18F]FDG PET/CT scans from four different centers. The dataset was dividedinto 900 scans for development/validation/testing phasesand 518 for multi-center external testing. The former consisted of 450 lymphoma, lung cancer, and melanoma scans, along with 450 negative scans, while the latter consisted of lymphoma patients from different centers with diffuse large B cell, primary mediastinal large B cell, and classic Hodgkin lymphoma cases. Our approach involves resampling PET/CT images into different voxel sizes in the first step, followed by training multi-resolution 3D U-Nets on each resampled dataset using a fivefold cross-validation scheme. The models trained on different data splits were ensemble. After applying soft voting to the predicted masks, in the second step, we input the probability-averaged predictions, along with the input imaging data, into another 3D U-Net. Models were trained with semi-supervised loss. We additionally considered the effectiveness of using test time augmentation (TTA) to improve the segmentation performance after training. In addition to quantitative analysis including Dice score (DSC) and TMTV comparisons, the qualitative evaluation was also conducted by nuclear medicine physicians. Our cascaded soft-voting guided approach resulted in performance with an average DSC of 0.68 ± 0.12 for the internal test data from developmental dataset, and an average DSC of 0.66 ± 0.18 on the multi-site external data (n = 518), significantly outperforming (p < 0.001) state-of-the-art (SOTA) approaches including nnU-Net and SWIN UNETR. While TTA yielded enhanced performance gains for some of the comparator methods, its impact on our cascaded approach was found to be negligible (DSC: 0.66 ± 0.16). Our approach reliably quantified TMTV, with a correlation of 0.89 with the ground truth (p < 0.001). Furthermore, in terms of visual assessment, concordance between quantitative evaluations and clinician feedback was observed in the majority of cases. The average relative error (ARE) and the absolute error (AE) in TMTV prediction on external multi-centric dataset were ARE = 0.43 ± 0.54 and AE = 157.32 ± 378.12 (mL) for all the external test data (n = 518), and ARE = 0.30 ± 0.22 and AE = 82.05 ± 99.78 (mL) when the 10% outliers (n = 53) were excluded. TMTV-Net demonstrates strong performance and generalizability in TMTV segmentation across multi-site external datasets, encompassing various lymphoma subtypes. A negligible reduction of 2% in overall performance during testing on external data highlights robust model generalizability across different centers and cancer types, likely attributable to its training with resampled inputs. Our model is publicly available, allowing easy multi-site evaluation and generalizability analysis on datasets from different institutions.

T-Cell-Rich Hodgkin Lymphoma With Features of Classic Hodgkin Lymphoma and Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Borderline Category With Overlapping Morphologic and Immunophenotypic Features.

It is known that a subset of cases of classic Hodgkin lymphoma (CHL) with B-cell-rich nodules (lymphocyte-rich CHL) exhibits morphologic and immunophenotypic features that overlap with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), raising diagnostic difficulties that can be resolved in most cases by performing an adequate battery of immunohistochemical studies. To fully characterize cases of T-cell-rich Hodgkin lymphoma where a specific diagnosis of NLPHL (ie, pattern D) or CHL could not be made even after complete immunophenotypic investigation. The clinical, immunomorphologic, and molecular (when applicable) presentation of 3 cases of T-cell-rich Hodgkin lymphoma was thoroughly investigated. These 3 cases harbored lymphocyte-predominant-like and Hodgkin and Reed-Sternberg-like cells that partially expressed B-cell and CHL markers and were negative for Tiftein-Barr virus-encoded small RNA, in a T-cell-rich background with residual follicular dendritic cell meshworks; 1 case had frequent and the other 2 cases scant/absent eosinophils and plasma cells. Two patients with advanced-stage (III or IV) disease presented with axillary and supraclavicular lymphadenopathy, respectively, and without B symptoms. These patients underwent NLPHL-like therapeutic management with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], vincristine sulfate [Oncovin], and prednisone) chemotherapy; both are in complete remission 7 years posttherapy. One patient presented with stage I disease involving an internal mammary lymph node without B-symptoms and was treated with surgical excision alone; this patient is also in complete remission 1 year later. These cases illustrate overlapping features of T-cell-rich NLPHL and CHL with neoplastic cells expressing both B-cell program and CHL markers. This underrecognized overlap has not been fully illustrated in the literature, although it portrays a therapeutic challenge. These neoplasms may deserve in-depth investigation in the future that may bring up diagnostic or theragnostic implications.

Comparative Outcome Analysis of Nodular Lymphocyte-Predominant Hodgkin Lymphoma Vs Classical Hodgkin's Lymphoma - a SEER Based Study

Introduction Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a slower-growing variant of Hodgkin lymphoma that is uniquely characterized by its growth pattern and cellular appearance. While patients with NLPHL tend to demonstrate more promising prognoses than their counterparts with classical Hodgkin lymphoma (CHL), recent comparative studies remain limited. The objective of this study was to investigate the disparities in survival rates between NLPHL and CHL patients, accounting for variations in patient demographics and disease attributes. Methodology We utilized Surveillance, Epidemiology, and End Results (SEER) 17 registries database to identify patients diagnosed with NLPHL and CHL between 2000 - 2020. Univariate survival analysis was done using a Kaplan Meir plot with a log-rank test, and the Cox proportion hazard regression model was used for multivariate survival analysis. Results A total of 2,723 NLPHL cases and 42,581 CHL cases were included in the study. The median age of NLPHL patients stood at 44 years, whereas for CHL patients it was observed to be 38 years. Over an 83-month median follow-up, NLPHL demonstrated superior 5-year (92.2%) and 10-year (83.84%) survival rates compared to CHL (82.45% and 75.45%, respectively). When controlled for all available characteristics, NLPHL showed a significantly higher overall survival (HR: 2.373; 95% CI, 2.131 - 2.644; P&amp;lt;.001) than CHL. For those diagnosed with NLPHL, our data indicated that patients who underwent radiation therapy had better survival rate (HR: 1.98; 95% CI, 1.55 - 2.53; p&amp;lt;.001). Additionally, younger age and male gender were associated with a more favorable prognosis. Conclusion Our analysis highlights the superior survival outcomes for NLPHL patients as compared to those with CHL, even when accounting for available patient and disease characteristics. The further enhanced survival rates observed in NLPHL patients undergoing radiation therapy suggests potential for more tailored therapeutic approaches. Factors such as younger age and male gender were also identified as indicative of a more favorable prognosis, underscoring the need for further exploration of demographic and clinical influences on survival outcomes in Hodgkin lymphomas.

A Subset of Classical Hodgkin Lymphoma Cases Demonstrate CD19 Expression on Hodgkin Reed-Sternberg Cells By Immunohistochemistry

Background: The neoplastic Hodgkin Reed-Sternberg (HRS) cells in Classical Hodgkin Lymphoma (CHL) are thought to lose their B-cell phenotype and lack expression of most B-cell markers. Improvements in antibodies and detection methods have revealed that a subset of CHL cases may express some B-cell markers, including CD19 and CD20, with currently unclear significance. Introduction of CD19-directed therapies has changed the landscape of salvage treatment in CD19 expressing Non-Hodgkin Lymphomas. As such, we sought to characterize CD19 expression in HRS cells and its clinical implications and potential utility as a therapeutic target. Methods: We conducted an Institutional Review Board-approved retrospective review of records for CHL cases from 01/2015 to 07/2020 at a tertiary care center. 42 cases met the criteria and had sufficient tissue for analysis: 39 CHL, 2 CHL mixed with other B-cell lymphomas, and 1 Epstein Barr Virus Post-Transplant Lymphoproliferative Disease (EBV-PTLD)-CHL type. Cases were assessed for CD19 immunohistochemical (IHC) staining using the EP169 Rabbit Monoclonal Antibody. HRS cells were identified via morphology and characteristic immunoprofile, with all HRS cells expressing strong CD30 and dim PAX-5. CD19 staining intensity (0-3+) and pattern of expression (cytoplasmic, Golgi body, membranous) in HRS cells was independently evaluated by three hematopathologists. Based on their consensus, CD19 staining was categorized as negative, weak (variable across HRS cells), or positive. CD19 staining was compared with histologic subtype, other B-cell marker staining, EBV association (via EBER-ISH), and clinical data and outcomes, including, age, stage, treatment, response, overall survival, and demise. Results: Histologically, cases were composed of the following subtypes: 26 nodular sclerosis, 8 mixed cellularity, 3 lymphocyte-rich, 1 lymphocyte-depleted, 2 other (EBV-PTLD and malignant B-cell lymphoma) and 2 unclassifiable (due to treatment effect and biopsy size). Nine of 42 cases (21%) were EBV-associated by EBER-ISH. CD19 staining of any kind in HRS cells was found in 13/42 cases (31%), with 10/42 (24%) demonstrating positive staining and 3/42 (7%) demonstrating weak staining. Staining intensity and pattern varied across positive cases (Table 1 and Figure 1). CD19 staining was seen in 4/26 nodular sclerosis (15%), 6/8 mixed cellularity (75%), 1/3 lymphocyte-rich (33%), and 1/1 lymphocyte-depleted (100%) cases. The strongest correlation with other markers was seen with EBV, with 7/9 (78%) EBV+ cases staining with CD19. Five cases with CD19 staining also demonstrated predominantly patchy/dim CD20 staining. The clinical characteristics of CHL cases with CD19 expression varied, with an age range of 10-78 years old and variable clinical stage at time of tissue sampling. Following initial treatment, 4/13 patients failed to achieve remissions after frontline chemotherapy (mostly ABVD), with 3 of these patients now deceased due to disease. Conclusions: A significant subset of CHL cases demonstrate CD19 expression on HRS cells, and EBV-associated CHL has a high rate of CD19 expression, which may reflect its different underlying disease mechanism. Larger studies are necessary to characterize the staining pattern and intensity that may be most amenable to specific therapies and to better elucidate the prognostic implications of CD19 expression. Given the accessibility of CD19 IHC and the growing list of effective CD19-directed therapies, it is worthwhile assessing CD19 expression, particularly in EBV associated CHL, and further research into the utility of CD19 expression on HRS as a potential therapeutic target is warranted.

Specific Polo-Like Kinase 1 Expression in Nodular Lymphocyte-Predominant Hodgkin Lymphoma Suggests an Intact Immune Surveillance Program

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare and relatively indolent B-cell lymphoma. Characteristically, the [lymphocyte-predominant (LP)] tumor cells are embedded in a microenvironment enriched in lymphocytes. More aggressive variants of mature B-cell and peripheral T-cell lymphomas exhibit nuclear expression of the polo-like kinase 1 (PLK1) protein, stabilizing MYC (alias c-myc) and associated with worse clinical outcomes. This study demonstrated expression of PLK1 in the LP cells in 100% of NLPHL cases (n=76). In contrast, <5% of classic Hodgkin lymphoma cases (n=70) showed PLK1 expression within the tumor cells. Loss-of-function approaches demonstrated that the expression of PLK1 promoted cell proliferation and increased MYC stability in NLPHL cell lines. Correlation with clinical parameters revealed that the increased expression of PLK1 was associated with advanced-stage disease in patients with NLPHL. A multiplex immunofluorescence panel coupled with artificial intelligence algorithms was used to correlate the composition of the tumor microenvironment with the proliferative stage of LP cells. The results showed that LP cells with PLK1 (high) expression were associated with increased numbers of cytotoxic and T-regulatory T cells. Overall, the findings demonstrate that PLK1 signaling increases NLPHL proliferation and constitutes a potential vulnerability that can be targeted with PLK1 inhibitors. An active immune surveillance program in NLPHL may be a critical mechanism limiting PLK1-dependent tumor growth.

The Association of Plasma Cell Density of the Microenvironment with Classical Hodgkin Lymphoma Stage

Background&#x0D; Plasma cells are important prognostic factors in various malignancies including Classical Hodgkin lymphoma (CHL). In the CHL microenvironment, plasma cells are the main prognostic factors, but research of relationship between plasma cell density in the microenvironment and CHL stage is still very limited. This study aims to determine the relationship between plasma cell density in the microenvironment and the CHL stage.&#x0D; &#x0D; Methods&#x0D; A case series procedure was conducted. The samples were paraffin blocks of CHL patients at Anatomic Pathology Department of Faculty of Medicine Universitas Sriwijaya/Mohammad Hoesin General Hospital. Among 47 cases of CHL diagnosed from 1st Januari 2018 to 30th November 2022, only 30 cases were included. Immunohistochemistry was performed by using specific antibody of plasma cells (anti-CD138 antibody). The number of plasma cells in each sample was calculated based on the expression of CD138 in the cell membrane and cytoplasm with weak-strong intensity. Then the cut-off point value was determined based on the ROC curve to classify the high and low plasma cell densities. The density of plasma cells was correlated to clinicopathological characteristics including age, sex, tumor location, CHL subtypes and stage. Statistical analysis was performed using Spearman test of SPSS with significant consideration if p&lt;0.05.&#x0D; &#x0D; Results&#x0D; A high proportion (&gt;10,9) of tumour-associated plasma cells of the tumor microenvironment was found in CHL advanced stage. Spearman test resulted in a significant correlation between density of plasma cell with advanced stage classical Hodgkin lymphoma (p=0.000).&#x0D; &#x0D; Conclusions&#x0D; There is significant relationship between high density of plasma cells with CHL stage.

ROLE OF GATA3 AND STAT6 IMMUNOHISTOCHEMISTRY IN CLASSIC HODGKIN LYMPHOMA (CHL) AND NODULAR LYMPHOCYTE PREDOMINANT HODGKIN LYMPHOMA (NLPHL)

Objective: The purpose of our study is to investigate the utility of immunohistochemical expression of GATA3 and STAT6 in differentiating Classic Hodgkin Lymphoma (CHL) from Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL). Material and Methods: We approached database of Shaukat Khanum Memorial Cancer Hospital and Research Centre and selected a total of 79 CHLs and 15 NLPHLs diagnosed either on Trucut biopsy or excision biopsy diagnosed during the time 2020-2021. One slide from each of these 94 cases was stained with GATA3 and STAT6 independently and pattern of staining (either nuclear or cytoplasmic or dual nuclear and cytoplasmic) was accessed. Results: 75/79(95%) cases of CHL were positive for GATA3 staining [60/79(75.9%) cases showed nuclear GATA3 staining, 15/79(18.9%) cases showed both nuclear and cytoplasmic staining] and 4/79(5%) CHL cases were negative for GATA3. 15/15(100%) cases of NLPHL were negative for GATA3[12/15(80%) cases showed no staining and 3/15(20%) cases showed only cytoplasmic blush]. 65/79(82%) cases of CHL were positive for STAT6[17/79(21.5%) cases showed nuclear STAT6 expression, 48/79(60.7%) cases showed both nuclear and cytoplasmic staining], and 14/79(18%) cases of CHL were negative for STAT6 expression [8/79(10%) cases showed only cytoplasmic staining and 6/79(8%) showed neither nuclear nor cytoplasmic staining]. 14/15(93.3%) cases of NLPHL were negative for STAT6[5/79(33.3%) cases showed only cytoplasmic staining and 9/15(60%) cases showed no staining] and 1/15(6.7%) case of NLPHL was positive for STAT6[showed nuclear STAT6 staining]. Conclusion: Nuclear staining of GATA3 and STAT6 either alone or in combination with cytoplasmic staining can be used to differentiate CHL from NLPHL. GATA3 effectively excludes NLPHL with 100% negative predictive value. Keywords: GATA3, STAT6, Classic Hodgkin lymphoma, Nodular lymphocyte predominant Hodgkin lymphoma

Diagnostic Utility of CD200 Immunohistochemistry in Distinguishing EBV-Positive Large B-Cell Lymphoma From Classic Hodgkin Lymphoma.

Epstein-Barr virus-positive large B-cell lymphoma (EBV+ LBCL) is a heterogeneous group of diseases that may resemble classic Hodgkin lymphoma (CHL) both morphologically and immunophenotypically. However, these diseases are treated with different therapies and carry distinct prognoses. We examined CD200 expression by immunohistochemistry in EBV+ LBCL and evaluated its diagnostic utility in the differential diagnosis with CHL. CD200 immunohistochemistry was performed on archival material from 20 cases of CHL (11 EBV+, 9 EBV-), 11 cases of EBV+ LBCL, and 10 cases of diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS). Staining pattern and intensity (0-3+ scale) were recorded. CD200 positivity was seen in Reed-Sternberg cells in 19 (95%) of 20 cases of CHL, predominantly in a strong (3+, 15/19) and diffuse (>50% of cells, 17/19) pattern. In contrast, CD200 was negative in 8 (73%) of 11 cases of EBV+ LBCL; the 3 positive cases showed 1 to 2+ staining in less than 50% of lesional cells. All cases of DLBCL NOS were negative for CD200. CD200 may be a useful immunophenotypic marker in differentiating EBV+ LBCL from CHL, with negative to partial/weak staining favoring a diagnosis of EBV+ LBCL and strong diffuse staining favoring a diagnosis of CHL.

CLINICO-PATHOLOGICAL EXAMINATION OF WALDEYER RING LYMPHOMAS

Introduction: Waldeyer's ring (WR) is the second most common site of extranodal lymphomas. Its clinical course may resemble those of nodal lymphomas. In this study, we evaluated the histopathological and clinical findings, the presence of Epstein-Barr virus (EBV), and overall survival of WR lymphomas diagnosed in our department. Materials and Methods: Retrospectively, 32 patients diagnosed with WR lymphoma between 2017-2022 were included. The demographic, clinical data of the patients and lymphoma types according to the latest classification of the World Health Organization, the presence of EBV (EBV early RNAs (EBER) by chromogenic in-situ hybridization (ISH) method) were examined. Descriptive statistics, categorical data were evaluated as percentage and frequency. Kaplan-Meier analysis was used for survival rate. A P value less than 0.05 was considered statistically significant. Results: The majority of 32 cases in our study were male. The mean age was 57.97±16.15 years. The clinical prediagnosis was carcinoma in 46.9% of the cases. Tonsil and nasopharynx had equal proportions as lymphoma origin. Only 3 (9.4%) cases are classic hodgkin lymphoma (CHL). Others were NHL, of which 16 (50.0%) were diffuse large B-cell lymphoma (DLBCL). EBER was positive only in tonsillar CHL cases. The survival of patients with lymphoma of nasopharyngeal origin was shorter than those of tonsillar origin (p=0.037). Conclusion: WR lymphomas are most often confused with carcinomas clinically. DLBCL is the most common type of lymphoma. EBER has been detected only in CHL. Survival is lower in lymphomas originating from the nasopharynx.&#x0D; Keywords: Non-Hodgkin Lymphoma, Nasopharynx, Tonsil, Hodgkin Lymphoma

PD-L1 immunohistochemistry assay optimization to provide more comprehensive pathological information in classic Hodgkin lymphoma

Overexpression of PD-L1 can be a predictive marker for anti-PD-1 therapeutic efficacy in classic Hodgkin lymphoma (CHL); however, harmonization of different IHC assays remains to be accomplished, and interpretations of PD-L1 immunostaining results remain controversial in CHL. In this study, we sought to optimize the PD-L1 immunohistochemistry (IHC) assay in CHL. All tests were performed on a tumour tissue microarray established from 54 CHL cases. Three IHC antibodies (405.9A11, SP142, 22C3) for detecting PD-L1 expression were compared semi quantitatively with the RNAscope assay (No. 310035, ACD), and the difference in the expression in background immune cells (ICs) between assays and the associations of expression levels with densities of TILs/TAMs were also analysed. 405.9A11 demonstrated best specificity in HRS cells and best sensitivity in ICs. Positive expression of PD-L1 was more frequent in ICs (85.2%) than in HRS cells (48.1%). Different subgroups of background ICs, including tumour-associated macrophages (TAMs), were assessed and scored for CD4, CD8, FOXP3, and CD163 expression. PD-L1 expression on ICs was the factor most associated with the density of TAMs. 405.9A11 provided the most convincing PD-L1 expression results. Pathologists should report PD-L1 expression in a combined manner, including both the status of HRS cells and the percentage of PD-L1-positive ICs.

Hodgkin Lenfomada B Hücre Transkripsiyon Faktörlerinin İmmünohistokimyasal İfadesi ve Ayırıcı Tanıda Kullanımı

Aim: Classical Hodgkin lymphoma is common, it is one of the lymphomas whose differential diagnosis can be difficult. It is thought that Hodgkin cell may originate from the germinal center. Our aim in this study was to determine the germinal center transformation markers OCT-2, BOB.1, BCL-6, PAX-5, CD20 and MUM-1 in Classic Hodgkin Lymphoma (CHL), Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) and Diffuse Large B-cell Lymphoma (DLBCL) to evaluate the expressions of by immunohistochemical method and chromogenic in-situ hybridization (ISH) of EBV early RNAs (EBER).&#x0D; Material and methods: 49 biopsies diagnosed with Hodgkin lymphoma (HL), 5 with NLPHL and 19 with DLBCL were evaluated for CD30, PAX-5, OCT-2, BOB.1, MUM-1, BCL-6, and CD20, and EBER positivity. SPSS 18 was used for statistical analysis.&#x0D; Results: 73 lymphoma cases were included in the study, 61.6% males and 38.4% females. The median age of patients was 50 years. CHL (67.1%) was the most common lymphoma type, and mixed cellular Hodgkin lymphoma (MSHL) was the most common subtype. There was a statistically significant difference in CD30, OCT-2, BOB.1, MUM-1, PAX-5, CD20, BCL-6, EBER expression between CHL and DLBCL cases (p

Aberrant synaptophysin expression in classic Hodgkin lymphoma

BackgroundSynaptophysin is an immunohistochemical marker for neuroendocrine differentiation and is widely used in pathologic diagnosis. Its expression in malignant lymphoma has not yet been described. However, we experienced an index case of classic Hodgkin lymphoma with synaptophysin expression. This experience prompted us to investigate synaptophysin expression in classic Hodgkin lymphoma.MethodImmunohistochemical staining of synaptophysin was performed in 59 diagnosed cases of classic Hodgkin lymphoma, 10 anaplastic large cell lymphomas, 16 diffuse large B-cell lymphomas, and 5 extranodal marginal zone lymphoma of the mucosa-associated tissue. Synaptophysin-positive cases were stained for both chromogranin and CD56a.ResultOf 59 classic Hodgkin lymphoma cases, 11 (19%) were positive for synaptophysin. None of the anaplastic large cell lymphomas expressed synaptophysin. Synaptophysin showed weak but specific expression in the cytoplasm of the Hodgkin lymphoma tumor cells. Other background inflammatory cells (such as macrophages, B-, and T-lymphocytes) were all negative for synaptophysin expression. Chromogranin and CD56a were not expressed in the synaptophysin-positive classic Hodgkin lymphomas.ConclusionsSynaptophysin is an integral glycoprotein present in presynaptic vesicles of neurons and neuroendocrine cells. It is a diagnostic marker for neuroendocrine tumors. Aberrant synaptophysin expression has been reported in non-neuroendocrine tumors but not in lymphoma or leukemia. To the best of our knowledge, synaptophysin positivity has only been reported in a single case of precursor T-lymphoblastic leukemia/lymphoma to date. Our study showed that aberrant synaptophysin expression in classic Hodgkin lymphoma is an unexpectedly frequent finding. The mechanism underlying, and prognostic significance of, such aberrant expression is unclear. Thus, in a small biopsy, aberrant synaptophysin expression could be a diagnostic pitfall and should be carefully avoided.

A Unusual Case of Classic Hodgkin Lymphoma (cHL) with Aberrant T-Antigens Expression

Abstract Introduction/Objective T-cell-associated antigens (TCA) are rarely expressed by Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) and is associated with uncertain clinical significance. Methods/Case Report We present a very recent case of a 68 year-old female with no significant past medical history presented with a large right groin mass for 1 month. She denied any fever, night sweats, fatigue or weight loss. CT abdomen/pelvis showed inguinal/pelvic lymphadenopathy. Resection showed effaced nodal architecture with a vague nodular appearance and with large, atypical nucleolated cells in a background of small, mature lymphocytes and histiocytes. Eosinophils are conspicuously absent in the background. The large cells were polylobated lymphocyte and histiocyte rich (L &amp; H) like, classic HRS cells as well as multinucleated in appearance. The morphologic features overlapped between Classic Hodgkin Lymphoma, and Nodular Lymphocyte Predominant Hodgkin Lymphoma. Given the immunohistochemical (IHC) features of the neoplastic cells [CD45 negative, PAX5+ (weak), CD30+ (strong), CD15+ (majority) and MUM1 +] the diagnosis was most compatible with CHL. Interestingly, a subset of the Hodgkin cells (10-20%) aberrantly expressed a number of T-cell markers (CD2, CD3, CD4, and CD8). However, the background smaller T-cells did not show cytologic atypia or aberrancies of T-cell antigen markers. The large cells were negative for CD43 and ALK1. TCR gamma gene rearrangement was also negative for clonal T-lymphocytes, thus excluding the possibility of peripheral T-cell lymphoma with Hodgkin-like cells. Based on the morphology and IHC profile, this case proves to be CHL with multiple TCA expression including CD2, CD3, CD4 and CD8. She was planned for chemotherapy. Four months after the initial diagnosis and after completion of 2 cycles of chemotherapy, her PET CT scan showed improvement with right inguinal adenopathy being smaller in size and decreased avidity, indicating a response to treatment. She is due for 2 more cycles. Till todate she is doing well with no further symptoms. Results (if a Case Study enter NA) NA. Conclusion So far reported cases of classic Hodgkin lymphoma (CHL) with aberrant T-cell antigen (TCA) expression were associated with decreased event-free survival and overall survival when compared with TCA-negative CHLs. Our finding contributes to the literature and improves our knowledge of the disease.

HL-048 Clinicopathological, Immunohistochemical Characteristics, and Outcomes of Hodgkin Lymphoma Patients in Erbil City, Iraq

Hodgkin lymphoma (HL) has unique epidemiological features with diverse pathologies and exhibits considerable clinicopathological variations in different parts of the world. In this study, we aimed to assess the clinicopathological features, immunohistochemistry, and outcomes of HL patients treated in Erbil, northern Iraq. This was a retrospective study conducted in Nanakaly Hospital for Blood Diseases and Oncology in Erbil, Iraq. A total of 125 patients diagnosed between January 2012 and December 2016 were assessed for their clinical characteristics, histopathology, immunophenotype, and outcome. The median age was 28 years (range: 18-71 years); 55% were male and 41% had Stage II HL. The most common histological type was nodular sclerosis (51.2%) followed by mixed cellularity (43.2%). CD30 was positive in nearly all cases of classical HL. CD15 and CD20 were positive in 98.7% and 75% of patients with the nodular lymphocyte predominant subtype, respectively. Most of the patients received adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy, and the 5-year overall survival in our study is 70%. Advanced stage (IV), high lactate dehydrogenase levels, low hemoglobin, and splenomegaly are significant predictors of poor survival. Our patients exhibited outcomes that were lower than those reported in developed countries.

The Association of Programmed Death Ligand 1 (PD-L1) and Cluster of Differentiation 95 Ligand (CD95L) Immunoexpression with Chemotherapy Response in Classical Hodgkin Lymphoma

Background: Programmed Death Ligand (PD-L1) and Cluster of Differentiation 95 (CD95L) are influenced by oncogenes and function in the anti-apoptosis process which is thought to play a role in chemotherapy resistance. This study aimed to analyze the association of PD-L1 and CD95L immunoexpression with chemotherapy response in Classical Hodgkin Lymphoma (CHL).Method: This study involved 40 cases of histopathologically diagnosed CHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PD-L1 and CD95L immunohistochemical staining were performed in selected paraffin-embedded tissue blocks of all cases. The chemotherapy response status of the patients was taken from the medical recordResults: High PDL-1 immunoexpression was evident in 19 (47.5%) cases while positive CD95L immunoexpression was found in 14 (35%) CHL cases. High PD-L1 immunoexpression was significantly associated with the Non-Responsive (NR) group (78.9%) with p-value = 0.0001. Positive CD95L immunoexpression was greater in the NR group (71.4%) with p-value = 0.37.Conclusion: : High PD-L1 immunoexpression indicated an unfavorable response to ABVD chemotherapy in CHL. CD95L immunoexpression was not associated with ABVD chemotherapy response in CHL.

IRF8 as a Novel Marker to Differentiate Between CD30-Positive Large Cell Lymphomas.

Interferon regulatory factor 8 (IRF8) is a new biomarker shown to be positive in monocytic leukemias as well as in B cells. As a transcription factor, it plays a critical role in pre-B-cell differentiation and induction of tolerance pathways, among other functions. Given the frequent diagnostic dilemma in CD30-positive large cell lymphomas that could resemble both Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL), we sought to determine whether IRF8 can be useful in distinguishing between these neoplasms that require different treatment strategies. In this retrospective study, 74 cases of classic Hodgkin lymphoma (CHL) and 7 cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) on a tissue microarray (TMA), as well as 15 individual cases of ALK-negative ALCL and 4 cases of ALK-positive ALCL, were stained for IRF8. Paired box 5 (PAX5) immunostaining of the TMA was also performed and compared alongside since that marker is occasionally the only marker to help clinically differentiate between T- and B-cell lymphomas with anaplastic/Hodgkin-like cytology. None (0%) of the ALCLs were positive for IRF8 while all (100%) of the NLPHLs and 85% of the CHLs were positive for IRF8. Six (8%) cases of CHL were PAX5 negative but IRF8 positive. Conversely, seven (10%) cases of CHL were PAX5 positive but IRF8 negative. Four (6%) cases of CHL were negative for both PAX5 and IRF8. There is significant morphologic and immunophenotypic (CD30 positive and CD45 and CD20 negative) overlap between CHL and ALCL. Since many ALCLs show downregulation of lineage-specific T-cell markers or are "null cell" type, only PAX5 has been a reliable marker to differentiate between borderline cases. This is further confounded by positivity of PAX5 in some ALCLs due to amplification of PAX5. On the basis of recent discoveries of IRF8 function as well as performance as an immunostain, we tested this marker in human lymphoma samples and found that it aids in the discrimination between these tumors.