Nodular Lymphocyte Predominant Hodgkin Lymphoma Research Articles

Exploring the complexity, treatment challenges, and outcomes in pediatric nodular lymphocyte predominant Hodgkin lymphoma: a perspective from a low–middle-income country

BackgroundIn children, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Given the lack of data on the best chemotherapy regimen, there is a knowledge gap in best management.MethodsThis retrospective study included all pediatric patients with NLPHL diagnosed and treated at the Children’s Cancer Hospital, Egypt (2007–2018). We analyzed the clinical characteristics, and treatment outcome according to disease stage (early and advanced), treatment strategy (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD] or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] and explored the prognostic factors for progression-free survival.ResultsThe median age at diagnosis was 12 years; 40 (68%) patients had early-stage disease, and 19 (32%) had advanced-stage disease. The median follow-up was 70 months; the 5-year EFS and OS were 75% and 97%, respectively. The 5-year EFS was 78% for early-stage disease and 60% for advanced-stage disease; the 5-year OS was 100% for early-stage disease and 88% for advanced-stage disease. The patients who underwent R-CHOP had a better 3-year EFS (100%) compared with those who underwent ABVD (65%) regimen (P = 0.01). Seventeen (25%) patients relapsed: 9/40 (22%) had early-stage disease, and 8/19 (42%) had advanced-stage disease. Splenic involvement, mediastinal disease, extranodal disease, and slow early response were independent predictors of relapse risk.ConclusionPediatric patients with early-stage NLPHL have an excellent prognosis, with a 5-year OS of 100%. However, those with advanced stages had a high relapse rate. R-CHOP was associated with a better response and relapse-free rate than ABVD.

Flow Cytometry for Non-Hodgkin and Hodgkin Lymphomas.

Multiparametric flow cytometry is a powerful diagnostic tool that permits rapid assessment of cellular antigen expression to quickly provide immunophenotypic information suitable for disease classification. This chapter describes a general approach for the identification of abnormal lymphoid populations by flow cytometry, including B, T, NK, and Hodgkin lymphoma cells suitable for the clinical and research environment. Knowledge of the common patterns of antigen expression of normal lymphoid cells is critical to permit identification of abnormal populations at disease presentation and for minimal residual disease assessment. We highlight an overview of procedures for processing and immunophenotyping non-Hodgkin B- and T-cell lymphomas and also describe our strategy for the sensitive and specific diagnosis of classic Hodgkin lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and T-cell/histiocyte-rich large B-cell lymphoma.

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.

T-Cells Rich Classical Hodgkin Lymphoma, a Pathology Diagnostic Pitfall for Nodular Lymphocyte-Predominant Hodgkin Lymphoma; Case Series and Review

T-Cells Rich Classical Hodgkin Lymphoma, a Pathology Diagnostic Pitfall for Nodular Lymphocyte-Predominant Hodgkin Lymphoma; Case Series and Review

Adult Hodgkin lymphoma incidence trends in the United States from 2000 to 2020

Hodgkin lymphoma (HL) is a rare malignancy affecting the lymphatic system. Our study examined the incidence rates of adult HL based on sex, race/ethnicity, age, and histological subgroups in the United States (US) from 2000 to 2020. Data for this study were extracted from the Surveillance, Epidemiology, and End Results 22 database. HL patients were identified utilizing the International Classification of Diseases for Oncology version 3 and categorized as classical HL, lymphocyte-rich/mixed cell/lymphocyte depleted, nodular sclerosis, classical HL, not otherwise specified, and nodular lymphocyte-predominant HL. The study reported average annual percent change (AAPC). All estimates were presented as counts and age-standardized incidence rates (ASIRs) per 100,000 individuals. Between 2000 and 2019, a total of 70,924 cases of HL were reported in the US. Classical HL was the predominant subtype (94.27%), and most incident cases were among non-Hispanic Whites (66.92%) and those aged 20–29 years (24.86%). The ASIR per 100,000 population was 3.83 for men and 2.92 for women. Both sexes showed declines in the AAPCs between 2000 and 2019 (− 0.64% [− 0.99, − 0.28] and − 0.40% [− 0.77, − 0.03] for men and women, respectively). There was a significant decrease in ASIRs after COVID-19 among both sexes (percent change: − 7.49% [− 11.58, − 3.40]). Throughout all age groups, men had a higher incidence rate compared to women, except for those aged 20–29 years. Although the overall HL incidence rate was lowered in the study period from 2000 to 2019, a dramatic decrease in ASIRs of HL patients following COVID-19 pandemic was observed.

Anti-RGS8 paraneoplastic cerebellar ataxia is preferentially associated with a particular subtype of Hodgkin’s lymphoma

Ataxia with anti-regulator of G-protein signaling 8 autoantibodies (RGS8-Abs) is an autoimmune disease recently described in four patients. The present study aimed to identify other patients with RGS8-Abs, describe their clinical features, including the link between RGS8-related autoimmune cerebellar ataxia (ACA) and cancer. Patients with RGS8-Abs were identified retrospectively in the biological collections of the French Reference Center for Paraneoplastic Neurological Syndrome and the University of California San Francisco Center for Encephalitis and Meningitis. Clinical data were collected, and cerebrospinal fluid, serum, and tumor pathological samples were retrieved to characterize the autoantibodies and the associated malignancies. Only three patients with RGS8-Abs were identified. All of them presented with a pure cerebellar ataxia of mild to severe course, unresponsive to current immunotherapy regimens for ACA. Two patients presented with a Hodgkin lymphoma of the rare specific subtype called nodular lymphocyte-predominant Hodgkin lymphoma, with very mild extension. Autoantibodies detected in all patients enriched the same epitope on the RGS8 protein, which is an intracellular protein physiologically expressed in Purkinje cells but also ectopically expressed specifically in lymphoma cells of patients with RGS8-related ACA. The present results and those of the four cases previously described suggest that RGS8-Abs define a new paraneoplastic neurological syndrome of extreme rarity found mostly in middle-aged males that associates pure cerebellar ataxia and a particular lymphoma specifically expressing the RGS8 antigen. As in other paraneoplastic ACA with intracellular antigen, the disease course is severe, and patients tend to exhibit a poor response to immune therapy.

Demographics and Survival Outcomes of Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): A Retrospective Analysis of SEER Database

Demographics and Survival Outcomes of Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): A Retrospective Analysis of SEER Database

HL-697 Demographics and Survival Outcomes of Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): A Retrospective Analysis of SEER Database

HL-697 Demographics and Survival Outcomes of Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): A Retrospective Analysis of SEER Database

Management Algorithm for Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Management Algorithm for Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Intra-tumoral and peripheral blood TIGIT and PD-1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma.

In classical Hodgkin lymphoma (cHL), responsiveness to immune-checkpoint blockade (ICB) is associated with specific tumor microenvironment (TME) and peripheral blood features. The role of ICB in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is not established. To gain insights into its potential in NLPHL, we compared TME and peripheral blood signatures between HLs using an integrative multiomic analysis. A discovery/validation approach in 121 NLPHL and 114 cHL patients highlighted >2-fold enrichment in programmed cell death-1 (PD-1) and T-cell Ig and ITIM domain (TIGIT) gene expression for NLPHL versus cHL. Multiplex imaging showed marked increase in intra-tumoral protein expression of PD-1+ (and/or TIGIT+) CD4+ T-cells and PD-1+CD8+ T-cells in NLPHL compared to cHL. This included T-cells that rosetted with lymphocyte predominant (LP) and Hodgkin Reed-Sternberg (HRS) cells. In NLPHL, intra-tumoral PD-1+CD4+ T-cells frequently expressed TCF-1, a marker of heightened T-cell response to ICB. The peripheral blood signatures between HLs were also distinct, with higher levels of PD-1+TIGIT+ in TH1, TH2, and regulatory CD4+ T-cells in NLPHL versus cHL. Circulating PD-1+CD4+ had high levels of TCF-1. Notably, in both lymphomas, highly expanded populations of clonal TIGIT+PD-1+CD4+ and TIGIT+PD-1+CD8+ T-cells in the blood were also present in the TME, indicating that immune-checkpoint expressing T-cells circulated between intra-tumoral and blood compartments. In in vitro assays, ICB was capable of reducing rosette formation around LP and HRS cells, suggesting that disruption of rosetting may be a mechanism of action of ICB in HL. Overall, results indicate that further evaluation of ICB is warranted in NLPHL.

Histopathologic Features and Differential Diagnosis in Challenging Cases of Nodular Lymphocyte Predominant B-cell Lymphoma/Nodular Lymphocyte Predominant Hodgkin Lymphoma.

Nodular lymphocyte predominant Hodgkin lymphoma was termed "nodular lymphocyte predominant B-cell lymphoma" in the International Consensus Classification (ICC), to emphasize clinical and biological differences from classic Hodgkin lymphoma (CHL). The abbreviation "NLP" represents both terms in the ICC and World Health Organization classifications. Variations in the growth pattern, originally reported as Fan patterns A-F, are designated as either grade 1 or grade 2 in the ICC. NLP is uncommon, and in some cases an accurate diagnosis is challenging. The objectives of this article were to review the histopathologic features of NLP and the differential diagnosis from other key entities including de novo T-cell/histiocyte-rich large B-cell lymphoma (THRLBL) and lymphocyte-rich classic Hodgkin lymphoma (LRCHL). Histologically, NLP Fan pattern E (THRLBL-like) can be indistinguishable from de novo THRLBL. However, focal nodular areas, clustering of tumor cells, presence of few admixed small B-cells or FDC meshworks, and T-cell rosettes favor NLP Fan pattern E and argue against de novo THRLBL. NLP may also be confused with LRCHL. Patients with NLP are younger than those with LRCHL, and LRCHL may show mediastinal involvement. In LRCHL, the nodular pattern often contains eccentrically located small regressed germinal centers and intact small dense FDC meshworks, in contrast to the expanded, and fragmented FDC meshworks in NLP. Neoplastic cells that are positive for CD30 and CD15 but negative for CD20 and CD79a are characteristic of LRCHL. Additionally, Fascin and Gata3 are commonly positive in LRCHL but usually negative in NLP.

Spatial phenotyping of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma with sparse tumor B-cells and a favorable prognosis. Variant growth patterns of NLPHL, however, often show advanced stage, progression to T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) and a worse prognosis. We studied the tumor microenvironment (TME) of NLPHL and THRLBCL using highplex imaging and spatial profiling at the single cell level. Our findings show distinct differences in TME composition and spatial configuration that differ among typical and variant NLPHL and THRLBCL. Typical NLPHL show abundant helper T-cell subsets, while THRLBCL show abundant cytotoxic T-cells and macrophages. Tumor B-cell size and content is lowest in typical NLPHL, followed by variant NLPHL, and highest in THRLBCL, whereas an opposite trend characterized TME B-cells. CD4/CD8 double-positive T-cells are seen in all NLPHL but not in the majority of THRLBCL and are spatially distant from LP-cells and TFH-rosettes. The differences in macrophage/monocyte content in distinguishing NLPHL pattern E from THRLBCL is further corroborated in independent cohorts of cases. Our results validate the current approach to classification and in addition provide novel insights that could be leveraged to refine clinical management for patients with this spectrum of lymphomas.

Current Standards in the Treatment of Hodgkin Lymphoma

This review discusses current trends in the treatment of Hodgkin lymphoma, focusing on optimizing therapy outcomes while minimizing toxicity. We summarize advances made by the incorporation of Brentuximab Vedotin into first line therapy for advanced stage Hodgkin lymphoma. Similarly, the incorporation of checkpoint-inhibition into first-line therapy holds great promise and early results suggest superior efficacy with reduced toxicity. In relapsed or refractory Hodgkin lymphoma, salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation remains the standard approach. However, the remarkable efficacy of checkpoint inhibition in this setting has the potential to redefine treatment paradigms and obviate the need for HD-ASCT in select patients. Finally, we discuss the evolving landscape of nodular lymphocyte predominant Hodgkin lymphoma and reclassification to nodular lymphocyte predominant B-cell lymphoma, with increasing recognition of its distinct characteristics and treatment strategies.

The impact of immunoarchitectural patterns on clinical presentation and response to therapy in children with nodular lymphocyte predominant Hodgkin lymphoma

The impact of immunoarchitectural patterns on clinical presentation and response to therapy in children with nodular lymphocyte predominant Hodgkin lymphoma

ЛИМФОМА ХОДЖКИНА И СИНДРОМ КЛАЙНФЕЛЬТЕРА: ОПИСАНИЕ КЛИНИЧЕСКОГО СЛУЧАЯ

Klinefelter syndrome is the most common chromosomal abnormality among others and is manifested mainly by hypogonadism, gynecomastia, and infertility. Against the background of KS, oncological diseases can develop, more often nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) due to genetic reparations, as well as osteoporosis as a result of androgen deficiency. This article describes a clinical case of a patient with Klinefelter syndrome and the onset of Hodgkin’s lymphoma (HL) in order to assess the risk of osteopenia/osteoporosis in this patient. A patient with previously diagnosed KS went to the doctor complaining of weakness, fatigue, weight loss, local enlargement of the inguinal lymph nodes. The patient was diagnosed with NLPHL and standard pathogenetic therapy was performed. Taking into account the presence of risk factors for osteoporosis (the presence of Klinefelter syndrome, HL, chemotherapy), the patient underwent two-energy densitometry in the lumbar spine, neck and proximal femur in order to assess the condition of bone tissue. As a result, a decrease in bone mineral density was found in all measurement areas. This clinical case describes a rather rare combination of three significantly different nosologies. Interestingly, two of them, namely HL and Klinefelter syndrome, contribute to the development of the third through various mechanisms. The presence of a decrease in bone density in this patient necessitates prevention. Despite the rare occurrence of such combined pathologies, the issue of timely diagnosis and prevention of complications from the musculoskeletal system in this category of patients remains relevant today

A Real-World Single-Center Study of Adult Hodgkin's Lymphoma

To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, β2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

International Prognostic Score for Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation. We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41). In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).

Abstract 6468: Nodular lymphocyte predominant hodgkin lymphoma: A national cancer database analysis with focus on hispanics

Abstract Background:Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare and distinct subtype of Hodgkin Lymphoma.(PMID 26149294) 80% manifest at early stages, with a male and black race predilection.(PMID 26149195) Previous analysis have shown similar survival of Hispanics (HI) compared to Non-Hispanics (NH).(J Clin Oncol 10.1200/JCO.2023.41.16_suppl.e19512) This National Cancer Database (NCDB) analysis aims to clarify how sociodemographic factors affect presentation and survival in HI vs NH patients with NLPHL. Methods:Data were analyzed on NLPHL patients in the United States reported to the NCDB 2004-2019. Demographic and treatment characteristics were compared between ethnic groups. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) between HI and NH populations. Multivariate analysis and propensity score matching was performed. Results:Of 5517 of NLPHL patients, 379 were HI, and 4904 NH. Male gender and white race predominated for both. HI were diagnosed at a younger median age of 44 years (y) vs 48 y for NH, p=0.001. Most patients were diagnosed between years 2016-2019. Stage I predominated for both, p&amp;lt;0.001. As to Charlson-Deyo score ≥2, both HI and NH had 4%. Private insurance as primary payer was the most prevalent type for HI (53%) and NH (65%). HI had a higher percentage of unknown/uninsured, 12% vs 6% for NH, p&amp;lt;0.001. In relation to census median income (2008-2012), the most prevalent bracket for HI (27%) was $48,000-$62,000, and for NH (35%) was &amp;gt;$63,000. Regarding median income of &amp;lt;$38,000, HI were 29% vs 16% for NH, p&amp;lt;0.001. For median distance in miles (mi) between the patient’s residence and the hospital that reported the case (great circle distance), HI lived at a median of 6.3mi, vs NH at median of 9.5mi. Majority of HI (56%) were treated at Academic/Research programs; while most of NH (39%) were treated at Comprehensive Community Cancer programs, p&amp;lt;0.001. On survival analysis, the survival probability at 2, 5 and 10 y for HI was 96%, 92%, 86%, vs for NH was 96%, 92%, 84%, respectively. The median survival time wasn’t reached for both HI and NH, and no statically significant difference was seen, p=0.57. On multivariate analysis, HI was not associated with worse OS (HR 0.76, CI 0.44-1.31, p=0,33). The propensity matched analysis confirmed not reached OS on both cohorts. Conclusion:NLPHL is a disease that affects young males, at early stages, for both HI and NH. Unlike previous studies, in this analysis white race predominates; which could be explained by the increase in reported cases over years. Despite HI having more uninsured population with lower median income quartiles, this wasn’t a barrier to access care at academic/research programs. Although no difference in OS was seen among ethnicities, there is a tendency that might favor HI. More studies are needed to determine if specific demographic factors truly influence survival in NLPHL. Citation Format: Esteban Toro Velez, Daniel Rosas, Carolina Velez-Mejia, Qianqian Liu, Joel Michalek, Adolfo Enrique Diaz Duque. Nodular lymphocyte predominant hodgkin lymphoma: A national cancer database analysis with focus on hispanics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6468.

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.

IgD expression in various immunoarchitectural patterns of nodular lymphocyte predominant Hodgkin lymphoma in children

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) consist of lymphocyte predominant cell or LP-cell. Despite their origin from active germinal centers, in some cases LP-cells express IgD, which is characteristic of naive B-lymphocytes of the mantle zone. Due to the rarity of NLPHL, assessing the frequency of IgD-positive cases is difficult. This marker can serve not only for differential diagnosis with other diseases, but also indicate the possible heterogeneity of NLPHL, which is currently represented by six immunoarchitectural patterns. To determine the frequency of IgD-positive cases of NLPHL in children with subsequent assessment of the association with types of immunoarchitectural patterns. The study included 52 cases of NLPHL, which were divided to typical and atypical patterns. Differences between two groups were compared using Fisher's exact tests. IgD expression was found in LP-cells in 26 of 52 cases (50%) and was positively correlated with atypical types (typical - 5/23, 21.7% vs atypical - 21/29, 72.4%, p=0.0003), among which pattern C was most common. Due to the high incidence of IgD-positive cases in NLPHL, this marker may be useful in differential diagnosis with histologic mimics. At the same time, positive IgD status was associated with atypical patterns, which may likely determine the different biology of neoplastic cells within the same form.