[IgD expression in various immunoarchitectural patterns of nodular lymphocyte predominant Hodgkin lymphoma in children]. / Ekspressiya IgD pri razlichnykh immunoarkhitekturnykh patternakh nodulyarnoi limfomy Khodzhkina s limfotsitarnym preobladaniem u detei.

BACKGROUND: 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. OBJECTIVE: To determine the frequency of IgD-positive cases of NLPHL in children with subsequent assessment of the association with types of immunoarchitectural patterns. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Nodular lymphocyte predominant Hodgkin lymphoma (paragranuloma of Poppema) in children: Case report, review of the literature and treatment]. / Lymphome de Hodgkin nodulaire à prédominance lymphocytaire (paragranulome de Poppema) chez l'enfant : à propos d'un cas, revue de la littérature et traitement.

We present the case of a 12 year old child with a limp. The diagnostic work-up reveals splenomegaly, multifocal bone involvement and abdominal adenopathies. A biopsy of an intra-abdominal lesion shows a lymphoid mass with a nodular architecture composed of poorly defined nodules. We identify large cells with irregular, sometimes poly-lobulated nuclei with a particular immunohistochemical profile. Those "pop-corn" cells are positive for CD20, CD79a, pax-5 and bcl-6 and are negative for CD15, CD30, bcl-2, TdT, CD56 and EMA. There is a diffuse follicular helper T cell population that is located in between the tumour cells. The overall picture is indicative of a nodular lymphocyte predominant Hodgkin lymphoma. Advanced stage of this disease is rare in children and there is currently little data to guide optimal treatment. Because of a stage IV disease, the patient is treated with chemotherapy after which complete metabolic remission is observed. 3.5 years after the initial diagnosis, our patient relapses. He is treated with chemotherapy and an autologous peripheral blood stem cell transplantation. He remains in complete remission since then. This case illustrates the favorable prognosis of the disease even after relapse.

Characterizing the immune microenvironment for nodular lymphocyte-predominant Hodgkin lymphoma.

The microenvironment of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and its relationship to presentation and outcomes has not been widely investigated. In a large cohort of patients with NLPHL, Hartmann and colleagues showed an association between microenvironmental factors and clinical presentation serving to inform future studies evaluating the prognostic impact of the immunoarchitectural patterns and cell types present. Commentary on: Hartmann et al. Tumor cell characteristics and microenvironment composition correspond to clinical presentation in newly diagnosed nodular lymphocyte predominant Hodgkin lymphoma. Br J Haematol 2022;199:392-401.

Tumour cell characteristics and microenvironment composition correspond to clinical presentation in newly diagnosed nodular lymphocyte-predominant Hodgkin lymphoma.

Different studies have characterized the microenvironment and its prognostic impact in classic Hodgkin lymphoma whereas such analyses are pending for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). We thus investigated characteristics of tumour cells and microenvironment in NLPHL and evaluated possible correlations with the clinical presentation. Lymph node samples from 152 NLPHL patients who had first-line treatment within the randomized German Hodgkin Study Group HD16-HD18 trials were available and analysed with regard to IgD status and nuclear size of the tumour cells as well as presence of PD1-positive follicular T helper cells and CD163-positive macrophages in the microenvironment. While large tumour cell nuclei and high numbers of PD1-positive follicular T helper cells in the microenvironment were more common in patients presenting with early/intermediate stages than in patients with advanced-stage disease (p < 0.0001, unpaired t-test; p = 0.0022, Mann-Whitney test), no differences between risk groups were observed in terms of the IgD status of the tumour cells and the content of CD163-positive macrophages in the microenvironment. PD1-positive follicular T helper cells were present in both cases with typical and variant growth patterns and rosetting around the tumour cells was observed in 96% of patients, indicating an important role of PD1-positive follicular T helper cells in NLPHL.

Histopathological growth patterns in patients with advanced nodular lymphocyte-predominant Hodgkin lymphoma treated within the randomized HD18 study: a report from the German Hodgkin Study Group.

We retrospectively investigated histopathological growth patterns in individuals with advanced nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) treated within the randomized HD18 study. In all, 35/60 patients (58%) presented with atypical growth patterns. Patients with atypical growth patterns more often had stage IV disease (P = 0·0354) and splenic involvement (P = 0·0048) than patients with typical growth patterns; a positive positron emission tomography after two cycles of chemotherapy (PET-2) tended to be more common (P = 0·1078). Five-year progression-free survival [hazard ratio (HR) = 0·86; 95% confidence interval (CI) = 0·49-1·47] and overall survival (HR = 0·85; 95% CI = 0·49-1·51) did not differ between the groups after study treatment with PET-2-guided escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). Thus, advanced NLPHL is often associated with atypical growth patterns but their prognostic impact is compensated by PET-2-guided escalated BEACOPP.

The utility of IMP3 immunohistochemical staining in differentiating nodular lymphocyte predominant Hodgkin Lymphoma from T-Cell/Histiocyte-Rich large B-Cell lymphoma.

INTRODUCTION: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and T cell/histiocyte-rich large B-cell lymphoma (THRLBCL) have overlapping histological features that make their diagnosis challenging. Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is a recently proposed diagnostic marker for Hodgkin's lymphoma. The aim of this study was to determine the ability of IMP3 in differentiating NLPHL from THRLBCL. METHODS: In this retrospective study, the formalin-fixed paraffin-embedded blocks from 56 patients (28 NLPHL and 28 large B cell lymphoma (LBCL, including 16 THRLBCL and 12 DLBCL, NOS) cases based on immunohistochemistry (IHC) were included. Sample sections were stained for IMP3 using IHC method. Moderate to strong staining in at least 10% of tumor cells was considered positive IMP3 expression. RESULTS: The mean age of the patients was 41.25 ± 16.08 years old. The majority of the patients were male. There was a significant age difference between NLPHL (34.61 ± 16.44 years old) and LBCL (47.89 ± 12.85 years) groups (p = 0.001). No significant difference was seen in gender and site between NLPHL and LBCL groups. The expression of IMP3 was mainly strong in LBCL group, while it was heterogeneously distributed among NLPHL samples ranging from weak to strong (p < 0.001). It was determined that strong IMP3 expression at 55.00% can differentiate LBCL from NLPHL with 71.4% sensitivity and 71.4% specificity. CONCLUSION: Our findings showed that IMP3 may be a good complement in differentiating NLPHL cases from THRLBCL.

Risk of hematological malignancies in the families of patients treated for nodular lymphocyte-predominant Hodgkin lymphoma.

BACKGROUND: Familial clustering of lymphoid and/or hematological malignancies (FHM) provides an opportunity to study the responsible genes. The data is limited in patients with lymphoid and hematological malignancies. METHODS: The lymphoma database was used to identify patients seen in our institution from 1998 to 2019 with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). We studied FHM by collecting detailed history of any malignancy in the family (FM). RESULTS: Two hundred NLPHL patients were identified. Contacting was not possible in 30 patients due to no response to the phone calls (22) and death [1]. 170/200 patients were interviewed; represented 167 families (3 patients with a family member with NLPHL). These 170 patients provided information about 8225 family members. These 167 families had a total of 329 family members with 334 malignancies (including 167 NLPHL patients and 5 members with 2 malignancies each). Of these 167 patients, 77 (46.1%) had no FM while 90 (53.9%) patients had a positive FM; 162 family members with 167 malignancies. Among these 167 families, 31 families (18.6%) had members with FHM +/- solid cancers. These 31 families had 35 family members (25 males:10 females) with 16 lymphomas: diffuse large B cell lymphoma [2], follicular center cell lymphoma [3], chronic lymphocytic leukemia/small lymphocytic lymphoma [3], non-Hodgkin lymphoma [2], classical HL [2], and NLPHL [4]. Total of 8 leukemia: acute lymphoblastic leukemia [4], acute myeloid leukemia [3], and leukemia - no subtyping [5]. These 35 FHM members are 1st [6], 2nd (16), and 3rd [7] degree relatives of 31 NLPHL patients. There are 4 families with NLPHL in family members; all these 8 NLPHL patients are male and are alive. The median total number of 1st + 2nd +3rd degree members are 81. The decrease in the age of diagnosis from 1st generation to the 2nd generation (anticipation) was noted in 13/17 patients; 2nd generation median age at diagnosis was 29.7 years vs 1st generation age 53 years (developed malignancy 23.3 years earlier). CONCLUSION: FHM is frequent in NLPHL. This study provided us many important insights for planning future studies in terms of interviewing technique, time, and resource allocation and genetic testing.

Nodular lymphocyte predominant Hodgkin lymphoma: Experience of Polish Pediatric Leukemia/Lymphoma Study Group.

Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) is a rare clinical entity. To investigate NLPHL clinical course and treatment a survey was performed within Polish Pediatric Leukaemia/Lymphoma Study Group (PPLLSG) participating centers. A questionnaire was sent to all participating centers and analysis of clinical data was performed. From 2010 to 2019, 19 pediatric patients with confirmed NLPHL were registered in Poland. Median age of patients was 12.2 (5.5 - 17.8) years. NLPHL occurred mainly in males (n = 17). Most of the patients (n = 16) had early stage disease - Stage I (n = 6) and stage II (n = 10). Four of the six patients with stage I disease (I A, n = 5; I B, n = 1) underwent complete primary resection. One of these relapsed and was treated with CVP (cyclophosphamide, vinblastine, prednisone) chemotherapy. Two other patients who were not resected completely received CVP chemotherapy and no relapses were observed. Thirteen patients presented with unresectable disease. Of these, eight received three CVP chemotherapy cycles, and five were treated with other chemotherapy regimens. Three relapses were observed and these patients were further treated with chemotherapy and rituximab. One patient underwent autologous stem cell transplantation (auto-SCT). All patients remain alive. Five-year progression-free survival and overall survival for the entire group of patients was 81.6% and 100%, respectively. NLPHL treatment results are consistent with results noted in other countries. Early stage patients have very good outcomes with surgery and observation or low intensity chemotherapy, but this approach may be insufficient in advanced disease.

Primary therapy and survival among patients with nodular lymphocyte-predominant Hodgkin lymphoma: a population-based analysis in the Netherlands, 1993-2016.

In this nationwide, population-based study, we assessed trends in primary treatment and survival among 687 patients with nodular lymphocyte-predominant Hodgkin lymphoma (75% males; median age, 40 years; and 74% stage-I/II disease) diagnosed in the Netherlands between 1993-2016. There were no noteworthy changes in the application of primary therapy over time among adult patients across the different disease stages and age groups. Survival among various subgroups of adult patients was largely comparable to the expected survival of the general population. A particularly encouraging finding was that young adult patients experienced virtually no excess mortality, as compared to the general population.

Anti-Ma-associated paraneoplastic cerebellar degeneration in a patient with nodular lymphocyte-predominant Hodgkin lymphoma: a case report.

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a devastating paraneoplastic syndrome that occasionally occurs in patients with Hodgkin lymphoma (HL). Anti-Ma2 is a well-characterized onconeuronal antibody and one of the causes of PCD. There has been only one previous report of anti-Ma2-associated paraneoplastic syndrome as a complication of HL. Here we present a rare case of anti-Ma2-associated PCD in a patient with nodular lymphocyte-predominant HL (NLPHL). CASE PRESENTATION: A 77-year-old man with a 3-month history of gait instability and a 2-month history of oscillopsia was referred to our hospital for further investigation. On examination, his cognition was normal. He had nystagmus in all directions of gaze; specifically, he had horizontal and rotatory nystagmus in the primary position, downbeat nystagmus after right, left, and up gaze, and upbeat nystagmus after down gaze. Although his limb ataxia was mild, his trunk ataxia was so pronounced that he was unable to walk without support. We strongly suspected paraneoplastic syndrome and tested for neuronal autoantibodies. The anti-Ma2 antibody was strongly positive in the blood and cerebrospinal fluid but other antineuronal autoantibodies were negative. Computed tomography showed an enlarged lymph node in the right axilla but no masses. Biopsy confirmed a diagnosis of NLPHL. The NLPHL cells stained with anti-Ma-2 antibody in the cytoplasm, suggesting these abnormal cells contained protein that was cross-reactive with Ma-2. CONCLUSIONS: To the best of our knowledge, this is the first case of anti-Ma2-associated PCD in a patient with NLPHL that was confirmed using immunostaining of the lymph node tissue with anti-Ma2 antibody. Our case confirms an association between anti-Ma2-associated PCD and NLPHL.

Modern principles in the management of nodular lymphocyte-predominant Hodgkin lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a unique rare subtype of Hodgkin lymphoma (HL) which differs clinically, pathologically and biologically from classic HL, warranting a nuanced approach to treatment. CD20 expression by malignant lymphocyte-predominant cells, a tendency for late relapses, and the risk of transformation to aggressive large B-cell lymphoma are characteristic features with important implications for treatment and follow-up. Recognition of histopathological variant patterns is also critical, with important implications for prognosis and treatment. The optimal management for NLPHL is unclear and opinions differ as to whether treatment paradigms should be similar to, or differ from, those for classic HL. Therapy differs for early versus advanced stage disease and for frontline versus relapsed or refractory disease. Potential treatment strategies include radiotherapy, combined modality therapy, chemotherapy, rituximab and watchful waiting. Given the excellent overall survival of NLPHL, treatment choices should be geared towards reducing long-term toxicity and optimizing survivorship. In this review, we provide an overview of the current literature and discuss modern principles in the management of NLPHL.

Diagnosis of Hodgkin lymphoma in the modern era.

The Hodgkin lymphomas are a family of unique lymphoma subtypes, in which the nature of the neoplastic cell was enigmatic for many years. Much of the mystery has been solved, with all forms now considered to be of B-cell origin, in most cases of germinal centre derivation. Today we recognize Hodgkin lymphoma as an eponym that encompasses multiple entities. One of the unifying themes is the major contribution from the tumour microenvironment. Both the character of the neoplastic cells and the nature of the immune environment are critical to accurate diagnosis. Moreover, an understanding of the molecular alterations that characterize both the neoplastic cells and their microenvironment have led to therapeutic advances, targeting both neoplastic and reactive components. Other conditions may foster a similar inflammatory milieu and lead to lymphoproliferations that mimic the Hodgkin lymphomas. In this review we provide an update on the diagnostic features of the various subtypes and include additional information relevant for prognostic evaluation and investigation of potential therapeutic targets. Additionally, we also discuss those conditions that often cause confusion in diagnosis and need to be distinguished from the Hodgkin lymphomas.

American Registry of Pathology Expert Opinions: Immunohistochemical evaluation of classic Hodgkin lymphoma.

The diagnosis of classic Hodgkin lymphoma requires immunohistochemical confirmation in most cases and one can argue for these studies as standard-of-care in the diagnostic workup. The authors propose a panel of studies for primary identification of CHL to include: CD3, CD20, CD15, CD30 and PAX5. When pattern discordances are identified, additional assessment is recommended. In the case of overexpression of B lineage markers by Hodgkin/Reed-Sternberg cells, or a differential diagnosis that includes large B-cell lymphoma or variants, additional markers recommended are: CD45, OCT2, BOB1, CD79a and MUM1/IRF4. If primary mediastinal large B cell lymphoma is considered in the differential diagnosis, suggested additional markers include: P63, CD23, CD45 and CD79a. When considering a differential diagnosis that includes anaplastic large cell lymphoma we suggest: ALK, CD45, pan T cell antigens (such as CD2, CD5, CD7, and CD43), and cytotoxic markers (granzyme, perforin, and TIA1). If peripheral T cell lymphoma or T cell lymphomas of follicular helper origin are considered in the differential diagnosis, the following panel is recommended: pan T cell antigens, CD4, CD8, one or more follicular dendritic cell markers, and assessment for Epstein-Barr virus (EBV) infection, preferably EBV encoded RNA (EBER) as assessed by in situ hybridization When the differential diagnosis includes nodular lymphocyte predominant Hodgkin lymphoma, recommended additional studies include OCT2, CD21 and/or CD23, PD1, and assessment for EBV infection. The authors recognize that these panels may not be adequate to completely characterize other lymphomas, but these panels will usually be sufficient to distinguish classic Hodgkin lymphoma from other lymphoma types.

Nodular lymphocyte predominant Hodgkin's lymphoma in daily practice: A multicenter experience.

Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of Hodgkin's lymphoma. In this study, we aimed to investigate the clinical features and therapeutic outcomes of patients with NLPHL who were diagnosed at different institutes in Turkey. We retrospectively reviewed the records of the patients diagnosed with NLPHL. Adult patients who were diagnosed after 2005 with histological confirmation were selected for the study. Forty-three patients were included in the study. Median age of patients was 37.5 years (18-70) at the time of diagnosis. About 60.5% patients were diagnosed as stage I and II NLPHL, and remaining 39.5% had stage III and IV disease. Median follow-up was 46 months. During follow-up, none of the patients died. Seven patients relapsed or progressed after initial therapy at a median of 12 months. Five of 7 relapsed/refractory patients (71.4%) were salvaged with chemotherapy only (DHAP, ICE), and the remaining 2 (28.6%) were salvaged with chemoimmunotherapy. All of relapsed/refractory patients were able to achieve complete remission after salvage therapy. Lactate dehydrogenase levels were significantly higher in patients with progressive disease compared with nonprogressive disease. Our study showed an excellent outcome with all patients alive at last contact with a median follow up of 46 months despite a wide range of different therapeutic approaches. All relapsed and refractory patients were successfully salvaged despite a low frequency of patients received immunotherapy in conjunction with chemotherapy. Our results suggest that immunotherapy may be reserved for further relapses.

Long-term follow-up of 2 patients treated with 90 Y-rituximab radioimmunotherapy for relapse of nodular lymphocyte-predominant Hodgkin lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma (<5% of Hodgkin's lymphomas) predominantly affecting the middle-aged man, with an indolent behavior. Given the rare occurrence of this lymphoma, there are currently no clear guidelines for initial treatment or relapse. In this report, we present the follow-up of 2 patients treated by radioimmunotherapy for first relapse of their NLPHL. Both patients were initially treated with rituximab and relapsed 1 year after the end of their treatment.

Advanced stage nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents: clinical characteristics and treatment outcome - a report from the SFCE & CCLG groups.

Advanced stage nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is extremely rare in children and as a consequence, optimal treatment for this group of patients has not been established. Here we retrospectively evaluated the treatments and treatment outcomes of 41 of our patients from the UK and France with advanced stage nLPHL. Most patients received chemotherapy, some with the addition of the anti CD20 antibody rituximab or radiotherapy. Chemotherapy regimens were diverse and followed either classical Hodgkin lymphoma or B non-Hodgkin lymphoma protocols. All 41 patients achieved a complete remission with first line treatment and 40 patients are alive and well in remission. Eight patients subsequently relapsed and 1 patient died of secondary cancer (9 progression-free survival events). The median time to progression for those who progressed was 21 months (5·9-73·8). The median time since last diagnosis is 87·3 months (8·44-179·20). Thirty-six (90%), 30 (75%) and 27 (68%) patients have been in remission for more than 12, 24 and 36 months, respectively. Overall, the use of rituximab combined with multi-agent chemotherapy as first line treatment seems to be a reasonable therapeutic option.

Nodular lymphocyte predominant Hodgkin lymphoma in Sweden between 2000 and 2014: an analysis of the Swedish Lymphoma Registry.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent CD20+ lymphoma. Its scarcity has made clinical trials difficult and there is no consensus on first-line treatment. We conducted a population-based study of all patients diagnosed with NLPHL in Sweden between 2000 and 2014 (N = 158; 41 women and 117 men), focusing on clinical features, therapy and overall survival. The median female and male age was 59 and 44 years, respectively (P = 0·002). In early-stage disease, there was little mortality and no survival differences between therapies. In patients with advanced-stage disease, mortality was relatively high in patients who did not receive first-line rituximab but absent in those who did (10-year survival, 55% vs. 100%; P = 0·033); there were no imbalances of prognostic factors between those two groups. In advanced stages, first-line rituximab use increased markedly between 2000-2004 and 2005-2014 (7% vs. 67%; P < 0·00005), as did 10-year survival, 53% vs. 72% (multivariate P = 0·027). Although all patients were diagnosed in the 2000s, this is the longest-followed (and largest) population-based cohort. We report a hitherto unreported 15-year median age difference between sexes, increasing rituximab use and improved survival.

Cyclin D1 expression and polysomy in lymphocyte-predominant cells of nodular lymphocyte-predominant Hodgkin lymphoma.

Cyclin D1 protein expression in lymphocytes is classically associated with mantle cell lymphoma. Although increasingly recognized in other lymphoproliferative disorders, cyclin D1 expression and CCND1 gene abnormalities have not been well studied in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Using a double stain for CD20/cyclin D1, we quantified cyclin D1 expression in 10 cases of NLPHL and correlated those findings with SOX11 expression, CCND1 gene abnormalities, and clinical data. For comparison, we examined 5 cases of T cell-/histiocyte-rich large B-cell lymphoma (THRLBCL). All cases of NLPHL stained for cyclin D1 showed at least rare positivity in lymphocyte-predominant (LP) cells. In 4 cases, at least 20% of LP cells were positive for CD20/cyclin D1. Neither SOX11 expression nor CCND1 gene rearrangement was found in any of the cases, but fluorescence in situ hybridization showed a proportion of the large cells with 3 to 4 copies of nonfused IGH and CCND1 signals or 3 intact CCND1 break-apart signals. Further study with CCND1/CEP11 showed polysomy in 6 of 9 cases with cyclin D1 expression and 5 of 16 NLPHL not examined for cyclin D1. Two of 5 cases of THRLBCL showed rare positive staining for CD20/cyclin D1; 1 case showed polysomy with CCND1/CEP11. Results show that cyclin D1 may be expressed in LP cells without SOX11 expression or CCND1 translocation. Polysomy with increased copies of CCND1 may account for cyclin D1 expression in some cases. Cyclin D1 expression is not useful for distinguishing NLPHL from THRLBCL and has no apparent clinical significance in NLPHL.

A 20-year population-based study on the epidemiology, clinical features, treatment, and outcome of nodular lymphocyte predominant Hodgkin lymphoma.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma characterized by a unique clinical and histological presentation. Because of the rare nature of this disease, few large-scale studies are available. We conducted a cohort study in which patients were identified in the Netherlands Cancer Registry in the Southeast of the Netherlands between 1990 and 2010. Of these patients, we collected all clinical characteristics and re-reviewed pathologic material to confirm NLPHL diagnosis. Seventy-three histologically confirmed cases of NLPHL were analyzed with a median follow-up of 65 months (range 4-257 months). Median age at diagnosis was 43 years (range 1-87); 84.9 % of the patients were male; B symptoms were present in 5.5 %; and stage I/II disease was most common (75.4 %). Patients were primarily treated with radiotherapy (50.7 %), chemotherapy (26 %), combined modality (radiotherapy and chemotherapy) (11 %), or surgical excision with careful watch-and-wait (12.3 %). Relapses occurred in seven patients (9.6 %) after a median of 26 months (21-74 months). Six patients (8.2 %) developed histologic transformation to large cell lymphoma. Five patients (6.8 %) died during follow-up due to progression of NLPHL (n = 1), histologic transformation (n = 2) and intercurrent deaths (n = 2). The estimated 10-year overall survival was 94.0 % and the 10-year progression-free survival 75.8 %. Our study confirms the distinct characteristics of NLPHL with a relatively good long-term prognosis. It may be possible to reduce treatment intensity in early stage NLPHL without affecting long-term outcome.