{"entity":{"id":"nodular-lymphocyte-predominant-hodgkin-lymphoma","kind":"cancer","name":"Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma)","aka":["NLPHL","NLPBL","Nodular lymphocyte-predominant B-cell lymphoma","Lymphocyte-predominant Hodgkin disease","Popcorn cell lymphoma"],"tldr":"Nodular lymphocyte-predominant Hodgkin lymphoma is the rare, slow-growing cousin of classical Hodgkin lymphoma, so different in its CD20-bearing cells that the WHO renamed it a B-cell lymphoma in 2022. Early disease is usually cured with radiotherapy alone or surgery in children, advanced disease with rituximab-based chemotherapy, and patients are followed for life because it can return late.","summary":"Nodular lymphocyte-predominant Hodgkin lymphoma was separated from classical Hodgkin lymphoma in 1994 because its tumour cells, the 'popcorn' or LP cells, are CD20-positive, CD30- and CD15-negative B cells that keep their B-cell programme, sit in nodules of small B lymphocytes and follicular T-helper cells, and lack EBV; the 2022 WHO classification took the logic to its end and renamed the disease nodular lymphocyte-predominant B-cell lymphoma, while the International Consensus Classification kept the older name. It presents with a single group of peripheral nodes (neck, axilla or groin) in a young man, rarely in the mediastinum, and stays indolent for years; but a proportion of cases show T-cell-rich or diffuse growth patterns (Fan patterns C to F) that behave more aggressively and blur into T-cell/histiocyte-rich large B-cell lymphoma, into which the disease transforms in a minority over the following decades.\n\nTreatment is gentler than for classical disease. Stage IA disease without risk factors is cured in most patients by involved-site radiotherapy alone (30 Gy), and children with a completely excised single node can be watched without further treatment, as Children's Oncology Group and EuroNet studies showed. Stage II to IV disease is treated with chemotherapy, usually ABVD or, because the cells are CD20-positive, R-CHOP or R-CVP with rituximab, which some centres prefer for its lower risk of transformation; single-agent rituximab produces responses in most patients but they are not durable. Relapse is common but slow, and relapsed disease is treated with rituximab alone or with chemotherapy, radiotherapy or, rarely, autologous transplantation; transformation is treated as diffuse large B-cell lymphoma. Survival is excellent and most deaths in older series were from treatment or second cancers, which is the reason to treat as little as possible. Because the disease is rare and heterogeneous, trials are small, and the current questions are whether rituximab-based regimens should replace ABVD in advanced disease and how to identify the variant patterns that need more.","asOf":"2026-09-18","wikipedia":"https://en.wikipedia.org/wiki/Nodular_lymphocyte_predominant_Hodgkin_lymphoma","links":[{"label":"NCCN Hodgkin Lymphoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1439"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Nodular_lymphocyte_predominant_Hodgkin_lymphoma"}],"tags":["subtype-page","haematologic"],"related":["early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","hodgkin-lymphoma","follicular-lymphoma"],"cancers":[],"sections":[],"technologies":["imrt-igrt","fdg-pet","histopathology-ihc","autologous-stem-cell-transplant","active-surveillance"],"targets":[],"drugs":["rituximab","doxorubicin","vinblastine","dacarbazine","cyclophosphamide","vincristine","bendamustine"],"companies":[],"institutions":[],"pathways":[],"terms":["r-chop","abvd-beacopp","lymphoma-type","lugano-classification","lymphoma-tx-radiotherapy","lymphoma-tx-hodgkin-late-effects","lymphoma-tx-watch-and-wait","lymphoma-tx-regimen-alphabet"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-who-2022-lymphoid-alaggio-leukemia-2022","paper-eichenauer-nlphl-ghsg-hd7-hd15-long-term-jco-2020"],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"About one in twenty Hodgkin lymphomas, mostly in men in their thirties and forties and in boys; it is indolent, rarely fatal, but relapses over decades and can transform into an aggressive B-cell lymphoma.","subtypes":["Stage IA nodular lymphocyte-predominant Hodgkin lymphoma (radiotherapy alone or excision and observation in children)","Stage II to IV nodular lymphocyte-predominant Hodgkin lymphoma (ABVD or R-CHOP)","Typical nodular growth pattern (Fan patterns A and B; indolent)","Variant growth patterns (Fan patterns C to F; T-cell-rich or diffuse, more aggressive)","Relapsed nodular lymphocyte-predominant Hodgkin lymphoma (rituximab-based)","Transformation to T-cell/histiocyte-rich large B-cell lymphoma"],"biomarkers":["CD20-positive, CD30- and CD15-negative LP cells with OCT2 and PAX5 expression","Fan growth pattern (A to F) on the biopsy","Absence of EBV","Stage and number of nodal sites","Lactate dehydrogenase and B symptoms (transformation suspicion)","FDG-PET (staging; avid)"],"standardOfCare":[{"setting":"Diagnosis","approach":"Excisional node biopsy with expert haematopathology review to distinguish from classical Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma; FDG-PET/CT staging.","refs":["histopathology-ihc","fdg-pet","lugano-classification","lymphoma-type"],"guideline":{"version":"NCCN Guidelines: Hodgkin Lymphoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1439"}},{"setting":"Stage IA without risk factors","approach":"Involved-site radiotherapy alone (30 Gy); in children, complete excision followed by observation.","refs":["imrt-igrt","active-surveillance","childrens-oncology-group"],"guideline":{"version":"NCCN Guidelines: Hodgkin Lymphoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1439"}},{"setting":"Stage IB to IV","approach":"ABVD or rituximab-containing chemotherapy (R-CHOP, R-CVP, R-ABVD) with or without involved-site radiotherapy; rituximab alone for frail patients.","refs":["rituximab","r-chop","abvd-beacopp","doxorubicin","cyclophosphamide","vincristine","imrt-igrt"],"guideline":{"version":"NCCN Guidelines: Hodgkin Lymphoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1439"}},{"setting":"Relapse","approach":"Rebiopsy to exclude transformation; rituximab alone or with chemotherapy, radiotherapy for localised relapse; autologous transplantation only for early or repeated relapse.","refs":["rituximab","autologous-stem-cell-transplant","imrt-igrt"],"guideline":{"version":"NCCN Guidelines: Hodgkin Lymphoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1439"}},{"setting":"Transformation","approach":"Treat as diffuse large B-cell lymphoma with R-CHOP.","refs":["r-chop","rituximab"],"guideline":{"version":"NCCN Guidelines: Hodgkin Lymphoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1439"}},{"setting":"Nodular lymphocyte-predominant Hodgkin lymphoma: a different disease that keeps the name","approach":"The malignant cell expresses CD20 and not CD30 or CD15, which is the opposite of classical Hodgkin lymphoma and the reason rituximab works and brentuximab vedotin does not. The WHO fifth edition renames it nodular lymphocyte-predominant B-cell lymphoma, which is a better description. It is indolent, affects men more than women, and relapses late.\n\nStage IA disease without risk factors is treated with involved-site radiotherapy alone, typically 30 Gy, and a substantial proportion never relapse. Complete surgical excision of a single node followed by observation is used in children and in selected adults.\n\nMore advanced disease is treated with rituximab-containing systemic treatment: R-CHOP, R-ABVD or bendamustine with rituximab, with or without radiotherapy to a residual site. A retrospective population series of 23 patients treated with bendamustine and rituximab in Alberta reported a response rate of 100 per cent, complete response in 78 per cent, and four-year progression-free survival of 83 per cent and overall survival of 87 per cent, which is the kind of evidence this uncommon disease has.\n\nThe long-term data make the central point about how gently it should be treated. Across 471 patients in the German Hodgkin Study Group HD7 to HD15 trials, ten-year progression-free survival was 75.5 per cent and overall survival 92.1 per cent, but second malignancies occurred in 10.2 per cent, and of 43 deaths only 10 were from the lymphoma against 20 from second cancers and 13 from possibly treatment-related conditions. Over-treatment, not the lymphoma, is the main threat to life here.\n\nTransformation to a T-cell/histiocyte-rich large B-cell lymphoma occurs in a minority and is treated as aggressive lymphoma.","refs":["paper-eichenauer-nlphl-ghsg-hd7-hd15-long-term-jco-2020","rituximab","bendamustine","r-chop","doxorubicin","cyclophosphamide","vincristine","prednisone","imrt-igrt","lymphoma-tx-radiotherapy","lymphoma-tx-watch-and-wait","lymphoma-tx-hodgkin-late-effects","secondary-malignancy"],"guideline":{"version":"NCCN Hodgkin Lymphoma; ESMO; GHSG HD7 to HD15 long-term follow-up","url":"https://doi.org/10.1111/ejh.14443"}}],"stateOfArt":["Radiotherapy alone or excision cures most early-stage patients with minimal toxicity.","Rituximab, useless in classical Hodgkin lymphoma, is active here because the cells are CD20-positive.","The 2022 renaming reflects a disease now understood as an indolent B-cell lymphoma."],"history":[{"year":1944,"title":"Jackson and Parker describe the paragranuloma form of Hodgkin disease","refs":[]},{"year":1966,"title":"Lukes and Butler define lymphocyte-predominant Hodgkin disease","refs":[]},{"year":1994,"title":"REAL classification separates nodular lymphocyte-predominant from classical Hodgkin lymphoma","refs":["lymphoma-type"]},{"year":2003,"title":"Fan describes the six growth patterns that predict behaviour","refs":[]},{"year":2017,"title":"Children's Oncology Group shows excision alone is enough for completely resected stage IA disease in children","refs":["childrens-oncology-group"]},{"year":2022,"title":"WHO renames the disease nodular lymphocyte-predominant B-cell lymphoma","refs":["lymphoma-type"]}],"pipeline":["rituximab"],"openProblems":["No randomised trial has compared ABVD with rituximab-based chemotherapy.","Variant growth patterns are hard to reproduce between pathologists.","Late relapse and transformation over decades make lifelong follow-up necessary.","The rarity of the disease limits every study to retrospective series."],"parent":"hodgkin-lymphoma"},"route":"/cancers/nodular-lymphocyte-predominant-hodgkin-lymphoma/","neighbours":{"cancer":[{"id":"advanced-stage-classical-hodgkin-lymphoma","kind":"cancer","name":"Advanced-stage classical Hodgkin lymphoma (stage III to IV)","route":"/cancers/advanced-stage-classical-hodgkin-lymphoma/"},{"id":"early-stage-classical-hodgkin-lymphoma","kind":"cancer","name":"Early-stage classical Hodgkin lymphoma (stage I to II)","route":"/cancers/early-stage-classical-hodgkin-lymphoma/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"t-cell-histiocyte-rich-large-b-cell-lymphoma","kind":"cancer","name":"T-cell/histiocyte-rich large B-cell lymphoma","route":"/cancers/t-cell-histiocyte-rich-large-b-cell-lymphoma/"}],"technology":[{"id":"active-surveillance","kind":"technology","name":"Active surveillance","route":"/technologies/active-surveillance/"},{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"palliative-care","kind":"technology","name":"Early integrated palliative care","route":"/technologies/palliative-care/"},{"id":"exercise-during-chemotherapy","kind":"technology","name":"Exercise during chemotherapy and radiotherapy","route":"/technologies/exercise-during-chemotherapy/"},{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"multidisciplinary-tumour-board","kind":"technology","name":"Multidisciplinary tumour boards","route":"/technologies/multidisciplinary-tumour-board/"},{"id":"fertility-preservation","kind":"technology","name":"Oncofertility and fertility preservation","route":"/technologies/fertility-preservation/"},{"id":"peer-support-groups","kind":"technology","name":"Peer support and support groups","route":"/technologies/peer-support-groups/"},{"id":"prehabilitation","kind":"technology","name":"Prehabilitation before cancer surgery","route":"/technologies/prehabilitation/"},{"id":"psycho-oncology","kind":"technology","name":"Psycho-oncology and distress screening","route":"/technologies/psycho-oncology/"},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/"}],"drug":[{"id":"bendamustine","kind":"drug","name":"Bendamustine","route":"/drugs/bendamustine/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"dacarbazine","kind":"drug","name":"Dacarbazine","route":"/drugs/dacarbazine/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"vinblastine","kind":"drug","name":"Vinblastine","route":"/drugs/vinblastine/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"term":[{"id":"abvd-beacopp","kind":"term","name":"ABVD, BEACOPP and BrECADD (Hodgkin lymphoma regimens)","route":"/terms/abvd-beacopp/"},{"id":"lymphoma-living-hodgkin-survivorship-screening","kind":"term","name":"After Hodgkin lymphoma: the late effects, and the screening that follows them","route":"/terms/lymphoma-living-hodgkin-survivorship-screening/"},{"id":"cancer-related-fatigue","kind":"term","name":"Cancer-related fatigue (tiredness)","route":"/terms/cancer-related-fatigue/"},{"id":"central-venous-access","kind":"term","name":"Central venous access (port, PICC line)","route":"/terms/central-venous-access/"},{"id":"febrile-neutropenia","kind":"term","name":"Febrile neutropenia","route":"/terms/febrile-neutropenia/"},{"id":"financial-toxicity","kind":"term","name":"Financial toxicity","route":"/terms/financial-toxicity/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"},{"id":"lymphoma-tx-hodgkin-late-effects","kind":"term","name":"Late effects of Hodgkin lymphoma treatment, and the follow-up that answers them","route":"/terms/lymphoma-tx-hodgkin-late-effects/"},{"id":"lugano-classification","kind":"term","name":"Lugano classification / Ann Arbor staging","route":"/terms/lugano-classification/"},{"id":"lymphoma-type","kind":"term","name":"Lymphoma (tissue type)","route":"/terms/lymphoma-type/"},{"id":"neutropenia","kind":"term","name":"Neutropenia","route":"/terms/neutropenia/"},{"id":"r-chop","kind":"term","name":"R-CHOP (lymphoma chemoimmunotherapy)","route":"/terms/r-chop/"},{"id":"lymphoma-tx-radiotherapy","kind":"term","name":"Radiotherapy in lymphoma: involved-site fields, 24 Gy, 4 Gy and total skin electron therapy","route":"/terms/lymphoma-tx-radiotherapy/"},{"id":"secondary-malignancy","kind":"term","name":"Secondary malignancy (therapy-related cancer)","route":"/terms/secondary-malignancy/"},{"id":"lymphoma-tx-regimen-alphabet","kind":"term","name":"The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest","route":"/terms/lymphoma-tx-regimen-alphabet/"},{"id":"lymphoma-decision-watch-and-wait","kind":"term","name":"Watch and wait in follicular lymphoma: being told you have cancer and that nobody will treat it","route":"/terms/lymphoma-decision-watch-and-wait/"},{"id":"lymphoma-tx-watch-and-wait","kind":"term","name":"Watch and wait in lymphoma: when the right treatment is none yet","route":"/terms/lymphoma-tx-watch-and-wait/"},{"id":"watchful-waiting","kind":"term","name":"Watchful waiting, and how it differs from active surveillance","route":"/terms/watchful-waiting/"}],"paper":[{"id":"paper-eichenauer-nlphl-ghsg-hd7-hd15-long-term-jco-2020","kind":"paper","name":"Long-term follow-up of nodular lymphocyte-predominant Hodgkin lymphoma treated in the GHSG HD7 to HD15 trials","route":"/key-papers/paper-eichenauer-nlphl-ghsg-hd7-hd15-long-term-jco-2020/"},{"id":"paper-who-2022-lymphoid-alaggio-leukemia-2022","kind":"paper","name":"WHO classification of haematolymphoid tumours, fifth edition: lymphoid neoplasms","route":"/key-papers/paper-who-2022-lymphoid-alaggio-leukemia-2022/"}],"company":[{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"}]}}