Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children70310.24287/1726-1708-2023-22-1-156-164CLINICAL OBSERVATIONSКЛИНИЧЕСКИЕ НАБЛЮДЕНИЯProgressive transformation of germinal centers or nodular lymphocyte-predominant Hodgkin lymphoma? Issues of differential diagnosis: a clinical caseПрогрессивная трансформация герминативных центров или нодулярная лимфома Ходжкина с лимфоцитарным преобладанием? Вопросы дифференциальной диагностики на примере клинического случаяhttps://orcid.org/0000-0002-9921-5620SenchenkoM. A.СенченкоМ. А.
Russian Federation

Maria A. Senchenko, a postgraduate student, a junior researcher at the Department of Pathology

1 Samory Mashela St., Moscow 117997, Russia 

Сенченко Мария Анатольевна, аспирант, младший научный сотрудник отделения патологической анатомии

117997, Москва, ул. Саморы Машела, 1

mariya.senchenko@fccho-moscow.ruhttps://orcid.org/0000-0003-3664-2876AbramovD. S.АбрамовД. С.
Russian Federation

Moscow

 Москва 

https://orcid.org/0000-0002-4779-1896MyakovaN. V.МяковаН. В.
Russian Federation

Moscow

 Москва 

https://orcid.org/0000-0001-7732-8184KonovalovD. M.КоноваловД. М.
Russian Federation

Moscow

 Москва 

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России010320232211561643101202301032023Copyright ©; 2023, «D. Rogachev NMRCPHOI»Copyright ©; 2023, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2023«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/703

Progressive transformation of germinal centers (PTGC) is a benign reactive lymphadenopathy, which can be an independent disease or occur in association with other lymphomas, the most common variant of which is nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). To date, it has not been definitively clarified how PTGC and NLPHL are interconnected, despite the abundance of works presented on this topic. PTGC may precede NLPHL, occur synchronously with it, or develop after a course of therapy in patients with NLPHL. Despite similar clinical and morphological features, the approach to the treatment and management of patients is different. In the case of NLPHL, one of the therapeutic options is chemotherapy, which is not used in patients with PTGC. This article presents a clinical case of partial lymph node lesion of NLPHL associated with PTGC, on the example of which the main issues of differential diagnosis of PTGC and NLHLP will be considered. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.

Прогрессивная трансформация герминативных центров (ПТГЦ) – доброкачественная реактивная лимфаденопатия, которая может быть самостоятельным заболеванием или возникать ассоциированно с другими лимфомами, самым частым вариантом из которых является нодулярная лимфома Ходжкина с лимфоцитарным преобладанием (НЛХЛП). На сегодняшний день окончательно не выяснено, как взаимосвязаны между собой ПТГЦ и НЛХЛП, несмотря на обилие представленных работ на эту тему. ПТГЦ может предшествовать НЛХЛП, возникать с ней синхронно или развиваться после проведенного курса терапии у пациентов с НЛХЛП. Несмотря на схожие клинико-морфологические признаки, подход к лечению и ведению пациентов отличается. В случае НЛХЛП одной из терапевтических опций является проведение химиотерапии, что не показано для пациентов с ПТГЦ. В настоящей статье представлен клинический случай парциального поражения лимфатического узла НЛХЛП, ассоциированной с ПТГЦ, на примере которого будут рассмотрены основные вопросы дифференциальной диагностики ПТГЦ и НЛХЛП. Пациент и его законные представители дали согласие на использование информации, в том числе фотографий ребенка, в научных исследованиях и публикациях.

progressive transformation of germinal centersnodular lymphocyte predominant Hodgkin lymphomalymphomaschildrenпрогрессивная трансформация герминативных центровнодулярная лимфома Ходжкина с лимфоцитарным преобладаниемлимфомыдети1. Hicks J., Flaitz C. Progressive transformation of germinal centers: Review of histopathologic and clinical features. Int J Pediatr Otorhinolaryngol 2002; 65 (3): 195–202. DOI: 10.1016/S0165-5876(02)00176-3Hicks J., Flaitz C. Progressive transformation of germinal centers: Review of histopathologic and clinical features. Int J Pediatr Otorhinolaryngol 2002; 65 (3): 195–202. DOI: 10.1016/S0165-5876(02)00176-32. Özkan M.C., Özsan N., Hekimgil M., Saydam G., Töbü M. Progressive Transformation of Germinal Centers: Single-Center Experience of 33 Turkish Patients. Clin Lymphoma Myeloma Leuk 2016; 16: S149–51. DOI: 10.1016/j.clml.2016.03.010Özkan M.C., Özsan N., Hekimgil M., Saydam G., Töbü M. Progressive Transformation of Germinal Centers: Single-Center Experience of 33 Turkish Patients. Clin Lymphoma Myeloma Leuk 2016; 16: S149–51. DOI: 10.1016/j.clml.2016.03.0103. Kojima M., Nakamura S., Motoori T., Itoh H., Shimizu K., Yamane N., et al. Progressive transformation of germinal centers: A clinicopathological study of 42 Japanese patients. Int J Surg Pathol 2003; 11 (2): 101–7. DOI: 10.1177/106689690301100205Kojima M., Nakamura S., Motoori T., Itoh H., Shimizu K., Yamane N., et al. Progressive transformation of germinal centers: A clinicopathological study of 42 Japanese patients. Int J Surg Pathol 2003; 11 (2): 101–7. DOI: 10.1177/1066896903011002054. Furqan Shaikh R.G., Ngan B.-Y., Alexander S. Progressive transformation of germinal centers in children and adolescents: an intriguing cause of lymphadenopathy. Pediatr Blood Cancer 2013; 60 (1): 26–30. DOI: 10.1002/pbc.24234Furqan Shaikh R.G., Ngan B.-Y., Alexander S. Progressive transformation of germinal centers in children and adolescents: an intriguing cause of lymphadenopathy. Pediatr Blood Cancer 2013; 60 (1): 26–30. DOI: 10.1002/pbc.242345. Hansmann M.L., Fellbaum C., Hui P.K., Moubayed P. Progressive transformation of germinal centers with and without association to Hodgkin’s disease. Am J Clin Pathol 1990; 93 (2): 219–26. DOI: 10.1093/ajcp/93.2.219Hansmann M.L., Fellbaum C., Hui P.K., Moubayed P. Progressive transformation of germinal centers with and without association to Hodgkin’s disease. Am J Clin Pathol 1990; 93 (2): 219–26. DOI: 10.1093/ajcp/93.2.2196. Hartmann S., Winkelmann R., Metcalf R.A., Treetipsatit J., Warnke R.A., Natkunam Y., et al. Immunoarchitectural patterns of progressive transformation of germinal centers with and without nodular lymphocyte-predominant Hodgkin lymphoma. Hum Pathol 2015; 46 (11): 1655–61. DOI: 10.1016/j.humpath.2015.07.006Hartmann S., Winkelmann R., Metcalf R.A., Treetipsatit J., Warnke R.A., Natkunam Y., et al. Immunoarchitectural patterns of progressive transformation of germinal centers with and without nodular lymphocyte-predominant Hodgkin lymphoma. Hum Pathol 2015; 46 (11): 1655–61. DOI: 10.1016/j.humpath.2015.07.0067. Lim M.S., Straus S.E., Dale J.K., Fleisher T.A., Stetler-Stevenson M., Strober W., et al. Pathological findings in human autoimmune lymphoproliferative syndrome. Am J Pathol 1998; 153 (5): 1541–50. DOI: 10.1016/S0002-9440(10)65742-2Lim M.S., Straus S.E., Dale J.K., Fleisher T.A., Stetler-Stevenson M., Strober W., et al. Pathological findings in human autoimmune lymphoproliferative syndrome. Am J Pathol 1998; 153 (5): 1541–50. DOI: 10.1016/S0002-9440(10)65742-28. Sato Y., Inoue D., Asano N., Takata K., Asaoku H., Maeda Y., et al. Association between IgG4-related disease and progressively transformed germinal centers of lymph nodes. Mod Pathol 2012; 25 (7): 956–67. DOI: 10.1038/modpathol.2012.54Sato Y., Inoue D., Asano N., Takata K., Asaoku H., Maeda Y., et al. Association between IgG4-related disease and progressively transformed germinal centers of lymph nodes. Mod Pathol 2012; 25 (7): 956–67. DOI: 10.1038/modpathol.2012.549. Nguyen N.L., Ferry J.A., Harris N.L. Progressive Transformation of Germinal Centers and Nodular Lymphocyte Predominance Hodgkin’s Disease. Am J Surg Pathol 1999; 23 (1): 27–33.Nguyen N.L., Ferry J.A., Harris N.L. Progressive Transformation of Germinal Centers and Nodular Lymphocyte Predominance Hodgkin’s Disease. Am J Surg Pathol 1999; 23 (1): 27–33.10. Good D.J., Gascoyne R.D. Atypical Lymphoid Hyperplasia Mimicking Lymphoma. Hematol Oncol Clin North Am 2009; 23 (4): 729–45. DOI: 10.1016/j.hoc.2009.04.005Good D.J., Gascoyne R.D. Atypical Lymphoid Hyperplasia Mimicking Lymphoma. Hematol Oncol Clin North Am 2009; 23 (4): 729–45. DOI: 10.1016/j.hoc.2009.04.00511. Nam-Cha S.H., Roncador G., SanchezVerde L., Montes-Moreno S., Acevedo A., Domínguez-Franjo P., et al. PD-1, A follicular T-cell marker useful for recognizing nodular lymphocyte-predominant Hodgkin lymphoma. Am J Surg Pathol 2008; 32 (8): 1252–7. DOI: 10.1097/PAS.0b013e318165b0d6Nam-Cha S.H., Roncador G., SanchezVerde L., Montes-Moreno S., Acevedo A., Domínguez-Franjo P., et al. PD-1, A follicular T-cell marker useful for recognizing nodular lymphocyte-predominant Hodgkin lymphoma. Am J Surg Pathol 2008; 32 (8): 1252–7. DOI: 10.1097/PAS.0b013e318165b0d612. Braeuninger A., Küppers R., Strickler J.G., Wacker H.H., Rajewsky K., Hansmann M.L. Hodgkin and Reed-Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells. Proc Natl Acad Sci U S A 1997; 94 (17): 9337–42. DOI: 10.1073/pnas.94.17.9337Braeuninger A., Küppers R., Strickler J.G., Wacker H.H., Rajewsky K., Hansmann M.L. Hodgkin and Reed-Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells. Proc Natl Acad Sci U S A 1997; 94 (17): 9337–42. DOI: 10.1073/pnas.94.17.933713. Mason D.Y., Banks P.M., Chan J., Cleary M.L., Delsol G., de Wolf Peeters C., et al. Nodular lymphocyte predominance Hodgkin’s disease. A distinct clinicopathological entity. Am J Surg Pathol 1994; 18 (5): 526–30. DOI: 10.1097/00000478-199405000-00014Mason D.Y., Banks P.M., Chan J., Cleary M.L., Delsol G., de Wolf Peeters C., et al. Nodular lymphocyte predominance Hodgkin’s disease. A distinct clinicopathological entity. Am J Surg Pathol 1994; 18 (5): 526–30. DOI: 10.1097/00000478-199405000-0001414. Uherova P., Valdez R., Ross C.W., Schnitzer B., Finn W.G. Nodular lymphocyte predominant Hodgkin lymphoma: An immunophenotypic reappraisal based on a single-institution experience. Am J Clin Pathol 2003; 119 (2): 192–8. DOI: 10.1309/38RK238FCDCH5R22Uherova P., Valdez R., Ross C.W., Schnitzer B., Finn W.G. Nodular lymphocyte predominant Hodgkin lymphoma: An immunophenotypic reappraisal based on a single-institution experience. Am J Clin Pathol 2003; 119 (2): 192–8. DOI: 10.1309/38RK238FCDCH5R2215. Falini B., Bigerna B., Pasqualucci L., Fizzotti M., Martelli M.F., Pileri S., et al. Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin’s disease. Blood 1996; 87 (2): 465–71. DOI: 10.1182/blood.v87.2.465.bloodjournal872465Falini B., Bigerna B., Pasqualucci L., Fizzotti M., Martelli M.F., Pileri S., et al. Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin’s disease. Blood 1996; 87 (2): 465–71. DOI: 10.1182/blood.v87.2.465.bloodjournal87246516. Anagnostopoulos I., Hansmann M.L., Franssila K., Harris M., Harris N.L., Jaffe E.S., et al. European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: Histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes. Blood 2000; 96 (5): 1889–99. DOI: 10.1182/blood.V96.5.1889Anagnostopoulos I., Hansmann M.L., Franssila K., Harris M., Harris N.L., Jaffe E.S., et al. European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: Histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes. Blood 2000; 96 (5): 1889–99. DOI: 10.1182/blood.V96.5.188917. Kiil K., Bein J., Schuhmacher B., Thurner L., Schneider M., Hansmann M.-L., et al. A high number of IgG4-positive plasma cells rules out nodular lymphocyte predominant Hodgkin lymphoma. Virchows Arch 2018; 473 (6): 759–64. DOI: 10.1007/s00428-018-2460-8Kiil K., Bein J., Schuhmacher B., Thurner L., Schneider M., Hansmann M.-L., et al. A high number of IgG4-positive plasma cells rules out nodular lymphocyte predominant Hodgkin lymphoma. Virchows Arch 2018; 473 (6): 759–64. DOI: 10.1007/s00428-018-2460-818. Aguilera D.G., Vaklavas C., Tsimberidou A.M., Wen S., Medeiros L.J., Corey S.J. Pediatric therapy-related myelodysplastic syndrome/acute myeloid leukemia: the MD Anderson Cancer Center experience. J Pediatr Hematol Oncol 2009; 31 (11): 803–11. DOI: 10.1097/MPH.0b013e-3181ba43dcAguilera D.G., Vaklavas C., Tsimberidou A.M., Wen S., Medeiros L.J., Corey S.J. Pediatric therapy-related myelodysplastic syndrome/acute myeloid leukemia: the MD Anderson Cancer Center experience. J Pediatr Hematol Oncol 2009; 31 (11): 803–11. DOI: 10.1097/MPH.0b013e-3181ba43dc19. Josting A., Wiedenmann S., Franklin J., May M., Sieber M., Wolf J., et al. Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin’s disease: A report from the German Hodgkin’s Lymphoma Study Group. J Clin Oncol 2003; 21 (18): 3440–6. DOI: 10.1200/JCO.2003.07.160Josting A., Wiedenmann S., Franklin J., May M., Sieber M., Wolf J., et al. Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin’s disease: A report from the German Hodgkin’s Lymphoma Study Group. J Clin Oncol 2003; 21 (18): 3440–6. DOI: 10.1200/JCO.2003.07.16020. Nogová L., Reineke T., Brillant C., Sieniawski M., Rüdiger T., Josting A., et al. Lymphocyte-predominant and classical Hodgkin’s lymphoma: A comprehensive analysis from the german Hodgkin study group. J Clin Oncol 2008; 26 (3): 434–9. DOI: 10.1200/JCO.2007.11.8869Nogová L., Reineke T., Brillant C., Sieniawski M., Rüdiger T., Josting A., et al. Lymphocyte-predominant and classical Hodgkin’s lymphoma: A comprehensive analysis from the german Hodgkin study group. J Clin Oncol 2008; 26 (3): 434–9. DOI: 10.1200/JCO.2007.11.886921. Mauz-Körholz C., Gorde-Grosjean S., Hasenclever D., Shankar А., Dörffel W., Hamish Wallace W., et al. Resection alone in 58 children with limited stage, lymphocyte-predominant Hodgkin lymphoma-experience from the European network group on pediatric Hodgkin lymphoma. Cancer 2007; 110 (1): 179–85. DOI: 10.1002/cncr.22762Mauz-Körholz C., Gorde-Grosjean S., Hasenclever D., Shankar А., Dörffel W., Hamish Wallace W., et al. Resection alone in 58 children with limited stage, lymphocyte-predominant Hodgkin lymphoma-experience from the European network group on pediatric Hodgkin lymphoma. Cancer 2007; 110 (1): 179–85. DOI: 10.1002/cncr.2276222. Mauz-Körholz C., Lange T., Hasenclever D., Burkhardt B., Feller A.C., Dörffel W., et al. Pediatric Nodular Lymphocyte-predominant Hodgkin Lymphoma: Treatment Recommendations of the GPOH-HD Study Group. Klin Padiatr 2015; 227 (6–7): 314–21. DOI: 10.1055/s-0035-1559664Mauz-Körholz C., Lange T., Hasenclever D., Burkhardt B., Feller A.C., Dörffel W., et al. Pediatric Nodular Lymphocyte-predominant Hodgkin Lymphoma: Treatment Recommendations of the GPOH-HD Study Group. Klin Padiatr 2015; 227 (6–7): 314–21. DOI: 10.1055/s-0035-155966423. Couronné L., Schneider P., Picquenot J.M., Laberge S., Bastard C., Vannier J.P. Refractory nodular lymphocyte predominant hodgkin lymphoma transformed to T-cell/histiocyte-rich B-cell lymphoma in an adolescent: Salvage therapy with allogeneic bone marrow transplantation. J Pediatr Hematol Oncol 2008; 30 (12): 959–62. DOI: 10.1097/MPH.0b013e31818a9564Couronné L., Schneider P., Picquenot J.M., Laberge S., Bastard C., Vannier J.P. Refractory nodular lymphocyte predominant hodgkin lymphoma transformed to T-cell/histiocyte-rich B-cell lymphoma in an adolescent: Salvage therapy with allogeneic bone marrow transplantation. J Pediatr Hematol Oncol 2008; 30 (12): 959–62. DOI: 10.1097/MPH.0b013e31818a956424. Biasoli I., Stamatoullas A., Meignin V., Delmer A., Reman O., Morschhauser F., et al. Nodular, lymphocyte-predominant Hodgkin lymphoma: A long-term study and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the adult lymphoma study group. Cancer 2010; 116 (3): 631–9. DOI: 10.1002/cncr.24819Biasoli I., Stamatoullas A., Meignin V., Delmer A., Reman O., Morschhauser F., et al. Nodular, lymphocyte-predominant Hodgkin lymphoma: A long-term study and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the adult lymphoma study group. Cancer 2010; 116 (3): 631–9. DOI: 10.1002/cncr.2481925. Hall G.W., Katzilakis N., Pinkerton C.R., Nicolin G., Ashley S., McCarthy K., et al. Outcome of children with nodular lymphocyte predominant Hodgkin lymphoma – A Children’s Cancer and Leukaemia Group report. Br J Haematol 2007; 138 (6): 761–8. DOI: 10.1111/j.1365-2141.2007.06736.xHall G.W., Katzilakis N., Pinkerton C.R., Nicolin G., Ashley S., McCarthy K., et al. Outcome of children with nodular lymphocyte predominant Hodgkin lymphoma – A Children’s Cancer and Leukaemia Group report. Br J Haematol 2007; 138 (6): 761–8. DOI: 10.1111/j.1365-2141.2007.06736.x26. Shankar A., Hall G.W., Gorde-Grosjean S., Hasenclever D., Leblanc T., Hayward J., et al. Treatment outcome after low intensity chemotherapy [CVP] in children and adolescents with early stage nodular lymphocyte predominant Hodgkin’s lymphoma - An Anglo-French collaborative report. Eur J Cancer 2012; 48 (11): 1700–6. DOI: 10.1016/j.ejca.2011.10.018Shankar A., Hall G.W., Gorde-Grosjean S., Hasenclever D., Leblanc T., Hayward J., et al. Treatment outcome after low intensity chemotherapy [CVP] in children and adolescents with early stage nodular lymphocyte predominant Hodgkin’s lymphoma - An Anglo-French collaborative report. Eur J Cancer 2012; 48 (11): 1700–6. DOI: 10.1016/j.ejca.2011.10.018