Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children70110.24287/1726-1708-2023-22-1-126-138CLINICAL OBSERVATIONSКЛИНИЧЕСКИЕ НАБЛЮДЕНИЯA case report of mast cell leukemia in a child and literature reviewЛейкоз из тучных клеток: демонстрация клинического случая лейкоза из тучных клеток у ребенка и обзор литературыhttps://orcid.org/0000-0002-2731-4531BoychenkoE. G.БойченкоЭ. Г.
Russian Federation

Elmira G. Boychenko, Dr. Med. Sci., Head of the Department of Oncohematology, Chief Pediatric Hematologist of Saint Petersburg Healthcare Committee

14A Avangardnaya St., 198205 Saint-Petersburg, Russia 

Бойченко Эльмира Госмановна, д-р мед. наук, заведующая отделением онкогематологии, главный внештатный детский специалист гематолог Комитета по здравоохранению Санкт-Петербурга

198205, Санкт-Петербург, ул. Авангардная, 14А 

boychenko-elmira@yandex.ruSaint Petersburg Children’s City Multidisciplinary Clinical Specialized Center of High Medical TechnologiesСПб ГБУЗ «Детский городской многопрофильный клинический специализированный центр высоких медицинских технологий»010320232211261382010202228022023Copyright ©; 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/701

Mast cell leukemia (MCL) is a very rare form of aggressive systemic mastocytosis accounting for < 1% of all mastocytosis. Mastocytosis is a broad term used for a group of clonal disorders characterized by accumulation of mast cells in the skin with or without extracutaneous involvement. The clinical spectrum of the disease varies from only cutaneous lesions to highly aggressive systemic involvement such as MCL. Mastocytosis can present from birth to adulthood. In children, mastocytosis is usually benign, and there is a good chance of spontaneous regression at puberty, unlike adult-onset disease, which is generally systemic and more severe. Individuals with systemic mastocytosis may be at risk of developing hematologic malignancies. MCL diagnosis requires the presence of SM criteria with additional features including leukemic infiltration of bone marrow and/or blood by at least 20% high-grade MC as well as the infiltration of extracutaneous organs by neoplastic MC. Genetic aberrations, mainly the KIT D816V mutation, play a crucial role in the pathogenesis of mastocytosis and are detected in most patients. To date, there is no approved standard therapy. For MCL, few options are available for treatment and because of the rarity of the disease very few clinical trials address the question. Even if SM occurs occasionally, all children with mastocytosis require planned follow-up over time. We present an overview of literature on MCL and a rare case of MCL diagnosed in a 4-year-old girl who had had cutaneous mastocytosis since early childhood. A bone marrow examination revealed MCL. She ultimately died despite chemotherapy. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Лейкоз из тучных клеток (ЛТК) представляет собой редкую и чрезвычайно агрессивную форму системного мастоцитоза и составляет менее 1% в структуре заболевания. Мастоцитоз – это гетерогенная группа расстройств широкого клинического диапазона от изолированного поражения кожи до крайне тяжелого системного процесса, каким является ЛТК. Мастоцитоз может возникать на протяжении жизни: от рождения до старости. У детей, как правило, мастоцитоз является доброкачественным заболеванием с высокой вероятностью спонтанной регрессии в периоде полового созревания в отличие от взрослых, у которых эта болезнь часто носит системный и более тяжелый характер. Пациенты с системным мастоцитозом имеют высокий риск трансформации в злокачественные заболевания гемопоэза. Диагноз ЛТК требует сочетания критериев системного мастоцитоза с инфильтрацией костного мозга и внекожных сайтов с атипичными тучными клетками. За последнее десятилетие наше понимание мастоцитоза существенно улучшилось в результате установления важной роли соматической мутации KIT, которая играет решающую роль в патогенезе заболевания, и аберрантного иммунофенотипа атипичных тучных клеток. Для лечения ЛТК у детей не существует стандартных рекомендаций, представлены некоторые терапевтические опции. Несмотря на редкость системного мастоцитоза в детском возрасте, все дети с кожным мастоцитозом нуждаются в тщательно спланированном наблюдении. Мы представляем обзор литературы и редкий случай ЛТК, который развился у 4-летней девочки, с раннего возраста страдавшей кожным мастоцитозом. Родители пациентки дали согласие на использование информации, в том числе фотографий ребенка, в научных исследованиях и публикациях.

pediatric mastocytosissystemic mastocytosismast cell leukemiaKIT mutationtryptasediagnosistreatmentдетский мастоцитозсистемный мастоцитозлейкоз из тучных клетокKITмутациятриптазадиагнозлечение1. Valent P., Akin C., Gleixner K.V., Sperr W.R., Reiter A., Arock M., et al. Multidisciplinary challenges in mastocytosis and how to address with personalized medicine approaches. Int J Mol Sci 2019; 20: 1–17.Valent P., Akin C., Gleixner K.V., Sperr W.R., Reiter A., Arock M., et al. Multidisciplinary challenges in mastocytosis and how to address with personalized medicine approaches. Int J Mol Sci 2019; 20: 1–17.2. Pardanani A. Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management. Am J Hematol 2018; 94 (3): 363–77.Pardanani A. Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management. Am J Hematol 2018; 94 (3): 363–77.3. Valent P., Akin C., Metcalfe D.D. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood 2017; 129 (11): 1420–7.Valent P., Akin C., Metcalfe D.D. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood 2017; 129 (11): 1420–7.4. Horny H.P., Akin C., Arber D., Peterson L.A., Tefferi A., Metcalfe D.D., et al. Mastocytosis. In: Swerdlow S.H., Campo E., Harris N.L., Jaffe E.S., Pileri S.A., Stein H., et al. (eds.). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2017.Horny H.P., Akin C., Arber D., Peterson L.A., Tefferi A., Metcalfe D.D., et al. Mastocytosis. In: Swerdlow S.H., Campo E., Harris N.L., Jaffe E.S., Pileri S.A., Stein H., et al. (eds.). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2017.5. Meni C., Bruneau J., Gerogin-Lavialle S., Le Sachè de Peufeilhoux L., Damaj G., Hadj-Rabis S., et al. Pediatric mastocytosis: A systematic review of 1747 cases. Br J Dermatol 2015; 172 (3): 642–51.Meni C., Bruneau J., Gerogin-Lavialle S., Le Sachè de Peufeilhoux L., Damaj G., Hadj-Rabis S., et al. Pediatric mastocytosis: A systematic review of 1747 cases. Br J Dermatol 2015; 172 (3): 642–51.6. Lange M., Hartmann K., Carter M.C., Siebenhaar F., Alvarez-Twose I., Torrado I., et al. Molecular background, clinical features and management of pediatric mastocytosis: status 2021. Int J Mol Sci 2021; 22 (5): 2586.Lange M., Hartmann K., Carter M.C., Siebenhaar F., Alvarez-Twose I., Torrado I., et al. Molecular background, clinical features and management of pediatric mastocytosis: status 2021. Int J Mol Sci 2021; 22 (5): 2586.7. Giona F. Pediatric mastocytosis: an update. Mediterr J Hematol Infect Dis 2021; 13 (1): e2021069.Giona F. Pediatric mastocytosis: an update. Mediterr J Hematol Infect Dis 2021; 13 (1): e2021069.8. Carter M.C., Bai Y., Ruiz-Esteves K.N., Scott L.M., Cantave D., Bolan H., et al. Detection of KIT D816V in peripheral blood of children with manifestations of cutaneous mastocytosis suggests systemic disease. Br J Haematol 2018; 183 (5): 775–82.Carter M.C., Bai Y., Ruiz-Esteves K.N., Scott L.M., Cantave D., Bolan H., et al. Detection of KIT D816V in peripheral blood of children with manifestations of cutaneous mastocytosis suggests systemic disease. Br J Haematol 2018; 183 (5): 775–82.9. Czarny J., Zuk M., Zawrocki A., Plata-Nazar K., Biernat W., Niedoszytko M., et al. New Approach to Paediatric Mastocytosis: Implications of KIT D816V Mutation Detection in Peripheral Blood. Acta Derm Venerol 2020; 100 (10): adv00149.Czarny J., Zuk M., Zawrocki A., Plata-Nazar K., Biernat W., Niedoszytko M., et al. New Approach to Paediatric Mastocytosis: Implications of KIT D816V Mutation Detection in Peripheral Blood. Acta Derm Venerol 2020; 100 (10): adv00149.10. Carter M.C., Clayton S.T., Komarow H.D., Brittain E.H., Scott L.M., Cantave D., et al. Assessment of clinical findings, tryptase levels, and bone marrow histopathology in the management of pediatric mastocytosis. J Allergy Clin Immunol 2015; 136 (6): 1673–9.Carter M.C., Clayton S.T., Komarow H.D., Brittain E.H., Scott L.M., Cantave D., et al. Assessment of clinical findings, tryptase levels, and bone marrow histopathology in the management of pediatric mastocytosis. J Allergy Clin Immunol 2015; 136 (6): 1673–9.11. Lange M., Niedoszytko M., Nedoszytko B., Łata J., Trzeciak M., Biernat W. Diffuse cutaneous mastocytosis: Analysis of 10 cases and a brief review of the literature. J Eur Acad Dermatol Venereol 2012; 26 (12): 1565–71.Lange M., Niedoszytko M., Nedoszytko B., Łata J., Trzeciak M., Biernat W. Diffuse cutaneous mastocytosis: Analysis of 10 cases and a brief review of the literature. J Eur Acad Dermatol Venereol 2012; 26 (12): 1565–71.12. Valentini C.G., Rondoni M., Pogliani E.M., Van Lint M.T., Cattaneo C., Marbello L., et al. Mast cell leukemia: a report of ten cases. Ann Hematol 2008; 87 (6): 505–8.Valentini C.G., Rondoni M., Pogliani E.M., Van Lint M.T., Cattaneo C., Marbello L., et al. Mast cell leukemia: a report of ten cases. Ann Hematol 2008; 87 (6): 505–8.13. Georgin-Lavialle S., Lhermitte L., Dubreuil P., Chandesris M.-O., Hermine O., Damaj G. Mast cell leukemia. Blood 2013; 121 (8): 1285–95.Georgin-Lavialle S., Lhermitte L., Dubreuil P., Chandesris M.-O., Hermine O., Damaj G. Mast cell leukemia. Blood 2013; 121 (8): 1285–95.14. Lim K.H., Tefferi A., Lasho T.L., Finke C., Patnaik M., Butterfield J.H., et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2009; 113 (23): 5727–36.Lim K.H., Tefferi A., Lasho T.L., Finke C., Patnaik M., Butterfield J.H., et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2009; 113 (23): 5727–36.15. Cohen S.S., Skovbo S., Vestergaard H., Kristensen T., Møller M., Bindslev-Jensen C., et al. Epidemiology of systemic mastocytosis in Denmark. Br J Hematol 2014; 166 (4): 521–8.Cohen S.S., Skovbo S., Vestergaard H., Kristensen T., Møller M., Bindslev-Jensen C., et al. Epidemiology of systemic mastocytosis in Denmark. Br J Hematol 2014; 166 (4): 521–8.16. Van Doormaal J.J., Arends S., Brunekreeft K.L., van der Wal V.B., Sietsma J., van Voorst Vader P.C., et al. Prevalence of indolent systemic mastocytosis in a Dutch region. J Allergy Clin Immunol 2013; 131 (5): 1429–31.Van Doormaal J.J., Arends S., Brunekreeft K.L., van der Wal V.B., Sietsma J., van Voorst Vader P.C., et al. Prevalence of indolent systemic mastocytosis in a Dutch region. J Allergy Clin Immunol 2013; 131 (5): 1429–31.17. Klaiber N., Kumar S., Irani A.M. Mastocytosis in Children. Curr Allergy Asthma Reports 2017; 17 (11): 80.Klaiber N., Kumar S., Irani A.M. Mastocytosis in Children. Curr Allergy Asthma Reports 2017; 17 (11): 80.18. Hartmann K., Escribano L., Grattan C., Brockow K., Carter M.C., Alvarez-Twose I., et al. Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology. J Allergy Clin Immunol 2016; 137 (1): 35–45.Hartmann K., Escribano L., Grattan C., Brockow K., Carter M.C., Alvarez-Twose I., et al. Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology. J Allergy Clin Immunol 2016; 137 (1): 35–45.19. Méni C., Georgin-Lavialle S., Le Saché de Peufeilhoux L., Jais J.P., Hadj-Rabia S., Bruneau J., et al. Paediatric mastocytosis: Long-term follow-up of 53 patients with whole sequencing of KIT. A prospective study. Br J Dermatol 2018; 179 (4): 925–32.Méni C., Georgin-Lavialle S., Le Saché de Peufeilhoux L., Jais J.P., Hadj-Rabia S., Bruneau J., et al. Paediatric mastocytosis: Long-term follow-up of 53 patients with whole sequencing of KIT. A prospective study. Br J Dermatol 2018; 179 (4): 925–32.20. Joachim G. Uber Mastzellenleukamien. Deutsches Archives fur Klinische Medizin 1906; 87: 437.Joachim G. Uber Mastzellenleukamien. Deutsches Archives fur Klinische Medizin 1906; 87: 437.21. Azana J.M., Torrelo A., Matito A. Update on Mastocytosis (Part 1): Pathophysiology, Clinical Features, and Diagnosis. Actas Dermosifiliogr 2016; 107 (1): 5–14.Azana J.M., Torrelo A., Matito A. Update on Mastocytosis (Part 1): Pathophysiology, Clinical Features, and Diagnosis. Actas Dermosifiliogr 2016; 107 (1): 5–14.22. Theoharides T.C., Valent P., Akin C. Mast Cells, Mastocytosis, and Related Disorders. N Engl J Med 2015; 373 (2): 163–72.Theoharides T.C., Valent P., Akin C. Mast Cells, Mastocytosis, and Related Disorders. N Engl J Med 2015; 373 (2): 163–72.23. Frieri M., Quershi M. Pediatric Mastocytosis: A Review of the Literature. Pediatr Allergy Immunol Pulmonol 2013; 26 (4): 175–80.Frieri M., Quershi M. Pediatric Mastocytosis: A Review of the Literature. Pediatr Allergy Immunol Pulmonol 2013; 26 (4): 175–80.24. Martelli M., Monaldi C., De Santis S., Bruno S., Mancini M., Cavo M., et al. Recent Advances in the Molecular Biology of Systemic Mastocytosis: Implications for Diagnosis, Prognosis, and Therapy. Int J Mol Sci 2020; 21 (11): 3987.Martelli M., Monaldi C., De Santis S., Bruno S., Mancini M., Cavo M., et al. Recent Advances in the Molecular Biology of Systemic Mastocytosis: Implications for Diagnosis, Prognosis, and Therapy. Int J Mol Sci 2020; 21 (11): 3987.25. Komi D.E.A., Rambasek T., Wöhrl S. Mastocytosis: From a Molecular Point of View. Clin Rev Allergy Immunol 2018; 54 (3): 397–411.Komi D.E.A., Rambasek T., Wöhrl S. Mastocytosis: From a Molecular Point of View. Clin Rev Allergy Immunol 2018; 54 (3): 397–411.26. Arase N., Wataya-Kaneda M., Murota H., Nakagawa Y., Yamaoka T., Itoi-Ochi S., et al. Genotype and phenotype analysis of patients with pediatric cutaneous mastocytosis, especially wild-type KIT patients. J Dermatol 2020; 47 (4): 426–9.Arase N., Wataya-Kaneda M., Murota H., Nakagawa Y., Yamaoka T., Itoi-Ochi S., et al. Genotype and phenotype analysis of patients with pediatric cutaneous mastocytosis, especially wild-type KIT patients. J Dermatol 2020; 47 (4): 426–9.27. Chan I.J., Tharp M.D. Comparison of lesional skin c-KIT mutations with clinical phenotype in patients with mastocytosis. Clin Exp Dermatol 2018; 43 (4): 416–22.Chan I.J., Tharp M.D. Comparison of lesional skin c-KIT mutations with clinical phenotype in patients with mastocytosis. Clin Exp Dermatol 2018; 43 (4): 416–22.28. Ertugrul A., Bostanci I., Kaymak A.O., Gurkan A., Ozmen S. Pediatric cutaneous mastocytosis and c-KIT mutation screening. Allergy Asthma Proc 2019; 40 (2): 123–8.Ertugrul A., Bostanci I., Kaymak A.O., Gurkan A., Ozmen S. Pediatric cutaneous mastocytosis and c-KIT mutation screening. Allergy Asthma Proc 2019; 40 (2): 123–8.29. Bodemer C., Hermine O., Palmérini F., Yang Y., Grandpeix-Guyodo C., Leventhal P.S., et al. Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations. J Investig Dermatol 2010; 130 (3): 804–15.Bodemer C., Hermine O., Palmérini F., Yang Y., Grandpeix-Guyodo C., Leventhal P.S., et al. Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations. J Investig Dermatol 2010; 130 (3): 804–15.30. Otani I.M., Carroll R.W., Yager P., Kroshinsky D., Murphy S., Hornick J.L., et al. Diffuse cutaneous mastocytosis with novel somatic KIT mutation K509I and association with tuberous sclerosis. Clin Case Rep 2018; 6 (9): 1834–40.Otani I.M., Carroll R.W., Yager P., Kroshinsky D., Murphy S., Hornick J.L., et al. Diffuse cutaneous mastocytosis with novel somatic KIT mutation K509I and association with tuberous sclerosis. Clin Case Rep 2018; 6 (9): 1834–40.31. Peters F., Fiebig B., Lundberg P., Jaspers N.I., Holzapfel B., Ghadimi M.P., et al. Detection of the Germline KIT S476I Mutation in a Kindred with Familial Mastocytosis associated with Gastrointestinal Stromal Tumors. J Allergy Clin Immunol Pract 2021; 9 (5): 2123–5.Peters F., Fiebig B., Lundberg P., Jaspers N.I., Holzapfel B., Ghadimi M.P., et al. Detection of the Germline KIT S476I Mutation in a Kindred with Familial Mastocytosis associated with Gastrointestinal Stromal Tumors. J Allergy Clin Immunol Pract 2021; 9 (5): 2123–5.32. Li Y., Li X., Liu X., Kang L., Liu X. Genotypic and phenotypic characteristics of Chinese neonates with cutaneous mastocytosis: A case report and literature review. J Int Med Res 2020; 48 (9): 300060520952621.Li Y., Li X., Liu X., Kang L., Liu X. Genotypic and phenotypic characteristics of Chinese neonates with cutaneous mastocytosis: A case report and literature review. J Int Med Res 2020; 48 (9): 300060520952621.33. Valent P., Sotlar K., Sperr W.R., Escribano L., Yavuz S., Reiter A., et al. Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal. Anna Oncol 2014; 25 (9): 1691–700.Valent P., Sotlar K., Sperr W.R., Escribano L., Yavuz S., Reiter A., et al. Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal. Anna Oncol 2014; 25 (9): 1691–700.34. Kristensen T., Vestergaard H., Bindslev-Jensen C., Mortz C.G., Kjaer H.F., Ollert M., et al. Prospective evaluation of the diagnostic value of sensitive KIT D816V mutation analysis of blood in adults with suspected systemic mastocytosis. Allergy 2017; 72 (11): 1737–43.Kristensen T., Vestergaard H., Bindslev-Jensen C., Mortz C.G., Kjaer H.F., Ollert M., et al. Prospective evaluation of the diagnostic value of sensitive KIT D816V mutation analysis of blood in adults with suspected systemic mastocytosis. Allergy 2017; 72 (11): 1737–43.35. Swerdlow S.H., Campo E., Harris N.L., Jaffe E.S., Pileri S.A., Stein H., et al. (eds.). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer; 2008.Swerdlow S.H., Campo E., Harris N.L., Jaffe E.S., Pileri S.A., Stein H., et al. (eds.). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer; 2008.36. Azana J.M., Torrelo A., Matito A. Update on Mastocytosis (Part 2): Categories, Prognosis, and Treatment. Actas Dermosifiliogr 2016; 107 (1): 15–22.Azana J.M., Torrelo A., Matito A. Update on Mastocytosis (Part 2): Categories, Prognosis, and Treatment. Actas Dermosifiliogr 2016; 107 (1): 15–22.37. Zheng Y., Nong L., Liang L., Wang W., Li T. De novo mast cell leukemia without CD25 expression and KIT mutations: A rare case report in a 13-year-old child. Diagn Pathol 2018; 13: 14.Zheng Y., Nong L., Liang L., Wang W., Li T. De novo mast cell leukemia without CD25 expression and KIT mutations: A rare case report in a 13-year-old child. Diagn Pathol 2018; 13: 14.38. Matito A., Blázquez-Goñi C, Morgado J.M., Alvarez-Twose I., Mollejo M., Sánchez-Muñoz L., et al. Short-term omalizumab treatment in an adolescent with cutaneous mastocytosis. Ann Allergy Asthma Immunol 2013; 111 (5): 425–6.Matito A., Blázquez-Goñi C, Morgado J.M., Alvarez-Twose I., Mollejo M., Sánchez-Muñoz L., et al. Short-term omalizumab treatment in an adolescent with cutaneous mastocytosis. Ann Allergy Asthma Immunol 2013; 111 (5): 425–6.39. Liu M.M., Kohn L.A., Roach G.D., Sun G., Garcia-Lloret M.I., Butte M.J. Treatment of systemic mastocytosis in an infant with midostaurin. J Allergy Clin Immunol Pract 2019; 7 (8): 2929–31.Liu M.M., Kohn L.A., Roach G.D., Sun G., Garcia-Lloret M.I., Butte M.J. Treatment of systemic mastocytosis in an infant with midostaurin. J Allergy Clin Immunol Pract 2019; 7 (8): 2929–31.40. Czarny J., Lange M., Ługowska-Umer H., Nowicki R.J. Cutaneous mastocytosis treatment: Strategies, limitations, and perspectives. Adv Dermatol Alergol 2018; 35 (6): 541–5.Czarny J., Lange M., Ługowska-Umer H., Nowicki R.J. Cutaneous mastocytosis treatment: Strategies, limitations, and perspectives. Adv Dermatol Alergol 2018; 35 (6): 541–5.