Myeloid Sarcoma with Skin and Spinal Lesions and KRAS Gene Mutation, Complicated by Secondary Hemophagocytic Syndrome: A Case Report and Literature Review

Myeloid sarcoma (MS) is a rare hematologic tumor of immature myeloid cells with lesions located outside the bone marrow. The disease can develop de novo as extramedullary myeloid tumor, be a manifestation of acute myeloid leukemia (AML) or be diagnosed as an AML relapse after previously achieved remission. MS occurs in all age groups, although more commonly in elderly people. Diagnosis is based on immunomorphological and molecular genetic analyses of the tumor tissue. The most effective treatment regimens in MS are those used for AML therapy with subsequent allogeneic hematopoietic stem cell transplantation provided that the first complete remission was achieved. In addition to that, radiotherapy as well as biological and targeted drugs are administered. Nevertheless, the prognosis of the disease remains generally unfavorable. The present paper reports a clinical case of MS with KRAS mutation, tumor skin and Th5–Th6 lesions, spinal cord compression, and developing flaccid paraplegia. The patient received chemotherapies of varying intensity as well as hypomethylating agents combined with venetoclax and the targeted drug trametinib. The course of the disease was complicated by secondary hemophagocytic syndrome (SHS). The present case report demonstrates the challenges of both diagnosis and treatment of this rare and poor-prognosis extramedullary myeloid tumor complicated by SHS.

• Tatyana Nikolaevna Tolstykh City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182; IM Sechenov First Moscow State Medical University, 2 korp. 4 Bolshaya Pirogovskaya ul., Moscow, Russian Federation, 119435 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет) Минздрава России, ул. Большая Пироговская, д. 2, стр. 4, Москва, Российская Федерация, 119435 https://orcid.org/0000-0001-7308-0927 (unauthenticated)
• O.L. Kochneva City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182 https://orcid.org/0000-0003-1338-8203 (unauthenticated)
• E.N. Misyurina City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182; IM Sechenov First Moscow State Medical University, 2 korp. 4 Bolshaya Pirogovskaya ul., Moscow, Russian Federation, 119435 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет) Минздрава России, ул. Большая Пироговская, д. 2, стр. 4, Москва, Российская Федерация, 119435 https://orcid.org/0000-0003-2419-4850 (unauthenticated)
• E.A. Baryakh City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182; IM Sechenov First Moscow State Medical University, 2 korp. 4 Bolshaya Pirogovskaya ul., Moscow, Russian Federation, 119435; Russian Medical Academy of Postgraduate Education, 2/1 Barrikadnaya ul., Moscow, Russian Federation, 125993 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет) Минздрава России, ул. Большая Пироговская, д. 2, стр. 4, Москва, Российская Федерация, 119435; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, ул. Баррикадная, д. 2/1, Москва, Российская Федерация, 125993 https://orcid.org/0000-0001-6880-9269 (unauthenticated)
• M.A. Mingalimov City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182; IM Sechenov First Moscow State Medical University, 2 korp. 4 Bolshaya Pirogovskaya ul., Moscow, Russian Federation, 119435 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет) Минздрава России, ул. Большая Пироговская, д. 2, стр. 4, Москва, Российская Федерация, 119435 https://orcid.org/0000-0002-8491-2140 (unauthenticated)
• K.V. Yatskov City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182 https://orcid.org/0000-0003-0125-9068 (unauthenticated)
• S.A. Kardovskaya City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182 https://orcid.org/0000-0002-4220-7582 (unauthenticated)
• D.D. Ivanova City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182 https://orcid.org/0009-0004-3632-9198 (unauthenticated)
• T.S. Chudnova City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182; IM Sechenov First Moscow State Medical University, 2 korp. 4 Bolshaya Pirogovskaya ul., Moscow, Russian Federation, 119435 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет) Минздрава России, ул. Большая Пироговская, д. 2, стр. 4, Москва, Российская Федерация, 119435 https://orcid.org/0000-0002-8012-1640 (unauthenticated)
• D.V. Lebedev AI Burnazyan Federal Medical Biophysical Center, 46 Zhivopisnaya ul., Moscow, Russian Federation, 123098 ; ФГБУ «Государственный научный центр Российской Федерации — Федеральный медицинский биофизический центр им. А.И. Бурназяна ФМБА России», ул. Живописная, д. 46, Москва, Российская Федерация, 123098 https://orcid.org/0009-0001-8480-5505 (unauthenticated)
• A.N. Titova AI Burnazyan Federal Medical Biophysical Center, 46 Zhivopisnaya ul., Moscow, Russian Federation, 123098 ; ФГБУ «Государственный научный центр Российской Федерации — Федеральный медицинский биофизический центр им. А.И. Бурназяна ФМБА России», ул. Живописная, д. 46, Москва, Российская Федерация, 123098 https://orcid.org/0009-0004-0107-4594 (unauthenticated)
• E.I. Zhelnova City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182; IM Sechenov First Moscow State Medical University, 2 korp. 4 Bolshaya Pirogovskaya ul., Moscow, Russian Federation, 119435 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет) Минздрава России, ул. Большая Пироговская, д. 2, стр. 4, Москва, Российская Федерация, 119435 https://orcid.org/0000-0002-0343-9348 (unauthenticated)

1. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405. doi: 10.1182/blood-2016-03-643544. DOI: https://doi.org/10.1182/blood-2016-03-643544
2. Kawamoto K, Miyoshi H, Yoshida N, et al. Clinicopathological, Cytogenetic, and Prognostic Analysis of 131 Myeloid Sarcoma Patients. Am J Surg Pathol. 2016;40(11):1473–83. doi: 10.1097/PAS.0000000000000727. DOI: https://doi.org/10.1097/PAS.0000000000000727
3. Савченко В.Г., Паровичникова Е.Н., Афанасьев Б.В. и др. Клинические рекомендации по диагностике и лечению острых миелоидных лейкозов взрослых. М.: Национальное гематологическое общество, 2014. 65 с. [Savchenko V.G., Parovichnikova E.N., Afanasyev B.V., et al. Klinicheskie rekomendatsii po diagnostike i lecheniyu ostrykh mieloidnykh leikozov vzroslykh. (Clinical guidelines for diagnosis and treatment of acute myeloid leukemias in adults.) Moscow: Natsionalnoe gematologicheskoe obshchestvo Publ.; 2014. p. (In Russ)]
4. Loscocco GG, Vannucchi AM. Myeloid sarcoma: more and less than a distinct entity. Ann Hematol. 2023;102(8):1973–84. doi: 10.1007/s00277-023-05288-1. DOI: https://doi.org/10.1007/s00277-023-05288-1
5. Zhao H, Dong Z, Wan D, et al. Clinical characteristics, treatment, and prognosis of 118 cases of myeloid sarcoma. Sci Rep. 2022;12(1):6752. doi: 10.1038/s41598-022-10831-7. DOI: https://doi.org/10.1038/s41598-022-10831-7
6. Bakst RL, Tallman MS, Douer D, et al. How I treat extramedullary acute myeloid leukemia. Blood. 2011;118(14):3785–93. doi: 10.1182/blood-2011-04-347229. DOI: https://doi.org/10.1182/blood-2011-04-347229
7. Tsimberidou AM, Kantarjian HM, Wen S, et al. Myeloid sarcoma is associated with superior event-free survival and overall survival compared with acute myeloid leukemia. Cancer. 2008;113(6):1370–8. doi: 10.1002/cncr.23691. DOI: https://doi.org/10.1002/cncr.23691
8. Shimizu H, Saitoh T, Tanaka M, et al. Allogeneic hematopoietic stem cell transplantation for adult AML patients with granulocytic sarcoma. Leukemia. 2012;26(12):2469–73. doi: 10.1038/leu.2012.156. DOI: https://doi.org/10.1038/leu.2012.156
9. Simanshu DK, Nissley DV, McCormick F. RAS proteins and their regulators in human disease. Cell. 2017;170(1):17–33. doi: 10.1016/j.cell.2017.06.009. DOI: https://doi.org/10.1016/j.cell.2017.06.009
10. Otoukesh S, Zhang J, Nakamura R, et al. The efficacy of venetoclax and hypomethylating agents in acute myeloid leukemia with extramedullary involvement. Leuk Lymphoma. 2020;61(8):2020–3. doi: 10.1080/10428194.2020.1742908. DOI: https://doi.org/10.1080/10428194.2020.1742908
11. Belhadj M, Burroni B, Kosmider O, et al. Clinico-biological features, treatment and prognosis of primary myeloid sarcoma: a French retrospective multi-centric observational study. Br J Haematol. 2023;202(6):e50–e53. doi: 10.1111/bjh.18961. DOI: https://doi.org/10.1111/bjh.18961
12. Ball S, Knepper TC, Deutsch YE, et al. Molecular annotation of extramedullary acute myeloid leukemia identifies high prevalence of targetable mutations. Cancer. 2022;128(21):3880–7. doi: 10.1002/cncr.34459. DOI: https://doi.org/10.1002/cncr.34459
13. Frietsch JJ, Hunstig F, Wittke C, et al. Extra-medullary recurrence of myeloid leukemia as myeloid sarcoma after allogeneic stem cell transplantation: impact of conditioning intensity. Bone Marrow Transpl. 2021;56(1):101–9. doi: 10.1038/s41409-020-0984-4. DOI: https://doi.org/10.1038/s41409-020-0984-4
14. Kanate AS, Vos J, Chargualaf MJ. Venetoclax for refractory myeloid sarcoma. J Oncol Pract. 2019;15(7):413–5. doi: 10.1200/JOP.18.00753. DOI: https://doi.org/10.1200/JOP.18.00753
15. Condorelli A, Matteo C, Leotta S, et al. Venetoclax penetrates in cerebrospinal fluid of an acute myeloid leukemia patient with leptomeningeal involvement. Cancer Chemother Pharmacol. 2022;89(2):267–70. doi: 10.1007/s00280-021-04356-5. DOI: https://doi.org/10.1007/s00280-021-04356-5
16. De la Garza-Salazar F, Peña-Lozano SP, Gómez-Almaguer D, et al. Orbital myeloid sarcoma treated with low-dose venetoclax and a potent cytochrome P450 inhibitor. J Oncol Pharm Pract. 2023;29(2):493–7. doi: 10.1177/10781552221110826. DOI: https://doi.org/10.1177/10781552221110826
17. Banks M, Crowell K, Proctor A, et al. Cardiovascular Effects of the MEK Inhibitor, Trametinib: A Case Report, Literature Review, and Consideration of Mechanism. Cardiovasc Toxicol. 2017;17(4):487–93. doi: 10.1007/s12012-017-9425-z. DOI: https://doi.org/10.1007/s12012-017-9425-z
18. Seipel K, Schmitter K, Bacher U, et al. Rationale for a Combination Therapy Consisting of MCL1- and MEK-Inhibitors in Acute Myeloid Leukemia. Cancers (Basel). 2019;11(11):1779. doi: 10.3390/cancers11111779. DOI: https://doi.org/10.3390/cancers11111779
19. Burgess MR, Hwang E, Firestone AJ, et al. Preclinical efficacy of MEK inhibition in Nras-mutant AML. Blood. 2014;124(26):3947–55. doi: 10.1182/blood-2014-05-574582. DOI: https://doi.org/10.1182/blood-2014-05-574582
20. Pileri SA, Ascani S, Cox MC, et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia. 2007;21(2):340–50. doi: 10.1038/sj.leu.2404491. DOI: https://doi.org/10.1038/sj.leu.2404491
21. Bai CR, Li X, Wang JS, et al. Diagnosis and surgical treatment of primary isolated aggressive lumbar myeloid sarcoma: a rare case report and review of the literatures. BMC Musculoskelet Disord. 2021;22(1):220. doi: 10.1186/s12891-021-04066-2. DOI: https://doi.org/10.1186/s12891-021-04066-2
22. Kumar M, Sonia F, Hamadani SM, et al. A Rare Case of Acute Cord Compression From Spinal Myeloid Sarcoma: A Complication of Acute Myeloid Leukemia. Cureus. 2020;12(8):e9502. doi: 10.7759/cureus.9502. DOI: https://doi.org/10.7759/cureus.9502
23. Kumar N, Yadav S, Reddy V, et al. Leukaemia cutis. Lancet. 2012;380(9848):1179. doi: 10.1016/S0140-6736(12)60352-3. DOI: https://doi.org/10.1016/S0140-6736(12)60352-3
24. Bakst R, Powers A, Yahalom J. Diagnostic and Therapeutic Considerations for Extramedullary Leukemia. Curr Oncol Rep. 2020;22(7):75. doi: 10.1007/s11912-020-00919-6. DOI: https://doi.org/10.1007/s11912-020-00919-6
25. Cairoli R, Beghini A, Grillo G, et al. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood. 2006;107(9):3463–8. doi: 10.1182/blood-2005-09-3640. DOI: https://doi.org/10.1182/blood-2005-09-3640
26. Shan M, Lu Y, Yang M, et al. Characteristics and transplant outcome of myeloid sarcoma: a single-institute study. Int J Hematol. 2021;113(5):682–92. doi: 10.1007/s12185-021-03081-2. DOI: https://doi.org/10.1007/s12185-021-03081-2
27. Sakaguchi H, Miyamura T, Tomizawa D, et al. Effect of extramedullary disease on allogeneic hematopoietic cell transplantation for pediatric acute myeloid leukemia: a nationwide retrospective study. Bone Marrow Transplant. 2021;56(8):1859–65. doi: 10.1038/s41409-021-01250-9. DOI: https://doi.org/10.1038/s41409-021-01250-9
28. Nahas MR, Stroopinsky D, Rosenblatt J, et al. Hypomethylating agent alters the immune microenvironment in acute myeloid leukaemia (AML) and enhances the immunogenicity of a dendritic cell/AML vaccine. Br J Haematol. 2019;185(4):679–90. doi: 10.1111/bjh.15818. DOI: https://doi.org/10.1111/bjh.15818
29. Okamoto H, Kamitsuji Y, Komori Y, et al. Durable Remission of Chemotherapy-Refractory Myeloid Sarcoma by Azacitidine. Tohoku J Exp Med. 2021;254(2):101–5. doi: 10.1620/tjem.254.101. DOI: https://doi.org/10.1620/tjem.254.101
30. Katagiri T, Ushiki T, Masuko M, et al. Successful 5-azacytidine treatment of myeloid sarcoma and leukemia cutis associated with myelodysplastic syndrome: A case report and literature review. Medicine (Baltimore). 2017;96(36):e7975. doi: 10.1097/MD.0000000000007975. DOI: https://doi.org/10.1097/MD.0000000000007975
31. Tian FQ, Zhang LS, Li JH, et al. Venetoclax combined with azacitidine in the treatment of elderly patients with acute myeloid leukemia or myeloid sarcoma: Three cases reports and literature review. Zhonghua Xue Ye Xue Za Zhi. 2020;41(8):694–6. doi: 10.3760/cma.j.issn.0253-2727.2020.08.016.