Multiple myeloma associated with diffuse pulmonary calcifications: pathomorphological study

Authors

DOI:

https://doi.org/10.26641/1997-9665.2024.4.6-14

Keywords:

multiple myeloma, lung histopathology, pulmonary complications, metastatic pulmonary calcification, secondary immunodeficiency, pneumonia.

Abstract

Background. Multiple myeloma is an aggressive lymphoproliferative disease with plasma cell dyscrasia, with symptoms associated with bone marrow infiltration, damage of the hematopoiesis, finally leading to renal failure, bone damage, hypercalcemia, and metastatic calcification. As with all lymphatic tumors, multiple myeloma is characterized by the development of secondary immunodeficiency. Antibody deficiency syndrome is the cause of increased susceptibility of patients to bacterial infections, primarily of the bronchopulmonary system. Objective: to study the nature of pathomorphological changes in the lungs of patients who died from multiple myeloma, and to establish the relationship between multiple myeloma disease with renal dysfunction and metastatic pulmonary calcification. Methods. A pathomorphological study of the autopsy material of two cases of deceased persons, who were diagnosed with multiple myeloma during their lifetime, was carried out. According to autopsies, morphological changes in internal organs were studied, with an emphasis on changes in the lungs. A detailed morphological examination of the kidneys, bone marrow in the sternum, vertebral bodies and the ilium was carried out also. Results. Two cases of multiple myeloma associated with diffuse pulmonary calcinosis in patients in whom renal and pulmonary-cardiac failure were the immediate cause of death are presented. Myeloma disease with damage to many bones was complicated by nephropathy, diffuse metastatic calcification in the lungs and focal - in the myocardium and blood vessels. Diffuse focal deposits of calcium in the interstitium and interalveolar membranes, numerous intraalveolar polypous growths of loose connective tissue (according to the type of organized pneumonia), foci of carnification were found in the lungs. In the lumen of the alveoli there is a thick edematous liquid, fibrin threads, separate siderophages, desquamated alveolocytes, macrophages. There are widespread hemorrhages, focal round cell infiltration of the interstitium, emphysema, dystelectasis, foci of purulent pneumonia, erythrostasis in the microhemocirculatory channel. Conclusion. Metastatic calcification and metastatic pulmonary calcification are rare complications in patients with multiple myeloma, even in patients with renal failure. The risk of metastatic calcification in multiple myeloma is likely strongly related to renal impairment.

References

  1. Brigle K, Verina D, Faiman B. A Focus on Newly Diagnosed Multiple Myeloma. J Adv Pract Oncol. 2022;13(4):7-14. doi: 10.6004/jadpro.2022.13.5.10. Epub 2022 Jul 28. PMID: 35937466; PMCID: PMC9342925
  2. Jurczyszyn A, Suska A. Multiple Myeloma. Encycl. Biomed. Gerontol. 2019, 2, 461–478. http://dx.doi.org/10.1016/B978-0-12-801238-3.11412-6
  3. Padala SA, Barsouk A, Barsouk A, Rawla P, Vakiti A, Kolhe R, Kota V, Ajebo GH. Epidemiology, Staging, and Management of Multiple Myeloma. Med Sci (Basel). 2021;9(1):3. doi: 10.3390/medsci9010003. PMID: 33498356; PMCID: PMC7838784
  4. Global Cancer Observatory: Cancer Today. Lyon (France): International Agency for Research on Cancer; 2020. https://gco.iarc.fr/today
  5. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492
  6. Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. Bethesda, MD, /, based on November 2018 SEER data submission, posted to the SEER web site, April 2019. Available from: https://seer.cancer.gov/csr/1975_2016.
  7. [Bulletin of the National Cancer Registry No. 25 - Cancer in Ukraine, 2022–2023]. Ukrainian. http://www.ncru.inf.ua/publications/BULL_25/index.htm
  8. Chakraborty R, Majhail NS. Treatment and disease-related complications in multiple myeloma: Implications for survivorship. Am J Hematol. 2020;95(6):672-690. doi: 10.1002/ajh.25764. Epub 2020 Mar 13. PMID: 32086970; PMCID: PMC7217756
  9. Vakiti A, Anastasopoulou C, Mewawalla P. Malignancy-Related Hypercalcemia. 2023 Apr 16. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. PMID: 29494030
  10. Fukuta T, Tanaka T, Hashimoto Y, Omura H. The Relationship between Multiple Myeloma with Renal Failure and Metastatic Calcification. Case Rep Hematol. 2018;2018:7819792. doi: 10.1155/2018/7819792. PMID: 30026990; PMCID: PMC6031209
  11. Leleu X, Masszi T, Bahlis NJ, Viterbo L, Baker B, Gimsing P, Maisnar V, Samoilova O, Rosiñol L, Langer C, Song K, Izumi T, Cleeland C, Berg D, Lin HM, Zhu Y, Skacel T, Moreau P, Richardson PG. Patient-reported health-related quality of life from the phase III TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone versus placebo-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma. Am J Hematol. 2018;93:985-993. doi: 10.1002/ajh.25134. Epub ahead of print. PMID: 29726031
  12. Morgan AE, Smith WK, Levenson JL. Reversible dementia due to thalidomide therapy for multiple myeloma. N Engl J Med. 2003;348(18):1821–1822. doi: 10.1056/NEJM200305013481822. PMID: 12724497
  13. McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C, Tosi P, Bringhen S, Musto P, Anderson KC, Caillot D, Gay F, Moreau P, Marit G, Jung SH, Yu Z, Winograd B, Knight RD, Palumbo A, Attal M. Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis. J Clin Oncol. 2017;35(29):3279-3289. doi: 10.1200/JCO.2017.72.6679. Epub 2017 Jul 25. PMID: 28742454; PMCID: PMC5652871
  14. Kristinsson SY, Pfeiffer RM, Björkholm M, Goldin LR, Schulman S, Blimark C, Mellqvist UH, Wahlin A, Turesson I, Landgren O. Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study. Blood. 2010;115(24):4991-4998. doi: 10.1182/blood-2009-11-252072. PMID: 20299513; PMCID: PMC2890150
  15. Cornell RF, Ky B, Weiss BM, Dahm CN, Gupta DK, Du L, Carver JR, Cohen AD, Engelhardt BG, Garfall AL, Goodman SA, Harrell SL, Kassim AA, Jadhav T, Jagasia M, Moslehi J, O'Quinn R, Savona MR, Slosky D, Smith A, Stadtmauer EA, Vogl DT, Waxman A, Lenihan D. Prospective Study of Cardiac Events During Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma. J Clin Oncol. 2019;37(22):1946-1955. doi: 10.1200/JCO.19.00231. Epub 2019 Jun 12. PMID: 31188726; PMCID: PMC9798911
  16. Waxman AJ, Clasen S, Hwang WT, Garfall A, Vogl DT, Carver J, O'Quinn R, Cohen AD, Stadtmauer EA, Ky B, Weiss BM. Carfilzomib-Associated Cardiovascular Adverse Events: A Systematic Review and Meta-analysis. JAMA Oncol. 2018;4(3):e174519. doi: 10.1001/jamaoncol.2017.4519. Epub 2018 Mar 8. PMID: 29285538; PMCID: PMC5885859
  17. Friman V, Winqvist O, Blimark C, Langerbeins P, Chapel H, Dhalla F. Secondary immunodeficiency in lymphoproliferative malignancies. Hematol Oncol. 2016;34(3):121-132. doi: 10.1002/hon.2323. Epub 2016 Jul 12. PMID: 27402426
  18. Kumar SK, Rajkumar V, Kyle RA, van Duin M, Sonneveld P, Mateos MV, Gay F, Anderson KC. Multiple myeloma. Nat Rev Dis Primers. 2017;3:17046. doi: 10.1038/nrdp.2017.46. PMID: 28726797
  19. Michels TC, Petersen KE. Multiple Myeloma: Diagnosis and Treatment. Am Fam Physician. 2017;95(6):373-383. PMID: 28318212. https://www.aafp.org/pubs/afp/issues/2017/0315/p373.html
  20. Röllig C, Knop S, Bornhäuser M. Multiple myeloma. Lancet. 2015;385(9983):2197-2208. doi: 10.1016/S0140-6736(14)60493-1. Epub 2014 Dec 23. PMID: 25540889
  21. Cowan AJ, Green DJ, Kwok M, Lee S, Coffey DG, Holmberg LA, Tuazon S, Gopal AK, Libby EN. Diagnosis and Management of Multiple Myeloma: A Review. JAMA. 2022;327(5):464-477. doi: 10.1001/jama.2022.0003. PMID: 35103762
  22. Kaburagi T, Nagai H, Sasaki T, Oka T, Yoneda R, Mouri M. [Case report of multiple myeloma associated with diffuse pulmonary calcinosis]. Nihon Kyobu Shikkan Gakkai Zasshi. 1991;29(11):1479-1483. Japanese. PMID: 1770690
  23. Crippa C, Ferrari S, Drera M, Tardanico R, Ungari M, Facchetti F, Cancarini G, Rossi G. Pulmonary calciphylaxis and metastatic calcification with acute respiratory failure in multiple myeloma. J Clin Oncol. 2010;28(9):e133-135. doi: 10.1200/JCO.2009.25.1587. Epub 2010 Jan 4. PMID: 20048175
  24. Li YJ, Tian YC, Chen YC, Huang SF, Huang CC, Fang JT, Yang CW. Fulminant pulmonary calciphylaxis and metastatic calcification causing acute respiratory failure in a uremic patient. Am J Kidney Dis. 2006;47(4):e47-53. doi: 10.1053/j.ajkd.2005.11.033. PMID: 16564932
  25. Couto FM, Chen H, Blank RD, Drezner MK. Calciphylaxis in the absence of end-stage renal disease. Endocr Pract. 2006;12(4):406-410. doi: 10.4158/EP.12.4.406. PMID: 16901796
  26. Feng J, Gohara M, Lazova R, Antaya RJ. Fatal childhood calciphylaxis in a 10-year-old and literature review. Pediatr Dermatol. 2006;23(3):266-272. doi: 10.1111/j.1525-1470.2006.00232. x. PMID: 16780477
  27. Breitkreutz I, Raab MS, Vallet S, Hideshima T, Raje N, Mitsiades C, Chauhan D, Okawa Y, Munshi NC, Richardson PG, Anderson KC. Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma. Leukemia. 2008;22(10):1925-1932. doi: 10.1038/leu.2008.174. PMID: 18596740
  28. Conger JD, Hammond WS, Alfrey AC, Contiguglia SR, Stanford RE, Huffer WE. Pulmonary calcification in chronic dialysis patients. Clinical and pathologic studies. Ann Intern Med. 1975;83(3):330-336. doi: 10.7326/0003-4819-83-3-330. PMID: 1190631
  29. Kuzela DC, Huffer WE, Conger JD, Winter SD, Hammond WS. Soft tissue calcification in chronic dialysis patients. Am J Pathol. 1977;86(2):403-424. PMID: 836675; PMCID: PMC2032079
  30. Allegra A, Tonacci A, Musolino C, Pioggia G, Gangemi S. Secondary Immunodeficiency in Hematological Malignancies: Focus on Multiple Myeloma and Chronic Lymphocytic Leukemia. Front Immunol. 2021;2:738915. doi: 10.3389/fimmu.2021.738915. PMID: 34759921; PMCID: PMC8573331
  31. Marcia Garnica. Multiple myeloma and infection: this association is still close. Hematol Transfus Cell Ther. 2019;41(4):281–82. https://doi.org/10.1016/j.htct.2019.09.002

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Published

2025-01-15

How to Cite

Volos , L., & Stoliar , H. (2025). Multiple myeloma associated with diffuse pulmonary calcifications: pathomorphological study. Морфологія / Morphologia / Morfologìâ, 18(4), 6–14. https://doi.org/10.26641/1997-9665.2024.4.6-14

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Vol. 18 No. 4 (2024)

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