μ-Heavy chain disease associated with systemic amyloidosis and non-amyloid deposits. Diffi culties in diagnosis and therapy
https://doi.org/10.35754/0234-5730-2020-65-2-190-207
Abstract
Introduction. Heavy-chain diseases (HCDs) are rare B-cell lymphoproliferative diseases that do not have a classical clinical picture. A characteristic feature of this disease is the secretion of fragmented heavy chains of various immunoglobulin isotypes. Currently, there are four known variants of this disease: μ, γ, α, and δ.
Aim. To describe the clinical observation of μ-HCD, hidden under the mask of systemic amyloidosis, and the associated diffi culties of primary diagnosis.
Main Findings. A rare clinical case of μ-HCD in combination with systemic amyloidosis (light chain amyloidosis-AL), transthyretin amyloidosis (transthyretin amyloidosis-ATTR), and non-amyloid deposits in a 64-year-old patient is presented. The severity of the condition was due to the clinical picture of chronic heart failure, polyneuropathy. Upon examination, Waldenstrom’s macroglobulinemia was diagnosed while a diagnosis of amyloidosis was not established. Immuno-chemotherapy was performed under the RB program (rituximab and bendamustine). The effect of the therapy was minimal and short-term. The patient’s condition progressively worsened, and the patient died due to acute cardiovascular failure. The main diagnosis was revised in favor of μ-HCD. The autopsy revealed widespread amyloid and non-amyloid lesions of organs and tissues.
Conflict of interest: the authors declare no conflict of interest
Financial disclosure: the study had no sponsorship
Keywords
Supporting agencies: We express our sincere gratitude to Dr. V.V. Baykov and Dr. I.A. Kuznetsova working at the Department of Pathological Anatomy of the Pavlov First State Medical University of St. Petersburg for their assistance in investigating autopsy materials.
About the Authors
V. K. Okhota
National Research Center for Hematology
Russian Federation
Russian Federation
Valeriya K. Okhota, hematologist in the Consultative Hematology Department with a Day Hospital for Intensive High-Dose Chemotherapy
phone: +7 (925) 128-79-76
V. V. Ryzhko
National Research Center for Hematology
Russian Federation
Vyacheslav V. Ryzhko, Cand. Sci. (Med.), Hematologist of the Department of intensive high-dose chemotherapy of hematological diseases with round-theclock and day hospitals
Russian Federation
Vyacheslav V. Ryzhko, Cand. Sci. (Med.), Hematologist of the Department of intensive high-dose chemotherapy of hematological diseases with round-theclock and day hospitals
A. M. Kovrigina
National Research Center for Hematology
Russian Federation
Alla M. Kovrigina, Dr. Sci. (Biol.), Head of the Pathology Department
Russian Federation
Alla M. Kovrigina, Dr. Sci. (Biol.), Head of the Pathology Department
I. A. Shupletsova
National Research Center for Hematology
Russian Federation
Irina A. Shupletsova, Cand. Sci. (Med.), pathologist of the Pathology Department
Russian Federation
Irina A. Shupletsova, Cand. Sci. (Med.), pathologist of the Pathology Department
N. P. Soboleva
National Research Center for Hematology
Russian Federation
Nataliya P. Soboleva, Clinical laboratory diagnostics doctor of the Centralized Clinical Diagnostic Laboratory
Russian Federation
Nataliya P. Soboleva, Clinical laboratory diagnostics doctor of the Centralized Clinical Diagnostic Laboratory
E. O. Gribanova
National Research Center for Hematology
Russian Federation
Elena O. Gribanova, Cand. Sci. (Med.), Head of the Department of intensive high-dose chemotherapy of hematological diseases with round-the-clock and day hospitals
Russian Federation
Elena O. Gribanova, Cand. Sci. (Med.), Head of the Department of intensive high-dose chemotherapy of hematological diseases with round-the-clock and day hospitals
References
1. Bianchi G., Anderson K. C., Harris N.L., Sohani A.R. The heavy chain diseases: clinical and pathologic features. Oncology. 2014; 28(1): 45–53.
2. Andreeva N.E., Balakireva T.V. Heavy chain diseases. Klinicheskaya onkogematologiya: rukovodstvo dlya vrachei. Ed. M.A. Volkova. 2nd edition. Moscow: Medicine, 2007: 885–90 (In Russian).
3. Courtois L. Sujobert P. Morphologic features of μ-heavy-chain disease. Blood. 2017; 130(4): 558. DOI: 10.1182/blood-2017-04-781344.
4. Burmester G.-D., Pezzutto A. B-lymphocyte development and differentiation. In: Color atlas of immunology. Stuttgar; New York: Thieme. 2003: 32–46.
5. Witzig T.E., Wahner-Roedler D.L. Heavy chain disease. Curr Treat Opt Oncol. 2002; 3(3): 247–54. DOI: 10.1007/s11864-002-0014-3.
6. Ria R., Dammacco F., Vacca A. Heavy-chain diseases and myeloma-associated Fanconi syndrome: an update. Mediterr J Hematol Infect Dis. 2018; 10(1): e2018011. DOI: 10.4084/MJHID.2018.011.
7. Seligmann, M., Danon, F., Hurez, D., et al. Alpha-chain disease: a new immunoglobulin abnormality. Science. 1968; 162(3860): 1396–7. DOI: 10.1126/science.162.3860.1396.
8. Lecuit M., Abachin E., Martin A., et al. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med. 2004; 350(3): 239– 48. DOI: 10.1056/NEJMoa031887.
9. Fine K.D., Stone M.J. α-Heavy chain disease, Mediterranean lymphoma, and immunoproliferative small intestinal disease: a review of clinicopathological features, pathogenesis, and differential diagnosis Am J Gastroenterol. 1999; 94(5): 1139–52. DOI: 10.1111/j.1572-0241.1999.01057.x.
10. Kurimoto, M., Sonoki, T., Nakamura, Y., et al. Severe enteropathy caused by α-heavy chain disease lacking detectable M-proteins. Intern Med. 2014; 53(6): 581–5. DOI: 10.2169/internalmedicine.53.1625.
11. Franklin E.C., Lowenstein, J., Bigelow, B., et al. Heavy chain disease — a new disorder of serum γ-globulins: report of the fi rst case. Am J Med. 1964; 37(3): 332–50. DOI: 10.1016/0002-9343(64)90191-3.
12. Wahner-Roedler D.L., Kyle R.A. Heavy chain diseases. Best Pract Res Clin Haematol. 2005; 18: 729–46. DOI: 10.1016/j.beha.2005.01.029.
13. Fermand J.P., Brouet, J.C., Danon, F., et al. Gamma heavy chain “disease”: heterogeneity of the clinicopathologic features. Report of 16 cases and review of the literature. Medicine. 1989; 68(6): 321–35. DOI: 10.1097/00005792-198911000-00001.
14. Wahner-Roedler D.L. Witzig, T.E., Loehrer, L.L., et al. γ-Heavy chain disease: review of 23 cases. Medicine. 2003; 82(4): 236–50. DOI: 10.1097/01.md.0000085058.63483.7f.
15. San-José P., Aguadero V., Perea G., et al. Gamma heavy-chain disease accompanied with follicular lymphoma: a case report. Biochem Med. 2018; 28(1): 010802. DOI: 10.11613/BM.2018.010802.
16. Ramasamy, I., Rudzki, Z. Two Cases of γ-Heavy Chain Disease and a Review of the Literature Case Rep Hematol. 2018; 4832619. DOI: 10.1155/2018/4832619.
17. Cook J.R., Harris N.L., Isaacson P.G., et al. Heavy chain diseases. In: S.H. Swerdlow, E Campo, N.L., Harris, et al., eds. WHO Classifi cation of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th Edition. Lyon: IARC. Press; 2017: 238–9.
18. Van Keer J., Meijers B., Delforge M., et al. Two cases of heavy chain MGUS. Case reports in oncological medicine. 2016; 8749153. DOI: 10.1155/2016/8749153.
19. Forte F.A., Prelli F., Yount W.J., et al. Heavy chain disease of the μ (γM) type: Report of the fi rst case. Blood. 1970; 36(2): 137–44. DOI: 10.1182/blood.v36.2.137.137
20. Ballard H.S., Hamilton L.M., Marcus A.J., Illes C.H. A new variant of heavychain disease (μ-chain disease). N Engl J Med. 1970; 282(19): 1060–2. DOI: 10.1056/nejm197005072821902.
21. Haas I.G., Wabl M. Immunoglobulin heavy chain binding protein. Nature. 1983; 306: 387–9. DOI: 10.1038/306387a0.
22. Alexander A., Anicito I., Buxbaum J. Gamma heavy chain disease in man: genomic sequence reveals two noncontiguous deletions in a single gene. J Clin Invest. 1988; 82: 1244–52. DOI: 10.1172/JCI113722.
23. Leach I.H., Jenkins J.S., Murray-Leslie C.F., Powell R.J. μ-Heavy chain and monoclonal IgG K paraproteinaemia in systemic lupus erythematosus. Rheumatology. 1987; 26(6): 460–2. DOI: 10.1093/rheumatology/26.6.460.
24. Gordon J., Hamblin T. J., Smith J. L., et al. A human b-cell lymphoma synthesizing and expressing surface mu-chain in the absence of detectable light chain. Blood. 1981; 58(3): 552–6. DOI: 10.1182/blood.V58.3.552.bloodjournal583552.
25. Bonhomme J., Seligmann M., Mihaesco C., et al. Mu-chain disease in an African patient. Blood. 1974; 43(4): 485–92. DOI: 10.1182/blood.V43.4.485.485.
26. Witzens M., Egerer G., Stahl D., et al. A case of μ heavy-chain disease associated with hyperglobulinemia, anemia, and a positive Coombs test. Ann Hematol. 1998; 77(5): 231–4. DOI: 10.1007/s002770050448.
27. Wahner-Roedler D. L., Kyle R. A. μ-heavy chain disease: Presentation as a benign monoclonal gammopathy. Am J Hematol. 1992; 40(1): 56–60. DOI: 10.1002/ajh.2830400112.
28. Dammacco F., Bonomo L., Franklin E.C. A new case of mu heavy chain disease: clinical and immunochemical studies. Blood. 1974; 43(5): 713–9.
29. Yanai M., Maeda A., Watanabe N., et al. Successful treatment of μ-heavy chain disease with fludarabine monophosphate: a case report. Int J Hematol. 2004; 79(2): 174–7. DOI: 10.1532/IJH97.03053.
30. Guglielmo P., Granata P., Raimondo F.D., et al. ‘μ’ Heavy Chain Type ‘NonExcretory’ Myeloma. Scand J Haematol. 1982; 29(1): 36–40. DOI: 10.1111/j.1600-0609.1982.tb00559.x.
31. Leglise M.C., Briere J., Abgrall J.F., et al. Non-secretory myeloma of heavy mu-chain type. Nouv Rev Fr Hematol. 1983; 25(2): 103–6.
32. Maeda A., Mori M., Torii S., et al. Multiple Extranodal Tumors in μ-Heavy Chain Disease. Int J Hematol. 2006; 84(3): 286. DOI: 10.1532/IJH97.06124.
33. Vilpo J. A., Irjala K., Viljanen M. K., et al. δ-Heavy chain disease: A study of a case. Clin Immunol Immunopathol. 1980; 17(4): 584–94. DOI: 10.1016/0090-1229(80)90154-3.
34. Piradov M.A., Suponeva N.A., Ginzberg M.A., et al. POEMS-syndrome: review of the literature and clinical cases. Zhurnal nevrologii i psichiatrii im. SS Korsakova 2014; 114(4): 4–10 (In Russian).
35. Balakireva T.V., Andreeva N.E. Waldenström macroglobulinemia. Klinicheskaya onkogematologiya. Fundamental`nye issledovaniya i klinicheskaya praktika. 2009; 2(2): 121–36 (In Russian).
36. Gertz M.A., Kyle R.A. Amyloidosis with IgM monoclonal gammopathies. Seminars in oncology 2003; 30(2): 325–8. DOI: 10.1053/sonc.2003.50060.
37. Ghobrial I.M. Are you sure this is Waldenström macroglobulinemia? Hematology 2010, the American Society of Hematology Education Program Book. 2012(1): 586–94. DOI: 10.1182/asheducation-2012.1.586.
38. Gertz M.A. Waldenström macroglobulinemia: 2017 update on diagnosis, risk stratifi cation, and management. Am J. Hematol. 2017; 92(2): 209–17. DOI: 10.1002/ajh.25292.
39. Corcos D., Osborn M.J., Matheson L.S. B-cell receptors and heavy chain diseases: guilty by association? Blood. 2011; 117(26): 6991–8. DOI: 10.1182/blood-2011-02-336164.
40. Kinoshita K., Yamagata T., Nozaki Y., et al. μ-Heavy Chain Disease Associated with Systemic Amyloidosis. Hematology. 2004; 9(2): 135–7. DOI: 10.1080/10245330410001671561.
41. Palladini G., Merlini G. What is new in diagnosis and management of light chain amyloidosis? Blood. 2016; 128(2): 159–68. DOI: 10.1182/blood-2016-01-629790.
42. Milani P., Merlini G., Palladini G. Light chain amyloidosis. Mediterr J Hematol Infect Dis. 2018; 10(1): e2018022. DOI: 10.4084/MJHID.2018.022.
43. Kumar S., Dispenzieri A., Lacy M. Q., et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin. Oncol. 2012; 30(9): 989. DOI: 10.1200/JCO.2011.38.5724.
44. De Larrea C.F., Verga L., Morbini P., et al. A practical approach to the diagnosis of systemic amyloidoses. Blood. 2015; 125(14): 2239–44. DOI: 10.1182/blood-2014-11-609883.
45. Manabe S., Iwasaki C., Hatano M., et al. AL amyloidosis with non-amyloid forming monoclonal immunoglobulin deposition; a case mimicking AHL amyloidosis. BMC nephrol. 2018; 19(1): 337. DOI: 10.1186/s12882-018-1050-y.
46. Mai H.L., Sheikh-Hamad D., Herrera G.A., et al. Immunoglobulin heavy chain can be amyloidogenic: morphologic characterization including immunoelectron microscopy. Am J Surg Pathol. 2003; 27(4): 541–5. DOI: 10.1097/00000478-200304000-00016.
47. Miyazaki D. Yazaki M., Gono T., et al. AH amyloidosis associated with an immunoglobulin heavy chain variable region (VH1) fragment: a case report. Amyloid. 2008; 15(2): 125–8. DOI: 10.1080/13506120802006229.
48. Yazaki M., Fushimi T., Tokuda T., et al. A patient with severe renal amyloidosis associated with an immunoglobulin γ-heavy chain fragment. Am J Kid Dis. 2004; 43(5): e22-1. DOI: 10.1053/j.ajkd.2003.12.056.
49. Dyudina I.A. Transthyretin amyloidosis: current state of the problem. Serdceva nedostatnist` ta komorbidni stani. 2017; 1: 63–8 (In Russian).
50. Coelho T., Maurer M. S., Suhr O. B. THAOS — The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013; 29(1): 63–76. DOI: 10.1185/03007995.2012.754348.
Review
For citations:
Okhota V.K., Ryzhko V.V., Kovrigina A.M., Shupletsova I.A., Soboleva N.P., Gribanova E.O. μ-Heavy chain disease associated with systemic amyloidosis and non-amyloid deposits. Diffi culties in diagnosis and therapy. Russian journal of hematology and transfusiology. 2020;65(2):190-207. (In Russ.) https://doi.org/10.35754/0234-5730-2020-65-2-190-207
Views:
4433
Email this article 
