HEAVY-CHAIN DISEASES AND MYELOMA-ASSOCIATED FANCONI SYNDROME: AN UPDATE
Main Article Content
Keywords
B-cell malignancies, Fanconi syndrome, heavy chain disease, monoclonal gammopathy, multiple myeloma
Abstract
The heavy chain diseases (HCDs) are rare B-cell malignancies characterized by the production of a monoclonal immunoglobulin heavy chain without an associated light chain. There are three types of HCD, defined by the class of immunoglobulin heavy chain produced: IgA (?-HCD), IgG (?-HCD), and IgM (?-HCD). Alpha-HCD is the most common and usually occurs as intestinal malabsorption in a young adult from a country of the Mediterranean area. Gamma- and ?-HCDs are more rare and associated to a B-cell non-Hodgkin lymphoma that produces an abnormal Ig heavy chain. These patients may occasionally be diagnosed with a monoclonal gammopathy of undetermined significance (MGUS). Fanconi syndrome, on the other hand, can be primary (inherited) or secondary (acquired). The only exception to this rule is the idiopathic form. Adult acquired Fanconi syndrome can be a rare complication of a monoclonal gammopathy. At diagnosis, most patients have a MGUS or smoldering multiple myeloma, with renal failure and evidence of osteomalacia. During follow-up, patients can develop end-stage renal disease. Chemotherapy provides little benefit on renal function.
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References
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2. Fermand JP, Brouet JC. Heavy-chain diseases. Hematol Oncol Clin North Am. 1999;13:1281-94.
3. Goossens T, Klein U, Kuppers R. Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease. Proc Natl Acad Sci U S A. 1998;95:2463-8.
4. Munshi NC, Digumarthy S, Rahemtullah A. Case records of the Massachusetts General Hospital. Case 13-2008. A 46-year-old man with rheumatoid arthritis and lymphadenopathy. N Engl J Med. 2008;358:1838-48.
5. Corcos D, Osborn MJ, Matheson LS. B-cell receptors and heavy chain diseases: guilty by association? Blood. 2011;117:6991-8.
6. Harris NL, Isaacson PG, Grogan TM, Jaffe ES. Heavy chain diseases. In: Swerdlow SH, Campo E, Harris NL, et al, editors. WHO classification of tumours of the haematopoietic and lymphoid tissues. Lyon: IARC; 2008;196-9.
7. Fanconi G. Der fruhinfantile nephrotisch-glykosurische Zwergwuchs mit hypophosphatamischer Rachitis. Jahrb Kinderheilkunde (Berlin). 1936;147:299-338.
8. Lobitz S, Velleuer E. Guido Fanconi (1892–1979): a jack of all trades. Nat Rev Cancer. 2006;6:893-898.
9. Hall AM, Bass P, Unwin RJ. Drug-induced renal Fanconi syndrome. QJM. 2014;107:261-9.
10. Foreman JW. Fanconi syndrome and other proximal tubule disorders. In: Comprehensive Clinical Nephrology , 5th Edition. Richard JJ, Feehally J, Floege J eds. 2014; pp 590-600.
11. Maldonado JE, Velosa JA, Kyle RA, Wagoner RD, Holley KE, Salassa RM. Fanconi syndrome in adults. A manifestation of a latent form of myeloma. Am J Med. 1975;58:354–364.
12. Schillinger F, Hopfner C, Montagnac R, Milcent T. IgG kappa myeloma with Fanconi's syndrome and crystalline inclusions. Immunohistochemical and ultrastructural study. Presse Méd . 1993;22:675–679.
13. Seligmann M, Danon F, Hurez D, Mihaesco E, Preud'homme JL. Alpha-chain disease: a new immunoglobulin abnormality. Science. 1968;162:1396-7.
14. Wahner-Roedler DL, Kyle RA. Heavy chain diseases. Best Pract Res Clin Haematol.2005;18:729-46.
15. Doe WF, Henry K, Hobbs JR, Jones FA, Dent CE, Booth CC. Five cases of alpha chain disease. Gut. 1972;13:947-57.
16. Takahashi K, Naito M, Matsuoka Y, Takatsuki K. A new form of alpha-chain disease with generalized lymph node involvement. Pathol Res Pract. 1988;183:717-23.
17. Stoop JW, Ballieux RE, Hijmans W, Zegers BJ. Alpha-chain disease with involvement of the respiratory tract in a Dutch child. Clin Exp Immunol. 1971;9:625-35.
18. Franklin EC, Lowenstein J, Bigelow B, Meltzer M. Heavy chain disease—a new disorder of serum gamma-globulins: report of the first case. Am J Med. 1964;37:332-50.
19. Dammacco F, Rigoli E, Ferrarese M, Bonomo L. Gamma heavy chain disease in a young girl. Haematologica. 1976;61:278-290.
20. Wahner-Roedler DL, Witzig TE, Loehrer LL, Kyle RA. Gamma-heavy chain disease: review of 23 cases. Medicine (Baltimore). 2003;82:236-50.
21. Bieliauskas S, Tubbs RR, Bacon CM, Eshoa C, Foucar K, Gibson SE, Kroft SH, Sohani AR, Swerdlow SH, Cook JR. Gamma heavy-chain disease: defining the spectrum of associated lymphoproliferative disorders through analysis of 13 cases. Am J Surg Pathol. 2012;36:534-43.
22. Fermand JP, Brouet JC, Danon F, Seligmann M. Gamma heavy chain “disease”: heterogeneity of the clinicopathologic features. Report of 16 cases and review of the literature. Medicine (Baltimore). 1989;68:321-35.
23. Lecuit M, Abachin E, Martin A, Poyart C, Pochart P, Suarez F, Bengoufa D, Feuillard J, Lavergne A, Gordon JI, Berche P, Guillevin L, Lortholary O. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med. 2004;350:239-48.
24. Peterson MC. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. Engl J Med. 2004;350:1685-6.
25. Isaacson PG. Extranodal marginal zone lymphoma: MALT lymphoma. In: Jaffe ES, Harris NL, Vardiman JW, et al, editors. Hematopathology. St. Louis: Elsevier; 2011. p. 291-305.
26. Forte FA, Prelli F, Yount WJ, Jerry LM, Kochwa S, Franklin EC, Kunkel HG. Heavy chain disease of the gamma (gamma M) type: report of the first case. Blood. 1970;36:137-44.
27. Ballard HS, Hamilton LM, Marcus AJ, Illes CH. A new variant of heavy-chain disease (mu-chain disease). N Engl J Med. 1970;282:1060-2.
28. Dammacco F, Bonomo L, Franklin EC. A new case of mu heavy chain disease: clinical and immunochemical studies. Blood. 1974;43:713-719.
29. Witzens M, Egerer G, Stahl D, Werle E, Goldschmidt H, Haas R. A case of mu heavy-chain disease associated with hyperglobulinemia, anemia, and a positive Coombs test. Ann Hematol. 1998;77:231-4.
30. Iwasaki T, Hamano T, Kobayashi K, Kakishita E. A case of mu-heavy chain disease: combined features of mu-chain disease and macroglobulinemia. Int J Hematol. 1997;66:359-65.
31. Maeda A, Mori M, Torii S, Nagai Y, Togami K, Fujita H, Kurata M, Matsushita A, Nagai K, Imai Y, Takahashi T. Multiple extranodal tumors in mu-heavy chain disease. Int J Hematol. 2006;84:286-7.
32. Kinoshita K, Yamagata T, Nozaki Y, Sugiyama M, Ikoma S, Funauchi M, Kanamaru A. Mu-heavy chain disease associated with systemic amyloidosis. Hematology. 2004;9:135-7.
33. Dammacco F, Antonaci S, Miglietta A. Two-dimensional immunolectrophoresis as a diagnostic tool for heavy chain disease. Boll Ist Sieroter Milan. 1975;54:460-465.
34. Seligmann M. Alpha chain disease: immunoglobulin abnormalities, pathogenesis and current concepts. Br J Cancer Suppl. 1975;2:356-61.
35. Al-Saleem T, Al-Mondhiry H. Immunoproliferative small intestinal disease (IPSID): a model for mature B-cell neoplasms. Blood. 2005;105:2274-80.
36. Halphen M, Najjar T, Jaafoura H, Cammoun M, Tufrali G. Diagnostic value of upper intestinal fiber endoscopy in primary small intestinal lymphoma. A prospective study by the Tunisian-French Intestinal Lymphoma Group. Cancer. 1986;58:2140-5.
37. Isaacson PG, Dogan A, Price SK, Spencer J. Immunoproliferative small-intestinal disease. An immunohistochemical study. Am J Surg Pathol. 1989;13:1023-33.
38. Parsonnet J, Isaacson PG. Bacterial infection and MALT lymphoma. N Engl J Med. 2004;350:213-5.
39. Presti BC, Sciotto CG, Marsh SG. Lymphocytic lymphoma with associated gamma heavy chain and IgM-lambda paraproteins. An unusual biclonal gammopathy. Am J Clin Pathol. 1990;93:137-41.
40. Maisnar V, Tichy M, Stulik J, Urban P, Adam Z, Kadlckova E, Vavrova J, Palicka V, Jebavy L, Kodet R, Buchler T, Hajek R. Capillary immunotyping electrophoresis and high resolution two-dimensional electrophoresis for the detection of mu-heavy chain disease. Clin Chim Acta. 2008;389:171-3.
41. Preud’homme JL, Bauwens M, Dumont G, Goujon JM, Dreyfus B, Touchard G. Cast nephropathy in mu heavy chain disease. Clin Nephrol. 1997;48:118-21.
42. Courtois L, Sujobert P. Morphologic features of ?-heavy-chain disease. Blood. 2017;130:558.
43. Yanai M, Maeda A, Watanabe N, Sugimoto N, Matsushita A, Nagai K, Oida T, Takahashi T. Successful treatment of mu-heavy chain disease with fludarabine monophosphate: a case report. Int J Hematol. 2004;79:174-7.
44. Bonomo L, Dammacco F, Marano R, Bonomo GM. Abdominal lymphoma and alpha chain disease. Report of three cases. Am J Med. 1972;52:73–86.
45. Alpha-chain disease and related small-intestinal lymphoma: a memorandum. Bull World Health Organ. 1976;54:615-24.
46. Fine KD, Stone MJ. Alpha-heavy chain disease, Mediterranean lymphoma, and immunoproliferative small intestinal disease: a review of clinicopathological features, pathogenesis, and differential diagnosis. Am J Gastroenterol. 1999;94:1139-52.
47. Ben-Ayed F, Halphen M, Najjar T, Boussene H, Jaafoura H, Bouguerra A, Ben Salah N, Mourali N, Ayed K, Ben Khalifa H, Garoui H., Gargouri M., Tufrali G. Treatment of alpha chain disease. Results of a prospective study in 21 Tunisian patients by the Tunisian-French intestinal Lymphoma Study Group. Cancer. 1989;63:1251-6.
48. Salem PA, Estephan FF. Immunoproliferative small intestinal disease: current concepts. Cancer J. 2005;11:374-82.
49. Akbulut H, Soykan I, Yakaryilmaz F, Icii F, Aksoy F, Haznedaroglu S, Yildirim S. Five-year results of the treatment of 23 patients with immunoproliferative small intestinal disease: a Turkish experience. Cancer. 1997;80:8-14.
50. Martin IG, Aldoori MI. Immunoproliferative small intestinal disease: Mediterranean lymphoma and alpha heavy chain disease. Br J Surg. 1994;81:20-4.
51. Inoue D, Matsushita A, Kiuchi M, Takiuchi Y, Nagano S, Arima H, Mori M, Tabata S, Yamashiro A, Maruoka H, Oita T, Imai Y, Takahashi T. Successful treatment of gamma-heavy-chain disease with rituximab and fludarabine. Acta Haematol. 2012;128:139-43.
52. Witzig TE, Wahner-Roedler DL. Heavy chain disease. Curr Treat Options Oncol. 2002;3:247-54.
53. Lee DB, Drinkard JP, Rosen VJ, Gonick HC. The adult Fanconi syndrome: observations on etiology, morphology, renal function and mineral metabolism in three patients. Medicine (Baltimore). 1972;51:107–138,
54. Aucouturier P, Bauwens M, Khamlichi AA, Denoroy L, Spinelli S, Touchard G, Preud'homme JL, Cogné M. Monoclonal Ig L chain and L chain V domain fragment crystallization in myeloma-associated Fanconi's syndrome. J. Immunol. 1993;150:3561–3568.
55. Engle RL, Wallis LA. Multiple myeloma and the adult Fanconi syndrome. I. Report of a case with crystal-like deposits in the tumor cells and in the epithelial cells of the kidney. Am. J. Med. 1957;22:5–12
56. Costanza DJ, Smoller M. Multiple myeloma with the Fanconi syndrome: study of a case, with electron microscopy of the kidney. Am J Med. 1963;34:125–133
57. Deret S, Denoroy L, Lamarine M Vidal R, Mougenot B, Frangione B, Stevens FJ, Ronco PM, Aucouturier P. Kappa light chain-associated Fanconi’s syndrome: molecular analysis of monoclonal immunoglobulin light chains from patients with and without intracellular crystals. Protein Eng 1999; 12: 363–369.
58. Messiaen T, Deret S, Mougenot B, Bridoux F, Dequiedt P, Dion JJ, Makdassi R, Meeus F, Pourrat J, Touchard G, Vanhille P, Zaoui P, Aucouturier P, Ronco PM: Adult Fanconi syndrome secondary to light chain gammopathy. Clinicopathologic heterogeneity and unusual features in 11 patients. Medicine (Baltimore) 2000; 79: 135–154.
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