OJBD  Vol.5 No.3 , September 2015
Rare Case of a Patient Presenting with Parathyroid Hormone-Related Peptide Mediated Hypercalcemia and IgG Heavy Chain Disease: Case Report and Review of Literature
ABSTRACT
IgG Heavy Chain Disease (γHCD) is a rare plasma cell disorder. Hypercalcemia related to plasma cell dyscrasias is related to non-PTHrP related mechanisms. Here we describe the first case of a patient with γHCD and PTHrP related hypercalcemia. Methods: Patient case derived from chart review from 2011 to 2015. Literature review performed searching PubMed 1968-current. Results: The patient was diagnosed with hypercalcemia with elevated PTHrP and exclusion of other etiologies of hypercalcemia. She was diagnosed with (γHCD) by M-spike 0.64 g/dL, IFE showing a broad band of IgG heavy chain, without associated light chains and severe depression of the non-mono-clonal IgG. Serum immunoglobulins demonstrated elevated IgG (2110 mg/dL), normal IgA (46 mg/dL) and decreased IgM (<21 mg/dL). Bone marrow biopsy showed 5% PCs, non-clonal by kappa/lambda, but exclusive for IgG by IHC, without any staining for IgA or IgM. The patient was started on therapy with improved hypercalcemia and PTHrP levels. Conclusions: This is the first reported case of γHCD presenting with PTHrP related hypercalcemia. Given that skeletal involvement is uncommon in γHCD, hypercalcemia secondary to γHCD may at times be a PTHrP driven phenomenon and we recommend that this test be ordered in such cases.

Cite this paper
Hansra, D. , Liege, D. , Sujoy, V. , Offiong, I. , Wunsch, C. and Hoffman, J. (2015) Rare Case of a Patient Presenting with Parathyroid Hormone-Related Peptide Mediated Hypercalcemia and IgG Heavy Chain Disease: Case Report and Review of Literature. Open Journal of Blood Diseases, 5, 31-38. doi: 10.4236/ojbd.2015.53005.
References
[1]   Bieliauskas, S., et al. (2012) Gamma Heavy-Chain Disease: Defining the Spectrum of Associated Lymphoproliferative Disorders through Analysis of 13 Cases. The American Journal of Surgical Pathology, 36, 534-543. http://dx.doi.org/10.1097/PAS.0b013e318240590a

[2]   Tan, J.N., Kroll, M.H., O’Hara, C.J., Everett, P.C. and Erdogan, E. (2012) Gamma Heavy Chain Disease in a Patient with Underlying Lymphoplasmacytic Lymphoma of the Thyroid. Report of a Case and Comparison with Other Reported Cases with Thyroid Involvement. Clinica Chimica Acta, 413, 1696-1699.
http://dx.doi.org/10.1016/j.cca.2012.04.020

[3]   Zhang, L., et al. (2013) Unusual Concurrence of T-Cell Large Granular Lymphocytic Leukemia with Franklin Disease Manifested with Massive Splenomegaly. Leuk Lymphoma, 54, 205-208.
http://dx.doi.org/10.3109/10428194.2012.697561

[4]   Fermand, J.P., Brouet, J.C., Danon, F. and Seligmann, M. (1989) Gamma Heavy Chain “Disease”: Heterogeneity of the Clinicopathologic Features. Report of 16 Cases and Review of the Literature. Medicine (Baltimore), 68, 321-335. http://dx.doi.org/10.1097/00005792-198911000-00001

[5]   Witzig, T.E. and Wahner-Roedler, D.L. (2002) Heavy Chain Disease. Current Treatment Options in Oncology, 3, 247- 254. http://dx.doi.org/10.1007/s11864-002-0014-3

[6]   Matsubayashi, S., et al. (1985) Extramedullary Plasmacytoma of the Thyroid Gland Producing Gamma Heavy Chain. Endocrinol Jpn, 32, 427-433.

[7]   Ottó, S., Péter, I., Végh, S., Juhos, E. and Besznyák, I. (1986) Gamma-Chain Heavy-Chain Disease with Primary Thyroid Plasmacytoma. Archives of Pathology & Laboratory Medicine, 110, 893-896.

[8]   Ockhuizen, T., Jilderda, J.F. and Cazemier, T. (1984) Sequential Development of Waldenström’s Macroglobulinemia and Gamma-1-Heavy Chain Disease in a Single Patient. Clinical, Immunochemical, Immunofluorescent and Protein Studies. Acta Haematologica, 71, 53-59.
http://dx.doi.org/10.1159/000206510

[9]   Wahner-Roedler, D., Witzig, T.E., Loehrer, L.L. and Kyle, R.A. (2003) γ-Heavy Chain Disease Review of 23 Cases. Medicine, 84, 236-250. http://dx.doi.org/10.1097/01.md.0000085058.63483.7f

[10]   Takano, H., Nagata, K., Mikoshiba, M., Nakane, M., Kato, A. and Hamaguchi, H. (2008) Combination of Rituximab and Chemotherapy Showing Anti-Tumor Effect in Gamma Heavy Chain Disease Expressing CD20. American Journal of Hematology, 83, 938-939. http://dx.doi.org/10.1002/ajh.21284

[11]   Dickson, J.R., Harth, M., Bell, D.A., Komar, R. and Chodirker, W.B. (1989) Gamma Heavy Chain Disease and Rheumatoid Arthritis. Seminars in Arthritis and Rheumatism, 18, 247-251.
http://dx.doi.org/10.1016/0049-0172(89)90045-0

[12]   Castelino, D., Gray, F., D'Apice, A., et al. (1994) Primary Sjögren’s Syndrome and Gamma Heavy Chain Disease. Pathology, 26, 337-338. http://dx.doi.org/10.1080/00313029400169791

[13]   Alexander, M.P., Nasr, S.H., Watson, D.C., Méndez, G.P. and Rennke, H.G. (2011) Renal Crescentic Alpha Heavy Chain Deposition Disease: A Report of 3 Cases and Review of the Literature. American Journal of Kidney Diseases, 58, 621-625.

[14]   Oe, Y., Nakaya, I., Yahata, M., Sakuma, T., Sato, H. and Soma, J. (2010) A Case of γ1-Heavy Chain Deposition Disease Successfully Treated with Melphalan and Prednisolone Therapy. Internal Medicine, 49, 1411-1415. http://dx.doi.org/10.2169/internalmedicine.49.3499

[15]   Moulin, B., et al. (1999) Nodular Glomerulosclerosis with Deposition of Monoclonal Immunoglobulin Heavy Chains Lacking C(H)1. Journal of the American Society of Nephrology, 10, 519-528.

[16]   Rott, T., Vizjak, A., Lindic, J., Hvala, A., Perkovic, T. and Cernelc, P. (1998) IgG Heavy-Chain Deposition Disease Affecting Kidney, Skin, and Skeletal Muscle. Nephrology Dialysis Transplantation, 13, 1825-1828.
http://dx.doi.org/10.1093/ndt/13.7.1825

[17]   Herzenberg, A.M., Lien, J. and Magil, A.B. (1996) Monoclonal Heavy Chain (Immunoglobulin G3) Deposition Disease: Report of a Case. American Journal of Kidney Diseases, 28, 128-131.
http://dx.doi.org/10.1016/S0272-6386(96)90141-9

[18]   Lassoued, K., Picard, C., Danon, F., et al. (1990) Cutaneous Manifestations Associated with Gamma Heavy Chain Disease. Report of an Unusual Case and Review of Literature. Journal of the American Academy of Dermatology, 23, 988-991. http://dx.doi.org/10.1016/S0190-9622(08)80110-7

[19]   Papae, R.J., Rosenstein, R.W., Richards, F. and Yesner, R. (1978) Gamma Heavy Chain Disease Seen Initially as Gastric Neoplasm. Archives of Internal Medicine, 138, 1151-1153.
http://dx.doi.org/10.1001/archinte.138.7.1151

[20]   Faguet, G.B., Barton, B.P., Smith, L.L. and Garver, F.A. (1977) Gamma Heavy Chain Disease: Clinical Aspects and Characterization of a Deleted, Noncovalently Linked Gamma1 Heavy Chain Dimer (BAZ). Blood, 49, 495-505.

[21]   Franklin, E.C., Lowenstein, J., Bigelow, B. and Meltzer, M. (1964) Heavy Chain Disease—A New Disorder of Serum γ-Globulins: Report of the First Case. The American Journal of Medicine, 37, 332-350.
http://dx.doi.org/10.1016/0002-9343(64)90191-3

[22]   Cooper, D.L., Bolognia, J.L. and Lin, J.T. (1991) Atrophie Blanche in a Patient with Gamma-Heavy-Chain Disease. Archives of Dermatology, 127, 272-273.
http://dx.doi.org/10.1001/archderm.1991.01680020144031

[23]   Tasca, G., Iorio, R., Basile, U., et al. (2009) Progressive Multifocal Leukoencephalopathy in a Patient with Franklin Disease and Hypogammaglobulinemia. Journal of the Neurological Sciences, 284, 203-204.
http://dx.doi.org/10.1016/j.jns.2009.04.035

[24]   Yunokawa, K., Hagiyama, Y., Mochizuki, Y., Tanaka, N. and Ochi, M. (2007) Hypertrophic Spinal Pachymeningitis Associated with Heavy-Chain Disease. Journal of Neurosurgery: Spine, 7, 459-462.
http://dx.doi.org/10.3171/SPI-07/10/459

[25]   Shirakura, T., Kobayashi, Y., Murai, Y., Inoue, T. and Imamura, Y. (1976) A Case of Gamma Heavy Chain Disease Associated with Autoimmune Haemolytic Anaemia: Clinical, Haematological, Immunological and Pathological Details. Scandinavian Journal of Haematology, 16, 387-393.
http://dx.doi.org/10.1111/j.1600-0609.1976.tb00332.x

[26]   Eisner, S.B. and Mitnick, P.D. (1986) Hypercalcemia and Reversible Renal Failure in Heavy-Chain Disease. Southern Medical Journal, 79, 507-509. http://dx.doi.org/10.1097/00007611-198604000-00030

[27]   Swerdlow, S.H., Campo, E., Harris, N.L., et al. (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon.

[28]   Van Bergeijk, L., Biewenga, J. and Langenhuijsen, M.M.A.C. (1980) Gamma Heavy Chain Disease with an Unusually Benign Course. Clinical Laboratory Hematology, 2, 83-88.

[29]   Yazaki, M., Fushimi, T., Tokuda, T., et al. (2004) A Patient with Severe Renal Amyloidosis Associated with an Immunoglobulin Gamma-Heavy Chain Fragment. American Journal of Kidney Diseases, 43, e23-e28. http://dx.doi.org/10.1053/j.ajkd.2003.12.056

[30]   Ellis, V.M., Cowley, D.M., Taylor, K.M. and Marlton, P. (1992) Gamma Heavy Chain Disease Developing in Association with Myelodysplastic Syndrome. British Journal of Haematology, 81, 125-126.
http://dx.doi.org/10.1111/j.1365-2141.1992.tb08184.x

[31]   O’connor, G.T., Wyant, H.E., Innes, D.J., Normansell, D.E. and Hess, C.E. (1985) Gamma Heavy Chain Disease; Report of a Case with Trisomy of Chromosome 7. Cancer Genetics and Cytogenetics, 15, 1-5.
http://dx.doi.org/10.1016/0165-4608(85)90125-6

[32]   Gallart, T., Canals, J., Cañadell, E., et al. (1978) A New Case of Gamma-Heavy Chain Disease. Acta Haematologica, 59, 262-276.
http://dx.doi.org/10.1159/000207781

[33]   Kuroyanagi, T., Kura, K., Akamatau, Y. and Arao, T. (1979) A Case Report of the Immunodysplasia Syndrome and Heavy Chain Disease Associated with Subacute Bacterial Endocarditis. The Tohoku Journal of Experimental Medicine, 128, 325-331. http://dx.doi.org/10.1620/tjem.128.325

[34]   Roda, L., David, M.J., Souche, S. and Creyssel, R. (1985) Gamma Heavy Chain Disease DUB: Clinical Immunochemical and Pathological Studies. Haematologica, 70, 115-119.

[35]   Inoue, D., Matsushita, A., Kiuchi, M., et al. (2012) Successful Treatment of Gamma-Heavy-Chain Disease with Rituximab and Fludaribine. Acta Haematologica, 128, 139-143. http://dx.doi.org/10.1159/000339097

[36]   Wager, O., Rasanen, J.A., Lindeberg, L. and Makala, V. (1969) Two Cases of IgG Heavy-Chain Disease. Acta Pathologica Microbiologica Scandinavica, 75, 350-352.

[37]   Agrawal, S., Abboudi, Z., Matutes, E. and Catovsky, D. (1994) First Report of Fludarabine in Gamma-Heavy Chain Disease. British Journal of Haematology, 88, 653-655.
http://dx.doi.org/10.1111/j.1365-2141.1994.tb05094.x

[38]   Brioli, A., Zamagni, E., Pasquali, S., et al. (2012) Long-Term Follow-Up after Autologous Stem Cell Transplantation for Light- and Heavy-Chain Deposition Disease. Bone Marrow Transplantation, 47, 1248-1249. http://dx.doi.org/10.1038/bmt.2011.252

 
 
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