Diffuse plane normolipemic xanthomatosis and necrobiotic xanthogranuloma associated with monoclonal gammopathy – determining the disease stage with PET‑ CT and treatment experience. Two case studies and literature review
Authors:
Z. Adam 1; L. Zahradová 1; M. Krejčí 1; L. Pour 1; R. Koukalová 2; Z. Řehák 2; J. Feit 3; L. Křen 3; M. Mechl 4; V. Vašků 5; A. Sirotková 6; R. Hájek 1; J. Mayer 1
Authors place of work:
Interní hematologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Jiří Vorlíček, CSc. 2 Oddělení PET CT Masarykova onkologického ústavu Brno, přednosta prim. MU Dr. Karol Bolčák, Ph. D. 3 Ústav patologie Lékařské fak
1
Published in the journal:
Vnitř Lék 2010; 56(11): 1158-1168
Category:
Case Reports
Summary
Monoclonal gammopathy may manifest itself through a range of skin disorders, including plane normolipemic xanthoma and necrobiotic xanthogranuloma. The present paper describes two patients with these cutaneous symptoms. The first has extensive areas of skin affected by flat xanthomas, monoclonal gammopathy with > 10% infiltration of bone marrow with clonal plasmocytes and, according to PET‑ CT, unclear lymphadenopathy in the retroperitoneal area. The size of this lymphadenopathy (histologically no malignant infiltration and no confirmed infectious aetiology) has not changed significantly over a 4‑year follow‑up. Repeated PET‑ CT scans showed decrease in SUV value in this infiltration from 7.5 to 3.8. Four cycles of treatment with a combination of bortezomib, cyclophosphamide and dexamethasone brought neither reduction in monoclonal immunoglobulin nor change to skin morphology. We believe that the abdominal lymphadenopathy is associated with xanthomatosis but have been unable to confirm this unequivocally. The second patient is being followed up for more than 10 years, originally for MGUS, later for asymptomatic multiple myeloma. Last year, painful subcutaneous and cutaneous infiltrates, isolated on an upper limb and more frequent on lower limb, started to occur. These infiltrates are palpable. PET‑ CT imaging provided an excellent depiction of these infiltrates, showing no pathology on the head, chest and abdomen and no osteolytic foci on the skeleton. CT imaging showed clearly numerous infiltrates in the skin and subcutaneous tissue of lower limbs, particularly both shanks, reaching up to 2 cm in depth. The largest infiltrate, measuring 3.5 by 2 by 10 cm, was identified in the distal dorsal part of the right shank. PET imaging of lower limbs showed distinctly pathological accumulation in all infiltrates described above; the accumulation of glucose in the lower part of the right shank reached 10.0 SUV. CT images of lower limbs showed increased density saturated hypodermis even in the areas where there is no increased accumulation of 18fluoroglucose. Following 40 Gy irradiation, the size of infiltrate in the radiated area decreased and their soreness ceased. Conclusion: PET‑ CT imaging offered information on extra- cutaneous signs of plane normolipemic xanthomas and provided excellent depiction of the areas of the skin and hypodermis affected by necrobiotic xanthogranuloma. Chemotherapy with cyclophosphamide, bortezomib and dexamethasone brought no reduction in monoclonal immunoglobulin concentration, and no reduction in plane normolipemic xanthomas. Radiotherapy targeted at large foci of xanthogranulomas led to partial regression and ceased infiltrate soreness.
Key words:
monoclonal gammopathy – multiple myeloma – normolipemic xanthomas – necrobiotic xanthogranuloma – bortezomib – dexamethasone – cyclophosphamide – PET‑ CT imaging
Zdroje
1. Janssen D, Fölster‑ Holst R, Harms D et al. Clonality in juvenile xanthogranuloma. Am J Surg Pathol 2007; 31: 812– 813.
2. Decaux O, Laurat E, Perlat A et al. Systemic manifestations of monoclonal gammopathy. Eur J Intern Med 2009; 20: 457– 461.
3. Alexander AS, Turner R, Uniate L et al. Xanthoma disseminatum: a case report and literature review. Br J Radiol 2005; 78: 153– 157.
4. Vick VL, Wilson MW, Fleming JC et al. Orbital and eyelid manifestations of xanthogranulomatous diseases. Orbit 2006; 25: 221– 225.
5. Asarch A, Thiele JJ, Ashby‑ Richardson et al. Cutaneous disseminated xanthogranuloma in adult: a case report and review of the literature. Cutis 2009; 83: 243– 249.
6. Altman J, Winkelmann RK. Diffuse normolipemic planae xanthoma. Generalized xanthelasma. Arch Dermatol 1962; 85: 633– 640.
7. Lynch PJ, Winkelmann RK. Generalized plane xanthoma and systemic disease. Arch Dermatol 1966; 93: 639– 640.
8. Williford PM, White WL, Jorizzo JL et al. The spectrum of normolipemic plane xanthoma. Am J Dermatopathol 1993; 15: 572– 575.
9. Taylor JS, Lewis LA, Battle JD Jr et al. Plane xanthoma and multiple myeloma with lipoprotein‑paraprotein complexing. Arch Dermatol 1978; 114: 425– 431.
10. Marcoval J, Moreno A, Bordas X et al. Diffuse plane xanthoma: clinicopathologic study of 8 cases. J Am Acad Dermatol 1998; 39: 439– 442.
11. Wood AJ, Wagner MV, Abbott JJ et al. Necrobiotic xanthogranuloma: a review of 17 cases with emphasis on clinical and pathologic correlation. Arch Dermatol 2009; 145: 279– 284.
12. Kossard S, Winkelmann RK. Necrobiotic xanthogranuloma with paraproteinemia. J Am Acad Dermatol 1980; 3: 257– 270.
13. Ugurlu S, Bartley GB, Gibbon LE. Necrobiotic xanthogranuloma: long term outcome of ocular and systemic involvement. Am J Ophthalmol 2000; 129: 651– 657.
14. Mehregan DA, Winkelmann RK. Necrobiotic xanthogranuloma. Arch Dermatol 1992; 128: 94– 100.
15. Finan MC, Winkelmann RK. Necrobiotic xanthogranuloma with paraproteinemia. A review of 22 cases. Medicine (Baltimore) 1986; 65: 376– 388.
16. Martínez Fernández M, Rodríguez Prieto MA, González J et al. Necrobiotic xanthogranloma associated with myeloma. J Eur Acad Dermatol Venereol 2004; 18: 328– 331.
17. Oumeish OY, Oumeish I, Tarawneh Met al. Necrobiotic xanthogranuloma asso-ciated with paraproteinemia and non‑Hodg-kin’s lymphoma developing into chronic lymphocytic leukemia: the first case reported in the literature and review of the literature. Int J Dermatol 2006; 45: 306– 310.
18. Winkelmann RK, Dahl PR, Perniciaro C. Asteroid bodies and other cytoplasmic inclusions in necrobiotic xanthogranuloma with paraproteinemia. J Am Acad Dermatol 1998; 38: 967– 970.
19. Randell PL, Heenan PJ. Necrobiotic xanthogranuloma with paraproteinaemia. Australas J Dermatol 1999; 40: 114– 115.
20. Robertson DM, Winkelmann RK. Ophthalmic features of necrobiotic xanthogranuloma with paraproteinemia. Am J Ophthalmol 1984; 97: 173– 183.
21. Adam Z, Balšíková K, Pour L et al. Diabetes insipidus, následovaný po 4 letech dysartrií a lehkou pravostrannou hemiparézou – první klinické příznaky Erdheimovy-Chesterovy nemoci. Popis a zobrazení případu s přehledem informací o této nemoci. Vnitřní Lék 2009; 55: 1173–118.
22. Martínez Fernández M, Rodríguez Prieto MA, González J et al. Necrobiotic xanthogranloma associated with myeloma. J Eur Acad Dermatol Venereol 2004; 18: 328– 331.
23. Fernández‑ Herrera J, Pedraz J. Necrobiotic xanthogranuloma. Semin Cutan Med Surg 2007; 26: 108– 113.
24. Machado S, Alves R, Lima M et al. Cutaneous necrobiotic xanthogranuloma (NXG): successfully treated with low dose chlorambucil. Eur J Dermatol 2001; 11: 458– 462.
25. Hunter L, Burry AF. Necrobiotic xanthogranuloma: a systemic disease with paraproteinemia. Patology 1985; 17: 533– 536.
26. Fortson JS, Schroeter AL. Necrobiotic xanthogranuloma with IgA paraproteinemia and extracutaneous involvement. Am J Dermatopathol 1990; 12: 579– 584.
27. Bara C, Barbarot S, Hamitou M et al. Systemic necrobiotic xanthogranuloma with initial pericardial and pulmonary involvement. Ann Dermatol Venereol 2003; 130: 341– 344.
28. Novak PM, Robbins TO, Winkelmann RK. Necrobiotic xanthogranuloma with myocardial lesions and nodular transformation of the liver. Hum Pathol 1992; 23: 195– 196.
29. Shah KC, Poonnoose SI, Georgie R et al. Necrobiotix xanthogranuloma with cutaneous and cerebral manifestations. Case report and review of the literature. J Neurosurg 2004; 100: 1111– 1114.
30. Umbert I, Winkelmann RK. Necrobiotic xanthogranuloma with cardiac involvement. Br J Dermatol 1995; 133: 438– 443.
31. Yasukawa K, Kato N, Hamasaka A et al. Necrobiotic xanthogranuloma: isolated skeletal and muscle involvement and unusual changes. J Am Acad Dermatol 2005; 52: 729– 731.
32. Winkelmann RK, Litzow MR, Umbert IJ et al. Giant cell granulomatous pulmonary and myocardial lesions in necrobiotic xanthogranuloma with paraproteinemia. Mayo Clin Proc 1997; 72: 1028– 1033.
33. Bakir B, Unuvar E, Terzibasioglu E et al. Atypical lung involvement in a patient with systemic juvenile xanthogranuloma. Pediatr Radiol 2007; 37: 325– 327.
34. Amer R, Peer J. Pappo O et al. Necrobiotic xanthogranuloma associated with choroidal infiltration and syncytial giant cell hepatitis. J Neuroophthalmol 2005; 25: 189– 192.
35. Betts CM, Pasquinelli C, Costa AM et al. Necrobiotic xanthogranuloma without periorbital involvement: an ultrastructural investigation. Ultrastruct Pathol 2001; 25: 437– 444.
36. Orsey A, Paessler M, Lange BJ et al. Central nervous system juvenile xanthogranuloma with malignant transformation. Pediatr Blood Cancer 2008; 50: 927– 930.
37. Ozcelik U, Dogru D, Akcoren Z et al. Xanthoma disseminatum: a child with respiratory system involvement and bronchiectasias. Pediatr Pulmonol 2005; 39: 84– 87.
38. Smith HC, Sargent LD, Lundin DB. Necrobiotic xanthogranuloma of the chest wall. Dermatol Online J 2006; 12: 12– 16.
39. Stockman A, Delanghe J, Geerts ML et al. Diffuse plane normolipaemic xanthomatosis in a patient with chronic lymphatic leukaemia and monoclonal gammopathy. Dermatology 2002; 204: 351– 354.
40. Stork J, Kodetová D, Vosmík E et al. Necrobiotic xanthogranuloma presenting as a solitary tumor. Am J Dermatopathol 2000; 22: 453– 456.
41. Spicknall KE, Mehregan DA et al. Necrobiotic xanthogranuloma. Int J Dermatol 2009; 48: 1– 10.
42. Tucker NA, Discepola MJ, Blanco G et al. Necrobiotic xanthogranuloma without dermatologic involvement. Can J Ophthalmol 1997; 32: 396– 399.
43. Ferrara G, Palombi N, Lipizzi A et al. Nonnecrobiotic necrobiotic xanthogranuloma. Am J Dermatopathol 2007; 29: 306– 308.
44. Bullock JD, Bartley GB, Campbell RJ et al. Necrobiotic xanthogranuloma with paraproteinemia. Case report and pathogenetic theory. Trans Am Ophthalmol Soc 1986; 84: 342– 354.
45. Hafner O, Witte T, Schmidt RE et al. Necrobiotic xanthogranuloma in IgG κ plasmacytoma and Quincke edema. Hautarzt 1994; 45: 339– 343.
46. Matsuura F, Yamashita S, Hirano K et al. Activation of monocytes in vivo causes intracellular accumulation of lipoprotein‑derived lipids and marked hypocholesterolemia – a possible pathogenesis of necrobiotic xanthogranuloma. Atheroslerosis 1999; 142: 355– 365.
47. Jeziorska M, Hassan A, Mackness MI et al. Clinical, biochemical, and immunohistochemical features of necrobiotic xanthogranulomatosis. J Clin Pathol 2003; 56: 64– 68.
48. Langlois S, Brochot P, Reguiai Z et al. Necrobiotic xanthogranuloma with multiple myeloma. Case report and pathogenic hypotheses. Joint Bone Spine 2006; 73: 120– 122.
49. Zelger B, Eisendle K, Mensing C et al. Detection of spirochetal micro‑organism by focus bloating microscopy in necrobiotic xanthogranuloma. J Am Acad Dermatol 2007; 57: 1026– 1030.
50. Chang SE, Lee WS, Lee MW et al. A case of necrobiotic xanthogranuloma without paraproteinemia presenting as a solitary tumor on the thigh. Int J Dermatol 2003; 42: 470– 472.
51. Yagci B, Varan A, Altinock G et al. Xanthoma disseminatum in a child with cranial involvement. J Pediatr Hematol Oncol 2008; 30: 310– 312.
52. Weitzman S, Jaffe R. Uncommon histiocytic disorders: the non Langerhans cell histiocytoses. Pediatr Blood Cancer 2005; 45: 256– 264.
53. Moore FO, Berne JD, Fox AD. Mesenteric panniculitis and Erdheim‑ Chester disease: xanthogranulomatous diseases confused with malignancy. J Am Coll Surg 2007; 204: 326– 327.
54. Nestle FO, Hofbauer G, Burg G. Necrobiotic xanthogranuloma with monoclonal gammopathy of the IgG l type. Dermatology 1999; 198: 434– 435.
55. Wee SA, Shupack JL. Necrobiotic xanthogranuloma. Dermatol Online J 2005; 11: 24– 25.
56. Cornblath WT, Dotan SA, Trobe JD et al. Varied clinical spectrum of necrobiotic xanthogranuloma. Ophthalmology 1992; 99: 103– 107.
57. Elner VM, Mintz R, Demirci H et al. Local corticosteroid treatment of eyelid and orbital xanthogranuloma. Trans Am Ophthalmol Soc 2005; 103: 69– 73.
58. Sabet LM, Wexler D, Salama S et al. An unusual cause of refractive chronic bilateral leg ulceration. J Cutan Med Surg 2004; 8: 432– 437.
59. Chave TA, Chowdhury MM, Holt PJ. Recalcintrant necrobiotic xantohogranuloma responding do pulsed high‑dose dexamethasone plus maintenance therapy with oral prednisone. Br J Dermatol 2001; 144: 158– 161.
60. Valentine EA, Friedman HD, Zamkoff KW et al. Necrobiotic xanthogranuloma with IgA multiple myeloma: a case report and literature review. Am J Hematol 1990; 35: 283– 285.
61. Venencie PY, Le Bras P, Toan ND et al. Recombinant interferon a‑ 2b treatment of necrobiotic xanthogranuloma with paraproteinemia. J Am Acad Dermatol 1995; 32: 666– 667.
62. Scupham RK, Fretzin DB. Necrobiotic xanthogranuloma with paraproteinemia. Arch Pathol Lab Med 1989; 113: 1389– 1391.
63. Plotnick H, Taniguchi Y, Hashimoto K et al. Periorbital necrobiotix xanthogranuloma and stage I multiple myeloma. Ultrastructure and response to pulsed dexamethasone documented by magnetic resonance imaging. J Am Acad Dermatol 1991; 25:373– 377.
64. Kossard S, Chow E, Wilkinson B et al. Lipid and giant cell poor necrobiotic xanthogranuloma. J Cutan Pathol 2000; 27: 374– 378.
65. Wells J, Gillespie R, Zardawi I. A case of recalcitrant necrobiotic xanthogranuloma. Australas J Dermarol 2004; 45: 213– 215.
66. Meyer S, Szeimies RM, Landthaler M et al. Cyclophosphamide‑ dexamethasone pulsed therapy for treatment of recalcitrant necrobiotic xanthogranuloma with paraproteinemia and ocular involvement. Br J Dermatol 2005; 153: 443– 445.
67. Stover DG, Alapati S, Regueira O et al. Treatment of juvenile xanthogranuloma. Pediatr Blood Cancer 2008; 51: 130– 133.
68. Seaton, ED, Pillai GJ, Chu AC. Treatment of xanthoma disseminatum with cylophosphamide. Br J Dermatol 2004; 150: 346– 349.
69. Flann S, Wain EM, Halpern S et al. Necrobiotic xanthogranuloma with paraproteinaemia. Clin Exp Dermatol 2006; 31: 248– 251.
70. Chave TA, Hutchinson PE. Necrobiotic xanthogranuloma with two monoclonal paraproteins and no periorbital involvement at presentation. Clin Exp Dermatol 2001; 26: 493– 496.
71. Hauser C, Schifferli J, Saurat JH. Complement consumption in a patient with necrobiotic xanthogranuloma and paraproteinemia. J Am Acad Dermatol 1991; 24: 908– 911.
72. Torabian SM, Fazel N, Knuttel R. Necrobiotic xanthogranuloma treated with chlorambucil. Dermatol Online J 2006; 12: 11– 12.
73. Luck J, Layton A, Noble BA. Necrobiotix xanthogranuloma with orbital involvement. J R Soc Med 1992; 85: 357– 358.
74. Criado PR, Vasconcellos C, Pegas JR et al. Necrobiotic xanthogranuloma with l paraproteinemia: case report of successful treatment with melphalan and prednisone. J Dermatolog Treat 2002; 13: 87– 89.
75. Ito Y, Nishimura K, Yamanaka K et al. Necrobiotic xanthogranuloma with paraproteinemia: an atypical case. J Dtsch Dermatol Ges 2008; 6: 40– 43.
76. Russo CG. Necrobiotic xanthogranuloma with scleroderma. Cutis 2002; 70: 311– 316.
77. Saeki H, Tomita M, Kai H et al. Necro-biotic xanthogranuloma with paraproteinemia successfully treated with melphalan, prednisolone and skin graft. J Dermatol 2007; 34: 795– 797.
78. Wilhelmus KR, Yen MT, Rice L et al. Necrobiotic xanthogranuloma with posterior scleritis. Arch Ophthalmol 2006; 124: 748.
79. Ziemer M, Wedding U, Sander CS et al. Necrobiotic xanthogranuloma – rapid progression under treatment with melphalan. Eur J Dermatol 2005; 15: 363– 365.
80. Hayden A, Wilson DJ, Rosenbaum JT. Management of orbital xanthogranuloma with methotrexate. Br J Ophthalmol 2007; 91: 434– 436.
81. Georgiou S, Monastirli A, Kapranos N et al. Interferon a monotherapy for necrobiotic xanthogranuloma. Acta Derm Venereol 1999; 79: 484– 485.
82. Finelli LG, Ratz JL. Plasmapheresis, a treatment modality for necrobiotic xanthogranuloma. J Am Acad Dermatol 1987; 17: 351– 354.
83. Lorenz S, Hohenleutner S, Hohenleutner U et al. Treatment of diffuse plane xanthoma of the face with the erbium: YAG laser. Arch Dermatol 2001; 137: 1413– 1415.
84. Vieira V, Del Pozo J, Martínez W et al. Necrobiotic xanthogranuloma associated with lymphoplasmacytic lymphoma. Palliative treatment with carbon dioxide laser. Eur J Dermatol 2005; 15: 182– 185.
85. Goede JS, Misselwitz B, Taverna C et al. Necrobiotic xanthogranuloma successfully treated with autologous stem cell transplantation. Ann Hematol 2007; 86: 303– 306.
86. Silapunt S, Chon SY. Generalized necrobiotic xanthogranuloma successfully treated with lenalidomide. J Drugs Dermatol 2010; 9: 273– 276.
87. Histiocyte society. Available from: www.histiocytesociety.org/ site/ .
Štítky
Diabetology Endocrinology Internal medicineČlánok vyšiel v časopise
Internal Medicine
2010 Číslo 11
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