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marrow necrosis in a patient with non-Hodgkin lymphoma

Dilek ARGON1, Mustafa ÇET‹NER1, Cafer ADIGÜZEL1, Ifl›k KAYGUSUZ1, Tülin F. TU⁄LULAR1, Tülay TEC‹MER2, Mahmut BAYIK1

1 Department of Hematology, Marmara University Medical Faculty, 2 Department of Pathology, Marmara University Medical Faculty, Istanbul, TURKEY

Turk J Haematol 2004;21(2): 97-100

Received: 31.10.2003 Accepted: 23.03.2004

ABSTRACT necrosis is a rare but ominous finding in various malignant and nonmalignant disorders. It is usually a postmortem diagnosis, but with the advent of modern imaging methods and clinical suspicion, bone marrow necrosis can be diagnosed as antemortem, especially in malignant disorders. We report a 60-years old man with newly diagnosed non-Hodgkin lymphoma presenting with anemia and very high level of alkaline phosp- hatase. On bone marrow biopsy, it was noted with extensive BMN characterized by cellular debris with indistinct cellular margin and abnormally eosinophilic staining cytoplasm. Despite the prompt institution of aggressive che- motherapy, one week later, function tests gradually deteriorated and the patient succumbed. Given the high mortality rate, when the bone marrow necrosis is suspected especially in a patient with malignancy, disease specific treatment and vigorous supportive measures should be immediately commenced. Key Words: Bone marrow necrosis, Hematologic malignancy.

ÖZET Non-Hodgkin lenfomal› bir hastada kemik ili¤i nekrozu Kemik ili¤i nekrozu nadir görülen, kötü prognozlu bir klinik tablodur. Tümöral ve tümör d›fl› çeflitli neden- lerle oluflmakla beraber en s›k lösemilerde karfl›lafl›lmaktad›r. Sunulan olgu, 60 yafl›nda anemi, iki tarafl› servi- kal lenfadenopatileri ve hepatosplenomegalisi olan, kan tetkiklerinde çok yüksek alkalen fosfataz seviyesi, ke- mik ili¤i biyopsisinde silüet fleklinde tipik hücre boyanmas› ile karakterize görünümüyle yayg›n kemik ili¤i nek- rozu saptanan ve agresif tedaviye ra¤men kaybedilen Hodgkin-d›fl› lenfomal› bir hastad›r. Bu tip hastalar›n sa- ¤alt›m›nda erken tan›n›n, yo¤un bir destek tedavisinin ve altta yatan nedene yönelik agresif tedavinin önemini vurgulamak istiyoruz. Anahtar Kelimeler: Kemik ili¤i nekrozu, Hematolojik malignite.

97 Argon D, Çetiner M, Ad›güzel C, Kaygusuz I, Tu¤lular TF, Tecimer T, Bay›k M. Bone marrow necrosis in a patient with non-Hodgkin lymphoma

INTRODUCTION Table 1. Associated disorders in BMN

Although it has been described sixty ye- Disorders % ars ago, little is known on bone marrow nec- Malignant disorders 91 rosis (BMN) in medical practice[1]. The first Hematologic malignancies 60 antemortem definition was made by Nies in patients with acute in 1965[2]. Acute BMN is defined as necrosis of myeloid Chronic myeloproliferative disorders and medullary stroma in large areas of the Lymphomas bone marrow (BM)[3]. This clinicopathologic Solid tumors 31 entity is completely different from both avas- Unknown primary tumors cular bone necrosis in which there is no destruction of spicular architecture and marrow aplasia in which there is only a loss of not reticular structure[4,5]. By now, about 270 cases have been reported in the literature. Table 1 lists all causes of and BMN that has reported so far. Malignancy Neuroblastoma/medulloblastoma which constitutes 90% of cases is the most Carsinoid common underlying disorder of BMN[3,6]. Up Nonmalignant disorders 9 to 10% of patients with BMN have nonmalig- Infections nant disorders. As shown in Table 1, there is a wide variety of disorders causing BMN. Drugs Sickle cell disease The most important diagnostic sign is bo- Others ne pain[7]. The pain is acute, intense and Hyperparathyroidism usually located in lower back. It is more evi- dent in malignant disorders. More than half Anorexia nervosa of patients with BMN present with fever[7]. Hemolytic uremic syndrome Embolization of fat and necrotic marrow to Antiphospholipid syndrome lung are the other rare but life-threatening DIC [8] complications of BMN . Among the labora- Idiopathic tory findings, various cytopenias, leuko- erythroblastic differential count, and incre- ased levels of lactic dehydrogenase (LDH) raphy. Both methods are useful in the moni- and alkaline phosphatase (AP) are the most torization of the recovery period[12,13]. prominent features[9]. In BM examination, it is noted that the cells lose their normal sta- A CASE REPORT ining pattern and have irregular shape and A 60-years old man was referred by his margin on cytology[3]. It is usually required family physician to the Department of Hema- to aspirate the marrow from multiple sites to tology of Marmara University complaining obtain enough material[10]. The combination with anorexia, weight loss, itching, and inter- of gelatinous transformation and necrosis is mittent mild fever. On examination, he was the hallmark of BM biopsy[11]. Adjunctive to noted to have a pale appearance. He was clinicopathologic diagnose, BM scintigraphy afebrile, the and examination with Technetium and indium is a highly sen- were normal. Abdominal examination reve- sitive method. Magnetic resonance imaging aled moderate hepatosplenomegaly. Among is another useful noninvasive diagnostic tool, his peripheral lymph nodes, cervical, suprac- though its sensitivity not superior to scintig- lavicular, axillary and inguinal nodes were

98 Turk J Haematol 2004;21(2):97-100 Argon D, Çetiner M, Ad›güzel C, Kaygusuz I, Bone marrow necrosis in a patient with non-Hodgkin lymphoma Tu¤lular TF, Tecimer T, Bay›k M.

palpable bilaterally. There was no cyanosis, jaundice, dyspnea or edema. His past medi- cal history was significant for coronary heart disease. He was taking a vasodilator, an an- giotensin converting enzyme inhibitor and aspirin. He had no history of surgical inter- vention. Complete cell analysis revealed mild anemia with normocytic normochrom appe- arance (Hb: 9.9 g/dL), and lymphocytosis. Erythrocyte sedimentation rate was 22 mm/h. In biochemical analysis the most prominent Figure 1. Bone marrow necrosis (H&E stain 400x). finding was the increased level of AP (2758 mg/dL). LDH and transaminase levels also had increased minimally. All the other bioc- Table 2. Survival rates in BMN hemical parameters were normal. Disorder n Median survival (mo) At the end of first part of diagnostic work- up, the patient was thought to have a kind of ALL 35 4 lymphoma and referred to surgery unit for AML 25 2 excisional biopsy of one of the enlarged cer- Lymphoma 24 1 vical nodes. Cervical node biopsy revealed MPD 7 3 diffuse large B-cell lymphoma. Then, the pa- Solid tumors 18 5 weeks tient underwent bone marrow biopsy and to- racoabdominal and cervical axial computeri- Infections 5 3 weeks zed tomography (CT) for staging purpose. CT Others 5 2.5 weeks scan of body revealed mediastinal and para- MPD: Myeloproliferative disorders. aortic lymphadenomegalies in addition to pe- ripheral enlarged nodes. BM aspiration re- tients with BMN in whom achieved complete sulted in dry-tap. On examination of BM bi- remission usually relapse early[15,16]. BMN in opsy, it was noted extensive BMN characteri- solid tumors reflects widespread metastasis zed by cellular debris with indistinct cellular including bone marrow and bad outcome. margin and abnormally eosinophilic staining Despite the notorious outcome, some aut- cytoplasm (Figure 1). hors have reported resolved patients with At the completion of diagnostic studies, chemotherapy and supportive measures the patient was diagnosed to have stage IVB even if, rare. For this reason, when an un- diffuse large B-cell lymphoma and treated derlying pathology is detected, vigorous sup- with aggressive chemotherapy. Despite che- portive care together with special treatment motherapy, one week later, liver function must be started including transfusion of blo- tests gradually deteriorated and the patient od components, adequate antibiotic treat- succumbed. ment, hydration, oxygenation and alkaliniza- tion to permit a time for spontaneous reco- DISCUSSION very of the normal hematopoiesis. Given the Although the survival of BMN depends on complex pathophysiology of BMN, some no- the underlying disorder, the ultimate progno- vel therapies such as anti tumor necrosis α sis is poor[14]. Table 2 lists survival rates in factor (TNF)- antibodies and various cytoki- various disorders[3]. In hematologic malig- nes may be promising modalities in future. nancy, especially leukemias, most of the pa-

Turk J Haematol 2004;21(2):97-100 99 Argon D, Çetiner M, Ad›güzel C, Kaygusuz I, Tu¤lular TF, Tecimer T, Bay›k M. Bone marrow necrosis in a patient with non-Hodgkin lymphoma

REFERENCES 11. Kundel D, Brecher G, Bodey G, et al. Reticulin fib- rosis and bone infarction in acute leukemia. Implica- 1. Wade L, Stevenson L. Necrosis of bone marrow with tions for prognosis. Blood 1964;23:526-44. fat embolism in sickle cell anemia. Am J Path 1941; 12. Musto P, La Sala A. Again about bone marrow nec- 17:47-54. rosis: particular diagnostic aspects. Hematol Pathol 2. Nies BA, Kundel DW, Thomas LB, et al. Leukope- 1989;3:185-7. nia, bone pain, and bone necrosis in patients with 13. Weissman DE, Negendank WG, Al-Katibb AM, et al. acute leukemia. Ann Intern Med 1965;62:698-705. Bone marrow necrosis in lymphoma studied by mag- 3. Janssens AM, Offner FC, Van Hove WZ. Bone mar- netic resonance imaging. Am J Hematol 1992; row necrosis. Cancer 2000;15:1769-80. 40:42-6. 4. Hughes RG, Islam A, Lewis SM, et al. Spontaneous 14. Ranaghan L, Morris TC, Desai ZR, et al. Bone mar- remission following bone marrow necrosis in chronic row necrosis. Am J Hematol 1994;47:225-8. lymphocytic leukemia. Clin Lab Haematol 1981; 15. Kunieda Y, Okabe M, Kunita Y, et al. Bone marrow 3:173-84. necrosis in thymic T-cell lymphoma. Rinsho Ketsueki 5. Smith RR, Spivak JL. Marrow cell necrosis in anore- 1990;31:492-6. xia nervosa and involuntary starvation. Br J Haema- 16. Uoshima N, Yamazaki N, Linuma S, et al. Acute tol 1985;60:525-30. unclassified leukemia with bone marrow necrosis. 6. Paydas S, Ergin M, Baslamisli F, et al. Bone marrow Rinsho Ketsueki 1991;32:61-6. necrosis: clinicopathologic analysis of 20 cases and review of the literature. Am J Hematol 2002;70: 300-5. Address for Correspondence: 7. Pennaforte JL, Dufour M, Etienne JC, et al. Diag- Dilek ARGON, MD nostic problems in bone marrow necrosis. Report of a case revealing acute leukemia. Arch Anat Cytol Doğancılar Halkdersanesi Sokak, No: 27/1 Pathol 1986;34:111-6. 81160, Üsküdar, İstanbul, TURKEY 8. Bermejo A, Gonzales FA, Villegas A, et al. Bone marrow necrosis. Am J Hematol 1995;50:65-6. e-mail: [email protected] 9. Kiraly JF, Wheby MS. Bone marrow necrosis. Am J Med 1976;60:361-8. 10. Norgard MJ, Carpenter JT, Conrad ME. Bone mar- row necrosis and degeneration. Arch Intern Med 1979;139:905-11.

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