Journal of Internal Medicine 1 9 9 2 : 2 3 2 : 193-194
Case report Acute myelomonocytic leukaemia with infiltrative peripheral neuropathy R. BILLSTROM & A. LUNDQUIST From the Department of Medicine. Central Hospital. Helsingborg. Sweden
Abstract. Billstrom R, Lundquist A (Department of Medicine, Central Hospital, Helsingborg, Sweden). Acute myelomonocytic leukaemia with infiltrative peripheral neuropathy. Journal of Internal Medicine 1992 : 232 : 193-194. The case of a 71-year-old woman with acute myelomonocytic leukaemia and severe pains in her arms, legs and back during treatment is described. Signs of a generalized polyneuropathy subsequently developed. Autopsy revealed massive leukaemic infiltration of peripheral nerves. Peripheral nerve involvement in acute leukaemia appears to 'be rare as judged from the very few previously reported cases. The condition should be suspected whenever inexplicable pain problems and signs of peripheral neuropathy occur in patients with acute leukaemia. Keywords: leukaemia, nerve infiltration, polyneuropathy.
Introduction Infiltration of the central nervous system (CNS) is not uncommon in acute myeloid leukaemia (AML), demonstrable in up to 10%ofcases [l]. For unknown reasons, CNS leukaemia is especially frequent in AML with monocytic differentiation (FAB types M4 and M5). In contrast, leukaemic infiltration of peripheral nerves appears to be rare. Only a small number of cases are reported in the literature [ 2 4 ] . We here describe a case of acute myelomonocytic leukaemia (AML M4) with leukaemic infiltration of peripheral nerves leading to severe pain problems and diagnostic difficulties.
Case report A 71-year-old woman was admitted in December 1989 with a few weeks' history of fatigue, palpitations, and symptoms of upper respiratory tract infection. She had previously been in good health. The haemoglobin level was 65 g I-l, white cell count was 8 4 x lo9I-' with 80%blasts and 8%monocytes, and platelet count was 32 x lo0I-'. Impressive gingival swellings were present. A bone-marrow aspirate from sternum was hypercellular with 33 %
myeloblasts and 2 5 % promonocytes/monoblasts. After confirmatory cytochemistry with Sudan Black B and alpha-naphtyl butyrate esterase, a diagnosis of acute myelomonocytic leukaemia (AML M4) was made. S-lysozyme was moderately raised to 7 mg 1-' (1-5 mg 1-l). Cytogenetic analysis showed a normal female karyotype in 2 0 bone-marrow metaphases. After three courses of chemotherapy with daunorubicin, etoposide and ara-C, a partial remission was achieved. Thus in March 1990 peripheral blood cell counts were normal and a moderately cellular bonemarrow aspirate contained 8% blasts. In cerebrospinal fluid (CSF), 1 4 x 10' 1-' mononuclear cells were found. Cytospin preparation showed scattered small lymphocytes, neutrophilic granulocytes and monocytes, but no blast cells. During the following month, severe continuous incapacitating pain developed in the right arm and both legs. Oral and subcutaneous (s.c.) morphine as well as corticosteroids had only a partial effect. In a repeated CSF analysis, 3 0 x 10' I-' nucleated cells were found, mostly promonocytes and myeloblasts. In addition, bone-marrow aspirates were now dominated by promonocytes and myeloblasts. Weekly intrathecal methotrexate and low dose (20 mg) AraC S.C. daily were given for 3 weeks. This resulted in 193
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complete bone-marrow remission, but promonocytes and rare myeloblasts were still seen in the CSF samples. The pains in the arms and legs progressed, and various regimes of heavy analgesics, antidepressants and corticosteroids had little effect. The condition was difficult to evaluate, as repeated neurological examinations gave normal findings. The patient was also depressed and had a complicated social situation. Non-organic causes of the pain problems were considered. Eventually. extremity weakness and peripheral numbness with arreflexia also developed, with inability to elevate the arms or legs from the bed. Electromyography showed reduction of conduction velocity and action-potential amplitude. Fibrillations were found predominantly in distal muscles, and positive sharp waves were detected in both tibialis anterior muscles, indicating a moderately severe polyneuropathy . During her last weeks, severe headache and a right ophtalmoplegia developed. In CSF, the white cell count was 66 x lo6I-', still dominated by more mature forms-atypical monocytes, neutrophils, and rare myelo/monoblasts. Cranial or spinal CT scans were not performed. Just before death due to bronchopneumonia, Bhaemoglobin was 147 g I-', platelets were 140 x 10"I-', and the white cell count was 11 .O x lo9I-', with a normal differential. On autopsy, imprints of bone marrow showed early relapse with a population of myeloblasts and promonocytes. Neuropathological investigation revealed discrete CNS infiltration of meninges and corpus callosum. In addition, massive leukaemic infiltration of peripheral nerve (right femoral nerve) with axonal and myelin sheath destruction, as well as moderate infiltration of spinal nerve roots, were found.
Discussion Although overt signs of CNS leukaemia ultimately developed, the clinical picture for this patient was for several months dominated by an extremely painful progressive peripheral neuropathy. In the light of the autopsy findings, infiltration of leukaemic cells in peripheral nerves fully explains the symptoms. In a series of 202 patients with acute leukaemia of various types. five out of 45 subjects with CNS leukaemia were reported to have peripheral nerve involvement [l]. As in our case, some evidence of
CNS leukaemia preceding or concomitant with the evolution of peripheral nerve infiltration is most often, but not always [4], present. Most cases reported have had AML of monocytic or myelomonocytic types r2-41. Successful treatment with intrathecal chemotherapy with clearance of leukaemic cells from CSF does not abrogate the risk of peripheral nerve involvement [ 2 , 31. Neurological symptoms in a patient under treatment for acute leukaemia pose a challengc due to the many differential diagnostic possibilities ; druginduced neuropathy 151, leukaemia-associated polyneuropathy [6], and the Guillain-Barre syndrome [71. Nerve biopsy is the logical approach to verification of peripheral nerve infiltration, but might give a non-specific result due to the patchy nature of infiltration [ 3 ] .The condition should be suspected in any patient with pathological cytological findings in CSF and symptoms/signs of peripheral neuropathy. It is not clear whether the nerve infiltrates progress peripherally from meninges and nerve roots, or if they are present early in the course of disease and spared from the effect of cytotoxic drugs by the blood-nerve barrier. In a younger patient, treatment with high-dose Ara-C-or other agents which might penetrate the blood-nerve barrier-would seem rational.
References 1 Stewart DJ. Keating MI, McCredie KB et nl. Natural history of central nervous system leukaemia in adults. Cnrrcer 198 I : 4 7 : 184-96. 2 Grisold W. Mokrusa W. Mamoli B. Weber R. Lutz 1). Akute myelomonocytiire und monoblastenleukamicn mit polyradikularer symtomatik. Wietr Klirr Wocliensclrr 1985 : 16: 662-6. 3 Krendel DA. Albright RE. Graham DG. Infiltrative polyneuropathy due to acute monoblastic leukaemia in hematologic remission. Neurology 1987; 3 7 : 474-7. 4 Hertler AA, Rosenwasser GO, Cluck WL. Isolated anterior chamber relapse in acute monoblastic leukemia. Am Herrtrifol 1986: 2 3 : 401-3. 5 Mena H. Garcia JH. Velandia F. Central and peripheral myelinopathy associated with systemic neoplasia and chemotherapy. Cancer 1981 : 48: 1724-37. 6 Phanthumchinda K. lntragumtornchai 1'. Kasantikul V. Cuillain-Barre syndrome and optic neuropathy in acute leukemia. Neurologg 1988 : 38 : 1324-6. 7 Sumi SM. Farrell DF. Knauss TA. Lymphoma and leukemia manifested by steroid-responsive polyneuropathy. Ardr Nerirol 1983: 40: 577-82.
Received 1 0 October 199 1, accepted 5 December 199 1 Correspondence: Rolf Billstrom. MD. Department of Medicine. Lasarettet (Central Hospital), S-251 87 Helsingborg. Sweden.
Case report Acute myelomonocytic leukaemia with infiltrative peripheral neuropathy R. BILLSTROM & A. LUNDQUIST From the Department of Medicine. Central Hospital. Helsingborg. Sweden
Abstract. Billstrom R, Lundquist A (Department of Medicine, Central Hospital, Helsingborg, Sweden). Acute myelomonocytic leukaemia with infiltrative peripheral neuropathy. Journal of Internal Medicine 1992 : 232 : 193-194. The case of a 71-year-old woman with acute myelomonocytic leukaemia and severe pains in her arms, legs and back during treatment is described. Signs of a generalized polyneuropathy subsequently developed. Autopsy revealed massive leukaemic infiltration of peripheral nerves. Peripheral nerve involvement in acute leukaemia appears to 'be rare as judged from the very few previously reported cases. The condition should be suspected whenever inexplicable pain problems and signs of peripheral neuropathy occur in patients with acute leukaemia. Keywords: leukaemia, nerve infiltration, polyneuropathy.
Introduction Infiltration of the central nervous system (CNS) is not uncommon in acute myeloid leukaemia (AML), demonstrable in up to 10%ofcases [l]. For unknown reasons, CNS leukaemia is especially frequent in AML with monocytic differentiation (FAB types M4 and M5). In contrast, leukaemic infiltration of peripheral nerves appears to be rare. Only a small number of cases are reported in the literature [ 2 4 ] . We here describe a case of acute myelomonocytic leukaemia (AML M4) with leukaemic infiltration of peripheral nerves leading to severe pain problems and diagnostic difficulties.
Case report A 71-year-old woman was admitted in December 1989 with a few weeks' history of fatigue, palpitations, and symptoms of upper respiratory tract infection. She had previously been in good health. The haemoglobin level was 65 g I-l, white cell count was 8 4 x lo9I-' with 80%blasts and 8%monocytes, and platelet count was 32 x lo0I-'. Impressive gingival swellings were present. A bone-marrow aspirate from sternum was hypercellular with 33 %
myeloblasts and 2 5 % promonocytes/monoblasts. After confirmatory cytochemistry with Sudan Black B and alpha-naphtyl butyrate esterase, a diagnosis of acute myelomonocytic leukaemia (AML M4) was made. S-lysozyme was moderately raised to 7 mg 1-' (1-5 mg 1-l). Cytogenetic analysis showed a normal female karyotype in 2 0 bone-marrow metaphases. After three courses of chemotherapy with daunorubicin, etoposide and ara-C, a partial remission was achieved. Thus in March 1990 peripheral blood cell counts were normal and a moderately cellular bonemarrow aspirate contained 8% blasts. In cerebrospinal fluid (CSF), 1 4 x 10' 1-' mononuclear cells were found. Cytospin preparation showed scattered small lymphocytes, neutrophilic granulocytes and monocytes, but no blast cells. During the following month, severe continuous incapacitating pain developed in the right arm and both legs. Oral and subcutaneous (s.c.) morphine as well as corticosteroids had only a partial effect. In a repeated CSF analysis, 3 0 x 10' I-' nucleated cells were found, mostly promonocytes and myeloblasts. In addition, bone-marrow aspirates were now dominated by promonocytes and myeloblasts. Weekly intrathecal methotrexate and low dose (20 mg) AraC S.C. daily were given for 3 weeks. This resulted in 193
194
K. BILLSTROM & A. LUNDQUIST
complete bone-marrow remission, but promonocytes and rare myeloblasts were still seen in the CSF samples. The pains in the arms and legs progressed, and various regimes of heavy analgesics, antidepressants and corticosteroids had little effect. The condition was difficult to evaluate, as repeated neurological examinations gave normal findings. The patient was also depressed and had a complicated social situation. Non-organic causes of the pain problems were considered. Eventually. extremity weakness and peripheral numbness with arreflexia also developed, with inability to elevate the arms or legs from the bed. Electromyography showed reduction of conduction velocity and action-potential amplitude. Fibrillations were found predominantly in distal muscles, and positive sharp waves were detected in both tibialis anterior muscles, indicating a moderately severe polyneuropathy . During her last weeks, severe headache and a right ophtalmoplegia developed. In CSF, the white cell count was 66 x lo6I-', still dominated by more mature forms-atypical monocytes, neutrophils, and rare myelo/monoblasts. Cranial or spinal CT scans were not performed. Just before death due to bronchopneumonia, Bhaemoglobin was 147 g I-', platelets were 140 x 10"I-', and the white cell count was 11 .O x lo9I-', with a normal differential. On autopsy, imprints of bone marrow showed early relapse with a population of myeloblasts and promonocytes. Neuropathological investigation revealed discrete CNS infiltration of meninges and corpus callosum. In addition, massive leukaemic infiltration of peripheral nerve (right femoral nerve) with axonal and myelin sheath destruction, as well as moderate infiltration of spinal nerve roots, were found.
Discussion Although overt signs of CNS leukaemia ultimately developed, the clinical picture for this patient was for several months dominated by an extremely painful progressive peripheral neuropathy. In the light of the autopsy findings, infiltration of leukaemic cells in peripheral nerves fully explains the symptoms. In a series of 202 patients with acute leukaemia of various types. five out of 45 subjects with CNS leukaemia were reported to have peripheral nerve involvement [l]. As in our case, some evidence of
CNS leukaemia preceding or concomitant with the evolution of peripheral nerve infiltration is most often, but not always [4], present. Most cases reported have had AML of monocytic or myelomonocytic types r2-41. Successful treatment with intrathecal chemotherapy with clearance of leukaemic cells from CSF does not abrogate the risk of peripheral nerve involvement [ 2 , 31. Neurological symptoms in a patient under treatment for acute leukaemia pose a challengc due to the many differential diagnostic possibilities ; druginduced neuropathy 151, leukaemia-associated polyneuropathy [6], and the Guillain-Barre syndrome [71. Nerve biopsy is the logical approach to verification of peripheral nerve infiltration, but might give a non-specific result due to the patchy nature of infiltration [ 3 ] .The condition should be suspected in any patient with pathological cytological findings in CSF and symptoms/signs of peripheral neuropathy. It is not clear whether the nerve infiltrates progress peripherally from meninges and nerve roots, or if they are present early in the course of disease and spared from the effect of cytotoxic drugs by the blood-nerve barrier. In a younger patient, treatment with high-dose Ara-C-or other agents which might penetrate the blood-nerve barrier-would seem rational.
References 1 Stewart DJ. Keating MI, McCredie KB et nl. Natural history of central nervous system leukaemia in adults. Cnrrcer 198 I : 4 7 : 184-96. 2 Grisold W. Mokrusa W. Mamoli B. Weber R. Lutz 1). Akute myelomonocytiire und monoblastenleukamicn mit polyradikularer symtomatik. Wietr Klirr Wocliensclrr 1985 : 16: 662-6. 3 Krendel DA. Albright RE. Graham DG. Infiltrative polyneuropathy due to acute monoblastic leukaemia in hematologic remission. Neurology 1987; 3 7 : 474-7. 4 Hertler AA, Rosenwasser GO, Cluck WL. Isolated anterior chamber relapse in acute monoblastic leukemia. Am Herrtrifol 1986: 2 3 : 401-3. 5 Mena H. Garcia JH. Velandia F. Central and peripheral myelinopathy associated with systemic neoplasia and chemotherapy. Cancer 1981 : 48: 1724-37. 6 Phanthumchinda K. lntragumtornchai 1'. Kasantikul V. Cuillain-Barre syndrome and optic neuropathy in acute leukemia. Neurologg 1988 : 38 : 1324-6. 7 Sumi SM. Farrell DF. Knauss TA. Lymphoma and leukemia manifested by steroid-responsive polyneuropathy. Ardr Nerirol 1983: 40: 577-82.
Received 1 0 October 199 1, accepted 5 December 199 1 Correspondence: Rolf Billstrom. MD. Department of Medicine. Lasarettet (Central Hospital), S-251 87 Helsingborg. Sweden.
