- Email: [email protected]
Acute lymphoblastic leukaemia presenting with low back pain
doi: 10.1053/ejpn.2002.0610 available online at http://www.idealibrary.com on European Journal of Paediatric Neurology 2002; 6: 285–287
CASE STUDY
Acute lymphoblastic leukaemia presenting with low back pain ROEL BECKERS,1 ANNE UYTTEBROECK,2 PHILIPPE DEMAEREL1 Department of 1Radiology and 2Pediatric Oncology, University Hospitals Leuven, Belgium
We report a 13-year-old boy with a 3-month history of low back pain following a mild trauma. Extensive osteoporosis and vertebral collapses were seen on conventional X-ray and computed tomography scan. Laboratory findings were non-specific. Bone marrow infiltration was observed on magnetic resonance imaging, suggesting a myeloproliferative disorder. Although not diagnostic, marrow infiltration in a child with osteoporosis should raise the suspicion of leukaemia. Keywords: Low back pain. Marrow infiltration. Osteoporosis. Leukaemia.
Case study A 13-year-old boy was referred to our hospital with a 3-month history of increasing low back pain and stiffness following a minor trauma. Clinical investigation showed no striking abnormalities. Conventional X-ray of the lumbosacral spine (Fig. 1) and pelvis showed a mild compression on several lumbar vertebrae with an overall decreased radiodensity and thinning of the vertebral endplates. Lumbar spine computed tomography (CT) showed a collapse of L3 and L4 on the topography and trabecular rarification on axial images. Both investigations suggested osteoporosis, which was confirmed by a bone mineral content investigation. Bone scintigraphy with 99m TC DP was normal. Peripheral blood showed haemoglobin (Hb) 13.4 g/dl, white blood cells (WBC) 12.56109/l with 31% lymphocytes, 34% neutrophils and decreased blood platelets 756109/l. On blood chemistry a mildly increased serum calcium 5.4 mg/dl (normal value: 4.56–5.16) and phosphate 5.9 mg/dl (normal value: 2.7–5.0 mg/dl) were detected. There was an elevated urine calcium of
4.6 mg/kg/24h (normal value < 4 mg/kg/24h). Xray of the wrist, skull and tibia showed a normal bone age (P90–97), without evidence of osteoporosis. Other causes of hypercalciuria with osteoporosis were excluded (low calcium intake, renal calcium leak, endocrine malfunction, vitamin D deficiency). Further investigations were performed to exclude sarcoidosis or malignancy. Abdominal ultrasound revealed splenomegaly and multiple lymph nodes in the liver hilum. Magnetic resonance imaging (MRI) of the thoracolumbar spine (Siemens vision, 1.5 Tesla, Erlangen, Germany) was performed using a 512 matrix. The following sequences were performed with a 256 by 128 matrix and a field of view of 350 mm: T1 weighted spin echo sequence (TE: 12 ms, TR: 640 ms), T2 weight spin echo (TE: 128 ms, TR: 4000 ms) and short T1 IR images (TE: 60 ms, TR: 5300 and TI: 150 ms) (Figs 2 and 3). There was a mild collapse of the vertebral bodies at T12, L3, L4 and L5. The bone marrow of the vertebral column revealed a low signal on T1 and a slightly increased signal on T2 and short T1 IR weighted sequences compared with age-matched controls, suggesting a diffuse marrow infiltration
Received 18.03.02. Revised 17.06.02. Accepted 1.07.02. Correspondence: Philippe Demaerel MD PhD, Department of Radiology, University Hospitals, Herestraat 49, B-3000 Leuven, Belgium; Tel: +32-16/343782; Fax: +32-16/343765; e-mail: [email protected]
1090-3798/02/06/0285+03 $35.00
& 2002 European Paediatric Neurology Society
286
Case study: R Beckers et al. years of age. In children 75% of cases are lymphocytic in origin (ALL), 15–20% are myelogenous leukaemias and 5–10% are of the non-lymphocytic leukaemia type. The onset of acute childhood leukaemia is often insidious and usually the diagnosis is made on clinical suspicion with laboratory findings. Bone pain, with related radiological changes (often in long bones) and leukopenia are well recognized features of ALL but were not observed in our patient. Low back pain as the presenting sign of ALL or leukaemic relapse without any clinical evidence of the disease is rare.1,2,3 The laboratory findings in the patient led the clinicians to first exclude other causes of hypercalcaemia and hypercalciuria. Osteoporosis as a result of disuse or nutritional factors, storage diseases, osteogenesis imperfecta, sarcoidosis, haematological and endocrinological disorders were all excluded. Conventional X-ray and lumbar spine CT in our patient showed signs suggestive of osteoporosis and compression fractures. All these investigations including bone scintigraphy failed to reveal bone marrow infiltration. The precise composition, physiology and anatomy of the bone marrow and its appearance on MRI have been discussed in detail.4
Fig. 1. Conventional X-ray of the lumbar spine shows wedge-formed compression fractures of several lumbar vertebrae.
as seen in lymphoproliferative disorders (Figs 2 and 3). Three weeks later peripheral blood showed Hb 11.8 g/dl, WBC 10.76109/l with 28% blasts and platelets 736109/l. A bone marrow puncture was performed. Morphological examination revealed 89% lymphoblasts. Immunophenotyping of the blastpopulation was compatible with a common B-cell acute lymphoblastic leukaemia: TDT, antiHLA-DR, CD10, CD19, CD38 positive with aberrant co-expression of CD15. Karyotype of the blasts was normal 46, XY. DNAindex was 1. Chemotherapy following the European Organization for Research on Treatment of Cancer protocol 58951 (a BFM-like protocol) was started for a total duration of 2 years. After the induction at day 35 the boy reached a complete remission. 54 months later he is still in first complete remission.
Discussion Acute leukaemia is the most frequent malignant childhood disease with a peak frequency at 2 to 5
Fig. 2. Sagittal T2 (a) and short T1 IR (b) weighted images of the thoracolumbar region shows wedge-formed vertebral bodies L1-L5, D12, D9 and D6-D7. Note the hyperintense signal of the endplates D12 and L5 on both sequences, confirming the bone oedema.
Case study: Acute lymphoblastic leukaemia with low back pain
Fig. 3. Sagittal T1 weighted images of the patient (a) compared with an age-matched control subject (b). There is a homogeneous and slightly hypointense signal in the spine of the patient compared with the dorsal muscles. In the control subject, vertebrae are inhomogeneous and isoto mildly hyperintense compared with the dorsal musculature. These findings are suggestive of diffuse bone marrow infiltration.
in signal intensity on T2 and short T1 IR weighted images though these changes are less specific.4 However, these marrow changes can be subtle on all sequences. In children difficulties in grading the signal intensities can be pronounced because of a physiological change of signal intensity caused by the presence of red marrow making it difficult to exclude cellular infiltration on both T1 and T2 weighted images.5 Comparing the bone marrow with age- and sex-matched controls is a useful way of assessing marrow infiltration. In our patient we found a decreased signal of several lumbar vertebrae on T1-weighted images and an increased signal on both T2 and short T1 IR weighted sequences together with compression fractures and signs of bone oedema at the endplates. Comparison with an age-matched control clearly confirmed these abnormalities which led us to the diagnosis of a marrow infiltration by an underlying disorder, most likely leukaemia in view of the patient’s age and the absence of inflammation or metabolic disorders.
References 1
2
MRI is highly sensitive to changes in bone marrow composition and it plays a role as a modality to confirm haematological malignancies.5 Furthermore its role in monitoring response to treatment as well as in diagnosing complications is well established.6,7,8 However, marrow signal is highly age- and sexrelated, and is dramatically influenced by the pulse sequence used as well as the exact composition of red and yellow marrow. Infiltration or replacement of marrow by tumour cells is seen in a group of disorders such as leukaemia, lymphoma, myeloma, metastatic disease, Gaucher disease and mucopolysaccharidoses. The changes in leukaemia have been explained by hypercellularity (tumour replacement of normal marrow) in the bone leading to increased pressure and secondary of the bone trabeculae, making them vulnerable to collapse. A decrease in signal at T1 weighted images lower than the disc or muscles is the most pronounced feature and should be considered abnormal. There is a variable increase
287
3
4 5
6
7
8
Rohn RD, Werner EJ, Byrd RL. Osteoporosis as the presenting sign of leukemic relapse in an adolescent: case report and literature review. J Adolesc Health 1992; 13: 306–310. Samuda GM, Cheng MY, Yeung CY. Back pain and vertebral compression: an uncommon presentation of childhood acute lymphoblastic leukemia. J Pediatr Orthop 1987; 7: 175–178. Panteli A, Pritsivelis N, Tsiara S, Vartholomatos G, Bourantas KL. A patient with acute lymphoblastic leukemia who presented with osteoporosis and vertebral fractures (letter). Eur J Haematol 1999; 63: 274–275. Vogler JB III, Murphy WA. Bone marrow imaging. Radiology 1988; 168: 679–693. Takagi S, Tanaka O. The role of magnetic resonance imaging in the diagnosis and monitoring of myelodysplastic syndromes or leukemia. Leuk Lymphoma 1996; 23: 443–450. Pieters R, van Brenk AI, Veerman AJ et al. Bone marrow magnetic resonance studies in childhood leukemia. Evaluation of osteonecrosis. Cancer 1987; 60: 2994–3000. van Zanten TE, Golding RP, Taets-van Amerongen AH, Pieters R, Veerman AJ. Nuclear magnetic resonance imaging of bone marrow in childhood leukaemia. Clin Radiol 1988; 39: 77–81. Tardivon AA, Vanel D, Munck JN, Bosq J. Magnetic resonance imaging of the bone marrow in lymphomas and leukemias. Leuk Lymphoma 1997; 25: 55–68.
CASE STUDY
Acute lymphoblastic leukaemia presenting with low back pain ROEL BECKERS,1 ANNE UYTTEBROECK,2 PHILIPPE DEMAEREL1 Department of 1Radiology and 2Pediatric Oncology, University Hospitals Leuven, Belgium
We report a 13-year-old boy with a 3-month history of low back pain following a mild trauma. Extensive osteoporosis and vertebral collapses were seen on conventional X-ray and computed tomography scan. Laboratory findings were non-specific. Bone marrow infiltration was observed on magnetic resonance imaging, suggesting a myeloproliferative disorder. Although not diagnostic, marrow infiltration in a child with osteoporosis should raise the suspicion of leukaemia. Keywords: Low back pain. Marrow infiltration. Osteoporosis. Leukaemia.
Case study A 13-year-old boy was referred to our hospital with a 3-month history of increasing low back pain and stiffness following a minor trauma. Clinical investigation showed no striking abnormalities. Conventional X-ray of the lumbosacral spine (Fig. 1) and pelvis showed a mild compression on several lumbar vertebrae with an overall decreased radiodensity and thinning of the vertebral endplates. Lumbar spine computed tomography (CT) showed a collapse of L3 and L4 on the topography and trabecular rarification on axial images. Both investigations suggested osteoporosis, which was confirmed by a bone mineral content investigation. Bone scintigraphy with 99m TC DP was normal. Peripheral blood showed haemoglobin (Hb) 13.4 g/dl, white blood cells (WBC) 12.56109/l with 31% lymphocytes, 34% neutrophils and decreased blood platelets 756109/l. On blood chemistry a mildly increased serum calcium 5.4 mg/dl (normal value: 4.56–5.16) and phosphate 5.9 mg/dl (normal value: 2.7–5.0 mg/dl) were detected. There was an elevated urine calcium of
4.6 mg/kg/24h (normal value < 4 mg/kg/24h). Xray of the wrist, skull and tibia showed a normal bone age (P90–97), without evidence of osteoporosis. Other causes of hypercalciuria with osteoporosis were excluded (low calcium intake, renal calcium leak, endocrine malfunction, vitamin D deficiency). Further investigations were performed to exclude sarcoidosis or malignancy. Abdominal ultrasound revealed splenomegaly and multiple lymph nodes in the liver hilum. Magnetic resonance imaging (MRI) of the thoracolumbar spine (Siemens vision, 1.5 Tesla, Erlangen, Germany) was performed using a 512 matrix. The following sequences were performed with a 256 by 128 matrix and a field of view of 350 mm: T1 weighted spin echo sequence (TE: 12 ms, TR: 640 ms), T2 weight spin echo (TE: 128 ms, TR: 4000 ms) and short T1 IR images (TE: 60 ms, TR: 5300 and TI: 150 ms) (Figs 2 and 3). There was a mild collapse of the vertebral bodies at T12, L3, L4 and L5. The bone marrow of the vertebral column revealed a low signal on T1 and a slightly increased signal on T2 and short T1 IR weighted sequences compared with age-matched controls, suggesting a diffuse marrow infiltration
Received 18.03.02. Revised 17.06.02. Accepted 1.07.02. Correspondence: Philippe Demaerel MD PhD, Department of Radiology, University Hospitals, Herestraat 49, B-3000 Leuven, Belgium; Tel: +32-16/343782; Fax: +32-16/343765; e-mail: [email protected]
1090-3798/02/06/0285+03 $35.00
& 2002 European Paediatric Neurology Society
286
Case study: R Beckers et al. years of age. In children 75% of cases are lymphocytic in origin (ALL), 15–20% are myelogenous leukaemias and 5–10% are of the non-lymphocytic leukaemia type. The onset of acute childhood leukaemia is often insidious and usually the diagnosis is made on clinical suspicion with laboratory findings. Bone pain, with related radiological changes (often in long bones) and leukopenia are well recognized features of ALL but were not observed in our patient. Low back pain as the presenting sign of ALL or leukaemic relapse without any clinical evidence of the disease is rare.1,2,3 The laboratory findings in the patient led the clinicians to first exclude other causes of hypercalcaemia and hypercalciuria. Osteoporosis as a result of disuse or nutritional factors, storage diseases, osteogenesis imperfecta, sarcoidosis, haematological and endocrinological disorders were all excluded. Conventional X-ray and lumbar spine CT in our patient showed signs suggestive of osteoporosis and compression fractures. All these investigations including bone scintigraphy failed to reveal bone marrow infiltration. The precise composition, physiology and anatomy of the bone marrow and its appearance on MRI have been discussed in detail.4
Fig. 1. Conventional X-ray of the lumbar spine shows wedge-formed compression fractures of several lumbar vertebrae.
as seen in lymphoproliferative disorders (Figs 2 and 3). Three weeks later peripheral blood showed Hb 11.8 g/dl, WBC 10.76109/l with 28% blasts and platelets 736109/l. A bone marrow puncture was performed. Morphological examination revealed 89% lymphoblasts. Immunophenotyping of the blastpopulation was compatible with a common B-cell acute lymphoblastic leukaemia: TDT, antiHLA-DR, CD10, CD19, CD38 positive with aberrant co-expression of CD15. Karyotype of the blasts was normal 46, XY. DNAindex was 1. Chemotherapy following the European Organization for Research on Treatment of Cancer protocol 58951 (a BFM-like protocol) was started for a total duration of 2 years. After the induction at day 35 the boy reached a complete remission. 54 months later he is still in first complete remission.
Discussion Acute leukaemia is the most frequent malignant childhood disease with a peak frequency at 2 to 5
Fig. 2. Sagittal T2 (a) and short T1 IR (b) weighted images of the thoracolumbar region shows wedge-formed vertebral bodies L1-L5, D12, D9 and D6-D7. Note the hyperintense signal of the endplates D12 and L5 on both sequences, confirming the bone oedema.
Case study: Acute lymphoblastic leukaemia with low back pain
Fig. 3. Sagittal T1 weighted images of the patient (a) compared with an age-matched control subject (b). There is a homogeneous and slightly hypointense signal in the spine of the patient compared with the dorsal muscles. In the control subject, vertebrae are inhomogeneous and isoto mildly hyperintense compared with the dorsal musculature. These findings are suggestive of diffuse bone marrow infiltration.
in signal intensity on T2 and short T1 IR weighted images though these changes are less specific.4 However, these marrow changes can be subtle on all sequences. In children difficulties in grading the signal intensities can be pronounced because of a physiological change of signal intensity caused by the presence of red marrow making it difficult to exclude cellular infiltration on both T1 and T2 weighted images.5 Comparing the bone marrow with age- and sex-matched controls is a useful way of assessing marrow infiltration. In our patient we found a decreased signal of several lumbar vertebrae on T1-weighted images and an increased signal on both T2 and short T1 IR weighted sequences together with compression fractures and signs of bone oedema at the endplates. Comparison with an age-matched control clearly confirmed these abnormalities which led us to the diagnosis of a marrow infiltration by an underlying disorder, most likely leukaemia in view of the patient’s age and the absence of inflammation or metabolic disorders.
References 1
2
MRI is highly sensitive to changes in bone marrow composition and it plays a role as a modality to confirm haematological malignancies.5 Furthermore its role in monitoring response to treatment as well as in diagnosing complications is well established.6,7,8 However, marrow signal is highly age- and sexrelated, and is dramatically influenced by the pulse sequence used as well as the exact composition of red and yellow marrow. Infiltration or replacement of marrow by tumour cells is seen in a group of disorders such as leukaemia, lymphoma, myeloma, metastatic disease, Gaucher disease and mucopolysaccharidoses. The changes in leukaemia have been explained by hypercellularity (tumour replacement of normal marrow) in the bone leading to increased pressure and secondary of the bone trabeculae, making them vulnerable to collapse. A decrease in signal at T1 weighted images lower than the disc or muscles is the most pronounced feature and should be considered abnormal. There is a variable increase
287
3
4 5
6
7
8
Rohn RD, Werner EJ, Byrd RL. Osteoporosis as the presenting sign of leukemic relapse in an adolescent: case report and literature review. J Adolesc Health 1992; 13: 306–310. Samuda GM, Cheng MY, Yeung CY. Back pain and vertebral compression: an uncommon presentation of childhood acute lymphoblastic leukemia. J Pediatr Orthop 1987; 7: 175–178. Panteli A, Pritsivelis N, Tsiara S, Vartholomatos G, Bourantas KL. A patient with acute lymphoblastic leukemia who presented with osteoporosis and vertebral fractures (letter). Eur J Haematol 1999; 63: 274–275. Vogler JB III, Murphy WA. Bone marrow imaging. Radiology 1988; 168: 679–693. Takagi S, Tanaka O. The role of magnetic resonance imaging in the diagnosis and monitoring of myelodysplastic syndromes or leukemia. Leuk Lymphoma 1996; 23: 443–450. Pieters R, van Brenk AI, Veerman AJ et al. Bone marrow magnetic resonance studies in childhood leukemia. Evaluation of osteonecrosis. Cancer 1987; 60: 2994–3000. van Zanten TE, Golding RP, Taets-van Amerongen AH, Pieters R, Veerman AJ. Nuclear magnetic resonance imaging of bone marrow in childhood leukaemia. Clin Radiol 1988; 39: 77–81. Tardivon AA, Vanel D, Munck JN, Bosq J. Magnetic resonance imaging of the bone marrow in lymphomas and leukemias. Leuk Lymphoma 1997; 25: 55–68.