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Case report: Magnetic resonance imaging of spinal amyloid
Chmcal Radiology (1989) 40, 632-633
Case Report: Magnetic Resonance Imaging of Spinal Amyloid J. F. C. OLLIFF, J. R. HARDY*, M. P. WILLIAMS and T. J. POWLES*
CRC Radiology Research Group, Department of Radiology and * Department of Medicine, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT.
This report describes a patient with a history of breast carcinoma who presented with back pain and multiple collapsed vertebrae. Magnetic resonance imaging (MRI) demonstrated a diffuse bone marrow abnormality, more in keeping with an infiltrative process than with metastases. A bone biopsy confirmed the suspected diagnosis of vertebral involvement by amyloid.
M R I o f the marrow has been shown to be a very sensitive technique for the detection of secondary deposits from diseases such as breast carcinoma and myeloma (Daffner et al., 1986; Ludwig et al., 1987). However, as this case report demonstrates, it is not a specific investigation.
CASE REPORT A 57-year-old woman presented with a 7 month history of back pain. Fifteen years previously she had undergone lumpectomy and radiotherapy for a right-sided breast carcinoma followed two years later by a right mastectomy for local recurrence. Since that time she had been well with no evidence of recurrence. Initial investigations had revealed a normochromic normocytic anaemia (10 g dl-1) and a marked elevation of erythrocyte sedimentahon rate at 130. Plain radiography o f the spine had shown generalised loss of bone density with partial collapse of L1, L3, L4 and L5 A myelogram demonstrated only minor disc bulges from L2 to L5 and some degenerative facet joint disease. Computed tomography (CT) examindtion of the lumbar spine confirmed loss of bony density but no bony metastatic deposits were identified. Bone biopsy of the posterior iliac crest was normal. She was referred to this hospital for further investigations to exclude a diagnosis of multiple myeloma and was found to have proteinuria excreting 15 g of protein per litre (selective for albumin and transferrin). There was no Bence Jones proteinuria and no para-protems were seen on serum electrophoresis. Skeletal survey again showed generalised osteopoenia with collapse of the lumbar vertebrae and the body of T 12. Bone marrow aspirate and trephine (Fig. l) showed no evidence of myeloma or carcinoma. MRI o f the thoracic and lumbar spines was performed. Surface coil images were obtained on a Siemens Magnetom Unit operating at 1.5 Tesla. T1 weighted images were obtained with a repetition time of 500 milliseconds and an echo time of 17 milliseconds. This sequence was selected as a routine screen for bone metastatic disease as it consistently d~fferentiates normal from abnormal marrow in the shortest time. T2 weighted images were not obtained as the appearance o f metastases on T2 weighted images is variable (Daffner et al., 1986). MRI demonstrated abnormally low signal throughout the vertebral bodies of the thoracic and lumbar spine with partial collapse of the bodies of T I2, L 1, L3, L4 and L5 (Fig. 2). The appearances were not felt to be typical of metastatic disease from carcinoma of the breast which usually appears as focal areas of reduced signal intensity on T1 weighted images (Daffner et al., 1986). A diffuse low signal from the marrow on T1 weighted images has been reported in leukaemia and myeloma (Porter et al., 1986) but as there was no other evidence o f myeloma or leukaemia the possibility of other diffuse infiltrative disorders was considered. A rectal biopsy was performed which showed deposition of eosinophilic material in the lamina propria which was shown to be amyloid. Amyloid was also present on renal biopsy. A large core bone biopsy performed under general anaesthesia of the vertebral bodies o f T12, L 1 and L3 showed extensive deposits of amyloid replacing the marrow spaces. In some areas the anayloid was undergoing ossification and Correspondence to: J. F. C. Olliff.
calcification. Congo red staining[ revealed positive apple green birefringence. She now remains well, apart from back pain, with no evidence of metastatic relapse from breast cancer.
DISCUSSION Primary amyloidosis is a systemic disorder characterised by the deposition of amyloid fibrils in the heart, kidneys, tongue, gastrointestinal tract, blood vessel walls, nerves, skin, muscles, peri-articular structures and calf ligaments. Men are affected more often than women, and unlike secondary amyloidosis there is no underlying disease and no known cause. Renal involvement is usual and protcinuria is very common affecting 90% of patients at the time of presentation. The sedimentation rate is generally raised. Even in primary amyloidosis, abnormalities in gamma globulins are seen in 50% of patients. Cardiac involvement is common with a restrictive cardiomyopathy, conduction defects due to amyloid deposition in the conducting system, or ischaemic heart disease because o f coronary artery infiltration. The gastrointestinal tract is also commonly involved with any area being affected and clinical findings depending on the site and type of involvement. Bone involvement by amyloid often results in pain at the site of disease. The radiologic manifestations of bone amyloidosis depend upon whether there is a diffuse or localised disease process (Subbarao and Jacobson, 1986). Generalised reduced bony density may be the only feature
Fig. 1 - Computed tomography section through a mid-lumbar vertebral body at the time of computed tomography guided vertebral body biopsy. The scan demonstrates decrease in bone density and abnormal texture from the cortical bone at this level.
MRI OF SPINAL AMYLOID
Fig. 2 Mid-line saggltal magnetic resonance image of the lumbar spine (TR 0.5 seconds TE 17 milliseconds). There are multiple levels of vertebral body collapse with compression of the anterior theca at L 1 and T12. The bone marrow sxgnal is diffusely low throughout. The signal intensity of the vertebral marrow is equal to or lower than adjacent disc spaces.
which is best seen in the axial skeleton. Changes in the appendicular skeleton are observed considerably later. The vertical and horizontal trabeculae of the vertebral bodies are usually obliterated. Thinning of the cortex occurs early and in later stages radiolucent defects appear in the medullary regions which may be confused with metastatic disease or myeloma. Solitary lesions can occur. They may be purely osteolytic and can be expansile or may have calcification within the matrix. Involvement of the hands has been reported resulting in a coarse trabecular pattern which has similar appearances to that of sarcoidosis. On MRI yellow marrow has a uniform high signal intensity on TI weighted images due to its high fat content. Red marrow, as found in the axial skeleton, has a rather lower signal than yellow marrow because it contains a proportion of haemopoietic cells. The MR appearances of vertebral marrow depend on the amount of fatty replacement which has occurred. Fat replacement increases with age which shortens the TI of normal vertebrae (Dooms et aL, 1985) and leads to higher signal from vertebral marrow on T1 weighted images. Focal deposition of fat within haemopoietic marrow may lead to
633
a 'spotty' appearance with focal areas o f high signal on T1 weighted images, often distributed around the periphery of the vertebral bodies, in the posterior elements and near the vertebral end plates (Hajek et al., 1987). Cellular malignant deposits replace the normal marrow fat and can usually be identified as discrete areas of low signal within the vertebral bodies (Porter et al., 1986). Diffuse malignant disorders, such as myeloma or leukaemia, can result in a generalised reduction in marrow signal without focal lesions. Marrow infiltration in such cases may be recognised as the signal from marrow may be the same or even less than that from adjacent intervertebral discs on T1 weighted images. A focal reduction in marrow signal on T1 weighted images has also been reported in other conditions such as infection, infarction or fibrosis (Modic et al., 1985). A generalised decrease in marrow signal can be seen in sickle cell disease and has been reported in myelofibrosis (Porter et al., 1986). In this patient the M R I examination showed a diffuse infiltrative disorder and prompted a further search for a non-malignant systemic condition. The diagnosis of amyloid was made by rectal and renal biopsy. Large core bone biopsy confirmed that the abnormal marrow signal was also due to amyloidosis. Acknowledgements. The CRC Radiology Research Group is generously supported by the Cancer Research Campaign who fund two of the authors (J.F.C.O. and M.P.W.). We thank Dr P. Gishen for obtaining the large core bone biopsy which successfully confirmed the diagnosis of marrow amyloid and Dr J. E. Husband for her help and advice. We also thank Miss Jan Gadd and Mrs Dorothy Mears for careful preparation of the manuscrtpt.
REFERENCES Daffner, RH, Lupetin, AR, Dash, N, Deeb, ZL, Sefczek, RJ & Schapiro, RL (t986). MRI in the detection of malignant infiltration of bone marrow. American Journal of Roentgenology, 146, 353-358. Dooms, GC, Fisher, MR, Hricak, H, Richardson, M, Crooks, LE & Genant, HK (1985). Bone marrow imaging: magnetic resonance studies related to age and sex. Radiology, 155, 429-432. Hajek, PC, Baker, LL, Goobar, JE, Sartoris, D J, Hesselink, JR, Haghighi, Pet al. (1987). Focal fat deposition in axial bone marrow: MR characteristic. Radiology, 162, 245-249. Ludwig, H, Fruhwald, F, Tscho|akofi, D, Rasoul, S, Neuhold, A & Fritz, E (1987). Magnetic resonance imaging of the spine in multiple myeloma. Lancet, ii, 364-366. Modic, MT, Feiglin, DH, Piraino, DW, Boumphrey, F, Weinstein, MA, Duchesneau, PM et al. (1985). Vertebral osteomyelitis: assessment using MR. Radiology, 157, 157-166. Porter, BA, Shields, AF & Olson, D (1986). Magnetic resonance imaging of bone marrow disorders. Radiologic Clinics of North America, 24, 269-289. Subbarao, K. & Jacobson, H G (1986). Amyloidosis and plasma cell dyscrasias of the musculoskeletal system. Seminars in Roentgenology, xxi, 139-149.
Case Report: Magnetic Resonance Imaging of Spinal Amyloid J. F. C. OLLIFF, J. R. HARDY*, M. P. WILLIAMS and T. J. POWLES*
CRC Radiology Research Group, Department of Radiology and * Department of Medicine, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT.
This report describes a patient with a history of breast carcinoma who presented with back pain and multiple collapsed vertebrae. Magnetic resonance imaging (MRI) demonstrated a diffuse bone marrow abnormality, more in keeping with an infiltrative process than with metastases. A bone biopsy confirmed the suspected diagnosis of vertebral involvement by amyloid.
M R I o f the marrow has been shown to be a very sensitive technique for the detection of secondary deposits from diseases such as breast carcinoma and myeloma (Daffner et al., 1986; Ludwig et al., 1987). However, as this case report demonstrates, it is not a specific investigation.
CASE REPORT A 57-year-old woman presented with a 7 month history of back pain. Fifteen years previously she had undergone lumpectomy and radiotherapy for a right-sided breast carcinoma followed two years later by a right mastectomy for local recurrence. Since that time she had been well with no evidence of recurrence. Initial investigations had revealed a normochromic normocytic anaemia (10 g dl-1) and a marked elevation of erythrocyte sedimentahon rate at 130. Plain radiography o f the spine had shown generalised loss of bone density with partial collapse of L1, L3, L4 and L5 A myelogram demonstrated only minor disc bulges from L2 to L5 and some degenerative facet joint disease. Computed tomography (CT) examindtion of the lumbar spine confirmed loss of bony density but no bony metastatic deposits were identified. Bone biopsy of the posterior iliac crest was normal. She was referred to this hospital for further investigations to exclude a diagnosis of multiple myeloma and was found to have proteinuria excreting 15 g of protein per litre (selective for albumin and transferrin). There was no Bence Jones proteinuria and no para-protems were seen on serum electrophoresis. Skeletal survey again showed generalised osteopoenia with collapse of the lumbar vertebrae and the body of T 12. Bone marrow aspirate and trephine (Fig. l) showed no evidence of myeloma or carcinoma. MRI o f the thoracic and lumbar spines was performed. Surface coil images were obtained on a Siemens Magnetom Unit operating at 1.5 Tesla. T1 weighted images were obtained with a repetition time of 500 milliseconds and an echo time of 17 milliseconds. This sequence was selected as a routine screen for bone metastatic disease as it consistently d~fferentiates normal from abnormal marrow in the shortest time. T2 weighted images were not obtained as the appearance o f metastases on T2 weighted images is variable (Daffner et al., 1986). MRI demonstrated abnormally low signal throughout the vertebral bodies of the thoracic and lumbar spine with partial collapse of the bodies of T I2, L 1, L3, L4 and L5 (Fig. 2). The appearances were not felt to be typical of metastatic disease from carcinoma of the breast which usually appears as focal areas of reduced signal intensity on T1 weighted images (Daffner et al., 1986). A diffuse low signal from the marrow on T1 weighted images has been reported in leukaemia and myeloma (Porter et al., 1986) but as there was no other evidence o f myeloma or leukaemia the possibility of other diffuse infiltrative disorders was considered. A rectal biopsy was performed which showed deposition of eosinophilic material in the lamina propria which was shown to be amyloid. Amyloid was also present on renal biopsy. A large core bone biopsy performed under general anaesthesia of the vertebral bodies o f T12, L 1 and L3 showed extensive deposits of amyloid replacing the marrow spaces. In some areas the anayloid was undergoing ossification and Correspondence to: J. F. C. Olliff.
calcification. Congo red staining[ revealed positive apple green birefringence. She now remains well, apart from back pain, with no evidence of metastatic relapse from breast cancer.
DISCUSSION Primary amyloidosis is a systemic disorder characterised by the deposition of amyloid fibrils in the heart, kidneys, tongue, gastrointestinal tract, blood vessel walls, nerves, skin, muscles, peri-articular structures and calf ligaments. Men are affected more often than women, and unlike secondary amyloidosis there is no underlying disease and no known cause. Renal involvement is usual and protcinuria is very common affecting 90% of patients at the time of presentation. The sedimentation rate is generally raised. Even in primary amyloidosis, abnormalities in gamma globulins are seen in 50% of patients. Cardiac involvement is common with a restrictive cardiomyopathy, conduction defects due to amyloid deposition in the conducting system, or ischaemic heart disease because o f coronary artery infiltration. The gastrointestinal tract is also commonly involved with any area being affected and clinical findings depending on the site and type of involvement. Bone involvement by amyloid often results in pain at the site of disease. The radiologic manifestations of bone amyloidosis depend upon whether there is a diffuse or localised disease process (Subbarao and Jacobson, 1986). Generalised reduced bony density may be the only feature
Fig. 1 - Computed tomography section through a mid-lumbar vertebral body at the time of computed tomography guided vertebral body biopsy. The scan demonstrates decrease in bone density and abnormal texture from the cortical bone at this level.
MRI OF SPINAL AMYLOID
Fig. 2 Mid-line saggltal magnetic resonance image of the lumbar spine (TR 0.5 seconds TE 17 milliseconds). There are multiple levels of vertebral body collapse with compression of the anterior theca at L 1 and T12. The bone marrow sxgnal is diffusely low throughout. The signal intensity of the vertebral marrow is equal to or lower than adjacent disc spaces.
which is best seen in the axial skeleton. Changes in the appendicular skeleton are observed considerably later. The vertical and horizontal trabeculae of the vertebral bodies are usually obliterated. Thinning of the cortex occurs early and in later stages radiolucent defects appear in the medullary regions which may be confused with metastatic disease or myeloma. Solitary lesions can occur. They may be purely osteolytic and can be expansile or may have calcification within the matrix. Involvement of the hands has been reported resulting in a coarse trabecular pattern which has similar appearances to that of sarcoidosis. On MRI yellow marrow has a uniform high signal intensity on TI weighted images due to its high fat content. Red marrow, as found in the axial skeleton, has a rather lower signal than yellow marrow because it contains a proportion of haemopoietic cells. The MR appearances of vertebral marrow depend on the amount of fatty replacement which has occurred. Fat replacement increases with age which shortens the TI of normal vertebrae (Dooms et aL, 1985) and leads to higher signal from vertebral marrow on T1 weighted images. Focal deposition of fat within haemopoietic marrow may lead to
633
a 'spotty' appearance with focal areas o f high signal on T1 weighted images, often distributed around the periphery of the vertebral bodies, in the posterior elements and near the vertebral end plates (Hajek et al., 1987). Cellular malignant deposits replace the normal marrow fat and can usually be identified as discrete areas of low signal within the vertebral bodies (Porter et al., 1986). Diffuse malignant disorders, such as myeloma or leukaemia, can result in a generalised reduction in marrow signal without focal lesions. Marrow infiltration in such cases may be recognised as the signal from marrow may be the same or even less than that from adjacent intervertebral discs on T1 weighted images. A focal reduction in marrow signal on T1 weighted images has also been reported in other conditions such as infection, infarction or fibrosis (Modic et al., 1985). A generalised decrease in marrow signal can be seen in sickle cell disease and has been reported in myelofibrosis (Porter et al., 1986). In this patient the M R I examination showed a diffuse infiltrative disorder and prompted a further search for a non-malignant systemic condition. The diagnosis of amyloid was made by rectal and renal biopsy. Large core bone biopsy confirmed that the abnormal marrow signal was also due to amyloidosis. Acknowledgements. The CRC Radiology Research Group is generously supported by the Cancer Research Campaign who fund two of the authors (J.F.C.O. and M.P.W.). We thank Dr P. Gishen for obtaining the large core bone biopsy which successfully confirmed the diagnosis of marrow amyloid and Dr J. E. Husband for her help and advice. We also thank Miss Jan Gadd and Mrs Dorothy Mears for careful preparation of the manuscrtpt.
REFERENCES Daffner, RH, Lupetin, AR, Dash, N, Deeb, ZL, Sefczek, RJ & Schapiro, RL (t986). MRI in the detection of malignant infiltration of bone marrow. American Journal of Roentgenology, 146, 353-358. Dooms, GC, Fisher, MR, Hricak, H, Richardson, M, Crooks, LE & Genant, HK (1985). Bone marrow imaging: magnetic resonance studies related to age and sex. Radiology, 155, 429-432. Hajek, PC, Baker, LL, Goobar, JE, Sartoris, D J, Hesselink, JR, Haghighi, Pet al. (1987). Focal fat deposition in axial bone marrow: MR characteristic. Radiology, 162, 245-249. Ludwig, H, Fruhwald, F, Tscho|akofi, D, Rasoul, S, Neuhold, A & Fritz, E (1987). Magnetic resonance imaging of the spine in multiple myeloma. Lancet, ii, 364-366. Modic, MT, Feiglin, DH, Piraino, DW, Boumphrey, F, Weinstein, MA, Duchesneau, PM et al. (1985). Vertebral osteomyelitis: assessment using MR. Radiology, 157, 157-166. Porter, BA, Shields, AF & Olson, D (1986). Magnetic resonance imaging of bone marrow disorders. Radiologic Clinics of North America, 24, 269-289. Subbarao, K. & Jacobson, H G (1986). Amyloidosis and plasma cell dyscrasias of the musculoskeletal system. Seminars in Roentgenology, xxi, 139-149.