Current and particular CT and MRI aspects of multiple myeloma

Current and particular CT and MRI aspects of multiple myeloma Poster No.: C-1257 Congress: ECR 2014 Type: Scientific Exhibit Authors: O. S. A. Alnuaimi, E. M. Preda, C. M. Capsa, I. G. Lupescu; Bucharest/RO Keywords: Oncology, Musculoskeletal bone, MR, CT, Diagnostic procedure, Neoplasia DOI: 10.1594/ecr2014/C-1257 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 33

Aims and objectives We chose to discuss this pathology because: we are working in a clinical center of hemato-oncology and see relatively large number of patients with multiple myeloma annually, its interesting wide range of clinical symptoms its variable imaging findings and differential diagnosis. In our study we tried to : 1. 2. 3. 4. 5. Illustrate elementary imaging findings of multiple myeloma, focusing on the bone lesions, Mention the still used conventional radiographies, Cover the used CT and MRI protocols used for diagnosis and follow up of this pathology, Deal with some particular complicated cases and the post treatment aspects, Describe some cases of differential diagnosis of this pathology. Methods and materials Retrospective study of 89 patients, extended on a period of 9 years. The male sex was predominant (male / female ratio: 1.95 / 1) (see Fig. 1 on page 3 ) and the mean age of the subjects was 55 + /-5Y. Clinical symptoms. Majority (88%) of our patients had a bone pain; some of them with pathological fractures (27%), weakness(13%), fatigue(45%), some with hypercalcimie (17%) and its neurological symptoms, different grades of anemia (10%) and some of them presented with renal failure (8%) (that's why it was not possible to use an IV contrast injection for this group) (see Fig. 2 on page 4 ). Imaging methods : Standard conventional radiographies. All the patients who had clinical pictures and lab results compatible with multiple myeloma (MM), had been evaluated using standard conventional radiographies firstly (cheaper and rapidly available); for the two or more bone segments to confirm the diagnosis ( so the hematologist sent the patients for skull and pelvic bones x rays Page 2 of 33

request, some of them had requested more bony segments like; skull, pelvic bones, ribs, upper limbs (humerus, radius and ulna) and lower limbs (femur, tibia and fibula). Relatively it was easier to see osteolytic bones lesions on these bones than on the others because of lung and digestive systems artifacts which accompany the thoracic and lumbar spine regions, then the next step (for some patients ) was the cross sectional imaging (CT and MRI) to determine the extent of the disease in the body, to describe each lesion with more details, to look for any complications or any region liable for complications and then to follow up the patients periodically after treatment trials (see Fig. 3 on page 5 and Fig. 4 on page 5 ). Computed tomography (CT) and Magnetic Resonance Imaging (MRI) evaluation. CT (48 patients - explored for suspected lesions in thoracic cage bones (34 patients) and some of them also for possible spinal lesions (21 patients) ) and MRI scans (41 patients - explored for spine, pelvic bones, upper and lower limbs bones) had been made for; further confirmation of the diagnosis and for the baseline evaluation data before the beginning of the treatment, then most (78 from 89) of our patients had been reevaluated periodically (in 6-12 months interval, according to the clinical status) for the follow up of the disease, for evaluation and monitoring of the first discovered lesions and there response to treatment and for any possible appeared complications. Protocols : Spiral CT acquisitions had been performed in precontrast mode and sometimes multiphase post contrast iodine IV followed by post processing in sagital, coronal and oblique reconstruction in a bone window. MRI evaluations were performed on a 1.5 T MR unit using T2-weighted sequences, STIR, T1SE and T1SE FatSat pre/ post contrast in multiple planes. Images for this section: Page 3 of 33

Fig. 1: Pie chart demonstrates the male sex predominance Page 4 of 33

Fig. 2: Bar chart demonstrates the types of clinical symptoms and their incidences Fig. 3: A and B : 43 years old male with clinical and biological pictures compatible with multiple myeloma, the hematologist sent it with requests of ribs and skull x rays, in the ribs x ray, rib fractures was discovered and the patient denied any type of trauma so the suspicion of pathological fracture is considered and the patient sent for CT thorax (see Fig. 4). Fig. 4: A, B, C and D : the same patient in Fig.3 with CT scan of the thorax; in addition to the rib fractures which were seen on the conventional x rays, the CT demonstrated many more typical lesions of MM (which were invisible on x ray) in the ribs, thoracic vertebrae, scapulae, humeral heads, clavicles, sternum and in the ribs. Page 5 of 33

Results Statistics (see Fig. 5 on page 10 and Fig. 6 on page 11): Nearly all our patients ( 87 din 89 = 97.7% ) demonstrated vertebral column involvement (cervical, thoracic and lumbo-sacral segments), 7 patients were with iliac bone involvement (7%), 6 with ribs involvement (6%), 2 patients with humeral bone involvement (2%) and 7 patients with parietal thoracic soft tissue mass lesions associated with bony destruction (7%), one of which localized in cranial base region. Radiological aspects: Conventional X ray films, are they still useful? What are the limitations? The typical appearance of MM (1) using conventional radiography in our study was (see Fig. 7 on page 11 and Fig. 8 on page 12): multiple, rounded, well defined, punched out, osteolytic lesions, around the one centimeter diameter, with endosteal scalloping with or without sclerotic margin or cortical erosions or periosteal reaction This pattern is very characteristic for multiple myeloma and it was described in the literature as Swiss cheese-pattern (2). Further radiological evaluation was necessary for the establishing whether there are or not other lesions in other bony segments, and here come the role of the advanced imaging procedures (CT and MRI), especially for the spine and other bony segments which are difficult to be evaluated using standard conventional x ray films because of the naturally existing artifacts (lung and bowel artifacts) (Fig. 9 on page 13 and Fig. 10 on page 14 ) and because of the limited informations gained from these conventional films in the evaluation of the complications and adjacent soft tissue involvement (Fig. 11 on page 15 ). Page 6 of 33

For the above mentioned causes it was necessary to proceed for the next steps in the evaluation of these segments using either MRI or CT scans. CT MM findings The typical appearance of multiple myeloma lesions in CT was represented by multiple well defined osteolytic lesions with or without cortical interruption) demonstrated in Fig. 12 on page 16 (A, B, C). MRI MM findings Regarding the MRI aspects, in our study, we had several morphological types of lesions: - multiple nodular and micronodular lesions (20 from 41 evaluated by MRI - 50%, as in Fig. 13 on page 17 ), - multiple nodular lesions, the second most common type (8 from 41-20%), - multiple micronodular lesions (like pepper and salt) type (3 from 41-7%, as in Fig. 14 on page 18 ), - focal nodular lesion which began as plasmacytoma and then progress to multiple myeloma (5 from 41-12 % as in Fig. 15 on page 20 - in which we see one of the rare locations of this pathology), - infiltrative type (3 from 41-7%) - focal (Fig. 16 on page 20 ) or diffuse (it means diffuse infiltration of spongious bone with a low T1 signal intensity lesion /compared to the MRI signal of the adjacent muscle). - two patients (4%) had negative MRI findings even though their clinical and laboratory pictures were compatible with multiple myeloma, so the normal MRI evatuation does not exclude the disease. One of the fundamental roles of advanced radiological investigations (CT and MRI) in the management of this pathology is there high specificity and sensitivity in the follow up of the disease (stabile/progression/regression), in the evaluation of post treatment aspects Page 7 of 33

of some lesions and in the diagnosis of any suspected complications ( intra and extra osseous extension). This affirm the conclusions of other studies from the literature, for e.g. Judith S. Schreiman and his colleagues had mentioned that : (The radiologic evaluation of multiple myeloma has included and should continue to include a conventional film skeletal survey. In those patients who have normal radiographs and bone pain, CT evaluation is frequently valuable. The CT demonstration of bony lesions that are not seen on radiographs often indicates the need to initiate therapy. CT is superior to radiographs in the evaluation of an extraosseous plasmacytoma, demonstrating both the bony involvement and the soft-tissue component. CT may be helpful in demonstrating disseminated disease in a patient who has an apparent solitary plasmacytoma) (3). and also Herman I. Libshitz and his colleagues said that : (Magnetic resonance (MR) imaging has been shown to be more sensitive than conventional imaging ; plain radiography and computed tomography at detecting skeletal abnormalities in multiple myeloma) and they also recognized in the same study that bone marrow infiltration in multiple myeloma takes two forms; the diffuse infiltration and the focal lesions. (4). Dynamic follow up : progression / regression majority of our patients (78 from 89) had a dynamic follow up evaluations by different methods, in the follow up of the disease we rely on three criteria; 1- the number of the lesions (whether it increases or decreases - in one bone segment or in all skeleton ), 2- the size of the known (target) lesions, 3- the appearance or not of any complication. Every increase in number of the lesions or dimensions of any lesion or every appearance of any complication are considered as disease progression, and then inversely are Page 8 of 33

considered as disease regression, otherwise in the absence of any of these changes the disease is then considered generally stable even if there are some possible appearing modifications in the radio-imagistic aspects of some lesions after treatment. In our study, we did not record any decrease in the lesions number, but majority (67 %) of the evaluated patients showed stable disease (lesions with same number and dimensionswith treatment), some of them show dimensional progression (Fig. 8 on page 12 and Fig. 18 on page 21), others had progressed by appearance of some complications (bone invasion, pathological fracture, vertebral collapse and spinal canal compression...etc) (Fig. 11 on page 15, Fig. 17 on page 21(5), Fig. 18 on page 21, Fig. 23 on page 26 and Fig. 24 on page 26) and small number of patients showed dimensional regression but not lesions disappearance (Fig. 19 on page 22 ). Post treatment imaging aspects : MM it supposed to be incurable but highly treatable disease with steroids, chemotherapy (in disseminated disease), proteasome inhibitors, osteoclast inhibitors, immunomodulatory drugs and stem cell transplants. Radiation therapy (for local disease) is sometimes used to reduce pain from bone lesions (6). Surgical treatment is also used (internal fixation of pathological fractures, decompresive laminectomy and vertebraoplasty. Even when there are no changes in the number of the size of the lesions and no complication appeared and the disease considered as stabile, we noticed some changes in the aspect of some lesions after treatment (especially after radiation) because this may give indication for somewhat a response to the treatment, these changes are : - the sclerotic borders which develop around the osteolytic lesions - visible in plain x rays (Fig. 8 on page 12) and CT scans (Fig. 20 on page 22), - the low signal intensity on T2 (lost high signal intensity on T2) and lower signal intensity on T1 (but still showed some enhancement) - visible in MRI (Fig. 21 on page 24 and Fig. 22 on page 24). Complications (Fig. 17 on page 21(5), Fig. 18 on page 21, Fig. 23 on page 26 and Fig. 24 on page 26): The more serious complications of the multiple myeloma are: - fractures, Page 9 of 33

- soft tissue extension and - spinal cord compression Differential diagnosis: There are several pathologies which have radiological picture similar to multiple myeloma with some differences; - lymphoma is one of them (appear as ivory dense vertebrae in standard x ray but the MRaspect is similar to MM with later cortical destruction)(fig. 25 on page 27)(5), - metastasis are another common differential diagnosis but these are ill defined lesions (not well defined like in multiple myeloma) with predominant early involvement of posterior portion of vertebral body and vertebral pedicles (the site of the blood vessels entry to the vertebrae (Fig. 26 on page 28) and the metastases also has high activity in bone scan (while the bone scan in multiple myeloma is normal due to minimal new bone formation and only increase uptake in 10 percent)(1). - hemangiomas (Fig. 27 on page 29) which show typical (pepper and salt in transverse CT images ) and (vertical striations in lateral X ray and sagital CT images ) and because of their vascular elements, they appear in MRI as a high intensity lesion in both T1/T2 weighted images (not in low in signal intensity on T1 like MM) and usually not enhance (only the aggressive types) and if cause secondary bone fracture not associated with soft tissue mass (1). Some others differential diagnosis which may resemble multiple myeloma are; osteoporosis (no cortical destruction, no endosteal scalloping and no soft tissue mass), leukemia (multiple osteolytic lesions with many types of periosteal reactions; lamellate, sunburst and the smooth type) langerhans cell histeocytosis (it is young ages disease and self limited) and Gaucher disease (glucocerebroside deposition) (which is also young ages disease, cause widening of the ends of long bones resembling a flask Erlenmeyer flask deformity and not associated with soft tissue mass) (1). Images for this section: Page 10 of 33

Fig. 5: Bar Chart demonstrates the predominant axial skeleton involvement Fig. 6: Line Chart demonstrates the predominant axial skeleton involvement Page 11 of 33

Fig. 7: Standard skull x rays (lateral and AP views) to demonstrate the role of standard x ray in the diagnosis and follow up of some cases of multiple myeloma : multiple rounded, well defined, punched out, osteolytic lesions, around the one centimeter diameter, with endosteal scalloping but without sclerotic margin or cortical erosions or periosteal reaction. Page 12 of 33

Fig. 8: Standard skull x rays (lateral views) to demonstrate the role of standard x ray in the diagnosis and follow up of some cases of multiple myeloma : multiple rounded, well defined, punched out, osteolytic lesions, around the one centimeter diameter, with endosteal scalloping but without sclerotic margin or cortical erosions or periosteal reaction. Dynamic evaluation (in 11 weeks interval), notice dimensional progression of one of these lesions after stop of treatment; we can notice also the sclerotic margins surrounding the lesion. Page 13 of 33

Fig. 9: Pelvic bones of the 46 years female with MM difficulties to discover the osteolytic lesions because of the bowel content overlying the iliosacral bones. Page 14 of 33

Fig. 10: AP X ray of the thoracic cage bones of the 58 years male with MM : Lung "artifacts" overlying the ribs and thoracic spine. Page 15 of 33

Fig. 11: 43 years male with MM: multiple osteolytic lesions, in the humeral diaphysis some with cortical erosions; difficulty to evaluate the cortical destruction and the degree of soft tissue involvement near the medial aspect of this bone segment. Page 16 of 33

Fig. 12: 56 years old male with MM. CT scan ( cross sections - A, B and MIP reconstruction - C ) : huge number of small rounded well defined osteolytic lesions, some of the with cortical erosions, involving nearly all the bony segments of axial skeleton (ribs, sternum, spine, scapulae, iliac and sacral bones). Page 17 of 33

Fig. 13: 71 years old male with bone pain on rest. MRI of the lumbar spine (T2-A, STIR-B, T1 FS precontrast -C, T1 FS after contrast injection-d) : multiple nodular and micronodular vertebral bony lesions which have high signal intensity on T2, high signal intensity on STIR, intermediate to low signal intensity on T1 FS and show marked enhancement in T1 FS with contrast Page 18 of 33

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Fig. 14: 60 years old female, MRI of the lumbar spine (T2-A, T1 FS -B, STIR-C) : multiple micronodular vertebral bony lesions like pepper and salt. Fig. 15: Cerebral MRI of 60 years old female show a plasmacytoma as a focal mass located in the right half of the sphenoid sinus, near the right cavernous sinuous,in contact with the right ICA, extended posteriorly to the basisphenoid bone(one of the rare locations of this disease,in low T1 signal intensity and high signal intensity on T2/FLAIR/STIR, without restriction of diffusion in DWI/ADC map, with marked heterogeneous contrast enhancement. Page 20 of 33

Fig. 16: Pelvic MRI of 50 years old female with multiple myeloma showing infiltrative focal type lesion (in high signal intensity on T2/STIR- A,B, low signal intensity on T1-C, with non homogenous contrast enhancement- D ) at the level of the left iliac bone Fig. 17: MRI of thoracic spine of patient with MM : (T1SE, STIR, T1FS, T1FS+C), collapse of T10 vertebral body with prevertebral and epidural extension and spinal cord compression (13). Fig. 18: 60 years old male with MM. CT scan of the thorax (A and B): marked dimensional progression of the disease following one year after stop taking treatment with appearance of cortical destruction of the rib and invasion adjacent soft tissue Page 21 of 33

Fig. 19: T2 weighted MRI images (A and B) of the 58 years old male with MM: dimensional regression of the target lesion following seven months treatment, notice the diffuse infiltrative type of the lesion. Page 22 of 33

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Fig. 20: CT scans of the thoracic spine of 56 years old male with multiple myeloma demonstrate the development of sclerotic borders around the osteolytic lesions. Fig. 21: Typical and post treatment (post radiation) MRI appearance, notice the lost T2 high signal intensity Page 24 of 33

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Fig. 22: A T2, B STIR, C T1FS, D T1FS + C with zoom. MRI of the lumbar spine of 55 years old female with MM showed the post treatment changes in one lesion (more low signal intensity on T1 (but still show some enhancement) and low signal intensity on T2 (lost high signal intensity on T2/STIR). Fig. 23: A,B,C and D : 71 years old female with MM. NE Head CT. large occipital bone lesion in the right side which cause cortical destruction and extra osseous extent in both extra (subcutaneous) and intracranial (meningeal) tissues Page 26 of 33

Fig. 24: A T2, B STIR, C T1FS and D T1FS +C : 51 years old female with MM. MRI of the left shoulder: extensive bone lesion involving the humeral head which extend to the metaphysis, proximal diaphysis and cause cortical destruction and soft tissue invasion. Notice the similar smaller lesion visible in the scapular side of this shoulder joint. Page 27 of 33

Fig. 25: Patient with Hodgkin disease : Thoracic and lumbar spine MRI : vertebral body lesions with high signal intensity (STIR) and intermediate/low signal intensity (T1)(13) Page 28 of 33

Fig. 26: (A to I) example of young age male spine metastasis from brain with posterior element involvement, epidural and paravertebral tumor extension. Page 29 of 33

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Fig. 27: CT (A) and MRI (B, C,D,E): The typical aspects of hemangioma : (pepper and salt ) in transverse CT images, vertical striations in sagital CT images and high intensity in both T1/T2 weighted MRI images because of their vascular elements and mixed signal intensity on STIR. Page 31 of 33

Conclusion Multiple myeloma is a disease with a wide clinical spectrum, mutisystemic involvement and specific biological pictures and lab results. The role of radiological procedures is to evaluate the lesions and to follow up the disease. The high light points of our study are : - The disease may begins as a solitary lesion in the bone or soft tissue (Plasmocytoma) and then progress to multiple myeloma which also may complicate to cortical destruction, soft tissue involvement and extensions to some vital organs like spinal cord compression or orbital invasion or cerebral venous sinuous invasions, - The standard conventional radiographical procedures still have a role in first evaluation and in follow up in some but not all body areas (because of the natural existing artifacts ), - CT and MRI were better and more sensitive and specific in the detailed evaluation of the extent of the disease, the complications and the effect of the treatment, - Differential diagnosis is made with metastases, lymphomas and hemangiomas, so it is imperative to correlate imaging findings to the clinico-biological background, -In all our patients the disease was not curable one, usually stable with treatment but some of patients had progression or less frequently regression, - Even if the disease appeared stable but still there were some changes occurred in some dimensionally and numerically stable lesions after certain types of the treatments, these changes were visible in all radiological procedures (like sclerosis in standard X-rays/CT and lost high signal intensity on T2 weighted images in MRI). Personal information Osama S. Abdulrahman Alnuaimi M.D. Radiology resident Department of radiology, medical imaging and interventional radiology, Fundeni Clinical Institute, Bucharest, Romania alnuaimi62003@yahoo.com Ioana Gabriela Lupescu Page 32 of 33

Professor in Radiology and Medical Imaging specialty, Ph D Head of Department of radiology, medical imaging and interventional radiology of Fundeni Clinical Institute, Bucharest, Romania University of Medicine and Pharmacy "Carol Davila" Bucharest, Romania ilupescu@gmail.com References 1. David W Stoller, Phillip F.J. Tirman, Miriam A. Bredella, Salvador Beltran, Robert M. Branstetter, Simon C. P. Blease, Diagnostic Imaging orthopaedics book, first edition, 2004, section 7, 18-21. 2. Henk J., Robin S., bone tumor H-0 (Bone tumors and tumor-like lesions in alphabetic order), radiology assistant, november 1, 2013. 3. Judith S. Schreiman, Richard A. McLeod, Robert A Kyle, John W. Beabout. Multiple Myeloma: Evaluation by CT, RSNA, Radiology 1985; 154: 483-486 4. Herman I. Libshitz, Simon R. Malthouse, D avid Cunningham, A. David MacVicar, Janet E. Husband. Multiple Myeloma: Appearance at MR Imaging, RSNA, Radiology 1992; 182:833-837 5. I. Lupescu. Spinal bone marrow disease. Erasmus course on MRI, CNS II, Bucharest 31.08-4.09.2013 6. Tim Kenny, Louise Newson, Myeloma, EMIS, 24/01/2012, 4884 Version: 41, page 5. Page 33 of 33