bone disease in plasma cell dyscrasias - lieberman's...
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Bone Disease in Plasma Cell Dyscrasias
Sarah BillmeierHarvard Medical School Year III
Gillian Lieberman, MD
July 2004
Courtesy of Dr. Ferris Hall
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Objectives
• Characterization of the plasma cell neoplasms
• Radiologic work up of Multiple Myeloma• A Visual Journey
Multiple Myeloma: LyticMultiple Myeloma: OsteopenicSclerotic Plasma Cell Neoplasms
Diffuse: Sclerotic Multiple MyelomaSolitary: Sclerotic PlasmacytomaMultifocal: POEMS
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Definitions• Multiple Myeloma (MM) = monoclonal malignant
proliferation of plasma cells
•
Plasmacytoma = discrete, solitary mass of neoplastic monoclonal plasma cells in either bone or soft tissue (extramedullary). Absence of multiple lesions, marrow plasmacytosis or other features of MM. Progresses to MM in 50-60%.
•
POEMS = syndrome of Polyneuropathy, Organomegally, Endocrinopathy, Monoclonal gammopathy & Skin problems
•
MGUS = Monoclonal Gammopathy of Undetermined Significance: Presence of M-protein in urine without evidence of multiple myeloma. With long term follow up 25% develop MM.
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Multiple Myeloma• Minimal diagnostic criteria:
Presence of >10% plasma cells in the BM or plasmacytoma
Serum or urine monoclonal protein
Related organ or tissue impairment (↑ calcium, renal insufficiency, anemia, lytic bone lesions, hyperviscosity, amyloidosis, recurrent infections)
• Epidemiology: MM represents 1-2% of all malignant disease & 10-33% hematologic malignancies. Incidence increases with age. Men > Women. Blacks >Whites
• Presentation: Bone pain precipitated by movement = most common. Other common symptoms include weakness, fatigue and weight loss.
http://radiology.uchc.edu/Code/1454.ht m
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Staging of MM – Durie & Salmon
Stage I – Low cell mass
All of the following Present:
• Hgb > 10 g/dl
• Serum IgG < 5 g/dl
• Serum IgA <3 g/dl
• Normal serum calcium
• Urine monoclonal prtn excretion <4 g/day
• No generalized lytic bone lesions
Stage III - High Cell Mass
>1 of the following:
• Hgb <8.5 g/dl
• Serum IgG > 7 g/dl
• Serum IgA > 5 g/dl
• Serum calcium >12 mg/dl
• Urine monoclonal prtn excretion >12 g/day
• Advanced lytic bone lesions
Stage II – Intermediate cell mass Fitting neither I nor III
Based on staging and other prognostic indicators median survival ranges from 5 years
to 15 months
Systemic tx is indicated for Stage II & III patients
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
The Skeletal SurveyThe skeletal survey used at dx of MM to detect bone pathology for:
• Establishment of a baseline for future follow-up • Assessment of fracture risk• Staging
The skeletal survey in an adult consists of plain radiographs of the• skull (AP and lateral)• ribs (AP global, AP on the lower thoracic grid, two oblique views)• spine (AP and lateral of cervical, thoracic and lumbar areas)• pelvis (AP)• femurs (AP and lateral)• humerus (AP and lateral)
Bone scintigraphy is less sensitive than plain films in identifying lytic lesions. Most lesions of MM are not apparent unless a fracture occurred or the lesion is in a healing phase.
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
MRI for lesion detection in MM?Several studies suggest
that MR is superior to radiographs for detection
of lesions in the spine.
The Durie and Salmon staging system was
developed in 1975 when only plain film was
available to image the skeleton.
Currently, MRI is not standardly used in MM
patients.Spine imaging of the same patient using
MRI and plain film
Baur A. et al. Cancer. 2002 Sep 15.
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Role for PET?
By directly imaging the increased metabolic activity of the bone
marrow PET may be able to:
• detect early lesions missed by skeletal
surveys or MRI
• may be useful to monitor response to
therapy
Currently PET is not commonly used for MM
imaging.PACS, BIDMC
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
What Causes Lytic Lesions in MM?
• Patients taking bisphosphonates (which inhibit osteoclasts) do not have an increase in bone formation within lytic lesions
• Long search for a secreted factor that activates osteoclasts
• Myeloma cells secrete RANKL to increase osteoclast activity and DKKI to inhibit osteoblasts, creating a bias toward negative bone balanceGlass DA 2nd. Patel MS. Karsenty G. NEJM 2003 Dec
25.
• Formation of osteolytic lesions involves uncoupling of bone resorption and formation
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
A Visual Journey by Case Series• Multiple Myeloma: Lytic
Patient 1: GWPatient 2: SL
• Multiple Myeloma: OsteopenicPatient 3: BV
• Sclerotic Plasma Cell NeoplasmsDiffuse: Sclerotic Multiple Myeloma
Patient 4: HMSolitary: Sclerotic PlasmacytomaMultifocal: POEMS
Patient 5: OJ (Plasmocytoma)Patient 6: BP (Mixed lytic-sclerotic)
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Sarah Billmeier, HMS IIIGillian Lieberman, MD Lytic Lesions of MM:
Patient 1 - GWGW is a 71 y.o. female who presents to the EW with mild pain and an inability to walk. Labs indicate M-protein by electrophoresis.
Pathologic fracture
Multiple lytic lesions without sclerotic margins
Courtesy of Dr. Ferris Hall
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Lytic MM: GW, Additional Radiographs
Lateral skull film with classic
punched out lytic lesions of various sizes
Courtesy of Dr. Ferris Hall
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
DDx Multiple Punched-Out Lytic Lesions of Bone with Nonsclerotic Margins
Common:
• Arthritis (eg, gout, rheumatoid, osteoarthritis)
• Brown tumors of hyperparathyroidism
• Langerhans Cell Histiocytosis
• Metastases
• Multiple Myeloma
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Lytic MM Patient 2: Disease ProgressionSL was diagnosed in 1971 at age 28, initially with an isolated
plasmacytoma.
10% of MM patients have an indolent course.
June 1976 April 1985
All films this slide courtesy of Dr. Ferris Hall
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Complications of Bone Destruction
Pathologic Fracture
Additional Lesions
Courtesy of Dr. Ferris Hall
Lytic lesions may cause:
• hypercalcemia
• pathologic fractures
• loss of height
• cord compression
• osteoporosis
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Osteopenia in MM
• Evidence for diffuse bone loss in 60% of multiple myeloma patients
• In 5% of patients bone loss occurs without focal lytic lesions
• Bisphosphonates often used for treatment of bone disease in MM. Use of palmidronate is associated with:
↓ pathologic fractures↓ need for irradiation/surgery of bone↓ spinal cord compressionPrevention of hypercalcemia↓ bone pain.
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Osteopenic MM: Patient 3 - BV
Lateral thoracic spine illustrates diffuse osteopenia
PACS, BIDMC
History: BV is a 54 y.o. female diagnosed with MM following a fall onto her hip, which lead to the discovery of lytic lesions in the pubic bone, leukopenia, anemia, and an monoclonal IgG lambda spike. A confirming bone marrow biopsy showed greater than 30% plasma cells. Compression Fracture
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Osteosclerotic MM• 3-4% plasma cell neoplasms are sclerotic
• Sclerotic plasma cell neoplasms can be divided into:
Solitary: Sclerotic plasmacytoma
Diffuse: Sclerotic MM
Multifocal: POEMS
• 85% sclerotic myeloma patients present with polyneuropathy
• More indolent course
• Affects younger patients
• Lambda > Kappa chains
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Diffuse Osteosclerotic MM: Patient 4 - HM
Bone “superscan” with symmetrically diffuse increase of tracer uptake and diminished renal activity
Lateral spine radiograph of diffuse
sclerosisPACS, BIDMC
PACS, BIDMC
History: HM is 77 y.o. woman who presented with DOE and
pancytopenia. Initial work-up for lymphoproliferative disease prompted a CXR, CT, bone scan, skeletal survey and
electrophoresis.
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
POEMS• Polyneuropathy – predominantly sensorimotor
• Organomegally – liver, spleen or lymph nodes
• Endocrinopathy – impotence, amenorrhea, gynecomastia, IGT
• Monoclonal gammopathy – myeloma in >50%, MGUS or others
• Skin Changes – hyperpigmentation, thickening, hirsutism
• Rare! • Affected patients may not have all findings• Pathogenesis remains unknown• Skeletal findings usually on axial and proximal appedicular skeleton and are usually sclerotic or infrequently mixed lytic-sclerotic
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Sclerotic Plasmacytoma POEMS Pt. 5: OJHistory: OJ is a 42 y.o. male who presented with back pain,
endocrinopathy, parasthesias & leg weakness. IgG was slightly ↑, Bx diagnosed a plasmacytoma. MRI was performed to evaluate
CC.
PACS, BIDMC PACS, BIDMC
CT: well defined lytic lesion with
sclerotic rim. No cortical
destruction or bony
expansion.
PET fusion: Homogenous
focus of intense FDG uptake
T2W fat suppressed MRI: lesion with dark
signal margin & high
intensity central aspect.
T1W MRI: lesion with a dark margin
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Mixed Lytic-sclerotic POEMS Patient 6: BP
Plain film of the pelvis: multiple foci of sclerosis
Round lytic lesion within
sclerotic focus
BP is a 27 y.o. male
who presents with
gynecomasti a, impotence
& papilledema
Courtesy of Dr. Ferris Hall
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Mixed Lyic-sclerotic POEMS
Patient PB’s Axial CT of the pelvis at the level of
the lytic lesion seen on plain film
Courtesy of Dr. Ferris Hall
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
SummaryPlasma cell neoplasms are often first diagnosed radiologically
Plain film & potentially MRI or PET findings influence tumor prognosis and therapy decisions
Skeletal surveys may be supplemented by additional imaging modalities in the future for lesion detection and follow-up
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Sarah Billmeier, HMS IIIGillian Lieberman, MD References
• Aggarwal S. Goulatia RK. Sood A. Prasad K. Ahuja GK. Mitchell MJ. Kumar A. POEMS syndrome: a rare variety of plasma cell dyscrasia. AJR. American Journal of Roentgenology. 155(2):339-41, 1990 Aug.
• Baur A. Stabler A. Nagel D. Lamerz R. Bartl R. Hiller E. Wendtner C. Bachner F. Reiser M. Magnetic resonance imaging as a supplement for the clinical staging system of Durie and Salmon?. Cancer. 95(6):1334-45, 2002 Sep 15.
• Croucher PI. Apperley JF. Bone disease in multiple myeloma. British Journal of Haematology. 103(4):902-10, 1998 Dec.
• Edelman RR. Kaufman H. Kolodny GM. Case report 350: Multiple myeloma--blastic type. Skeletal Radiology. 15(2):160-3, 1986.
• Glass DA 2nd. Patel MS. Karsenty G. A new insight into the formation of osteolytic lesions in multiple myeloma. New England Journal of Medicine. 349(26):2479-80, 2003 Dec 25.
• Jadvar H. Conti PS. Diagnostic utility of FDG PET in multiple myeloma. Skeletal Radiology. 31(12):690-4, 2002 Dec.
• Hall FM. Gore SM. Osteosclerotic myeloma variants. Skeletal Radiology. 17(2):101-5, 1988.• Kyle, RA. Clinical and laboratory manifestations of multiple myeloma. UpToDate. 2004, Jan
24.• Lecouvet FE. Malghem J. Michaux L. Maldague B. Ferrant A. Michaux JL. Vande Berg BC.
Skeletal survey in advanced multiple myeloma: radiographic versus MR imaging survey. British Journal of Haematology. 106(1):35-9, 1999 Jul.
• Longo, DL. Plasma Cell Disorders. Harrisons Online. www.harrisonsonline.com accessed 2004, July 20.
• Pathweb. Diseases of Bone, Multiple Myeloma. http://radiology.uchc.edu/Code/1454.htm•
Reeder, Maurice M. Reeder and Felson's Gamuts in Radiology: Comprehensive Lists of Roentgen differential diagnosis, 3rd ed. Springer-Verlag, New York, 1993.
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Sarah Billmeier, HMS IIIGillian Lieberman, MD
Acknowledgements
• Ferris Hall, MD• Mary Hochman, MD• Stephanie DiPerna, MD• Gillian Lieberman, MD• Pamela Lepkowski• Larry Barbaras our Webmaster