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A 61-year-old male has a 6 month history of low back pain with increasing left sciatic leg pain for 5 weeks. On examination, he has bone tenderness in the lumbar and thoracic spine. Neurological examination shows 4/5 weakness in the L5 distribution in the left leg. MRI images of the thoracic and lumbar spine are shown in Figures A. Follow-up laboratory studies show anemia associated with the presence of a serum monoclonal protein. What would be the next most appropriate investigation in the diagnostic work-up of this patient?
CT scan of head
Lower extremity electromyelography
Bone marrow aspiration and biopsy
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The patient's clinical history, imaging, and lab values are indicative of multiple myeloma. The next most appropriate investigation for the diagnosis of multiple myeloma would be bone marrow aspiration and biopsy.
A diagnosis of multiple myeloma may be based on the Durie and Salmon criteria. The criterion considers findings of plasmacytomas on tissue biopsy, plasmacytosis in bone marrow, monoclonal immunoglobulin spike on serum or urine electrophoresis, and radiographic evidence of lytic bone lesions (commonly in the spine, long bones and skull).
Walker et al. looked at the effectiveness of MRI on the clinical diagnosis of multiple myeloma. They showed that MRI detected focal lesions in 74% of cases, compared to 56% with standard metastatic bone surveys (e.g. radiographs) of imaged anatomic sites.
Palumbo et al. reviewed multiple myeloma. They state that bony lesions are evident on MRI in 80% of patients with newly diagnosed disease. Anemia, which is present in about 73% of patients at diagnosis, is related to bone marrow infiltration and/or renal dysfunction.
Figures A shows T2 MRI images of the thoracic and lumbar spine with diffuse lucencies throughout. Illustration A and B demonstrate a sheet of round plasma cells consistent with the histology of multiple myeloma. There is an eccentric nucleus, prominent nucleolus, and clock-face organization of chromatin. Illustration C shows the most common sites of multiple myeloma in the body.
Answer 1: A CT head is not necessary. Bony lesions in the skull can typically be detected on radiographs.
Answer 2: Urine electrophoresis would not be needed as there was presence of a serum monoclonal protein.
Answer 3: Electromyelography technique is used to evaluate the electrical activity produced by skeletal muscles, which can help diagnose peripheral nerve damage. This would not be used for the diagnostic work-up of multiple myeloma, however it may be used as adjunctive test for the investigation of his left leg sciatica.
Answer 4: There is no evidence to suggest lumbar puncture is indicated for the diagnosis of multiple myeloma.
Walker R, Barlogie B, Haessler J, Tricot G, Anaissie E, Shaughnessy JD Jr, Epstein J, van Hemert R, Erdem E, Hoering A, Crowley J, Ferris E, Hollmig K, van Rhee F, Zangari M, Pineda-Roman M, Mohiuddin A, Yaccoby S, Sawyer J, Angtuaco EJ.
J Clin Oncol. 2007 Mar 20;25(9):1121-8. Epub 2007 Feb 12. PMID: 17296972 (Link to Abstract)
Palumbo A, Anderson K.
N Engl J Med. 2011 Mar 17;364(11):1046-60. PMID: 21410373 (Link to Abstract)
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Lytic bone lesions, commonly seen in metastatic bone disease or multiple myeloma, are due to which of the following mechanisms?
RANK ligand action on neoplastic cells
RANK action on neoplastic cells
Osteoprotegrin action on osteoclastic cells
RANK ligand action on osteoclastic cells
RANK action on osteoclastic cells
Tumor induced osteolysis, commonly seen in metastatic bone disease, is caused by increased osteoclastic bone resorption. This cascade is caused by tumor induced cytokine signaling through the RANK to RANK ligand pathway which activates the osteoclast and encourage local bone resorption (Illustration A). Medical blockade of this pathway through the use of bisphosphonates or deactivators of the RANK/RANK ligand pathway like denosumab are an active area of current research (Illustration B). Illustration C shows a video that illustrates bone remodeling and regulation involving osteoprotegrin, RANK, RANK-ligand.
In these images, RANK is a cell surface receptor which is NOT secreted. RANK ligand is the "ligand" which is secreted by osteoblasts and binds and activates RANK receptor. Osteoprotegrin is the "decoy" receptor which blocks the action of RANK ligand binding RANK.
Nannuru et al used animal model to evaluate the regulation of RANKL expression and its functional significance in tumor-induced osteolysis. They found that increased RANK ligand expression potentiates tumor-induced osteolysis and blockade of this pathway prevents bone lysis.
In a related publication, Anastasilakis et al review the inhibition of this same cell signaling cascade and its role in the clincal treatment and prevention of complications related to metastatic bone disease such as pain and pathologic fracture.
Taranta et al report on the decreased bone mineral density associated with celiac disease. They propose a "cytokine imbalance" in the RANK, RANK ligand, Osteoprotegrin (OPG) signaling pathway as the likely cause of low bone mineral density.
Nannuru KC, Futakuchi M, Sadanandam A, Wilson TJ, Varney ML, Myers KJ, Li X, Marcusson EG, Singh RK.
Clin Exp Metastasis. 2009;26(7):797-808. Epub 2009 Jul 10. PMID: 19590968 (Link to Abstract)
Anastasilakis AD, Toulis KA, Polyzos SA, Terpos E
Expert Opin Investig Drugs. 2009 Aug;18(8):1085-102. PMID: 19558335 (Link to Abstract)
Taranta A, Fortunati D, Longo M, Rucci N, Iacomino E, Aliberti F, Facciuto E, Migliaccio S, Bardella MT, Dubini A, Borghi MO, Saraifoger S, Teti A, Bianchi ML
J. Bone Miner. Res.. 2004 Jul;19(7):1112-21. PMID: 15176994 (Link to Abstract)
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A 55-year-old male with chronic low grade back pain, intermittent fevers, and anemia underwent a bone biopsy for a lytic lesion in the spine. The biopsy is seen in Figure A. A urine protein electrophoresis is likely to show which of the following?
Polyclonal heavy chain immunoglobins
Polyclonal light chain immunoglobins
Monoclonal heavy chain immunoglobin
Monoclonal light chain immunoglobin
Decreased urine albumin
The answer is Monoclonal light chain immunoglobin.
Figure A shows multiple plasma cells suggestive of multiple myeloma. Multiple myeloma is a neoplastic process involving the proliferation of plasma cells. It is often associated with anemia, chronic pain, low-grade fevers, and skeletal lesions that are often "cold" on bone scans. Affected B-cells produce a single, non-functional antibody (ie “monoclonal”, and this can either be the light chain or the heavy chain, most commonly part of an IgG protein) which becomes the predominant antibody (nonfunctional) produced as the disease progresses. Quantitative measurements by urine electrophoresis can be used to diagnose and monitor the disease. Alternatively serum electrophoresis can be used to detect monoclonal heavy chain immunoglobins as monoclonal light chains are preferentially excreted by the kidneys.
Additional findings include: hypercalemia (when osteoclasts are breaking down bone, releasing calcium into the bloodstream), raised serum creatinine due to reduced renal function, which may be due to light chain deposition in the kidney.
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A 55-year-old male has chronic thoracic back pain and undergoes a biopsy of a suspicious lesion in the T6 vertebral body seen in Figure A. The asterisk in Figure B represents what type of cell seen by the pathologist?
Figure A shows a lytic destructive lesion in the vertebral body. Figure B shows multiple plasma cells. Multiple myeloma is a neoplastic process involving the proliferation of plasma cells. It is often associated with anemia, chronic pain, low-grade fevers, and skeletal lesions that are often "cold" on bone scans.
Weber showed that the main differential diagnosis for a patient older than 40 with a destructive bone lesion should include metastatic bone disease, multiple myeloma, lymphoma, and, less commonly, primary bone tumors.
J Am Acad Orthop Surg. 2010 Mar;18(3):169-79. PMID: 20190107 (Link to Abstract)
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HPI - 62 y/o male with 6 months of left shoulder pain. Had x-rays done at primary care office that did not show anything abnormal by report three months prior to presentation. He was thought to have rotator cuff tear/tendonitis and was given a steroid inje
Histologic and radiographic review of Multiple Myeloma by Dr. John Minarcik.
This video is an educational presentation discusses current trends in the medica...