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A case of multiple myeloma with navicular bone involvement
Abstract
Multiple myeloma is a haematological disease caused by proliferation of malignant plasma cells in bone marrow. It frequently has lytic bone lesions. However, involvement of the small bones of the hands and feet is extremely rare. We report a unique multiple myeloma patient with first recurrence in navicular bone after allogenic stem cell transplantation.
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Introduction:
Patients with myeloma develop localized and generalized bone loss leading to hypercalcaemia, accelerated osteoporosis, vertebral wedge fractures, other pathological fractures, spinal cord compression and bone pain. Bone loss is mediated by a variety of biological modifiers including osteoclast-activating factors (OAF) and osteoblast (OB) inhibitory factors produced either directly by malignant plasma cells (MPCs) or as a consequence of their interaction with the bone marrow microenvironment (BMM). Raised levels of OAFs such as receptor activator of nuclear factor-kappa B ligand (RANKL), macrophage inflammatory protein 1 alpha, tumour necrosis factor-alpha and interleukin 6 stimulate bone resorption by recruiting additional osteoclasts. Via opposing mechanisms, increases in OB inhibitory factors, such as dickkopf-1 (Dkk-1), soluble frizzled-related protein-3 and hepatocyte growth factor (HGF), suppress bone formation by inhibiting the differentiation and recruitment of OBs. These changes result in an uncoupling of physiological bone remodelling, leading to myeloma bone disease (MBD). Moreover, the altered BMM provides a fertile ground for the growth and survival of MPCs. Current clinical management of MBD is both reactive (to pain and fractures) and preventive, with bisphosphonates (BPs) being the mainstay of pharmacological treatment. However, side effects and uncertainties associated with BPs warrant the search for more targeted treatments for MBD. This review will summarize recent developments in understanding the intimate relationship between MBD and the BMM and the novel ways in which they are being therapeutically targeted.
Sources of data:
All data included were sourced and referenced from PubMed.
Areas of agreement:
The clinical utility of BP therapy is well established. However, there is general acknowledgement that BPs are only partially successful in the treatment of MBD. The number of skeletal events attributable to myeloma are reduced by BPs but not totally eliminated. Furthermore, existing damage is not repaired. It is widely recognized that more effective treatments are needed.
Areas of controversy:
There remains controversy concerning the duration of BP therapy. Whether denosumab is a viable alternative to BP therapy is also contested. Many of the new therapeutic strategies discussed are yet to translate to clinical practice and demonstrate equal efficacy or superiority to BP therapy. It also remains controversial whether reported anti-tumour effects of bone-modulating therapies are clinically significant.
Growing points:
The potential clinical utility of bone anabolic therapies including agents such as anti-Dkk-1, anti-sclerostin and anti-HGF is becoming increasingly recognized.
Areas timely for developing research:
Further research effectively targeting the mediators of MBD, targeting both bone resorption and bone formation, is urgently needed. This should translate promptly to clinical trials of combination therapy comprising anti-resorptives and bone anabolic therapies to demonstrate efficacy and improved outcomes over BPs.
Myeloma bone disease (MBD) is a devastating complication of multiple myeloma (MM). More than 80% of MM patients suffer from destructive bony lesions, leading to pain, fractures, mobility issues, and neurological deficits. MBD is not only a main cause of disability and morbidity in MM patients but also increases the cost of management. Bone destruction and lack of bone formation are main factors in the development of MBD. Some novel factors are found to be involved in the pathogenesis of MBD, eg, receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) system (RANKL/OPG), Wingless (Wnt), dickkopf-1 (Wnt/DKK1) pathway. The addition of novel agents in the treatment of MM, use of bisphosphonates and other supportive modalities such as radiotherapy, vertebroplasty/kyphoplasty, and surgical interventions, all have significant roles in the treatment of MBD. This review provides an overview on the pathophysiology and management of MBD.
Medical imaging is of crucial importance for diagnosis and initial staging as well as for differentiation of multiple myeloma (MM) from other monoclonal plasma cell diseases. Conventional radiography represents the reference standard for diagnosis of MM due to its wide availability and low costs despite its known limitations such as low sensitivity, limited specificity and its inability to detect extraosseous lesions. Besides conventional radiography, newer cross-sectional imaging modalities such as whole-body low-dose computed tomography (CT), whole-body magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT are available for the diagnosis of osseous and extraosseous manifestations of MM. Whole-body low-dose CT is used increasingly, replacing conventional radiography at selected centers, due to its higher sensitivity for the detection of osseous lesions and its ability to diagnose extraosseous lesions. The highest sensitivity for both detection of bone marrow disease and extraosseous lesions can be achieved with whole-body MRI and (18)F-FDG PET/CT. According to current evidence, MRI is the most sensitive method for initial staging while (18)F-FDG PET/CT allows monitoring of treatment of MM. There is an evolving role for assessment of treatment response using newer MR imaging techniques. Future studies are needed to further define the exact role of the different imaging modalities for individual risk stratification and therapy monitoring.
A patient is reported who developed five plasmacytomas over a four-year period and developed a pleural mesothelioma 12 years later. The relationship of these two entities is discussed and the question of a common environmental carcinogen is raised.
Solitary myeloma can present as either extramedullary plasmacytoma or solitary plasmacytoma of bone (SPB). More than half of reported cases of SPB are localized to the spine. The rest include appendage long bones of the skeleton, pelvis, and skull. The first case of SPB (to the authors' knowledge) is reported involving the talus bone of the foot. Although approximately 50% of SPB patients progress to multiple myeloma in the first 3 years after diagnosis, aggressive local therapy is indicated because the median survival of patients with SPB is better than that for multiple myeloma.
Solitary plasmacytoma is an isolated malignant lesion of plasma cell origin. More than half of the reported cases of solitary plasmacytomas occur in the spine. Lesions occurring in the appendicular skeleton have a lower local recurrence rate and a favorable long-term survival rate. This is the first report of a solitary plasmacytoma involving a bone of the foot. With accurate diagnosis and effective medical treatment, long-term remission can be anticipated. © 1988, American Orthopaedic Foot & Ankle Society. All rights reserved.
Radiography of the hand often reflects the picture of generalized diseases, affecting both the muscolo-skeletal system and the others. Some of the most common hematologic disorders may be detected in roentgenograms of the hand, especially in the anemias, but also in plasma cell dyscrasias and proliferative malignant diseases (i.e., lymphomas and leukemias). On the basis of their experience, the authors have reviewed and discussed the radiographic "pattern" of the hand in several hematologic conditions (i.e., anemias; thalassemias; sickle-cell disease; lymphomas; multiple myeloma; etc.), and their pathogenesis. Radiographies of both the hands, in antero-posterior view, were performed using Kodak-Min R film; xeroradiography was performed--in the same projection--using Rank Xerox plate, developed always in "positive mode" in 125 Rank Xerox System, conditioned with contrast "D", for emphasizing osseous details. Recently, digital radiography--employing PCR system--has substituted xeroradiography, because of its well-known properties and diagnostic advantages: in this manner, changes in bone and soft tissue are demonstrated on the same image, with augmentation of diagnostic information, with reduced dose to patient. In our series, hand is always involved (100% of cases) in thalassemias: lesions are characterized by diffuse osteopenia (washed out melted appearance), with widening of bone marrow space, diaphyseal convex aspect of the long bones, thinning of the cortex, and cyst-like changes (rain drops). Lesions disappear completely after the hypertransfusion regimen (HTR). Following chelation therapy, lesions of the wrist and hand are similar to those described in rickets and/or scurvy. Sometimes, the hand is characteristically affected in sickle-cell disease--particularly in the so called hand-foot syndrome--as "cone-deformity". In multiple myeloma incidence of hand involvement is 2.9%: lesions reflect general abnormalities observed in other skeletal sites, and they consist in multiple well-circumscribed lytic lesions. In amyloidosis, poorly defined radiolucent areas may be discovered. In non-Hodgkin lymphoma, incidence of hand involvement is less frequent, approximately 0.2%: the radiographic pattern is aspecific (mottled lytic lesions), sometimes simulating multiple myeloma and/or leukemias. In hemophilia, swelling of soft tissues, around the interphalangeal joint, related to intra-articular and/or per-articular hematoma, is observed. The other conditions reflect general radiographic features of anemias, which are of three main types: 1. the over active marrow (i.e., polycythemia); 2. the infarction of bone (i.e., sickle-cell disease); 3. non-specific findings, resulting from chronic illness (delays of maturation; dwarfism; osteopenia; tendency to infection).
Simultaneous occurrence of localized plasmacytomas of both hands and feet has not been reported so far. Here we report a 40-year old female patient, who had at presentation pain and deformity. Of hands and feet, with numerous cystic lytic lesions of phalangeal, metacarpal and metatarsal bones, detected by X-rays. The biopsy of the affected bone showed moderately differentiated plasmacytoma of lambda light chain type (lambda-LC). Serum and urine biochemical analysis revealed the existence of lambda LC monoclonal component. The patient was treated by local radiotherapy and subsequent systemic chemotherapy, which consisted of 3 cycles of the M-2 protocol and 7 cycles of melphalan-prednisone. Five years after the diagnosis, the absence of plasmacytoma was confirmed by puncture biopsy of the left hand phalanx. Monoclonal protein in serum and urine was not detected.
Wintrobe’s clinical hematology
- A Dispenzieri
- Mq Lacy
- S Kumar
- Multiple
- Jp Greer
- Da Arber
- B Glader
- Af List
- Rt Means
- F Paraskevas
- Gm Rodgers
cancerresearchuk.org/about-cancer/type/myeloma/treatment/statistics-and-outlook-for-myeloma
- Uk Cancer Research