You are in: eMedicine Specialties > Radiology > MUSCULOSKELETAL Lymphoma, BoneArticle Last Updated: Apr 7, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Michael E Mulligan, MD, Associate Professor, Assistant Chief of Musculoskeletal Imaging, Department of Radiology, University of Maryland School of Medicine; Chief, Division of Radiology, Kernan Hospital Michael E Mulligan is a member of the following medical societies: American Roentgen Ray Society, International Skeletal Society, Radiological Society of North America, and Society of Skeletal Radiology Editors: Amilcare Gentili, MD, Clinical Professor of Radiology, University of California at San Diego; Consulting Staff, Department of Radiology, Thornton Hospital; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Murali Sundaram, MBBS, FRCR, FACR, Consulting Staff, Department of Diagnostic Radiology, The Cleveland Clinic Foundation; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Felix S Chew, MD, MBA, EdM, Professor, Department of Radiology, Vice Chairman for Radiology Informatics, Section Head of Musculoskeletal Radiology, University of Washington Author and Editor Disclosure Synonyms and related keywords: primary lymphoma of bone, PLB, primary bone lymphoma, PBL, primary lymphocytic lymphoma, reticulum cell sarcoma, non-Hodgkin lymphoma, non-Hodgkin's lymphoma INTRODUCTIONSection 2 of 11
  BackgroundPrimary lymphoma of bone (PLB) is a rare, malignant, neoplastic disorder of the skeleton. In 1939, it was described as a distinct clinical condition by Parker and Jackson.1 Later that year, Ewing included it among the bone tumors listed in the Bone Sarcoma Registry, under the heading of reticulum cell lymphosarcoma.2 In 1963, the term PLB was introduced by Ivins and Dahlin.3 PathophysiologyMost (94%) PLB cases result from non–Hodgkin lymphoma. In the past, most authorities considered all cases of Hodgkin disease in bone to be metastatic. Currently, Hodgkin disease is reported as occurring as a primary bone tumor. In one referral series, 6% of PLB cases resulted from Hodgkin disease. A review of Hodgkin-type PLB was provided by Gerbert and colleagues in 2004.4 PLB tumors produce osteoclast-stimulating factors that cause lytic bone destruction. FrequencyUnited StatesIn most series, PLB is responsible for approximately 5% of primary malignant bone tumors and 5% of all cases of extranodal non-Hodgkin lymphoma; however, the incidence of all types of lymphoma is increasing in the United States. The Leukemia and Lymphoma Society reported a 73% increase in the number of patients with all types of non-Hodgkin lymphoma from 1973-1991, based on statistics from the National Cancer Institute.5 This increase may in part be the result of an aging population and a rise in the number of immunocompromised patients. Mortality/Morbidity A report by Fidias and colleagues indicated that 5- and 10-year survival rates of 91% and 87% (respectively) are achievable with combined modality therapy6; in a 2004 study by Barbieri and colleagues, patients who underwent such treatment had an overall survival rate of 88% at 15 years.7 A report from the Cleveland Clinic demonstrated a 100% 5-year survival rate.8 RacePatients of all races are affected. SexMale-to-female ratio ranges from 1.5-2:1. AgePLB has been reported in patients as young as 2 years and as old as 88 years. The incidence of disease is distributed fairly evenly in the second through eighth decades. This disease is rare in children younger than 10 years, as are most primary bone malignancies.11 Clinical DetailsProlonged pain is the usual clinical symptom. Patients may detect an area of swelling at the site of pain. The diagnostic criteria enumerated by Coley and co-authors in 1950 include the following12:
It is now recognized that PLB may involve multiple bones, as long as the other 2 criteria are met. The World Health Organization recognizes the following 4 groups of lymphoma involving bone:
This author would consider only groups 1 and 2 to represent primary lymphoma of bone. Groups 3 and 4 would most likely represent metastatic involvement of bone. Preferred ExaminationAfter biopsy of the bone lesion confirms the diagnosis of lymphoma, computed tomography (CT) scanning of the chest, abdomen, and pelvis is needed to exclude a primary, soft-tissue origin or distant disease. The CT scan may be combined with fluorodeoxyglucose (FDG) positron emission tomography (PET). Technetium-99m (99mTc) bone scintigraphy also can be used to look for additional sites of involvement that may be clinically silent.13 Once soft-tissue origin and distant disease are excluded, magnetic resonance imaging (MRI) is the preferred examination to stage the extent of disease within the affected bone. DIFFERENTIALSSection 3 of 11
Bone Metastases Ewing Sarcoma Multiple Myeloma Osteomyelitis Other Problems to Be ConsideredOther round cell tumors (can mimic appearance of PLB) RADIOGRAPHSection 4 of 11
Findings
Degree of ConfidenceBecause PLB is one of the least common primary skeletal malignancies and varies widely in appearance on conventional radiographs, a confident diagnosis based on initial radiographs usually is not possible. CT SCANSection 5 of 11
FindingsCross-sectional imaging studies are useful adjuncts to conventional radiographs in PLB. One pattern of involvement observed with either CT scanning or MRI is specific for round cell tumors, such as PLB. The pattern appears as extensive evidence of disease within the marrow cavity associated with a surrounding soft-tissue mass but without extensive cortical destruction (Image 3). This pattern has been reported only in PLB, Ewing sarcoma, and myeloma. However, in one report, 31% of cases had a nonaggressive appearance by MRI.15 Degree of ConfidenceWhen the pattern of involvement described above is demonstrated on CT or MRI scans, the degree of confidence is high that the process is one of the round cell tumors. The pattern is not specific for individual entities. MRISection 6 of 11
FindingsMRI findings are described also in CT Scan. MRI signal intensities are nonspecific, with the signal typically lower than muscle on T1-weighted sequences and higher or brighter than muscle on T2-weighted sequences. These tumors are usually treated with radiation therapy, and in that setting, it is not necessary to define a precise surgical margin; thus, intravenous (IV) contrast (ie, gadolinium) usually is not administered. These tumors typically demonstrate diffuse heterogeneous to homogeneous enhancement when IV contrast is used, and it may be needed when surgery is to be employed for local control. Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. NUCLEAR MEDICINESection 7 of 11
FindingsBone scintigraphy with 99mTc may be performed as part of the initial workup when considering other diagnoses, especially metastatic disease. In one study, 64% of patients had a marked increase in uptake of 99mTc in the solitary lesion. Bone scintigraphy is more sensitive than conventional radiography. The pattern of extensive abnormality within a bone on a bone scan, accompanied by normal findings on conventional radiographs, suggests a round cell tumor, such as PLB (Image 7). A scintigraphic pattern that is suggestive of multifocal PLB is reported to be a combination of lesions in the skull, distal femur, and proximal tibia. Of the patients described in a 1997 report by Melamed and colleagues, 5 out of 8 of them demonstrated this pattern of involvement.16 Gallium-67 (67Ga) citrate and thallium-201 (201Tl) also are positive in patients with PLB. Whole-body 67Ga scanning can help with initial staging by identifying or excluding soft-tissue foci of disease. 67Ga scanning also may be more helpful than other imaging modalities when determining the response of the tumor to the clinical treatment. FDG-PET is also useful for initial staging and follow-up. Degree of ConfidenceFindings are not specific, but the pattern of uptake helps to limit the differential diagnosis. Only a few conditions reveal a marked uptake increase with bone scintigraphy, including Paget disease, fibrous dysplasia, and osteosarcoma. Because most cases of PLB demonstrate increased uptake with bone scanning, one may be able to exclude plasmacytoma or multiple myeloma from consideration, because the latter conditions usually do not show significant increased uptake with 99mTc. ANGIOGRAPHYSection 8 of 11
FindingsCurrently, few conventional angiograms are performed in the diagnostic imaging workup of primary bone tumors. Large feeding arteries or draining veins can be depicted with dynamic, contrast-enhanced CT scanning or MRI. Degree of ConfidenceConventional angiographic findings are nonspecific. Lesions typically demonstrate hypervascular flow with tumor neovascularity, but they may be hypovascular or avascular.17 INTERVENTIONSection 9 of 11
Treatment for PLB often involves radiation therapy to control the tumor in the affected bone. In certain instances, surgical intervention for control of the primary bone lesion may be desirable or necessary. Chemotherapeutic regimens are employed as well; they may be used alone or can be administered before and/or after radiation therapy or surgery, to control the primary bone lesion. These treatment decisions are complex and are made in concert by the orthopedic surgeon, radiation oncologist, and medical oncologist. A 2007 study by Ramadan and colleagues revealed improved disease free survival and overall survival rates with chemotherapy alone in a group of 131 patients.18 Patients with PLB have the best prognosis compared to those with other primary bone sarcomas. MULTIMEDIASection 10 of 11
REFERENCESSection 11 of 11
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