DOI: 10.1148/rg.236025056
(Radiographics. 2003;23:1371-1383.)
© RSNA, 2003
Primary Bone Lymphoma: Radiographic–MR Imaging Correlation1
Anant Krishnan, MD,
Ali Shirkhoda, MD,
Jamshid Tehranzadeh, MD,
Ali R. Armin, MD,
Ronald Irwin, MD and
Kimberly Les, MD
1 From the Departments of Diagnostic Radiology (A.K., A.S.), Pathology (A.R.A.), and Orthopedic Oncology (R.I., K.L.), William Beaumont Hospital, 3601 W 13 Mile Rd, Royal Oak, MI 48073; and Department of Radiological Sciences and Orthopedics, University of California, Irvine (J.T.). Presented as an education exhibit at the 2001 RSNA scientific assembly. Received March 14, 2002; revision requested April 16; revision received February 24, 2003; accepted March 24. Address correspondence to A.K. (e-mail: tadaastu@yahoo.com).
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Abstract
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Primary bone lymphoma is an uncommon malignancy that accounts for less than 5% of all primary bone tumors. The radiographic appearances of primary bone lymphoma are variable, and, because the lesion can appear near normal on plain radiographs, a second modality such as bone scintigraphy or magnetic resonance (MR) imaging should be used. Despite this variability, the presence of a solitary, permeative, metadiaphyseal lesion with a layered periosteal reaction on plain radiographs and a soft-tissue mass on MR images, especially in a patient older than 30 years, is highly suggestive of lymphoma. The case for a diagnosis of primary bone lymphoma is further strengthened if the soft-tissue mass and marrow changes are associated with surprisingly little cortical destruction. Primary bone lymphoma has a better prognosis than many other malignant bone tumors; therefore, early identification allows for appropriate treatment. MR imaging not only permits early identification but also depicts the extent of soft-tissue involvement and can be used to assess the outcome of treatment.
© RSNA, 2003
Index Terms: Bone neoplasms, 40.343 • Lymphoma, 40.343 • Lymphoma, MR, 40.12141
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LEARNING OBJECTIVES FOR TEST 1
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After reading this article and taking the test, the reader will be able to:
- Identify the radiographic findings of primary bone lymphoma.
- Discuss the utility of MR imaging and bone scintigraphy in the work-up of patients.
- Describe the clinical and radiologic features peculiar to primary bone lymphoma.
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Introduction
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Primary lymphoma of bone is a rare malignant condition that accounts for less than 5% of all primary bone tumors (1). It has also been called reticulum cell sarcoma (2), malignant lymphoma of the bone (3), and more recently osteolymphoma (4). The vast majority of cases are of the non-Hodgkin type, with Hodgkin disease accounting for 6% of cases in one series (1). Distinguishing primary bone lymphoma from other bone tumors is important because the former has a better response to therapy and a better prognosis. In this article, we describe and illustrate the varied appearances of primary bone lymphoma on plain radiographs and magnetic resonance (MR) images. Our discussion is based on our review of cases from the archives of our tumor registry and from the departments of orthopedic oncology and diagnostic radiology that were pathologically confirmed as primary bone lymphoma. Our goal is to acquaint the reader with the spectrum of imaging findings in this relatively uncommon malignancy and thus ensure early referral for appropriate management.
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Clinical and Histologic Features
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Primary bone lymphoma occurs in a broad range of patients, aged 1 year 6 months to 86 years (median range, 36–52 years) (5), with a peak prevalence among patients in the 6th to 7th decades of life. It is rare in patients younger than 10 years and occurs slightly more often in males (male-to-female ratio, 1.5 to 1) (6). Male children also appear to be affected more frequently than female children (6:1 ratio) (5). The femur is the most common site (especially the metadiaphysis) and is affected in 25% of cases. Other sites include the pelvis, humerus, head and neck, and tibia (7). Vertebral involvement is not unusual and occurred in six of 24 cases (25%) reviewed in a recent study (8).
Clinical Characteristics
Primary lymphoma of bone manifests with insidious and intermittent bone pain that can persist for months. Other signs and symptoms include local swelling, a palpable mass, and systemic symptoms such as weight loss and fever (8). Vertebral involvement can cause radicular symptoms and can even lead to compression of the spinal cord (9).
Histopathologic Characteristics
The proposed World Health Organization (WHO) classification of lymphoid neoplasms (10,11) adopts the Revised European-American Classification of Lymphoid Neoplasms (REAL), proposed by the International Lymphoma Study Group (Table). They attempted to define distinct disease entities based on a combination of morphologic, immunophenotype, genetic, and clinical features. Thus, the classification combines the features of the Working formulation and the Kiel classification. Broadly, three types of lymphoma—namely, B cell, T cell, and Hodgkin disease and their subsets—are enumerated. Detailed discussion of the various subtypes is beyond the extent of this article, and interested readers are directed to a summary version by Chan et al (11).
Although osseous involvement of disseminated malignant lymphoma is not uncommon, primary lymphoma of bone is infrequent. The diagnosis implies the exclusion of any evidence of nodal or disseminated disease on the basis of modern staging techniques. Pathologic studies of primary bone lymphoma before the mid-1970s, when current radiologic staging techniques became widely available, should be interpreted with this in mind. Primary extranodal lymphomas (which includes primary bone lymphomas) are classified as stage E in the Ann Arbor classification to distinguish them from the disseminated form of the disease, which carries a poorer prognosis (12). Primary non-Hodgkin lymphoma of bone is rare, accounting for approximately 4%–5% of extranodal lymphomas and less than 1% of all non-Hodgkin lymphomas (5).
Primary bone lymphomas most commonly are large cell or mixed small and large cell lymphomas of the B-cell lineage. In a large series from the Mayo Clinic (13), 75% of all classifiable lymphomas were intermediate grade (diffuse mixed small and large cell or large cell lesions) in the Working formulation. On the basis of the current WHO classification, the overwhelming majority of cases would be characterized as diffuse large B-cell lymphoma. T-cell primary bone lymphomas are rare, except in Japan where they are reported to constitute 10% of primary bone lymphomas (14).
At low-power microscopy, primary non-Hodgkin lymphomas of bone have a diffuse cellular population that infiltrates between bone trabeculae and medullary fat (15) (Fig 1a). Occasionally, lymphoma of bone will have a spindled morphology. The histologic differential diagnosis includes other diffuse round cell infiltrates (such as Ewing sarcoma and granulocytic sarcoma) or spindled metastatic sarcomas and spindled carcinomas (such as renal cell carcinoma). The differential diagnosis is readily resolved by means of immunohistochemical analysis (Fig 1b, 1c). Nearly all lymphomas will express common leukocyte antigen and B-cell markers CD20 and CD79a. There are no reliable histologic or immunocytologic features with which to distinguish primary bone lymphoma from secondary bone involvement.
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Figure 1a. Lytic permeative pattern. (a) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) of an intramedullary lesion of primary bone lymphoma reveals diffuse replacement of marrow elements by large atypical lymphocytes with large nuclei and a small amount of eosinophilic cytoplasm. (b, c) Photomicrographs (original magnification, x100; immunoperoxidase stain) show that the atypical cells stain strongly for common leukocyte antigen (b) but negatively for cytokeratin stain (c). Further testing showed that the cells stained positively for B-cell antigen. (For radiologic images, see Fig 2.)
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Figure 1b. Lytic permeative pattern. (a) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) of an intramedullary lesion of primary bone lymphoma reveals diffuse replacement of marrow elements by large atypical lymphocytes with large nuclei and a small amount of eosinophilic cytoplasm. (b, c) Photomicrographs (original magnification, x100; immunoperoxidase stain) show that the atypical cells stain strongly for common leukocyte antigen (b) but negatively for cytokeratin stain (c). Further testing showed that the cells stained positively for B-cell antigen. (For radiologic images, see Fig 2.)
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Figure 1c. Lytic permeative pattern. (a) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) of an intramedullary lesion of primary bone lymphoma reveals diffuse replacement of marrow elements by large atypical lymphocytes with large nuclei and a small amount of eosinophilic cytoplasm. (b, c) Photomicrographs (original magnification, x100; immunoperoxidase stain) show that the atypical cells stain strongly for common leukocyte antigen (b) but negatively for cytokeratin stain (c). Further testing showed that the cells stained positively for B-cell antigen. (For radiologic images, see Fig 2.)
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Primary Hodgkin disease of bone is even more rare than primary non-Hodgkin lymphoma of bone (16–18). A review of 25 patients with osseous Hodgkin disease (12) revealed that only three patients had solitary osseous tumors and two had primary, multifocal, osseous Hodgkin disease. Again, and similar to patients with non-Hodgkin lymphoma of bone, patients with clinically symptomatic osseous Hodgkin disease have a prognosis similar to, or slightly better than that of patients with lymphatic Hodgkin disease alone (12). Hodgkin disease of bone often manifests as fibrotic lesions that contain mixed inflammatory cells and scattered Reed-Sternberg cells and variants. The identity of the latter can be confirmed on the basis of their characteristic immunohistochemical pattern of reactivity (CD15 and CD30 positive and CD45 negative). Immunohistochemical staining allows these cells to be distinguished from mimics, including Reed-Sternberg–like cells, which may be found in anaplastic large cell lymphoma.
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Radiographic Characteristics
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The criteria for a diagnosis of primary bone lymphoma initially suggested by Coley in 1950 (2) with minor modifications are as follows: "lymphoma presenting in an osseous site with no evidence of disease elsewhere for at least 6 months after diagnosis." The presence of regional lymph node involvement does not exclude a diagnosis of primary bone lymphoma, but histologic confirmation of the diagnosis is necessary.
The radiographic appearance of primary bone lymphoma is variable and to some authors nonspecific (8). Although the latter opinion may be reasonable given the wide spectrum of findings—from a near-normal-appearing bone to a focal lytic lesion with geographic margins to a mixed sclerotic-lytic lesion to a diffusely permeative process with cortical destruction and soft-tissue involvement—there are some peculiar features worth noting. One such pattern described as being typical of lymphomatous bone involvement is a solitary lytic lesion near the end of a long bone that has a permeative or moth-eaten pattern of destruction and aggressive periosteal reaction (19). This pattern is a feature of round cell tumors (including Ewing sarcoma and multiple myeloma), of which lymphoma is an example.
In our assessment of 20 cases of histologically proved cases of primary bone lymphoma, we identified certain radiographic patterns. Although these patterns are not specific to primary bone lymphoma, they are similar to those reported in literature. We describe them first, before proceeding to a discussion of MR imaging findings, which add a degree of specificity to this diagnosis.
Lytic-Destructive Pattern
The lytic-destructive pattern is the most common radiographic appearance of primary bone lymphoma, as it was reported in approximately 70% of 237 cases reviewed by Mulligan et al (1). It is believed to result from an osteoclast-stimulating factor. The lytic pattern may be permeative—characterized by numerous small, elongated rarefactions that are parallel to the long axis of the bone and relatively uniform in size—Fig 2) or moth-eaten—a pattern of many medium to large areas of radiolucency in a poorly marginated area of bone (19). Occasionally, the lesion may manifest with focal lytic areas with well-defined margins (Fig 3).
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Figure 2a. Lytic permeative pattern. (a) Lateral radiograph of a 56-year-old woman shows permeative changes within the distal femur. (b) Coronal T2-weighted image (repetition time msec/echo time msec = 3,000/90) shows high signal intensity within the marrow and associated soft-tissue masses (arrows). (c) Sagittal contrast material-enhanced T1-weighted image (600/30) shows areas of enhancement within the intramedullary lesion and a soft-tissue mass off the posterior aspect of the femur (arrow). (d) Lateral view obtained 6 years after irradiation and combination chemotherapy shows sclerotic changes related to therapy.
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Figure 2b. Lytic permeative pattern. (a) Lateral radiograph of a 56-year-old woman shows permeative changes within the distal femur. (b) Coronal T2-weighted image (repetition time msec/echo time msec = 3,000/90) shows high signal intensity within the marrow and associated soft-tissue masses (arrows). (c) Sagittal contrast material-enhanced T1-weighted image (600/30) shows areas of enhancement within the intramedullary lesion and a soft-tissue mass off the posterior aspect of the femur (arrow). (d) Lateral view obtained 6 years after irradiation and combination chemotherapy shows sclerotic changes related to therapy.
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Figure 2c. Lytic permeative pattern. (a) Lateral radiograph of a 56-year-old woman shows permeative changes within the distal femur. (b) Coronal T2-weighted image (repetition time msec/echo time msec = 3,000/90) shows high signal intensity within the marrow and associated soft-tissue masses (arrows). (c) Sagittal contrast material-enhanced T1-weighted image (600/30) shows areas of enhancement within the intramedullary lesion and a soft-tissue mass off the posterior aspect of the femur (arrow). (d) Lateral view obtained 6 years after irradiation and combination chemotherapy shows sclerotic changes related to therapy.
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Figure 2d. Lytic permeative pattern. (a) Lateral radiograph of a 56-year-old woman shows permeative changes within the distal femur. (b) Coronal T2-weighted image (repetition time msec/echo time msec = 3,000/90) shows high signal intensity within the marrow and associated soft-tissue masses (arrows). (c) Sagittal contrast material-enhanced T1-weighted image (600/30) shows areas of enhancement within the intramedullary lesion and a soft-tissue mass off the posterior aspect of the femur (arrow). (d) Lateral view obtained 6 years after irradiation and combination chemotherapy shows sclerotic changes related to therapy.
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Figure 3a. Lytic pattern with well-defined margins. (a) Lateral radiograph of a 77-year-old woman shows a large but fairly well-defined lytic lesion (arrows) of the proximal tibia that appears to extend superiorly into the tibial plateau. (b) Sagittal T2-weighted image (3,030/70) shows that the lesion is confined within the marrow but extends superiorly into the anterior aspect of the proximal tibia (arrowheads). No soft-tissue mass is seen.
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Figure 3b. Lytic pattern with well-defined margins. (a) Lateral radiograph of a 77-year-old woman shows a large but fairly well-defined lytic lesion (arrows) of the proximal tibia that appears to extend superiorly into the tibial plateau. (b) Sagittal T2-weighted image (3,030/70) shows that the lesion is confined within the marrow but extends superiorly into the anterior aspect of the proximal tibia (arrowheads). No soft-tissue mass is seen.
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Cortical breakthrough, pathologic fractures (in about 25% of our cases) (Fig 4a), and soft-tissue masses represent a more aggressive pattern of involvement and a poorer prognosis (19). Cortical breakthrough, which refers to a sudden interruption in the continuity of the cortex, was better seen at computed tomography (CT) in our experience (Fig 5b) and correlated with a more aggressive tumor. CT also demonstrated sequestra (Fig 5b), findings that have been reported in osseous lymphomas (20).
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Figure 4a. Cortical destruction. (a) Plain radiograph of a 24-year-old man with right elbow pain shows a pathologic fracture through the markedly eroded ulna and extensive cortical breakthrough. A soft-tissue mass is also seen. (b, c) Coronal STIR image (4,800/30; flip angle, 180°) (b) and axial contrast-enhanced T1-weighted image (700/12; flip angle, 90°) (c) reveal a large soft-tissue mass and marrow involvement. On c, areas of necrosis are seen within the soft-tissue part of the lesion.
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Figure 4b. Cortical destruction. (a) Plain radiograph of a 24-year-old man with right elbow pain shows a pathologic fracture through the markedly eroded ulna and extensive cortical breakthrough. A soft-tissue mass is also seen. (b, c) Coronal STIR image (4,800/30; flip angle, 180°) (b) and axial contrast-enhanced T1-weighted image (700/12; flip angle, 90°) (c) reveal a large soft-tissue mass and marrow involvement. On c, areas of necrosis are seen within the soft-tissue part of the lesion.
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Figure 4c. Cortical destruction. (a) Plain radiograph of a 24-year-old man with right elbow pain shows a pathologic fracture through the markedly eroded ulna and extensive cortical breakthrough. A soft-tissue mass is also seen. (b, c) Coronal STIR image (4,800/30; flip angle, 180°) (b) and axial contrast-enhanced T1-weighted image (700/12; flip angle, 90°) (c) reveal a large soft-tissue mass and marrow involvement. On c, areas of necrosis are seen within the soft-tissue part of the lesion.
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Figure 5a. Lytic pattern with a sequestrum. (a) Frontal radiograph of an 83-year-old man reveals a mottled appearance of the right medial femoral condyle. (b) Axial CT scan shows destruction of the medial femoral condyle, sequestrum formation (arrow), and cortical erosion with a small soft-tissue mass (arrowheads).
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Figure 5b. Lytic pattern with a sequestrum. (a) Frontal radiograph of an 83-year-old man reveals a mottled appearance of the right medial femoral condyle. (b) Axial CT scan shows destruction of the medial femoral condyle, sequestrum formation (arrow), and cortical erosion with a small soft-tissue mass (arrowheads).
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Periosteal reaction has been reported in about 60% of cases and may be either lamellated or layered, wherein layers of periosteal bone are seen parallel to the long axis of the bone (also called onion-peel appearance), or broken, when discontinuous or interrupted periosteal new bone is seen. The latter appearance of disrupted periosteal bone is believed to be a helpful radiographic sign that indicates a poorer prognosis (Fig 6).
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Figure 6a. Periosteal reaction. (a) Frontal radiograph of a 9-year-old boy shows permeative changes of the distal femoral shaft with a dense periosteal reaction. (b) Lateral view clearly shows the laminated and interrupted periosteal reaction (arrow), a feature of round cell tumors including lymphoma and Ewing sarcoma. (c) Axial T2-weighted image (4,500/80) reveals the circumferential nature of the soft-tissue mass and abnormal marrow. Note disuse atrophy of muscles in the affected side.
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Figure 6b. Periosteal reaction. (a) Frontal radiograph of a 9-year-old boy shows permeative changes of the distal femoral shaft with a dense periosteal reaction. (b) Lateral view clearly shows the laminated and interrupted periosteal reaction (arrow), a feature of round cell tumors including lymphoma and Ewing sarcoma. (c) Axial T2-weighted image (4,500/80) reveals the circumferential nature of the soft-tissue mass and abnormal marrow. Note disuse atrophy of muscles in the affected side.
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Figure 6c. Periosteal reaction. (a) Frontal radiograph of a 9-year-old boy shows permeative changes of the distal femoral shaft with a dense periosteal reaction. (b) Lateral view clearly shows the laminated and interrupted periosteal reaction (arrow), a feature of round cell tumors including lymphoma and Ewing sarcoma. (c) Axial T2-weighted image (4,500/80) reveals the circumferential nature of the soft-tissue mass and abnormal marrow. Note disuse atrophy of muscles in the affected side.
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Blastic-Sclerotic Pattern
Primarily blastic-sclerotic lesions are rare in primary bone lymphoma compared with metastatic bone lymphoma. However, a mixed lytic lesion with sclerotic areas can be seen (Figs 7–9). Sclerotic changes in primary bone lymphoma may seem scarce, since of the two types of lymphoma, it is Hodgkin disease of bone (the less common subtype of primary bone lymphoma) that tends to be sclerotic and even in Hodgkin disease, lytic lesions predominate) (16). Sclerotic areas can, however, develop in an originally lytic pattern after therapy (irradiation and chemotherapy).
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Figure 7a. Mixed lytic-sclerotic pattern. (a) Frontal radiograph of a 24-year-old woman shows a predominantly sclerotic appearance of the distal femur with a few lytic areas. (b) Coronal STIR image (4,800/30; flip angle, 180°) reveals increased signal intensity primarily involving the medial condyle. Although cortical erosion is seen (arrow), there is no indication of a definite soft-tissue mass. (c, d) Axial T1-weighted images (800/12; flip angle 180°) obtained before (c) and after (d) the administration of contrast material reveal enhancement of the lesion in the medial femoral condyle.
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Figure 7b. Mixed lytic-sclerotic pattern. (a) Frontal radiograph of a 24-year-old woman shows a predominantly sclerotic appearance of the distal femur with a few lytic areas. (b) Coronal STIR image (4,800/30; flip angle, 180°) reveals increased signal intensity primarily involving the medial condyle. Although cortical erosion is seen (arrow), there is no indication of a definite soft-tissue mass. (c, d) Axial T1-weighted images (800/12; flip angle 180°) obtained before (c) and after (d) the administration of contrast material reveal enhancement of the lesion in the medial femoral condyle.
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Figure 7c. Mixed lytic-sclerotic pattern. (a) Frontal radiograph of a 24-year-old woman shows a predominantly sclerotic appearance of the distal femur with a few lytic areas. (b) Coronal STIR image (4,800/30; flip angle, 180°) reveals increased signal intensity primarily involving the medial condyle. Although cortical erosion is seen (arrow), there is no indication of a definite soft-tissue mass. (c, d) Axial T1-weighted images (800/12; flip angle 180°) obtained before (c) and after (d) the administration of contrast material reveal enhancement of the lesion in the medial femoral condyle.
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Figure 7d. Mixed lytic-sclerotic pattern. (a) Frontal radiograph of a 24-year-old woman shows a predominantly sclerotic appearance of the distal femur with a few lytic areas. (b) Coronal STIR image (4,800/30; flip angle, 180°) reveals increased signal intensity primarily involving the medial condyle. Although cortical erosion is seen (arrow), there is no indication of a definite soft-tissue mass. (c, d) Axial T1-weighted images (800/12; flip angle 180°) obtained before (c) and after (d) the administration of contrast material reveal enhancement of the lesion in the medial femoral condyle.
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Figure 8. Mixed lytic-sclerotic pattern. Frontal radiograph of the left shoulder in a 44-year-old man reveals a sclerotic lesion involving the coracoid process and extending into the glenoid. No MR imaging was performed, as biopsy was done with fluoroscopic guidance.
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Figure 9. Mixed lytic-sclerotic pattern. Frontal radiograph of the left shoulder in an 83 year-old-woman reveals an expansile, predominantly lytic lesion of the scapula. The lesion is slightly more extensive than the one seen in Figure 8. No MR imaging was performed.
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Subtle or "Near-Normal" Findings
A third pattern seen and described in primary bone lymphoma is the near absence of detectable abnormalities on plain radiographs (21). Cases with remarkably normal-appearing radiographs may show striking abnormalities on radionuclide bone scans and MR images (Figs 10, 11). As a result, in patients with symptoms but negative radiographic findings, further assessment with a second, more sensitive modality such as scintigraphy or MR imaging is essential.
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Figure 10a. Subtle radiographic findings. (a) Frontal radiograph of the right femur in a 31-year-old woman with a 10-month history of right thigh pain was unremarkable. Because of the patient’s continued pain, whole-body bone scintigraphy was performed to rule out possible metastasis. (b) Anterior and posterior views of the whole-body bone scan reveal increased uptake in the midshaft of the right femur. (c) Coronal T1-weighted image (400/14) reveals two lesions in the marrow of the femoral shaft. No cortical erosion or soft-tissue mass was seen.
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Figure 10b. Subtle radiographic findings. (a) Frontal radiograph of the right femur in a 31-year-old woman with a 10-month history of right thigh pain was unremarkable. Because of the patient’s continued pain, whole-body bone scintigraphy was performed to rule out possible metastasis. (b) Anterior and posterior views of the whole-body bone scan reveal increased uptake in the midshaft of the right femur. (c) Coronal T1-weighted image (400/14) reveals two lesions in the marrow of the femoral shaft. No cortical erosion or soft-tissue mass was seen.
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Figure 10c. Subtle radiographic findings. (a) Frontal radiograph of the right femur in a 31-year-old woman with a 10-month history of right thigh pain was unremarkable. Because of the patient’s continued pain, whole-body bone scintigraphy was performed to rule out possible metastasis. (b) Anterior and posterior views of the whole-body bone scan reveal increased uptake in the midshaft of the right femur. (c) Coronal T1-weighted image (400/14) reveals two lesions in the marrow of the femoral shaft. No cortical erosion or soft-tissue mass was seen.
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Figure 11a. Subtle radiographic findings. (a) Frontal radiograph of the right humerus in a 42-year-old man reveals a subtle permeative appearance of the proximal third of the bone. (b) Anterior view of a whole-body bone scan shows diffuse uptake involving almost the entire proximal half of the right humerus. (c, d) Coronal T1-weighted (488/14) (c) and STIR T2-weighted (3,400/70) (d) images show that the lesion is associated with a small soft-tissue mass, which is best seen on the STIR image (arrows).
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Figure 11b. Subtle radiographic findings. (a) Frontal radiograph of the right humerus in a 42-year-old man reveals a subtle permeative appearance of the proximal third of the bone. (b) Anterior view of a whole-body bone scan shows diffuse uptake involving almost the entire proximal half of the right humerus. (c, d) Coronal T1-weighted (488/14) (c) and STIR T2-weighted (3,400/70) (d) images show that the lesion is associated with a small soft-tissue mass, which is best seen on the STIR image (arrows).
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Figure 11c. Subtle radiographic findings. (a) Frontal radiograph of the right humerus in a 42-year-old man reveals a subtle permeative appearance of the proximal third of the bone. (b) Anterior view of a whole-body bone scan shows diffuse uptake involving almost the entire proximal half of the right humerus. (c, d) Coronal T1-weighted (488/14) (c) and STIR T2-weighted (3,400/70) (d) images show that the lesion is associated with a small soft-tissue mass, which is best seen on the STIR image (arrows).
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Figure 11d. Subtle radiographic findings. (a) Frontal radiograph of the right humerus in a 42-year-old man reveals a subtle permeative appearance of the proximal third of the bone. (b) Anterior view of a whole-body bone scan shows diffuse uptake involving almost the entire proximal half of the right humerus. (c, d) Coronal T1-weighted (488/14) (c) and STIR T2-weighted (3,400/70) (d) images show that the lesion is associated with a small soft-tissue mass, which is best seen on the STIR image (arrows).
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MR Imaging Characteristics
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Bone Marrow Replacement
T1-weighted pulse sequences are the best (compared with other sequences) for demonstrating marrow changes, as T1-weighted images reveal areas of low signal intensity within the marrow (Fig 10c). On T2-weighted images (Figs 12, 13), these areas generally appear bright. Peritumoral edema and reactive marrow change can also produce high signal intensity on T2-weighted images. However, if fibrosis is present in a lesion, it may show low signal intensity (7). STIR (short-inversion-time inversion recovery) images, which are obtained with heavily T2-weighted pulse sequences, similarly delineate the normal from abnormal marrow (Figs 4b, 7b). When contrast material is administered, MR images can demonstrate areas of enhancement within the lesion.
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Figure 12a. MR imaging appearance. (a) Coronal T2-weighted fat-suppressed image (4,100/102) of a 21-year-old woman reveals a large lesion in the distal right femur with an associated soft-tissue mass. Plain radiograph (not shown) was reported to have shown a lytic lesion. (b) Sagittal T2-weighted image (4,100/102) reveals the posterior extent of the soft-tissue mass, which provided an ample site for biopsy.
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Figure 12b. MR imaging appearance. (a) Coronal T2-weighted fat-suppressed image (4,100/102) of a 21-year-old woman reveals a large lesion in the distal right femur with an associated soft-tissue mass. Plain radiograph (not shown) was reported to have shown a lytic lesion. (b) Sagittal T2-weighted image (4,100/102) reveals the posterior extent of the soft-tissue mass, which provided an ample site for biopsy.
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Figure 13a. MR imaging appearance. (a) Frontal radiograph of the right knee in a 31-year-old man with a history of knee injuries reveals a mixed lytic and sclerotic lesion in the distal femur. (b) Coronal T1-weighted image (600/15) shows the predominantly intramedullary lesion with minimal cortical erosion. (c) Axial T2-weighted image (2,500/80) also shows the intramedullary component, as well as a small joint effusion. Analysis of the biopsy specimen revealed primary Hodgkin lymphoma of the bone.
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Figure 13b. MR imaging appearance. (a) Frontal radiograph of the right knee in a 31-year-old man with a history of knee injuries reveals a mixed lytic and sclerotic lesion in the distal femur. (b) Coronal T1-weighted image (600/15) shows the predominantly intramedullary lesion with minimal cortical erosion. (c) Axial T2-weighted image (2,500/80) also shows the intramedullary component, as well as a small joint effusion. Analysis of the biopsy specimen revealed primary Hodgkin lymphoma of the bone.
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Figure 13c. MR imaging appearance. (a) Frontal radiograph of the right knee in a 31-year-old man with a history of knee injuries reveals a mixed lytic and sclerotic lesion in the distal femur. (b) Coronal T1-weighted image (600/15) shows the predominantly intramedullary lesion with minimal cortical erosion. (c) Axial T2-weighted image (2,500/80) also shows the intramedullary component, as well as a small joint effusion. Analysis of the biopsy specimen revealed primary Hodgkin lymphoma of the bone.
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Soft-Tissue Involvement
Nearly all our cases that had a permeative pattern on plain radiographs were associated with soft-tissue masses on MR images. Interestingly, the pattern of extensive marrow disease and surrounding soft-tissue masses but without extensive cortical destruction has been reported nearly exclusively in round cell tumors such as primary bone lymphoma, multiple myeloma, and Ewing sarcoma (Fig 11c) (1,21). One explanation for this finding is the spread of tumor cells from the marrow through small vascular channels that run through the cortex into the surrounding soft tissue (22).
Cortical Erosion
Both MR imaging and CT demonstrate cortical erosion, although the former permits early detection.
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Primary Multi-focal Osseous Lymphoma
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Before considering the differential diagnosis, we must review briefly a radiographic subtype of lymphoma in which more than one bone is affected, known as primary multifocal osseous lymphoma. Although the original criteria of Coley implied the involvement of a solitary bone, an expansion was suggested by Ostrowski et al (13) in 1986 when they attempted to subclassify osseous lymphoma into four groups. In their classification, group 1 consisted of solitary primary bone lymphoma, and group 2 encompassed cases in which more than one bone was affected but no nodal or visceral disease was present. (Groups 3 and 4 included cases with distant nodal or visceral disease.) The difficulty and controversy with the multifocal involvement discussed by Ostrowski et al is in distinguishing the cases with multiple osseous sites (ie, group 2) from those with disseminated disease (ie, groups 3 and 4), which would effectively exclude them from being called primary bone lymphomas. As a result, some authors do not consider multifocal osseous lymphoma at all, whereas others may have excluded it from their studies. Authors who support the concept have observed that multifocal osseous lymphoma has a predilection for bones around the knee, similar to the pattern of solitary primary bone lymphoma. In fact, as suggested by Melamed et al (23), the combination of scintigraphic abnormalities in the proximal tibia, distal femur, and skull is very uncommon in metastatic disease and may, therefore, suggest the diagnosis of primary multifocal osseous lymphoma.
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Differential Diagnosis
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A permeative or moth-eaten appearance in the metadiaphysis on a radiograph is not unique to primary bone lymphoma and can be seen in other conditions such as osteosarcoma, metastatic disease, and even secondary osseous lymphoma. Although not pathognomonic of primary bone lymphoma, an important radiographic feature is the presence of a lytic process at the end of a long bone with an aggressive periosteal reaction. Secondary or metastatic lymphoma is indistinguishable from primary bone lymphoma without whole-body surveillance to diagnose the source. This survey may include CT of the entire body (which is often performed when an osseous lymphomatous site is identified), positron emission tomography, or even bone marrow analysis. Unfortunately, osteosarcomas can be remarkably similar to lymphoma, especially in younger patients in whom the former lesions are more common. One important feature is the presence of a sequestrum in the lesion that may suggest the diagnosis of lymphoma (Fig 5). With respect to metastatic disease, the multiplicity of lesions, their location (which unlike lymphoma may not be along the articular surface), and the presence of a primary lesion elsewhere can help guide the diagnosis.
One MR imaging feature that is suggestive of infiltrative processes such as lymphoma and Ewing sarcoma is the replacement of bone marrow, especially in the setting of near-normal radiographic findings. Another and even more specific feature of round cell tumors such as lymphoma is the relatively minimal cortical destruction in the presence of extensive soft-tissue and marrow involvement. Observation of these two factors in patients with suspected bone lymphoma will add a further degree of certainty to the diagnosis.
Lastly, the consideration of lymphoma in the appropriate differential diagnosis is important to ensure that an adequate biopsy sample be obtained for immunophenotyping and other analysis.
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Treatment
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Treatment of primary bone lymphoma is controversial, and there is no consensus with regard to radiation therapy (8,24). A number of authors treat primary bone lymphoma with chemotherapy as the mainstay and use adjuvant radiation therapy (9,25). The optimal treatment has not been determined and is still being debated (26).
In general, patients with monostotic primary bone lymphoma treated with a combination of radiation therapy and chemotherapy do well. A total 5-year survival rate of 83% was seen in a study by Tondini et al (27). The overall 5-year survival rate is better than that for most other primary osseous malignancies. For this reason, recognition of lymphoma as a possible cause for the described radiologic findings is important.
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Conclusions
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The presence of a solitary, permeative, metadiaphyseal lesion with a layered periosteal reaction on plain radiographs and a soft-tissue mass on MR images, especially in a patient older than 30 years, is highly suggestive of lymphoma. The case for a diagnosis of primary bone lymphoma is further strengthened if the soft-tissue mass and marrow changes are associated with surprisingly little cortical destruction.
However, primary bone lymphoma can appear near normal on plain radiographs, and a second modality such as bone scintigraphy or MR imaging should be used. Although a radionuclide scan is useful for surveying the entire skeleton, MR images help assess the exact extent of local involvement.
Evaluation of our cases indicated that lytic lesions and those with a permeative pattern on radiographs were nearly always associated with soft-tissue masses, which were seen best on MR images. CT is helpful for detecting cortical erosion, demonstrating a sequestrum, and biopsy guidance.
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Footnotes
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See the commentary by Manaster
following this article.
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References
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Related Article
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Invited Commentary • Authors' Response
- B. J. Manaster, Jamshid Tehranzadeh, Anant Krishnan, and Ali Shirkhoda
RadioGraphics 2003 23: 1384-1387.
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