DOI: 10.1148/rg.236035118
(Radiographics. 2003;23:1384-1387.)
Invited Commentary • Authors' Response
B. J. Manaster, MD, PhD
Department of Radiology, University of Colorado Health Sciences Center, Denver, Colorado
Primary lymphoma of bone has a long history of being misunderstood and likely underdiagnosed. Many bone tumors were recognized as having individual histologic and radiographic characteristics in the early 20th century, but primary lymphoma of bone was not among these. It was lumped with the other small round cell tumors until 1928 when Oberling described it as a separate entity and termed it reticulum cell sarcoma (1). In 1963, Ivins and Dahlin (2) suggested using the term primary lymphoma of bone, and this term has slowly gained acceptance.
Many osseous neoplasms are readily diagnosed by using a combination of parameters, including patient age, location of the lesion, and degree of aggressiveness, as well as other imaging characteristics. Primary lymphoma of bone does not have such reliable characteristics. Unlike most other bone tumors, primary lymphoma of bone occurs in a very wide age range of patients, being fairly evenly distributed among patients in the 2nd through 8th decades of life (3). It is found in many sites of the skeleton, including long bones, flat bones, and vertebrae, being exceedingly rare only in the skull and small bones of the appendicular skeleton. Therefore, location of the lesion is less helpful in diagnosis than in many other osseous tumors. Finally, the radiographic appearance of lesions is variable, ranging from virtually normal to severely permeative. For all these reasons, primary lymphoma of bone is often not considered as a diagnosis in individual cases and may be underdiagnosed based on imaging characteristics.
The largest series of primary lymphoma of bone was reported in a seminal article from the Armed Forces Institute of Pathology, authored by Mulligan et al (3). They emphasized the above points and also noted periosteal reaction in 58% of cases, soft-tissue mass in 48%, and sequestra in 16%. They found that, like radiographic features of the tumor, radionuclide, CT, and MR imaging features are usually nonspecific.
Dr Krishnan and coauthors, in the preceding article "Primary Bone Lymphoma: Radiographic and MR Imaging Correlation" extend and emphasize many of these observations. Their cases beautifully demonstrate the wide spectrum of radiographic and MR imaging findings in primary lymphoma of bone. Some of their cases demonstrate two other features of primary lymphoma of bone that I have personally observed but not found to be mentioned in the radiology literature. First, although I certainly agree that periosteal reaction is a frequent feature of this lesion, I would also note that prominent endosteal reaction can be seen. Thus, with sclerotic reactive change seen on both periosteal and endosteal surfaces, the cortex can become substantially thickened. This finding is demonstrated well in Figures 4, 6, 10, and particularly 11 of the preceding article by Krishnan et al. It also can be seen in Figures 5 and 6 of the article from the AFIP group (3). I offer two other examples from my own case collection (Figs 1, 2). Therefore, an aggressive lesion that also shows endosteal thickening should lead to consideration of primary lymphoma of bone as a diagnosis. Other aggressive bone lesions that might occasionally have a similar appearance of endosteal thickening include Ewing sarcoma and osteomyelitis, as well as the occasional lytic chondrosarcoma.
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Figure 1a. Lateral (a) and anteroposterior (b) radiographs of the leg in a 35-year-old man. The marrow abnormality is barely discernible as a permeative pattern. The more prominent, but still subtle, abnormality is the endosteal thickening of the cortex, seen posteriorly on the lateral view and medially on the anteroposterior view. Results of biopsy of the marrow showed primary lymphoma of bone.
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Figure 1b. Lateral (a) and anteroposterior (b) radiographs of the leg in a 35-year-old man. The marrow abnormality is barely discernible as a permeative pattern. The more prominent, but still subtle, abnormality is the endosteal thickening of the cortex, seen posteriorly on the lateral view and medially on the anteroposterior view. Results of biopsy of the marrow showed primary lymphoma of bone.
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Figure 2a. Anteroposterior (a) and lateral (b) views of the midfemur in a 30-year-old woman. The lesion is quite permeative, and there is periosteal reaction. The presence of endosteal thickening, seen particularly posteriorly and medially, helps suggest the diagnosis of primary lymphoma of bone, which was confirmed at biopsy.
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Figure 2b. Anteroposterior (a) and lateral (b) views of the midfemur in a 30-year-old woman. The lesion is quite permeative, and there is periosteal reaction. The presence of endosteal thickening, seen particularly posteriorly and medially, helps suggest the diagnosis of primary lymphoma of bone, which was confirmed at biopsy.
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Another observation made by Krishnan and colleagues is that nearly all their cases had a soft-tissue mass, best demonstrated by MR imaging. The prevalence of this finding contrasts somewhat with the 48% of cases in the AFIP group that demonstrated such a mass. I agree with Krishnan et al that the majority of cases of primary lymphoma of bone have a soft-tissue mass. I would extend this statement, however, to suggest that the character of the mass can sometimes suggest the diagnosis. Whereas the soft-tissue mass in most osseous sarcomas usually is round or oval, displacing adjacent musculature and neurovascular bundles, the soft-tissue mass in primary lymphoma of bone is often disproportionately large and infiltrative. It extends over long distances, infiltrates more than one compartment, and does not have the pseudoencapsulated appearance of most bone sarcomas. This elongated and infiltrating nature of the soft-tissue mass is illustrated in Figures 2 and 4 of the current article, as well as in Figure 6 of the AFIP article (3). It can be seen in another of my own cases (Fig 3).
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Figure 3a. (a) Anteroposterior radiograph of the left hip in a 31-year-old woman. A highly permeative lesion is seen to involve the superior acetabulum and extend to the ischium and superior pubic ramus. (b, c) T2-weighted MR images (2,700/104) obtained at the level of the ischium (b) and at the junction of the proximal and middle thirds of the thigh (c) demonstrate a high-signal-intensity soft-tissue mass that infiltrates surrounding muscle and extends far beyond the osseous involvement; multiple muscle compartments are involved. The long proximal and distal extent, coupled with the involvement of multiple compartments and invasiveness, distinguish this lesion from the round and more focal masses usually seen in osseous sarcomas, and suggest the diagnosis of primary lymphoma of bone.
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Figure 3b. (a) Anteroposterior radiograph of the left hip in a 31-year-old woman. A highly permeative lesion is seen to involve the superior acetabulum and extend to the ischium and superior pubic ramus. (b, c) T2-weighted MR images (2,700/104) obtained at the level of the ischium (b) and at the junction of the proximal and middle thirds of the thigh (c) demonstrate a high-signal-intensity soft-tissue mass that infiltrates surrounding muscle and extends far beyond the osseous involvement; multiple muscle compartments are involved. The long proximal and distal extent, coupled with the involvement of multiple compartments and invasiveness, distinguish this lesion from the round and more focal masses usually seen in osseous sarcomas, and suggest the diagnosis of primary lymphoma of bone.
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Figure 3c. (a) Anteroposterior radiograph of the left hip in a 31-year-old woman. A highly permeative lesion is seen to involve the superior acetabulum and extend to the ischium and superior pubic ramus. (b, c) T2-weighted MR images (2,700/104) obtained at the level of the ischium (b) and at the junction of the proximal and middle thirds of the thigh (c) demonstrate a high-signal-intensity soft-tissue mass that infiltrates surrounding muscle and extends far beyond the osseous involvement; multiple muscle compartments are involved. The long proximal and distal extent, coupled with the involvement of multiple compartments and invasiveness, distinguish this lesion from the round and more focal masses usually seen in osseous sarcomas, and suggest the diagnosis of primary lymphoma of bone.
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The differential diagnosis of these cases of primary lymphoma of bone can be variable, depending on the age of the patient and whether the case appears more or less aggressive. Dr Krishnan and colleagues have offered a reasonable differential diagnosis, upon which I would expand slightly. First, the authors mention quite correctly that primary lymphoma of bone can share with Ewing sarcoma the characteristics of having extensive marrow disease, a large soft-tissue mass, and little cortical destruction. There is an overlap in age range for these two lesions, particularly for patients aged 20–30 years; therefore, both lesions belong in the differential diagnosis of a lesion of this appearance in a young adult patient. On the other hand, in a middle-aged to older adult, a primary bone tumor of moderate to marked aggressiveness often carries the differential diagnosis of primary lymphoma of bone, osseous malignant fibrous histiocytoma, and chondrosarcoma (which may lack chondroid matrix). Although there are occasionally other findings that allow differentiation among these lesions (eg, subtle matrix in chondrosarcoma, serpiginous tracking of a bone infarct degenerating to malignant fibrous histiocytoma, local enlarged lymph node in primary lymphoma of bone), when these characteristics are not present, all three lesions may be appropriate to include in the differential diagnosis.
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References
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- Melamed JW, Martinez S, Hoffman CJ. Imaging of primary multifocal osseous lymphoma. Skeletal Radiol 1997; 26:35-41.[CrossRef][Medline]
- Ivins JC, Dahlin DC. Malignant lymphoma (reticulum cell sarcoma) of bone. Mayo Clin Proc 1963; 38:375-385.[Medline]
- Mulligan MD, McRae GA, Murphey MD. Imaging features of primary lymphoma of bone. AJR Am J Roentgenol 1999; 173:1691-1697.[Abstract]
Authors’ Response
Jamshid Tehranzadeh, MD,
Anant Krishnan, MD and
Ali Shirkhoda, MD
Department of Diagnostic Radiology, William Beaumont Hospital, Royal Oak, Michigan
We appreciate Dr Manaster’s complimentary comments and fully agree with her additional observations. In primary lymphoma of bone, the medullary cavity is extensively permeated and tumor cells traverse the cortical Haversian system and stimulate periosteal new bone formation. This activity would lead to reactive sclerotic changes that may cause periosteal as well as endosteal cortical thickening. These reactive sclerotic changes may be responsible for false-negative results from closed needle biopsy in cases of osteolymphoma. The periosteal new bone formation in primary bone lymphoma is not, however, often as striking as the onion-peel layering or sunburst appearance of Ewing sarcoma, but it can be easily confused with it radiographically. Sometimes, the periosteal response, lamellated or sunburst, is the only sign of disease seen with conventional radiography.
As commented, primary bone lymphoma often is associated with a disproportionately large and infiltrative soft-tissue mass. The presence of a large soft-tissue mass and swelling in primary bone lymphoma is considered an aggressive sign. Other signs that may suggest a poor prognosis include pathologic fracture, lamellated or interrupted periosteal new bone formation, and cortical destruction.
Primary bone lymphoma affects a wide age range of patients and may have a radiographic appearance similar to that of other small cell tumors such as Ewing sarcoma. However, we concur with Dr Manaster and emphasize that the average age of patients who present with primary bone lymphoma is older than that of patients with Ewing tumor (the majority of whom are less than 25 years old). The other important differentiating feature in primary bone lymphoma is the patient’s clinical condition, which remains good even when the local disease is extensive.
Historically, Parker and Jackson (1) in their original article state: "Perhaps the most important clinical feature is that an extensive painful destructive process in a long bone is found in a patient whose general condition is good. In no other bone sarcoma is the contrast between the comparative well being of the patient and the size of the lesion so marked."
We agree that the differential diagnosis of primary bone lymphoma may be broadened to include Ewing sarcoma; neuroblastoma; metastasis; and other osseous lesions capable of expanding the bone such as osteomyelitis, lytic chondrosarcoma, and bone infarct degenerating to malignant fibrous histiocytoma. In addition, we note that the purely osteolytic form of osteosarcoma cannot, in many instances, be differentiated from primary bone lymphoma.
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References
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- Parker F, Jr, Jackson H, Jr. Primary reticulum cell sarcoma of bone. Surg Gynecol Obstet 1939; 68:45.
Related Article
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Primary Bone Lymphoma: Radiographic–MR Imaging Correlation
- Anant Krishnan, Ali Shirkhoda, Jamshid Tehranzadeh, Ali R. Armin, Ronald Irwin, and Kimberly Les
RadioGraphics 2003 23: 1371-1383.
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