Bone Lymphoma Imaging 

Primary 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]

See the images of bone lymphoma below.

The World Health Organization recognizes the following 4 groups of lymphoma involving bone:

• A single primary bone site with or without regional nodes
• Multiple bone sites but no visceral involvement
• A bone lesion and involvement of multiple visceral or lymph node sites
• Soft-tissue lymphoma, with bone involvement detected by bone biopsy or marrow aspirate

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 examination

After 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 (^99m Tc) bone scintigraphy also can be used to look for additional sites of involvement that may be clinically silent.^{[4, 5, 6]}

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.

Because primary lymphoma of bone (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.

In a review of 237 cases, Mulligan and colleagues listed the most common radiographic features, which included those listed below (also see the images below)^[7] :

• Permeative, lytic pattern of bone destruction (74%)
• Metadiaphyseal location (69%)
• Periosteal reaction (58%)
• Soft-tissue mass (80-100%)

The range of appearances is broad, including the following (see also the images below):

• Some patients (< 5%) present with no detectable abnormal findings on initial conventional radiographs.
• Some patients (11%) demonstrate focal geographic lesions that may have a mixed or blastic appearance.
• The location can be epiphyseal, metaphyseal, or diaphyseal (see the image below).Variant location. A 51-year-old man with left leg pain. Lateral radiograph demonstrates a lytic lesion with a moth-eaten appearance centered in the middiaphysis of the tibia.
• Primary intracortical and periosteal lesions have been reported.
• Typical lesions occasionally are large enough for patients to present with pathologic fracture (22%).
• Periosteal reaction varies, ranging from a single, continuous layer to interrupted multiple layers. Interrupted single or multiple layers were the most common type of periosteal reaction (52%) found in the study.

Detection of a soft-tissue mass depends on the type of imaging modality used. CT scanning and MRI are more sensitive than are conventional radiographs (see the images below).

Sequestrum formation is a feature of PLB that can help to differentiate it from most other diagnostic possibilities, because sequestra typically are not observed in the other conditions. Sequestra have been reported in 11-16% of patients with PLB.^[8]

Another uncommon feature of PLB is involvement of adjacent bones (4%).

Cross-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 (see the image below).

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.^[9]

When 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.

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. (See the image below.)

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have 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.

The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or magnetic resonance angiography (MRA) scans. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Bone scintigraphy with technetium-99m (^99m Tc) 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^99m Tc 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 primary lymphoma of bone (PLB) (see the image below). 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.^[10]

Gallium-67 (⁶⁷ Ga) citrate and thallium-201 (²⁰¹ Tl) also are positive in patients with PLB. Whole-body⁶⁷ Ga scanning can help with initial staging by identifying or excluding soft-tissue foci of disease.⁶⁷ Ga scanning also may be more helpful than other imaging modalities when determining the response of the tumor to the clinical treatment. Fluorodeoxyglucose positron emission tomography (FDG-PET) is also useful for initial staging and follow-up.

Findings 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^99m Tc.

Currently, 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.

Conventional angiographic findings are nonspecific. Lesions typically demonstrate hypervascular flow with tumor neovascularity, but they may be hypovascular or avascular.^[11]