Nonoperative Therapy
Radiation therapy (RT) for primary lymphoma of bone (PLB; also referred to as reticulum cell sarcoma, malignant lymphoma of bone, or osteolymphoma) provides adequate local control rates; however, when used alone, it results in high rates of systemic failure. The addition of chemotherapy provides superior overall survival and a decreased incidence of relapse. [19, 20] Multimodal chemoradiation can often even allow bone healing. Only approximately one third of patients with PLB ultimately require surgery for impending pathologic fractures. [9]
Patients should be monitored radiographically and clinically during chemoradiation for bone healing. Those with persistent activity-related pain should be evaluated for surgery before progressing to less restrictive weightbearing precautions.
Chemotherapy typically consists of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and prednisone (CHOP), either with (RCHOP) or without the anti-CD-20 antibody rituximab. Intrathecal methotrexate may be given for central nervous system (CNS) prophylaxis. RT of 40-60 Gy, fractionated over several weeks, usually follows chemotherapy. [21, 22, 23] Refractory cases have been treated with allogeneic bone marrow transplantation. [24]
In children, aggressive chemotherapy alone appears to be as effective as combined-modality therapy. Because RT in children is associated with an increased incidence of adverse growth-related consequences, it should be avoided in this population.
Surgical Management
Surgery is not a primary modality of treatment for PLB, aside from biopsy and treatment of skeletal complications. Before the advent of effective RT and chemotherapy, some patients were treated with amputation. Indications for the operative involvement of orthopedic surgeons in PLB most commonly fall into one of the following three categories:
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Diagnosis
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Treatment of pathologic or impending pathologic fractures
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Decompression of spinal canal compromise
No clear role for surgical debulking or wide resection currently exists for PLB.
Indications for prophylactic stabilization of impending pathologic fractures
Because lymphomas involving bone may result in pathologic fractures, appropriate steps should be taken to prevent such fractures before they occur.
In most patients, particularly those who are younger and compliant, protected weightbearing and use of a gait-aid devices suffice during chemoradiation and until there is improvement of the radiographic appearance. Prophylactic stabilization may be indicated in selected patients who are either unable or unwilling to take such measures to avoid fracture, or if there is an increase in activity-related pain indicating structural insufficiency and microfractures.
The evaluation for impending pathologic fracture in PLB is similar to that for metastatic bone lesions. The highest-risk lesions are those of a lytic nature that involve more than one half to two thirds of the bone diameter. This is particularly true for lesions that are located in the peritrochanteric region and cause pain with weightbearing. Lesions that have cortical destruction are at higher risk than those that are primarily marrow-replacing.
Prophylactic stabilization typically involves curettage, cementation, and augmentation of the lesion with internal fixation. An adjuvant such as cryotherapy may be used.
Indications for fixation of pathologic fractures
If a pathologic fracture occurs, the surgical decision-making changes. On average, approximately one third of all pathologic fractures from metastases to bone heal after surgical fixation. This rate varies depending on the type of primary malignancy. There are no published rates for PLB, but with the addition of radiation therapy that further hinders bone healing, the surgeon should assume that the fracture will not heal.
Because the survival for PLB is fairly high, the construct chosen should be very durable. Several trauma studies have demonstrated the ability of a statically locked intramedullary nail at least 12 mm in diameter to support early weightbearing of an average adult male, even with comminution or a segmental bone defect. Nevertheless, the bone stock in patients with malignancy may be compromised, and it is likely that long-term weightbearing on a nail with no bony support will result in hardware failure.
If the pathologic fracture occurs in an area amenable to bone resection and replacement with a megaprosthesis, this should be strongly considered. Cemented endoprostheses provide immediate stability and early resumption of activity.
Surgery for spinal involvement
Lymphoma can occur in the spine and cause nerve or cord compression. In cases of foraminal or central stenosis from soft-tissue extension of PLB, decompression may be necessary to prevent progressive neurologic deficit. If there is spinal instability either from the decompression or from a lytic lesion, spinal fusion also may be necessary.
Contraindications
Contraindications for surgery are similar to those noted in other conditions and are not specific to PLB. Needle biopsies are often adequate and can obviate the need for surgical biopsy. Because RT and chemotherapy are effective modalities of treatment, a cure can be achieved without surgical intervention.
Complications
Complications from PLB and its treatment can include the following:
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Fracture [25]
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Fracture nonunion
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Wound infection
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Failure of prophylactic fixation
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Secondary arthritis following collapse of osteonecrotic bone
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Toxicity of chemotherapy
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Thrombophlebitis
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Avascular necrosis (AVN) of bone
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Secondary malignancy from chemotherapy or RT
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Total skeleton technetium-99m (99mTc) nuclear medicine scan reveals an isolated increased uptake in the left proximal femur at the site of this patient's bone lymphoma.
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Total skeleton technetium-99m (99mTc) nuclear medicine scan shows increased uptake in the left acromion, the site of bony involvement by lymphoma in this patient. The initial differential diagnosis suggested metastatic disease to bone in addition to multiple myeloma and lymphoma, in that order.
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Coronal, T1-weighted magnetic resonance imaging (MRI) scan of the left shoulder reveals the replacement of the left acromion by a low-signal process extending into the surrounding soft tissue.
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Coronal, T2-weighted magnetic resonance imaging (MRI) scan of the left shoulder reveals a high-signal process involving the left acromion and extending to the surrounding soft tissue. The MRI scan's features are suggestive only of a very high cellularity fluid-containing process, but they are nonspecific. Biopsy is required for a specific diagnosis.
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Sections of the biopsy show a diffuse infiltrate of atypical large lymphoid cells with vesicular nuclei, small nucleoli, and moderate cytoplasm. Small reactive lymphocytes are in the background.
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An immunohistochemical stain using an antibody directed against CD20 (B-cell marker) shows strong positivity in the large lymphoid cells. This is an example of a diffuse large B-cell lymphoma.
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A woman who is in the early part of her fifth decade presents with progressive left thigh pain and a limp. An anteroposterior radiograph of her left proximal femur reveals a lytic destructive process involving the subtrochanteric region, with medical cortical erosion, soft-tissue extension, and an associated lesser trochanteric avulsion fracture. The proximal femur is the most common site for primary bone lymphoma.
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An elderly woman presents with complaints of left shoulder pain of several months duration. A plain radiograph of the left shoulder (glenoid view) reveals a destructive lytic process eroding the cortical margins of the acromial process.
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Diffuse infiltrate of large lymphoid cells is present, with cleared cytoplasm and hyperchromatic nuclei. Admixed small, reactive lymphocytes also are noted.
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Immunohistochemical stain using an antibody against CD20 is positive in the large cells; this is a diffuse large B-cell lymphoma.
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Clinical photo of a left shoulder shows a prominence in the midportion of the left clavicle. This 45-year-old man was suffering from local pain and tenderness but had no history of prior trauma.
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Technetium-99m (99mTc) total skeleton nuclear medicine scan shows increased uptake in the midportion of the left clavicle, an area corresponding to the clinical site of bone enlargement.
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Anteroposterior radiograph of the left clavicle reveals a mixed lytic and sclerotic destructive process within the midportion of the bone, with indistinct, permeative borders.
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Another example of a diffuse large cell lymphoma. In addition to the large lymphoid cells with moderate cytoplasm, a few cells with lobate nuclei also are seen. Such cells are often observed in large cell lymphoma of the bone.
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Plain radiographs in this 12-year-old patient with severely progressive right shoulder pain were interpreted as being normal. At most, they showed the existence of localized osteopenia in the right proximal humerus, but they did not demonstrate the presence of a discrete lesion within the bone. Based on the initial evaluation and plain radiographs, the patient was thought to have referred pain from the cervical region or brachial plexus.
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Coronal, T1-weighted magnetic resonance imaging (MRI) scan of the upper thorax and bilateral shoulders reveals a marrow replacement low-signal process involving the entire right proximal humerus. The corresponding T2-weighted MRI scan showed a high-signal process in this area. This MRI scan was produced after plain radiographs were interpreted as normal and an MRI scan of the cervical spine and brachial plexus revealed the unsuspected findings in the humerus.
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Histologic sections reveal a highly cellular neoplasm composed of cells with a high nucleus-to-cytoplasm ratio, scant cytoplasm, and fine nuclear chromatin. The cells showed immunohistochemical evidence of B-cell lineage and expressed terminal deoxynucleotidyl transferase (TdT), consistent with a precursor B-lymphoblastic lymphoma.
