Primary (Malignant) Lymphoma of Bone

Updated: Nov 14, 2017
  • Author: Vincent Y Ng, MD; Chief Editor: Harris Gellman, MD  more...
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Overview

Background

Primary lymphoma of bone (PLB; also referred to as reticulum cell sarcoma, malignant lymphoma of bone, or osteolymphoma) is an uncommon entity that accounts for fewer than 5% of all primary bone tumors. [1] (See the images below.) Orthopedic surgeons typically encounter PLB as a solitary lesion with a variable radiographic appearance. Alternatively, patients with stage IV systemic lymphoma and skeletal involvement may be referred to orthopedic surgeons for the treatment of impending or pathologic fractures. Osseous involvement of disseminated lymphoma is not uncommon.

Total skeleton technetium-99m (99mTc) nuclear medi 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.
A woman who is in the early part of her fifth deca 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.
Diffuse infiltrate of large lymphoid cells is pres Diffuse infiltrate of large lymphoid cells is present, with cleared cytoplasm and hyperchromatic nuclei. Admixed small, reactive lymphocytes also are noted.

There have been no randomized therapeutic trials for this rare disease. Most of the literature consists of retrospective reports on various chemotherapy and radiation therapy regimens.

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Pathophysiology

The definition of PLB includes the following criteria:

  • Histologic documentation of lymphoma in the bone
  • A solitary bone lesion or multiple skeletal lesions
  • No involvement of lymph nodes (except regional lymph nodes) or other lymphoid tissue

Soft-tissue extension from the bone is a common feature of PLB.

Commonly involved bones in PLB, in order of decreasing frequency, include the following:

  • Femur
  • Humerus
  • Tibia
  • Spine
  • Pelvis
  • Sternum
  • Ribs
  • Bones of the skull and face

The metadiaphyseal portion of bone is the most common site of disease. Involvement of the small bones of the hands and feet is rare. Some studies suggest that the mandible and maxilla are frequently affected sites, but confirmation that bone is the primary site of disease is not well documented.

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Etiology

The etiology of PLB is unknown. Viral agents and immunosuppression have been implicated in some cases. PLB has been documented as a posttransplant lymphoproliferative disorder in patients who have been immunosuppressed. Bone has also been documented as a site for primary lymphoma in patients with AIDS. Rarely, patients with Paget disease of bone may develop malignant lymphoma in the involved bone.

Cytogenetic and molecular abnormalities are associated with many different lymphomas. These also can be documented in the setting of primary bone lymphoma.

Some common recurrent abnormalities are as follows:

  • t(14;18)(q32;q21) - Overexpression of Bcl-2 protein, seen in 80-90% of follicular B-cell lymphomas and in 20% of diffuse large B-cell lymphomas
  • Rearrangements involving band 3q27 - Rearrangement of BCL6 gene, seen in 35% of diffuse large B-cell lymphomas
  • t(8:14)(q24;q32) - Overexpression of Myc protein, seen in 80% of Burkitt lymphomas; variant translocations t(2;8)(p11;q24) or t(8;22)(q24;q11), found in the remaining 20% of cases
  • t(2;5)(p23;q35) - Formation of nucleophosmin–anaplastic lymphoma kinase (NPM-ALK) fusion protein, seen in T-cell anaplastic large cell lymphoma
  • t(11;14)(q13;q32) - Overexpression of cyclin D1, seen in mantle cell lymphoma (not reported as a primary bone lymphoma)
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Epidemiology

PLB accounts for fewer than 5% of primary bone tumors and fewer than 5% of extranodal lymphomas (or ~1% of all primary non-Hodgkin lymphomas). [2]

Secondary involvement of bone marrow is seen in 5-15% of patients with Hodgkin disease and 30-53% of patients with non-Hodgkin lymphoma. As many as 50% of patients with AIDS-associated Hodgkin disease have secondary bone marrow involvement. [3, 4]

The median age range for PLB is 36-52 years, but the peak prevalence is between the ages of 50 and 70 years. It is rare in children. Males are affected more frequently than females (male-to-female ratio, 1.51.8:1).

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Prognosis

In general, PLB has a better prognosis than most primary bone sarcomas or metastatic lesions do. The Surveillance, Epidemiology, and End Results (SEER) database reported 5- and 10-year survival rates of 58% and 45%, respectively, including patients from 1973-2005. [5] These rates are lower than are reported in most other literature.

A study from Memorial Sloan-Kettering Cancer Center reported a 5-year overall survival rate of 95% with chemoradiation and 78% with single-modality treatment. [6] The patients treated with only chemotherapy, however, tended to have more advanced stage disease. The University of Miami reported a progression-free survival rate of 83% at 4 years. [7] Demircay et al reported a disease-free 5-year survival rate for patients younger than 60 years and older than 60 years of 90% and 62%, respectively. [8]

Positive prognostic factors for outcome include younger age at diagnosis, multimodal treatment, and localized disease; it has been suggested that inclusion of rituximab in the treatment regimen may improve the prognosis. [9] Other factors (eg, type of lymphoma, sex, and lesion size) do not seem to be significant on multivariate analysis.

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