Primary lymphoma of bone in adults

Primary lymphoma of bone (PLB) is defined as malignant, lymphoid infiltrate within bone, without evidence of lymph nodes or other tissues at presentation. It arises from the medullary cavity and manifests as a localised, solitary lesion.

It is rare, accounting for only 3% of primary bone malignancies and 5% of extra nodal lymphomas(1). Bone lymphoma is not uncommon in advanced lymphoma originating from other sites, but PLB accounts for less than 2% of all lymphomas in adults (2).

To be defined as primary bone lymphoma there must be:

(i) a primary focus in a single bone

(ii) positive histological diagnosis

(iii) no evidence of distant soft tissue or distant lymph node involvement.

However this definition of PLB is controversial. Some studies have included patients with Ann Arbor stage 1 and 2 only, whereas others have also included patients with stage 4 disease (3).  Regional lymph node involvement at diagnosis is therefore accepted by some, as is involvement of multiple skeletal sites, as long as the other criteria are met (4).

The majority of PLB is Non-Hodgkin lymphoma, with large B-cell lymphoma being the most common subtype. Other types include follicular lymphoma and Burkitt lymphoma. Differential diagnosis includes Ewing’s sarcoma, neuroblastoma, and other round cell tumours. It can also be associated with AIDS, immunosuppression and Paget’s disease.

The most common presentations are bone pain not relieved by rest, a palpable mass, pathological fracture or cord compression. About 10% have systemic symptoms at presentation including night sweats, weight loss and fever. Common sites include the femur, humerus, tibia, spine, pelvis, sternum, ribs and skull.

PLB most often involves the diametaphysis of major long bones. Radiological findings are of an aggressive pattern of lytic bone destruction and associated soft tissue mass. CT or MRI will show a large soft tissue mass and abnormal marrow attenuation without extensive cortical destruction (5).

Because PLB is rare, there have been few randomised control trials to evaluate treatment. Traditionally radiotherapy has been used as treatment with or without chemotherapy. However more recently the standard treatment has consisted of chemotherapy (CHOP regime) with or without radiotherapy depending on the histological type and stage. Several studies have established that a combination of chemotherapy and radiotherapy is better than radiotherapy alone (6,7).

The evidence is conflicting as to which regimen produces the best survival rates. Most studies are of small sample size and are therefore limited in their value in identifying prognostic factors.

A study by Alencar et al recorded progression free survival at 83% at 4 years with no difference between treatment with chemotherapy and a combination of chemotherapy and radiotherapy (8).  Jawed et al, in a review of 1500 adults, estimated 5 year survival at 58% and 10 year survival at 45%, and the only positive prognostic indicators identified were localised disease and younger age (9).

Disease free and overall survival rates have also been reported to be 78% and 91% at 5 years and 73% and 87% at 10 years, respectively (10).

Surgical management is limited to biopsy, stabilisation of pathological fracture and decompression of spinal canal compromise. There is no clear role for debulking surgery or resection.

The introduction of rituximab in March 2001 for treatment of diffuse large cell lymphoma has shown increased survival rates compared to those treated without rituximab, for example 3 year progression free survival has been demonstrated at 88% verses 52% without rituximab (11).

Dr Ruth Blackwell MBBS

GPST1

Newcastle Upon Tyne

References:

1. Baar J, Burkes RL, Bell R, Blackstein ME, Fernandes B, Langer F. Primary non-Hodgkin’s lymphoma of bone. A clinicopathologic study. Cancer. Feb 15 1994;73(4):1194-9.
2 Ramadan KM, Shenkier T, Sehn LH, Gascoyne RD, Connors JM. A clinicopathological retrospective study of 131 patients with primary bone lymphoma: A population-based study of successively treated cohorts from the British Columbia Cancer Agency. Ann Oncol 2007;18:129-35.
3 Jawad et al. Primary Lymphoma of bone in adult patients. Cancer 2010;116(4):871
4 Singh T, Satheesh CT, Lakshmaiah KC, Suresh TM, Babu GK, Lokanatha D, Jacob LA, Halkud R. Primary bone lymphoma: A report of two cases and review of the literature. J Can Res Ther 2010;6:296-8
5 Mulligan ME, McRae GA, Murphey MD. Imaging features of primary lymphoma of bone AJR Am J Roentgenol 1999;173:1691-7.
6 Dubey P, Ha CS, Besa PC et al. Localized primary malignant lymphoma of bone. Int J Radiat Oncol Biol Phys 1997;37:1087-1093.
7 Baar J, Burkes RL, Bell R, Blackstein ME, Fernandes B, Langer F. Primary non-Hodgkin’s lymphoma of bone. A clinicopathologic study. Cancer. Feb 15 1994;73(4):1194-9.
8 Alencar et al Primary bone lymphoma – the university of Miami experience. Leuk lymphoma. Jan 2010;51(1):39-49
9 Jawad et al. Primary Lymphoma of bone in adult patients. Cancer 2010;116(4):871
10 Fidias P, Spiro I, Sobczak ML, Nielsen GP, Ruffolo EF, Mankin H, et al. Long-term results of combined modality therapy in primary bone lymphomas. Int J Radiat Oncol Biol Phys 1999;45:1213-8.
11 Ramadan KM, Shenkier T, Sehn LH, Gascoyne RD, Connors JM. A clinicopathological retrospective study of 131 patients with primary bone lymphoma: A population-based study of successively treated cohorts from the British Columbia Cancer Agency. Ann Oncol 2007;18:129-35.

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