Journal of Cancer Research and Therapeutics Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI) ISSN: 0973-1482 EISSN: 1998-4138 Vol. 6, Num. 3, 2010, pp. 296-298

Journal of Cancer Research and Therapeutics, Vol. 6, No. 3, July-September, 2010, pp. 296-298

Brief Communication

Primary bone lymphoma: A report of two cases and review of the literature

Tejinder Singh¹, CT Satheesh¹, KC Lakshmaiah¹, TM Suresh¹, Govind K Babu¹, D Lokanatha¹, Linu A Jacob¹, Rajashekar Halkud²

¹ Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore - 560 030, India
² Head and Neck Surgery, Kidwai Memorial Institute of Oncology, Bangalore - 560 030, India

Correspondence Address:Tejinder Singh, Dept of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore - 560 029, India, drtejinderseera@gmail.com

Code Number: cr10066

PMID: 21119256

DOI: 10.4103/0973-1482.73366

Abstract

Keywords: Chemotherapy, extra nodal, primary bone lymphoma

Introduction

Primary lymphoma of bone (PLB), which is defined as lymphoma localized to the bone without evidence of lymph nodes or other tissues at presentation, is one of the rarest primary bone malignancies, accounting for less than 5% of all primary bone tumors. ^[1] Diffuse large-B-cell lymphoma (DLBCL) accounts for the majority of cases of PBL. ^[2],[3] Non-Hodgkin′s lymphoma is found outside of nodal tissues in 24-45% of cases. Common extranodal sites include the GI tract, skin, and, less often, bone. As primary bone lymphoma is a highly curable disease, differentiation from other causes of lytic bone lesion such as secondaries from carcinomas and other primary bone tumors is important. PBL have excellent prognosis following chemotherapy and radiotherapy. Here we report two cases primary non-Hodgkin′s lymphoma of bone diagnosed and treated in our hospital.

Case Reports

Case 1

A 44-year-old male presented with pain and swelling in left thigh since two months. X-ray of left thigh showed multiple lytic and sclerotic areas involving the lower end of left femur. Open biopsy of the lesion was done. Histopathological examination showed small round cell tumor. Immunohistochemistry of the lesion showed positivity for LCA and CD 20 and negative for CD 99, cytokeratin, desmin and CD 3. Further work up including bone marrow aspiration and biopsy, CT scan of neck, chest, abdomen/ pelvis and bone scan was normal. Final diagnosis was diffuse large B cell lymphoma of left femur and his disease was staged as stage I-E. He was treated with six cycles of CHOP and he had complete response to the therapy. This was followed by radiation therapy 35Gy in 15 fractions over 3 weeks followed by a boost of 500cGy with a reduced field. Patient is now on regular follow up and is disease free since last three years after treatment.

Case 2

A 35-year-male presented with swelling and ulcerative lesion in left knee joint since one month. One year prior to this presentation, he complained of swelling and tenderness over both knee joints and left elbow joint and also had left cervical lymphadenopathy. Fine needle aspiration cytology from left cervical lymph node showed granulomatous lesion and he was treated with antituberculosis drugs for four months. Patient improved initially with antituberculosis drugs but after four months, swelling and tenderness over both knee joints recurred. He was then referred to rheumatologist and since his rheumatoid factor and ESR was high he was started on low dose methotrexate. He showed gradual improvement for first two months but then he developed swelling and ulcerative lesion over left knee joint. Histopathological examination from lesion showed small round cell tumor [Figure - 1]. Patient was then referred to us in view of the same. Immunohistochemistry of the lesion showed positivity for LCA, CD 20, CD79a [Figure - 2] and negative for CD 99, cytokeratin, desmin and CD 3. Final diagnosis was diffuse large B cell lymphoma of left femur. Further work up including, bone marrow aspiration and biopsy, CT scan of neck, chest, abdomen and pelvis was normal. CT scan of left knee joint showed multiple lytic and sclerotic areas involving the lower end of left femur with adjacent soft tissue swelling [Figure - 3] and [Figure - 4]. Bone scan revealed multiple osteolytic lesions involving lower end of both femur, upper end of right humerus, scapula and cervical and thoracic vertebras. MRI of the spine revealed multiple osteolytic lesions involving cervical, thoracic and lumbar vertebras. His disease was staged as stage IV in view of multiple extra nodal diseases. He was treated with six cycles of CHOP and he had partial response to the therapy. Presently he is undergoing radiotherapy of 35Gy in 15 fractions over 3 weeks followed by a boost of 500cGy to lower end of femur.

Review of Literature

Primary lymphoma of bone is rare, representing only 5% of all extranodal lymphomas and <2% of all lymphomas in adults. ^[1] The cell architecture and histology is indistinguishable from nodal or lymphoid derived lymphomas. They arise from the medullary cavity and manifest as a localized, solitary lesion. To be defined as primary bone lymphoma (also known as Coley′s criteria), there should be ^[4]

(i) a primary focus in a single bone

(ii) positive histological diagnosis

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

Regional lymph node involvement at diagnosis is not considered as exclusion criteria. ^[5] Currently, it is recognized that primary bone lymphoma may involve multiple bones, as long as the other two criteria are met. Present case fulfills above criteria of being a primary NHL of bone.

PBL occurs commonly between 20 and 50 years of age and shows male preponderance with male to female ratio of 3:2. The femur (29%) is the most common site followed by (in descending order of frequency): pelvis (19%), humerus (13%), skull (11%) and tibia (10%). ^[6] Some series have found that long bones and flat bones are equally affected. ^[7] Clinical presentation includes local pain and swelling. Radiologically bony lesions may be extensive, destructive or infiltrative. ^[1] Extensive lesions involve 25-50% of affected bone, sometimes entire bone. Destructive lesions are radiolucent, mottled, patchy, moth eaten and sometimes the outline of the bone is completely lost. Infiltrative or permeative lesions have poorly defined interface with normal bone, 50% have a mixture with small areas of sclerosis. Nearly all variants destroy cortical bone and 25% thicken the cortex. Often large, obvious soft-tissue extension may be present along with bony lesion. Diagnosis is established by biopsy. Other investigations include skeletal survey, bone scan, bone marrow biopsy, CT scan of whole abdomen and chest to assess lymph node involvement and serum LDH estimation are done as part of the staging procedure. Plain radiographs often underestimate the extent of the lesion. CT scan is useful for disease staging and delineating spinal lesions. MRI is helpful in demonstrating bone marrow and soft tissue involvement. Role of positron emission tomography (PET) scan is not well defined in PBL due to its rarity. Lymphoma has an increased uptake on bone scan. With the combined use of CT, MRI and now PET scan, a higher proportion of patients are diagnosed with stage IV disease. ^[2] Primary bone lymphoma needs to be differentiated from metastatic carcinoma, Ewing′s sarcoma, osteosarcoma, eosinophilic granuloma (skeletal) and chronic osteomyelitis. ^[8]

Over the last two decades, chemotherapy (CHOP based) has become the standard treatment with or without consolidative irradiation. Traditionally, irradiation has been used alone or in combination with chemotherapy. Irradiation alone in limited-stage disease has resulted in a poor five-year overall survival (OS) of around 45% even when patients have been carefully chosen for apparently limited-stage disease. ^[9] The introduction of rituximab since March 2001 has been accompanied by a remarkable improvement in the PFS for patients with PBL compared with those treated earlier without rituximab (3-year PFS 88% versus 52%). ^[7] Although the median follow-up is only 28 months, this is similar to reports for DLBCL in general and suggests a real improvement in the outcome of this condition.

Role of radiation in advanced stage PBL is controversial. In a study by Ramadan et al, ^[7] patients with advanced-stage disease who received chemotherapy plus irradiation actually had a poorer outcome compared with those who received chemotherapy alone (10-year OS were 25% and 56%, respectively). However, this difference must be very cautiously interpreted because the decision to use irradiation was individualized.

Surgery is only indicated for pathologic fractures. Disease free and overall survival rates have been reported to be 78% and 91% at 5 years and 73% and 87% at 10 years, respectively. ^[8] Multivariate analysis of prognostic factors identified three distinct groups, those with age <60 years with IPI 1-3, age ≥ 60 years with IPI 0-3 and age ≥ 60 years with IPI 4-5 with markedly different 5-year OS of 90%, 61% and 25%, respectively. ^[7] Neither presenting bony site of lymphoma nor presence of pathological fracture has any prognostic impact. Disease progression or relapse, especially in patients ≥ 60, confers a very poor prognosis.

Thus, primary lymphoma of bone should be considered in the differential diagnosis of bony tumors in young patients in second to fourth decade. Chemotherapy followed by radiotherapy is the treatment of choice and is associated with good outcome. We did not use rituximab, but addition may have benefited these patients. It is reasonable to re-examine the role of irradiation since highly effective chemotherapy is available for DLBCL, especially in advanced disease.

References

Copyright 2010 - Journal of Cancer Research and Therapeutics

The following images related to this document are available:

Photo images