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Primary Lymphomas of Bone
Brief Communication Primary Lymphomas of Bone Paula Gill, Doris E. Wenger, David J. Inwards
Abstract Primary bone lymphoma is rare. The majority of cases are diffuse large B-cell non-Hodgkin’s lymphomas. Classification, staging, and treatment are controversial. The relatively small number of cases has led to many case reports and series describing institutional experiences but precludes the use of randomized clinical trials to address the question of optimal management. This article will review clinical and radiologic presentations, diagnostic techniques, and histologic characteristics. Most important, it will present what limited information we do have regarding effective treatment options for this unusual type of lymphoma.
Clinical Lymphoma & Myeloma, Vol. 6, No. 2, 140-142, 2005 Key words: Extranodal disease, Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma
Introduction Lymphoma is one of the most common hematologic malignancies. Generally divided into Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (NHL) and further classified by histologic type, the majority of lymphomas present with lymphadenopathy. Whereas extranodal presentation is uncommon in Hodgkin’s lymphoma, 10%-35% of patients with NHL have primary extranodal disease at initial diagnosis.1 The most common site is the gastrointestinal tract, followed by skin, testes, kidney, and bone. Primary lymphoma of bone (PLB) constitutes approximately 2% of all bone tumors and 5% of all extranodal lymphomas.2 It was first described by Oberling in 1928,3 and in 1939 Jackson and Parker reported the first case series of 17 patients with primary reticulum cell sarcoma of bone, or, as it is now known, PLB. Although PLB has been an established clinical entity for > 6 decades, its definition, diagnosis, and treatment remain controversial.
Clinical Presentation Primary lymphoma of bone has been described as a malignant lymphoid infiltrate within bone without concurrent lymph node or distant visceral involvement.2 However, there is no agreed-upon definition or diagnostic criteria for PLB. Some contend that there may be lymph node involvement as long as there is a 6-month window between diagnosis of the primary Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN Submitted: Jan 19, 2004; Revised: Sep 13, 2004; Accepted: Sep 13, 2004 Address for correspondence: David J. Inwards, MD, Mayo Clinic, Division of Hematology, 200 First St SW Rochester, MN 55905 Fax: 507-266-4972; e-mail: [email protected]
bone focus and emergence of lymph node disease. Clinically, it can be difficult to differentiate PLB and lymphomatous involvement of bone as a component of extraosseous lymphoma, which makes the diagnosis of PLB challenging. For the purposes of this review, PLB is considered a malignant lymphocytic infiltrate of bone with no lymph node or distant visceral disease. Primary lymphoma of bone predominantly affects men, with a male-to-female ratio of 1.8:1.2,4,5 Although age of onset varies, a study of 237 pathologically proven cases reported a mean age of 42 years.6 The most common presenting symptom is bone pain not relieved by rest. The pain can be insidious and intermittent, clinically similar to chronic osteomyelitis.5 Consequently, patients may wait several months before seeking medical attention. Approximately 50% of patients experience associated soft tissue swelling as a result of direct extension of bony disease into adjacent soft tissues.6 The long bones, specifically the femur and tibia, are most frequently affected. Vertebral involvement is common as well.4,7,8 Because PLB often affects weight-bearing bones, pathologic fractures are a specific concern and may be a presenting sign or a late complication. As with any lymphoma, patients may experience B symptoms such as fever, weight loss, and/or night sweats.
Diagnosis Imaging Studies The radiologic appearance of PLB is variable and nonspecific. Conventional radiography typically shows an osteolytic pattern of bone destruction, but may show a sclerotic or mixed lytic and sclerotic pattern (Figures 1A and 1B). Despite extreme medullary infiltration, periosteal reaction is typically minimal. Soft tissue masses are common but are better detected by cross-sectional imaging.
Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cancer Information Group, ISSN #1526-9655, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
140 • Clinical Lymphoma & Myeloma September 2005
If a clinician suspects PLB based on plain radiographs or if PLB is suspected at the outset what imaging modality is best? Although technetium bone scanning may show activity, as with conventional radiography, these findings are nonspecific.4 Magnetic resonance imaging is the most sensitive technique for the presence of intraosseous tumor; however, the appearance of PLB is variable (Figures 1C and 1D). A pattern of extensive marrow involvement with minimal plain radiographic findings is highly suspicious of hematologic malignancy, including PLB. Although T2-weighted images are variable, T1-weighted images show low signal intensity and usually define the extent of disease better.3 Computed tomography may show soft tissue extension, cortical involvement, or marrow invasion suggestive of malignancy, but these findings are nonspecific (Figures 1E and 1F). Positron emission tomography may be helpful for staging or detecting residual disease after treatment, but it has little role in the initial workup of suspected PLB. The differential diagnosis of PLB based on radiographic features is age-dependent. In young patients, the differential includes osteosarcoma, Ewing sarcoma, and leukemia. In older patients, multiple myeloma and metastatic carcinoma are more common.5 Biopsy Techniques If any type of malignancy is suspected based on radiographic findings, a biopsy must be performed. Fine needle aspiration (FNA) of a suspected osseous tumor can be challenging. It may be difficult to obtain adequate tissue for diagnosis, and sampling error may produce a false-negative result. Also, fine needle aspiration and core biopsies may make a pathologic diagnosis difficult as a result of crush artifact. Consequently, when PLB is suspected, an open biopsy is preferred if technically feasible.3 If unable to obtain an open biopsy, generous core biopsy is preferred over FNA. An open biopsy technique harvests tissue by extraction rather than compression, as with FNA or core needle biopsies. Although this technique requires a surgical procedure, the diagnostic yield may be greater. Histopathology Primary lymphoma of bone is mainly of B-cell origin. Although T-cell PLB has been described, it is more common in Japan and Hong Kong where there is a higher overall incidence of T-cell lymphoma. Of the B-cell PLBs, the majority are of diffuse largecell type. Lewis et al performed a retrospective analysis of 18 patients diagnosed with PLB from 1984 to 1994. Seventy-five percent of cases were diffuse large B-cell, whereas the remainder were equally divided among follicular, small noncleaved, and T-cell types.2 Cytogenetics and immunohistochemistry vary among tumors of this type. The histologic grade is of little prognostic value in PLB. No significant survival difference between indolent and aggressive PLB has been documented to date.9,10 Additionally, the treatment recommendations are the same regardless of grade.2
Staging Complete staging with computed tomography scans and bone marrow biopsy is essential in the evaluation of any new
Figure 1 B-Cell Large-Cell Non-Hodgkin's Lymphoma of the Femur A
B
C
D
E
F
Anteroposterior (A) and lateral (B) radiographs of the right femur show a subtle mixed osteolytic and sclerotic process involving the distal half of the femur consistent with lymphoma. There is a small focus of endosteal erosion along the anterolateral aspect of the femoral diaphysis, but no evidence of frank cortical destruction or periosteal new bone formation. The sagittal T1-weighted magnetic resonance image (C) and T2-weighted magnetic resonance image with fat saturation (D) show an extensive destructive lesion involving the distal half of the femur that correlates with the subtle lesion seen on the conventional radiographs. The magnetic resonance images show that the lesion occupies the entire diameter of the medullary canal with associated endosteal erosion and has intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Although the signal characteristics are nonspecific, this constellation of imaging features, with magnetic resonance findings out of proportion to those predicted on the basis of the conventional radiographs, is highly suggestive of a diagnosis of lymphoma. The axial computed tomography images with bone (E) and soft tissue windows (F), with the left leg included for comparison, show complete replacement of the normal medullary fat in the right femoral canal by a lesion of soft tissue density, along with subtle thinning and permeation of the cortical bone.
case of lymphoma. Lymphomatous involvement of bone can occur in patients with extraosseous lymphoma as well, which should be distinguished from PLB. To ensure a correct diagnosis of PLB, disease involvement in extraosseous sites (ie, lymph nodes, viscera) must be ruled out. Previous studies have suggested that patients with PLB have a favorable prognosis compared with those with extraosseous disease.7,11-14 However, a recent retrospective analysis by Lewis et al of 28 patients with
Clinical Lymphoma & Myeloma September 2005 • 141
Primary Lymphomas of Bone lymphomatous involvement of bone suggests that PLB does not confer an improved prognosis compared with extraosseous disease.2 Whether this will be confirmed by other studies is unknown. Currently, the distinction between PLB and systemic lymphoma appears clinically significant.
Treatment Treatment options for PLB, as with any malignancy, include surgery, radiation, and/or chemotherapy. The role of surgery is limited to biopsy and the management of pathologic fractures.3,15 Because of the rarity of this disease, there are minimal data available regarding optimal management. Deciding what treatment regimen is best for an individual patient is a challenge. Historically, the standard of care for localized disease (stage IE per Ann Arbor classification) was radiation therapy alone at a dose of 40-60 Gy.8,12,15 Although local control was achieved in 87%-100% of cases,12,14,15 there was a high rate of distant relapse. In one study of 28 patients with stage IE disease who exhibited excellent local control with radiation, 13 had relapses at distant sites and eventually died of their disease.15 Because of this, there has been a trend toward combined-modality therapy. Several small studies have shown some advantage to the use of anthracycline-based chemotherapy (ie, CHOP [cyclophosphamide/ doxorubicin/vincristine/prednisone]) and radiation versus radiation alone. Fairbanks et al suggested an improved disease-free survival (DFS) with combined-modality therapy in patients with stage IE disease, but this did not translate into an increase in overall survival (OS).8 Dubey et al showed no difference in OS or DFS when comparing radiation alone versus CMT.7 Fidias et al found a statistically significant benefit in DFS (78% vs. 42%) and OS (91% vs. 50%) for patients who received combined-modality therapy versus radiation alone.14 Given the rarity of this disease and the differences in how primary lymphoma of bone has been defined in previous studies, it is difficult to know how to proceed based on current data. The high risk of distant relapse with use of radiation alone for stage IE PLB appears relatively well defined. With the small number of patients affected, a phase III randomized controlled trial comparing radiation therapy and chemotherapy versus chemotherapy alone is not feasible. Despite the lack of formal treatment guidelines, it seems reasonable to treat patients with localized PLB with combined-modality therapy. In cases in which radiation therapy would be relatively contraindicated because of previous treatment or toxicity concerns, chemotherapy alone should be considered. For patients with multifocal PLB
142 • Clinical Lymphoma & Myeloma September 2005
(stage IVE per Ann Arbor classification), combination chemotherapy is recommended as primary treatment.
Conclusion Even though it was first described > 6 decades ago, primary lymphoma of bone is associated with continuing controversy regarding diagnosis, staging, and treatment. The rarity of this disorder makes study design and literature interpretation extremely challenging. Although some authors suggest that the distinction between PLB and lymphomatous involvement of bone with systemic disease may become purely academic, the current thought is that these remain separate clinical entities. There seems to be little doubt that the use of anthracycline-based chemotherapy decreases the risk of distant relapse. However, whether this confers an OS benefit remains controversial.
References 1. Anderson T, Chabner BA, Young RC, et al. Malignant lymphoma. 1. The histology and staging of 473 patients at the National Cancer Institute. Cancer 1982; 50:2699-2707. 2. Lewis VO, Primus G, Anastasi J, et al. Oncologic outcomes of primary lymphoma of bone in adults. Clin Orthop Rel Res 2003; 90-97. 3. Misgeld E, Wehmeier A, Kromeke O, et al. Primary non-Hodgkin’s lymphoma of bone: three cases and a short review of the literature. Ann Hematol 2003; 82:440-443. 4. Baar J, Burkes RL, Bell R, et al. Primary non-Hodgkin’s lymphoma of bone. A clinicopathologic study. Cancer 1994; 73:1194-1199. 5. de Camargo OP, dos Santos Machado TM, Croci AT, et al. Primary bone lymphoma in 24 patients treated between 1955 and 1999. Clin Orthop Rel Res 2002; 271-280. 6. Mulligan ME, McRae GA, Murphey MD. Imaging features of primary lymphoma of bone. AJR Am J Roentgenol 1999; 173:1691-1697. 7. Dubey P, Ha CS, Besa PC, et al. Localized primary malignant lymphoma of bone. Int J Radiat Oncol Biol Phys 1997; 37:1087-1093. 8. Fairbanks RK, Bonner JA, Inwards CY, et al. Treatment of stage IE primary lymphoma of bone. Int J Radiat Oncol Biol Phys 1994; 28:363-372. 9. Ostrowski ML, Unni KK, Banks PM, et al. Malignant lymphoma of bone. Cancer 1986; 58:2646-2655. 10. Rathmell AJ, Gospodarowicz MK, Sutcliffe SB, et al. Localised lymphoma of bone: prognostic factors and treatment recommendations. The Princess Margaret Hospital Lymphoma Group. Br J Cancer 1992; 66:603-606. 11. Christie DR, Barton MB, Bryant G, et al. Osteolymphoma (primary bone lymphoma): an Australian review of 70 cases. Australasian Radiation Oncology Lymphoma Group (AROLG). Aust N Z J Med 1999; 29:214-219. 12. Bacci G, Jaffe N, Emiliani E, et al. Therapy for primary non-Hodgkin’s lymphoma of bone and a comparison of results with Ewing’s sarcoma. Ten years’ experience at the Istituto Ortopedico Rizzoli. Cancer 1986; 57:1468-1472. 13. Ferreri AJM, Reni M, Ceresoli G, et al. Primary non-Hodgkin’s lymphoma of the bone (PLB): management of 21 cases. Eur J Cancer 1995; 31A:786-786. 14. Fidias P, Spiro I, Sobczak ML, et al. Long-term results of combined modality therapy in primary bone lymphomas. Int J Radiat Oncol Biol Phys 1999; 45:1213-1238. 15. Marshall DT, Amdur RJ, Scarborough MT, et al. Stage IE primary nonHodgkin’s lymphoma of bone. Clin Orthop Rel Res 2002; 216-222.
Abstract Primary bone lymphoma is rare. The majority of cases are diffuse large B-cell non-Hodgkin’s lymphomas. Classification, staging, and treatment are controversial. The relatively small number of cases has led to many case reports and series describing institutional experiences but precludes the use of randomized clinical trials to address the question of optimal management. This article will review clinical and radiologic presentations, diagnostic techniques, and histologic characteristics. Most important, it will present what limited information we do have regarding effective treatment options for this unusual type of lymphoma.
Clinical Lymphoma & Myeloma, Vol. 6, No. 2, 140-142, 2005 Key words: Extranodal disease, Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma
Introduction Lymphoma is one of the most common hematologic malignancies. Generally divided into Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (NHL) and further classified by histologic type, the majority of lymphomas present with lymphadenopathy. Whereas extranodal presentation is uncommon in Hodgkin’s lymphoma, 10%-35% of patients with NHL have primary extranodal disease at initial diagnosis.1 The most common site is the gastrointestinal tract, followed by skin, testes, kidney, and bone. Primary lymphoma of bone (PLB) constitutes approximately 2% of all bone tumors and 5% of all extranodal lymphomas.2 It was first described by Oberling in 1928,3 and in 1939 Jackson and Parker reported the first case series of 17 patients with primary reticulum cell sarcoma of bone, or, as it is now known, PLB. Although PLB has been an established clinical entity for > 6 decades, its definition, diagnosis, and treatment remain controversial.
Clinical Presentation Primary lymphoma of bone has been described as a malignant lymphoid infiltrate within bone without concurrent lymph node or distant visceral involvement.2 However, there is no agreed-upon definition or diagnostic criteria for PLB. Some contend that there may be lymph node involvement as long as there is a 6-month window between diagnosis of the primary Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN Submitted: Jan 19, 2004; Revised: Sep 13, 2004; Accepted: Sep 13, 2004 Address for correspondence: David J. Inwards, MD, Mayo Clinic, Division of Hematology, 200 First St SW Rochester, MN 55905 Fax: 507-266-4972; e-mail: [email protected]
bone focus and emergence of lymph node disease. Clinically, it can be difficult to differentiate PLB and lymphomatous involvement of bone as a component of extraosseous lymphoma, which makes the diagnosis of PLB challenging. For the purposes of this review, PLB is considered a malignant lymphocytic infiltrate of bone with no lymph node or distant visceral disease. Primary lymphoma of bone predominantly affects men, with a male-to-female ratio of 1.8:1.2,4,5 Although age of onset varies, a study of 237 pathologically proven cases reported a mean age of 42 years.6 The most common presenting symptom is bone pain not relieved by rest. The pain can be insidious and intermittent, clinically similar to chronic osteomyelitis.5 Consequently, patients may wait several months before seeking medical attention. Approximately 50% of patients experience associated soft tissue swelling as a result of direct extension of bony disease into adjacent soft tissues.6 The long bones, specifically the femur and tibia, are most frequently affected. Vertebral involvement is common as well.4,7,8 Because PLB often affects weight-bearing bones, pathologic fractures are a specific concern and may be a presenting sign or a late complication. As with any lymphoma, patients may experience B symptoms such as fever, weight loss, and/or night sweats.
Diagnosis Imaging Studies The radiologic appearance of PLB is variable and nonspecific. Conventional radiography typically shows an osteolytic pattern of bone destruction, but may show a sclerotic or mixed lytic and sclerotic pattern (Figures 1A and 1B). Despite extreme medullary infiltration, periosteal reaction is typically minimal. Soft tissue masses are common but are better detected by cross-sectional imaging.
Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cancer Information Group, ISSN #1526-9655, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
140 • Clinical Lymphoma & Myeloma September 2005
If a clinician suspects PLB based on plain radiographs or if PLB is suspected at the outset what imaging modality is best? Although technetium bone scanning may show activity, as with conventional radiography, these findings are nonspecific.4 Magnetic resonance imaging is the most sensitive technique for the presence of intraosseous tumor; however, the appearance of PLB is variable (Figures 1C and 1D). A pattern of extensive marrow involvement with minimal plain radiographic findings is highly suspicious of hematologic malignancy, including PLB. Although T2-weighted images are variable, T1-weighted images show low signal intensity and usually define the extent of disease better.3 Computed tomography may show soft tissue extension, cortical involvement, or marrow invasion suggestive of malignancy, but these findings are nonspecific (Figures 1E and 1F). Positron emission tomography may be helpful for staging or detecting residual disease after treatment, but it has little role in the initial workup of suspected PLB. The differential diagnosis of PLB based on radiographic features is age-dependent. In young patients, the differential includes osteosarcoma, Ewing sarcoma, and leukemia. In older patients, multiple myeloma and metastatic carcinoma are more common.5 Biopsy Techniques If any type of malignancy is suspected based on radiographic findings, a biopsy must be performed. Fine needle aspiration (FNA) of a suspected osseous tumor can be challenging. It may be difficult to obtain adequate tissue for diagnosis, and sampling error may produce a false-negative result. Also, fine needle aspiration and core biopsies may make a pathologic diagnosis difficult as a result of crush artifact. Consequently, when PLB is suspected, an open biopsy is preferred if technically feasible.3 If unable to obtain an open biopsy, generous core biopsy is preferred over FNA. An open biopsy technique harvests tissue by extraction rather than compression, as with FNA or core needle biopsies. Although this technique requires a surgical procedure, the diagnostic yield may be greater. Histopathology Primary lymphoma of bone is mainly of B-cell origin. Although T-cell PLB has been described, it is more common in Japan and Hong Kong where there is a higher overall incidence of T-cell lymphoma. Of the B-cell PLBs, the majority are of diffuse largecell type. Lewis et al performed a retrospective analysis of 18 patients diagnosed with PLB from 1984 to 1994. Seventy-five percent of cases were diffuse large B-cell, whereas the remainder were equally divided among follicular, small noncleaved, and T-cell types.2 Cytogenetics and immunohistochemistry vary among tumors of this type. The histologic grade is of little prognostic value in PLB. No significant survival difference between indolent and aggressive PLB has been documented to date.9,10 Additionally, the treatment recommendations are the same regardless of grade.2
Staging Complete staging with computed tomography scans and bone marrow biopsy is essential in the evaluation of any new
Figure 1 B-Cell Large-Cell Non-Hodgkin's Lymphoma of the Femur A
B
C
D
E
F
Anteroposterior (A) and lateral (B) radiographs of the right femur show a subtle mixed osteolytic and sclerotic process involving the distal half of the femur consistent with lymphoma. There is a small focus of endosteal erosion along the anterolateral aspect of the femoral diaphysis, but no evidence of frank cortical destruction or periosteal new bone formation. The sagittal T1-weighted magnetic resonance image (C) and T2-weighted magnetic resonance image with fat saturation (D) show an extensive destructive lesion involving the distal half of the femur that correlates with the subtle lesion seen on the conventional radiographs. The magnetic resonance images show that the lesion occupies the entire diameter of the medullary canal with associated endosteal erosion and has intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Although the signal characteristics are nonspecific, this constellation of imaging features, with magnetic resonance findings out of proportion to those predicted on the basis of the conventional radiographs, is highly suggestive of a diagnosis of lymphoma. The axial computed tomography images with bone (E) and soft tissue windows (F), with the left leg included for comparison, show complete replacement of the normal medullary fat in the right femoral canal by a lesion of soft tissue density, along with subtle thinning and permeation of the cortical bone.
case of lymphoma. Lymphomatous involvement of bone can occur in patients with extraosseous lymphoma as well, which should be distinguished from PLB. To ensure a correct diagnosis of PLB, disease involvement in extraosseous sites (ie, lymph nodes, viscera) must be ruled out. Previous studies have suggested that patients with PLB have a favorable prognosis compared with those with extraosseous disease.7,11-14 However, a recent retrospective analysis by Lewis et al of 28 patients with
Clinical Lymphoma & Myeloma September 2005 • 141
Primary Lymphomas of Bone lymphomatous involvement of bone suggests that PLB does not confer an improved prognosis compared with extraosseous disease.2 Whether this will be confirmed by other studies is unknown. Currently, the distinction between PLB and systemic lymphoma appears clinically significant.
Treatment Treatment options for PLB, as with any malignancy, include surgery, radiation, and/or chemotherapy. The role of surgery is limited to biopsy and the management of pathologic fractures.3,15 Because of the rarity of this disease, there are minimal data available regarding optimal management. Deciding what treatment regimen is best for an individual patient is a challenge. Historically, the standard of care for localized disease (stage IE per Ann Arbor classification) was radiation therapy alone at a dose of 40-60 Gy.8,12,15 Although local control was achieved in 87%-100% of cases,12,14,15 there was a high rate of distant relapse. In one study of 28 patients with stage IE disease who exhibited excellent local control with radiation, 13 had relapses at distant sites and eventually died of their disease.15 Because of this, there has been a trend toward combined-modality therapy. Several small studies have shown some advantage to the use of anthracycline-based chemotherapy (ie, CHOP [cyclophosphamide/ doxorubicin/vincristine/prednisone]) and radiation versus radiation alone. Fairbanks et al suggested an improved disease-free survival (DFS) with combined-modality therapy in patients with stage IE disease, but this did not translate into an increase in overall survival (OS).8 Dubey et al showed no difference in OS or DFS when comparing radiation alone versus CMT.7 Fidias et al found a statistically significant benefit in DFS (78% vs. 42%) and OS (91% vs. 50%) for patients who received combined-modality therapy versus radiation alone.14 Given the rarity of this disease and the differences in how primary lymphoma of bone has been defined in previous studies, it is difficult to know how to proceed based on current data. The high risk of distant relapse with use of radiation alone for stage IE PLB appears relatively well defined. With the small number of patients affected, a phase III randomized controlled trial comparing radiation therapy and chemotherapy versus chemotherapy alone is not feasible. Despite the lack of formal treatment guidelines, it seems reasonable to treat patients with localized PLB with combined-modality therapy. In cases in which radiation therapy would be relatively contraindicated because of previous treatment or toxicity concerns, chemotherapy alone should be considered. For patients with multifocal PLB
142 • Clinical Lymphoma & Myeloma September 2005
(stage IVE per Ann Arbor classification), combination chemotherapy is recommended as primary treatment.
Conclusion Even though it was first described > 6 decades ago, primary lymphoma of bone is associated with continuing controversy regarding diagnosis, staging, and treatment. The rarity of this disorder makes study design and literature interpretation extremely challenging. Although some authors suggest that the distinction between PLB and lymphomatous involvement of bone with systemic disease may become purely academic, the current thought is that these remain separate clinical entities. There seems to be little doubt that the use of anthracycline-based chemotherapy decreases the risk of distant relapse. However, whether this confers an OS benefit remains controversial.
References 1. Anderson T, Chabner BA, Young RC, et al. Malignant lymphoma. 1. The histology and staging of 473 patients at the National Cancer Institute. Cancer 1982; 50:2699-2707. 2. Lewis VO, Primus G, Anastasi J, et al. Oncologic outcomes of primary lymphoma of bone in adults. Clin Orthop Rel Res 2003; 90-97. 3. Misgeld E, Wehmeier A, Kromeke O, et al. Primary non-Hodgkin’s lymphoma of bone: three cases and a short review of the literature. Ann Hematol 2003; 82:440-443. 4. Baar J, Burkes RL, Bell R, et al. Primary non-Hodgkin’s lymphoma of bone. A clinicopathologic study. Cancer 1994; 73:1194-1199. 5. de Camargo OP, dos Santos Machado TM, Croci AT, et al. Primary bone lymphoma in 24 patients treated between 1955 and 1999. Clin Orthop Rel Res 2002; 271-280. 6. Mulligan ME, McRae GA, Murphey MD. Imaging features of primary lymphoma of bone. AJR Am J Roentgenol 1999; 173:1691-1697. 7. Dubey P, Ha CS, Besa PC, et al. Localized primary malignant lymphoma of bone. Int J Radiat Oncol Biol Phys 1997; 37:1087-1093. 8. Fairbanks RK, Bonner JA, Inwards CY, et al. Treatment of stage IE primary lymphoma of bone. Int J Radiat Oncol Biol Phys 1994; 28:363-372. 9. Ostrowski ML, Unni KK, Banks PM, et al. Malignant lymphoma of bone. Cancer 1986; 58:2646-2655. 10. Rathmell AJ, Gospodarowicz MK, Sutcliffe SB, et al. Localised lymphoma of bone: prognostic factors and treatment recommendations. The Princess Margaret Hospital Lymphoma Group. Br J Cancer 1992; 66:603-606. 11. Christie DR, Barton MB, Bryant G, et al. Osteolymphoma (primary bone lymphoma): an Australian review of 70 cases. Australasian Radiation Oncology Lymphoma Group (AROLG). Aust N Z J Med 1999; 29:214-219. 12. Bacci G, Jaffe N, Emiliani E, et al. Therapy for primary non-Hodgkin’s lymphoma of bone and a comparison of results with Ewing’s sarcoma. Ten years’ experience at the Istituto Ortopedico Rizzoli. Cancer 1986; 57:1468-1472. 13. Ferreri AJM, Reni M, Ceresoli G, et al. Primary non-Hodgkin’s lymphoma of the bone (PLB): management of 21 cases. Eur J Cancer 1995; 31A:786-786. 14. Fidias P, Spiro I, Sobczak ML, et al. Long-term results of combined modality therapy in primary bone lymphomas. Int J Radiat Oncol Biol Phys 1999; 45:1213-1238. 15. Marshall DT, Amdur RJ, Scarborough MT, et al. Stage IE primary nonHodgkin’s lymphoma of bone. Clin Orthop Rel Res 2002; 216-222.