Primary lymphoma of bone
- Ann S LaCasce, MD
Ann S LaCasce, MD
- Associate Professor of Medicine
- Harvard Medical School
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- Section Editors
- Thomas F DeLaney, MD
Thomas F DeLaney, MD
- Section Editor — Bone and Soft Tissue Tumors
- Professor of Radiation Oncology
- Harvard Medical School
- Julie R Park, MD
Julie R Park, MD
- Section Editor — Lymphoma; Pediatric Oncology
- Professor of Pediatrics
- University of Washington
Primary non-Hodgkin lymphoma of bone (PLB) presents as solitary or multiple, destructive bone lesions. The clinical presentation, diagnosis, and treatment of PLB will be discussed here.
A more general discussion of the approach to the patient with non-Hodgkin lymphoma is presented separately, as are discussions concerning the pathophysiology, diagnosis, and treatment of diffuse large B cell non-Hodgkin lymphoma, the most common tumor type found in this setting. (See "Clinical presentation and diagnosis of non-Hodgkin lymphoma" and "Evaluation, staging, and response assessment of non-Hodgkin lymphoma" and "Epidemiology, clinical manifestations, pathologic features, and diagnosis of diffuse large B cell lymphoma" and "Initial treatment of advanced stage diffuse large B cell lymphoma".)
Primary lymphoma of bone (PLB) is a rare disease that accounts for less than 2 percent of all lymphomas in adults . In the pediatric population it represents approximately 3 to 9 percent of non-Hodgkin lymphoma cases [2-5]. It is estimated that PLB accounts for 3 to 7 percent of primary bone tumors [6,7] and 3 to 5 percent of all extranodal non-Hodgkin lymphomas [8,9].
Men are diagnosed slightly more frequently than women with a male:female ratio ranging from 1.2 to 1.8 [10-13]. The vast majority of patients present over the age of 30 years (92 percent) with the largest cohort consisting of those over age 60 (56 percent) [10,12]. While PLB occurs in children, pediatric PLB is considered a distinct clinical entity and the approach to treatment differs from that of adults.
The majority of patients present with bone pain not relieved by rest. A palpable mass due to soft tissue extension of the bony disease is seen in about one-half of the cases . Swelling, pathologic fracture, cord compression and systemic "B" symptoms (ie, fever, weight loss, night sweats) may also be present at the time of diagnosis . Occasionally, symptoms may persist for many months before the patient seeks medical attention.
- Dubey P, Ha CS, Besa PC, et al. Localized primary malignant lymphoma of bone. Int J Radiat Oncol Biol Phys 1997; 37:1087.
- Loeffler JS, Tarbell NJ, Kozakewich H, et al. Primary lymphoma of bone in children: analysis of treatment results with adriamycin, prednisone, Oncovin (APO), and local radiation therapy. J Clin Oncol 1986; 4:496.
- Furman WL, Fitch S, Hustu HO, et al. Primary lymphoma of bone in children. J Clin Oncol 1989; 7:1275.
- Anderson JR, Wilson JF, Jenkin DT, et al. Childhood non-Hodgkin's lymphoma. The results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2). N Engl J Med 1983; 308:559.
- Lones MA, Perkins SL, Sposto R, et al. Non-Hodgkin's lymphoma arising in bone in children and adolescents is associated with an excellent outcome: a Children's Cancer Group report. J Clin Oncol 2002; 20:2293.
- Limb D, Dreghorn C, Murphy JK, Mannion R. Primary lymphoma of bone. Int Orthop 1994; 18:180.
- Hogendoorn PCW, Kluin PM. Primary non-Hodgkin lymphoma of bone. In: WHO Classification of Tumours of Soft Tissue and Bone, 4th, Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. (Eds), International Agency for Research on Cancer, Lyon 2013. p.316.
- Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of extranodal lymphomas. Cancer 1972; 29:252.
- ROSENBERG SA, DIAMOND HD, JASLOWITZ B, CRAVER LF. Lymphosarcoma: a review of 1269 cases. Medicine (Baltimore) 1961; 40:31.
- Jawad MU, Schneiderbauer MM, Min ES, et al. Primary lymphoma of bone in adult patients. Cancer 2010; 116:871.
- Mulligan ME, McRae GA, Murphey MD. Imaging features of primary lymphoma of bone. AJR Am J Roentgenol 1999; 173:1691.
- Cai L, Stauder MC, Zhang YJ, et al. Early-stage primary bone lymphoma: a retrospective, multicenter Rare Cancer Network (RCN) Study. Int J Radiat Oncol Biol Phys 2012; 83:284.
- Bruno Ventre M, Ferreri AJ, Gospodarowicz M, et al. Clinical features, management, and prognosis of an international series of 161 patients with limited-stage diffuse large B-cell lymphoma of the bone (the IELSG-14 study). Oncologist 2014; 19:291.
- Stokes SH, Walz BJ. Pathologic fracture after radiation therapy for primary non-Hodgkin's malignant lymphoma of bone. Int J Radiat Oncol Biol Phys 1983; 9:1153.
- Pant V, Jambhekar NA, Madur B, et al. Anaplastic large cell lymphoma (ALCL) presenting as primary bone and soft tissue sarcoma--a study of 12 cases. Indian J Pathol Microbiol 2007; 50:303.
- Lima FP, Bousquet M, Gomez-Brouchet A, et al. Primary diffuse large B-cell lymphoma of bone displays preferential rearrangements of the c-MYC or BCL2 gene. Am J Clin Pathol 2008; 129:723.
- Jelinek JS, Murphey MD, Welker JA, et al. Diagnosis of primary bone tumors with image-guided percutaneous biopsy: experience with 110 tumors. Radiology 2002; 223:731.
- Söderlund V, Tani E, Skoog L, et al. Diagnosis of skeletal lymphoma and myeloma by radiology and fine needle aspiration cytology. Cytopathology 2001; 12:157.
- Gianelli U, Patriarca C, Moro A, et al. Lymphomas of the bone: a pathological and clinical study of 54 cases. Int J Surg Pathol 2002; 10:257.
- Suryanarayan K, Shuster JJ, Donaldson SS, et al. Treatment of localized primary non-Hodgkin's lymphoma of bone in children: a Pediatric Oncology Group study. J Clin Oncol 1999; 17:456.
- O'Connor AR, Birchall JD, O'Connor SR, Bessell E. The value of 99mTc-MDP bone scintigraphy in staging primary lymphoma of bone. Nucl Med Commun 2007; 28:529.
- Parker F, Jackson H. Primary reticulum cell sarcoma of bone. Surg Gynecol Obstet 1939; 68:45.
- Baar J, Burkes RL, Bell R, et al. Primary non-Hodgkin's lymphoma of bone. A clinicopathologic study. Cancer 1994; 73:1194.
- Israel O, Mekel M, Bar-Shalom R, et al. Bone lymphoma: 67Ga scintigraphy and CT for prediction of outcome after treatment. J Nucl Med 2002; 43:1295.
- Heyning FH, Kroon HM, Hogendoorn PC, et al. MR imaging characteristics in primary lymphoma of bone with emphasis on non-aggressive appearance. Skeletal Radiol 2007; 36:937.
- Buchmann I, Reinhardt M, Elsner K, et al. 2-(fluorine-18)fluoro-2-deoxy-D-glucose positron emission tomography in the detection and staging of malignant lymphoma. A bicenter trial. Cancer 2001; 91:889.
- Moog F, Bangerter M, Diederichs CG, et al. Extranodal malignant lymphoma: detection with FDG PET versus CT. Radiology 1998; 206:475.
- Moog F, Kotzerke J, Reske SN. FDG PET can replace bone scintigraphy in primary staging of malignant lymphoma. J Nucl Med 1999; 40:1407.
- Rathmell AJ, Gospodarowicz MK, Sutcliffe SB, Clark RM. Localised lymphoma of bone: prognostic factors and treatment recommendations. The Princess Margaret Hospital Lymphoma Group. Br J Cancer 1992; 66:603.
- Mendenhall NP, Jones JJ, Kramer BS, et al. The management of primary lymphoma of bone. Radiother Oncol 1987; 9:137.
- Heyning FH, Hogendoorn PC, Kramer MH, et al. Primary non-Hodgkin's lymphoma of bone: a clinicopathological investigation of 60 cases. Leukemia 1999; 13:2094.
- Ferreri AJ, Reni M, Ceresoli GL, Villa E. Therapeutic management with adriamycin-containing chemotherapy and radiotherapy of monostotic and polyostotic primary non-Hodgkin's lymphoma of bone in adults. Cancer Invest 1998; 16:554.
- Messina C, Ferreri AJ, Govi S, et al. Clinical features, management and prognosis of multifocal primary bone lymphoma: a retrospective study of the international extranodal lymphoma study group (the IELSG 14 study). Br J Haematol 2014; 164:834.
- Marshall DT, Amdur RJ, Scarborough MT, et al. Stage IE primary non-Hodgkin's lymphoma of bone. Clin Orthop Relat Res 2002; :216.
- 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.
- 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.
- Ramadan KM, Shenkier T, Sehn LH, et al. 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.
- Beal K, Allen L, Yahalom J. Primary bone lymphoma: treatment results and prognostic factors with long-term follow-up of 82 patients. Cancer 2006; 106:2652.
- Catlett JP, Williams SA, O'Connor SC, et al. Primary lymphoma of bone: an institutional experience. Leuk Lymphoma 2008; 49:2125.
- Power DG, McVey GP, Korpanty G, et al. Primary bone lymphoma: single institution case series. Ir J Med Sci 2008; 177:247.
- Ford DR, Wilson D, Sothi S, et al. Primary bone lymphoma--treatment and outcome. Clin Oncol (R Coll Radiol) 2007; 19:50.
- Alencar A, Pitcher D, Byrne G, Lossos IS. Primary bone lymphoma--the University of Miami experience. Leuk Lymphoma 2010; 51:39.
- Christie D, Dear K, Le T, et al. Limited chemotherapy and shrinking field radiotherapy for Osteolymphoma (primary bone lymphoma): results from the trans-Tasman Radiation Oncology Group 99.04 and Australasian Leukaemia and Lymphoma Group LY02 prospective trial. Int J Radiat Oncol Biol Phys 2011; 80:1164.
- Link MP, Donaldson SS, Berard CW, et al. Results of treatment of childhood localized non-Hodgkin's lymphoma with combination chemotherapy with or without radiotherapy. N Engl J Med 1990; 322:1169.
- Link MP, Shuster JJ, Donaldson SS, et al. Treatment of children and young adults with early-stage non-Hodgkin's lymphoma. N Engl J Med 1997; 337:1259.
- Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 2007; 25:571.
- Govi S, Christie D, Messina C, et al. The clinical features, management and prognostic effects of pathological fractures in a multicenter series of 373 patients with diffuse large B-cell lymphoma of the bone. Ann Oncol 2014; 25:176.
- Wu H, Zhang L, Shao H, et al. Prognostic significance of soft tissue extension, international prognostic index, and multifocality in primary bone lymphoma: a single institutional experience. Br J Haematol 2014; 166:60.
- CLINICAL PRESENTATION
- Imaging studies
- - Plain films
- - Computed tomography
- - MRI findings
- - Positron emission tomography
- - Chemotherapy with or without radiation
- - Surgical intervention
- Patterns of relapse