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Primary Non-Hodgkin’s Lymphoma Of Bone: A Case Report                                   

Girish H R, Gopinathan Patinharayil*, Anwar Marthya,Kumaran C M, Han  C W

* Deparment of Orthopedics, Medical college, Calicut ,Kerala,India

Address for Correspondence:  

Dr. Girish H R 
Dept of orthopaedics 
MCH Calicut ,Kerala, India


The incidence of primary non-hodgkin’s lymphoma or simply known as primary bone lymphoma (PBL) is so rare that many of its aspects remain unknown. Till date only a few reports are available especially from Asia . Primary lymphoma of bone is uncommon, and because of  its unusual presentation patterns in bone, it can be difficult to diagnose. According to literature, even though it can occur at any age, the peak incidence is in the fifth decade of life and it is more common in males. But we report a twenty one year old young female, who was diagnosed to have primary B-cell bone lymphoma of the lower end of left femur. 

J.Orthopaedics 2008;5(1)e22


Primary bone lymphoma is a rare disease, first described by Oberling in 1928.[1]. But it was first acknowledged as a clinico-pathologic entity in 1939 when Parker and Jackson [2] reported the results of 17 cases of primary reticulum cell carcinoma of bone. Primary lymphoma of bone, constitutes approximately 2% of all bone tumors and 5% of all extra-nodal lymphomas.[3,4].  Primary lymphoma of bone occurs predominantly in males, a male to female ratio of 1.8:1. [5]. It may occur at any age and the reported average age of onset varies considerably in the literature [5] Peak incidence is in the fifth decade, with a median age of 44. The male to female ratio is 1.8:1.  The femur is the most commonly involved site(29%), followed by the pelvis(19%), humerus(13%), head/neck(11%), and tibia(10%). Usually patients present with localized pain, with approximately 50% having a palpable mass at initial evaluation. [2,6,7, 8,9,10,11,12,13].

Primary lymphoma of bone has been described as a malignant lymphoid infiltrate within bone with or without cortical invasion or soft tissue extension and without concurrent involvement of regional lymph nodes or distant viscera.[9,14].   This entity must be differentiated from other small round  cell tumors originating in bone as well as osseous manifestations of primary extra-skeletal lymphomas.[12]   An accurate diagnosis requires obtaining a specimen without crush artifact, as this can alter the cellular morphologic features and make the diagnosis more challenging.[15,16,17,18]. Also, lymphoma and osteomyelitis can coexist.[19,20].   

Case Report :

Twenty one year old young female presented to our institute in 2007 with history of pain and swelling left knee for three months duration. Initially she had gradually increasing pain aggravated by activities like walking and running. Two weeks later she developed swelling on the medial aspect of left knee. There was no history of fever, chills or night sweats. There was a history of weight loss during these three months.

On clinical examination, she had a diffuse swelling on the medial aspect of the lower end of left femur.with mild effusion in the left knee joint. Swelling was bony hard, tender, arising from medial condyle of left femur. Skin was free from the swelling. She had a decreased range of movements in the left knee. She had no other masses or lymphadenopathy.

General and systemic examination revealed no abnormalities. Haematological examination was within normal limits. Ultrasound examination of abdomen was normal. Mantuox test was negative.

Plain roentgenogram of lower end of left femur showed a diffuse lytic lesion just above the medial femoral condyle.(figure-1). Magnetic resonance imaging of left femur with knee showed abnormal signal changes with areas of left femur, predominantly involving the medial condyle.(figure-2).  99Tc MDP whole body bone scan showed expansile non uniform intense uptake in lower end of left femur. Rest of the skeleton showed normal tracer activity and kidneys were normally visualized.

Incisional biopsy was done and the histopathological report showed immature appearing mononuclear cells with mature lymphocytes. (figure-3) and (figure-4).

Gross appearance of the specimen was  specimen - grayish , firm with fragments of bone and soft tissue, and small areas of haemorrhage with the cortex being thinned out and distended.

Microscopic appearance was Sections showing  bone and soft tissue with sheets of cells with pale cytoplasm and large nuclei- immature appearing mononuclear cells with mature lymphocytes.The cells possessed slightly basophilic cytoplasm with poorly defined borders, and the nuclei were large, oval to reniform and were poor in chromatin.

Immunohistochemistry showed CD20: diffusely positive in large cells. CD3: negative in large cells, thus confirming the diagnosis of diffuse large B cell lymphoma of lower end of left femur.(figure-5) and (figure-6). There was sympathetic effusion in the left knee joint, since the aspirated synovial fluid was sterile on culture.The patient was treated with CHOP regime(Cyclophosphamide,Hydroxyl –Doxorubicin,Oncovin,Prednisolone)i.e: Cyclophosphomide- 600 mg/ m2 ,Hydroxyl-doxorubicin [Adriamycin]- 50 mg/m2 ,Oncovin [Vincristine]- 1.4 mg/m2 and Prednisolone- 60 mg/m2 .

First three drugs were  given on day 1 and prednisolone is given from day 1 to day 5. This is repeated every 3 weeks. Six cycles of chemotherapy (each cycle lasting for three weeks) is followed by radiotherapy, the dose being 400 cGy units in 20 fractions for a period of 4 weeks.

At the time writing this report after eight months of first detection   there is no recurrence or evidence of disease elsewhere in the body as followed up by Technitium 99 MDP Bone scan.   

Discussion :

Even though it was first described by Oberling in 1928 [1], primary bone lymphoma (PBL) was considered as a separate clinicopathologic entity in 1939 when Parker and Jackson [2] reported results of 17 cases of primary reticulum cell carcinoma of bone.

Even after five to six decades of its description, the reports of PBL are so rare that many aspects remain controversial, particularly the definition of PBL, appropriate treatment strategies, response criteria and prognostic factors.[ 5,21].

PBL is notorious for presenting diagnostic difficulties and  mimics other disease processes, especially infection. Tumors diagnosed and treated as infections are not uncommon. [22] . Blum et al reported cases of malignant lymphoma, presenting as infection and treated as such thereby delaying the true diagnosis and appropriate treatment.[22] . According to a study by Marshall et al, earlier detection and treatment can effect a better prognosis.[23] .

Primary lymphoma of bone is uncommon, comprising from 0.2 to 5% of primary bone tumors.[15,16] . By reviewing the literature, PBL predominantly affects the males, and the femur has been reported to be the most commonly involved location as a single site [21] and the peak incidence is in the fifth decade [5] with median age of forty four. The patient we reported was a twenty one year old, young female. To the best of our knowledge, the incidence of primary bone lymphoma in children and young adults is very rare [5] . The site of involvement was medial condyle of left femur, with femur being the most common site of involvement as per the previous case reports in the literature.[ 2,6,7,8,9,10,11,12,13]

According to the WHO classification [24] , lymphoma involving bone can be classified into four groups: Group 1, lymphoma with a single bone site with or without regional lymph-node involvement; Group 2, lymphoma with multiple bones involved, but no visceral or lymph-node involvement; Group 3, bone tumor with involvement of other visceral sites or lymph nodes at multiple sites; and Group 4, lymphoma involving any other sites and found by bone biopsy which was done to rule out possible involvement.

The WHO classification and some previous reports have indicated that Groups 1 and 2 should be  considered as PBL, but Group 3 should be excluded from PBL and considered to be systemic lymphoma regardless of the bone lesion size. An appropriate definition has not been established by verification, and hence, the subject continues to be controversial.[21] .

Histopathologically , the previous studies reported that majority of patients with PBL were Diffuse Large B Cell Lymphoma (DLBCL) [14,24,25,26,27]. Immunohistochemical staining showed CD20,CD79a, and bcl-2 positive and CD3,CD5,CD10 and CD23, cyclin D1  and terminal deoxynucleotidyl tranferase negative.[21] . In the patient we reported, the histopathology revealed a diagnosis of  Diffuse Large B Cell lymphoma [DLBCL] (figure-4),(figure-5)  and immunohistochemistry revealed CD3 negative and CD20 positive. (figure-6) and (figure-7) confirming the diagnosis of DLBCL.

Regarding treatment of primary bone lymphomas, there is no universally accepted therapeutic approach to the management of PBL. [28] . Even though the literature recommends combined modality therapy with both chemotherapy and radiotherapy, a formal treatment guideline  have not been developed. [5] . Although no formal treatment guidelines have been established, combined modality therapy has been shown to yield better prognosis and results superior to those of radiation therapy alone for primary bone lymphoma [25,29,30,31,32] . Recent studies have suggested that a combination of chemotherapy and radiotherapy was the best treatment for patients with primary bone lymphoma.[33,34] . Hence, our patient was treated with six cycles ( each cycle lasting for three weeks) of chemotherapy followed by radiotherapy.


Primary lymphoma of bone is rare and uncommon, especially in young individuals and in females. To the best of our knowledge, the case we reported is a rare occurrence as per the review of literature . This condition being rare and could mimic other diseases especially infection, it should be included in the differential diagnosis, so that the pathologist will be prepared in handling biopsied specimen appropriately. If not considered in the differential diagnosis, the possibility is not raised and the patient may end up with a wrong diagnosis and inadequate treatment.

Reference :

  1. Oberling C. Les Reticulosarcomes et les reticuloendotheliosarcomes de la moelle osseuse (sarcomas d’Ewing). Bull Assoc Fr Etude Cancer 1928;17:259–96 (in French).  

  2. Parker F, Jackson H. primary reticulum cell sarcoma of bone. Surg Gynecol Obstet 1939;68:45-53.

  3. Freeman C, Berg JW, Cutler SJ: Occurrence and prognosis of extranodal lymphomas. Cancer 29:252– 260, 1972.  

  4. Rudders RA, Ross ME, DeLellis RA: Primary extranodal lymphoma: Response to treatment and factors influencing prognosis. Cancer 42:406–416, 1978.  

  5. Valerae O. Lewis, MD, Gregory Primus, MD, Oncologic Outcomes of Primary Lymphoma of Bone in Adults. Clinical Orthopaedics And Related Research  415, Pp. 90 – 97.  

  6. Mendenhall NP,Jones JJ, Kramer BS, et al. the management of primary lymphoma of bone. Radiother Oncol 1987;9:137-45.  

  7. Parvinen LM, Jereb B, Nisce L. Primary non-hodgkin’s lymphoma( reticulum cell sarcoma) of bone in adults. ACT A Radiol Oncol 1983;22:449-54.  

  8. Bacci G, Jaffe N, Emiliani E, et al. Therapy for primary no-hodgkin’s lymphoma of bone and a comparison of results with Ewing’s sarcoma. Cancer 1986;57:1468-72.  

  9. Boston HC, Dahlin DC , Ivins JC, Cupps RE. Malignant lymphoma ( so called reticulum cell sarcoma) of bone. Cancer 1974;34:1131-7.  

  10. Dosoretz DE, Raymond AK, Murphy GF, et al. Primary lymphoma of bone. Cancer 1982;50:1009-14.  

  11. Reimer RR, Chabner BA, Young RC, et al. lymphoma presenting in bone. Ann intern Med 1977;87(1):50-5.  

  12. Shoji H, Miller TR. Primary reticulum cell sarcoma of bone. Cancer 1971;28:1234-44.  

  13. Wang CC, Fleischli DJ. Primary reticulum cell sarcoma of bone. Cancer 1968;22:994-8.  

  14.  Pettit CK, Zukerberg LR, Gray MH, et al: Primary lymphoma of bone. Am J Surg Pathol 14:329–334, 1990.  

  15. Lewis SJ, Bell RS, Fernandes BJ, et al: Malignant lymphoma of bone. Can J Surg 37:43–49, 1994.  

  16. Mirra JM: Bone Tumors: Clinical, Radiologic, and Pathologic Correlation. Philadelphia , Lea and Febiger 1989.  

  17. Ostrowski ML, Unni KK, Banks PM, et al: Malignant lymphoma of bone. Cancer 58:2646–2655,  1986.  

  18. Postovsky S, Bialik V, Keidar Z, et al: Large cell lymphoma of bone presented by limp. J Pediatr Orthop B 10:81–84, 2001.  

  19. Eismont FJ, Green BA, Brown MD, et al: Coexistent infection and tumor of the spine: A report of three cases. J Bone Joint Surg 69A:452–457, 1987.  

  20.  McGrory JE, Pritchard DJ, Unni KK, et al: Malignant lesions arising in chronic osteomyelitis. Clin Orthop 362:181–189, 1999.  

  21. Dai Maruyama, Takashi Watanabe. Primary Bone Lymphoma: A New and Detailed Characterization of 28 Patients in a Single-Institution Study  Jpn J Clin Oncol 2007;37(3)216–223.  

  22. Y. C. Blum, MD, J. L. Esterhai, MD. Case Report: Lymphoma Masquerading as Infection .Clinical Orthopaedics And Related Research , 432, pp. 267–271.  

  23. Marshall DT, Amdur RJ, Scarborough MT , et al: Stage 1E primary nonHodgkin’s lymphoma of bone. Clin Orthop 405:216–222, 2002.  

  24. Fletcher C, Unni K, Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone: World Health Organization Classification of Tumours. Lyon , France : International Agency for Research on Cancer; 2002; 306–8.  

  25. Heyning FH, Hogendoorn PC, Kramer MH, Hermans J, Kluin-Nelemans JC, Noordijk EM, et al. Primary non-Hodgkin’s  lymphoma of bone: a clinicopathological investigation of 60 cases. Leukemia 1999;13:2094–8.  

  26. Leval L, Braaten KM, Ancukiewicz M, Kiggundu E, Delaney T, Mankin HJ, et al. Diffuse large B-cell lymphoma of bone. An analysis of differentiation-associated antigens with clinical correlation. Am J Surg Pathol 2003;27:1269–77.  

  27. Radaszkiewcz T, Hansmann ML. primary high grade malignant lymphomas of bone. Virch Arch[A] 1988;413:269-74.  

  28. M.Salter, M.D.,R. J.Sollaccio,M.D. primary lymphoma of bone: the use of MRi in pretreatment evaluation. Am J Clin Oncol(CCT)12(2):101-105. 1989. 

  29. Baar J, Burkes R, Gospodarowicz M: Primary non- Hodgkin’s lymphoma of bone. Semin Oncol 26: 270–275, 1999.  

  30. Dubey P, Ha CS, Besa PC, et al: Localized primary malignant lymphoma of bone. Int J Radiat Oncol Biol Phys 37:1087–1093, 1997.  

  31. 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 45: 1213–1218, 1999  

  32. 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 4:496–501, 1986.  

  33. Barbieri E, Cammelli S, Mauro F, Perini F, Cazzola A, Neri S, et al. Primary non-Hodgkin’s lymphoma of the bone: treatment and analysis of prognostic factors for stage I and stage II. Int J Radiat Oncol Biol Phys 2004;59:760–4.  

  34. Beal K, Allen L, Yahalom J. Primary bone lymphoma: treatment results and prognostic factors with long-term follow-up of 82 patients. Cancer 2006;106:2652–6.  


This is a peer reviewed paper 

Please cite as : Gopinathan Patinharayil : Primary Non-Hodgkin’s Lymphoma Of Bone:A Case Report 

J.Orthopaedics 2008;5(1)e22





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