Mikhaeel NG
Primary bone lymphoma.
Clin Oncol (R Coll Radiol). 2012; 24(5):366-70 [PubMed]

Primary bone lymphoma is a distinct clinical entity that accounts for 5% of extra-nodal lymphoma. Most patients have diffuse large B-cell lymphoma and present with bone pain, a mass or both. The involvement could be in a single focus or disseminated. There are no prospective clinical studies in this disease. Patients have been treated with radiotherapy, chemotherapy or a combination. There is a trend towards improved outcome with combined modality treatment and further improvement with the addition of rituximab. Assessment of response may be difficult with current imaging techniques. The prognosis of primary bone lymphoma is generally good. Here, the current evidence for the optimal treatment of primary bone lymphoma is reviewed and questions for future investigation are addressed.

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(1):284-91 [PubMed]

PURPOSE: Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL.
PATIENTS AND METHODS: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cycles was six (range, 2-8). Median follow-up was 41 months (range, 6-242).
RESULTS: The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score ≤1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC.
CONCLUSION: This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome.

Singh R, Al Wattar BH, Mohanty K
A rare case of primary bone lymphoma mimicking a pelvic abscess.
Ann R Coll Surg Engl. 2011; 93(7):e141-3 [PubMed]

Primary bone lymphoma (PBL) is a rare, malignant, neoplastic disorder of the skeleton that accounts for less than 5% of all primary bone tumours. We present an extremely rare case of PBL mimicking a pelvic abscess around the sacroiliac joint, which has never been reported in the medical literature, and discuss learning points highlighted from this case.

Pellegrini C, Gandolfi L, Quirini F, et al.
Primary bone lymphoma: evaluation of chemoimmunotherapy as front-line treatment in 21 patients.
Clin Lymphoma Myeloma Leuk. 2011; 11(4):321-5 [PubMed]

BACKGROUND: We performed a retrospective investigation to assess the efficacy of chemotherapy and rituximab as front-line treatment for primary bone lymphoma (PBL).
PATIENTS AND METHODS: Between 1999 and 2009, 21 previously untreated patients received a diagnosis of PBL. All the patients were treated with anthracycline-containing chemotherapeutic regimens, with the addition of rituximab; 11 patients received consolidative radiation therapy after induction treatment.
RESULTS: Patients' median age was 34 years (range, 18-82 years); all presented with diffuse large B-cell lymphoma. Complete responses were seen in 95.2% of the patients treated. No relapses were observed at a median follow-up of 43.9 months. Eight-year overall survival and disease-free survival were 95.2% and 100.0%, respectively.
CONCLUSION: These data indicate that the combined chemotherapy plus rituximab treatment may represent a suitable front-line approach in PBL, with a high rate of responses and an excellent long-term survival.

de Rooy JW, Hambrock T, Vriens D, et al.
F-18 FDG PET/CT as a crucial guide toward optimal treatment planning in a case of postirradiation sarcoma 10 years after primary bone lymphoma of the pelvis.
Clin Nucl Med. 2011; 36(7):565-7 [PubMed]

Ten years after chemoradiation for primary lymphoma of the left pelvic bone, a 38-year-old man presented with a 4-month history of gradually increasing pain in his left upper leg and thigh. Initial radiographs and contrast-enhanced magnetic resonance imaging were consistent with recurrent lymphoma, infection, or postirradiation sarcoma. Subsequent F-18 fluorodeoxyglucose positron emission tomography/computed tomography demonstrated a focal area of F-18 fluorodeoxyglucose-avidity within the previously irradiated bone consistent with tumor and the location was confirmed by advanced magnetic resonance imaging techniques and histopathology, thus optimizing treatment planning.

Singh T, Satheesh CT, Lakshmaiah KC, et al.
Primary bone lymphoma: a report of two cases and review of the literature.
J Cancer Res Ther. 2010 Jul-Sep; 6(3):296-8 [PubMed]

Primary bone lymphoma (PBL) is an uncommon tumor accounting for approximately 4-5% of extra nodal lymphoma and less than 1% of all non-Hodgkin's lymphoma. Disease may be complicated at presentation by pathological fracture or spinal cord compression. Diffuse large-B-cell lymphoma (DLBCL) accounts for the majority of cases of PBL. Owing to its rarity, only a few retrospective studies have been published addressing the prognosis and treatment of primary bone lymphoma. In this paper, we report our experience with two cases of PBL treated with chemotherapy and radiotherapy and review literature to elucidate the optimal treatment of primary bone lymphoma.

Ortiz-Fernandez L, Sainz-Berrio B, Perez-Ruiz F, et al.
Primary bone lymphoma: polyostotic disease presenting as a cauda equina syndrome.
J Clin Rheumatol. 2010; 16(8):392-4 [PubMed]

We report a patient with B-cell primary bone lymphoma with involvement of multiple vertebrae at presentation and rapid development of cauda equina syndrome. The patient presented subacute low-back pain, initially with good response to corticosteroid treatment.Primary bone lymphoma is a very unusual disease, commonly affecting only 1 vertebra. Despite this, our case involved multiple levels at the onset; furthermore, there were no adenopathies. Because of the information of the magnetic resonance imaging, an open biopsy of the vertebrae was performed for diagnosis. The reported cases of radicular syndromes secondary to a lymphoma as an initial symptom are extremely infrequently reported in the literature, above all for a B-cell lymphoma.

Garrett KM, Kim HK, Stanek J, Emery KH
MR findings of primary bone lymphoma in a 15-year-old girl: emphasis on diffusion-weighted imaging.
Pediatr Radiol. 2011; 41(5):658-62 [PubMed]

We report a case of primary bone lymphoma (PBL) in a 15-year-old girl assessed by MR imaging with diffusion-weighted imaging (DWI). DWI has been shown to help characterize the cellularity of solid tumors and this case correlates well with previous data.

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(4):1164-70 [PubMed]

PURPOSE: To establish benchmark outcomes for combined modality treatment to be used in future prospective studies of osteolymphoma (primary bone lymphoma).
METHODS AND MATERIALS: In 1999, the Trans-Tasman Radiation Oncology Group (TROG) invited the Australasian Leukemia and Lymphoma Group (ALLG) to collaborate on a prospective study of limited chemotherapy and radiotherapy for osteolymphoma. The treatment was designed to maintain efficacy but limit the risk of subsequent pathological fractures. Patient assessment included both functional imaging and isotope bone scanning. Treatment included three cycles of CHOP chemotherapy and radiation to a dose of 45 Gy in 25 fractions using a shrinking field technique.
RESULTS: The trial closed because of slow accrual after 33 patients had been entered. Accrual was noted to slow down after Rituximab became readily available in Australia. After a median follow-up of 4.3 years, the five-year overall survival and local control rates are estimated at 90% and 72% respectively. Three patients had fractures at presentation that persisted after treatment, one with recurrent lymphoma.
CONCLUSIONS: Relatively high rates of survival were achieved but the number of local failures suggests that the dose of radiotherapy should remain higher than it is for other types of lymphoma. Disability after treatment due to pathological fracture was not seen.

Bhagavathi S, Fu K
Primary bone lymphoma.
Arch Pathol Lab Med. 2009; 133(11):1868-71 [PubMed]

Primary bone lymphomas are rare, even though secondary involvement of the bone marrow is a common event in systemic lymphomas. Most primary bone lymphomas are primary bone diffuse large B-cell lymphomas (PBDLBCLs) with a rare occurrence of follicular, marginal zone, anaplastic large cell, Hodgkin, and T-cell lymphomas. The PBDLBCL affects the middle-aged to elderly population, with a slight predominance in men. The patients present with bone pain, palpable mass, fractures, or neurologic symptoms. The metaphysis of bones is a common location of PBDLBCL. Morphologically, the lymphoma consists of a polymorphous mixture of small to large cells with multilobated nuclei, fine chromatin, and inconspicuous to prominent nucleoli. Differential diagnoses for PBDLBCL include chronic osteomyelitis, primary bone sarcoma, leukemic infiltrate, Ewing sarcoma, metastatic sarcomas, and carcinoma. Most PBDLBCLs are treated with combined radiotherapy and chemotherapy with good prognosis.

Alencar A, Pitcher D, Byrne G, Lossos IS
Primary bone lymphoma--the University of Miami experience.
Leuk Lymphoma. 2010; 51(1):39-49 [PubMed]

Primary bone lymphoma (PBL) is a rare disease. There has been paucity of studies addressing its therapy and prognosis. We retrospectively examined PBL cases seen at the University of Miami from June 2000 to August 2007 to describe our single institution experience and review the literature. Fifty-three patients were identified with a median age of 52 (18-87) and a median follow-up of 40 months (0-106). The most common histologic type was diffuse large B-cell lymphoma (83%). Forty-one patients (77%) presented with localized disease and 48 were treated at our institution. Forty-six patients underwent chemotherapy (40 patients) and/or radiation (36 patients). Forty-four patients achieved a complete response and all patients were alive at last follow-up. The progression-free survival (PFS) was 83% at 4 years. No difference in PFS was observed between patients treated with chemotherapy or combined chemotherapy plus radiation. There was a trend toward improvement in PFS (p = 0.062) of patients with DLBCL treated with rituximab plus chemotherapy. Our single institutional experience demonstrates that the outcome of patients with PBL is excellent. Although the current data support the use of combined modality treatment for localized PBL, randomized controlled trials are needed especially now, when rituximab is routinely added to chemotherapy regimens.

Ahmad I, Saeed U, Rehmani R, Ahmed ME
Primary bone lymphoma: a series from a cancer institute in Pakistan.
J Pak Med Assoc. 2009; 59(3):179-81 [PubMed]

Primary bone lymphoma (PBL) is an uncommon tumour. Numerous studies have been reported from Western countries, but none from Southeast Asia. We reviewed a series of seven consecutive patients diagnosed and treated with PBL at our hospital between March 2002 and January 2007. All patients underwent chemotherapy with half receiving radiotherapy as their initial treatment. Six (84%) patients were male and 1 (16%) female with a median age of 33 (range: 23-85). All had diffuse large B-cell lymphoma (DLBCL) of bone except one (85 - M) who had chest wall cutaneous T-cell lymphoma with iliac blade involvement. The femur was the most frequently involved site (43%). Except for three patients that involved the lymph nodes, all patients had disease limited to bone. The 5-year overall survival rate was 43%. Although the number of patients was small, the data presented here revealed several characteristics of PBL.

Power DG, McVey GP, Korpanty G, et al.
Primary bone lymphoma: single institution case series.
Ir J Med Sci. 2008; 177(3):247-51 [PubMed]

BACKGROUND: Primary bone lymphoma (PBL) is a rare condition and accounts for less than 2% of adult lymphomas and 3% of all primary bone malignancies. Because of the rarity of this disease, there is a lack of prospective randomised clinical trials and hence optimal treatment is uncertain.
AIM: We report on our experience of treating PBL over 20 years.
METHODS: Using our hospital database, we identified all patients with PBL, their treatment, and long-term follow-up.
RESULTS: From January 1989 to July 2007, we identified 12 patients with PBL. Long extremity bones were the most common presenting sites. Multifocal disease was present in three cases. Treatment modalities included surgery, chemotherapy, and radiotherapy. Median follow-up was 8 years (range 0.5-18.5 years), and overall survival was 100%.
CONCLUSIONS: Combined modality therapy, i.e. chemotherapy followed by radiotherapy, is the preferred treatment option unless adverse neurology or an unstable fracture presents first.

Ibáñez M, Cortina B, Gómez V, et al.
Aggressive transformation of a quiescent primary bone lymphoma simulating Paget's disease.
Clin Exp Rheumatol. 2008 Jan-Feb; 26(1):133-5 [PubMed]

Primary multifocal osseous lymphoma is a rare and poorly recognized entity. Here, we present an instructive case of a young man who, six years after a local contusion of the left ankle, developed a painful polylobulated large soft tissue mass. This mass turned out to have arisen from the transformation of a centro follicular non-Hodgkin's lymphoma into a diffuse large B-cell lymphoma involving the calcaneus, talus, cuboid and navicular bones. The diagnostic difficulties as well as the implications of this aggressive transformation are highlighted here.

Maruyama D, Watanabe T, Beppu Y, et al.
Primary bone lymphoma: a new and detailed characterization of 28 patients in a single-institution study.
Jpn J Clin Oncol. 2007; 37(3):216-23 [PubMed]

BACKGROUND: The incidence of primary bone lymphoma (PBL) is so rare that many of its aspects remain unknown. A number of studies have been reported from Western countries, but only a few reports are available from Asia.
METHODS: We retrospectively analyzed 28 consecutive patients diagnosed with PBL initially treated at our hospital between 1995 and 2004. All patients underwent chemotherapy with half receiving radiotherapy as their initial treatment. A log-rank test was used in a univariate analysis to identify factors affecting overall survival.
RESULTS: Fifteen (54%) patients were male and 13 (46%) female with a median age of 47 (range: 5-81). Although 19 (68%) patients had diffuse large B-cell lymphoma (DLBCL), other histopathological subtypes (three B-lymphoblastic lymphoma, two anaplastic large cell lymphoma, two indolent B-cell lymphoma, one NK/T-cell lymphoma (NTCL) and one Hodgkin lymphoma) were also included. The pelvis was the most frequently involved site (54%). While 68% of patients had stage IV disease, none of them showed bone marrow involvement at their initial diagnosis. Despite 61% high intermediate-risk and high-risk patients based on the International Prognostic Index, the estimated 3-year overall and progression-free survival rates were 84% and 77%, respectively. Only 'histopathological subtype (immunoblastic variant of DLBCL or NTCL versus others)' and 'response to initial treatment (progression versus remission)' were factors significantly affecting overall survival.
CONCLUSIONS: Although the total number of patients was relatively small, the detailed clinical data analyses presented here revealed several new characteristics of PBL and some aspects that may be unique to Japanese patients.

Ford DR, Wilson D, Sothi S, et al.
Primary bone lymphoma--treatment and outcome.
Clin Oncol (R Coll Radiol). 2007; 19(1):50-5 [PubMed]

AIMS: A retrospective review of patients with histologically confirmed primary bone lymphoma (PBL) diagnosed and treated at a single tertiary referral centre between 1985 and 2003.
MATERIALS AND METHODS: The medical records of all patients treated for histologically primary bone lymphoma were identified using the hospital data base. Data was obtained on patient demographics, stage, treatment and outcome.
RESULTS: Twenty-two patients with PBL were identified. Seventeen had localised disease and five had multifocal bone involvement. The median age was 50 years. Of the patients who could be graded according to the International Prognostic Index (IPI), 12 cases were classified as low risk, seven as intermediate risk and one as high risk. All patients received chemotherapy; 19 with an anthracycline-containing regimen. Eighteen patients were treated with radiotherapy to a median total dose of 40 Gy (range 30-50 Gy). Three patients had surgery instead of radiotherapy as local treatment (one fibulectomy and two endoprosthetic replacements). The median follow-up was 84.5 months (range 3-206 months). The overall 10-year survival was 74%; 92% for low-risk IPI vs 73% for intermediate-risk IPI (P = 0.27). The 10-year relapse-free survival was 85% overall and 83% for both low- and intermediate-risk IPI (P = 0.87). Local relapse was seen in one patient. Orthopaedic complications occurred in two patients--one developed a pathological fracture after biopsy before radiotherapy and the other developed avascular necrosis outside the irradiated area.
CONCLUSIONS: Combined modality treatment for PBL results in good local control and survival rates with acceptable toxicity.

Zhao XF, Young KH, Frank D, et al.
Pediatric primary bone lymphoma-diffuse large B-cell lymphoma: morphologic and immunohistochemical characteristics of 10 cases.
Am J Clin Pathol. 2007; 127(1):47-54 [PubMed]

Most primary bone lymphomas (PBLs) are diffuse large B-cell lymphomas (DLBCLs). Pediatric PBL-DLBCL has a favorable prognosis but remains poorly characterized. Herein, 10 such cases are detailed. They involved 11- to 20-year-old males with bone lesions that were often painful. They were diagnosed often after months to years of symptoms, suggesting an indolent disease. All were successfully treated with chemotherapy with or without radiotherapy (0.5- to 24-year followup). Biopsy revealed that the lymphomas were paratrabecular or diffuse and were medium- to large-sized with round to irregular nuclei, dispersed chromatin, indistinct to small nucleoli, and abundant cytoplasm. Other features included varying levels of necrosis, cytoplasmic retraction, and myeloid hyperplasia. All cases marked as mature B cells, and most were CD10+ (7/10). Typical centroblastic morphologic features with nucleoli were rare, multilobated nuclei were uncommon, and CD10 negativity did not predict poor prognosis, unlike in the adult PBL-DLBCL. These findings suggest that pediatric and adult PBL-DLBCLs are distinct entities.

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(1):129-35 [PubMed]

BACKGROUND: Primary bone lymphoma (PBL) is a distinct clinicopathological entity. Although PBL has been reviewed in several small studies, few reflect recent improvements in primary treatment.
METHODS: We used the British Columbia Cancer Agency Lymphoid Cancer Database to identify all patients with PBL (1983-2005). All were staged in a uniform manner and treated with era-specific protocols.
RESULTS: We identified 131 patients with a median age of 63 years (18-87). One third had disease in long bones and another one third had disease in the spine, of which half presented with spinal cord compression. Patients with diffuse large-cell lymphoma (DLCL) (n=103, 79%) had 5- and 10-year overall survivals (OS) of 62% and 41%, respectively. Multivariate analysis identified three prognostic groups: age<60 with International Prognostic Index (IPI) 1-3 (n=43), age>or=60 with IPI 0-3 (n=23) and age>or=60 with IPI 4-5 (n=33), with markedly different 5-year OS of 90%, 61% and 25%, respectively (P<0.0001). Neither primary site nor pathological fracture at presentation had an impact on OS. The 3-year progression-free survival in patients who received rituximab plus combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOPR) chemotherapy was 88% compared with 52% in those who received CHOP-like chemotherapy without rituximab (P=0.005). The 10-year OS for those with advanced-stage disease who received irradiation plus chemotherapy was 25% versus 56% for those who received chemotherapy alone (P=0.025). Patients received irradiation if spinal cord compression was present or residual disease at the end of chemotherapy was thought to require it.
CONCLUSIONS: PBL is usually of DLCL type and has an improved outcome with CHOPR. Younger patients with good IPI score have a favorable prognosis.

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(12):2652-6 [PubMed]

BACKGROUND: To the authors' knowledge, there is limited information on the preferred treatment and long-term prognosis of primary bone lymphomas (PBLs). All PBL cases treated at the study center between 1963 and 2003 were analyzed to determine patient, disease, and treatment factors that could affect outcome measured by overall survival (OS), cause-specific survival (CSS), and freedom-from-treatment failure (FFTF).
METHODS: A total of 101 patients with PBL diagnosed at the study institution were identified. Nineteen patients were excluded because they transferred their treatment or follow-up to another center. Disease control, survival, and prognostic factors were analyzed for all 82 remaining patients.
RESULTS: The median age of the patients was 48 years (range, 11-83 years). Approximately 80% presented with diffuse large-cell lymphoma (DLCL), and 81% presented with Ann Arbor Stage I or II disease. Approximately 57% were treated with combined modality therapy, 14% were treated with radiation therapy alone, and 30% were treated with chemotherapy alone. The median follow-up was 67 months (range, 2-280 months). The 5-year OS, CSS, and FFTF were 88%, 96%, and 81%, respectively. The 5-year OS for patients treated with combined modality versus single-modality therapy was 95% versus 78% (P = .013), and the 5-year FFTF for patients treated with combined modality versus single-modality therapy was 90% versus 67% (P = .025). The 5-year CSS for patients treated with combined modality versus single-modality therapy was 95% versus 83% (P = .065). Using a Cox regression for multivariate analysis, age < 40 years and use of combined modality therapy were found to be favorable prognostic factors for OS, CSS, and FFTF.
CONCLUSIONS: To the authors' knowledge, the current study is the largest series of patients with PBL treated with modern curative modalities. The data demonstrate that primary lymphoma involving the bone has an excellent prognosis. Patients with PBL treated with combined modality versus single modality therapy were found to have a superior outcome, with a significantly better survival.

Horsman JM, Thomas J, Hough R, Hancock BW
Primary bone lymphoma: a retrospective analysis.
Int J Oncol. 2006; 28(6):1571-5 [PubMed]

The aim of this study was to retrospectively define those patients with unequivocal primary bone lymphoma presenting to the Sheffield Lymphoma Group and document patient and tumour characteristics and management strategies, and correlate these with survival. Thirty-seven patients were documented from a total of 3148 cases of non-Hodgkin's lymphoma seen over 34 years. There were 17 males and 20 females, with a mean age of 55.4 years (range, 27-78). Pain was the most commonly presented symptom (67.5%), and the pelvis was the most frequently presented site (21.3%). Grade 2 and diffuse large B cell lymphoma comprised the majority of histologies (78.7% and 70.3%, respectively). Treatment was most often with radiotherapy alone (41.8%) or combined with CHOP-like chemotherapy (37.9%). The overall response rate was 56.7%, and 5- and 10-year survival rates were 64.5% and 49.6%, respectively. Univariate analysis showed an age of <60 years and complete response to be favourable prognostic factors. There was a trend toward better survival with combined modality therapy involving CHOP-like chemotherapy. Bone lymphoma has a better survival than other extranodal lymphomas. Younger age and complete response are favourable predictive factors. Combined modality treatment is likely to be the treatment of choice but this remains to be confirmed in large prospective multicentre studies.

Míguez Sánchez C, Hebrero ML, Mesa C, et al.
Primary bone lymphoma.
Clin Transl Oncol. 2006; 8(3):221-4 [PubMed]

Primary bone lymphoma is a rare condition which represents a low percentage of both the malignant primary bone tumours and the non-Hodgkin extranodal lymphoma. This explains the lack of publications, lines of investigations, and specific diagnostic and treatment protocols. In the following article we will carry out a revision of the existing literature on this rare subject, using as argument a clinical case of left femoral location stage IE treated with CHOP chemotherapy and radiotherapy.

Baiocchi OC, Colleoni GW, Rodrigues CA, et al.
Importance of combined-modality therapy for primary bone lymphoma.
Leuk Lymphoma. 2003; 44(10):1837-9 [PubMed]

Primary bone lymphoma (PBL) is a rare entity and comprises about 5% of all extranodal non-Hodgkin's lymphomas (NHL) and 7% of all primary bone tumors. To date there is no consensus about the optimal treatment for PBL. We retrospectively reviewed all cases of PBL treated at Hospital São Paulo, Brazil, over a 10-year-period (January 1992-January 2002). Medical records of 7 patients with PBL were reviewed and information on age at diagnosis, sex, NHL clinical staging (CS), treatment and response to treatment were retrieved. Five patients (72%) received combined-modality therapy (CMT) and all of them are in complete remission (CR) with a median follow up of 19 months (ranging from 12 to 144 months). We conclude that PBL is a potentially curable malignancy and treatment should be undertaken in a multiprofessional approach, in order to provide the best support which probably has to include chemotherapy, radiotherapy and, for patients with IPI higher than 2, consolidation with stem-cell transplantation.

Krishnan A, Shirkhoda A, Tehranzadeh J, et al.
Primary bone lymphoma: radiographic-MR imaging correlation.
Radiographics. 2003 Nov-Dec; 23(6):1371-83; discussion 1384-7 [PubMed]

Primary bone lymphoma is an uncommon malignancy that accounts for less than 5% of all primary bone tumors. The radiographic appearances of primary bone lymphoma are variable, and, because the lesion can appear near normal on plain radiographs, a second modality such as bone scintigraphy or magnetic resonance (MR) imaging should be used. Despite this variability, the presence of a solitary, permeative, metadiaphyseal lesion with a layered periosteal reaction on plain radiographs and a soft-tissue mass on MR images, especially in a patient older than 30 years, is highly suggestive of lymphoma. The case for a diagnosis of primary bone lymphoma is further strengthened if the soft-tissue mass and marrow changes are associated with surprisingly little cortical destruction. Primary bone lymphoma has a better prognosis than many other malignant bone tumors; therefore, early identification allows for appropriate treatment. MR imaging not only permits early identification but also depicts the extent of soft-tissue involvement and can be used to assess the outcome of treatment.

Zinzani PL, Carrillo G, Ascani S, et al.
Primary bone lymphoma: experience with 52 patients.
Haematologica. 2003; 88(3):280-5 [PubMed]

BACKGROUND AND OBJECTIVES: A retrospective analysis was performed to assess the efficacy of various treatments of non-Hodgkin's primary bone lymphomas (PBL).
DESIGN AND METHODS: Fifty-two consecutive, previously untreated PBL patients were seen between the years 1982 and 1998. Information was obtained regarding each patient's presentation and clinical course. Histology was reviewed in all cases. Modern immunohistochemical stains were performed on each case.
RESULTS: Regarding therapeutic approach, we observed a complete response (CR) in 35/41 (85%) patients treated with chemotherapy with/without radiation therapy and in 7/11 (64%) patients who received radiation therapy alone. Relapses were observed in only 2/35 (6%) patients after chemotherapy (with/without radiation therapy), as compared with 4/7 (57%) patients after radiation therapy alone (p = 0.004); the relapse-free survival curves of these two subsets were significantly different. At both univariate and multivariate analysis only type of front-line therapeutic approach (chemotherapy with/without radiation therapy vs. radiation therapy alone) turned out to have a significant prognostic influence.
INTERPRETATION AND CONCLUSIONS: Our data indicate that in PBL use of chemotherapy or combined-modality therapy seems to provide more durable CRs than radiation therapy alone.

Stein ME, Epelbaum R, Zaidan J, et al.
Excellent long-term survival in patients with early-stage primary bone lymphoma treated with doxorubicin-based chemotherapy and local radiotherapy.
Am J Clin Oncol. 2002; 25(6):603-5 [PubMed]

Primary bone lymphoma accounts for less than 5% of primary extranodal presentations, and the majority are of the diffuse, large cell, B-cell type. The study presents the authors' 21 years of experience (1979-2000) in ten patients with early stage (IE-IIE) primary bone lymphoma. All patients were treated with doxorubicin-based chemotherapy. Seven received consolidation radiotherapy to an area encompassing the primary tumor with generous margins, including the adjacent soft tissues, and in two stage IIE patients also to the regional lymph nodes. Mean total dose was 3989 cGy. Nine patients are alive with no evidence of recurrent disease. There are no severe late side effects, and only one patient died due to therapy-resistant small cell lung cancer (second primary), while in complete remission from his primary lymphoma. Albeit retrospective in nature with a small patient accrual, this study demonstrates that primary bone lymphoma is a curable disease following aggressive doxorubicin-based chemotherapy. The exact rule of radiation therapy is yet to be determined.

de Camargo OP, dos Santos Machado TM, Croci AT, et al.
Primary bone lymphoma in 24 patients treated between 1955 and 1999.
Clin Orthop Relat Res. 2002; (397):271-80 [PubMed]

The authors present their experience in the treatment of 24 patients with primary bone lymphoma. Eighty-one patients treated between 1955 and 1999 were evaluated, and 57 were excluded because of misdiagnosis. The male to female ratio was 7:5 and the median age was 38.5 years (range, 18-69 years). Two patients had human immunodeficiency virus. Seventeen patients had intermediate-grade lymphomas (Working Formulation), nine patients had centroblastic subtype (Kiel), and 22 patients had B immunophenotype. Nine patients had combined treatment with chemotherapy and radiation therapy, and nine patients had chemotherapy alone. The mean followup was 13.2 years (range, 1.5-37.3 years). Three patients had surgery, two because of subtrochanteric fractures (one patient had closed reduction and internal fixation and the other patient had resection and endoprosthesis reconstruction). The third patient presented with myelocompression at the thoracic level, and he had decompression surgery. Only one patient had radiation therapy and two patients had no treatment. There have been no local recurrences in 17 patients (70.8%). Seven patients (29.2%) died with evidence of disease within a followup of 11 months. The results of the current study showed that patients with primary bone lymphoma have a good prognosis when they are treated with chemotherapy, regardless of whether radiation therapy was given. Surgery usually is appropriate for patients with fractures.

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(2):214-9 [PubMed]

BACKGROUND: To examine prognostic factors, treatment outcomes and design future studies for Osteolymphoma (OL)--also known as primary bone lymphoma.
METHODS: Between 1979 and 1993, 70 patients with OL were treated in nine Australian centres. The effect of patient-, tumour-, and treatment-related factors on local control, distant disease-free survival and overall survival were assessed by multivariate analysis.
RESULTS: Most patients (94%) received radiotherapy (RT) (median dose 40 Gy) and 56% received chemotherapy. Multifocal disease was present in 20% of patients. The five year rates of overall survival and local control were 59% and 82%. Although there was a trend towards better results with the addition of chemotherapy, on multivariate analysis, there were no factors identified which appeared to impact upon overall and disease-free survival. Among the distant recurrences, there was a high proportion in bone (33%). Six patients suffered pathological fractures after treatment.
CONCLUSION: High rates of local control were achieved by RT, but the overall survival remains relatively poor, worse than nodal lymphoma. The natural history of the disease suggests that OL may be a distinct entity, different to nodal lymphomas, so the results of clinical trials in nodal lymphoma may not be relevant to OL. Prospective studies could define the outcome of combined modality therapy and set a benchmark for testing further proposals, as well as improving our knowledge of the clinical features of OL.

Song YG, Hahn JS, Choi YH, et al.
A case of primary bone lymphoma associated with acquired immunodeficiency syndrome.
Yonsei Med J. 1998; 39(4):383-9 [PubMed]

A 33-year old man with acquired immunodeficiency syndrome was admitted to Severance hospital following 1 year of diarrhea and 2 to 3 months of low sternal pain. The patient had progressive generalized lymphadenopathy for the previous 3 years. Whole body bone scan for evaluation of bone pain showed multiple abnormal hot uptakes at the low sternal body and T8 and T10 vertebra. Chest CT showed multifocal cortical erosion of the bone with soft tissue mass at the low sternal body and spine MRI showed multiple low-signal density in T1WI and high-signal density in T2WI at the T8 and T10 vertebral body. Biopsy was performed at the sternochondral junction and it showed high-grade malignant lymphoma of the large cell immunoblastic type. Immunostaining showed positive for the B-cell markers (CD79a and L26) and negative for the T-cell marker (UCHL1). Radiotherapy of 3,000 cGy was delivered to the sternum and vertebra. Since then, systemic chemotherapy with m-BACOD regimen (except dexamethasone) and anti-retroviral therapy with a combination of 3 drugs (didanosine, lamivudine, indinavir) has been performed. This is the first case report of primary bone lymphoma associated with acquired immunodeficiency syndrome in Korea.

Christie DR, Cahill SP, Barton MB
Primary bone lymphoma (osteolymphoma).
Australas Radiol. 1996; 40(3):319-23 [PubMed]

Seventeen patients with primary lymphoma of bone are reviewed. In 15 patients treated with radical radiotherapy, local progression or recurrence occurred in four. The results support the use of radiotherapy alone, using doses of 45-50 Gy. Although small numbers prevent firm conclusions, the inclusion of the whole bone or regional nodes in the irradiated volume did not appear to improve results. Eight patients received systemic chemotherapy with no apparent improvement in rates of relapse. Two patients suffered pathological fractures after radiotherapy in the absence of recurrence at the fracture site; however, osteomyelitis, older age, Paget's disease, high-dose prednisolone and whole-bone radiotherapy may have added to the risk of fracture. Because of the many complex names and selection criteria applied to this condition, literature searching and comparison between studies was difficult. The simple term osteolymphoma is proposed, consistent with other primary bone conditions.

Shannon JA, Bell DR, Levi JA, et al.
Bone presentation of non-Hodgkin's lymphoma: experience at the Royal North Shore Hospital, Sydney; highlighting primary bone lymphoma.
Aust N Z J Med. 1994; 24(6):701-4 [PubMed]

BACKGROUND: Primary lymphoma of bone (PLB) is a rare form of extranodal lymphoma. Between 1975 and 1992 39 patients with lymphoma presenting in bone were seen at the Royal North Shore Hospital (RNSH), Sydney. Of these, 12 (31%) had truly localised disease (Stage IE).
AIMS: Patients were studied retrospectively to determine the prognostic significance of bony involvement per se versus involvement of a single bony site, and to determine the impact of treatment modality on outcome.
METHODS: The 39 patients were divided into three groups according to extent of disease; single osseous site (Stage IE), multifocal bone, and bone plus visceral and/or nodal disease. Kaplan-Meier survival curves were constructed, and five year actuarial survival stated. Cox regression analysis was used to determine hazard ratios. Overall survival was used as the end-point.
RESULTS: A trend for better survival was noted with Stage IE disease. Multifocal and disseminated disease appeared to have a poorer outcome when assessed by hazard ratio, with a value of 3 (95% CI 0.87-10.4; p = 0.08), compared to unifocal disease. Radiotherapy alone was as effective as combined modality treatment although patient numbers were too small for statistical confirmation.
CONCLUSIONS: The stage of lymphoma, rather than bony involvement per se, seems to have more prognostic importance. Radiotherapy alone offered equivalent results to combined modality treatment in this series.