Primary bone lymphoma involving bilateral tibia
Authors: Angela A. Giardino, Atul B. Shinagare, Shweta A. Shinagare, Rajan Dewar, Doug Weckstein, Peter Mauch, Nikhil H. Ramaiya, Arnold S. Freedman
Journal: American Journal of Hematology (2012)

A 77-year-old man with history of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma without bone marrow involvement which was treated with involved field radiation was in complete remission for 7 years. He presented in April 2010 with a fall and right knee pain. Magnetic resonance imaging (MRI) in June 2010 showed a meniscal tear and abnormal marrow signal in the tibial plateau. Persistent knee pain prompted biopsy of the proximal right tibia. Hematoxylin and eosin stain showed a dense infiltrate of intermediate to large-sized lymphocytes with dispersed chromatin and variably distinct nucleoli (Image 1A,B), which, on immunohistochemistry, were positive for CD20 (+) (Image 1C), BCL-2, and BCL-6, but negative for CD5, CD10, CD43, and Cyclin D1. MIB-1 proliferative index was around 40–50% within the larger neoplastic cells (Image 1D). All the findings were consistent with large B cell type non-Hodgkin lymphoma and were not suggestive of transformation of prior indolent gastric marginal zone lymphoma. [18F] fluorodeoxyglucose positron emission tomography (FDG-PET/CT) showed very intense focal uptake in proximal tibia bilaterally (SUVmax 48.3 on right side and 46.4 on left), more extensive on the right side (Image 2A,B). An FDG-avid right popliteal lymph node (SUVmax 4.2) was also noted. (A) Low power (10×) photomicrograph stained with hematoxylin and eosin shows a dense lymphocytic infiltrate of intermediate to large-sized cells with round nuclei, dispersed chromatin and variably distinct nucleoli. (B) High power (20×) photomicrograph of the neoplastic cells stained with hematoxylin and eosin. (C) High power (20×) photomicrograph shows positivity for CD20. (D) High power (20×) photomicrograph shows 40–50% of MIB-1 proliferative index within the larger neoplastic cells. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] (A) Coronal [18F] FDG-PET image of the lower limbs shows intensely FDG-avid areas of uptake in proximal tibia bilaterally (arrows), and a small mildly FDG-avid right popliteal lymph node (arrowhead). (B) Fused FDG-PET/CT image in the axial plane demonstrates FDG uptake in bilateral proximal tibia (arrows), more on the right side. No evidence of disease was seen elsewhere (not shown). (C) Coronal FDG-PET image and (D) axial fused FDG-PET/CT image obtained after three cycles of R-CHOP treatment show near-total resolution of the FDG-avidity in bilateral proximal tibias (arrows). Previously seen FDG-avid right popliteal lymph node is not visible. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] The patient was treated with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy completed in April 2011. FDG-PET/CT after three cycles (Image 2C,D) showed near-total resolution of tibial uptake as well as the popliteal lymph node. FDG-PET/CT after completion of treatment showed no evidence of disease (not shown). Patient remains well after 15 months, with no evidence of disease noted on FDG-PET/CT obtained in January 2012. Primary lymphoma of bone (PBL) is a rare form of non-Hodgkin's lymphoma, first described in 1939 [1]. It represents 3% of all primary bone malignancies, <2% of all adult lymphomas, and 5% of extranodal lymphomas [2-5]. Diffuse large B-cell lymphoma accounts for approximately 80% of cases [3, 4]. PBL occurs in older patients with a slight male preponderance, commonly involves femur, pelvis, humerus, skull, and tibia, and presents with local pain or B symptoms [3, 6-8]. PBL is defined as lymphomatous involvement of a single osseous site with or without regional lymph node involvement, or involvement of multiple bones without visceral or nodal involvement [3, 6]. Plain radiographs and CT usually show a lytic metaphyseal lesion with periosteal reaction; however, with limited sensitivity and specificity [9, 10]. CT may also appear normal, or rarely, can show a sclerotic area [10]. MRI is the preferred modality on which PBL appears isointense or hypointense on T1-weighted images, isointense to slightly hyperintense on T2-weighted images, and shows moderate homogeneous enhancement [10]. The differential considerations include metastatic carcinoma, Ewing's sarcoma, osteosarcoma, and chronic ostoemyelitis. The imaging appearance is nonspecific, and pathologic diagnosis is required in all cases. CHOP-based chemotherapy has become the standard of care, with or without radiation treatment [3]. The reported 5- year and 10-year survival rates of PBL are 58–62% and 41–45%, respectively [3, 8]. Progression free survival (PFS) has improved with the addition of rituximab (88% 3-year PFS for CHOP plus rituximab versus 52% for CHOP only) [3]. In summary, we present a case of PBL involving tibia, which was treated with R-CHOP, and patient is in remission at 15 months. Although rare, this case demonstrates the typical features of PBL including age, gender predilection, a common anatomic location, typical imaging features, as well as treatment and outcome. The remote history of gastric MALT lymphoma did not dissuade the necessity for biopsy of the bone abnormality.