Primary Lymphoma of Bone

Missing Key Test Topics

Primary Lymphoma of Bone (PBL) is a rare tumor usually noted as a solitary bone lesion, or as multiple lesions, without nodal or extra-nodal disease. They tend to present with bone pain, often with minimal findings on plain x-ray due to the permeative behavior of this tumor wherein it can permeate medullary bone trabeculae without causing lysis. Despite this, PBL has the best prognosis of any malignant primary bone tumor.

Epidemiology

These tumors typically belong to the class of non-Hodgkin lymphomas with the most common form being Diffuse Large B-Cell Lymphoma, not otherwise specified (DLBCL,NOS) which accounts for 80% of these lesions. The most common age range is adults in the 5th and 6th decades. These tumors occur most commonly in the large long bones, spine and pelvis. Males are affected more commonly than females.

Clinical Findings

The most common presenting symptom in these patients is a history of bone pain which may mimic other more common, non-neoplastic conditions such as arthritis, muscle sprains, etc. In addition to bone pain, these tumors can also present with systemic “B symptoms” which include fever, night sweats and unintended weight loss. Because of the rarity of this lesion and its ability to mimic common disorders clinically, there is often a prolonged history of pain before the diagnosis is made. When these tumors do involve the large long bones, they are most often metaphyseal in location.

Radiologic Features

Plain x-rays are usually the first imaging study obtained. Importantly, a normal plain x-ray in does not rule out the presence of an underlying lymphoma. This is due to the tendency for these lesions to cause intra-medullary permeation without lysis (Figure 1 and 2). Despite this, many lesions do demonstrate intra-medullary lysis, usually with a moth eaten margin with adjacent medullary bone. In rare instances PLB’s incite a blastic reaction and these cases reveal dense reactive bone formation within the lesion similar to that commonly seen with metastatic prostate carcinoma.

Figure 1: AP and lateral radiographs of right proximal femur demonstrating a subtle permeative lytic lesion in the peritrochanteric area. Biopsy was positive for diffuse large B-cell lymphoma.
Figure 2: AP radiograph of distal femur lymphoma of bone. Despite normal radiographs, the marrow-replacing lesion is obvious on MRI scan as seen in Figure 3.

Despite subtle radiographic findings, MRI scans demonstrate uniform marrow replacement by tumor seen as hypointense signal on T1 images and hyperintense signal on fat sensitive images, namely T2 fat suppressed and STIR (Figure 3), similar to most other tumors. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans are valuable for  detecting viable neoplastic tissue due to the hypermetabolic nature  of the tumor and, therefore, its high FDG uptake. As such these scans are able to screen for distant involvement.

Figure 3: T1 coronal (A), and STIR coronal (B) MRI scan of femur shown in the Figure 2 radiograph. Lymphoma of bone has displaced the normal marrow.

Pathology

Histologically, these tumors are composed of sheets of somewhat irregular, roundish cells. These cells are not as perfectly round and regular as those seen in Ewing Sarcoma, for example, but despite being somewhat irregular in shape they do not have a spindled appearance (Figure 4). These tumors stain positively with B-cell markers such as CD19 and CD 20 as well as Leukocyte Common Antigen (LCA).

Figure 4: H&E stained histology slide, showing sheets of large atypical lymphoid cells infiltrating bone marrow fat with vesicular chromatin, prominent nucleoli, and scant to moderate cytoplasm. Numerous mitotic figures and frequent apoptotic bodies are present. (Image courtesy of Dr. Gord Zhu)

Differential Diagnosis

Radiographically, these tumors overlap all aggressive bone lesions in adults including myeloma, metastases and sarcomas requiring a biopsy to confirm a diagnosis. Pathologically these tumors resemble small cell metastatic adenocarcinomas and frequently require Immunohistochemical stains (IHC)to differentiate from the latter group.

Disease Course, Treatment and Prognosis

The role of surgery for this disease is limited to biopsy and potential internal fixation of impending or established pathologic fractures. The major current treatment options include chemotherapy, immunotherapy and radiation therapy. The typical drug regimen includes cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with or without the addition of rituximab (R-CHOP). The 5-year overall survival is approximately 70% with current treatment. Unfavorable prognostic factors include advanced patient age and primary location within the spine.

Key Test Topics

  • These lesions in bone are very permeative and not destructive so they may be difficult to see on plain x-rays.
  • The most common presenting symptom is bone pain but also look for “B Symptoms” including fever, night sweats and weight loss.
  • These bone lesions are easily seen on MRI images where they demonstrate clear marrow replacement.
  • On histology- small round blue cells which are positive for lymphoid markers such as CD19, CD20 and LCA.
  • Primary tumor treatment is chemotherapy and radiation.
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