Primary Bone Lymphoma (PBL)

PBL is a rare bone malignancy first described in 1928 by Oberling as a reticulum cell sarcoma [1] followed by a case series of 17 cases by Parker and Jackson [2]. It accounts for 7% of all bone tumors. It is characterized by the proliferation of malignant lymphoid cells within bone. Patients can present with single or multiple osseous lesions, with or without regional lymph node involvement; but to be classified as a primary bone tumor, there cannot be any extra-nodal lesions or supraregional lymph node involvement [3].

PBL is most commonly identified within long bones, with the femur being the most affected bone overall [3-5]. It can present in any age group, with most cases presenting in older adults. There is a male predominance, with some reports noting up to a 1.5:1 ratio [3,6].

The most common symptom is pain in the absence of trauma, which can be associated with swelling and a palpable mass in some patients [3]. The presence of B symptoms, a finding usually seen in systemic lymphomas, is not common in PBL. Pathologic fractures and spinal cord compression are rare in PBL, and are more associated with systemic lymphoma with secondary bone involvement. Histologic findings show various types of lymphoma, the most common being diffuse large B-cell lymphoma [7].

We describe a case of a rare presentation of PBL in the patella associated with weight loss and pathological fracture in a 15-year old patient.

A 15 year-old young man presented with insidious onset of right peripatellar pain, which was intermittent in nature and increasing in frequency and severity. He had had a thirty-pound weight loss over the previous year. He did not have fevers, chills or other systemic symptomatology. On examination, there was a small right knee effusion and patellar tenderness, associated with thigh atrophy. Right inguinal adenopathy was identified but there were no abdominal masses, visceromegaly or lymphadenopathy in the cervical, supraclavicular or axillary areas.

Radiographs demonstrated a well-circumscribed, radiolucent lesion in the inferior pole of the patella (Figure 1). MR images showed a marrow-replacing lesion with cystic changes in the inferior pole of the patella that was heterogeneous but mostly hypointense in the fatsuppressed T1-weighted sequences (Figure 2), and heterogeneous and mostly hyperintense on the T2-weighted images (Figure 2B). There was heterogeneous enhancement within the lesion and perilesional edema on the gadolinium-enhanced sequences (Figure 2C). In the distal femoral epiphysis, another lesion of somewhat different characteristics was identified, with moderate signal on the T2-weighted series (Figure 2B) and heterogeneous enhancement on the post-contrast sequences (Figure 2C). Due to a high suspicion for a malignant process, a CTguided biopsy of the patella was performed. Histologic evaluation of the right patella needle core biopsies showed predominantly necrotic tumor; however focal regions demonstrated a proliferation of large pleomorphic lymphoid cells with irregular nuclear contours and inconspicuous nucleoli. By immunohistochemical stains, the lesional cells expressed strong reactivity to CD45, CD20, CD79a, PAX5 (variable), CD10, and BCL6 (variable). These histologic and immunohistochemical features are consistent with a diagnosis of diffuse large B cell lymphoma, and, given the setting, a primary bone lymphoma (Figure 3). A pathologic fracture of the patella occurred while walking down the stairs (Figure 4) during the work-up and prior to the biopsy. He was treated for the fracture with a knee brace to limit force across his extensor mechanism since it was not displaced and had a good chance of healing with chemotherapy. He received chemotherapy with cyclophosphamide, vincristine, prednisone and doxorubicin (COPAD protocol) with good response and he has been disease-free after two years. The fracture healed uneventfully (Figure 5) and he is now back to playing sports without restrictions.

Figure 1: (A) AP and (B) lateral radiographs of the knee show an osteolytic lesion in the inferior pole of the patella.

Figure 2: MRI with and without contrast of the right knee demonstrating T1 fat-suppressed and T2 fat-suppressed sequences. (A) T1 axial sequence, (B) T2 axial sequence, (C) T1 axial without and (D) with gadolinium contrast technique, (E) T2 sagittal sequence, and (F) T1 sagittal sequence. T1-weighted sequences show bone marrow infiltration and heterogeneity within the patella. T2-weghted sequences show bone marrow edema.

Figure 3: Histologic features of primary bone lymphoma. (A) Hematoxylin and eosin stain (400X) demonstrating a focus of large pleomorphic lymphoid cells with irregular nuclear contours and inconspicuous nucleoli. (B) By immune histochemical stains, the lesional cells expressed strong CD20 (400X). These features are consistent with a diagnosis of diffuse large B cell lymphoma.

Figure 4: Lateral radiograph of the knee after the patient’s sudden onset of pain while walking down the stairs showing a transverse, non-displaced fracture of the patella.

Figure 5: (A) AP and (B) lateral radiograph of the knee 2 years after diagnosis showing complete healing of the fracture and without evidence of osteolytic lesions.

PBL is an uncommon bone malignancy overall, but even more so during early adolescence. The most common bones involved are the femur and other long bones, followed by marrow-rich bones like the pelvic bones, spine and ribs [3]; patella involvement is rare despite the presence of active bone marrow into young adulthood. The most common symptom of PBL is pain without a history of trauma, much like our patient, but pathologic fractures are unusual [3,4,6-8]. Weight loss is also uncommon in PBL and is more often associated with standard non-osseous lymphomas. These factors make this a unique case and to our knowledge, the first patellar lymphoma of bone being reported during adolescence.

Anterior knee pain is a common cause for consultation in young active patients and its differential diagnosis is very broad [9,10]. Benign causes like meniscal tears, ligamentous injuries, patellar malalignment, impingement syndromes, tendinitis and hip pathology are some of the diagnoses to consider when a patient presents with anterior knee pain. Nevertheless, other disease categories including primary malignant bone tumors should be considered; especially, if there is no response to conventional treatments [9]. Due to the uncommon presentation of patellar tumors, diagnosis is usually delayed because neoplasia, let alone a malignancy, is almost never considered as an option in the diagnostic process. In this case, our patient consulted multiple times because of his symptoms and was repeatedly treated for an inflammatory process. It was eventually the persistence of his symptoms beyond seven months and lack of response to anti-inflammatory treatment that prompted further workup and consultation with the subspecialist. Other reports on patellar tumors have noted a similar delay in diagnosis, ranging from 3-24 months [11,12].

Most case series of PBL in the literature do not distinguish between pediatric and adult populations [7,8,13]. What we can glean from the reports of only pediatric series and those that distinguish populations by age are some similar features to the adults. Pediatric cases of PBL occur most commonly in males and in the long bones, with the femur being the most prevalent site [14-19]. Reported overall 5-year survival in pediatric PBL is 83.5–100% [20,21], the highest survival in patients with early stage disease. This excellent survival was found to be reproducible with the use of chemotherapy without the need for radiation [14,18,22], compared to the standard of chemotherapy with radiation to the bone lesions in adults [4,8]. There is typically no need for surgical intervention beyond the initial biopsy in any age patient unless there is the presence of a displaced pathologic fracture or spinal cord compression [7]. In our case, the patient presented with a pathologic fracture that required no further intervention than immobilization.

Patellar tumors in general are also rare. In Dahlin’s [5] landmark series of tumors from the Mayo Clinic only 14 out of 9,973 bone tumors were primarily located in the patella. Of those 14 cases, 8 were benign and 6 were malignant, including 3 PBL. In a literature review performed by Mercuri and Casadei [12], 384 patellar tumors were identified (including 31 patients from the authors’ institution), 105 of which were malignant with only 14 of those being PBL (13%). When excluding patellar metastases, there were only 60 malignant lesions arising from the patella, so it is important to note PBL would thus represent 23% of all primary patellar malignancies. Most of the cases of malignant patellar tumors occurred in patients in the 5th decade of life. Most case reports and series on primary tumors of the patella show a majority of benign lesions, the most common being giant cell tumor and chondroblastoma [12,23-26]. Amongst the malignant lesions of the patella, the most common are metastases, whilst the most common primary malignant lesion is osteosarcoma. Out of 7 case series [11,12,23-27] and 2 case reports [28,29] found in the literature on patellar tumors reviewed by our group, there were a total of 154 cases of primary patellar tumors, with only 10 cases being reported as PBL; all of them adults or patients of unknown age.

The treatment and prognosis of patellar tumors vary depending on the histologic type of the tumor and the extent of the disease when diagnosed. Most benign tumors require only intralesional curettage with or without allograft packing or cementation or partial patellectomy depending on the extent of the lesion. Malignant lesions, excepting lymphoma and multiple myeloma, require more aggressive surgical treatments ranging from subtotal patellectomy to amputation, with or without the use of adjuvant therapies such as chemotherapy or radiation [11,12].

Our patient underwent treatment with chemotherapy only, following the standard management of PBL in the pediatric population, unlike PBL in adulthood, where the use of both chemotherapy and radiotherapy is recommended [14]. The use of radiotherapy for PBL in pediatric patients is no longer widely used. Several reports have showed the negative results from using radiotherapy in pediatric patients such as musculoskeletal development and growth abnormalities and secondary tumors due to radiation exposure [18,21], while there are many reports of excellent outcome in pediatric patients with PBL using chemotherapy alone (COPAD and COPAD-like regimens) [14,20,22].

In conclusion, a detailed medical interview should raise suspicion of an underlying unusual and possibly neoplastic process in a patient with anterior knee pain without improvement in symptoms. Early imaging should be obtained and interpreted by physicians with a reasonable comfort level in evaluating musculoskeletal images, and in a pediatric population if appropriate. Tumors arising from the patella are not common but they should be suspected in patients with persistent pain in the patellar region. Even though most patellar lesions are benign, malignant tumors should be considered as part of the differential diagnosis because failure to do so could eventually lead to a delayed diagnosis and possible extension of the disease.