Clinicopathologic characteristics and prognostic factors for primary spinal epidural lymphoma: report on 36 Chinese patients and review of the literature

Primary spinal epidural lymphomas (PSELs) are very rare, and relatively few such tumors have been reported in the literature. Although PSEL accounts for 10% of all epidural spinal tumors [ 1], the epidural location is a rare site of presentation for lymphomas, characterizing only 0.1 to 3.3% of all lymphomas [ 2, 3]. Due to the rarity of the condition, it is difficult to enroll a sufficient number of patients with PSEL to adequately evaluate possible factors associated with survival. The largest series to date, reported by Monnard et al. [ 4], identified 52 patients over 20 years (1982–2002). However, the limited number of patients and the long time span have made it difficult to establish the disease parameters, such as the natural history of the disease, prognostic indicators, treatment techniques employed, and survival rates. For this study, we identified only retrospective studies, which included reports on relatively small numbers of patients or single case reports. The goal of this study was to help identify the clinical profile, treatment outcomes, and significant prognostic indicators in PSEL patients.

With a study cohort of 130 patients treated over a 30-year period, the current study represents the largest one to focus on PSEL. Prior to this, the largest one reported on only 52 patients, and predated modern radiotherapy and chemotherapy protocols.

The origin of primary spinal epidural lymphomas (PSEL) remains controversial. It is known that lymphoma may arise anywhere lymphatic tissue is found. However, whether there is lymphoid tissue in the epidural space has been debated [ 5, 6]. Rubinstein was the first to demonstrate the presence of lymphoid cells in epidural tissue, and he introduced the theory of antigenic stimulation with a transformation cascade [ 7]. Some have suggested that PSEL may originate from either paraspinal, spinal, or retroperitoneal tissues, accessing the epidural space via the interspinal foramina [ 8, 9]. However, the occurrence of lymphoma in this location indicates that lymphoid precursor cells are present in the space. Metastasis is the most common sacral malignancy, whereas chordoma in the most common primary sacral tumor [ 10]. PSELs represent 10% of epidural spinal tumors, but the epidural location is a rare presenting site for lymphomas, being seen in only 0.1 to 3.3% of all lymphomas. When lymphoma has been found in the spine, it has been reported most often in the lumbar or lower dorsal area [ 11]. However, in this study, we found the thoracic spine to be the most common site (62%) for lymphoma.

The most common presenting symptoms reported in the literature have included lower limb weakness, localized back pain, and bladder dysfunction [ 8, 9]. However, in this study, the most common symptoms seen were motor weakness or hypoesthesia (62%), back pain (59%), lumbosacral pain (32%), limb pain (28%), neck pain (9%), bowel dysfunction (23%), bladder dysfunction (19%), and low-grade fevers (2%). It is noteworthy that most patients presented with persistent back pain for considerably long periods of time prior to diagnosis. Therefore, persistent back pain in a patient should be considered a warning symptom for a more serious illness.

On histopathological examination, these tumors show atypical lymphoid cell proliferation. On immunohistochemistry, tumor cells are positive for leukocyte common antigen (LCA) and CD20, but negative for CD138, CD30, and CD3. B-cell lymphoma is the most common type at this site [ 12], which is consistent with our findings. Our study found that tumor pathologies consisted of B-cell lymphoma (76%), T-cell lymphoma (11%), and Burkitt’s lymphoma (13%). Furthermore, tumor cells were associated with the strong expression of leukocyte common antigen (100%) and the absence of CD20 expression (78%). PSELs are almost invariably of the B-cell type, although indolent B-cell and T-cell variants are sometimes seen.

There has been no optimization of treatment strategies for PSEL patients to improve patient outcomes. Unfortunately, there is a high mortality rate within the first year of diagnosis due to early metastasis and tumor recurrences. Accordingly, the importance of aggressive, systemic therapy has been recognized over the last few decades, although there have been reports of patients being cured with local radiotherapy alone [ 13]. In cases of patients who present with signs of spinal cord compression, surgical intervention for tissue diagnosis and decompression is required. Aabo et al. [ 14] reported no difference between the outcomes in patients who underwent decompressive laminectomy and radiotherapy and those who received spinal radiation only. Chemoradiotherapy remains the mainstay of treatment because lymphomas are highly radio- and chemosensitive tumors. The CHOP regime, in particular, is still considered the gold standard for treatment. A radiotherapy dose of 3500 cGy to 4000 cGy delivered in 20–25 fractions over 3–4 weeks is required to achieve radical cure [ 9]. Intensive chemotherapy should also be initiated immediately following diagnosis and be delivered over a short period of time. From reviewing several studies, we found that combined modality treatment is associated with a lower recurrence rate and improved disease-free survival in PSEL, but not overall survival. Similar findings have not been reported by other researchers. In this study, the median survival time of 36 Chinese patients is 12 month. It shorter than non-Chinese cases (12 VS. 27). Optimization of treatment strategies for Chinese patients included surgery (33/35, 94.3%), surgery followed by chemotherapy (17/35, 56.7%), surgery only (15/35, 42.9%), and surgery followed by chemotherapy and radiotherapy (5/35, 14.3%). There are less Chinese patients with PSEL treated with combined modality treatment compared to non-Chinese cases because of medical expenses. Kaplan–Meier analysis revealed that combined modality treatment is associated with improved disease-free survival for all 130 PSEL cases. Therefore, to our knowledge, combined modality treatment should be considered an standardized treatment strategy for PSEL presently.

The results of the present study indicate that PSEL has a relatively good prognosis, that thoracic spine location is a significant poor prognostic factor, and that combined modality treatment is associated with improved disease-free survival, but not overall survival. This study represents the largest to date on PSEL although it is limited by its retrospective design and the relatively small patient cohort. Nevertheless, our findings give important insight into this rare, challenging disease, and expand our knowledge base on this aggressive tumor.