MASC is a rare clinical scenario, occurring in only 0.1 to 3.3% of patients with non-Hodgkin’s lymphoma . In our cohort, MASC was found to occur in 2.21% of patients with DLBCL. Moreover, two patients (Patients 8 and 11) in our cohort did not receive any treatment until 2 weeks after the neurological deficit occurred. Since DLBCL is a malignancy with rapid tumor proliferation, spinal cord compression may occur within weeks of the onset of MASC. Early and correct diagnosis is therefore an important issue in DLBCL patients with MASC, and magnetic resonance imaging, which has an accuracy of 95% (sensitivity 93%, specificity 97%) , should be performed early and correctly when DLBCL patients have any symptoms or signs associated with spinal compression.
To further understand whether surgical decompression was the best treatment for complete restoration of neurological function in DLBCL patients with MASC, we compared the complete neurological deficit recovery rate between patients who received surgical decompression and those who did not. Results showed that all of the patients who received surgical decompression had complete abrogation of their neurological dysfunction (100%, 6/6). On the contrary, only 20.0% (1/5) of the patients who did not receive surgical decompression recovered. These data suggest that even though DLBCL is highly sensitive to both chemotherapy  and radiotherapy , immediate surgical decompression was the cornerstone for improving neurological deficit in DLBCL patients with MASC. Delayed treatment for patients in the nonsurgical group in our cohort, however, could be one of the factors affecting this result. Although it was not statistically significant, patients who received surgical decompression seemed to have a shorter time from symptom onset to spinal compression treatment than those who received nonsurgical intervention (3.5 days vs. 10.8 days; Table 2). Unfortunately, this delay is unavoidable because pathological proof always takes time. In addition, the pretreatment ASIA scores in patients who did not receive surgical intervention seemed worse, which could be another possibility responsible for the superior neurological deficit recovery in patients who received immediate surgical decompression. Because one of the five patients in the nonsurgical group exhibited complete recovery, further investigation is still required to determine whether surgical decompression should be applied to all DLBCL patients with spinal cord compression.
One factor that may provide some clues for the assessment of the utility of surgical decompression is the spine instability neoplastic score proposed by the Spine Oncology Study Group. These scores were established through systemic reviews to determine which patients harbor high risk of spinal instability and are in need of surgical treatment . In this classification system, six components of spinal instability – including spine location, mechanical pain, bone lesion quality, spinal alignment, vertebral body collapse, and posterolateral involvement of spinal elements – are used in the risk score calculation. Patients with a score ≥7 are considered candidates for surgical intervention. Because this scoring system was initially established for MASC resulting from solid malignancies, such as cancers of the breast, prostate, and lung, its application to DLBCL patients with spinal cord compression remains uncertain and further validation is needed. However, this question will not be answered until more studies examining DLBCL-associated spinal cord compression in larger cohorts are available.
Since patients receiving surgical decompression had a better chance to completely abrogate their neurological deficit, we further investigated whether surgical decompression could have an additional positive impact on patient survival. Our results suggest that surgical decompression may result in superior overall survival of DLBCL patients with spinal compression, even though statistical significance was lacking. This result is in contrast to the findings of a study conducted by Peng and colleagues that showed the 5-year overall survival rates for patients with primary non-Hodgkin's lymphoma of the spine with neurological compression in surgical and nonsurgical groups were 60% and 100%, respectively . More well-designed clinical trials will therefore be required to clarify this controversial conclusion.
To strengthen our conclusion that surgical decompression provided patients of DLBCL-associated spinal cord compression with an improved chance of survival by eliminating the neurological deficit, we analyzed the impact of complete recovery from neurological deficit on these patients’ survival. Our data showed that even though statistical significance could not be reached, there was an obvious trend toward better overall survival in DLBCL-associated spinal cord compression patients who completely abrogated their neurological deficit. From this result, we suggested that decreases in comorbidities associated with spinal cord compression, such as cardiopulmonary dysfunction , poor infection control , and psychological problems , could play an important role in the superior overall survival observed in patients with DLBCL-associated spinal cord compression who received surgical decompression.
Another issue surrounding the prediction of prognosis in DLBCL-associated MASC patients was raised by this study. Currently, the International Prognosis Index – which takes into account age, disease stage, extent of extra-nodal involvement, performance status, and serum lactate dehydrogenase level  – is widely used for risk classification in patients with DLBCL. However, International Prognosis Index scores could not precisely predict survival in our cohort (data not shown), possibly due to an invalid staging system and performance status evaluation. According to the Ann-Arbor staging system, the disease was classified as stage IV if the spine was not the primary site. However, it was difficult to distinguish primary spinal DLBCL from DLBCL with spinal involvement but other primary sites. In addition, patients with the involvement of multiple spinal segments were also defined as stage IV, regardless of whether there was an absence of closely associated or distant lymph node involvement. According to these staging criteria, only stage I and stage IV disease were present in our cohort. Moreover, the evaluation of performance status in patients with DLBCL-associated spinal cord compression may be imprecise. According to Eastern Cooperative Oncology Group performance status evaluation criteria, a patient is classified as grade 3 if they are capable of only limited self-care, and are confined to a bed or chair for more than 50% of waking hours. However, the neurological deficit of DLBCL-associated spinal cord compression patients could cause them to be bed-ridden at diagnosis, resulting in an underestimated performance status. This underestimated performance status can further lead to an imprecise International Prognosis Index score, causing it to be inferior to the true score. To compensate for the effects of invalid staging system and performance status evaluation, a modified prognostic prediction system specific to patients with DLBCL-associated spinal cord compression should be developed.
The major limitations of this study were the small study cohort and its retrospective nature. Because of the small cohort, we were unable to validate the spine instability neoplastic score specific to DLBCL patients with MASC. We were also unable to establish a revised International Prognosis Index score to identify the risk classification in DLBCL-associated spinal cord compression patients. In addition, although six to eight cycles of CHOP or CHOP-like regimens were sequentially delivered to all the patients in our cohort as the standard treatment for DLBCL, the roles of rituximab and radiotherapy on patients in our cohort were not evaluated due to the retrospective nature of this study.