Spontaneous Resorption Of A Lumbar Disc Herniation In A Patient With Multiple Myeloma: A Rare Association

Background: The phenomenon of spontaneous resorption of a herniated disc (HD) is a common occurrence. In literature, there are many studies attempting to explain the mechanism for regression, including imaging techniques and immunohistologic analyses. Nevertheless, the exact mechanism remains uncertain. In addition, the connection between HD regression and general conditions of patients is not concerned yet. Here we report a case of spontaneous resorption of a lumbar disc herniation in a patient with multiple myeloma, which had not reported before. Case presentation: An illustrative patient, a 42-year-old Chinese man, was admitted to our hospital with a disc herniation at L 5 -S 1 , experiencing 2-months history of low back pain and 1-month left leg pain. He was treated conservatively with medication and physical therapy. Then he was symptom-free after 2 months. The low back pain of the patient recurred with the herniated lumbar disc disappearing after 2 years. The disappearance demonstrated by magnetic resonance imaging (MRI). And besides, the patient was diagnosed with multiple myeloma (MM). The emergence of MM might result in the recurred backache, and the process of HD resorption might be accelerated by the high serum Vascular endothelial growth factor (VEGF) of the MM patient. Conclusions: For patients who suffering from intervertebral disc herniation together with diseases upregulating VEGF level, such as MM, surgical treatment should be limited and the conservatively treating time can be lengthened.

months. The low back pain of the patient recurred with the herniated lumbar disc disappearing after 2 years. The disappearance demonstrated by magnetic resonance imaging (MRI). And besides, the patient was diagnosed with multiple myeloma (MM). The emergence of MM might result in the recurred backache, and the process of HD resorption might be accelerated by the high serum Vascular endothelial growth factor (VEGF) of the MM patient.
Conclusions: For patients who suffering from intervertebral disc herniation together with diseases upregulating VEGF level, such as MM, surgical treatment should be limited and the conservatively treating time can be lengthened.

Background
Spontaneous resorption of herniated disc (HD) is a well-known occurrence which the herniated nucleus pulposus shrink or even disappear spontaneously without invasive therapy. A lot of similar cases have been presented ever since Guinto rst reported a case of spontaneous resorption of HD at lumbar spine in 1984, which demonstrated by computed tomography (CT) [1] . The underlying mechanism remains unclear despite the fact that numerous studies have been done by researchers. Unfortunately, most of researchers pay close attention to local situations of patients whose HDs are diminished, and the general conditions of patients are ignored [2][3][4] . In our study, the spontaneous disc resorption of a patient with multiple myeloma (MM) has been presented and the clinical signi cance has been discussed.

Case Presentation
Chief complaints A 42-year-old Chinese male patient experienced 2-months history of low back pain and 1-month left leg pain with no obvious cause.

History of past illness
The patient had a free previous medical history.

Personal and family history
He denied any other family history.

Physical examination upon admission
Neurological examination was decreased sensation of touch in the left lateral calf and was neither motor de cit nor cauda equine lesion. Furthermore, the straight-leg-raising test was positive on the left side (30°) and Knee-jerk Re ex together with Achilles-jerk Re ex was normal.

Imagingexaminations
A MRI examination of lumbar spine suggested the presence of a HD at L 5 -S 1 level on the left side and the left nerve root was seen to be compressed by the HD (Fig.1).

Preliminary diagnosis and treatment
Based on the clinical symptom Physical examination and the computed tomography nding of herniated disc at L5-S1 level, a diagnosis of lumber disc herniation was made. The patient chose to have conservative ways including physical and medical therapies and was symptom-free after 2 months.
Outcome and follow-up However, the patient returned 6 months later with the complaint of recurred low back pain, which aggravating during the night. Follow-up MRI images showed complete disappearance of the extruded HD that had been found at L 5 -S 1 level and there were many inhomogeneous MRI signals within spinal centrums (Fig.2). The patient was diagnosed with multiple myeloma (MM) according to the results of bone marrow puncture and determination of M-protein. The plasmacyte was 7.5% indicated by bone marrow biopsy, and all of them were immature (Fig.3). As the immunoreactive electrophoresis identi ed, the component of the monoclonal protein was λ light chain, and the background protein was decreased.
Besides, the 24 hours of the M protein was 1.232g and β 2 microglobulin was 3.82 mg/L.

Final diagnosis and treatment
Finally, the patient was diagnosed with multiple myeloma and resorption of the herniated disc occurred.
Patient was transferred to hematology department to accept further treatment.

Discussion
The spontaneous resorption of HD in a patient treated non-operatively is a well-documented phenomenon, which is observed at almost all spinal compartments, cervical, thoracic, and lumbar [5][6][7] .
There were 42.5% enrolled patients (68 of 160) with spontaneous regression of HD demonstrated by MRI within 2 months in the study by Autio [8] . In other researches, the occurrence of spontaneous resorption of HD was about 35%-63% over 6 months to 1 year [8,9] .
Many a theory exist to explain the mechanism behind the spontaneous regression of HD, including dehydration theory, retraction theory with the retraction of posterior longitudinal ligament (PLL), resorption theory with macrophage phagocytosis [7,10−12] . In the third theory, neovascularization of HD plays an important role in resorption process with VEGF (vascular endothelial growth factor) assistance. VEGF, a highly speci c mitogen for endothelial cell, plays an indispensable role in the formation of newborn blood vessels, containing the differentiation of angioblasts and the subsequent formation of vascular tubules [13] . Moreover, capillaries that invade the hernia are regarded as essential factors in resorption of the HD [14] . On the other hand, VEGF is an effective inducer of plasmin through plasminogen activators (PAs). Plasmin activates MMPs, which are necessary for the matrix degradation that occurs during the HD resorption process [15] . Obviously, VEGF plays a crucial role in the process of spontaneous regression of HD. It's well-known that VEGF is really highly expressed in serum of MM patients [16,17] .
Myeloma cells can directly secrete VEGF, which combing with VEGF-2 receptors, facilitating the process of new-born capillaries formation. Thus we can suppose the HD resorption process of the patient have connections, to some extent, with the high VEGF level due to MM.
Disc herniation was categorized into three types by Komori, comprising intact disc margin (type 1), discontinuous disc margin (type 2), and extrusion beyond the height of the disc (type 3) [18] . In their study, the further the HD migrated, mean type 3, the more decrease degree could be observed, and type 1 showed few or even no variation on follow-up MRI [9] . Henmi noticed that the larger the disc fragments protruded, the more they diminished [19] . Ahn considered that the exposure of HD materials to the epidural vascular supply through the ruptured PLL might facilitate the resorption progress [20] .
On the contrary, the HD in the case we performed diminished thoroughly even if it's only a medium or small size, non-sequestrated, subligamentous herniation. We can presume the abnormal phenomenon is related to the special general conditions of the MM patient, which have relatively higher level of serum VEGF.

Conclusions
The likelihood of spontaneous resorption of HD can be estimated approximately by making use of enhanced imaging together with the Komori classi cation 18 . However, for patients suffering from intervertebral disc herniation together with diseases upregulating VEGF level, such as MM, surgical treatment should be limited and the conservatively treating time can be lengthened as long as no severe neurological de cits or intractable low back and leg pain exist, even though the possibility of spontaneous resorption of HD is not high enough assessed by former methods.

Availability of data and materials
The datasets during and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.

Funding
There is no funding source.
Authors' contributions XCY is the primary author and contributed in drafting and revising the manuscript. YZW/LQ contributed to the data collection and drafting of the manuscript. XRD contributed to the conception of the article and manuscript revision. All authors read and approved the nal manuscript. Figure 1 Sagittal (A) and Axial (B) T2-weighted MRI of the lumbar spine images show a medium extruded disc herniation on the left side (white arrowhead) at the L5-S1 level (black arrowhead).