Although there have been many experimental studies on disc material - mostly post-mortem tissue samples in animal experimental models - and some investigations on human post-mortem cohorts, little information on the quantitative amount of histomorphological changes in surgical material is available. Several histological studies [33–36] have shown the occurrence of granulation tissue with an abundant neovascularisation as a hallmark of prolapsed and protruded disc material. Weidner et al.  stated that the occurrence of edge neovascularisation is a reliable histological clue that intervertebral disc prolapse has occurred. However, this has been refuted by several authors as no significant differences were seen between sequestered and non-sequestered material with respect to neovascularisation in these studies [24, 37]. Other studies have focussed on the composition of the herniated material, which has been the subject of several histological studies [19–21, 23, 25, 38]. The results of these studies are conflicting with different statements about the composition of herniated material (annular, nuclear and endplate). These contradictory observations may partly result from different histological criteria used for the distinction between nuclear and annular tissue. Few of these studies [19, 20, 25] have correlated the histological composition of the herniated disc material with clinical outcome. While some authors did not find any correlation between histological composition and clinical outcome [19, 25], others found an association with increased pain intensity and clinical outcome . Furthemore, there is an ongoing widely unresolved dispute  concerning the interplay of the different intervertebral disc compartments in the process of disc degeneration and sciatica. Especially the discussion concerning the chronology of observed disc alterations, such as weakening of the annulus fibrosus with secondary degeneration of the nucleus pulposus or synchronous degeneration of both compartments or vice versa is still under examination [26, 40, 41].
The scope of our investigation was the assessment of histological alterations of disc tissue in routine pathology on the basis of a specialized histologic degeneration score (HDS) [31, 42]. Although we examined surgical - mostly fragmented - disc material, we were able to establish a HDS in all available cases. In accordance with previous investigations [31, 32, 42], we found similar results concerning the occurrence of histological changes in the different disc compartments with more pronounced changes in the nucleus pulposus. We are aware of the fact that the allocation of the scoring system (initially developed for whole intervertebral discs) to surgical material might lead to some imprecision. Some of the assessed factors are weighted to different degrees, for instance granular changes could be underestimated due to "wash out" effects and on the other hand, tears and clefts could be overestimated due to the mostly fragmented character of the specimens. However, both the present study as well as previous evaluations [31, 42] for example in a post-mortem analysis and a small surgical specimen study  strongly supports the notion that the HDS can also be applied to surgical tissue in a reliable manner. The only slight modification that had to be taken into account covered few criteria that cannot be evaluated in a safe and reliable manner in the fragmented surgical tissue, such as rim lesions or necrosis.
This is, to our knowledge, the first study which demonstrates a significant correlation between the extent of the histologic degeneration score (HDS) and the pre-operative BMI. Previous investigations [43–60], which were mainly based on radiological criteria, showed heterogeneous results although the majority [44–51, 54, 58–60, 60, 61] favours obesity or increased BMI as a risk factor. Interestingly, despite our extensive literature review, we could not find any study that takes the amount of histopathological changes in the surgical excised material into account, possibly because of a missing classification system.
Although genetic and epidemiologic studies in the past provide some evidence for a hereditary background [5, 8, 9, 13, 62–65], several occupational or lifestyle related potential risk factors have been identified [46, 66–69]. Even though the assessment of this epidemiologic data is difficult and the results of these surveys are partially controversial, there is a strong belief that obesity plays an important role [4, 44, 47, 51, 54, 60, 61, 66, 70] among the potential risk factors. From a biomechanical point of view, mechanical overstraining is sufficient to explain the possible association to LPB or disc degeneration. We fully agree with the point that biomechanics plays a role in disc degeneration, but from our experience [32, 42, 71], there might be another - perhaps more important - influence in terms of a dysregulation of the metabolic and immune system . For example obesity, insulin resistance and type 2 diabetes are closely associated with chronic "inflammation" and characterized by an abnormal cytokine production and activation of a network of inflammatory signalling pathways, e.g. leading to an overexpression of TNF-α in the tissue of obese humans [73, 74]. Interestingly, there is substantial evidence [32, 42, 71, 75–79] that inflammatory cytokines play a significant role in the process of accelerated disc degeneration. One might speculate that obesity could possibly influence the process of disc degeneration through two - perhaps synergistic - pathways. Disc degeneration is a multifactorial process involving both environmental and genetic factors, synergistic effects have already been shown in a gene-environment interaction by Solovieva et al. .
Why should we classify histological changes in excised disc material? There is a substantial bulk of literature [27, 29, 30, 80, 81] suggesting that routine histopathological examination of disc specimen is not justified for reasons of cost effectiveness. However, taking the results of the present study into account, we provide clear evidence that the determination of the histologic degeneration score (e.g. by the HDS) in the clinical setting is reliable and feasible with regard to its requirements (personnel, equipment), work load and costs and thus presents important data on the constitution of the sample. This morphological data might be of importance because it possibly allows an inference about the status of disc degeneration in the remaining intervertebral discs. Secondly, the evaluation of histo-degenerative changes in the excised disc material serves as a document for medicolegal purposes and quality control.
Finally, future therapeutic consideration, for example by selective inhibition of inflammatory cytokines or cell based transplantation therapies, will require a morphologic rationale for those therapies. In these cases, detailed information about the current status of intervertebral disc tissue might be mandatory to choose the right therapeutic options.