S Kotwal, H Mohan, R Bahadur, A Bal
S Kotwal, H Mohan, R Bahadur, A Bal. A Clinicopathological Study Of Changes In Intervertebral Discs. The Internet Journal of Pathology. 2002 Volume 2 Number 2.
OBJECTIVES: To identify the most important histomorphological indicators of disc degeneration by comparing with asymptomatic control intervrtebral discs (IVD) from cadavers; highlight the magnitude of symptomatic degenerative disc disease (DDD) compared to other spinal diseases resulting in surgical excision of IVD; study the utility of grading system to analyse the degenerative changes.
DESIGN: Surgically excised intervertebral discs from 100 patients were studied by histomorphology aided with histochemistry. This included patients with prolapsed IVD due to degenerative causes, tuberculosis spine and trauma. Ten control IVD removed at autopsy were studied for comparison. Based on histomorphology and histochemistry, the four features viz. matrix depletion, matrix fibrillation, chondrocyte cloning and edge neovascularisation were graded; the grades were added for study and control cases to represent a score.
RESULTS: Degenerative causes accounted for 67% of cases indicating this as the leading cause of disc excision. Edge neovascularisation and chondrocyte cloning were nearly absent in controls in contrast to study group. Mean scores of the histological features were the highest in the degenerative causes of intervertebral disc prolapse (IVDP).
CONCLUSIONS: Chondrocyte cloning and edge neovascularisation are more specific indicators of degeneration. Edge neovascularisation, though labelled a specific indicator of prolapse due to DDD, has low percentage positivity.
Progressive degenerative changes in the spine start in 3rd decade with first manifestations occurring in the intervertebral disc (IVD) followed by changes in the bone and articular cartilage.1 The IVD transmits load hydrodynamically from one vertebra to the next. If normal intradisc pressure exists in standing position, a forward flexion or stooping increases it by as much as 400%2. In a disc in the young, the water content of nucleus pulposus (NP) is 85% and that of annulus fibrosus (AF) is 78%. Decreased imbibing capability due to loss of negatively charged proteoglycans leads to a fall in water content to 70% in both tissues. The pathoanatomical and biochemical alterations in IVD with aging and/or degeneration, disturb structural integrity and impair function. Symptoms can arise at any unpredictable point along the continuum of degenerative changes. Also symptoms due to senescence versus pathologic processes can be very difficult to differentiate.3 Excision of IVD is frequently done in symptomatic cases not responding to conservative treatment, and curetted disc material is sent for histopathologic assessment. A macroscopic grading system given by some workers is difficult to apply as we do not have access to the entire disc.4 Histopathologists do mention about presence of the various morphological parameters, but rarely do they agree on the degree of changes.
In the present study our aim was to study the histological changes in the spectrum of conditions leading to disc excision in 100 consecutive cases, with a focus on degenerative causes of prolapse as this forms a major category. The alterations will be compared to asymptomatic control discs. Histomorphology aided by histochemistry is used to delineate important indicators of disc degeneration. The utility of a grading system to analyse degenerative changes will be discussed so as to assess its predictive value.
Materials And Methods
One hundred consecutive specimens of IVD excision done for symptomatic, radiologically evaluated patients and sent for histopathological examination formed the study group. Ten IVDs removed at autopsy from patients dying of causes unrelated to spinal or disc disease formed the control group.
The entire volume of the material sent was processed and fixed in 10% neutral buffered formalin, dehydrated in graded ethanol/water mixtures, cleared in xylene, embedded in paraffin and stained by hematoxylin and eosin to study morphology. In addition representative sections were stained with toluidine blue5 and safranin O6 to illustrate the proteoglycan content of extracellular matrix and van Gieson stain to highlight fibrillation. Histologic features selected for grading degeneration in the two groups were: matrix depletion(
The grades of all the four features were added to obtain a score for study as well as control group which would range from 0 to 12. Scores were analyzed to give a meaningful interpretation of degenerative changes. The grades of histological features of study group were compared to those of control groups by analysis of variance (ANOVA).
There was a wide age range of patients undergoing disc excision ranging from 18 to 75 yrs. (mean age 43.21 yrs.). Maximum patients were in their 4th decade (39 patients, 39%) followed by 5th decade (25 patients, 25%). Very few patients were seen at extremes of age groups i.e. 4% (4 cases) in 2nd decade and 6% (6 cases) in seventh decade. Control cases were equally divided in 4th and 5th decades of life. Out of 100 patients, 62 were males and 38 females. In general, males were predominantly represented in all age groups, with maximum sex difference being in 4th decade (males 29, females 10; M:F =3:1).The commonest presenting symptom was low back ache seen in 40% cases of study group.
Microscopic features were as follows (Table II):
Figures in parenthesis indicate mean grade of parameters in each group.
Based on clinical profile, the study group was divided into 4 categories: degenerative disc disease (DDD) with intervertebral disc prolapse (IVDP), lumbar canal stenosis (LCS) with IVDP, tuberculosis spine and trauma. The score range and mean calculated in each category are given in Table III.
(*DDD- Degenerative disc disease; ** LCS- Lumbar canal stenosis)
Depletion and fibrillation of matrix were seen both in study and control group with no significant difference. Thus it is important to analyse the frequency of the other two microscopic parameters,
Table IV highlights the significantly higher positivity of
The IVD excised were from lumbar, dorsal and cervical regions. Correlating clinicopathological diagnosis with spinal levels, IVD from lumbar region is affected maximum (79%). DDD in 93.5% cases affected the IVD from lumbar region. Also LCS with IVDP had all (100%) cases at lumbar levels.
Figures in parenthesis indicate the mean grade of Cc and En in each category
( p<0.05, ANOVA test). Total score was the most reliable parameter with
Out of the 100 patients constituting the present study, 67 belonged to the degenerative categories (59 from DDD and 8 from LCS with disc prolapse). Thus degenerative causes of disc excision constituted 67% of study cases, a fairly high percentage to demand focus on this entity. A few previous studies9,10 involved purely IVDP caused by degeneration and do not mention the magnitude of DDD vis-à-vis other spinal diseases leading to discectomy. By studying 100 consecutive cases, other causes for IVDP identified were tuberculosis spine and trauma.
Stenosis or narrowing of the vertebral canal with IVDP due to degeneration will cause signs of neurovascular compression earlier in a narrow or asymmetrical canal. Adult IVD lacks blood supply and blood-borne infections are extremely rare.12 In India, tuberculosis of the spine is common and surgically excised tissue from the involved spine often includes IVD. Trauma has unequivocally shown to produce acute prolapse; the main cause of disc prolapse being degeneration. In the present study, 15% had antecedent trauma causing prolapse, including 6% having accompanying fracture vertebrae indicating severe intensity of trauma.
Males constituted 62% of total cases and 62.9% of DDD patients. This is explained by higher exposure of males to physical back strain13. Butler et al14 stated that lumbar IVDs are more frequently affected due to their position at lordotic apex. In our study, low back ache (LBA) was the presenting symptom in 40% of study cases. 82% of total cases and 93.5% cases of DDD were from the lumbar region.
The upper value in the range of scores was higher in the degenerative categories i.e. DDD with IVDP and LCS with IVDP. The score was lower in tuberculosis and trauma cases which was largely due to
Analysing the histopathological changes in the disc tissue, it has been emphasized in literature that distinction between the two components of IVD- nucleus pulposus (NP) and annulus fibrosus (AF), is purely histomorphologic i.e. areas showing chondrocytes were in NP and those showing predominantly collagen fibres were in AF. On hematoxylin and eosin, proteoglycan depletion in extracellular matrix can be seen as an area showing pallor of eosinophilic staining of matrix. This can be recognised better as well as graded by the use of specific stains like safranin O or toluidine blue, both of which show lack of staining in the region of matrix depletion. We used both these stains to highlight loss of proteoglycans so that early and subtle changes of degeneration can be identified and graded.
Histological features specific to tuberculosis (i.e. epithelioid cell granulomas and caseation necrosis) were essentially present in the marrow spaces and soft tissue adjoining IVD. The disc tissue here only showed age-related changes i.e.
IVD excised for trauma too showed age related changes.
Harsh Mohan Professor & Head, Department of Pathology, Government Medical College, Sarai Building, Sector-32-A, Chandigarh- 160047, INDIA. Tel No. (+91) 172-665253 Ext. 1050, 1055 E-mail: email@example.com