Calcium pyrophosphate crystal deposition in the ligamentum flavum of degenerated lumbar spine: histopathological and immunohistological findings

Abstract

We investigated the histological and immunohistochemical features of degenerative changes in the ligamentum flavum of the lumbar spine with calcium crystal deposition. We investigated degenerative changes in 270 ligamentum flavum specimens harvested from 198 patients who underwent decompressive surgeries for lumbar spinal canal stenosis. En bloc sections of the ligamentum flavum were examined histologically. We also examined immunoreactivity for transforming growth factor (TGF)-beta, vascular endothelial growth factor (VEGF), CD34, and CD68; immunoblot analysis for VEGF; and terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end-labeling (TUNEL) method. The ligamentum flavum showed fragmented and disorganized elastic fiber bundles with increased collagen fibrils in the matrix. Calcium deposition, which was identified as calcium pyrophosphate dihydrate crystals, was evident in 72 of 198 patients and in 99 of 270 samples, and was associated with appearance of hypertrophic chondrocytes and new blood vessel formation. Areas of calcium deposits were surrounded by abundant hypertrophic chondrocytes (with marked immunoreactivity to TGF-beta and VEGF) and a significant number of TUNEL-positive chondrocytes. Calcium crystal deposition in the lumbar ligamentum flavum progresses with reduction in elastic fibers and accumulation of collagen fibrils in the matrix as well as expansion of chondrometaplastic areas.

Calcium pyrophosphate dihydrate deposition disease of the filum terminale

“…Matrix mineralization, changes in the constitution of proteoglycans, secretion of amorphous materials and proteoglycans by hypertrophic chondrocytes are some of the more frequent hypotheses described in the literature [11]. The focal occurrence of CPPD on the filum terminale may hardly be explained by one of those theories, even if we consider the fibrous component of the filum.…”

“…More recently, Yayama et al [11] analysed a series of consecutive patients undergoing decompressive laminectomy spinal stenosis with no history and/or evidence of genetically bound bone, joint, or muscolo-ligamentous tissue abnormalities and who had not taken specific therapeutic agents such as corticosteroids or immunosuppressants and reported CPPDCD in the ligamentum flavum in 36 % of patients. This study does not report any consideration on the surgical success rate (this was not the purpose of the study).…”

“…At present, the specific mechanism underlying the formation of CPPD deposits remains unknown [3,11]. Matrix mineralization, changes in the constitution of proteoglycans, secretion of amorphous materials and proteoglycans by hypertrophic chondrocytes are some of the more frequent hypotheses described in the literature [11].…”

Progressive thoracic myelopathy caused by spinal calcium pyrophosphate crystal deposition because of proximal junctional vertebral compression fracture after lumbopelvic fusion

“…Yayama et al [20] investigated the histological and immunohistochemical features of degenerative changes in the LF with CPPD crystal deposition. Based on the histopathologic analysis, they postulated that rupture of elastic fiber bundles was the first change to occur in degeneration of the LF.…”

Ligamentum flavum hematoma in the lumbar spine

“…Some mechanisms have been proposed to explain the development of LFH. The most current mechanism is that there must have been internal disruption of the ligament itself, that is, intra-ligamental bleeding may occur because of a partial tear in a degenerative ligament [24,28]. Another candidate mechanism is that the bleeding in the facet joint flows out into the degenerated ligamentum flavum and forms a hematoma in it, because the LFH is connected with the facet joint intraoperatively [5].…”