Degenerative disc disease can lead to a chronic debilitating condition and can have a serious negative impact on a persons quality of life. When pain from degenerative disc disease is severe, traditional nonoperative treatment may be ineffective. Cause
There is a disc between each of the vertebrae in the spine. A healthy, well-hydrated disc will contain a great deal of water in its center, known as the nucleus pulposus, which provides cushioning and flexibility for the spine. Much of the mechanical stress that is caused by everyday movements is transferred to the discs within the spine and the water content within them allows them to effectively absorb the shock. At birth, a typical human nucleus pulposus will contain about 80% water. However natural daily stresses and minor injuries can cause these discs to gradually lose water as the annulus fibrosus, or the tough outer fibrous material of a disc, weakens. Because degenerative disc disease is largely due to natural daily stresses, the American Academy of Orthopaedic Manual Physical Therapists have suggested it is not truly a "disease" process.This water loss makes the discs more flexible and results in the gradual collapse and narrowing of the gap in the spinal column. As the space between vertebrae gets smaller, extra pressure can be placed on the discs causing tiny cracks or tears to appear in the annulus. If enough pressure is exerted, it is possible for the nucleus pulposus material to seep out through the tears in the annulus and can cause what is known as a herniated disc.
The histopathology of anogenital and ectopic papillary hidradenomas are similar to each other. Immunohistochemistry
Immunohistochemical analyses of anogenital papillary hidradenoma tumors have detected the expression of both the estrogen and progesterone receptors in 18 and the androgen receptor in 4 of 20 cases. In another study of anogenital papillary hidradenomas, expression of the estrogen receptor was restricted to the tumors glandular epithelial cells while the tumors myoepithelial cells expressed tumor protein p63 and alpha-smooth muscle actin protein. Presence of the estrogen and progesterone receptors may underlie the female prevalence of anogenital papillary hidradenomas as well as their development in females only after puberty. The anogenital tumor cells may also express vimentin, various cytokeratin proteins, and in a minority of cases the DNA of human papillomavirus (infection by this virus and the presence of its DNA does not appear involved in the development of papillary hidradenoma). These immunohistochemistry findings have not as yet been reported in atypical papillary hidradenomas. Gene and signaling pathway abnormalities
Several studies have reported the presence in anogenital papillary hidradenoma tumor cells of mutations in one or multiple genes that lead to the production of proteins that directly or indirectly stimulate the PI3K/AKT/mTOR intracellular signaling pathway. The mutated genes include PIK3CA, AKT1, PIK3CA, MAGI1, SYNE1, USP9X, KLNI (also termed CASC5), RNF213, FLCN, PDGFRB, AR (i.e. the androgen receptor gene), BTK, MLL3, KAT6A, BRD3, EP400, TET2, IL6, and IL7R. The PI3K/AKT/mTOR pathway promotes the grow (i.e.