Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight loss, shortness of breath, palpitations, and feeling faint with standing. In AL amyloidosis, specific indicators can include enlargement of the tongue and periorbital purpura. In wild-type ATTR amyloidosis, non-cardiac symptoms include: bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, small fiber neuropathy, and autonomic dysfunction.There are about 36 different types of amyloidosis, each due to a specific protein misfolding. Within these 36 proteins, 19 are grouped into localized forms, 14 are grouped as systemic forms, and 3 proteins can identify as either. These proteins can become irregular due to genetic effects, as well as through acquired environmental factors. The four most common types of systemic amyloidosis are light chain (AL), inflammation (AA), dialysis-related (Aβ2M), and hereditary and old age (ATTR and familial amyloid polyneuropathy).Diagnosis may be suspected when protein is found in the urine, organ enlargement is present, or problems are found with multiple peripheral nerves and it is unclear why. Diagnosis is confirmed by tissue biopsy. Due to the variable presentation, a diagnosis can often take some time to reach.Treatment is geared towards decreasing the amount of the involved protein. This may sometimes be achieved by determining and treating the underlying cause. AL amyloidosis occurs in about 3–13 per million people per year and AA amyloidosis in about 2 per million people per year.
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.