Papillary hidradenoma

In a review of 264 women diagnosed with anogenital papillary hidradenomas, patients ranged in age from 25 to 82 years (median: 49 years); in 25 cases where the information was available, the tumors had been present for 2–120 months (median: 12 months) with 13 patients reporting their tumor's presence for less than 1 year before diagnosis. All patients had a solitary tumor in the anogenital area except for one patient who presented with four clustered tumors. Most tumors involved the vulva (71.6%) and areas around the anus (14%) or space between the anus and vulva, i.e. the perineum (3.8%). Their lesions ranged in size from 0.2 to 2 centimeters (cm.) in largest dimension (median: 0.7 cm.). in women of Caucasian origin between the ages of 25–66 years. While usually symptomless, patients may complain that the tumor is ulcerated, bleeds, or is painful. This pain may be simple tenderness, more or less constant but usually mild, or, in females with anogenital lesions, dyspareunia. The rare cases of ectopic papillary hidradenoma in the external auditory canal have presented with unilateral conductive hearing loss sometimes associated with ear pain, drainage of ear fluid, or weakness of a facial muscle(s). ==Histopathology==

Microscopic histopathological analyses of papillary hidradenoma tumors typically reveal a nodule in the dermis, i.e. layer of skin between the epidermis and subcutaneous tissue. The tumor consists of complex patterns of interconnecting tubular and papillary (i.e. thin finger-like or frond-like) structures. These structures are lined with glandular epithelial and myoepithelial cells. The glandular epithelial cells appear to be excessively proliferating in the ducts leading to the epidermis and show oxyphilic changes, (i.e. cytoplasm filled with large mitochondria, glycogen, and ribosomes) while the myoepithelial cells often appear clear cell-like, i.e. have uncolored cytoplasm when stained with hematoxylin and eosin. The histopathology of anogenital and ectopic papillary hidradenomas are similar to each other. Image: Papillary hidradenoma - intermed mag.jpg | Intermediate magnification Image: Papillary hidradenoma - very high mag.jpg | Very high magnification ==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. proliferation) and survival of cells and is abnormally activated in, and appears to contribute to the development and or progression of, a wide range of tumors. While further studies are needed, these findings suggest that the cited mutations lead to stimulation of the PI3K/AKT/mTOR pathway and thereby promote the development and/or progression of anogenital papillary hidradenoma in the majority of cases. These abnormalities have not yet been reported in ectopic papillary hidradenomas. ==Diagnosis==

The diagnosis of anogenital papillary hidradenoma lesions, while often suggested based on their clinical presentations, must be differentiated from a wide range of other similarly presenting anogenital lesions such as hemorrhoidal disease, anorectal abscesses, virus-related wart-like lesions, sebaceous cysts, mucous cysts, lipomas, neurofibromas, metastatic carcinomas with papillary histopathology, syringocystoadenocarcinoma papilliferum (i.e. malignant syringocystadenoma papilliferum), However, some cases diagnosed as ectopic papillary hidradenomas, particularly those occurring in men, have subsequently been found to be syringocystadenoma papilliferums or trichoepitheliomas. Further studies are required to better define the criteria for ectopic papillary hidradenomas. ==Treatment and prognosis==

The treatment of choice for anogenital and ectopic papillary hidradenomas, regardless of their locations, is similar: resection of the tumor while preserving the surrounding structures. It is not clear that these cases actually represent true progression of papillary hidradenoma into a cancer. == See also ==