Pathogenesis of Alopecia Areata and Vitiligo: Commonalities and Differences.

Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-ß (TGF-ß), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/ß-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.

A case of trichogerminoma: a rare cutaneous follicular neoplasm.

Trichogerminoma, first described by Sau et al. in 1992, is a rare cutaneous adnexal neoplasm of the hair germ cell and usually associated with benign clinical course and favorable outcome. About 30 cases have been reported, all with similar histological features. However, due to a small but potential risk of malignancy, complete excision of the tumor is the treatment of choice. There is still controversy over its inclusion into the spectrum of trichoblastoma.Herein, we report an additional case occurring in the left buttock of a 47-year-old female, presenting with a subcutaneous solitary nodule composed of lobules of basaloid cells, with peripheral palisading and round cell nests or "cell balls" arranged in the central part. The lobules are separated by a fibrous or myxoid stroma. There are no clefts separating the tumor cells and surrounding stroma, but clefts separating stroma by the surrounding adipose tissue can be seen. Typical mitotic figures are frequently present (4-5 per 10 high-power fields). Immunohistochemistry shows the tumor cells are positive for pan-CK (AE1/AE3), CK5/6, p40, GATA 3, whereas they are negative for CK7, CK20, chromogranin A, synaptofisin, androgen receptor, estrogen receptor, and calretinin. Staining for CK20, synaptofisin, and chromogranin A detect Merkel cells scattered within the lobules. Ki67 highlights a nuclear proliferative rate of about 20%.Trichogerminoma should be distinguished from other trichogenic tumors made up of basoloid cells or hair follicular differentiation. The mainly differential diagnosis includes trichoblastoma, trichoepitelioma, tricholemmoma, and basal cell carcinoma.Herein, we report a case of trichogerminoma which, unlike the cases previously reported, showed numerous mitotic figures and a higher Ki67 nuclear proliferative rate.

Recent progress in hair follicle stem cell markers and their regulatory roles.

Hair follicle stem cells (HFSCs) in the bulge are a multipotent adult stem cell population. They can periodically give rise to new HFs and even regenerate the epidermis and sebaceous glands during wound healing. An increasing number of biomarkers have been used to isolate, label, and trace HFSCs in recent years. Considering more detailed data from single-cell transcriptomics technology, we mainly focus on the important HFSC molecular markers and their regulatory roles in this review.

Generation of Hair Follicle Germs In Vitro Using Human Postnatal Skin Cells.

Modeling organoids with hair follicle germ-like properties provides an opportunity for developing strategies for alopecia drug discovery and replacement therapy, as well as investigating the molecular mechanisms underlying human hair follicle regeneration in vitro. Hair follicle germ reconstruction in vitro is based on dermal papilla hair-inducing abilities and the plasticity of skin epidermal keratinocytes. The current protocol describes a highly efficient approach suitable for adult human skin cell applications. This method allows to obtain hair follicle germs using tissues from one donor. Isolated and cultured for 2 weeks, adult hair follicle dermal papilla cells and skin epidermal keratinocytes self-organize in hanging drop cultures generating organoids that exhibit the features of folliculogenesis onset.

The importance of basonuclin 2 in adult mice and its relation to basonuclin 1.

BNC2 is an extremely conserved zinc finger protein with important functions in the development of craniofacial bones and male germ cells. Because disruption of the Bnc2 gene in mice causes neonatal lethality, the function of the protein in adult animals has not been studied. Until now BNC2 was considered to have a wider tissue distribution than its paralog, BNC1, but the precise cell types expressing Bnc2 are largely unknown. We identify here the cell types containing BNC2 in the mouse and we show the unexpected presence of BNC1 in many BNC2-containing cells. BNC1 and BNC2 are colocalized in male and female germ cells, ovarian epithelial cells, sensory neurons, hair follicle keratinocytes and connective cells of organ capsules. In many cell lineages, the two basonuclins appear and disappear synchronously. Within the male germ cell lineage, BNC1 and BNC2 are found in prospermatogonia and undifferentiated spermatogonia, and disappear abruptly from differentiating spermatogonia. During oogenesis, the two basonuclins accumulate specifically in maturing oocytes. During the development of hair follicles, BNC1 and BNC2 concentrate in the primary hair germs. As follicle morphogenesis proceeds, cells possessing BNC1 and BNC2 invade the dermis and surround the papilla. During anagen, BNC1 and BNC2 are largely restricted to the basal layer of the outer root sheath and the matrix. During catagen, the compartment of cells possessing BNC1 and BNC2 regresses, and in telogen, the two basonuclins are confined to the secondary hair germ. During the next anagen, the BNC1/BNC2-containing cell population regenerates the hair follicle. By examining Bnc2(-/-) mice that have escaped the neonatal lethality usually associated with lack of BNC2, we demonstrate that BNC2 possesses important functions in many of the cell types where it resides. Hair follicles of postnatal Bnc2(-/-) mice do not fully develop during the first cycle and thereafter remain blocked in telogen. It is concluded that the presence of BNC2 in the secondary hair germ is required to regenerate the transient segment of the follicle. Postnatal Bnc2(-/-) mice also show severe dwarfism, defects in oogenesis and alterations of palatal rugae. Although the two basonuclins possess very similar zinc fingers and are largely coexpressed, BNC1 cannot substitute for BNC2. This is shown incontrovertibly in knockin mice expressing Bnc1 instead of Bnc2 as these mice invariably die at birth with craniofacial abnormalities undistinguishable from those of Bnc2(-/-) mice. The function of the basonuclins in the secondary hair germ is of particular interest.

A case of trichogerminoma.

Trichogerminoma is a rare neoplasm which was first described in 1992 and there is still controversy over its inclusion into the spectrum of trichoblastoma. A 79-year-old woman presented with a 5-year history of an asymptomatic nodule on the left posterior neck. Histologically, the lesion revealed a well-demarcated deep dermal nodule surrounded by a pseudocapsule. The tumor was composed of lobules with basophilic cells and some of the lobules displayed a distinctive pattern of densely packed 'cell balls' with peripheral condensation. Immunohistochemically, the tumor cells showed zonal CK5/6 immunoactivity in contrast with the negatively stained 'cell balls'. These characteristics were compatible with the diagnosis of trichogerminoma. We report here on a rare case of a hair germ tumor called trichogerminoma.

A Case of Trichogerminoma

Trichogerminoma is a rare neoplasm which was first described in 1992 and there is still controversy over its inclusion into the spectrum of trichoblastoma. A 79-year-old woman presented with a 5-year history of an asymptomatic nodule on the left posterior neck. Histologically, the lesion revealed a well-demarcated deep dermal nodule surrounded by a pseudocapsule. The tumor was composed of lobules with basophilic cells and some of the lobules displayed a distinctive pattern of densely packed 'cell balls' with peripheral condensation. Immunohistochemically, the tumor cells showed zonal CK5/6 immunoactivity in contrast with the negatively stained 'cell balls'. These characteristics were compatible with the diagnosis of trichogerminoma. We report here on a rare case of a hair germ tumor called trichogerminoma.

Pigmented Trichogerminoma: A Case Report

Trichogerminoma is a rare cutaneous adnexal tumor that dysplays differentiation toward the hair germ epithelium. This tumor was first described by Sau et al. in 1992 and it is characterized by densely packed round nests or cell balls resembling hair bulbs. Herein, we report on a deeply pigmented and sharply circumscribed nodular tumor that was excised on the abdomen of a 48-year-old woman. Histologically the tumor involved both dermis and subcutis without any epidermal connection. The main nodule was subdivided into the smaller lobules by fibrous stroma. The lobules were composed of masses of basaloid cells that displayed peripheral palisading. Within the lobules, the basaloid cells formed numerous cell balls. The tumor presented the characteristic features of trichogerminoma. Interestingly, our case was the pigmented type, which was remarkable by virtue of the heavy melanin deposits found within and around the tumor nests. To the best of our knowledge, this is the first case of pigmented trichogerminoma that has been reported worldwide.

Trichogerminoma: A case report

Though trichogenic tumors were classified as trichoblastoma, trichoblastic fibroma, trichogenic trichoblastoma and trichogenic myxoma by Headington(1970), their true classification depends upon the epithelial and mesodermal component as well as evidence of their induction. Because of the rarity of hair germ cell tumors their classification is still controversial. In this report, we describe a case of trichogerminoma which is not included in the above classification. The trichogerminoma was first described by Sau et al. in 1992 and characterized by its morphologic pattern of germinal centers and lymphoid follicle-like structures in the nests of trichoblasts. Herein we reporte a tumor which arose on the skin on the back of a 51-year-old man and presented as a sharply circumscribed mass(4.5x2.0x1.5 cm) involving both the dermal and subcutaneous tissues without any epidermal connection. The tumor had many germinal center-like structures in the basaloid trichoblasts. Lobular cell nests were separated by variable amounts of stroma, but no horn cyst were noted. The germinal center-like cells showed early differentiation of hairs, resembling early hair bulbs. Trichogerminoma is considered to be a type of tumor located between trichoblastoma and trichoblastic fibroma.

Morphological Observations on the Hair Development of Human Fetal Skin

The developing process of the hair of the fetal skin was studied. The ages of 103 human embryos and fetuses ranged from 4 to 40 gestation weeks. Ten different sites were selected, i.e., scalp, forehead, cheek, chest, abdomen, back, palm, sole, finger and toe. For the embryos 3 sites were studied, i.e., cephalic, trunk, and caudal portions. Following results were made: 1) The primitive hair germ was first noted the 10th week in the face skin as nubbins of mesenchymal cells beneath discrete foci of crowdes, elongated germinative epithelial cells. The developing hair germs and hair pegs were observes at the cephalic portion by 11 weeks. At 15 weeks the hair pegs including hair germs were noted in the trunk skin. The bulbous hair peg stage started at the 16th week in the cephalic portion and at the 18th week in the trunk. 2) Relative number of fetal hairs progressively increase up to 20 weeks of gestation but, thereafter decreased although it was different by the site of the body. 3) The diameter of fetal hair follicles increased with fetal age to the term with slight difference by the portion of body. 4) The developmental process of hair was more rapid in the cephalic portion than the trunk in views of morphologic changes of the hair structures, number and diameter of hair follicles.