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Journal of the American Academy of Dermatology : JAAD 86(3), 640-642 (2022). doi:10.1016/j.jaad.2021.02.009, Published by Elsevier, Amsterdam [u.a.]

Stem cell-based therapies are expected to have a great impact on the medicine of the 21st century. The focus of dermatologic stem cell research is on the epidermis and the hair follicle. In contrast, the characterization of stem cells in the mesenchymal compartments of the skin has largely escaped the attention of the dermatologic community. This is surprising because the dermis may represent a larger reservoir for adult stem cells than the epidermis and the hair follicle together. In 2001, mesenchymal stem cells residing within the dermis were first isolated. They have the capacity to differentiate into adipocytes, smooth muscle cells, osteocytes, chondrocytes, and even neurons and glia as well as hematopoietic cells of myeloid and erythroid lineage. The perifollicular connective tissue sheath and the papilla crystallize as the likely anatomic niche for these multipotent dermal cells. These previously unidentified mesenchymal stem cells have the potential to function as an easily accessible, autologous source for future stem cell transplantation. Potential therapeutic applications include the treatment of acute and steroid-refractory graft-versus-host disease, systemic lupus erythematosus resistant to currently available therapies, or idiopathic pulmonary fibrosis. The neuronal differentiation potential of cutaneous mesenchymal stem cells may also be exploited in the treatment of neurodegenerative disorders. The most immediate impact can be expected in the field of wound healing. In line with the cancer stem cell hypothesis, the potential contributions to dermatopathology include a conceptual understanding of mesenchymal skin-based neoplasms as evolving from a genetically altered dermal stem cell clone.

Background Whereas keratinocytic bulge stem cells are well characterized, comparably little is known about cutaneous mesenchymal stem cells. The follicular connective tissue sheath is proposed as a niche for dermal stem cells. Objective Because the neuroepithelial stem cell marker nestin represents a marker for mesenchymal stem cells in various tissues, our aim was to characterize its spatiotemporal expression pattern in the skin with special reference to the follicular mesenchyme. Methods We studied immunohistochemically nestin expression over the course of human cutaneous embryogenesis, in postnatal skin, in scalp wounds, and in the peritumoral stroma of basal cell carcinomas and compared its expression with that of other known mesenchymal markers. Results Nestin is expressed throughout the entire early embryonic dermis but confined later during development to the follicular connective tissue sheath, where it can also be found in postnatal human hair follicles. Its expression is up-regulated in scalp wounds and the nestin-positive cells seem to originate from the follicular mesenchyme. Nestin is also expressed in a thin layer of fibroblasts in the immediate vicinity of basal cell carcinomas. Limitations The examination for nestin expression of scalp wounds is considered preliminary, because we examined scalp wounds representing re-excisions of previously diagnosed neoplasms from which we had no exact time table available as to when the original excision took place. Conclusion We propose that nestin functions as a stem cell marker of the follicular mesenchyme and has a major regulatory role in dermal homeostasis, cutaneous neovasculogenesis, and tumor stroma development.

Background Trichoadenoma is a rare benign follicular tumor first described by Nikolowski 50 years ago. Both trichoadenoma and desmoplastic trichoepithelioma are composed of cords of epithelial cells and cornifying cysts embedded in sclerotic stroma. In trichoadenoma the cystic component predominates, while desmoplastic trichoepithelioma is a mostly solid neoplasm. Therefore trichoadenoma was suggested to represent a cystic variant of desmoplastic trichoepithelioma. Objective The aim of this study was to investigate whether the morphologic overlap between trichoadenoma and desmoplastic trichoepithelioma translates into a similar immunohistochemical profile. Methods We studied 19 trichoadenomas and 21 desmoplastic trichoepitheliomas for cytokeratin 20, Ber-EP4, and androgen receptor expression. Results Eighteen of 19 trichoadenomas and all desmoplastic trichoepitheliomas demonstrated the presence of Merkel cells as detected by a monoclonal antibody against cytokeratin 20. In contrast, while all desmoplastic trichepitheliomas were positive for Ber-EP4, only 4 of 19 trichoadenomas showed any kind of reactivity for this marker. None of the trichoadenomas or desmoplastic trichoepitheliomas expressed androgen receptor. Limitations This study is limited by the moderate number of these rare tumors available for immunohistochemical analysis. Conclusion Our data demonstrate that trichoadenoma typically retains cytokeratin 20–positive Merkel cells but lacks Ber-EP4 and androgen receptor expression. Trichoadenoma is a distinct follicular tumor related but not identical to desmoplastic trichoepithelioma.

Background Basal cell carcinoma (BCC) is still viewed by many dermatologists as a tumor of the interfollicular epidermis, although references were made early in the dermatopathologic literature to the resemblance of BCC to the hair follicle. Objective Our aim was to characterize the common expression pattern for the epithelial cell adhesion molecule (Ep-CAM) in BCCs, various stages of follicular embryogenesis, and adult hair follicles and, thereby, in analogy point to the similarity between BCC and the hair follicle. Methods We studied immunohistochemically 16 superficial BCCs for Ep-CAM and compared the expression pattern with that during hair follicle, nail, and eccrine gland development in human embryos and fetuses. In addition, we examined terminal scalp and vellus hair follicles. Results All BCCs expressed Ep-CAM similar to the early stages of the embryonic human hair follicle, the secondary hair germ, and the outer root sheath of the vellus hair follicle. The embryonic nail organ and the adult anagen hair follicles were completely negative. Limitations The conclusions are based on the similarity in the immunohistochemical expression profile for a single adhesion molecule. Conclusion BCC expresses the cell-cell adhesion molecule Ep-CAM similar to the embryonic hair germ, the secondary hair germ of the terminal hair follicle, and the outer root sheath of the vellus hair follicle. We suggest that this may be a clue to the adnexal nature of BCC and propose that BCC is the most primitive follicular tumor.

Granuloma annulare perforans limited to a thoracic dermatome that was previously involved by herpes zoster occurred in a 51-year-old woman who also had Lennert's lymphoma. Of the various local granulomatous infiltrates described after herpes zoster, granuloma annulare perforans is unique, although ordinary granuloma annulare has been described in a few patients. A high incidence of specific and nonspecific reaction patterns in herpes zoster scars has been described in patients with malignant lymphoma. In contrast to previous patients, all of whom had chronic lymphatic leukemia, our patient had Lennert's lymphoma.

Basal cell carcinoma (BCC) is still viewed by many dermatologists as a tumor of the interfollicular epidermis, although references were made early in the dermatopathologic literature to the resemblance of BCC to the hair follicle.Our aim was to characterize the common expression pattern for the epithelial cell adhesion molecule (Ep-CAM) in BCCs, various stages of follicular embryogenesis, and adult hair follicles and, thereby, in analogy point to the similarity between BCC and the hair follicle.We studied immunohistochemically 16 superficial BCCs for Ep-CAM and compared the expression pattern with that during hair follicle, nail, and eccrine gland development in human embryos and fetuses. In addition, we examined terminal scalp and vellus hair follicles.All BCCs expressed Ep-CAM similar to the early stages of the embryonic human hair follicle, the secondary hair germ, and the outer root sheath of the vellus hair follicle. The embryonic nail organ and the adult anagen hair follicles were completely negative.The conclusions are based on the similarity in the immunohistochemical expression profile for a single adhesion molecule.BCC expresses the cell-cell adhesion molecule Ep-CAM similar to the embryonic hair germ, the secondary hair germ of the terminal hair follicle, and the outer root sheath of the vellus hair follicle. We suggest that this may be a clue to the adnexal nature of BCC and propose that BCC is the most primitive follicular tumor.