Role of Wnt signaling in dermatofibroma induction phenomenon.

BACKGROUND: Dermatofibroma (DF) is a common benign skin neoplasm. Induction above DF lesions, including follicular unit induction, is a frequently observed phenomenon. Wnt signaling is known to be critical in hair follicle morphogenesis. Our study assesses the role of Wnt signaling in DF induction by evaluating intracellular localization of ß-catenin in various types of DF induction. METHODS: Archived tissue collected between 1 October 1980 and 1 October 2013 was stained per protocol using hematoxylin and eosin and anti-ß-catenin monoclonal antibody. Specimens were grouped into categories based on the presence or absence and type of induction. All specimens were scored for nuclear ß-catenin localization. RESULTS: Of 62 specimens, 42 (68%) showed induction while 20 (32%) showed none. Nuclear ß-catenin staining was detected in 23 (55%) of the induction and in none of the no-induction specimens (P-value < 0.001). Types of induction included: 15 (24%) follicular induction, 31 (50%) acanthosis, and 4 (6%) sebaceous induction. For follicular induction, 13 (87%) showed positive nuclear ß-catenin staining compared to 11 (35%) for acanthosis and 1 (25%) for sebaceous induction (P-value = 0.002). CONCLUSION: Our findings support the hypothesis that DFs promote an ectopic activation of Wnt pathway signaling in follicular induction phenomenon.

Basaloid tumors arising from seborrheic keratosis: Malignant basal cell carcinoma or benign basaloid follicular hamartomatous proliferation?

BACKGROUND: Basaloid tumors arising from seborrheic keratosis (SK) that resembled basal cell carcinoma (BCC) were infrequently observed in our patients. They also exhibited morphologic features similar to those of trichoblastoma or basaloid follicular hamartoma. METHODS: We retrospectively collected cases of SK with basaloid tumors from 2001 to 2017. Ten cases of BCC, five of nevus sebaceus with trichoblastoma, five of trichoblastoma, and five of trichoepithelioma were included as controls. Tumor-associated antigens Bcl-2, CD10, PHLDA1, and CK20 were tested. Antigenic markers CD34 and CD10 were used to analyze peritumoral stroma features and Ki-67 and pHH3 to measure the mitotic activity. RESULTS: Ten cases of SK with basaloid tumors were found and all located in non-sun-exposed areas, including five men and five women, with a mean age of 61 years. A distinct PHLDA1 staining was not observed. The staining patterns of basaloid tumor lobules associated with SK were similar to the benign control group. Bcl-2 staining in the tumor lobules was mostly negative. Peritumoral CD10 stain and CK20-positive Merkel cells in the lobules were observed and the mitotic counts were low. CONCLUSION: Basaloid tumors arising from SK are not always BCC. They were all benign follicular hamartomatous proliferation in this case series.

Follicular induction and CK20+ Merkel cells overlying cutaneous focal mucinosis.

BACKGROUND: Cutaneous focal mucinosis (CFM) or focal dermal mucinosis is a benign reactive process categorized as a primary mucinosis. Skin biopsy is essential for diagnosis, as the clinical appearance is often non-specific. Follicular induction is a phenomenon whereby the epidermis is induced by an underlying process to form primitive or mature hair follicles, and is commonly seen overlying dermatofibromas. Follicular induction has been rarely described in CFM. METHODS: We performed a retrospective histological review of lesions of CFM confirmed by skin biopsy from 2010 to 2015 in our department. RESULTS: We found that 11% (11/98) of CFM lesions showed follicular induction. Cytokeratin 20 (CK20) immunostaining was performed on all 11 of these biopsies that showed follicular induction and highlighted an increased density of CK20+ Merkel cells within the basaloid epidermal proliferations. CONCLUSION: As superficial basal cell carcinomas (BCC) often show a mucinous stroma around the basaloid islands, CFM with follicular induction may closely mimic a BCC histologically, particularly in superficial shave biopsies. Therefore, it is important that dermatopathologists be aware of this phenomenon. Furthermore, CK20+ staining within the basaloid epithelial proliferations may be helpful in differentiating CFM with follicular induction from a BCC.

Primitive follicular induction in molluscum contagiosum.

BACKGROUND: Molluscum contagiosum (MC) is the commonest human poxvirus infection. Follicular induction has rarely been observed in the epidermis surrounding lesions of MC. A virus-induced localized proliferation of germinative/stem cells of the folliculosebaceous-apocrine unit has been suggested as the underlying cause, however few reports of this peculiar phenomenon exist in the literature and the mechanisms involved in this proliferation require further study. METHODS: We prospectively collected MC cases showing multifocal areas of primitive follicular induction involving the adjacent undersurface epidermis. Immunohistochemical expression of BerEP4, PHLDA1 and cytokeratin 20 (CK20) was evaluated in the basaloid germs surrounding the lesions. For PHLDA1, we used epidermal melanocytes as a positive internal control. For BerEP4, we employed a basal cell carcinoma (BCC) and for CK20, colon as positive external controls. An incubation without the primary antibody functioned as an external negative control. RESULTS: All the cases studied showed an intense positive staining of the basaloid buds with BerEP4 and weaker stain for PHLDA1. CK20 showed the presence of scattered Merkel cells within the induced epidermal basaloid proliferations favoring their reactive origin. DISCUSSION: The pathogenetic mechanisms behind the development of these microscopic features and the link between follicular induction and poxvirus infection are explored. Awareness of this unusual phenomenon by dermatopathologists will be helpful in avoiding a misdiagnosis of a superficial BCC in such cases. CONCLUSIONS: BerEP4 and PHLDA1 were consistently expressed in the areas of primitive follicular induction surrounding lesions of MC. CK 20 stained the Merkel cells present in the basaloid buds. All these findings support the reactive origin of this phenomenon, which we believe is most probably viral-induced.