Distinct regulations driving YAP1 expression loss in poroma, porocarcinoma and RB1-deficient skin carcinoma.

AIMS: Recently, YAP1 fusion genes have been demonstrated in eccrine poroma and porocarcinoma, and the diagnostic use of YAP1 immunohistochemistry has been highlighted in this setting. In other organs, loss of YAP1 expression can reflect YAP1 rearrangement or transcriptional repression, notably through RB1 inactivation. In this context, our objective was to re-evaluate the performance of YAP1 immunohistochemistry for the diagnosis of poroma and porocarcinoma. METHODS AND RESULTS: The expression of the C-terminal part of the YAP1 protein was evaluated by immunohistochemistry in 543 cutaneous epithelial tumours, including 27 poromas, 14 porocarcinomas and 502 other cutaneous tumours. Tumours that showed a lack of expression of YAP1 were further investigated for Rb by immunohistochemistry and for fusion transcripts by real-time PCR (YAP1::MAML2 and YAP1::NUTM1). The absence of YAP1 expression was observed in 24 cases of poroma (89%), 10 porocarcinoma (72%), 162 Merkel cell carcinoma (98%), 14 squamous cell carcinoma (SCC) (15%), one trichoblastoma and one sebaceoma. Fusions of YAP1 were detected in only 16 cases of poroma (n = 66%), 10 porocarcinoma (71%) all lacking YAP1 expression, and in one sebaceoma. The loss of Rb expression was detected in all cases except one of YAP1-deficient SCC (n = 14), such tumours showing significant morphological overlap with porocarcinoma. In-vitro experiments in HaCat cells showed that RB1 knockdown resulted in repression of YAP1 protein expression. CONCLUSION: In addition to gene fusion, we report that transcriptional repression of YAP1 can be observed in skin tumours with RB1 inactivation, including MCC and a subset of SCC.

[Infectious genital lesions]. / Lésions infectieuses génitales.

External genital infections are multiple, possibly linked to viral, bacterial, mycosic, or parasitic infections. Viral and bacterial infections often integrate within the framework of Sexually Transmitted Diseases (STD/STI) and can be associated with a context of immunosuppression. Skin or mucosae damage is often isolated. Their diagnosis is often referred to clinically, and confirmed by local samples without the need for biopsy. Histological examination is indicated in unusual clinical cases or in cases of persistent lesions or atypical appearance or pseudotumoral, posing a challenge for clinical differential diagnosis. In these cases, the morphological analysis can be supplemented by special colorations, immunological techniques or even molecular analysis allowing in some cases the detection and identification of infectious agents. This chapter will integrate external genital infections of viral, bacterial and parasitic origin where histological analysis is the diagnostic element of orientation.

Folliculitis decalvans is characterized by a persistent, abnormal subepidermal microbiota.

Folliculitis decalvans (FD) is a chronic inflammatory disease of unknown aetiology. Although Staphylococcus aureus, frequently found on lesional skin, is thought to play a causal role, the importance of its involvement remains controversial. To examine the role of S aureus, we compared superficial and subepidermal microbiota in 20 FD patients who had S aureus on lesional skin and in 20 healthy controls using culture techniques and genomic identification, before and after an anti-staphylococcal treatment; we also screened for S aureus virulence factors. When present on lesional skin, S aureus colonized non-lesional and subepidermal skin in 80% of cases. These data imply a break in the epidermal barrier integrity and that an abnormal non-lesional skin microbiota persists in FD. S aureus had no superantigenic toxin in 31% of cases and no toxin specificity. Clinical improvement obtained in most cases upon treatment was associated with the disappearance of S aureus in all studied areas, with an incomplete restoration of normal microbiota and a significant increase in negative bacterial samples. This persistent unbalanced, subepidermal microbiota may act as a reservoir of abnormal flora and explain the chronicity of FD, suggesting new avenues of research to restore normal microbiota.

Epidermal psoriasiform hyperplasia, an unrecognized sign of folliculitis decalvans: A histological study of 26 patients.

BACKGROUND: Follicular hyperkeratosis along with hyperplasia of the follicular and interfollicular epithelia are major histopathological characteristics of hidradenitis suppurativa (HS). The presence of an occasional thickening of lesional skin in some folliculitis decalvans (FD) patients and histological similarities between FD and HS led us to look for epidermal hyperplasia and follicular hyperkeratosis in FD patients. PATIENTS AND METHOD: We performed a retrospective histological analysis of 26 patients with FD. OBJECTIVE: We sought to find out whether the presence of hyperplasia of the interfollicular epidermis and of the follicular epithelia could be verified in FD, with reference to the work of von Laffert et al. concerning HS. RESULTS: The main quantitative and qualitative data were: follicular hyperkeratosis (77%), hyperplasia of the interfollicular epidermis (92%) with a psoriasiform aspect (88%), atrophy of the follicular epithelia (85%), plasma cells in infiltrate (92%) in large quantities (42%), follicular microcysts (60%), atrophy of the sebaceous glands (85%) and polytrichia (54%). CONCLUSION: Epidermal hyperplasia, sometimes psoriasiform and follicular microcysts, are significant histological signs of FD, which have been ignored until now although they seem very common.

Syringotropic mycosis fungoides: clinical and histologic features, response to treatment, and outcome in 19 patients.

BACKGROUND: A rare variant of mycosis fungoides (MF), syringotropic MF (STMF) is characterized by a particular tropism of the lymphocytic infiltrate for the eccrine structures, and included in the follicular subtype of MF in the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. OBJECTIVE: We sought to determine the clinicopathologic features and disease course of patients with STMF. METHODS: A retrospective study was conducted to identify patients with STMF from 1998 to 2013. RESULTS: Nineteen patients were included: 15 men and 4 women, mean age 55 years (range, 24-86). Most had multiple lesions (n=16, 84%) with associated alopecia (n=12, 63%) and/or punctuated aspect (n=12, 63%). Palms or soles were involved in 10 cases (53%). Folliculotropism was found in 13 cases (68%). After a median follow-up of 70 months (range, 2-140), 3 patients died, 1 from disease-related death. The 5-year overall and disease-specific survival were 100%. The disease-specific survival was significantly higher than in 54 patients with folliculotropic MF without syringotropism (5-year disease-specific survival, 74%; 95% confidence interval, 58%-94%, P=.02). LIMITATIONS: Retrospective setting is a limitation. CONCLUSIONS: In the spectrum of adnexotropic MF, STMF appears as a distinct entity from follicular MF, with peculiar clinical characteristics and natural history.

EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression.

BACKGROUNDS: An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC) progression. METHODS: Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. RESULTS: OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner. CONCLUSIONS: Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.

Inflammatory complications after hair transplantation: Report of 10 cases.

BACKGROUND: Androgenetic alopecia (AGA) is a pathology involving the aesthetic prognosis. Hair transplantation is among best treatments. The principle of hair micro-grafts during AGA consists in taking hair from the non-androgen-dependent occipital area to transplant them with their root in the sparse androgen-dependent areas. Herein, we report 10 cases of the different types of post-transplant inflammatory complications. MATERIALS AND METHODS: We included patients referred to our center by their dermatologists or hair transplant surgeons for inflammatory cicatricial alopecia or hair loss observed after the hair transplant. RESULTS: Ten patients (eight men and two women) were included. These patients represented 0.08% of all consultations in our center. The indication for hair transplantation was AGA in all of our patients. The technique used for the transplant was follicular unit extraction (FUE) in seven cases and follicular unit transplantation (FUT) strip in three cases. None of the patients had pathology of the scalp or an inflammatory dermatosis before the operation. The inflammatory complications found were lichen planopilaris (LPP) in seven cases, erosive pustulosis of the scalp (EPS) in two cases, and superficial folliculitis (SF) in 1 case. CONCLUSION: Our series highlight the rarity of inflammatory complications that occur after a hair transplant. We demonstrate through this work that a hair transplant can trigger inflammatory pathology a few months after the act. We show also, the importance of detecting the rough forms of lichen before an intervention, hence the interest of the systematic dermatoscopic examination during the preoperative consultation.

Analysis of alterations adjacent to invasive squamous cell carcinoma of the penis and their relationship with associated carcinoma.

BACKGROUND: In contrast to vulvar squamous cell carcinoma (SCC), the etiologic factors and precancerous lesions associated with penile carcinoma remain uncertain. OBJECTIVES: To describe the morphologic features of lesions adjacent to invasive penile SCC and their relationship with the associated carcinoma and to compare these associations with vulvar carcinoma. METHODS: This was a retrospective histologic analysis of 68 cases of penile SCC. Adjacent lesions were considered to be premalignant lesions. They were classified as penile intraepithelial neoplasia (PIN), squamous hyperplasia (SH), and lichen sclerosus (LS). PIN cases were divided into two subtypes depending on the extension of atypia throughout the epithelium and, by analogy, with the classification of the vulvar intraepithelial neoplasia (VIN). Thus they were designated as undifferentiated (or bowenoid) PIN, defined by full-thickness atypia throughout the epithelium, and differentiated PIN, characterized by atypia confined to the lower third of the epithelium. SCC subtypes were classified as usual, verrucous, warty (condylomatous), basaloid, and mixed. RESULTS: Undifferentiated PIN was observed in 22 cases; LS was observed in 26 cases. Differentiated PIN and SH (except for two cases) were associated with underlying LS. Undifferentiated PIN was always associated with warty (condylomatous) (4 cases), basaloid (16 cases) or mixed SCC (2 cases), and LS with usual (19 cases) or verrucous SCC (7 cases). LIMITATIONS: This was a retrospective analysis CONCLUSION: This study suggests that, similarly to vulvar carcinoma, penile SCC occurs in association with two types of penile lesions: undifferentiated (or bowenoid) PIN and LS-linked differentiated PIN and/or SH. It appears that the subtype of these carcinomas is related to these adjacent lesions.

Successful Treatment of Generalized Eruptive Keratoacanthoma of Grzybowski with Acitretin.

INTRODUCTION: Keratoacanthomas (KA) are common cutaneous skin tumors originating from the hair follicles. Unlike squamous cell carcinoma, KA can regress spontaneously and have a benign evolution. Solitary KA is the most common form but familial multiple KA (Ferguson-Smith type), genetically predisposed KA (such as in xeroderma pigmentosum, or Muir-Torre syndrome), or sporadic multiple eruptive KA (Grzybowski type) have been described. Generalized eruptive KA of Grzybowski (GEKA) is a rare condition (around 40 reported cases). The pathophysiology is still unclear. Human papillomavirus (HPV) has been detected in sporadic KA but the presence of HPV39 has never been reported, to our knowledge, in GEKA. CASE REPORT: GEKA in an 80-year-old woman was successfully treated with acitretin (0.5 mg/kg/day) combined with surgical removal of the largest lesions. Treatment was well tolerated and led to decreased pruritus and tumor regression within 6 months. The presence of HPV39 was detected in a lesion by polymerase chain reaction and Sanger sequencing. No genetic alteration was found, in particular in the genes usually altered in squamous cell carcinoma (including NOTCH1, NOTCH2, CDKN2A, TP53). CONCLUSION: We report a case of GEKA associated with the presence of HPV39 and the successful use of acitretin combined with surgical removal of the larger lesions.

The Use of Direct Immunofluorescence in Frontal Fibrosing Alopecia.

BACKGROUND: Frontal fibrosing alopecia (FFA) differs from lichen planopilaris (LPP) in many clinical aspects, but histology fails to distinguish between these entities. Direct immunofluorescence (DIF) is a diagnostic technique used for autoimmune diseases, including those affecting skin and hair. OBJECTIVE: To characterize DIF patterns in patients with FFA. METHOD: Data was collected retrospectively from FFA cases presenting to the Centre de Santé Sabouraud Hair Clinic in Paris from November 2013 to November 2014. RESULTS: Of 149 patients with FFA, 44 cases underwent DIF. Thirteen cases showed positive results with DIF. Patterns characteristic of LPP and lupus erythematosus were observed, with nearly half showing nonspecific staining. CONCLUSION: DIF patterns in patients with FFA were variable. This diagnostic technique should be used with caution in cases of cicatricial alopecia, particularly FFA.

Vulvar lichen sclerosus: effect of long-term topical application of a potent steroid on the course of the disease.

BACKGROUND: Lichen sclerosus is an inflammatory disease of unknown etiology affecting the anogenital skin and associated with the development of squamous cell carcinoma. It is not known whether long-term topical treatment with a potent steroid can cure this disease and thus prevent malignant evolution. OBJECTIVES: To analyze the rates of remission, recurrence, and chronic evolution of vulvar lichen sclerosus (VLS) treated with 0.05% clobetasol propionate ointment and determine whether this treatment can decrease the risk of malignant evolution. DESIGN: Prospective study, conducted between 1981 and 2001, of 83 women with VLS who were treated until complete clinical and histologic remission and followed up for evidence of clinical and histologic recurrence (median follow-up, 4.7 years). SETTING: Dermatology department of a large urban teaching hospital. RESULTS: Complete remission was obtained in 45 patients (54%). The probability of remission was significantly associated with age (P<.001). The estimated incidence of remission at 3 years was 72% in women younger than 50 years, 23% in women aged between 50 and 70 years, and 0% in women older than 70 years. The incidence of relapse was estimated to be 50% at 16 months (95% confidence interval, 30%-64%) and 84% at 4 years (95% confidence interval, 57%-94%). Age had no effect on relapse prevalence. The 8 observed vulvar squamous cell carcinomas (9.6%) occurred in previously untreated or irregularly treated VLS lesions. CONCLUSIONS: Treatment with a potent steroid cream can improve but does not cure VLS in women older than 70 years, probably because of a long disease evolution. In younger patients who achieve complete remission, it seems to have only a temporary effect. Although a protective effect from malignant evolution is suggested (carcinoma developed only in nontreated or irregularly treated VLS lesions), the number of seemingly protected patients was too small to be statistically significant.

[Pigmented lesions of the vulva: histological features]. / Lésions pigmentées vulvaires: diagnostic histologique.

The vulva is an anatomical and histological combination of cutaneous and mucous components. It is the site of various pigmented lesions, in 10 to 12% of white women, often of unknown etiology. The clinical features are polymorph, non-specific, thus requiring a biopsy. Histological analysis helps to rule out the diagnosis of melanoma, which frequently leads to mutilating surgical treatment and which has an unfavorable prognosis. We present a review of the anatomical and histological characteristics of the normal vulva and of the process of melanogenesis. In addition, the histological criteria that enable the etiological diagnosis of vulvar pigmented lesions are presented. Some of these lesions are tumoral, melanocytic or non-melanocytic, isolated or related to a general pathology; others, non-tumoral, related to inflammatory, immunological, hormonal, or paraneoplasic mechanisms, can be manifestations of systemic diseases. Biopsy specimen analysis and anatomo-clinical correlation are essential for the appropriate diagnosis and the treatment of these lesions.

Neutrophilic skin lesions in autoimmune connective tissue diseases: nine cases and a literature review.

The pathophysiology of neutrophilic dermatoses (NDs) and autoimmune connective tissue diseases (AICTDs) is incompletely understood. The association between NDs and AICTDs is rare; recently, however, a distinctive subset of cutaneous lupus erythematosus (LE, the prototypical AICTD) with neutrophilic histological features has been proposed to be included in the spectrum of lupus. The aim of our study was to test the validity of such a classification. We conducted a monocentric retrospective study of 7028 AICTDs patients. Among these 7028 patients, a skin biopsy was performed in 932 cases with mainly neutrophilic infiltrate on histology in 9 cases. Combining our 9 cases and an exhaustive literature review, pyoderma gangrenosum, Sweet syndrome (n = 49), Sweet-like ND (n = 13), neutrophilic urticarial dermatosis (n = 6), palisaded neutrophilic granulomatous dermatitis (n = 12), and histiocytoid neutrophilic dermatitis (n = 2) were likely to occur both in AICTDs and autoinflammatory diseases. Other NDs were specifically encountered in AICTDs: bullous LE (n = 71), amicrobial pustulosis of the folds (n = 28), autoimmunity-related ND (n = 24), ND resembling erythema gyratum repens (n = 1), and neutrophilic annular erythema (n = 1). The improvement of AICTDS neutrophilic lesions under neutrophil targeting therapy suggests possible common physiopathological pathways between NDs and AICTDs.