Basosquamous cell carcinoma in organ transplant patients: a clinicopathologic study.

BACKGROUND: Basosquamous cell carcinoma (BSCC) is a poorly known tumor showing pathological features of both basal and squamous cell carcinomas. BSCC has never been specifically studied in organ transplant recipients (OTRs). OBJECTIVE: We sought to study the clinicopathologic features of BSCC in OTRs and compare them with BSCC from nongrafted patients. METHODS: Tumors diagnosed as BSCC were re-evaluated pathologically and immunohistochemically for the expression of the human epithelial antigen to confirm the diagnosis. The clinicopathologic features of BSCC in OTRs were compared with 30 BSCC obtained from nongrafted patients. RESULTS: In our cohort of 3520 OTRs, 12 patients (0.34%) developed BSCC after a mean postgraft delay of 13.2 years, ie, later than other skin carcinomas. As compared with control patients, the age of OTRs with BSCC and the tumor thickness were significantly lower. BSCC were located on the head/neck in both groups in more than 75% of cases. No metastases developed in OTRs (mean follow-up 2.8 years). During the follow-up period (mean 16 years), OTRs with BSCC developed up to 220 additional premalignant and malignant skin tumors. After the diagnosis of BSCC, two patients developed lymph node metastasis of distinct squamous cell carcinoma. LIMITATIONS: This is a single-center, retrospective study. CONCLUSIONS: BSCC is a rare tumor, even in OTRs who are at high risk of carcinomas. Its incidence (0.34%) is comparable with that of cutaneous lymphomas and melanomas, and much lower than that of other nonmelanoma skin cancers. Contrary to previous reports, BSCC do not seem to behave more aggressively than other nonmelanoma skin cancers.

Acne as seen by adolescents: results of questionnaire study in 852 French individuals.

Acne can have an important psychological impact. We surveyed 852 adolescents aged 12-25 years about their knowledge of acne and its treatment in a non-medical context. The study involved a questionnaire administered to callers to a youth telephone helpline in France. Callers were categorized into those who currently had acne, those who had had acne previously, and those who had never had acne. Most respondents (66.2%) had experienced acne symptoms, which were mild in 50.2% of cases and severe in 16% of cases. Often, acne had been long-lasting (>12 months in 49.6% of cases). Many thought that gender, excess weight, eating dairy products, and physical activity did not influence acne, and that frequent washing could improve acne. Eating chocolate and snacks, smoking cigarettes, sweating, not washing, touching/squeezing spots, eating fatty foods, using make-up, pollution, and menstruation were thought to worsen acne. The majority (80.8%) did not believe acne to be a disease, but rather a normal phase of adolescence, yet 69.3% agreed it should be treated. There was a preference for topical vs. systemic treatment. Many (38.6%) of the respondents with acne had not consulted a physician. Almost two-thirds of respondents wanted more information about acne. Providing more information about acne might increase the likelihood of them consulting a physician and getting better treatment for the condition.

Extensive pigmented vulvar basal-cell carcinoma presenting as pruritus in an elderly woman.

Basal cell carcinoma (BCC), the most common human cancer, is seldom seen in the genital area. We present a case of an extensive pigmented BCC that developed on the mucosal surface of the vulva of an elderly woman and briefly review the relevant literature on vulvar BCC.

[Issenheim's altarpiece: does the disease depicted on the altarpiece correspond to ergotism?]. / Apropos du retable d'Issenheim: la maladie représentée sur le retable correspond-elle a l'ergotisme?

The Issenheim altar by Mathias Grünenwald (Unterlinden museum in Colmar) shows various scenes from the life of St Antony, abbot. The Tentation panel has been considered as an illustration of the sacer ignis, or St Antony's disease (ergotism). In fact, it may more likely indicate an early representation of Syphilis, or the French disease, as discussed here.

Conversion from calcineurin inhibitors to sirolimus reduces vascularization and thickness of post-transplant cutaneous squamous cell carcinomas.

BACKGROUND: Immunosuppression favors the development of skin cancer. Experimental data suggest that sirolimus (SRL) has antitumoral and antiangiogenic properties. An investigation was undertaken into the effects of SRL on squamous cell carcinoma (SCC) developing in organ transplant recipients (OTR) receiving immunosuppressive treatments, with special emphasis on vascularization. MATERIALS AND METHODS: SCC that developed in eight OTR before and after conversion from calcineurin inhibitors (CNI) to SRL were compared for thickness, differentiation, ulceration, perineural invasion, density of peritumoral infiltrate, peritumoral vascularization, density of T-regulatory cells and of intratumoral Langerhans cells and growth fraction. RESULTS: SCC developing under SRL showed lower peritumoral vascularization and thickness, and higher growth fraction and density of peritumoral T-regulatory cells. CONCLUSION: Conversion from CNI to SRL at clinically relevant doses is associated in vivo with a reduced vascularization and thickness of post-transplant human cutaneous SCC. This effect could account for the beneficial effect of SRL on immunosuppression-induced skin carcinogenesis in humans.

Porokeratoma (porokeratotic acanthoma): immunohistological study of a new case.

Porokeratoma (porokeratotic acanthoma) is a very recently described tumor-like acanthoma with features of porokeratosis (cornoid lamellation). We report herein a new case of this poorly known lesion that was studied immunohistochemically and discuss briefly its relationship with porokeratosis.

Creation of a tool to assess adherence to treatments for acne.

BACKGROUND: Acne is a disorder in which adherence has a major impact on treatment outcome. OBJECTIVE: To create an easy-to-use tool to assess treatment adherence, based on a questionnaire that can be used on a daily basis by dermatologists. METHODS: First, we evaluated adherence by comparing responses to a self-administered questionnaire with the dermatologist's prescription. Second, concordance was assessed between adherence and each question of a dermatologist-directed questionnaire (DDQ) administered during the consultation. Third, DDQ questions were combined to construct a mini-questionnaire, and these combinations were tested to maximize specificity. RESULTS: The study included 246 patients, who were prescribed topical treatment alone, combined treatment (excluding oral isotretinoin) or oral isotretinoin alone. The mini-questionnaires for oral and topical treatments had 89% specificity for detecting poor adherence. An inappropriate answer to one question classified the patient as a probable poor compliance. CONCLUSIONS: Our mini-questionnaires provide dermatologists with specific tools to rapidly identify poor compliance.

Factors influencing the clinical evaluation of facial acne.

Existing scoring systems for facial acne focus on the lesions themselves, but clinical decisions are based on a general assessment of severity, including the time since onset, the site(s) of involvement, the patient's history, and the response to prior treatments. The aim of this study was to investigate the influence of some of these factors on the global assessment of acne severity. Involvement of the trunk, prior systemic treatment and a positive family history of acne increased the severity score. Inclusion of these factors could help to compose more homogeneous groups for clinical trials.

Multinucleate cell angiohistiocytoma: report of three new cases and literature review.

Multinucleate cell angiohistiocytoma (MCA) is a rare benign vascular proliferation of the skin of unknown cause. About 75 cases have been reported previously. We present herein three new cases of MCA studied immunohistologically and present a review the relevant literature that delineates the salient clinicopathological features of this unusual entity.

Granular parakeratosis in a patient treated with liposomal doxorubicin for ovarian carcinoma.

Granular parakeratosis is a rare benign dermatosis caused by an acquired disorder of keratinization that usually manifests with reddish-brown keratotic papules and plaques in intertriginous areas. It has specific histologic features but its pathogenesis remains unclear. Its frequency is probably underestimated because the condition is usually misdiagnosed as simple intertrigo. We report herein a new case of granular parakeratosis in a woman treated with liposomal doxorubicin for ovarian carcinoma that showed complete remission after discontinuation of chemotherapy. The relationship between granular parakeratosis and chemotherapy is discussed.

Living with acne. A study of adolescents' personal experiences.

BACKGROUND: Acne can have important psychological repercussions. OBJECTIVES: We studied adolescents' perceptions of acne, in a nonmedical context. METHODS: Between November 2004 and January 2005, a questionnaire was presented to adolescents calling a youth helpline. It focused on perceptions of acne and, among callers with personal experience of acne, its severity and treatment. Callers were divided into those with acne, those having had acne and those never having had acne. RESULTS: The questionnaire was completed by 1,566 callers. It showed that 51% of respondents with acne did not seek medical help; acne has as big a psychological impact as some far severer diseases; many respondents with no history of acne said they were very worried that they would develop this skin disorder. CONCLUSIONS: This study underlines the major psychological impact of acne. Young people need to be informed that acne can be treated.

Interaction of discoidin domain receptor 1 isoform b (DDR1b) with collagen activates p38 mitogen-activated protein kinase and promotes differentiation of macrophages.

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagen. DDR1 is constitutively expressed in a variety of normal and transformed epithelial cells and plays a role in cell migration and differentiation through as yet unidentified signaling pathways. We previously reported inducible expression of DDR1 in human leukocytes and suggested a role for the DDR1a isoform in leukocyte migration through extracellular matrix. Here, we evaluated the contribution of DDR1 in the differentiation of the human monocytic THP-1 cells overexpressing these isoforms and of primary macrophages. Interestingly, collagen activation of DDR1b, but not DDR1a, further promoted phorbol ester-induced differentiation of THP-1 cells as determined by reduced cell proliferation and up-regulated expression of HLA-DR, CD11c, CD14, and CD40. Collagen activation of DDR1b also induced the recruitment and phosphorylation of Shc and subsequent phosphorylation of p38 mitogen-activated protein (MAP) kinase and its substrate ATF2. A p38 MAP kinase inhibitor, SB203580, completely inhibited DDR1b-mediated HLA-DR expression. Activation of DDR1 endogenously expressed on macrophages also up-regulated their HLA-DR expression in a p38 MAP kinase-dependent manner. Thus, DDR1b in response to collagen transduces signals that promote maturation/differentiation of HLA-DR-positive antigen-presenting cells and contributes to the development of adaptive immunity in a tissue microenvironment.

Compensatory induction of MYC expression by sustained CDK9 inhibition via a BRD4-dependent mechanism.

CDK9 is the kinase subunit of positive transcription elongation factor b (P-TEFb) that enables RNA polymerase (Pol) II's transition from promoter-proximal pausing to productive elongation. Although considerable interest exists in CDK9 as a therapeutic target, little progress has been made due to lack of highly selective inhibitors. Here, we describe the development of i-CDK9 as such an inhibitor that potently suppresses CDK9 phosphorylation of substrates and causes genome-wide Pol II pausing. While most genes experience reduced expression, MYC and other primary response genes increase expression upon sustained i-CDK9 treatment. Essential for this increase, the bromodomain protein BRD4 captures P-TEFb from 7SK snRNP to deliver to target genes and also enhances CDK9's activity and resistance to inhibition. Because the i-CDK9-induced MYC expression and binding to P-TEFb compensate for P-TEFb's loss of activity, only simultaneously inhibiting CDK9 and MYC/BRD4 can efficiently induce growth arrest and apoptosis of cancer cells, suggesting the potential of a combinatorial treatment strategy.

Physiopathology of acne vulgaris: recent data, new understanding of the treatments.

Acne is the most frequent reason for seeing a dermatologist, but its physiopathology is not completely well-known. Yet understanding of the mechanisms of action of the different acne treatments is very important to optimize their use. A lot of new data on the physiopathology have recently been published in the acne field. This paper summarizes the main points of these new facts.

[Acne and hormones]. / Acné et hormones.

Androgens stimulate sebum production which is necessary for the development of acne. Acne in women may thus be considered as a manifestation of cutaneous androgenization. Most of acnes may be related to an idiopathic skin hyperandrogenism due to in situ enzyme activity and androgen receptor hypersensitivity, as also noted in idiopathic hirsutism. Some acne may correspond to elevated ovarian or adrenal androgen secretion. The presence of acne in women may lead to a diagnosis of functional hyperandrogenism, either polycysticovary syndrome or nonclassical 21-hydroxylase deficiency. Plasma level assays for testosterone, delta 4 androstenedione and 17-OH progesterone and ovarian echography are necessary to determine the possibility for an ovarian or adrenal hyperandrogenism, but not to better treat acne. The goal of hormonal therapy in acne is to oppose the effects of androgens on the sebaceous gland. Hormones may be used in female acne in the absence of endocrine abnormalities. Antiandrogens (cyproterone acetate or aldactone) may be useful in severe acne, hormonal contraceptives with cyproterone acetate or non androgenic progestins in mild or common acne often in association with other anti-acneic drugs. Glucocorticoids have to be administered in acne fulminans and other forms of acute, severe, inflammatory acne, for their anti-inflammatory properties.

Cutaneous cryptococcosis in solid organ transplant recipients: epidemiological, clinical, diagnostic and therapeutic features.

Data on post-graft cutaneous cryptococcosis (CC) are rare. The objective was to delineate the epidemiological, clinical, diagnostic, therapeutic features of CC in organ transplant recipients. We compared cases from a cohort of 3,670 transplanted adults with cases from a regional cryptococcosis registry including 122 patients. Four CC were diagnosed in the transplanted cohort (1‰) corresponding in the regional registry to 33% of the 12 cases of cryptococcosis after transplantation, while among the 110 non-grafted patients, only five cryptococcosis were cutaneous (4%). CC appeared as a single (3 patients) ulcer or nodule over 1cm in size in an uncovered body zone, on average 13 months post-graft. 3 patients had concomitant opportunistic infections or a recent increase in their immunosuppression. All CC after transplantation were localized exclusively to the skin, raising the question of the mode of contamination (through the skin or the lungs). Evidence of dissemination is difficult because of the poor sensitivity of diagnostic tests. Fluconazole was the treatment of choice in association with immunosuppressive treatment tapering.

[Dermatological side effects of epidermal growth factor receptor inhibitors]. / Effets secondaires dermatologiques des inhibiteurs de l'EGFR.

Epidermal growth cell receptors (EGFR) play a key role in tumor proliferation. Their inhibitors (anti-EGFR) are promising treatments for various types of cancers. Papulopustular follicular eruptions are the most frequent dermatological side effect and occur in 45 to 85% of patients receiving this treatment. Paronychias appear after several weeks of treatment. They are painful and impair hand and foot function. A positive correlation seems to exist between the intensity of the papulo-follicular eruption, tumor regression and survival.