Evaluation of Alitretinoin for the Treatment of Mycosis Fungoides and Sézary Syndrome.

BACKGROUND: Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is aimed at limiting disease progression. This study evaluated the efficacy and tolerability of alitretinoin in CTCL management. METHODS: A retrospective, multicenter study was conducted on CTCL patients treated with alitretinoin as a primary agent or in combination with standard therapies. RESULTS: Forty-eight patients with MF (n = 40) and SS (n = 8) with a median age of 59.7 years (±14.3) were eligible for study inclusion. Treatment response data were evaluated in 40 patients and safety in 42 patients. 40.0% of the patients had early-stage, 43.8% had advanced-stage CTCL, and in 16.7% of patients there was insufficient information for staging. 40.0% (16/40) of the patients achieved a complete or partial response, whereas 47.5% (19/40) achieved stable disease, 12.5% (5/40) had progressive disease, and there were no cases of disease relapses in responders. Both early and advanced stages of CTCL were responsive to alitretinoin as a primary or combined modality. Alitretinoin was well tolerated, and 64.3% (27/42) of patients did not report any side effects. The most commonly observed side effect was hypertriglyceridemia. CONCLUSIONS: This retrospective analysis supports the efficacy and safety of alitretinoin in clearing skin disease and preventing disease progression in CTCL as a monotherapy or in combination with standard therapies.

Overview of Ultrasound Imaging Applications in Dermatology [Formula: see text].

Complete visualization of lesions is critical for the accurate diagnosis and management of dermatological diseases. Currently, the most readily available technologies used by dermatologists include dermoscopy and photography. Nevertheless, ultrasound has emerged as a useful non-invasive modality in dermatology, which can be added to the clinical examination supporting an early and more accurate diagnosis. Moreover, there are significant technological advances in recent years, such as the development of handheld devices and ultra-high frequency probes that have expanded the integration of ultrasound into daily dermatology practice. In this article, we reviewed the most common applications of ultrasound in the field of dermatology.

Clinical Characteristics and Treatment Response With Checkpoint Inhibitors in Malignant Melanoma of the Vulva and Vagina.

OBJECTIVES: The aims of the study were to assess the clinical and histopathological characteristics of a comprehensive cohort of women with vulvovaginal melanoma (VVM) treated at our institution and to study the treatment response of checkpoint inhibitors in this patient cohort. MATERIALS AND METHODS: This is a retrospective study of women with invasive VVM treated at the Princess Margaret Cancer Centre in Toronto, Ontario, Canada, over a period of 15 years. Clinical and histopathological characteristics, treatment, as well as treatment-related outcome were analyzed in 32 women. Treatment response was evaluated retrospectively using the "response criteria for use in trials testing immunotherapeutics" (iRECIST). The objective response rate was defined as the proportion of patients with complete or partial response based on the best overall response. RESULTS: At a median follow-up of 37.8 months (5.8-110.4), 26 women (81.3%) had disease progression and 16 (50%) died. Thirteen patients with locally unresectable or metastatic melanoma were treated with immune checkpoint inhibitors. Ten additional cases were identified from previously published reports. The best objective response rate for immune checkpoint inhibitors was 30.4% (95% CI = 11.6%-49.2%) and the clinical benefit rate was 52.2% (95% CI = 31.8%-72.6%). The clinical benefit rate was significantly better for programmed cell death protein 1 inhibitors (or a combination) compared with ipilimumab alone (Fisher exact, p = .023). Grade 3/4 adverse events were observed in 3 (13.0%) of the 23 patients. CONCLUSIONS: Women with VVM constitute a high-risk group with poor overall prognosis. Immune checkpoint inhibitors are effective in the treatment of metastatic melanoma in this patient cohort.

Primary cutaneous T-cell lymphomas in childhood and adolescence.

Primary cutaneous lymphomas are extranodal non-Hodgkin lymphomas of T- or B- cell origin, that predominantly affect older patients but have been reported in all age groups and as early as in the first years of life. Diagnosis of cutaneous lymphomas is challenging and requires high clinical suspicion and close collaboration between dermatologists, pediatric oncologists and pathologists. Skin involvement of non-Hodgkin lymphomas in children or adolescents can either be primary cutaneous or secondary due to an underlying nodal lymphoma. The most common primary cutaneous lymphomas encountered in children are of T-cell origin, with mycosis fungoides being the most prevalent cutaneous T-cell lymphoma, followed by CD30+ lymphoproliferative disorders. While cutaneous lymphomas share clinicopathologic characteristics between juvenile and adult forms, there are important differences in terms of clinical presentation, diagnosis and treatment. The hypopigmented variant of mycosis fungoides seems to be overrepresented in the pediatric age group. Prognosis and treatment of mycosis fungoides are stage dependent. The majority of children present with early-stage disease and respond well to topical corticosteroids and phototherapy.

Primär kutane T-Zell-Lymphome im Kindes- und Jugendalter.

Primär kutane Lymphome sind extranodale T- oder B-Zell-Non-Hodgkin-Lymphome, die vorwiegend ältere Patienten betreffen, aber in allen Altersgruppen einschließlich der ersten Lebensjahre auftreten können. Die Diagnose kutaner Lymphome ist eine Herausforderung und erfordert einen hohen klinischen Verdacht sowie enge Zusammenarbeit zwischen Dermatologen, pädiatrischen Onkologen und Pathologen. Generell müssen primär kutane Lymphome von sekundär kutanen Lymphomen, welche meist von nodalen oder extranodalen Lymphomen ausgehen, unterschieden werden. Die häufigsten primär kutanen Lymphome im Kindesalter sind T-Zell Lymphome, wobei Mycosis fungoides das häufigste kutane T-Zell-Lymphom darstellt, gefolgt von CD30+ lymphoproliferativen Erkrankungen. Während klinisch-pathologische Merkmale kutaner Lymphome bei Jugendlichen und Erwachsenen ähnlich sind, gibt es wichtige Unterschiede bezüglich klinischer Präsentation, Diagnose und Behandlung. Die hypopigmentierte Variante der Mycosis fungoides scheint in der pädiatrischen Altersgruppe überrepräsentiert zu sein. Prognose und Behandlung der Mycosis fungoides sind stadienabhängig. Die Mehrheit der Kinder weist ein frühes Krankheitsstadium auf und spricht gut auf topische Kortikosteroide und Phototherapie an.

Clinical Monitoring of Sacrococcygeal Teratoma.

BACKGROUND: Sacrococcygeal teratomas (SCT) are often highly vascularized and may result in high-output cardiac failure, polyhydramnios, fetal hydrops, and demise. Delivery is guided by the SCT to fetus volume ratio (SCTratio), SCT growth rate, and cardiac output indexed for weight (CCOi). METHODS: We compared measurements and outcome in 12 consecutive fetuses referred with SCT. Adverse outcomes were: fetal surgery, delivery < 32 gestational weeks or neonatal demise. Only SCTratio and CCOi were used to manage the cases. SCT vascularization index (VI%) was derived from the 3D virtual organ computer-aided analysis (VOCAL) software. The SCTModel (modified from acardiac twins) calculated a hypothetical SCT draining vein size and derived a risk line, using diameters of the superior and inferior vena cava, the azygous and umbilical veins. VI% and a model of systemic and umbilical venous volumes (SCTModel) were tested as indicators for outcome in SCT. RESULTS: Fetuses were monitored from 20.1 to 36.4 gestational weeks and 5/12 had adverse outcomes: 1 had successful open fetal surgery at 23.8 weeks and delivered at term, 4 delivered at < 32 weeks with 3/4 having neonatal demise between 25 and 29 weeks. VI% was significantly higher in cases with adverse outcomes (mean 10.3 [8.9-11.6] vs. 4.4 [3.4-5.3], p < 0.0001). The additional fraction of the fetal cardiac output required to perfuse the SCT-draining vein (XSCO%) (p = 0.46), SCTratio (p = 0.08), and CCOi (p = 0.64) were not significant. All cases with adverse outcome had VI% > 8%. The SCTModel risk line predicted nonadverse outcomes well but lacked data in 2/5 cases with adverse outcomes. CONCLUSIONS: VI% is a significant indicator of SCT cases with adverse outcomes and combined with SCTratio may guide timing of delivery better than current measures.

Vulvamalignome: eine interdisziplinäre Betrachtung.

Vulvamalignome stellen die vierthäufigste Gruppe von gynäkologischen Krebserkrankungen dar. Erste Ansprechpartner sind typischerweise niedergelassene Dermatologen und Gynäkologen. Mit der jeweiligen Fachexpertise findet die Diagnose und Therapie idealerweise interdisziplinär zwischen spezialisierten Dermatoonkologen und gynäkologischen Onkologen statt. Vulvamalignome sind überwiegend Erkrankungen des höheren Lebensalters, obwohl alle histologischen Subtypen auch bei Frauen unter 30 Jahren vorkommen. Die Diagnose erfolgt oft verzögert. Eine genaue Kartierung von Biopsien (Mapping) ist von großer Bedeutung, da Lokalisation und Entfernung von der Mittellinie in Abhängigkeit von der zugrunde liegenden Histologie das operative Vorgehen bestimmen. Plattenepithelkarzinome machen mehr als 76 % der Vulvamalignome aus und vulväre intraepitheliale Neoplasien (VIN) sind dabei wichtige Vorstufen. Der zweithäufigste Typ der Vulvakarzinome ist das Basalzellkarzinom. Melanome machen 5,7 % der vulvären Malignome aus und ihre Prognose ist schlechter als die der kutanen Melanome. Die meisten Studien zu Checkpoint-Inhibitoren und zielgerichteten Therapien haben Patientinnen mit vulvären Melanomen nicht ausgeschlossen. Die vorliegende Evidenz wird im folgenden diskutiert. Die Methode der Wahl bei lokal resezierbaren Vulvamalignomen ist die Exzision. Angesichts ihrer Seltenheit sollte die Behandlung in spezialisierten Zentren erfolgen, um eine optimale Krankheitskontrolle zu erreichen und Kontinenz und sexuelle Funktion bestmöglich zu erhalten.

Vulvar malignancies: an interdisciplinary perspective.

Vulvar cancer represents the fourth most common gynecologic malignancy and is often encountered by the general Dermatologist or Gynecologist. Dermatooncologists and Gynecologic Oncologists share expertise in this field and the diagnosis and treatment should ideally be interdisciplinary. All subtypes are typically seen in the later decades of life, although all histologic subtypes have been described in women younger than 30 years. The diagnosis is often delayed. Exact mapping of biopsies is of high importance, as the location and distance from the midline guides the surgical approach depending on the underlying histology. Squamous cell carcinoma accounts for more than 76 % of vulvar cancer with vulvar intraepithelial neoplasia being an important precursor. Basal cell carcinoma is the second most common vulvar malignancy. Melanoma accounts for 5.7 % of vulvar cancer and has a worse prognosis compared to cutaneous melanoma. Most of the trials on checkpoint inhibitors and targeted therapy have not excluded patients with vulvar melanoma and the preliminary evidence is reviewed in the manuscript. Surgery remains the primary treatment modality of locally resectable vulvar cancer. In view of the rarity, the procedure should be performed in dedicated cancer centers to achieve optimal disease control and maintain continence and sexual function whenever possible.

Childhood alopecia areata-Data from the National Alopecia Areata Registry.

BACKGROUND/OBJECTIVES: Alopecia areata may occur at any age and is the third-most-common dermatosis in children. The objective of this study was to investigate the clinical and epidemiologic features of children and adolescents with alopecia areata based on the data of the National Alopecia Areata registry on children and adolescents. METHODS: Two thousand two hundred eighteen children and adolescents with alopecia areata self-enrolled in the National Alopecia Areata Registry and completed a web-based, self-administered, short-intake screening questionnaire (first tier). In the second tier, 643 patients participated in a clinical examination and completed a long-form questionnaire. RESULTS: Mean age of onset was 5.9 ± 4.1 years. With a female to male ratio of 1.5:1, alopecia areata was more prevalent in girls, but boys were significantly more likely to have a severe type (P = .009). One-fourth of all children had a positive family history, with 8% having more than three affected relatives. The disease most commonly associated with alopecia areata was atopic dermatitis (32.7%). CONCLUSION: Childhood alopecia areata is more prevalent in girls than in boys, but boys have more extensive alopecia areata. Despite the low prevalence, congenital alopecia areata is an important differential diagnosis for neonatal hair loss. Alopecia areata runs in families, suggesting an underlying genetic background. One-quarter of the children reported at least one affected first-degree relative; 8% had more than three affected relatives.

Mineral Depositions of Calcifying Skin Disorders are Predominantly Composed of Carbonate Apatite.

Subcutaneous calcifications can lead to complications, including pain, inflammation, ulceration and immobilization. Studies on the pathophysiology of mineral compositions and effective treatment modalities are limited. We therefore studied 14 patients with subcutaneous calcifications. Mineral material was collected and analysed by Fourier transform infrared spectrometry. Blood analyses were run to evaluate systemic alterations of mineral metabolism. Carbonate apatite (CAP) was found to be the single constituent in the majority of patients (n = 9, 64.3%), 3 cases (21.4%) had a composition of CAP and calcium oxalate dihydrate and one case had a combination of CAP and magnesium ammonium phosphate, whereas CAP was the major component in all 4 cases. Only one case showed predominantly calcium oxalate. Thus, CAP was found to be the only or predominant component in most cases of subcutaneous calcifications. Chemical analyses of the mineral compositions may aid in the development of new treatment regimes to improve the solubility of mineral components and to decrease extraosseous calcifications.

Telangiectasia macularis eruptiva perstans: an old terminology, still frequently used.

The term telangiectasia macularis eruptiva perstans (TMEP) was originally used to describe a rare form of cutaneous mastocytosis (CM) that was limited to the skin with lesions consisting of irregular, telangiectatic macules ranging in color from red to brown. Recent guidelines, however, recommended that the sole presence of telangiectasias should not form the basis of a distinct variant of CM. We conducted a review of the literature from 1930 to 2017 and found 76 cases that were reported as TMEP. Owing to a general misconception about diagnosis of CM and SM, there is a need for further discussion and awareness of the newly proposed World Health Organization (WHO) guidelines.

Lymphomatoid papulosis: Treatment response and associated lymphomas in a study of 180 patients.

BACKGROUND: Lymphomatoid papulosis (LyP) is a CD30(+) lymphoproliferative disorder, with a self-regressing clinical course and malignant histopathology. OBJECTIVE: The aim of this study was to evaluate characteristics, risk factors, associated malignancies, long-term outcome, and treatment of LyP in a large cohort representing the experience of the MD Anderson Cancer Center. METHODS: Patient charts and clinical and histopathologic data of 180 patients with LyP were retrospectively assessed. RESULTS: A total of 56.7% of patients was men. Histologic subtype A was found in 47.2%, type B in 17.2%, type C in 22.8%, type D in 7.8%, type E in 0.6%, and mixed subtype in 4.4% of the patients. One hundred fourteen lymphomas were observed in 93 patients, with mycosis fungoides (61.4%) and anaplastic large cell lymphoma (26.3%) being the most common forms. Risk factors for development of lymphoma included sex and histologic subtype. Number of lesions and symptom severity were not associated with lymphoma development. Patients with type D were less likely to have lymphomas. Treatment provided symptomatic relief but did not prevent progression to lymphoma. LIMITATIONS: The limitation of this study is the retrospective study design. CONCLUSION: Patients with LyP are at increased risk of associated lymphomas. Thorough patient counseling is needed and long follow-up periods are required to detect and treat secondary lymphomas.

Granulomatous Mycosis Fungoides in an Adolescent-A Rare Encounter and Review of the Literature.

Granulomatous mycosis fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by an infiltrate of atypical lymphocytes, histiocytes, and multinucleated giant cells. Clinically, GMF has a slowly progressing course with a worse prognosis than other forms of MF. With its peak incidence being in the fifth to sixth decade, GMF is rare in children and adolescents. Herein we describe a 14-year-old boy with GMF.

Primär kutane CD30(+) lymphoproliferative Erkrankungen.

Primär kutane CD30(+) lymphoproliferative Erkrankungen zählen zu der zweit häufigsten Gruppe der kutanen T-Zell-Lymphome (CTCL) und umfassen die Krankheitsbilder der lymphomatoiden Papulose (LyP) und des primär kutanen anaplastischen großzelligen Lymphoms (cALCL). Beide Erkrankungen haben klinische, histopathologische und molekulare Gemeinsamkeiten und repräsentieren ein Spektrum von kutanen CD30(+) lymphoproliferativen Erkrankungen. Man kann LyP vom cALCL anhand des Zusammenspiels von klinischen und histopathologischen Befunden unterscheiden. In manchen Patienten können LyP und MF gemeinsam auftreten, oder können während des Krankheitsverlaufes entstehen. Mycosis fungoides (MF), ist die häufigste Form von CTCL und zählt nicht zur Gruppe der primär kutanen CD30(+) lymphoproliferativen Erkrankungen. Manche LyP-Patienten können jedoch von beiden Krankheitsbildern gemeinsam betroffen sein. Es ist aber auch möglich, dass ein MF-Patient LyP-artige Läsionen entwickelt, die eher eine Manifestation der MF darstellen als zwei unterschiedliche Erkrankungen. Besondere Vorsicht ist jedoch im Zusammenhang mit CD30(+) transformierten MF-Läsionen geboten, da die Gefahr besteht, dass diese fälschlicherweise als LyP oder cALCL diagnostiziert werden, was möglicherweise zu einer inadäquaten Behandlung führt.

Primary cutaneous CD30(+) lymphoproliferative disorders.

Primary cutaneous CD30(+) lymphoproliferative disorders are the second most common group of cutaneous T-cell lymphomas (CTCL) and include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large T-cell lymphoma (cALCL). Both disease entities share overlapping clinical, histopathological, and molecular features, thus representing a spectrum of cutaneous CD30(+) lymphoproliferative disorders. LyP may be distinguished from cALCL by clinicopathological correlation. In some patients, both diseases may coexist at initial diagnosis or develop over the course of the disease. Mycosis fungoides (MF), the most common CTCL, is not considered a primary cutaneous CD30(+) lymphoproliferative disorder, but may occur in some LyP patients. In addition, LyP-like lesions may develop in MF patients. However, this is frequently a manifestation of MF rather than a representation of two different disease entities. Caution also has to be taken in the setting of transformed MF with lesions expressing CD30, as they may be mistaken for either LyP or cALCL, resulting in an inadequate therapeutic approach.

Cutaneous manifestations in trisomy 13 mosaicism: A rare case and review of the literature.

Trisomy 13 mosaicism is a rare genetic disorder affecting a small minority of all trisomy 13 cases. It occurs when two cell populations that are karyotypically different are present in the same individual and are derived from a single zygote. As a rule, the phenotype is mitigated to a less dysmorphic appearance and longer survival, making genetic counseling a difficult task. Capillary hemangiomas are a common feature of full trisomy 13, seen in 27-56% of all cases. We report on an 18-months-old girl with extensive cutaneous anomalies, mild dysmorphic features, and slight psychomotor delay, without structural defects and provide an up-to-date review of all cases of trisomy 13 mosaicism with skin involvement. To our knowledge, this is the second clinical report of a patient with trisomy 13 mosaicism with hemangiomas and port wine stains, but no structural defects. © 2015 Wiley Periodicals, Inc.

Preliminary Evidence for a Compromised T-Cell Compartment in Maltreated Children with Depression and Posttraumatic Stress Disorder.

OBJECTIVE: Adverse childhood experiences, such as maltreatment, and affective disorders are associated with a proinflammatory state and/or variably compromised counts in lymphocyte subsets in adults. Animal models of social stress indicate that recent thymic emigrant cells (RTE), which maintain the T-cell compartment, are affected. METHODS: In this study, we examined the association between lymphocyte subsets, and depression and posttraumatic stress disorder (PTSD) among 16 maltreated children (aged 6-17 years) 1-3 years after the intervention by the Child Protection Team and among 14 healthy age-matched controls. The participants completed psychological assessment and had blood drawn for fluorescent-activated cell sorting analysis. RESULTS: Among maltreated children and adolescents, depression was associated with lower counts of RTEs and T-helper cells after controlling for age. We found additional trends and large effect sizes with regard to the percentages of these cells, as well as for related lymphocyte subsets. Similar effects were found for PTSD, i.e. lower counts of naïve T cells, which was also supported by a trend for their percentage. Compared to controls, maltreated participants with a clinical level of depression had decreased percentages of RTEs, with a similar trend for PTSD. CONCLUSION: Limited by the nature of a pilot study and the small sample size, these preliminary findings of a compromised T-cell compartment related to psychiatric symptoms in maltreated children and adolescents need to be further studied; particularly the role of RTEs needs further evaluation.

Leonine facies (LF) and mycosis fungoides (MF): A single-center study and systematic review of the literature.

BACKGROUND: Leonine facies (LF) is defined as displaying facial features similar to that of a lion with prominent convexities and furrowed creases. LF develops in a very small population of patients with cutaneous T-cell lymphoma. OBJECTIVE: We aimed to study the clinicopathologic features and overall prognosis associated with LF in patients with mycosis fungoides and Sézary syndrome. METHODS: We conducted a single-center retrospective study, reviewing 1338 patients with mycosis fungoides seen from 1987 to 2015 at a tertiary referral center for cutaneous T-cell lymphoma, and a systematic review of 14 patients in the literature. RESULTS: We identified 10 patients with mycosis fungoides who developed LF. Folliculotropism was seen in all patients with LF who had facial biopsy specimens. Radiation was a beneficial therapy. Complete remission was achieved in 1 patient and overall 5-year survival was 26%. Systematic review of 10 additional patients showed that all patients with LF, including ours, had stage-IV disease and some degree of blood involvement, but not all met criteria for Sézary syndrome. LIMITATIONS: This was a retrospective study with a small sample size. CONCLUSION: LF is associated with stage-IV cutaneous T-cell lymphoma, is often accompanied by folliculotropism and blood involvement, and can be treated with local electron beam therapy.

Gynecologic Malignancies in Children and Adolescents: How Common is the Uncommon?

The aim of this study is to assess the projected incidence and prognostic indicators of gynecologic malignancies in the pediatric population. In this population-based retrospective cohort study, girls ≤18 years with ovarian, uterine, cervical, vaginal and vulvar malignancies diagnosed between 2000 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER)-18 registry. The Kaplan-Meier method was used to analyze overall survival (OS). The age-adjusted annual incidence of gynecologic malignancies was 6.7 per 1,000,000 females, with neoplasms of the ovary accounting for 87.5%, vagina 4.5%, cervix 3.9%, uterus 2.5% and vulva 1.6% of all gynecologic malignancies. Malignant germ-cell tumors represented the most common ovarian neoplasm, with an increased incidence in children from 5-18 years. Although certain subtypes were associated with advanced disease stages, the 10-year OS rate was 96.0%. Sarcomas accounted for the majority of vaginal, cervical, uterine and vulvar malignancies. The majority of vaginal neoplasms were observed in girls between 0-4 years, and the 10-year OS rate was 86.1%. Overall, gynecologic malignancies accounted for 4.2% of all malignancies in girls aged 0-18 years and the histologic subtypes and prognosis differed significantly from patients in older age groups.