EMBO MOLECULAR MEDICINE, Issue 4 2009
Shyra J. Miller
Abstract Understanding the biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour biomarkers, prognostic factors and therapeutics. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n,=,10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) (n,=,22), malignant peripheral nerve sheath tumour (MPNST) cell lines (n,=,13), benign neurofibromas (NF) (n,=,26) and MPNST (n,=,6). Dermal and plexiform NFs were indistinguishable. A prominent theme in the analysis was aberrant differentiation. NFs repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes up-regulated in sarcomas were significantly enriched for genes activated in neural crest cells. We validated the differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in NF and MPSNT tissue sections and targeting SOX9 , strongly expressed in NF1-related tumours , caused MPNST cell death. SOX9 is a biomarker of NF and MPNST, and possibly a therapeutic target in NF1. [source]

Policy on Acute Toxic Ingestion or Dermal or Inhalation Exposure

JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 7 2003
ANP-C FAANP, Mary Jo Goolsby EdD
ABSTRACT Many nurse practitioners (NPs) practice in emergency and urgent-care settings, and fir more practical remote settings. NPs in each of these settings should be familiar with the assessment, stabilization, and treatment of patients who seek treatment for suspected intentional or accidental poisoning. This month's Clinical practice guideline (CPG) column reviews the "Clinical Policy for the Initial Approach to Patients Presenting With Acute Toxic Ingestion or Dermal or Inhalation Exposure." SUMMARY The ACEP "Clinical Policy for the Initial Approach to Patients Presenting With Acute Toxic Ingestion or Dermal or Inhalation Exposure" includes several helpful resources. In addition to recommending specific clinical actions in response to patient variables, the document includes a table identifying the antidote for many of the most commonly ingested drugs. These include digoxin, iron, opioids, salicylates, acetaminophen, and tricyclic antidepressants. The table also includes both the adult and pediatric dose of each listed antidote. A quick reference is included. This form can be used to guide the history, physical examination, and subsequent actions for treating patients with acute toxic ingestion or dermal or inhalation exposure. Finally, there is a quality assurance form to guide chart reviews. Many of the attributes of a well-developed guideline are identified in the report. The authors clearly identify the situations for which the recommendations are intended as well as those in which they do not apply. For instance, the guidance is not intended for use when patients are unstable and stabilization is the primary focus. It is also not intended for cases of radiation, parenteral, or eye exposure or of food poisoning. The authors describe the process used to develop the recommendations and identify the strength of the evidence on which each recommendation is based. The role of provider judgment in application of the guidance is addressed. Prior to its dissemination, the CPG was subjected to external review by dinical experts. This ACEP policy has applicability for the growing number of NPs working in emergency and urgent cafe settings as well as for those who must provide front line emergency care in remote settings. It provides a framework for responding to acute toxic exposures and provides several useful resources to assist the clinician in responding to situations in which accidental or intentional poisoning is suspected. [source]

Policy on Acute Toxic Ingestion or Dermal or Inhalation Exposure

JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 7 2003
ANP-C, FAANP, Mary Jo Goolsby EdD
ABSTRACT Many nurse practitioners (NPs) practice in emergency and urgent-care settings, and far more practice in remote settings. NPs in each of these settings should be familiar with the assessment, stabilization, and treatment of patients who seek treatment for suspected intentional or accidental poisoning. This month's clinical practice guideline (CPG) column reviews the "Clinical Policy for the Initial Approach to Patients Presenting With Acute Toxic Ingestion or Dermal or Inhalation Exposure." [source]

Intense Pulsed Light for the Treatment of Refractory Melasma in Asian Persons

DERMATOLOGIC SURGERY, Issue 9 2004
Chia-Chen Wang MD
Background. Patients with dermal or mixed-type melasmas are often refractory to various treatments. Intense pulsed light has been used to treat melanocytic lesions with promising results. Objective. The purpose of this study was to clarify the effectiveness of intense pulsed light for refractory melasma in Asian persons. Methods. Seventeen patients were treated with intense pulsed light, during four sessions at 4-week intervals. The patients were also given 4% hydroquinone cream and broad-spectrum sunscreens to prevent and treat postinflammatory hyperpigmentation. Sixteen patients in the control group were treated with hydroquinone cream and sunscreens. The treatment efficacy was evaluated using reflectance spectrophotometer and patient satisfaction questionnaire. Results. Patients in the intense pulsed light group achieved an average of 39.8% improvement in relative melanin index, compared to 11.6% improvement in the control group (p<0.05) at Week 16. Six (35%) patients in the intense pulsed light group had more than 50% improvement, compared to two (14%) patients in the control group. Two patients in the intense pulsed light group, however, experienced transient postinflammatory hyperpigmentation, and partial repigmentation was noted 24 weeks after the last treatment session. Conclusion. Intense pulsed light is a safe and effective treatment for refractory melasma in Asian persons, with minimal side effects. Further treatment sessions are required for maintenance therapy. [source]

Increased Glycosaminoglycans Production in Sclerosing Basal Cell Carcinoma-Derived Fibroblasts and Stimulation of Normal Skin Fibroblast Glycosaminoglycans Production by a Cytokine-Derived from Sclerosing Basal Cell Carcinoma

DERMATOLOGIC SURGERY, Issue 11 2000
Ronald L. Moy MD
Sclerosing basal cell carcinoma (S-BCC) is characterized by an abundant stroma. There is evidence that some tumor cells secrete cytokines that are mitogenic for stromal fibroblasts (FBs). From this study we report increased glycosaminoglycan (GAG) production by cultures of S-BCC FBs in comparison to cultures of nodular BCC (N-BCC) FBs and normal skin FBs. GAG production was measured by cetylpyridinium chloride precipitation of incorporated [3H]-glucosamine. The sclerosing BCC FBs demonstrated a significant increase in production of GAG over control FBs (P < .001) and over N-BCC FBs (P < .001). Values reported as a mean percentage ± SEM for GAG production by S-BCC over control normal skin FBs are 359 ± 28 and over N-BCC FBs are 266 ± 27. In additional experiments, cell extract dilutions from S-BCC tumor, normal dermis, and normal epidermis were incubated with cultures of normal skin FBs. S-BCC-conditioned media was also incubated with normal FBs and GAG production was measured. For both S-BCC extracts and conditioned media, a dose response curve was established showing increased GAG production by normal FBs in relation to increasing the concentration of S-BCC extract or conditioned media. When S-BCC extract was added to normal FBs there was increased GAG production in comparison to normal FBs incubated with dermal or epidermal extracts (P < .001) for both. Two growth factors, transforming growth factor-, (TGF-,) and platelet-derived growth factor (PDGF), already known to be mitogenic for FBs, were incubated with N-BCC and normal FBs in an effort to elucidate the potential cytokine(s) released by S-BCC, causing increased GAG production by surrounding FBs. Neither of these cytokines proved to be effective in promoting a significant increase in GAG production. Our findings support the hypothesis that BCCs release factors that alter stromal FB production of GAG. [source]

Expression of the dlx gene family during formation of the cranial bones in the zebrafish (Danio rerio): Differential involvement in the visceral skeleton and braincase

DEVELOPMENTAL DYNAMICS, Issue 5 2006
L. Verreijdt
Abstract We have used dlx genes to test the hypothesis of a separate developmental program for dermal and cartilage bones within the neuro- and splanchnocranium by comparing expression patterns of all eight dlx genes during cranial bone formation in zebrafish from 1 day postfertilization (dPF) to 15 dPF. dlx genes are expressed in the visceral skeleton but not during the formation of dermal or cartilage bones of the braincase. The spatiotemporal expression pattern of all the members of the dlx gene family, support the view that dlx genes impart cellular identity to the different arches, required to make arch-specific dermal bones. Expression patterns seemingly associated with cartilage (perichondral) bones of the arches, in contrast, are probably related to ongoing differentiation of the underlying cartilage rather than with differentiation of perichondral bones themselves. Whether dlx genes originally functioned in the visceral skeleton only, and whether their involvement in the formation of neurocranial bones (as in mammals) is secondary, awaits clarification. Developmental Dynamics 235:1371,1389, 2006. © 2006 Wiley-Liss, Inc. [source]

Runx3 is involved in hair shape determination

DEVELOPMENTAL DYNAMICS, Issue 4 2005
Eli Raveh
Abstract Transcriptional regulators of the Runx family play critical roles in normal organ development and, when mutated, lead to genetic diseases and cancer. Runx3 functions during cell lineage decisions in thymopoiesis and neurogenesis and mediates transforming growth factor-, signaling in dendritic cells. Here, we study the function of Runx3 in the skin and its appendages, primarily the hair follicle, during mouse development. Runx3 is expressed predominantly in the dermal compartment of the hair follicles as they form and during the hair cycle, as well as in the nail and sweat gland skin appendages. Distinct expression is also detected periodically in isolated cells of the epidermis and in melanocytes, populating the hair bulb. Runx3 -deficient mice display a perturbation of the normal hair coat, which we show to be due to hair type and hair shape changes. Thus, one of the functions of Runx3 in skin may be to regulate the formation of the epithelial derived structural hair by affecting dermal to epidermal interactions. Developmental Dynamics 233:1478,1487, 2005. © 2005 Wiley-Liss, Inc. [source]

LOXL as a target to increase the elastin content in adult skin: a dill extract induces the LOXL gene expression

EXPERIMENTAL DERMATOLOGY, Issue 8 2006
Valérie Cenizo
Abstract:, The lysyl oxidases lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) are responsible for elastin cross-linking. It was shown recently that LOXL is essential for the elastic fibres homeostasis and for their maintenance at adult age. We first determined whether or not elastin, LOX and LOXL are less expressed during adulthood. The LOX and LOXL mRNA level, quantified by real-time reverse transcriptase-polymerase chain reaction decreased in adult skin fibroblasts compared with fibroblasts from children. In contrast, the elastin mRNA level remains stable at all ages. The goal of this study was to induce elastogenesis at the adult age. Therefore, both enzymes, and in particular LOXL, of which expression is the most affected by age, could be targeted to induce elastogenesis in adult skin. We screened a library of about 1000 active ingredients to find activators capable to stimulate specifically the LOXL gene expression in adult dermal fibroblasts. The positive effect of selected active ingredients was confirmed on fibroblasts grown on monolayers and on dermal and skin equivalent cultures. One extract, obtained from dill (LYS'LASTINE V, Engelhard, Lyon, France), stimulates the LOXL gene expression in dermal equivalents (+64% increase in the LOXL mRNA level when compared with control). At the same time, the elastin detection is increased in dermal equivalents and under the dermal,epidermal junction of skin equivalents, without increase of the elastin mRNA. In conclusion, LOXL can be considered as a new target to reinduce elastogenesis. Its stimulation by a dill extract is correlated with increased elastin detection, suggesting an increase in elastogenesis efficiency. [source]

Plasticity of hair follicle dermal cells in wound healing and induction

EXPERIMENTAL DERMATOLOGY, Issue 2 2003
A. Gharzi
Abstract: The capacity of adult hair follicle dermal cells to participate in new follicle induction and regeneration, and to elicit responses from diverse epithelial partners, demonstrates a level of developmental promiscuity and influence far exceeding that of interfollicular fibroblasts. We have recently suggested that adult follicle dermal cells have extensive stem or progenitor cell activities, including an important role in skin dermal wound healing. Given that up to now tissue engineered skin equivalents have several deficiencies, including the absence of hair follicles, we investigated the capacity of follicle dermal cells to be incorporated into skin wounds; to form hair follicles in wound environments; and to create a hair follicle-derived skin equivalent. In our study, we implanted rat follicle dermal cells labelled with a vital dye into ear and body skin wounds. We found that they were incorporated into the new dermis in a manner similar to skin fibroblasts, but that lower follicle dermal sheath also assimilated into hair follicles. Using different combinations of follicle dermal cells and outer root sheath epithelial cells in punch biopsy wounds, we showed that new hair follicles were formed only with the inclusion of intact dermal papillae. Finally by combining follicle dermal sheath and outer root sheath cells in organotypic chambers, we created a skin equivalent with characteristic dermal and epidermal architecture and a normal basement membrane , the first skin to be produced entirely from hair follicle cells. These data support the hypothesis that follicle dermal cells may be important in wound healing and demonstrate their potential usefulness in human skin equivalents and skin substitutes. While we have made progress towards producing skin equivalents that contain follicles, we suggest that the failure of cultured dermal papilla cells to induce follicle formation in wounds illustrates the complex role the follicle dermis may play in skin. We believe that it demonstrates a genuine dichotomy of activity for follicle cells within skin. [source]

Tenascin-C in primary malignant melanoma of the skin

HISTOPATHOLOGY, Issue 4 2004
S Ilmonen
Aims :,To investigate the expression and the prognostic role of glycoprotein Tenascin-C (Tn-C) in primary melanoma of the skin. Methods and results :,The immunohistochemical expression of Tn-C was studied in 98 primary melanomas and related to inflammation, invasion, and patient outcome. Patients were followed up for disease recurrence for 0.04,7.4 years (median 3.9) and for survival for 0.5 to 12.1 years (median 9.3). The expression of Tn-C was evaluated for each tumour invasion border; the stromal and intracytoplasmic Tn-C of the melanoma islets were also recorded. Tn-C is widely expressed in primary melanoma samples, the staining pattern varying from focal to diffuse in different parts of the tumour. No correlation existed between intensity of Tn-C staining and inflammation. No stromal Tn-C was detected at the upper dermal lateral border in 12 patients, nor at the deep, dermal or subcutaneous border in 14 patients. These patients showed better disease-free survival (DFS) than did those cases with focal or diffuse staining (P = 0.06, P = 0.05). Also, absence of intracytoplasmic Tn-C was a beneficial prognostic factor for DFS (P = 0.04). In multivariate analysis, tumour ulceration and intracytoplasmic Tn-C expression of melanoma cells were independent adverse prognostic factors for DFS. Conclusions :,In primary melanoma of the skin, absence of Tn-C in the stroma of invasion fronts and within tumour cells seems to be related to a more benign disease behaviour with a lower risk of developing metastases. [source]

Ocular, nasal, dermal and respiratory symptoms in relation to heating, ventilation, energy conservation, and reconstruction of older multi-family houses

INDOOR AIR, Issue 3 2003
K. Engvall
First page of article [source]

Quantitative model of cellulite: three-dimensional skin surface topography, biophysical characterization, and relationship to human perception

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 4 2005
L. K. Smalls
Gynoid lipodystrophy (cellulite) is the irregular, dimpled skin surface of the thighs, abdomen, and buttocks in 85% of post-adolescent women. The distinctive surface morphology is believed to result when subcutaneous adipose tissue protrudes into the lower reticular dermis, thereby creating irregularities at the surface. The biomechanical properties of epidermal and dermal tissue may also influence severity. Cellulite-affected thigh sites were measured in 51 females with varying degrees of cellulite, in 11 non-cellulite controls, and in 10 male controls. A non-contact high-resolution three-dimensional (3D) laser surface scanner was used to quantify the skin surface morphology and determine specific roughness values. The scans were evaluated by experts and na,ve judges (n = 62). Body composition was evaluated via dual-energy X-ray absorptiometry; dermal thickness and the dermal,subcutaneous junction were evaluated via high-resolution 3D ultrasound and surface photography under compression. Biomechanical properties were also measured. The roughness parameters Svm (mean depth of the lowest valleys) and Sdr (ratio between the roughness surface area and the area of the xy plane) were highly correlated to the expert image grades and, therefore, designated as the quantitative measures of cellulite severity. The strength of the correlations among na,ve grades, expert grades, and roughness values confirmed that the data quantitatively evaluate the human perception of cellulite. Cellulite severity was correlated to BMI, thigh circumference, percent thigh fat, architecture of the dermal,subcutaneous border (ultrasound surface area, red-band SD from compressed images), compliance, and stiffness (negative correlation). Cellulite severity was predicted by the percent fat and the area of the dermal,subcutaneous border. The biomechanical properties did not significantly contribute to the prediction. Comparison of the parameters for females and males further suggests that percent thigh fat and surface area roughness deviation are the distinguishing features of cellulite. [source]

Two-stage kinetic analysis of fragrance evaporation and absorption from skin

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2003
P. Saiyasombati
Synopsis Human in vivo fragrance evaporation data from a previously published study are reanalysed in terms of compartmental pharmacokinetic models in which the microscopic rate constants are functions of the physicochemical properties of the fragrance components. According to the proposed analysis, which is restricted to low doses, absorption and evaporation of each component are first-order processes occurring from either the skin (one-compartment model) or the skin and a more rapidly depleted vehicle layer (two-compartment models). Evaporation rates of ingredients from a 12-component mixture containing a musk fixative followed single exponential decays that were well described by the one-compartment model. An otherwise identical mixture without fixative yielded evaporation rates that could be characterized as biexponential decays associated with loss from two compartments. This result shows that ingredient interactions qualitatively and quantitatively change evaporation rate profiles of fragrance components; however, an attempt to account for these interactions explicitly by means of activity coefficients inserted as multipliers for the microscopic rate constants was unsuccessful. Re-examination of this approach in the context of a diffusion/evaporation model is suggested. The developed models have potential utility for dermal risk assessment and for prediction of aroma evolution following topical application of complex fragrances. Résumé Des données d'une étude publiée précédemment sur l'évaporation de parfum de humaine in vivo sont réanalysées en utilisant des modèles pharmacocinétiques compartimentés dont les constants microscopiques de taux sont des functions des propriétés physio-chimiques des composants de parfum. Selon l'analyse proposée, qui est limitée aux petites doses, l'absorption et l'évaporation de chaque composant sont des processus de premier ordre se produisant l'un de la peau (modèle d'un compartiment), ou l'autre de la peau et d'une couche de véhicule plus rapidement épuisée (modèles de deux compartiments). Les taux d'évaporation d'ingrédients d'un mélange de 12 composants contenant un fixatif de musc suivi par des décompositions exponentielles uniques qui ont été bien décrites par le modèle d'un compartiment. Un mélange sans fixatif mais identique pour le reste a rapporté des taux d'évaporation qui pourraient être caractérisés commes des décompositions bi-exponentielles avec une perte de deux compartiments. Ce résultat montre que les interactions d'ingrédient changent qualitativement et quantitativement les profils de taux d'évaporation des composants de parfum. Cependant, une tentative d'expliquer précisement ces interactions au moyen des coefficients d'activité insérés comme multiplicateurs pour les constants microscopiques de taux n'a pas été réussie. Le réexamen de cette approche dans le contexte d'un modèle de diffusion/evaporation est suggéré. Les modèles développés ont une utilité potentielle dans l'évaluation des risques cutané et pour la prévision de l'évolution d'arome suivant l'application topique des parfums complexes. [source]

Hair biology: an update

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 1 2002
B. A. Bernard
Synopsis In the past few years, the hair follicle has started revealing its beauty and mysteries. The existence of a growth and regeneration cycle, together with a unique tissue organization and complex regulatory network, make it a true paradigm of tissue homeostasis and dermal,epithelial crosstalk. In this brief review, I will describe some of the most recent results obtained in this very active research field of hair biology, underlining the diversity of the molecular signals that control hair growth and pigmentation. Résumé Au cours des dernières années, le follicule pileux a commencéà révéler sa beauté et ses mystères. L'existence d'un cycle de croissance et de régénération, d'une organization tissulaire unique et d'un circuit complexe de régulation désigne le follicule pileux comme un paradigme d'homéostasie tissulaire et d'interactions dermo,épithéliales. Dans cette courte revue, je décris quelques uns des résultats récemment obtenus dans ce domaine de recherche très actif, en soulignant l'extrême diversité des signaux moléculaires qui contrôlent la croissance du cheveu et sa pigmentation. [source]

Nodular vasculitis in systemic lupus erythematosus

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2008
Annet Westers-Attema MD
A 42-year-old man presented with fever, photosensitivity, headaches, myalgia, hyperhidrosis, muscle weakness, alopecia, nasal crustae, weight loss, painful nails, arthritis, oral ulcers, erythema, discoid cutaneous lesions, and painful subcutaneous nodes. We made a diagnosis of systemic lupus erythematosus (SLE), type II cryoglobulinemia, and nodular vasculitis. In the skin, different types of vasculitis may be observed. Typically, histology shows leukocytoclastic vasculitis of superficial vessels both in SLE and mixed cryoglobulinemia, which clinically results in palpable purpura. In our patient, however, histopathological examination of the subcutaneous nodes not only revealed leukocytoclastic vasculitis of the superficial vasculature but also showed even more extensive involvement of dermal and subdermal small and medium sized vessels, giving rise to a nodular vasculitis. [source]

Dermatitis cruris pustulosa et atrophicans , a frequent but poorly understood tropical skin condition , a case report from Burkina Faso

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2008
Guido Bens MD
Dermatitis cruris pustulosa et atrophicans (DCPA) is a benign inflammatory skin disease of the younger population in the tropics. Although this pustular skin condition of particular topography is frequently seen by dermatologists in tropical countries, its origin remains unknown. We report the case of a young woman with DCPA associated with prurigo nodularis. A bacterial origin has not been demonstrated in this case. Histology showed an intraepidermal neutrophilic pustule with dermal and subcutaneous infiltration by neutrophils and eosinophils forming flame figures. Different pathogenic hypotheses are discussed with special regard to a potential relationship between DCPA and eosinophilic cellulitis. [source]

Treatment of dermal and subcutaneous pheohyphomycosis of 55 years' duration

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2008
J. Pec Prof.
First page of article [source]

Linear-agminated juvenile xanthogranulomas

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2008
Despoina Kiorpelidou MD
An 8-month-old girl presented with an asymptomatic skin lesion on the right popliteal fossa, which had been present for approximately 6 months. The child had a past medical history of a urinary tract infection at the age of 1 month and had been on daily cotrimoxazole since. There was no history of trauma to the site. Examination revealed a solitary, well-demarcated, plaque-like lesion on the right popliteal fossa, with multiple agminated papules in an almost linear distribution (Fig. 1a). The lesion did not follow Blaschko's lines, but was vertical to them. The plaque was slightly indurated, measuring approximately 4 × 1.5 cm, fixed to the overlying skin but movable over the deeper tissue. The papules were yellowish in color and firm to palpation, showing a positive Darier's sign (Fig. 1b,c). There was no regional adenopathy and no other skin lesions were observed. The physical examination and laboratory investigations were otherwise unremarkable. There was no hepatosplenomegaly, and an ocular examination and chest X-ray were normal. Figure 1. Juvenile xanthogranuloma: agminated nodulopapular lesions on the right popliteal fossa (a) showing positive Darier's sign (b and c; arrows) ,A biopsy from the lesion (Fig. 2a) revealed a dermal infiltrate of histiocytes, some of which were foamy, and admixed Touton-type giant cells, lymphocytes, eosinophils, and mast cells. By immunohistochemistry, the predominant cell population was CD68 (KP-1, MIB-1, and PG-M1, all pursued from Dako) positive, but S-100 protein and CD1a negative (Fig. 2b,e). By Giemsa stain, scattered mast cells (< 5% of the total cell number) were detectable within the lesion. The morphology and immunohistochemistry of the lesion were diagnostic for juvenile xanthogranuloma. Eight months later, the lesion was still present but slightly elongated, proportional to the child's growth, and hyperpigmented. Figure 2. Juvenile xanthogranuloma: histomorphology of skin lesion showing a cell-rich histiocytic dermal infiltrate (a) with immunohistochemical characteristics (b,e) of non-Langerhans dendritic cells (a, hematoxylin and eosin; b, anti-S-100 protein; c, anti-CD-1a; d, e, anti-CD68 monocytic markers MIB-1 and KP-1, respectively; a,e, initial magnification ×40) [source]

Microcystic adnexal carcinoma: report of four cases treated with Mohs' micrographic surgical technique

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2005
Amor Khachemoune MD
Background, Microcystic adnexal carcinoma (MAC) is a rare and aggressive malignant tumor of the sweat glands. Clinically, it often presents as a firm subcutaneous nodule on the head and neck regions. On histology, MAC exhibits both pilar and sweat duct differentiation with a stroma of dense collagen. It often extends beyond the clinical margins with local spreading in the dermal, subcutaneous, and perineural tissue planes. It has a high local recurrence rate after standard excision. Recent preliminary reports have indicated more favorable cure rates with Mohs' micrographic surgery (MMS). Objective, To present our data on four cases of MAC treated by MMS. We also compared our findings with more recently reported series in the English language literature. Methods, We reviewed the medical records of four patients (two males and two females) with MAC treated by MMS over the last 3 years. We also obtained follow-up data. Results, In all four patients with MAC treated by MMS, there were no recurrences, with a mean follow-up of 1 year. Conclusion, We report an additional four MAC cases treated by MMS. The accumulated data continue to confirm that, if the diagnosis of MAC is made early, and if the anatomic location is accessible to excision by MMS, a favorable outcome can be expected. [source]

Sweet's syndrome revisited: a review of disease concepts

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2003
Philip R. Cohen MD
Sweet's syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by a constellation of symptoms and findings: fever, neutrophilia, erythematous and tender skin lesions that typically show an upper dermal infiltrate of mature neutrophils, and prompt improvement of both symptoms and lesions after the initiation of treatment with systemic corticosteroids. Hundreds of patients with this dermatosis have been reported. The manifestations of Sweet's syndrome in these individuals have not only confirmed those originally described by Dr Robert Douglas Sweet in 1964, but have also introduced new features that have expanded the clinical and pathologic concepts of this condition. The history, clinical characteristics, laboratory findings, associated diseases, pathology, and treatment options of Sweet's syndrome are reviewed. The evolving and new concepts of this dermatosis that are discussed include: (i) Sweet's syndrome occurring in the clinical setting of a disease-related malignancy, or medication, or both; (ii) detection of additional sites of extracutaneous Sweet's syndrome manifestations; (iii) discovery of additional Sweet's syndrome-associated diseases; (iv) variability of the composition and/or location of the cutaneous inflammatory infiltrate in Sweet's syndrome lesions; and (v) additional efficacious treatments for Sweet's syndrome. [source]

A case of necrobiotic xanthogranuloma without paraproteinemia presenting as a solitary tumor on the thigh

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2003
Sung Eun Chang MD
A 82-year-old Korean woman had had a 6-month history of an asymptomatic, flat, hard, red to brown tumor on her right thigh. This lesion had been slowly enlarging with an advancing margin. She had noted gradually developing pain associated with necrosis and ulceration on the lesion. Examination revealed a solitary, 8 × 7.5 cm, yellow to dark red, telangiectatic tumor with multiple areas of punched out ulceration and a peripheral elevated yellowish margin on the right inner upper thigh (Fig. 1). No clinically similar lesions on the periorbital area or other sites were seen. Histologic examination revealed a massive palisading granulomatous infiltration with several layers of extensive bands of necrobiotic zone in the entire dermis and deep subcutaneous tissue (Fig. 2a). In the granulomatous infiltrate in the dermis and subcutis, many various-shaped, some bizarre, angulated, foreign-body type multinucleated giant cells, many Touton giant cells, and a few Langhans giant cells were found to be scattered (Fig. 2b). There were numerous xanthomatized histiocytes. Dense infiltration of lymphoplasma cells was seen in the periphery of the granuloma and perivascularly. Conspicuous granulomatous panniculitis composed of lymphoplasma cells, polymorphonuclear cells, foam cells, and Touton and foreign-body giant cells was also seen. However, cholesterol clefts and lymphoid follicles were not seen. Subcutaneous septae were widened by necrobiotic change and fibrosis with thrombosed large vessels. Gram, Gomeri-methenamine silver and acid-fast stains were negative. The necrobiotic areas were positive to alcian blue. Laboratory investigation revealed elevated white blood cell counts, anemia and elevated erythrocyte sedimentation rate. The following parameters were within the normal range: lipids, glucose, renal and liver function tests, serum complements, serum immunoglobulins, cryoglobulins and antinuclear antibodies. The findings of chest X-ray, skull X-ray and ectorcardiography were normal. Serum electrophoresis and serum immunoelectrophoresis revealed no abnormality. The patient was diagnosed as having necrobiotic xanthogranuloma without paraproteinemia. She was treated with oral steroid (0.5,0.6 mg/kg) and NSAIDS for 1 month with partial improvement of pain and the lesion ceased to enlarge. In the following 1 year of follow-up, with only intermittent NSAIDS, her lesion did not progress and there were no signs of systemic involvement or new skin lesions. Figure Figure 1 . (a) A solitary, red to brown plaque with multiple ulcerations and a peripheral elevated yellowish margin on the inner upper thigh Figure 2. (a) A dermal and subcutaneous massive xanthogranulomatous infiltrate with zonal necrobiosis of collagen (× 20). (b) Prominent infiltrate of xanthomatized histiocytes and giant cells with perivascular lymphoplasma cells (H&E, × 100) [source]

Acute febrile neutrophilic dermatosis (Sweet's syndrome) with nodular episcleritis and polyneuropathy

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2002
Taizo Kato MD
A 56-year-old Japanese housewife presented with multiple erythematous lesions in association with ocular hyperemia and pain in the right upper and lower extremities, including the hands and feet. These symptoms were preceded by a sore throat with persistent fever higher than 38.5 °C for about 1 week. Dermatologic examination showed tender, dull-red, erythematous lesions, measuring 1,2 cm in diameter, located predominantly on the forehead, cheeks, auricular region, neck, forearm, hands, and feet. A biopsy specimen obtained from an erythematous lesion on the right forearm revealed prominent edema in the papillary dermis and remarkable inflammatory cell infiltration throughout the entire dermis (Fig. 1). The infiltrate predominantly consisted of neutrophils and nuclear dust without signs of vasculitis. In routine examination, the leukocyte count was 15,000/mL (normal range, 4000,8000/mL) with severe neutrophilia (80%). The C-reactive protein (CRP) level was 17.65 mg/dL (normal range, < 0.5 mg/dL) and the anti-streptolysin (ASLO) level was 611 IU/mL (normal range, < 166 IU/mL). In human leukocyte antigen (HLA) testing, HLA-A2, -B39, -B35, -Cw2, and -Cw7 were positive, and HLA-B51, -B54, and -Cw1 were negative. Figure Figure 1 . Histologic picture showing a dermal infiltrate of neutrophils Ocular hyperemia was caused by episcleritis forming a nodule and surrounding congestion of the superficial episcleritic vessels at the central portion of the sclera (Fig. 2). The patient suffered from pain once an hour, continuing for about 3 min, at the lateral portion of the right upper and lower extremities, as well as the right small finger. Neurologic examination demonstrated moderate or slight muscle weakness in the extremities. Hand grasping powers were 9 and 7 kg on the right and left, respectively. The patient was right-handed. Dysesthesia and paresthesia were also observed on the hands and feet. The deep tendon reflexes were preserved, however, even in the distal portion of the upper and lower limbs. In addition, essential tremor localized to the neck was recognized. Magnetic resonance imaging did not show any episodes of transient abnormal signal intensity in the central nervous system. Figure 2. Nodular episcleritis (right eye). Telangiectasia of winding vessels with nodular elevation was observed at the upper portion of the sclera The patient was treated with prednisolone (initial dose of 30 mg/day) and intravenous injection of cefazolin sodium (2 g/day for 5 days). Almost complete regression of the ocular and neurologic manifestations, as well as the skin lesions, was achieved in 2 weeks. Prednisolone was reduced gradually and suspended after 4 weeks. Leukocyte and neutrophil counts, CRP, and ASO returned to normal on suspension of therapy. Slight paresthesia remained in the right small finger even after stopping steroid. There was no recurrence at follow-up 6 months later. [source]

A case of mucosal leishmaniasis: beneficial usage of polymerase chain reaction for diagnosis

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2001
Hironori Onuma MD
A 36-year-old woman, who had emigrated from Japan to Paraguay as a 4-year-old child before returning to Japan in 1991, visited our clinic on November 10, 1997. She had suffered from a persistent ulcer on her forearm as a 6-year-old child and received intravenous injections for a few months, although she did not remember the details of therapy. Since May 1997, she had been aware of redness and swelling on her nose and had been treated with topical corticosteroid, but no improvement had been noted. Physical examination revealed erythematous plaque with crust from the left internal naris to nasolabial region (Fig. 1a). The atrophic plaque that had resulted from prolonged ulceration was found on the right forearm (Fig. 1b). In a biopsy specimen from the erythematous plaque on the nasolabial region, mononuclear dermal infiltrate, consisting of lymphocytes and histiocytes, was seen (Fig. 2a). The histiocytes were filled with Leishman-Donovan (L-D) bodies on a Giemsa staining sample (Fig. 2b). Fiberscopic examination revealed white plaque in the pharynx. The biopsy from the affected mucosa showed the same histopathological finding as with the skin. Figure 1. (a) Erythematous plaque with crust from the left internal naris to nasolabial region. (b) Atrophic plaque on the right forearm Figure 2. (a) In the biopsy specimen from the erythematous plaque on the nasolabial region, a mononuclear dermal infiltrate consisting of lymphocytes and histiocytes was seen. (Hematoxylin-Eosin stain, × 100) (b) The histiocytes were filled with Leishman-Donovan bodies. (Giemsa staining, × 400) Total DNA was purified from the skin biopsy specimen for polymerase chain reaction (PCR) analysis using a specific primer for L (V) braziliensis.1,2 A 70-bp product was amplified (Fig. 3a); furthermore, the specificity of the PCR product was confirmed by Southern hybridization with the probe for L (V) braziliensis (Fig. 3b) and DNA sequence analysis (data not shown). From December 2, 1997, the patient received 20 mg/kg/day sodium stibogluconate (PentostamTM) intravenously for 20 days. After 5 days of treatment, the redness and swelling of the skin lesion was improved, and faint erythema remained at the end of 20 days' treatment. After a 2-week interval, since the erythema remained, another 20-day treatment was performed. All of the skin lesion became scar tissue and L-D bodies could not be found in a skin biopsy specimen. However, L-D bodies were still found in a biopsy from the pharyngeal mucosa that had a normal appearance. Though another additional treatment was planned, the patient refused it. Figure 3. (a) The results of PCR. 70-bps bands appear in lanes 2 and 6. Lane 1, a size marker (pUC19/HapII); lane 2, DNA extracted from the formalin-fixed patient's sample; lane 3, DNA extracted from a formalin-fixed control sample; lane 4, DNA (,); lane 5, DNA extracted from L (V) tropica; lane 6, DNA extracted from L (V) braziliensis. (b) Results of Southern blotting using the PCR products. The PCR products were transferred from agarose gel as shown in Fig. 3 (a). Specific probes were hybridized with 70-bps bands on lanes 2 and 6 [source]

Transformation of the pectoral girdle in the evolutionary origin of frogs: insights from the primitive anuran Discoglossus

JOURNAL OF ANATOMY, Issue 1 2006
Pavla Havelková
Abstract Using cleared-and-stained whole mounts and computer-aided three-dimensional reconstructions made from serial histological sections, we studied the development of the pectoral girdle in Discoglossus pictus, an extant member of an ancient frog lineage, represented for example by Eodiscoglossus from the Middle Jurassic to Early Cretaceous periods in Europe. Basic developmental features were compared with those of extinct Temnospondyli, considered to be the most probable anuran ancestors, and with Triadobatrachus, an early Triassic proanuran. In the endochondral girdle, the separate scapula and coracoid of Discoglossus and other anurans (completed by suprascapular and procoracoid cartilages) evolved from the compact scapulocoracoid of temnospondyls by paedomorphosis. In parallel, the dermal ossifications of the girdle were reduced to a small clavicle and cleithrum. The overall reduction in ossification of the anuran pectoral girdle supports the hypothesis of a paedomorphic origin for Anura. The almost simultaneous appearance of dermal and endochondral ossifications may be explained by the accumulation of developmental events during a short, distinct metamorphosis (which did not occur in neotenic temnospondyls living permanently in water). The sternal elements seem to be neomorphs for the most part, which help to cushion the shock of landing in jumping anurans but which also evolved as functional substitutes (insertion area for the pectoralis muscles) of the temnospondyl interclavicle. [source]

Epidermotropic lesions: a review

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2009
Ossama Abbas
Epidermotropism describes the spread of cells of lymphocytic, epithelial melanocytic, neuroendocrine, histiocytic or muscular origin into the epidermis from an underlying dermal or subcutaneous pathology, that may be primary cutaneous or metastatic. In this review, we aim to discuss the differential diagnosis of epidermotropic lesions and highlight the histological and immunohistochemical characteristics that can help in their differentiation. [source]

Myopericytoma: report of two cases associated with trauma

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2008
Alvaro C. Laga
Myopericytoma is a rare, recently described tumor demonstrating a hemangiopericytoma-like vascular pattern. We present two cases of myopericytoma associated with trauma: a 64-year-old man who developed several nodules on his nose four months after sustaining multiple abrasions to his forehead and nose, and a 72-year-old woman with a solitary growth in the alveolar ridge of unknown duration. Biopsy specimens of the lesions in both cases demonstrated a striking concentric perivascular proliferation of bland spindle-shaped pericytic cells characteristic of myopericytoma. Despite sharing morphologic features with angioleiomyoma, myofibroma and glomus tumor, myopericytoma is thought to represent a distinct perivascular myoid neoplasm of skin and soft tissues. The tumor is characterized by a radial and perivascular arrangement of ovoid, spindled to round neoplastic cells that are immunoreactive to alpha-smooth muscle actin, often for h-caldesmon as well as smooth muscle myosin-heavy chain, and usually negative for desmin antibodies. Most cases of myopericytoma are benign, however, local recurrence and malignancy have recently been reported, Myopericytoma can be multifocal involving a single or multiple anatomic regions, and tends to occur in dermal and superficial soft tissues of adults primarily on the extremities. Our cases are unusual examples of myopericytoma manifesting as multiple nodules on the nose, and a solitary growth on the buccal mucosa after trauma. [source]

Primary Cutaneous Immunocytoma Presenting with Diffuse Subclinical Involvement and Demonstrating Kappa and Lambda Light Chain Restrictions

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005
C. Lorenzo
A 37 year-old man with primary cutaneous immunocytoma with lambda light chain restriction involving the left shoulder was treated with Rituxan with clinical resolution. Four years later, he presented with a six-month history of diffuse asymptomatic erythema. Physical examination revealed three grouped papules on the right upper arm and an irregular sclerotic patch with slight erythema superiorly on the left shoulder at the site of the initial tumor. There was no diffuse erythema. Biopsies were obtained from a papule on the right upper arm, the sclerotic patch on the left shoulder, and clinically uninvolved skin on the right anterior thigh. All three specimens showed a variably dense, predominantly periadnexal and perivascular dermal infiltrate of plasma cells and lymphocytes. The specimen from the right arm demonstrated kappa light chain restriction. The specimen from the right thigh showed lambda light chain restriction. Physical examination six weeks later demonstrated mottled erythema on the anterior thighs. Two biopsies were obtained from the right thigh. One showed immunocytoma. The other was unremarkable. The patient's primary cutaneous immunocytoma demonstrated two unusual findings: (1) histologic presence of tumor in clinically uninvolved and minimally involved skin; and (2) the presence of two distinct monoclonal populations. [source]

Cutaneous Rosai-Dorfman Disease

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005
L. Lin
Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy (SHML), is a rare benign disease of unknown etiology that involves the cervical lymph nodes. Histologic findings include emperiopolesis of lymphocytes and S-100 protein positivity. Extranodal involvement occurs in 30,40% of cases, often involving skin. However, cutaneous Rosai-Dorfman disease without lymph node involvement is uncommon. We describe a case of cutaneous Rosai-Dorfman disease and discuss its clinical and histopathologic findings. A 69-year-old Caucasian male presented with a two-year history of a slowly enlarging violaceous mass on the mid-upper abdomen. He had a history of renal cell carcinoma two-year ago and was asymptomatic without any systemic symptoms. Physical examination revealed a large, violaceous mass of mid-upper abdomen with several violaceous nodules surrounding the periphery. There was no palpable lymphadenopathy. Punch biopsy showed diffuse dermal infiltrates composed of central xanthomatous cells surrounded by lymphoplasmacytic cells. Focal germinal center was noted. Immunostaining revealed strong S-100 and CD68 reactivity of central xanthomatous cells and kappa and lambda polyclonal lymphoplasmacytic cells. Special stains for infectious disorder were negative. Cutaneous Rosai-Dorfman disease is a benign reactive process, often under-recognized due to lack of systemic symptoms and lymphadenopathy. A high index of diagnostic awareness is required for its recognition. [source]

Melanocytic nevi of the breast: a histologic case-control study

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2004
F. Rongioletti
Background:, Melanocytic nevi in the genital, acral, and flexural sites often display clinical and histologic features that may simulate melanoma. We verified whether this is the case also for nevi of the breast. Methods:, Eleven dermatopathologists, from nine Italian Institutions, collected the specimens of melanocytic lesions from the breast and other body sites, excluding the acral, genital, and flexural areas, as controls. Cases and controls were matched for sex and age. All nevi were observed ,blindly' and simultaneously by all participants. For each lesion, 10 histological parameters were analyzed: asymmetry, absence of lateral demarcation of melanocytes, lentiginous proliferation, nested and dyshesive pattern, intraepidermal melanocytes above the basal layer, involvement of the hair follicle, absence of maturation of dermal melanocytes, melanocytic atypia, fibroplasia of the papillary dermis, and lymphocytic dermal infiltrate. Each parameter was scored 2 when present and 1 when absent or not valuable. A total score was calculated for each lesion. Results were statistically analyzed by the chi-square test and the Mann,Whitney U -test. Results:, One hundred and one nevi came from the breast area and 97 from elsewhere. Breast nevi exhibited significantly more atypical features than nevi from other sites. In particular, breast nevi with intraepidermal melanocytes, melanocytic atypia, and dermal fibroplasia were significantly more numerous. We did not find any sexual difference. Conclusions:, To avoid undue concerns, dermatopathologists should be aware that melanocytic nevi of the breast may show a high degree of atypical features. [source]

The spectrum of cutaneous lesions in rheumatoid arthritis: a clinical and pathological study of 43 patients

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2003
C. M. Magro
Introduction:, Rheumatoid arthritis (RA) is an idiopathic arthropathy syndrome that has a propensity to affect the small joints of the hands and feet with extra-articular manifestations comprising skin lesions, neuropathy, pericarditis, pleuritis, interstitial pulmonary fibrosis and a systemic polyarteritis nodosa (PAN)-like vasculitic syndrome. The most widely recognized skin lesion is the rheumatoid nodule. Other skin manifestations are poorly defined. Materials and methods:, Using a natural language search of the authors' outpatient dermatopathology databases, skin biopsies from 43 patients with RA were selected for retrospective analysis in an attempt to define the dermatopathological spectrum of RA and its clinical correlates. Results:, The biopsies were categorized by the dominant histologic pattern, recognizing that in most cases there were additional minor reaction patterns. Palisading and/or diffuse interstitial granulomatous inflammation was the dominant pattern seen in 21 patients; the lesions included nodules, plaques and papules with a predilection to involve skin over joints. Besides interstitial histiocytic infiltrates and variable collagen necrobiosis, these cases also showed interstitial neutrophilia, vasculitis and pauci-inflammatory vascular thrombosis. The dominant morphology in 11 other patients was vasculopathic in nature: pauci-inflammatory vascular thrombosis, glomeruloid neovascularization, a neutrophilic vasculitis of pustular, folliculocentric, leukocytoclastic or benign cutaneous PAN types, granulomatous vasculitis, and lymphocytic vasculitis and finally occlusive intravascular histiocytic foci for which the designation of ,RA-associated intravascular histiocytopathy' is proposed. Rheumatoid factor (RF) positivity and active arthritis were common in this group, with anti-Ro and anticardiolipin antibodies being co-factors contributing to vascular injury in some cases. Immunofluorescent testing in three patients revealed dominant vascular IgA deposition. In nine patients, the main pattern was one of neutrophilic dermal and/or subcuticular infiltrates manifested clinically as urticarial plaques, pyoderma gangrenosum and panniculitis. Conclusions:, The cutaneous manifestations of RA are varied and encompass a number of entities, some of which define the dominant clinical features, such as the rheumatoid papule or subcutaneous cords, while others allude to the histopathology, i.e. rheumatoid neutrophilic dermatosis. We propose a more simplified classification scheme using the adjectival modifiers of ,rheumatoid-associated' and then further categorizing the lesion according to the dominant reaction pattern. Three principal reaction patterns are recognized, namely extravascular palisading granulomatous inflammation, interstitial and/or subcuticular neutrophilia and active vasculopathy encompassing lymphocyte-dominant, neutrophil-rich and granulomatous vasculitis. In most cases, an overlap of the three reaction patterns is seen. Co-factors for the vascular injury that we believe are integral to the skin lesions of RA include RF, anti-endothelial antibodies of IgA class, anti-Ro and anticardiolipin antibodies. [source]