Clinical efficacy of microwave in the treatment of axillary osmidrosis and primary hyperhidrosis.

Axillary osmidrosis (AO) and primary hyperhidrosis (PH) are common diseases, but there are still difficulties in treatment. Microwave therapy may become a new method. In order to evaluate long-time efficacy of patients with AO or PH treated by microwave and to discuss possible mechanism of microwave therapy by combining results of clinical and pathological, the study was carried out. Ten AO or PH patients with moderate or severe level were selected as subjects, and each subject received microwave treatment of bilateral armpits. The follow-up period lasted 2 years, and the changes of perspiration and odor were evaluated in subjective and objective ways. Each subject took skin biopsy in the treatment area before and after treatment or each follow-up. Hematoxylin-eosin and immunohistochemical staining were performed. Both subjective and objective index reflected the significant improvement of AO and PH after treatment (p < 0.05). Dermatology life quality index score decreased by 10.4 ± 4.6 (p < 0.05). The number of apocrine glands decreased significantly after treatment, and most of them changed from secretory phase to quiescent phase. In conclusion, microwave therapy can destroy apocrine sweat glands, reduce number of functional glands, so as to improve symptoms of AO and PH and elevate quality of life, which is safe, effective, and stable.

Genetic Analysis of Mismatch Repair Genes Alterations in Extramammary Paget Disease.

Extramammary Paget disease (EMPD) is a rare cutaneous malignant neoplasm. The familial occurrence of EMPD and the high risk of concomitant secondary tumors in EMPD patients have gained much attention. These findings highlight the importance of genetic alterations in the tumorigenesis of this skin cancer. Genetic tests and functional analysis of mismatch repair (MMR) genes were performed in EMPD. The results showed that 8 of 20 cases with germline MMR genes mutations and 5 of them exhibited microsatellite instability (MSI). Immunohistochemical staining showed that the tumor tissues from 20 patients had the normal expression of MLH1 but 5 cases had the reduced expression of MSH2. There is a nearly significant correlation between MSI and germline mutations. In 172 cases, rates of germline and somatic mutations were 34.3% and 13.4%, respectively. The mutations of MLH1 V384D (15.7%), R217C (4.1%), and I219V (5.2%) were common in this cancer. In addition, the yeast 2-hybrid and immunoprecipitation assays exhibited reduced interaction between MLH1 and PMS2 in MLH1 V384D and R217C but not I219V. Moreover, MLH1 V384D and R217C had impaired MMR activity compared with the wild-type and I219V mutation by an in vitro MMR assay. The germline mutations in MMR genes are involved in the pathogenesis of EMPD and partially explain the genetic abnormalities for this disease.

Microarray-based identification of differentially expressed genes in extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy accounting for approximately 1-2% of vulvar cancers. The rarity of this disease has caused difficulties in characterization and the molecular mechanism underlying EMPD development remains largely unclear. Here we used microarray analysis to identify differentially expressed genes in EMPD of the scrotum comparing with normal epithelium from healthy donors. Agilent single-channel microarray was used to compare the gene expression between 6 EMPD specimens and 6 normal scrotum epithelium samples. A total of 799 up-regulated genes and 723 down-regulated genes were identified in EMPD tissues. Real-time PCR was conducted to verify the differential expression of some representative genes, including ERBB4, TCF3, PAPSS2, PIK3R3, PRLR, SULT1A1, TCF7L1, and CREB3L4. Generally, the real-time PCR results were consistent with microarray data, and the expression of ERBB4, PRLR, TCF3, PIK3R3, SULT1A1, and TCF7L1 was significantly overexpressed in EMPD (P<0.05). Moreover, the overexpression of PRLR in EMPD, a receptor for the anterior pituitary hormone prolactin (PRL), was confirmed by immunohistochemistry. These data demonstrate that the differentially expressed genes from the microarray-based identification are tightly associated with EMPD occurrence.

Mycobacterium tuberculosis infection is associated with the development of erythema nodosum and nodular vasculitis.

BACKGROUND: Mycobacterium tuberculosis (MTB) infection has been suggested to contribute to the pathogenesis of erythema nodosum (EN) and nodular vasculitis (NV), the classic forms of panniculitis. However, there is little evidence to demonstrate the presence of MTB in the skin lesions. This study is aimed at evaluating the association between MTB infection and the development of EN and NV in a Chinese population. METHODS: A total of 107 patients (36 EN, 27 NV, and 44 others) with vasculitis and 40 control cases with other skin diseases were recruited and their skin lesion samples were subjected to real time polymerase chain reaction (PCR) analysis of the IS6110 and mpt64 gene fragments of MTB. Their blood mononuclear cells were tested for MTB antigen-specific IFN-γ responses by QuantiFERON®-TB Gold In-Tube (IT) assays. RESULTS: PCR analysis revealed that 7/23 (30.4%) and 7/18 (38.9%) of the EN and NV samples were positive for the IS6110 DNA, respectively, which were significantly higher than 3/34 (8.8%) of other vasculitis (OV) and 3/40 (7.5%) of the control samples (p<0.05). The nested Real-Time PCR assay indicated that 6/7 (86%) of the IS6110-positive EN samples, all of the IS6110-positive NV and control samples, but only 1/3 of the IS6110-positive OV samples, were positive for the mpt64 gene. Similarly, 19/32 (59.4%) of the EN patients, 20/26 (76.9%) of the NV patients, and 17/36 (47.2%) of the OV patients were positive for MTB antigen-specific IFN-γ responses, which were significantly higher than 6/40 (15%) of the controls (p<0.05). CONCLUSION: Our data strongly suggest that MTB infection and active TB are associated with the development of NV and EN in Chinese.

Oncogenic mutations in extramammary Paget's disease and their clinical relevance.

Extramammary Paget's disease (EMPD) is a rare cutaneous malignant neoplasm. The genetic alterations underlying its pathogenesis have less been described. Therefore, we analyzed the possible mutations in the KRAS, HRAS, NRAS, BRAF, ARAF, RAF1, PIK3CA, AKT1, CTNNB1 and APC genes as well as methylation and expression of CDH1 in 144 EMPD cases and 42 matched normal skin tissues. A distinct mutation profile was identified in EMPDs with 27 (19%) cases mutant for RAS and RAF genes and 50 (35%) cases harboring oncogenic mutations in PIK3CA and AKT1. Moreover, a mutually exclusive pattern was observed in the genetic variants in these two signaling pathways. No mutation was detected in CTNNB1 and APC genes. High prevalence of low expression and hypermethylation of CDH1 gene was detected in 33 and 48% of the EMPD cases, respectively. Furthermore, PIK3CA and AKT1 mutations were significantly correlated with CDH1 hypermethylation which could explain why the majority of EMPD cases with mutant PIK3CA and AKT1 were invasive. Our study demonstrates that genetic variants associated with constitutive activation of RAS/RAF and PI3K/AKT pathways are involved in the pathogenesis of EMPD. This may represent novel therapeutic targets for this skin cancer.

Correlation of DLC1 gene methylation with oncogenic PIK3CA mutations in extramammary Paget's disease.

Extramammary Paget's disease is a rare cutaneous malignant neoplasm. The genetic and epigenetic mechanisms underlying its pathology remain unknown. In this study, we investigated the expression levels, and mutation and methylation status of a common tumor suppressor gene, deleted in liver cancer 1 (DLC1), and an oncogene, PIK3CA, in tumor (n=132) and normal tissues (n=20) from unrelated patients. The presence of epigenetic and genetic lesions was then correlated to the patient pathology data to determine the potential role of these genes in extramammary Paget's disease etiology and progression. The DLC1 gene was found to be downregulated in 43 (33%) tumors, as compared with immunohistochemistry results from normal tissues. Methylation-sensitive, high-resolution melting analysis indicated that the DLC1 promoter was hypermethylated in 51 (39%) extramammary Paget's disease tumors. This hypermethylation was associated with significantly decreased DLC1 levels (P=0.011), and had a strong positive correlation with advanced age (P=0.002). PIK3CA mutations were detected by direct sequencing in 32 (24%) tumors, the majority of which were invasive. Furthermore, PIK3CA mutations significantly correlated with DLC1 hypermethylation. Thus, aberrant DLC1 methylation and PIK3CA mutations may have important roles in extramammary Paget's disease pathogenesis, and may represent potential molecular targets for therapy.

In vivo reflectance confocal microscopy of extramammary Paget disease: diagnostic evaluation and surgical management.

BACKGROUND: Extramammary Paget disease (EMPD) is a diagnostic challenge. In vivo reflectance confocal microscopy (RCM) has been reported to be useful for in vivo skin tumor evaluation. It may also assist in the surgical management of EMPD lesions. OBJECTIVE: We sought to describe confocal features of EMPD and correlate them with histopathologic findings. The potential of RCM to map the lesions for subsequent surgical management was also investigated. METHODS: A total of 23 lesions from 14 recruited patients were evaluated by RCM and histopathologic examination. RCM was used to delineate preoperative surgical margins in two patients. RESULTS: Erythematous, hyperpigmented, and hypopigmented lesions were evaluated by RCM and results were confirmed by histopathologic examination. Paget cells were observed throughout the epidermis. Typical Paget cells on RCM were characterized by a mild bright nucleus and dark cytoplasm, frequently twice the size of keratinocytes or larger. At the dermoepidermal junction, tumor nests were seen as dark glandular structures. A high density of dendritic cells was observed in pigmented lesions and a low density in erythematous lesions. Dilated vessels and inflammatory cells were seen in pigmented and erythematous lesions. Paget cells within the epidermis and nest structures at the dermoepidermal junction were seen in most lesions. These two features were useful for delineating the margins. Histologic examination corroborated the surgical margins found by RCM. LIMITATIONS: The sensitivity and specificity of these diagnostic features have not been fully studied, and differential diagnostic features require exploration. CONCLUSION: Features correlating well to histopathology are observed on the RCM of EMPD lesions. RCM may be used as an auxiliary diagnostic tool for the diagnosis and management of EMPD.

In vivo reflectance confocal microscopy for the differential diagnosis between vitiligo and nevus depigmentosus.

BACKGROUND: Nevus depigmentosus (ND) is frequently confused with vitiligo. Differential diagnosis can be difficult. In vivo reflectance confocal microscopy (RCM) is a noninvasive technique for real-time en face imaging of the superficial layers of the skin down to the superficial dermis with cellular level resolution close to conventional histopathology. In this study, we tried to use this new technology to study the features of the distribution of pigment cells of these two hypopigmentation disorders and then concluded the differential features. METHODS: Sixty vitiligo patients and 62 ND patients were enrolled in the study. Three points in each patient (lesional, margin of the lesions and adjacent non- lesional points) were examined with RCM. The gray value of image was quantified using software, and we calculated the relative gray value. RESULTS: The RCM image feature was different between vitiligo and ND patients. The differential diagnosis was made based on the following four RCM features: complete absence of pigment cells; the distribution of pigment cells; the margins; and the relative gray value. CONCLUSION: RCM can be used as an auxiliary diagnostic tool for the differential diagnosis between vitiligo and ND.