Metabolomic profiling between vitiligo patients and healthy subjects in plateau exhibited significant differences with those in plain.

Vitiligo is the most common disorder of depigmentation, which is caused by multiple factors like metabolic abnormality, oxidative stress and the disorders of immune. In recent years, several studies have used untargeted metabolomics to analyze differential metabolites in patients with vitiligo, however, the subjects in these studies were all in plain area. In our study, multivariate analysis indicated a distinct separation between the healthy subjects from plateau and plain areas in electrospray positive and negative ions modes, respectively. Similarly, a distinct separation between vitiligo patients and healthy controls from plateau and plain areas was detected in the two ions modes. Among the identified metabolites, the serum levels of sphingosine 1-phosphate (S1P) were markedly higher in vitiligo patients compare to healthy subjects in plain and markedly higher in healthy subjects in plateau compare to those in plain. There are significant differences in serum metabolome between vitiligo patients and healthy subjects in both plateau and plain areas, as well as in healthy subjects from plateau and plain areas. S1P metabolism alteration may be involved in the pathogenesis of vitiligo.

Hypopigmented Mycosis Fungoides: A Clinicopathological Review of 32 Patients.

Background: Hypopigmented mycosis fungoides (hMF) is gradually acknowledged by more dermatologists, yet a consensus regarding its characteristics is not reached. The profile of Chinese hMF patients has not been deeply reviewed previously. Our research may contribute to the understanding of hMF, especially the Chinese patients with Fitzpatrick phototypes of III and IV. Aim: To have a better understanding of hMF in terms of clinical, histopathological and immunohistochemical features in the Chinese population and to determine if there are differences between the Chinese population and other ethnic groups. Methods: We made a retrospective analysis of clinical, histopathological and immunohistochemical features of 32 hMF patients in our hospital from 2010 to 2020. These features were then summarized and compared with previous reports. Results: All patients belonged to Fitzpatrick phototypes of III or IV. Twenty-one male (65.63%) patients and 11 female (34.37%) patients were analyzed, and the male to female ratio was 1.9:1. The age at diagnosis of patients ranged from 4 to 39 years, and the average age at diagnosis of these patients was 18 years, the median age was 16.5. Back was the most frequent site (34.37%). The clinical and histological results of lesions had no distinctive points. Immunohistochemically, among these 32 patients, there were 30 patients whose information was complete, there was 19 patients (63.33%) who were CD8 positive lymphocytes predominance, 9 patients (30%) had CD8 and CD4 positive lymphocyte mixed infiltration, and other 2 patients (6.67%) had CD4 positive lymphocytes predominance. Partial loss of CD7 was only observed in 1 patient (3.33%). Nearly all patients adopted topical nitrogen mustard and topical steroid and most of them had an excellent prognosis. Conclusion: The clinical profiles of hMF in Chinese population shared differences with other ethnic groups, but its histopathological, immunohistochemical results and prognosis condition were resembled with other previous reports. Hence, more patients were needed to find the characteristics of hMF.

Clinicopathological analysis of primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoproliferative disorder: a retrospective study of 22 patients.

BACKGROUND: Primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoproliferative disorder has been defined as a type of lymphoproliferative disorder with indolent clinical course and excellent prognosis, yet a precise diagnosis is still hard to reach. METHODS: A retrospective analysis of 22 patients including 16 females and six males was performed. RESULTS: The age of patients ranged from 5 to 79 years. The average age of all patients was 43.5, and the median age of all patients was 44.5. Two patients had multiple lesions, and others were presented with a solitary asymptomatic lesion. Besides general features, folliculotropism was observed in four cases. In addition to express CD3 and CD4, CD30 were positive to some extent. Some reactive cells could express CD8 and CD20. For follicular helper T-cell markers, although CXCL-13 was negative in the stained cases (18/18), the expression of PD-1 (12/17), BCL-6 (12/16) and CD10 (11/15) was observed in most cases. In addition, we performed T-cell receptor (TCR) rearrangement on five patients, and all of them showed monoclonality. Nearly all patients had excellent prognosis. CONCLUSIONS: Primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoproliferative disorder is complex. Some features like folliculotropism should also be noted. Besides, the expression of follicular helper T-cell markers is not invariable. Moreover, CD8 positivity, Ki-67 index, and lesion number were perhaps not absolute prognostic indicators. To reach a diagnosis of this rare entity, putting all the pieces together is important.

CARD9 Deficiency in a Chinese Man with Cutaneous Mucormycosis, Recurrent Deep Dermatophytosis and a Review of the Literature.

Deficiency of caspase recruitment domain-containing protein 9 (CARD9) is an autosomal recessive primary immunodeficiency disorder, which typically predisposes immunocompetent individuals to single fungal infections and multiple fungal infections are very rare. We study an otherwise healthy 48-year-old man, who had been admitted to our hospital diagnosed with deep dermatophytosis caused by Trichophyton rubrum for three times at 29, 33 and 48 years old, respectively. At the age of 39 years, he suffered from cutaneous mucormycosis due to Mucor irregularis. Moreover, he had a long history of superficial fungal diseases and occasional oral candidiasis. Whole-exome sequencing revealed two compound heterozygous splicing variants in CARD9 gene, c. 184 + 5 G > T and c. 951G > A, confirmed by Sanger sequencing. Patients with recurrent fungal infections especially invasive fungal infections in the absence of known immunodeficiencies should be tested for CARD9 mutations.

miR-128 targets the CC chemokine ligand 18 gene (CCL18) in cutaneous malignant melanoma progression.

BACKGROUND: The CC chemokine ligand 18 (CCL18) has a higher expression in some tumors, while the CCL18 level can be a marker of tumor progression and prognosis. We previously reported that the expression of CCL18 gene was dramatically up-regulated in cutaneous malignant melanoma (CMM) and its expression levels were correlated with tumor thickness. OBJECTIVE: To investigate miRNAs which could target the CCL18 gene so as to mediate CMM development and improvement. METHODS: The expression of miR-128 and CCL18 in CMM were measured by qRT-PCR. The interaction of miR-128 with CCL18 3'UTR was verified by Luciferase reporter gene assay. The changes in expression of CCL18 after miR-128 mimic transfection of A375 melanoma cells were determined by both qRT-PCR and Western-bloting. Cell viability was accessed by CCK8-assay. Flow cytometry was employed to detect the incidence of apoptosis. Clonogenic assay was used to detect the ability of colony formation. Cell migration was evaluated by Transwell migration study. The protein levels of epithelial-mesenchymal transition (EMT), such as E-cadherin, N-cadherin and ß-catenin were analyzed by Western-bloting. RESULTS: The expression of miR-128 had negative relevance with CCL18 in CMM. miR-128 could interact with CCL18 3'UTR. Transfected miR-128 mimic significantly reduced CCL18 expression and this impairment of CCL18 gene promoted apoptosis, inhibited migration and colony formation of A375 melanoma cells. Furthermore, the relative expression of N-cadherin was decreased. CONCLUSION: CCL18 is a target gene of miR-128. Overexpression of miR-128 inhibits the oncogenic effect of CCL18.

Ovostatin 2 knockdown significantly inhibits the growth, migration, and tumorigenicity of cutaneous malignant melanoma cells.

BACKGROUND: We previously identified ovostatin 2 (OVOS2) as a new candidate gene for cutaneous malignant melanoma (CMM) in a Chinese population. In this study, we aimed to investigate the exact role of OVOS2 in cell proliferation, invasion, and tumorigenesis of melanoma A375 cells. METHODS: The downregulation of OVOS2 expression was performed using lentiviral vectors with specific shRNA. The effects of OVOS2 expression on cell proliferation, cell cycle, cell migration, cell invasion, and potential of tumorigenesis were further investigated. RESULTS: The downregulation of OVOS2 significantly suppressed the proliferation of A375 cells and led to a G2/M phase block. The transwell cell migration assay showed that the reduced expression of OVOS2 also significantly inhibited the transmigration of A375 cells. The western blot results showed downregulated expression of p-FAK, p-AKT, and p-ERK. This was accompanied by the upregulated epithelial phenotypes E-cadherin and ß-catenin, and downregulated expression of mesenchymal phenotype N-cadherin after OVOS2 knockdown. The transplantation tumor experiment in BALB/C nude mouse showed that after an observation period of 32 days, the growth speed and weight of the transplanted tumors were significantly suppressed in the BALB/c nude mice subcutaneously injected with OVOS2 knocked-down A375 cells. CONCLUSION: The inhibition of OVOS2 had significant suppressive effects on the proliferation, motility, and migration capabilities of A375 cells, suggesting a crucial promotive role of OVOS2 in the pathogenesis and progression of CMM. The involved mechanisms are at least partly associated with the overactivation of FAK/MAPK/ERK and FAK/PI3K/AKT signals.

[Clinicopathological analysis of 14 cases of early stage dermatofibrosarcoma protuberans].

OBJECTIVE: To improve understanding of the clinical and histopathological features of early stage dermatofibrosarcoma protuberans(DFSP). METHODS: The clinical data and histopathological findings of 14 cases of early stage DFSP diagnosed in Institute of Dermatology, Chinese Academy of Medical Sciences from 2008 to 2014 were retrospectively analyzed. RESULTS: The patients were mostly young people. The average age of onset was 21 years old. The progress was slow. The initial main manifestations were well-circumscribed atrophic erythema or sclerotic plaque, and subcutaneous nodules appeared gradually based on the erythema. Histopathology showed a small number of tumor cells in the upper dermis, aligned parallel to the epidermis with wavy arrangement, while the tumor cells exhibited typical DFSP changes in the lower dermis and the subcutaneous fat. The tumor cells expressed vimentin and CD34, but not S100 and CD68. CONCLUSIONS: Because the clinical and histological features are atypical, the early stage of DFSP is easily misdiagnosed as various benign diseases. Repeated biopsy and combining clinical features with pathological findings are helpful for diagnosis.

[Lymphomatoid papulosis: a clinicopathologic study of 22 cases].

OBJECTIVE: To investigate the clinical presentation, histopathological features, progression, and treatment of lymphomatoid papulosis (LyP). METHODS: A retrospective review was performed on clinicopathological data of 22 patients diagnosed with LyP from June 2010 to March 2015 in Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College. RESULT: The mean age of the 22 LyP patients was 39 years (range: 7-83 years). The male-to-female ratio was 1:1. The areas predominantly affected were the trunks, followed by limbs and face. Most lesions presented as recurrent eruption of erythema, papule, nodules, ulcer, necrosis and crusting. Some of them leaved hyperpigmentation or atrophic scars on healing. Histopathologically, LyP were devided into types A, B, C, D and E, with 12, 1, 1, 3, and 4 cases in each type, respectively, and one case of mixed type B and C. One of the patients was also diagnosed with primary cutaneous anaplastic large-cell lymphoma besides the diagnosis of LyP. Among the 15 patients with follow-up information available, 11 patients were treated with regimens including oral corticosteroids, methotrexate, tripchlorolide, intramuscular injection of interferon, phototherapy, and topical corticosteroids. The mean follow-up time was 22 (1-54) months.All the patients were alive at the end of the follow-up period. CONCLUSIONS: LyP is a low-grade malignant T-cell lymphoma with a benign clinical course but histologically malignant features. Multi-agent chemotherapy is unnecessary. Patients with LyP are likely to have an favorable prognosis.

Expression analysis of ovostatin 2 reveals its involvement in proliferation, invasion and angiogenesis of cutaneous malignant melanoma.

The relationship of ovostatin 2 (OVOS2) expression with the clinicopathological features of cutaneous malignant melanoma (CMM) was investigated to identify OVOS2 expression in cutaneous melanocytic lesions, and to reveal whether OVOS2 has a function in melanoma progression. Eight specimens of CMM and paracancerous tissue were analyzed using real-time polymerase chain reaction (PCR) and western blot for the mRNA and protein expression of OVOS2, respectively. Immunohistochemical staining was performed on 52 CMM and 62 nevi, followed by clinicopathological significance analysis. The proliferative cells were visualized by staining with Ki-67 antibody. The intensity of angiogenesis was assessed by staining with vascular endothelial growth factor (VEGF). Real-time PCR and western blot analyses showed that OVOS2 was significantly upregulated in cutaneous melanoma than in paired normal skins. Immunohistochemistry showed that 86.5% (45/52) of malignant cases showed OVOS2 cytoplasmic expression compared with 29% (18/62) in benign nevi. OVOS2 expression was significantly higher in invasive and metastatic melanoma than in in situ melanoma (P < 0.01). Furthermore, OVOS2 expression was positively correlated with the known prognostic variables of melanoma including clinical stage, Clark level and Breslow depth. It was also significantly associated with ulcer status, Ki-67 labeling index and VEGF expression in primary melanoma. OVOS2 expression was significantly increased in CMM, which increased incrementally from benign nevi to melanoma and appeared to be involved in the progression of melanoma.

Successful treatment of refractory cutaneous infection caused by Mycobacterium marinum with a combined regimen containing amikacin.

BACKGROUND: The incidence of Mycobacterium marinum infection has been increasing. First-line antituberculous drugs and other common antibiotics are effective for most cutaneous M. marinum infections; however, treatment failure still occurs in some rare cases. We report a case of a 70-year-old man with refractory cutaneous infection caused by M. marinum. Reasons for delayed diagnosis and related factors of the refractory infection are also discussed. METHODS: Samples of lesional skin were inoculated on Löwenstein-Jensen medium for acid-fast bacilli. Species of mycobacterium were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. We then carried out genotyping by using mycobacterial interspersed repetitive units and sequencing of heat shock protein 65 (hsp65) and 16S rDNA genes. RESULTS: Tissue cultures for acid-fast bacilli were positive. PCR-RFLP analysis and sequencing of hsp65 and 16S rDNA genes confirmed the isolated organisms to be M. marinum. Systemic therapy with rifampicin, clarithromycin, and amikacin empirically over 6 months led to complete resolution of skin lesions leaving only some residual scars. CONCLUSION: Key diagnostic elements for M. marinum infections include a high index of suspicion raised by chronic lesions, poor response to conventional treatments, and a history of fish-related exposure. Strong clinical suggestion of M. marinum infection warrants initial empirical treatment. The duration of therapy is usually several months or even longer, especially for elderly patients. Amikacin can be considered in multidrug therapy for treatment of some refractory M. marinum infections.

Cutaneous and systemic plasmacytosis showing histopathologic features as mixed-type Castleman disease: a case report.

Cutaneous and systemic plasmacytosis (CSP) is a rare disorder characterized by disseminated reddish brown plaques and polyclonal hypergammaglobulinemia. The lesions of CSP are histologically characterized by an infiltration of mature polyclonal plasma cells, which display similar pathological features to the plasma cell-type Castleman disease (CD). The relationship between CSP and CD is controversial. Herein, we described a 43-year-old man from China with disseminated reddish brown plaques and nodules on the cheek and temple. The serum level of immunoglobulin G and immunoglobulin A were higher than normal. In addition to mature plasma cell perivascular infiltrate in the dermis, the biopsy of the lesions showed small to medium-sized germinal follicles with hyalinized vessels and a concentrically arranged mantle zone. The patient had clinical features of CSP, but the biopsy revealed changes resembling mixed-type CD. To the best of our knowledge, this is the first case of CSP with the pathological features of mixed-type CD reported from China.

Gsdma3 mutation causes bulge stem cell depletion and alopecia mediated by skin inflammation.

Primary cicatricial alopecias (PCAs) are a group of permanent hair loss disorders, of which the pathogenesis is still poorly understood. The alopecia and excoriation (AE) mouse strain is a dominant mutant generated from ethyl nitrosourea mutagenesis. AE mice exhibit a progressive alopecia phenotype similar to that seen in PCAs, resulting from a point mutation in the gasdermin A3 gene. Mutant mice begin to show alopecia on the head from postnatal day 22 and experience complete hair loss by the age of 6 months, along with hyperkeratosis and catagen delay. The results of a histological examination showed that bulge stem cells in AE skin are gradually depleted, as indicated by decreased keratin 15 and CD34 expression, and reduced bromodeoxyuridine label-retaining cells in the AE bulge. In addition, AE mice display an inflammatory condition in the skin from postnatal day 7, including elevated tumor necrosis factor-α and monocyte chemotactic protein-1 mRNA levels and significantly increased macrophages and dendritic cell number. Immune privilege in the bulge was also compromised in AE skin. Consistently, after treatment with the immunosuppressive agent, cyclosporine A, immune privilege collapse, stem cell destruction, and alopecia phenotype of AE mice were all rescued. Collectively, our data demonstrate that immune-mediated destruction of bulge stem cells plays a crucial role in the pathogenesis of alopecia in AE mice, and this strain might be an interesting model for PCAs, especially for lichen planopilaris.

Eruptive microvenular hemangiomas in 4 Chinese patients: clinicopathologic correlation and review of the literature.

Microvenular hemangioma (MVH) is an uncommon benign vascular neoplasm that usually occurs as a solitary asymptomatic red or purple papule, nodule, or plaque with a predilection for the upper extremities. Patients with more than 1 lesion, that is, multiple MVHs, are extremely rare. We describe the clinicopathologic features of 4 Chinese patients who had a rapidly progressive abrupt onset of numerous MVHs numbering in the tens to hundreds. Clinically, the correct diagnosis of MVH could not be made in any of our patients; however, histologic examination revealed the characteristic features of MVH. Immunohistochemical stains were performed in all cases and showed the vessel lining cells to be positive for CD34, CD31, and factor VIII-related antigen. Polymerase chain reaction for human herpesvirus-8 was negative in all cases. The differential diagnosis and review of the literature of patients with multiple MVHs are presented.