Clinical characteristics and differences of 802 acral tumours, categorized by anatomical sites.

BACKGROUND: Acral skin tumours are common, but information in the literature regarding their incidence is scarce. AIM: To investigate the clinical characteristics and differences in incidence of benign and malignant acral tumours by anatomical site. METHODS: A retrospective review was conducted of 802 patients with acral skin tumours confirmed by skin biopsy between January 2010 and December 2019. Age, sex, duration, symptoms and sites were obtained from medical records and photographs. RESULTS: The mean age of onset was 43.8 years, the male/female ratio was 1 : 1.41, and the mean duration was 68.8 months. Most tumours were asymptomatic (66.7%). In total, 802 acral tumours were identified: 512 (63.8%) were benign and 290 (36.2%) were malignant. The most common benign tumours were benign melanocytic lesions (n = 239), and the most common malignant tumours were melanoma (n = 234). The most common site was the sole (n = 408). Benign melanocytic lesions, melanoma and epidermal cysts were more frequent on the foot, whereas pyogenic granuloma, glomus tumours, haemangiomas and mucous cysts were more frequent on the hand. Glomus tumours, fibromas, mucous cysts and osteomas were more frequent on the nail portion, and benign melanocytic lesions and epidermal cysts were more frequent on the non-nail portion. CONCLUSION: This study reports the incidence of various benign and malignant acral tumours according to site, and we believe the results will be helpful in making a clinical diagnosis.

Non-melanoma skin cancer as a clinical marker for internal malignancies: a nationwide population-based cohort study.

INTRODUCTION: Non-melanoma skin cancers (NMSCs) are the most common cancers in the world, but the risk of internal malignancy in patients with NMSC has not been well investigated. OBJECTIVES: We aimed to assess the risk of internal malignancy in patients with NMSC compared with controls without NMSC in Korean population. METHODS: This nationwide cohort study, compared 27 259 NMSC patients with 54 518 matched controls without NMSC, 40 years or older using the data from Korea Health Insurance Review and Assessment Service from 2007 to 2016. The first 2 years were washout period, and we followed the patients for 8 years to observe the development of any internal malignancies after a diagnosis of NMSC. The Cox proportional hazard model was used to determine the hazard ratios (HRs) for developing internal malignancies. RESULTS: The overall risk of internal malignancies at all sites was 2727.7 and 1392.4 per 100 000 person-years for the patients with NMSC and controls, respectively. The risk was significantly higher in the patients with NMSC (HR 1.866, 95% confidence interval [CI] 1.768-1.970). Bone cancer showed the highest risk (HR 12.745, 95% CI 6.288-25.834), followed by nasal cavity and larynx (HR 10.279, 95% CI 6.178-7.103), oral cavity and pharynx (HR 10.211, 95% CI 7.375-14.137), anus and anal canal (HR 8.147, 95% CI 3.893-17.051) and cervical (HR 5.900, 95% CI 3.694-9.423) cancers with risks greater than fivefold higher in NMSC patients compared with the controls. The risks of cancers of the thorax, oesophagus, breast, lung, stomach, thyroid gland and non-Hodgkin's lymphoma were also statistically higher in the patients with NMSC. In contrast, the risks of cancers of the colon and rectum were found to be significantly decreased in the patients with NMSC (HR 0.765, 95% CI 0.657-0.890). CONCLUSION: Patients with NMSC require careful screening and follow-up for internal malignancy.

Differentiating between hepatocellular carcinoma and intrahepatic cholangiocarcinoma using contrast-enhanced MRI features: a systematic review and meta-analysis.

AIM: To identify magnetic resonance imaging (MRI) features for differentiating hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (IHCC) and summarise their diagnostic accuracy. MATERIALS AND METHODS: PubMed and EMBASE were searched for studies that employed MRI features to differentiate HCC from IHCC. Overlapping descriptors used to denote the same imaging finding in different studies were subsumed under a single feature. The pooled diagnostic accuracies, including the diagnostic odds ratios (DORs) and 95% confidence intervals (CIs) of the identified features, were calculated using a bivariate random-effects model. RESULTS: In total, 1,370 patients with HCC and 687 patients with IHCC in 14 studies were included. Fifty-two descriptors were subsumed under 15 MRI features. Of these, 11 features were informative for differentiating HCC from IHCC. The five MRI features favouring HCC were capsule, arterial diffuse enhancement, portal venous washout, conventional washout, and intralesional fat; the six MRI features favouring IHCC were surface retraction, arterial rim enhancement, progressive enhancement, target appearance on diffusion-weighted and hepatobiliary phase (HBP) images, and bile duct dilatation. These features tended to show high specificity, but low sensitivity. Useful MRI features with high DORs (>20) were capsule (34; 95% CI, 5-215) and intralesional fat (23; 4-85) for HCC and arterial rim enhancement (31; 6-160), progressive enhancement (24; 8-73), and target appearance on HBP images (29; 3-261) for IHCC. CONCLUSION: Eleven informative MRI features for differentiating HCC from IHCC were identified. These features will assist in the accurate diagnosis of these diseases and in disease outcome prediction.

Factors affecting quality of life in patients with vitiligo: a nationwide study.

BACKGROUND: Little is known about factors affecting the quality of life (QoL) of patients with vitiligo, and previous studies have shown conflicting results. OBJECTIVES: To explore the QoL of patients with vitiligo and to identify factors affecting QoL. METHODS: A nationwide questionnaire-based study was conducted with 1123 patients with vitiligo recruited from 21 hospitals in Korea from July 2015 to June 2016. Data were collected using a structured questionnaire for demographic information and the Skindex-29 instrument. Mild or severely impaired QoL in patients with vitiligo was assessed according to each domain (symptoms, functioning and emotions) of Skindex-29. Multivariate logistic regression analyses were performed to determine the factors associated with QoL. RESULTS: Of the enrolled participants, 609 were male and 514 female, with a mean age of 49·8 years (range 20-84). The median duration of disease was 3·0 years (range 0-60). Using multivariate logistic regression modelling, the involvement of visible body parts and a larger affected body surface area were consistently associated with QoL impairment in all three domains of Skindex-29. Additionally, the QoL of patients aged 20-59 years, who potentially had a more active social life than older patients, was associated with functional impairment. Furthermore, a higher educational background was associated with emotional impairment. CONCLUSIONS: A multitude of factors significantly influence the QoL of patients with vitiligo. A better appreciation of these factors would help the management of these patients.

Skin photorejuvenation effects of light-emitting diodes (LEDs): a comparative study of yellow and red LEDs in vitro and in vivo.

BACKGROUND: Red-coloured light-emitting diodes (LEDs) can improve skin photorejuvenation and regeneration by increasing cellular metabolic activity. AIM: To evaluate the effectiveness of visible LEDs with specific wavelengths for skin photorejuvenation in vitro and in vivo. METHODS: Normal human dermal fibroblasts (HDFs) from neonatal foreskin were cultured and irradiated in vitro by LEDs at different wavelengths (410-850 nm) and doses (0-10 J/cm(2) ). In vivo experiments were performed on the skin of hairless mice. Expression of collagen (COL) and matrix metalloproteinases (MMPs) was evaluated by semi-quantitative reverse transcription PCR (semi-qRT-PCR), western blotting and a procollagen type I C-peptide enzyme immunoassay (EIA). Haematoxylin and eosin and Masson trichrome stains were performed to evaluate histological changes. RESULTS: In HDFs, COL I was upregulated and MMP-1 was downregulated in response to LED irradiation at 595 ± 2 and 630 ± 8 nm. In the EIA, a peak result was achieved at a dose of 5 J/cm(2) with LED at 595 ± 2 nm. In vivo, COL I synthesis was upregulated in a dose-dependent manner to both 595 and 630 nm LED irradiation, and this effect was prolonged to 21 days after a single irradiation with a dose of 100 J/cm(2) . These histological changes were consistent with the results of semi-qRT-PCR and western blots. CONCLUSION: Specific LED treatment with 595 ± 2 and 630 ± 8 nm irradiation was able to modulate COL and MMPs in skin, with the effects persisting for at least 21 days after irradiation. These findings suggest that yellow and red LEDs might be useful tools for skin photorejuvenation.

Differentiation of benign and metastatic axillary lymph nodes in breast cancer: additive value of MRI computer-aided evaluation.

AIM: To retrospectively determine the qualitative and quantitative cut-off values of the magnetic resonance computer-aided evaluation (MR CAE) parameters to differentiate between benign and metastatic axillary lymph nodes (ALNs) and to investigate the combined diagnostic performance of MR CAE imaging. MATERIALS AND METHODS: From July 2011 to June 2014, 124 patients who underwent preoperative conventional MR, diffusion-weighted (DW), and MR CAE imaging were included. Computer-generated qualitative and quantitative features for ALNs were recorded, and two breast imaging radiologists interpreted the MR images for the presence of metastatic ALNs using conventional MR and DW, and in combination with MR CAE images by consensus. The cut-off values of MR CAE and diagnostic performance were derived from the receiver operating characteristic (ROC) curve. RESULTS: Thirty-four (26.4%) were ALN positive and 90 (73.6%) were ALN negative on the final histopathological result. On qualitative analysis, visualization on the colour map (p=0.007) and kinetic curve type (p<0.001) were significantly different between the groups. On quantitative analysis, mean values (%) of persistent, plateau, and washout ratios differed significantly (p<0.001). Of these significant parameters, a washout ratio of >49% showed the greatest diagnostic accuracy (area under the ROC curve, 0.909). With conventional MR and DW images, sensitivity, specificity, and accuracy were 82.4%, 85.6%, and 84.7%, respectively. With added information from MR CAE images, accuracy significantly improved to 93.5% (p=0.043). The sensitivity and specificity improved to 91.2% (p=0.403) and 94.4% (p=0.086), respectively. CONCLUSION: The additive use of MR CAE improved diagnostic performance and can be helpful for differentiating benign from metastatic ALNs.

Factors predicting outcomes of penile rehabilitation with udenafil 50 mg following radical prostatectomy.

Udenafil is a selective phosphodiesterase type 5 inhibitor made available in recent years for the treatment of erectile dysfunction. Herein, we evaluated independent predictors of potency recovery in radical prostatectomy (RP) patients who underwent penile rehabilitation with udenafil 50 mg. One hundred and forty-three men who underwent RP were enrolled in a penile rehabilitation program using udenafil 50 mg every other day. The rate of regained potency in the study group was significantly higher compared with the recovery rate seen in patients who were not part of the penile rehabilitation program (41.3% vs 13.0%; P<0.001). On the multivariate Cox analyses, preoperative International Index of Erectile Function-5 scores (hazard ratio (HR), 1.049; P=0.040), alcohol consumption (HR, 2.043; P=0.020) and Gleason biopsy score (HR, 0.368; P=0.024) were independent preoperative predictors for potency recovery. Among post-RP variables, the use of robotic procedures (HR, 2.287; P=0.030) and pathologic stage (HR, 0.506; P=0.038) were significantly associated with potency recovery. This study identified predictive factors for the recovery of potency in patients undergoing penile rehabilitation with udenafil following RP. Our results could provide physicians with useful information for counseling RP patients and selecting optimal candidates for penile rehabilitation.

Expression of soluble adenylyl cyclase in acral melanomas.

Soluble adenylyl cyclase (sAC) regulates melanocytic cells, and is a diagnostic marker for pigmented skin lesions. Because only a few studies on sAC expression in acral melanomas have been performed, we investigated the histopathological significance of sAC expression in 33 cases of acral melanoma, and assessed its diagnostic value in distinguishing melanoma in situ (MIS, n = 17) from acral invasive melanomas (n = 16) and melanocytic naevi (n = 11). Acral melanomas exhibited more marked nuclear immunopositivity compared with acral melanocytic naevi. sAC expression significantly correlated with the nuclear morphology of melanocytes and melanoma cells, namely, hyperchromatic nuclei and prominent nucleoli within vesicular nuclei. sAC expression was predominantly observed in the hyperchromatic nuclei of MIS and the prominent nucleoli invasive melanomas, respectively. In vitro culture models of melanocytes and melanoma cell lines exhibited sAC staining patterns similar to those of acral melanomas. Differentiation induction showed that nuclear and nucleolar expression varied depending on cell morphology. sAC immunostaining may be useful for the differential diagnosis of acral melanocytic lesions, and sAC expressed in the nucleus and nucleolus might be related to cytological and nuclear changes associated with invasion and progression of acral melanomas.

Lichen planus pemphigoides associated with chronic hepatitis B virus infection.

Lichen planus pemphigoides (LPP) is a rare autoimmune dermatosis with the features of both lichen planus (LP) and bullous pemphigoid (BP). Although in rare cases, LPP has been associated with several medications and conditions, it is generally considered an idiopathic disorder, and its pathogenesis remains uncertain. We report a 56-year-old woman who presented with a 2-year history of flat-topped, polygonal, violaceous-colored papules and some bullae. She was diagnosed with chronic hepatitis B virus (HBV) infection, which had been treated intermittently with entecavir. Histopathological examination showed the typical features of LP with subepidermal blisters, and with linear deposits of IgG along the basement membrane zone on direct immunofluorescence. Immunoblotting revealed antibodies directed at the BP180 and BP230 antigens. We diagnosed the patient with LPP, and treated the condition with systemic steroids and dapsone. To our knowledge, this is the first report of LPP in a patient with chronic HBV infection.

Expression and localization of 20α-hydroxysteroid dehydrogenase (20α-HSD) in porcine reproductive tissues during pregnancy.

The aims of this study were to determine the specific site of 20α-HSD expression in the reproductive tissues on day 30 of pregnancy and during pre-parturition. 20α-HSD mRNA was demonstrated to have the highest expression in the placenta on day 30 of pregnancy and in the ovary during pre-parturition. Weak mRNA expression was observed in the uterus and ovary on day 30 of pregnancy. However, the mRNA was not expressed in the oviduct on day 30 of pregnancy. The mRNA was also specifically detected in the placenta on day 30 of pregnancy by northern blot analysis. Western blot analysis indicated that the expression pattern of the 20α-HSD protein in the reproductive tissues was similar to that of 20α-HSD mRNA. Immunohistochemical analysis also revealed that the pig 20α-HSD protein was localized in the trophoblast villus in the placenta on day 30 of pregnancy. It was highly expressed in the glandular epithelial cells of the endometrium and the luminal epithelial cells of the uterus. The 20α-HSD protein was highly localized in the large luteal cells of the ovary on day 30 of pregnancy and during pre-parturition. Taken together, our study demonstrated that the pig 20α-HSD mRNA and protein are mainly localized in the trophoblast villus in the placenta on day 30 of pregnancy. The expression of the protein is also localized in the large luteal cells of the ovary. In addition, the protein is highly expressed in the glandular epithelial cells of the endometrium and the luminal epithelial cells of the uterus.

S100A9 and EGFR gene signatures predict disease progression in muscle invasive bladder cancer patients after chemotherapy.

BACKGROUND: In our previous gene expression profile analysis, IL1B, S100A8, S100A9, and EGFR were shown to be important mediators of muscle invasive bladder cancer (MIBC) progression. The aim of the present study was to investigate the ability of these gene signatures to predict disease progression after chemotherapy in patients with locally recurrent or metastatic MIBC. PATIENTS AND METHODS: Patients with locally advanced MIBC who received chemotherapy were enrolled. The expression signatures of four genes were measured and carried out further functional analysis to confirm our findings. RESULTS: Two of the four genes, S100A9 and EGFR, were determined to significantly influence disease progression (P = 0.023, 0.045, respectively). Based on a receiver operating characteristic curve, a cut-off value for disease progression was determined. Patients with the good-prognostic signature group had a significantly longer time to progression and cancer-specific survival time than those with the poor-prognostic signature group (P < 0.001, 0.042, respectively). In the multivariate Cox regression analysis, gene signature was the only factor that significantly influenced disease progression [hazard ratio: 4.726, confidence interval: 1.623-13.763, P = 0.004]. In immunohistochemical analysis, S100A9 and EGFR positivity were associated with disease progression after chemotherapy. Protein expression of S100A9/EGFR showed modest correlation with gene expression of S100A9/EGFR (r = 0.395, P = 0.014 and r = 0.453, P = 0.004). Our functional analysis provided the evidence demonstrating that expression of S100A9 and EGFR closely associated chemoresistance, and that inhibition of S100A9 and EGFR may sensitize bladder tumor cells to the cisplatin-based chemotherapy. CONCLUSIONS: The S100A9/EGFR level is a novel prognostic marker to predict the chemoresponsiveness of patients with locally recurrent or metastatic MIBC.

Chronic active Epstein-Barr virus infection-associated hydroa vacciniforme-like eruption and Behçet's-like orogenital ulcers.

The cutaneous manifestations of chronic active Epstein-Barr virus (EBV) infection can be diverse. Among them, hydroa vacciniforme-like eruption is one of the best-known features. Although rare, mucosal ulcers have been reported to be associated with EBV as a result of primary infection or immune suppression. We describe a 65-year-old female with recurrent necrotic papulovesicles on the face and both arms for 2 years. She also complained of recurrent oral and genital mucosal ulcers developing simultaneously with skin eruptions. They appeared periodically during the spring and summer and were triggered or aggravated by sun exposure. Skin biopsies from the face and genitalia showed identical findings with dense lymphocytic infiltrations. In addition, in situ hybridization revealed EBV-positive lymphoid cells in both specimens. To our knowledge, this is the first case of serologically and pathologically proven chronic active EBV infection presenting hydroa vacciniforme-like eruption and orogenital ulcers at the same time in one patient.

Two cases of clear cell sarcoma with different clinical and genetic features: cutaneous type with BRAF mutation and subcutaneous type with KIT mutation.

Clear cell sarcoma (CCS), also known as malignant melanoma of soft parts, is a rare malignancy constituting approximately 1% of all soft-tissue sarcomas. It occurs predominantly in the lower extremities of young adults, manifesting as a deep, painless, slow-growing mass. CCS is sometimes confused with other types of melanoma because of its melanocytic differentiation. Although BRAF and KIT mutations are well-known melanocytic tumour-promoting mutations frequently found in cutaneous melanoma, they are rare or absent in CCS. We present two cases of CCS with different clinical and genetic features. Both female patients, aged 25 and 20 years, presented with a palpable nodule on a lower extremity. Biopsies of both tumours revealed features diagnostic of CCS. Each tumour cell was positive for S100 protein and HMB-45. However, one patient's tumour was localized to the dermis, with many multinucleated giant cells, whereas the other was located in the deep subcutaneous fat layer near bone. Fluorescence in situ hybridization demonstrated the presence of a characteristic Ewing sarcoma RNA-binding protein (EWSR)1 gene rearrangement in both cases. Reverse-transcription polymerase chain reaction (PCR) and sequencing of the PCR product revealed an EWSR1-activating transcription factor 1 type 1 fusion transcript in both cases. In addition, we detected BRAF mutation in the dermal type and KIT mutation in the subcutaneous type. It is of interest that the BRAF and KIT mutations are known to be very rare in CCS. On the basis of our observations, we suggest that mutation inhibitors may be useful in selected patients with mutated CCS lineages.

Foxp3(+) regulatory T cells are increased in the early stages of halo nevi: clinicopathological features of 30 halo nevi.

BACKGROUND: There have been few clinical studies of the role of regulatory T cells (Tregs) in halo formation of halo nevus. OBJECTIVE: To evaluate the clinicopathologic features and the presence of Tregs in halo nevi. METHODS: We analyzed 30 halo nevi and performed immunohistochemical analysis using antibodies against CD4, CD8, CD25 and Foxp3. We also performed double immunohistochemical staining for Foxp3 and CD25. RESULTS: We found significant increases in Foxp3(+) Tregs, and the shorter the halo nevus duration, the more Foxp3(+) Tregs were detected. Also, the ratio of Foxp3 to CD8 T cells was increased in early stages of halo nevi. Double immunohistochemical staining suggested that the Tregs in the halo nevi were CD25(+)Foxp3(+) T cells. CONCLUSIONS: Foxp3(+) Tregs were greatly increased in the halo nevi. The shorter the halo nevi duration, the more Foxp3(+) Tregs were involved in the earlier developmental stages of halo nevi.

RUNX3 methylation in normal surrounding urothelium of patients with non-muscle-invasive bladder cancer: potential role in the prediction of tumor progression.

PURPOSE: Previously, we reported a causal relationship between RUNX3 methylation and bladder tumor development. Thus, in order to clarify its role in tumorigenesis, this study aims to identify the function of RUNX3 methylation in normal adjacent urothelium of patients with non-muscle invasive bladder cancer (NMIBC). METHODS: Tumor tissue and donor-matched normal adjacent tissue from 55 patients who underwent transurethral resection (TUR) were selected for the study, and RUNX3 promoter methylation was assessed using methylation-specific polymerase chain reaction (MS-PCR). RESULTS: RUNX3 promoter methylation occurred more frequently in tumor samples than in histologically normal urothelium in patients with NMIBC (P = 0.02). The methylation rates for the RUNX3 promoter in normal adjacent urothelium and tumor tissue were 47% and 69%, respectively. Interestingly, RUNX3 methylation in normal adjacent urothelium was associated with tumor number (P = 0.022) and progression (P = 0.035). Kaplan-Meier estimates revealed that RUNX3 methylation in normal urothelium showed a significant association with time to progression (P = 0.017) in NMIBC patients. Stratifying the patients into 'both methylation', 'one methylation' and 'no methylation' groups for tumors and normal urothelium revealed that no progression occurred in the 'no methylation' group during follow-up. Multivariate Cox regression analysis demonstrated that RUNX3 methylation in normal urothelium [hazards ratio (HR): 5.692, P = 0.042] was an independent predictor of progression. CONCLUSIONS: RUNX3 methylation was associated with transition from normal urothelium to bladder tumor. More importantly, RUNX3 methylation in normal adjacent urothelium may predict progression in NMIBC patients who have undergone TUR.

Transcriptional repression of RUNX2 is associated with aggressive clinicopathological outcomes, whereas nuclear location of the protein is related to metastasis in prostate cancer.

BACKGROUND: Runt-related transcription factor 2 (RUNX2) is a transcription factor that is closely related to bone formation, and prostate cancer (CaP) is the most common cancer to metastasize to bone. The present study investigated the expression levels of RUNX2 in human prostate tissue, and the correlation between RUNX2 levels and the clinicopathological characteristics of CaP. METHODS: A case-control study was conducted including 114 cases of newly diagnosed CaP and 114 age-matched BPH patients as controls. RUNX2 expression was estimated using real-time PCR and immunohistochemical staining. RESULTS: The mRNA expression of RUNX2 did not differ between CaP tissues and non-cancer BPH controls (P=0.825). However, RUNX2 expression was significantly decreased in patients with elevated PSA levels (≥20 ng ml(-1)), a Gleason score ≥8 and metastatic disease compared to those with low PSA, low Gleason score and non-metastatic disease (P=0.023, 0.005 and 0.014, respectively). Immunohistochemical analysis showed that 65.2% of the patients with positive RUNX2 nuclear staining had metastatic disease, which was present in only 25.9% of those with negative staining (P=0.010). CONCLUSIONS: RUNX2 mRNA expression was negatively correlated with CaP aggressiveness. Moreover, the nuclear location of RUNX2 may be a prognostic marker of metastasis in CaP.