Autoimmunity and epithelial dysplasia in patients with oral lichenoid diseases.

OBJECTIVES: The primary objective of this study was to explore relationship between autoimmunity and epithelial dysplasia in patients with oral lichenoid diseases. MATERIALS AND METHODS: A total of 66 patients with oral lichen planus (OLP), 35 with oral lichenoid lesion (OLL), and 85 with oral lichenoid drug reaction (OLDR) were enrolled. OLP, OLL, and OLDR were diagnosed following the definitions of the modified World Health Organization criteria, except for the absence of epithelial dysplasia. All patients underwent diagnostic incisional biopsy and adjunctive direct immunofluorescence assays. An indirect immunofluorescence assay was conducted to determine the antinuclear antibody (ANA) positivity. RESULTS: OLP and OLDR patients with epithelial dysplasia demonstrated higher prevalence of serum ANA positivity compared to those without epithelial dysplasia. Elevated serum levels of high sensitivity-C reactive proteins were observed in the OLP, OLL, and OLDR patients with epithelial dysplasia. In the DIF analysis, patients with epithelial dysplasia in the OLP exhibited a higher prevalence of C3 deposition in the basement membrane zone. CONCLUSIONS: This study proposed that autoimmunity may contribute to elevating levels of focal and chronic systemic inflammation, potentially influencing abnormal wound healing and development of dysplastic changes in the oral epithelium among patients with oral lichenoid disease.

Unveiling the inhibition mechanism of Clostridioides difficile by Bifidobacterium longum via multiomics approach.

Antibiotic-induced gut microbiota disruption constitutes a major risk factor for Clostridioides difficile infection (CDI). Further, antibiotic therapy, which is the standard treatment option for CDI, exacerbates gut microbiota imbalance, thereby causing high recurrent CDI incidence. Consequently, probiotic-based CDI treatment has emerged as a long-term management and preventive option. However, the mechanisms underlying the therapeutic effects of probiotics for CDI remain uninvestigated, thereby creating a knowledge gap that needs to be addressed. To fill this gap, we used a multiomics approach to holistically investigate the mechanisms underlying the therapeutic effects of probiotics for CDI at a molecular level. We first screened Bifidobacterium longum owing to its inhibitory effect on C. difficile growth, then observed the physiological changes associated with the inhibition of C. difficile growth and toxin production via a multiomics approach. Regarding the mechanism underlying C. difficile growth inhibition, we detected a decrease in intracellular adenosine triphosphate (ATP) synthesis due to B. longum-produced lactate and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Via the differential regulation of proteins involved in translation and protein quality control, we identified B. longum-induced proteinaceous stress. Finally, we found that B. longum suppressed the toxin production of C. difficile by replenishing proline consumed by it. Overall, the findings of the present study expand our understanding of the mechanisms by which probiotics inhibit C. difficile growth and contribute to the development of live biotherapeutic products based on molecular mechanisms for treating CDI.

MET overexpression in ovarian cancer via CD24-induced downregulation of miR-181a: A signalling for cellular quiescence-like state and chemoresistance in ovarian CSCs.

Increased expression of CD24 and MET, markers for cancer stem-like cells (CSCs), are each associated with ovarian cancer severity. However, whether CD24 and MET are co-expressed in ovarian CSCs and, if so, how they are related to CSC phenotype manifestation remains unknown. Our immunohistochemistry analysis showed that the co-expression of CD24 and MET was associated with poorer patient survival in ovarian cancer than those without. In addition, analyses using KM plotter and ROC plotter presented that the overexpression of CD24 or MET in ovarian cancer patients was associated with resistance to platinum-based chemotherapy. In our miRNA transcriptome and putative target genes analyses, miR-181a was downregulated in CD24-high ovarian cancer cells compared to CD24-low and predicted to bind to CD24 and MET 3'UTRs. In OV90 and SK-OV-3 cells, CD24 downregulated miR-181a expression by Src-mediated YY1 activation, leading to increased expression of MET. And, CD24 or MET knockdown or miR-181a overexpression inhibited the manifestation of CSC phenotypes, cellular quiescence-like state and chemoresistance, in OV90 and SK-OV-3 cells: increased colony formation, decreased G0/G1 phase cell population and increased sensitivity to Cisplatin and Carboplatin. Our findings suggest that CD24-miR-181a-MET may consist of a signalling route for ovarian CSCs, therefore being a combinatory set of markers and therapeutic targets for ovarian CSCs.

A novel treatment for Riehl's melanosis targeting both dermal melanin and vessels.

BACKGROUND/PURPOSE: Riehl's melanosis is a difficult-to-treat condition characterized by persisting dermal hyperpigmentation. This study aimed to evaluate the efficacy of a histology-specific targeted therapy for Riehl's melanosis. METHODS: Skin biopsy samples of Riehl's melanosis were assessed to identify histology-specific targets for treatment. Subsequently, the efficacy of a combination involving a fractional picosecond laser and a pulsed dye laser (PDL) targeting the dermal melanin and vessels, respectively, was evaluated. Clinical improvement was assessed using the dermal pigmentation area and severity index (DPASI). The treatment outcomes were compared to those of a control, in this case a single laser treatment solely targeting pigmentation. RESULTS: Histological and immunohistochemical analyses identified dermal melanin pigment and dilated vessels as treatment targets for Riehl's melanosis. The combined treatment of the fractional picosecond laser and PDL showed a significant reduction of the DPASI scores, which was significantly better than the control group. Patients who underwent the combined laser treatment indicated high levels of satisfaction with no adverse events except of transient erythema and oedema. CONCLUSION: The combined treatment of a fractional picosecond laser and a PDL was more effective for Riehl's melanosis compared to single laser treatment. The treatment targets both dermal pigmentation and dilated vessels, offering promising results for those working to manage Riehl's melanosis.

Multiomics analysis reveals the biological effects of live Roseburia intestinalis as a high-butyrate-producing bacterium in human intestinal epithelial cells.

Butyrate-producing bacteria play a key role in human health, and recent studies have triggered interest in their development as next-generation probiotics. However, there remains limited knowledge not only on the identification of high-butyrate-producing bacteria in the human gut but also in the metabolic capacities for prebiotic carbohydrates and their interaction with the host. Herein, it was discovered that Roseburia intestinalis produces higher levels of butyrate and digests a wider variety of prebiotic polysaccharide structures compared with other human major butyrate-producing bacteria (Eubacterium rectale, Faecalibacterium prausnitzii, and Roseburia hominis). Moreover, R. intestinalis extracts upregulated the mRNA expression of tight junction proteins (TJP1, OCLN, and CLDN3) in human intestinal epithelial cells more than other butyrate-producing bacteria. R. intestinalis was cultured with human intestinal epithelial cells in the mimetic intestinal host-microbe interaction coculture system to explore the health-promoting effects using multiomics approaches. Consequently, it was discovered that live R. intestinalis only enhances purine metabolism and the oxidative pathway, increasing adenosine triphosphate levels in human intestinal epithelial cells, but that heat-killed bacteria had no effect. Therefore, this study proposes that R. intestinalis has potentially high value as a next-generation probiotic to promote host intestinal health.

Elevated expression of TLR2 and its correlation with disease activity and clinical manifestations in adult-onset Still's disease.

This study investigated the role of Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR7, and TLR9 in patients with adult-onset Still's disease (AOSD). This study included 20 patients with AOSD and 15 healthy controls (HCs). TLR expression in the peripheral blood was quantified using flow cytometry; TLR expression pattern, in the skin lesions and lymph nodes (LNs) of patients with AOSD, was evaluated immunohistochemically. Significantly higher mean intensities of cells presenting TLR2 and TLR7 from whole blood were observed in patients with AOSD than in HCs. TLR2 expression in whole cells correlated with systemic scores, levels of lactate dehydrogenase and ferritin and serum levels of interleukin-1ß (IL-1ß), IL-6, and IL-18. The percentage of TLR2-positive inflammatory cells was higher in skin biopsy samples from patients with AOSD than those in HCs. TLR9-expressing positive inflammatory cell counts were higher in skin lesions from patients with AOSD than those in the HC, eczema, and psoriasis groups. The expression levels of TLR1, TLR4, TLR7, and TLR9 were higher in LNs of patients with AOSD than in those with T cell lymphoma and reactive lymphadenopathy. Circulating TLR2- and TLR7-positive cells may contribute to the pathogenesis of AOSD. Furthermore, immunohistochemical staining for TLRs in skin lesions and LNs may aid in differentiating AOSD from similar conditions.

Laparoscopic versus open repeat liver resection for recurrent hepatocellular carcinoma in hepatectomy patients: inverse probability of treatment weighting.

Repeat liver resection (RLR) is a good treatment option for recurrent hepatocellular carcinoma (HCC). However, laparoscopic repeat liver resection (LRLR) is more technically demanding than open repeat liver resection (ORLR). The purpose of our study is to compare the surgical outcomes of ORLR and LRLR and to carefully present LRLR guidelines for HCC. We performed RLR at a single institution from January 2017 to November 2019. We divided the patients into an ORLR group and an LRLR group. Inverse probability of treatment weighting (IPTW) was applied in this study to compare the ORLR group and the LRLR group. There was no difference between the two groups in patient characteristics, preoperative blood tests and pathological characteristics. After stabilized IPTW, the LRLR group had a shorter hospital stay (5.52 vs. 9.27 days, p = 0.001) and superior disease-free survival (p = 0.020). LRLR yielded better short-term outcomes than ORLR. And if a regular radiologic examination is performed, most of the recurrent tumors could be detected less than 3 cm. In conclusion, LRLR might be feasible and useful for recurrent HCC located contralateral to the previous tumor at a size of less than 3 cm.

Principal Component Analysis to Differentiate Patients with Palmoplantar Pustulosis from Those with Palmoplantar Pustular Psoriasis.

BACKGROUND: Palmoplantar pustulosis (PPP) is initiated from the acrosyringium. However, it is unclear whether PPP should be considered a distinct entity or should be classified into the spectrum of pustular psoriasis, also known as palmoplantar pustular psoriasis (PPPP). OBJECTIVE: We evaluated the differences in immunohistochemical staining in patients with PPP to determine whether they can be classified into two groups based on psoriatic properties or acrosyringeal properties. METHODS: Nineteen punch biopsy specimens diagnosed with PPP were collected. Antibodies were chosen for identifying the acrosyringeal properties of α-3-nicotine acetylcholine receptors (α-3-nAChR), psoriatic properties of interleukin (IL)-23 and IL-36R, inflammatory cell properties of human cathelicidin antimicrobial peptide 18/LL-37, IL-8, lipocalin-2 (LCN2), and CD3. The degree of staining of the epidermis was evaluated using the ordinal scale (0~3). The principal component analysis was used to derive principal components (PCs) of common variation between the stains, and the two groups were divided using PCs and cluster analysis. RESULTS: Three main PCs explained 64% of the total variance in PPP. PC1 (pustular psoriasis properties) showed a higher correlation with IL-36R. PC2 (acrosyringeal/inflammatory properties) showed a higher correlation with α-3-nAChR, IL-8, LCN2, and CD3. PC3 (psoriasis properties) showed a higher correlation with IL-23. PC1 showed a statistically significant difference (p=0.0284) between the two groups. We identified three PCs associated with the pathomechanisms of PPP. CONCLUSION: Although PC1 showed a statistically significant difference between the two groups, we did not identify differential protein expression related to the pathogenesis between PPP and PPPP.

Effect of changes in Breslow thickness between the initial punch biopsy results and final pathology reports in acral lentiginous melanoma patients.

Acral lentiginous melanoma (ALM) is the most common subtype of cutaneous melanoma among Asians; punch biopsy is widely performed for its diagnosis. However, the pathologic parameters evaluated via punch biopsy may not be sufficient for predicting disease prognosis compared to the parameters evaluated via excisional biopsy. We investigated whether changes in Breslow thickness (BT) between initial punch biopsy results and final pathology reports can affect the prognosis of ALM. Pathologic parameters were recorded from specimens acquired through the initial punch biopsy and wide excision. Patients were classified into two groups based on a change in Breslow depth: the BT increased or decreased on comparing the samples from the initial punch biopsy and final wide excision. We compared clinical characteristics, and a Cox regression model was used to identify independent prognostic factors influencing melanoma-specific death (MSD). Changes in BT did not affect MSD (hazard ratio [HR]: 0.55, P = 0.447). In multivariate analysis, a higher BT (> 2 mm) (HR: 9.93, P = 0.046) and nodal metastasis (HR: 5.66, P = 0.041) were significantly associated with an increased MSD risk. The use of punch biopsy did not affect MSD despite the inaccuracy of BT measurement as long as ALM was accurately diagnosed.

Cell membrane and nuclear expression of programmed death ligand-1 in prostate needle biopsy tissue in prostate cancer patients undergoing primary radiation therapy.

BACKGROUND: Programmed death ligand-1 (PD-L1) expression in cancer is often associated with cancer aggressiveness and responsiveness to treatment with PD-1 pathway inhibitors. We conducted a systematic study on the expression of membranous PD-L1 (mPD-L1) and nuclear PD-1-L1 (nPD-L1) in prostate needle biopsy specimens of prostate cancer patients who underwent primary radiotherapy and analyzed the association between PD-L1 expression and clinicopathological characteristics and prognosis of patients. METHOD: A total of 971 cancer-containing prostate needle biopsy cores from 172 patients were immunohistochemically stained with anti-PD-L1 antibody. The association of PD-L1 expression with Gleason score and tumor volume percentage was evaluated for each biopsy core. Total of 171 patients were divided according to mPD-L1 or nPD-L1 expression, and clinicopathological characteristics were compared between the positive and negative groups. The prognostic significance of mPD-L1, nPD-L1 and common prognostic factors were analyzed in terms of biochemical recurrence. RESULT: Total of 15% and 46% of biopsy cores were stained positive for mPD-L1 and nPD-L1, respectively. There was a positive correlation between Gleason score and mPD-L1 and a negative correlation between Gleason score and nPD-L1. Between mPD-L1 and nPD-L1, there was no significant correlation. There was intraindividual heterogeneity in PD-L1 expression among different Gleason scores. For mPD-L1, only pretreatment PSA was significantly higher in the positive group than in the negative, but not Gleason score and T stage. For nPD-L1, Gleason score and T stage were significantly higher in the positive group than in the negative. Both mPD-L1 and nPD-L1 expression were not predictive of BCR-free survival in univariate and multivariate analyses. CONCLUSIONS: Our results suggest that PD-1 pathway inhibitor may be a potential therapeutic option in high risk prostate cancer patients as early as neoadjuvant setting. The novel discovery of PD-L1 expression in the nucleus of PC should be subjected to further research.

TERT promoter mutations in penile squamous cell carcinoma: high frequency in non-HPV-related type and association with favorable clinicopathologic features.

PURPOSE: Penile carcinoma is a rare malignant neoplasm with a largely unknown molecular pathogenesis. Telomerase reverse transcriptase promoter (TERT-p) mutations have been detected in several types of human malignancies. The aim of this study was to investigate the presence of TERT-p mutations in penile squamous cell carcinomas (SCCs) and their associations with clinicopathologic features. METHODS: In this retrospective study, Sanger sequencing was performed to detect TERT-p mutations in formalin-fixed paraffin-embedded tissue samples from 37 patients with penile SCC, 16 patients with cutaneous SCC, and 4 patients with non-neoplastic penile/skin tissue. The expression of p16INK4a and Ki-67 was investigated via immunohistochemistry. Associations of TERT-p mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed. RESULTS: Recurrent TERT-p mutations were identified in 18 out of 37 (48.6%) penile SCCs, including all 3 carcinoma in situ cases. TERT-p mutations were significantly more frequent in non-human papilloma virus (HPV)-related penile SCC types than in non-HPV-related penile SCC based on both histologic classification and p16INK4a immunoreactivity. Furthermore, TERT-p mutation was associated with a low histologic grade, low mitotic count, absence of necrosis, low Ki-67/MIB-1 labeling index, and absence of lymph node or distant metastasis. CONCLUSION: Our study shows TERT-p mutations are the most frequent somatic mutations in penile SCC. In addition, TERT-p mutations are far more frequent in non-HPV-related penile SCC than in HPV-related penile SCC, indicating TERT-p mutations may have a role in tumorigenesis distinct from HPV-related penile SCC.

Development of an in vitro coculture device for the investigation of host-microbe interactions via integrative multiomics approaches.

The commensal gut bacterium Akkermansia muciniphila is well known as a promising probiotic candidate that improves host health and prevents diseases. However, the biological interaction of A. muciniphila with human gut epithelial cells has rarely been explored for use in biotherapeutics. Here, we developed an in vitro device that simulates the gut epithelium to elucidate the biological effects of living A. muciniphila via multiomics analysis: the Mimetic Intestinal Host-Microbe Interaction Coculture System (MIMICS). We demonstrated that both human intestinal epithelial cells (Caco-2) and the anaerobic bacterium A. muciniphila can remain viable for 12 h after coculture in the MIMICS. The transcriptomic and proteomic changes (cell-cell junctions, immune responses, and mucin secretion) in gut epithelial cells treated with A. muciniphila closely correspond with those reported in previous in vivo studies. In addition, our proteomic and metabolomic results revealed that A. muciniphila activates glucose and lipid metabolism in gut epithelial cells, leading to an increase in ATP production. This study suggests that A. muciniphila improves metabolism for ATP production in gut epithelial cells and that the MIMICS may be an effective general tool for evaluating the effects of anaerobic bacteria on gut epithelial cells.

Hepatocellular Carcinoma Arising from Hepatocellular Adenoma in an Elderly Male Patient.

Hepatocellular adenoma is a benign tumor of the liver occurring predominantly in young women taking oral contraceptives. The malignant transformation of hepatocellular adenoma into hepatocellular carcinoma has rarely been reported. Herein, we report the case of an elderly male patient with hepatocellular carcinoma that developed from hepatocellular adenoma. The patient's high risk for surgery and conflicting biopsy and imaging results made it difficult to determine the treatment direction. Eventually, the mass was completely removed by laparoscopic left hemi-hepatectomy without complications.

Characteristics of the Gut Microbiome of Healthy Young Male Soldiers in South Korea: The Effects of Smoking.

BACKGROUND/AIMS: South Korean soldiers are exposed to similar environmental factors. In this study, we sought to evaluate the gut microbiome of healthy young male soldiers (HYMS) and to identify the primary factors influencing the microbiome composition. METHODS: We prospectively collected stool from 100 HYMS and performed next-generation sequencing of the 16S rRNA genes of fecal bacteria. Clinical data, including data relating to the diet, smoking, drinking, and exercise, were collected. RESULTS: The relative abundances of the bacterial phyla Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria were 72.3%, 14.5%, 8.9%, and 4.0%, respectively. Fifteen species, most of which belonged to Firmicutes (87%), were detected in all examined subjects. Using cluster analysis, we found that the subjects could be divided into the two enterotypes based on the gut microbiome bacterial composition. Compared with enterotype 2 subjects, subjects classified as enterotype 1 tended to be characterized by higher frequencies of potentially harmful lifestyle habits (current smoker: 55.6% vs 36.6%, p=0.222; heavy drinker: 16.7% vs 3.7%, p=0.120; insufficient physical activity: 27.8% vs 14.6%, p=0.318). We identified a significant difference in the microbiome compositions of current and noncurrent smokers (p=0.008); the former differed from the latter mainly in a relatively lower abundance of Bifidobacterium species and a higher abundance of Negativicutes. CONCLUSIONS: A high abundance of Actinobacteria and low abundance of Bacteroidetes were the main features distinguishing the gut microbiomes of HYMS, and current smokers could be differentiated from noncurrent smokers by their lower abundance of Bifidobacterium and higher abundance of Negativicutes.

Arthroscopic Treatment of Septic Arthritis of the Shoulder: Technical Pearls to Reduce the Rate of Reoperation.

BACKGROUND: The aim of this study was to evaluate clinical experience with arthroscopic debridement for septic arthritis of the shoulder joint and to report on our patient outcomes. METHODS: The retrospective analysis included 36 shoulders (male:female, 15:21), contributed by 35 patients (mean age, 63.8 years) treated by arthroscopy for septic arthritis of the shoulder between November 2003 and February 2016. The mean follow-up period was 14.3 months (range, 12-33 months). An additional posterolateral portal and a 70º arthroscope was used to access the posteroinferior glenohumeral (GH) joint and posteroinferior subacromial (SA) space, respectively. Irrigation was performed with a large volume of fluid (25.1±8.1 L). Multiple suction drains (average, 3.3 drains) were inserted into the GH joint and SA space and removed 8.9±4.3 days after surgery. Intravenous antibiotics were administered for 3.9±1.8 weeks after surgery, followed by oral antibiotic treatment for another 3.6±1.9 weeks. RESULTS: Among the 36 shoulders, reoperation was required in two cases (5.6%). The average range of motion achieved was 150.0º for forward flexion and T9 for internal rotation. The mean simple shoulder test score was 7.9±3.6 points. Nineteen shoulders (52.8%) had acupuncture or injection history prior to the infection. Pathogens were identified in 15 shoulders, with Staphylococcus aureus being the most commonly identified pathogen (10/15). Both the GH joint and the SA space were involved in 21 shoulders, while 14 cases involved only the GH joint and one case involved only the SA space. CONCLUSIONS: Complete debridement using an additional posterolateral portal and 70º arthroscope, a large volume of irrigation with >20 L of saline, and multiple suction drains may reduce the reoperation rate.

Subtype of intraductal papillary mucinous neoplasm of the pancreas is important to the development of metachronous high-risk lesions after pancreatectomy.

BACKGROUNDS/AIMS: Although intraductal papillary mucinous neoplasm (IPMN) has showed a favorable prognosis compared to pancreatic ductal adenocarcinoma, its recurrence patterns have somewhat questionable in detail. After partial pancreatectomy for IPMN, the evaluation for risk of metachronous occurrence of high-risk lesions (HRL) in the residual pancreas is important to establish a postoperative surveillance modality and duration of follow-up. This study aimed to evaluate the factors that may predict the metachronous occurrence of HRL in the remnant pancreas after surgery of the IPMN. METHODS: From 2005 to 2016, clinicopathologic and surveillance data for 346 consecutive patients who underwent surgical resection for IPMN were reviewed retrospectively. Histologic subtype was classified as gastric, intestinal, pancreato-biliary, or oncocytic type. RESULTS: All of IPMN were classified as main duct (n=64, 18.5%), branch duct (n=171, 49.4%), and mixed type (n=111, 32.1%). Forty-eight patients (13.9%) experienced recurrence during follow-up. Among these, 9 patients (2.6%) were identified to metachronous development of HRL in the remnant pancreas. After multivariate analysis, high-grade dysplasia (HGD) or invasive carcinoma (IC) compared to low- or intermediate dysplasia was only independent risk factor for recurrence (HR 3.688, 95% CI 2.124- 12.524, p=0.009). The independent risk factors for metachronous development were HGD/IC (HR 8.414, 95% CI 4.310- 16.426, p=0.001), and intestinal/pancreato-biliary subtype compared to gastric subtype (HR 7.874, 95% CI 3.650- 27.027, p=0.010). CONCLUSIONS: Patients with high-grade dysplasia or invasive carcinoma, and with intestinal or pancreatobiliary subtype should undergo close, long-term surveillance of the remnant pancreas after initial resection.

The levels of CXCL12 and its receptor, CXCR4, as a biomarker of disease activity and cutaneous manifestation in adult-onset Still's disease.

OBJECTIVES: This study evaluated the SDF-1/CXCL12 and soluble CXCR4 (sCXCR4) levels, and investigated their clinical relevance in adult-onset Still's disease (AOSD). METHODS: Forty-two AOSD patients and 30 healthy controls (HC) were enrolled for serum sampling. Expression levels of CXCL12 and CXCR4 in skin biopsy materials of 40 AOSD patients, 10 patients with eczema, or 10 psoriasis, and 10 HC skin were evaluated with immunohistochemistry. RESULTS: The serum CXCL12 levels in patients with AOSD (2,452±1,531 pg/mL) were higher than those in HC (1,708±1,322 pg/mL, p=0.017). The serum sCXCR4 levels in patients with AOSD (14,449±16,627 pg/mL) were higher than those in HC (3,046±2,554 pg/mL, p<0.001). Serum CXCL12 levels correlated positively with counts of leukocytes and neutrophils, erythrocyte sedimentation rate, ferritin, and C-reactive protein (CRP). Serum sCXCR4 levels correlated positively with systemic scores, platelet counts, and CRP levels. The serum levels of CXCL12 and sCXCR4 were decreased significantly in the patients with AOSD followed after resolution of disease activity. On immunohistochemical stain, the mean percentage of CXCR4-positive inflammatory cells was 51.4±27.5% and that of CXCL12-positive inflammatory cells was 16.7±13.3% in AOSD patients. CXCR4 was more frequently expressed in inflammatory cells from AOSD patients than in those with eczema or psoriasis and HC skin. CONCLUSIONS: These results provide that sCXCR4 could be a clinical biomarker of evaluation for disease activity in AOSD, and show that CXCR4/CXCL12 may influence the inflammatory condition and skin manifestations of AOSD.

Histopathology and expression of the chemokines CXCL10, CXCL13, and CXCR3 and the endogenous TLR-4 ligand S100A8/A9 in lymph nodes of patients with adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease manifesting with a persistent high-spiking fever, a typical rash, and lymphadenopathy. Endogenous factors related to interleukin-1, such as S100A8/A9 and several chemokines including CXCL10, CXCR3, and CXCL13, potentially play roles in its pathogenesis. We describe the histopathological features and chemokine expression pattern in lymph nodes (LNs) of patients with AOSD. Formalin-fixed, paraffin-embedded excisional LN tissues from 48 patients with AOSD were histologically reviewed. CXCL10, CXCR3, CXCL13, and S100A8/A9 expression was evaluated immunohistochemically. The pathology of LN was characterized by paracortical hyperplasia with proliferation of histiocyte, immunoblast, CD8-positive lymphoid cell and blood vessel. Most cases required differential diagnosis from dermatopathic lymphadenitis (n = 16, 33.3%), T cell lymphoma (n = 11, 22.9%), and histiocytic necrotizing lymphadenitis (HNL) (n = 9, 18.8%). The expression levels of CXCL10 and CXCR3 were higher in patients with AOSD than in those with T cell lymphoma, HNL, tuberculous lymphadenitis, and reactive hyperplasia. It is important to recognize the aforementioned histopathologic findings of nodal involvement of AOSD because improper diagnosis and treatment can be avoided. Immunohistochemical staining for chemokines, CXCL10 and CXCR3, may aid in differentiating AOSD from other mimickers.

Expression of EpCAM in adenoid cystic carcinoma.

The mutational landscape of adenoid cystic carcinoma (ACC) is currently being revealed, but further studies are needed to identify biomarkers as therapeutic targets or prognostic factors of ACC. In this study, we investigated the expression of epithelial cell adhesion molecule (EpCAM) in ACCs. We retrospectively collected 83 cases of surgically resected ACCs. Using tissue microarray, we conducted immunohistochemical staining using the anti-EpCAM antibody. EpCAM expression was analysed by intensity score and the total immunostaining score. The positivity was 97.6% (81/83 cases), regardless of the intensity score. A higher histological grade (p = 0.006) and specific tumour location (non-salivary gland origin, p = 0.02) showed a correlation with higher EpCAM intensity. Higher EpCAM expression by total immunostaining score was associated with histological grade (p = 0.004), distant metastasis (p = 0.004) and poorer prognosis (overall survival p = 0.015 and progression-free survival p = 0.033). We suggest EpCAM as a candidate prognostic marker and a putative therapeutic target in ACC. Also, ACCs arising from salivary gland and non-salivary gland sites, respectively, might display different pathophysiologies in which EpCAM could play a role.

Metastatic Blue Nevus-Like Melanoma Detected by Liquid-Based Catheterized Urine Cytology.

Primary or metastatic malignant melanoma can mimic benign blue nevus in rare cases, making the diagnosis challenging. Herein, we report an exceptionally rare case of blue nevus-like melanoma and its blue nevus-like metastasis which was detected by catheterized urine cytology. The patient presented with blue-colored papuloplaques on his temple which were diagnosed as blue nevus-like melanoma on punch biopsies. While he was admitted for administration of chemotherapy, hematuria was detected. Catheterized urine cytology revealed singly scattered oval to spindle-shaped pigmented cells with a moderate degree of variation in shape and size. Many of them had small nuclei with indiscernible to inconspicuous nucleoli while only a few cells showed nuclear enlargement and nuclear hyperchromasia, which could be diagnostic pitfalls. Most of the cells on the smear were positive for HMB45 immunostaining, which confirmed the diagnosis of metastatic blue nevus-like melanoma. To the best of our knowledge, the present case is the first report describing cytomorphologic findings of blue nevus-like metastasis of melanoma in the urine specimen.