Clinical practice consensus for the diagnosis and management of melanoma in Taiwan.

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.

Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries.

BACKGROUND: This study was designed to investigate the association between donor-derived cell-free DNA (dd-cfDNA) and renal allograft injuries. METHODS: This single-center study enrolled 113 adult kidney transplant recipients with kidney biopsies. Plasma and urine dd-cfDNA was detected by target region capture sequencing. RESULTS: Plasma dd-cfDNA fraction was increased in multiple types of injuries, but most significantly in antibody-mediated rejection. Plasma dd-cfDNA fraction in isolated antibody-mediated rejection (1.94%, IQR: 1.15%, 2.33%) was higher than in T cell-mediated rejection (0.55%, IQR: 0.50%, 0.73%, P = 0.002) and negative biopsies (0.58%, IQR: 0.42%, 0.78%, P < 0.001), but lower than in mixed rejection (2.49%, IQR: 1.16%, 4.90%, P = 0.342). Increased urine dd-cfDNA concentration was associated with several types of injury, but most significantly with BK polyomavirus-associated nephropathy. Urine dd-cfDNA concentration in BK polyomavirus-associated nephropathy (12.22 ng/mL, IQR: 6.53 ng/mL, 31.66 ng/mL) was respectively higher than that in T cell-mediated rejection (5.24 ng/mL, IQR: 3.22 ng/mL, 6.99 ng/mL, P = 0.001), borderline change (3.93 ng/mL, IQR: 2.45 ng/mL, 6.30 ng/mL, P < 0.001), and negative biopsies (3.09 ng/mL, IQR: 1.94 ng/mL, 5.05 ng/mL, P < 0.001). Plasma dd-cfDNA fraction was positively associated with glomerulitis (r = 0.365, P < 0.001) and peri-tubular capillaritis (r = 0.344, P < 0.001), while urine dd-cfDNA concentration correlated with tubulitis (r = 0.302, P = 0.002). CONCLUSIONS: Both plasma and urine dd-cfDNA are sensitive markers for renal allograft injuries. The interpretation of a specific disease by dd-cfDNA should be combined with other clinical indicators.

Tris(4'-Nitrobiphenyl)amine─An Octupolar Chromophore with High Two-Photon Absorption Cross-Section and Its Application for Uncaging of Calcium Ions in the Near-Infrared Region.

Compounds with high two-photon absorption (2PA) performance in the near-infrared region have attracted great attention because of their application in the material and biological science. In this study, we have developed a simple and novel octupolar chromophore, tris(4'-nitrobiphenyl)amine 1, with three nitro peripheral groups attached to a triphenylamine core via biphenyl linkers. A mono-branched analogue 2 has also been prepared to investigate the effects of octupolar and dipolar systems on photophysical and 2PA behaviors. Compound 1, despite having a much simpler structure than the previous three-branched scaffolds, exhibits comparable σ2 values, reaching 1330 GM at 730 nm and 900 GM at 820 nm in toluene. Combined with an outstanding σ2/MW ratio (2.2 GM g-1 mol) and a high fluorescence quantum yield (0.51), 1 displays potential as a promising two-photon (2P) probe for bioimaging. Subsequently, the ethylene glycol tetraacetic acid-substituted derivatives featuring octupolar (3 and 5) or dipolar (4 and 6) character have been synthesized and their one-photon (1P) and 2P photochemical reactions have been examined. Finally, 1P- and 2P-triggered uncaging of Ca2+ from these calcium chelators has been confirmed.

A new scoring system facilitating diagnosis of oral squamous malignancy on biopsy specimens.

BACKGROUND: Morphological evaluation of oral mucosal biopsy is sometimes inconclusive, which may delay the diagnosis and treatment of oral squamous malignancy. Immunohistochemical biomarkers denoting oral squamous malignancy would be clinically helpful in such scenario. METHODS: We first studied the expression patterns of four potential biomarkers (cytokeratin 13, cytokeratin 17, Ki-67 and laminin 5 gamma 2 chain) in an exploratory cohort containing 54 surgical specimens from confirmed oral squamous malignancies. A pattern score was assigned to each specific expression pattern of these four biomarkers. A total score from each specimen was then calculated by summing up the four pattern scores. A cut-off value of total score denoting oral squamous malignancy was then determined. Another 34 oral squamous malignancies that were misdiagnosed as non-malignant lesions on their pre-treatment biopsies were used as a validation cohort to test the clinical utility of this scoring system. RESULTS: In the exploratory cohort, fifty-two (96%) of the 54 confirmed oral squamous malignancies had a total score of 9 and above. In the validation cohort, thirty-one (91%) of the 34 pre-treatment oral biopsy specimens also had a total score of 9 or above, supporting the feasibility of using this scoring system to predict immediate risk of oral squamous malignancy. CONCLUSIONS: Our four-biomarker "oral squamous malignancy scoring system" provides reliable prediction for immediate risk of oral squamous malignancy on pre-treatment oral biopsies.

Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas.

The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.

Disulfiram Sensitizes a Therapeutic-Resistant Glioblastoma to the TGF-ß Receptor Inhibitor.

Despite neurosurgery following radiation and chemotherapy, residual glioblastoma (GBM) cells develop therapeutic resistance (TR) leading to recurrence. The GBM heterogeneity confers TR. Therefore, an effective strategy must target cancer stem cells (CSCs) and other malignant cancer cells. TGF-ß and mesenchymal transition are the indicators for poor prognoses. The activity of aldehyde dehydrogenases (ALDHs) is a functional CSC marker. However, the interplay between TGF-ß and ALDHs remains unclear. We developed radiation-resistant and radiation-temozolomide-resistant GBM models to investigate the underlying mechanisms conferring TR. Galunisertib is a drug targeting TGF-ß receptors. Disulfiram (DSF) is an anti-alcoholism drug which functions by inhibiting ALDHs. The anti-tumor effects of combining DSF and Galunisertib were evaluated by in vitro cell grow, wound healing, Transwell assays, and in vivo orthotopic GBM model. Mesenchymal-like phenotype was facilitated by TGF-ß in TR GBM. Additionally, TR activated ALDHs. DSF inhibited TR-induced cell migration and tumor sphere formation. However, DSF did not affect the tumor growth in vivo. Spectacularly, DSF sensitized TR GBM to Galunisertib both in vitro and in vivo. ALDH activity positively correlated with TGF-ß-induced mesenchymal properties in TR GBM. CSCs and mesenchymal-like GBM cells targeted together by combining DSF and Galunisertib may be a good therapeutic strategy for recurrent GBM patients.

Morphologic Diversity of Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of unknown origin. We performed a retrospective histologic review of primary cutaneous MCCs diagnosed from 1997 to 2018 in several clinical institutions and literature review to determine the frequency of various unusual morphologic appearances of MCC. Of the 136 primary MCCs identified, intraepidermal carcinoma or epidermotropism was noted in 11/136 (8%) cases. An association with pilar cyst in 1/136 (0.7%) case, with actinic keratosis in 2/136 (1.5%) cases, with either invasive or in situ squamous cell carcinoma (SCC) in 14/136 (10%) cases, with poroma in 1/136 (0.7%), and with basal cell carcinoma in 1/136 (0.7%) case was noted. Trabecular pattern and rosettes were noted in 7/136 (5%) and 3/136 (2%) cases, respectively. There was one case of metastatic MCC in a lymph node with chronic lymphocytic leukemia and one rare case of metastatic MCC and SCC in a lymph node. Although uncommon, differentiation toward other cell lineage can be observed in both primary and metastatic MCCs. The tumor can assume a variety of histologic appearances including association with SCC, basal cell carcinoma, melanocytic neoplasm, and follicular cyst; as well as exhibit glandular, sarcomatous, and mesenchymal differentiation. This diversity of morphologic appearance of MCC reflects the complexity of its underlying pathogenesis.

Senescence-associated Long Non-coding RNA (SALNR) Delays Oncogene-induced Senescence through NF90 Regulation.

Long non-coding RNAs (lncRNAs) have recently emerged as key players in many physiologic and pathologic processes. Although many lncRNAs have been identified, few lncRNAs have been characterized functionally in aging. In this study, we used human fibroblast cells to investigate genome-wide lncRNA expression during cellular senescence. We identified 968 down-regulated lncRNAs and 899 up-regulated lncRNAs in senescent cells compared with young cells. Among these lncRNAs, we characterized a senescence-associated lncRNA (SALNR), whose expression was reduced during cellular senescence and in premalignant colon adenomas. Overexpression of SALNR delayed cellular senescence in fibroblast cells. Furthermore, we found that SALNR interacts with NF90 (nuclear factor of activated T-cells, 90 kDa), an RNA-binding protein suppressing miRNA biogenesis. We demonstrated that NF90 is a SALNR downstream target, whose inhibition led to premature senescence and enhanced expressions of senescence-associated miRNAs. Moreover, our data showed that Ras-induced stress promotes NF90 nucleolus translocation and suppresses its ability to suppress senescence-associated miRNA biogenesis, which could be rescued by SALNR overexpression. These data suggest that lncRNA SALNR modulates cellular senescence at least partly through changing NF90 activity.

Candida glabrata induced infection of rat tracheal epithelial cells is mediated by TLR-2 induced activation of NF-κB.

An increasing number of reports identified Candida glabrata (C. glabrata) as the important causative agent of invasive pulmonary fungal infection. However, little is known about immune responses to C. glabrata in rat tracheal epithelial cell (RTEC). Here, the effect of C. glabrata on RTEC and the role of TLR-2 and NF-κB in the immune response were investigated by treatment with TLR-2 siRNA and NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC), respectively. Our results showed that the knockdown of TLR-2 and pretreatment of PDTC led to inhibition of cell proliferation by C. glabrata, further enhanced cells in G0/G1 phases, and promoted C. glabrata -induced apoptosis. C. glabrata infection induced the expression or secretion of TLR-2, NF-κB, TNF-α, and IL-6, and its effect was inhibited by knockdown of TLR-2. Pretreatment with PDTC inhibited the C. glabrata -induced expression of TLR2, and also inhibited the expression of p65 subunit of NF-κB in the first 4 h. Although the expression of p65 subunit at 6 h was elevated compared to baseline, the C. glabrata -induced expression of TNF-α and IL-6 remained attenuated by PDTC pretreatment. Therefore, C. glabrata recognized the TLR-2 in rat tracheal epithelial cell (RTEC), and then activated the transcription factor NF-κB and further promoted the secretion of TNF-α and IL-6 to contribute to the immune response and inflammation.

Dual role of CD44 isoforms in ampullary adenocarcinoma: CD44s predicts poor prognosis in early cancer and CD44ν is an indicator for recurrence in advanced cancer.

BACKGROUND: Although postoperative adjuvant chemoradiotherapies prevent recurrence for some patients with ampullary cancer, the recurrence rate is as high as 29% in patients with stage I cancer. In an effort to identify predictors of recurrence in patients with ampullary adenocarcinoma, we investigated the clinical value of assessing standard and variant forms of CD44. METHODS: Immunohistochemistry staining and reverse-transcription polymerase chain reaction (RT-PCR) was used to detect standard and variant forms of CD44 in samples of ampullary adenocarcinoma. The cDNA microarray analysis comparing tumors with or without pancreatic invasion was undertaken and analyzed by Ingenuity Pathway Analysis. RESULTS: The standard CD44 (CD44s) isoform was detected in 76 of 98 patients with ampullary adenocarcinoma, and the negative or weak expression of CD44s was correlated with pancreatic invasion, lymphovascular invasion, advanced stage and bone metastasis. Moderate to dense expression of CD44s was correlated with shorter overall survival in patients with localized cancer (T1 or T2 disease, P=0.0268). The patients with advanced cancer (T3 or T4 disease) and moderate or dense CD44s expression had a trend toward better survival. Alternative splicing of CD44 was confirmed using RT-PCR, which revealed that the CD44ν3-10 isoform was only expressed in patients with cancer recurrence. Fold change of CD44ν6-10 was also increased. In addition, networks containing CD44, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), transforming growth factor-ß (TGF-ß), matrix metalloproteinase 2 (MMP2), AKT, extracellular signal-regulated protein kinase 1 and 2 (ERK1/2), p38 MAPK, activated protein 1 (AP1)' and CTNNB1 were constructed after comparing microarray data from patients with and without pancreatic invasion. CONCLUSIONS: Whereas CD44s functions as tumor-promoting oncoprotein in early localized ampullary adenocarcinoma, CD44 variants are expressed in advanced cancer and patients with recurrence. Regional invasiveness and distant metastasis of ampullary cancer is controlled by a complex interacting network.

Generalized synchronization with uncertain parameters of nonlinear dynamic system via adaptive control.

An adaptive control scheme is developed to study the generalized adaptive chaos synchronization with uncertain chaotic parameters behavior between two identical chaotic dynamic systems. This generalized adaptive chaos synchronization controller is designed based on Lyapunov stability theory and an analytic expression of the adaptive controller with its update laws of uncertain chaotic parameters is shown. The generalized adaptive synchronization with uncertain parameters between two identical new Lorenz-Stenflo systems is taken as three examples to show the effectiveness of the proposed method. The numerical simulations are shown to verify the results.

Dual-state emission and two-wavelength amplified spontaneous emission behaviors observed from symmetric dyes based on functionalized fluorene and benzotriazole units.

Structurally symmetric dyes using functionalized fluorenes and benzotriazole as the main building moieties have been synthesized and found to exhibit efficient dual-state emission (DSE) and interesting two-wavelength or dual amplified spontaneous emission (dual-ASE) behaviors in the solution phase, which may benefit the development of organic gain materials with dual-wavelength amplification.

Concurrent JCPyV-DNAemia Is Correlated With Poor Graft Outcome in Kidney Transplant Recipients with Polyomavirus-associated Nephropathy.

BACKGROUND: Co-infection of JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) is uncommon in kidney transplant recipients, and the prognosis is unclear. This study aimed to investigate the effect of concurrent JCPyV-DNAemia on graft outcomes in BKPyV-infected kidney transplant recipients with polyomavirus-associated nephropathy (PyVAN). METHODS: A total of 140 kidney transplant recipients with BKPyV replication and PyVAN, 122 without concurrent JCPyV-DNAemia and 18 with JCPyV-DNAemia were included in the analysis. Least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to identify prognostic factors for graft survival. A nomogram for predicting graft survival was created and evaluated. RESULTS: The median tubulitis score in the JCPyV-DNAemia-positive group was higher than in JCPyV-DNAemia-negative group (P = 0.048). At last follow-up, the graft loss rate in the JCPyV-DNAemia-positive group was higher than in the JCPyV-DNAemia-negative group (50% versus 25.4%; P = 0.031). Kaplan-Meier analysis showed that the graft survival rate in the JCPyV-DNAemia-positive group was lower than in the JCPyV-DNAemia-negative group (P = 0.003). Least absolute shrinkage and selection operator regression and multivariate Cox regression analysis demonstrated that concurrent JCPyV-DNAemia was an independent risk factor for graft survival (hazard ratio = 4.808; 95% confidence interval: 2.096-11.03; P < 0.001). The nomogram displayed favorable discrimination (C-index = 0.839), concordance, and clinical applicability in predicting graft survival. CONCLUSIONS: Concurrent JCPyV-DNAemia is associated with a worse graft outcome in BKPyV-infected kidney transplant recipients with PyVAN.

CXCR7 activation evokes the anti-PD-L1 antibody against glioblastoma by remodeling CXCL12-mediated immunity.

The interaction between glioblastoma cells and glioblastoma-associated macrophages (GAMs) influences the immunosuppressive tumor microenvironment, leading to ineffective immunotherapies. We hypothesized that disrupting the communication between tumors and macrophages would enhance the efficacy of immunotherapies. Transcriptomic analysis of recurrent glioblastoma specimens indicated an enhanced neuroinflammatory pathway, with CXCL12 emerging as the top-ranked gene in secretory molecules. Single-cell transcriptome profiling of naïve glioblastoma specimens revealed CXCL12 expression in tumor and myeloid clusters. An analysis of public glioblastoma datasets has confirmed the association of CXCL12 with disease and PD-L1 expression. In vitro studies have demonstrated that exogenous CXCL12 induces pro-tumorigenic characteristics in macrophage-like cells and upregulated PD-L1 expression through NF-κB signaling. We identified CXCR7, an atypical receptor for CXCL12 predominantly present in tumor cells, as a negative regulator of CXCL12 expression by interfering with extracellular signal-regulated kinase activation. CXCR7 knockdown in a glioblastoma mouse model resulted in worse survival outcomes, increased PD-L1 expression in GAMs, and reduced CD8+ T-cell infiltration compared with the control group. Ex vivo T-cell experiments demonstrated enhanced cytotoxicity against tumor cells with a selective CXCR7 agonist, VUF11207, reversing GAM-induced immunosuppression in a glioblastoma cell-macrophage-T-cell co-culture system. Notably, VUF11207 prolonged survival and potentiated the anti-tumor effect of the anti-PD-L1 antibody in glioblastoma-bearing mice. This effect was mitigated by an anti-CD8ß antibody, indicating the synergistic effect of VUF11207. In conclusion, CXCL12 conferred immunosuppression mediated by pro-tumorigenic and PD-L1-expressing GAMs in glioblastoma. Targeted activation of glioblastoma-derived CXCR7 inhibits CXCL12, thereby eliciting anti-tumor immunity and enhancing the efficacy of anti-PD-L1 antibodies.

Resveratrol Prevents Vibrio vulnificus-Induced Sepsis by Attenuating Necroptosis.

Objective: This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol (RSV) regulate necroptosis during Vibrio vulnificus (V. vulnificus)-induced sepsis and the potential mechanism. Methods: The effect of RSV on V. vulnificus cytolysin (VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V. vulnificus-induced sepsis mouse model. Results: RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells. RSV also inhibited the inflammatory response, had a protective effect on histopathological changes, and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages, lung, spleen, and liver tissues of V. vulnificus-induced septic mice in vivo. Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V. vulnificus-induced septic mice. RSV also improved the survival of V. vulnificus-induced septic mice. Conclusion: Our findings collectively demonstrate that RSV prevented V. vulnificus-induced sepsis by attenuating necroptosis, highlighting its potency in the clinical management of V. vulnificus-induced sepsis.

High-Frequency Fluctuation Intensity as a Predictor of Post-Stenotic Dilatation in Swine.

OBJECTIVE: To identify the turbulent components of blood flow facilitating aortic lumen dilatation in a post-stenotic dilatation (PSD) porcine model. METHODS: The porcine abdominal aorta (AA) was moderately coarctated to induce overt flow turbulence in the downstream region and to lead to dilatation in time periods between four and twelve weeks. We propose a new metric, fluctuation intensity (FI), to quantify turbulent fluctuations of pulsatile aortic flow measured within twenty minutes post-coarctation. Lumen perimeter ratio (LPR) of the distal-to-suprarenal AA was used to assess the degree of PSD. Using k-means clustering analysis, we first divided FI frequency spectrum into low- and high-frequency fluctuation intensity (LFFI and HFFI), and subsequently grouped animals with coarctation. Receiver operating characteristic (ROC) analysis was performed to evaluate the ability of the proposed metric to predict PSD. RESULTS: The frequency band of the FI spectrum in facilitating aortic lumen dilatation was identified to be 40∼200 Hz. Using sham group as the reference, pigs receiving coarctation were clustered into two groups with (group A) and without (group B) increases in HFFI values. Coarctation significantly increased LPR values in group A, but not in group B. Moreover, group A exhibited a high probability density distribution on severe elastic fiber fragmentation. ROC analysis indicated HFFI to be capable of predicting PSD with excellent sensitivity and specificity. CONCLUSION: High-intensity, high-frequency components of blood flow fluctuations induced by moderate coarctation promote elastic lamella degradation and aortic lumen dilatation. SIGNIFICANCE: HFFI application in flowmeter programs may provide a useful predictor of PSD.

Tissue Quality Comparison Between Heparinized Wet Suction and Dry Suction in Endoscopic Ultrasound-Fine Needle Biopsy of Solid Pancreatic Masses: A Randomized Crossover Study.

Background/Aims: A high-quality sample allows for next-generation sequencing and the administration of more tailored precision medicine treatments. We aimed to evaluate whether heparinized wet suction can obtain higher quality samples than the standard dry-suction method during endoscopic ultrasound (EUS)-guided biopsy of pancreatic masses. Methods: A prospective randomized crossover study was conducted. Patients with a solid pancreatic mass were randomly allocated to receive either heparinized wet suction first or dry suction first. For each method, two needle passes were made, followed by a switch to the other method for a total of four needle punctures. The primary outcome was the aggregated white tissue length. Histological blood contamination, diagnostic performance and adverse events were analyzed as secondary outcomes. In addition, the correlation between white tissue length and the extracted DNA amount was analyzed. Results: A total of 50 patients were enrolled, and 200 specimens were acquired (100 with heparinized wet suction and 100 with dry suction), with one minor bleeding event. The heparinized wet suction approach yielded specimens with longer aggregated white tissue length (11.07 mm vs 7.96 mm, p=0.001) and less blood contamination (p=0.008). A trend towards decreasing tissue quality was observed for the 2nd pass of the dry-suction method, leading to decreased diagnostic sensitivity and accuracy, although the accumulated diagnostic performance was comparable between the two suction methods. The amount of extracted DNA correlated positively to the white tissue length (p=0.001, Spearman̕s ρ=0.568). Conclusions: Heparinized wet suction for EUS tissue acquisition of solid pancreatic masses can yield longer, bloodless, DNA-rich tissue without increasing the incidence of adverse events (ClinicalTrials.gov. identifier NCT04707560).

Distribution and clinical features of lymphomas involving skin in Taiwan.

A wide variety of primary and secondary lymphoma types involves the skin. However, reports with comparisons between both groups are limited in Taiwan. We retrospectively enrolled all cutaneous lymphomas and evaluated their clinicopathologic features. There were 221 cases of lymphoma: 182 (82.3%) primary and 39 (17.7%) secondary. Mycosis fungoides was the most common primary T-cell lymphoma, 92 (41.7%) cases, followed by CD30-positive T-cell lymphoproliferative disorders including lymphomatoid papulosis (n = 33, 14.9%) and cutaneous anaplastic large cell lymphoma (n = 12, 5.4%). The most frequent primary B-cell lymphomas were marginal zone lymphoma (n = 8, 3.6%) and diffuse large B-cell lymphoma (DLBCL), leg type (n = 8, 3.6%). DLBCL including variants was the most common secondary lymphoma involving skin. Most primary lymphomas presented at low-stage (T-cell, 86%; B-cell, 75%), whereas the majority of secondary lymphomas presented at high-stage (T-cell, 94%; B-cell, 100%). Patients with secondary lymphomas had an older mean age, more frequent B symptoms, lower serum albumin and hemoglobin, and a higher frequency of atypical lymphocytes in blood than those with primary lymphomas. In primary lymphomas, older age, lymphoma types, decreased lymphocyte counts and atypical lymphocytes in blood were poorer prognostic factors. In secondary lymphoma patients, lymphoma types, high serum lactate dehydrogenase and low hemoglobin levels predicted poorer survival. We found that the distribution of primary cutaneous lymphomas in Taiwan mirrors that of other Asian countries but shows some differences as compared with Western countries. Primary cutaneous lymphomas have a better prognosis than secondary lymphomas. Histologic classification of lymphomas highly correlated with disease presentation and prognosis.