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Malakoplakia is a rare pseudotumor that arises in the context of recurrent infections, particularly in immunocompromised states. We report a case of renal allograft parenchymal malakoplakia.A 59-year-old woman successfully received a cadaveric renal transplant in June 2018. Two months after transplantation, she was treated for a urinary tract infection (UTI). In March 2019, she underwent allograft biopsy for increasing creatinine. The biopsy identified T cell mediated rejection and steroid pulse therapy was performed. In December 2019, she was hospitalized for right flank pain and pyuria, and her creatinine level was 1.9 mg/dL. Radiographic findings were suggestive of a hematoma or abscess in the perirenal area, and septated fluid collection was suspected. Biopsy results suggested malakoplakia, and von Kossa stain was positive for Michaelis- Gutmann bodies. Tissue culture demonstrated Escherichia coli, and this was treated with antibiotics. The dose of tacrolimus was reduced. The patient was discharged after 1 month of hospitalization and was maintained on oral antibiotics. Follow-up imaging revealed an increase in the extent of lesion into the adjacent abdominal wall. Assuming the case to be refractory, we performed surgical resection and abscess drainage. Although the renal parenchymal involvement persisted, the size showed a decreasing trend over 2 months of serial observation with ultrasonography.Malakoplakia should be considered as a differential diagnosis for recurrent UTI with graft dysfunction. Malakoplakia can be successfully treated with reduction in immunosuppression and medical therapy using long-term antibiotic treatment in most cases. However, early surgical treatment must be considered for refractory cases.

Background: The association of invasive tracheobronchial aspergillosis (ITBA) with invasive pulmonary aspergillosis (IPA) is not well established. We aimed to compare clinical characteristics between patients who exhibited ITBA with IPA and those who exhibited isolated ITBA (iITBA). Additionally, the usefulness of serum or bronchial galactomannan (GM) tests in diagnosing ITBA was evaluated.Methods: This retrospective single-center case-control study was conducted over a period of 4 years. Fifteen patients were enrolled after confirming the presence of ITBA using bronchoscopy-guided biopsy (iITBA, 7 vs. ITBA+IPA, 8). Clinical characteristics of patients and results obtained from serum or bronchial GM tests were compared between the two groups. Mortality was assessed using data collected from a 6-month follow-up period.Results: The ITBA+IPA group showed a higher prevalence of hematologic malignancy (75% vs. 14%, p=0.029), a greater number of patients with multiple bronchial ulcers (75% vs. 14%, p=0.029), lower platelet counts (63,000/μL vs. 229,000/μL, p

CD47 is expressed in all human cancer cells, including head and neck cancer, and initiates a signaling cascade to inhibit macrophage phagocytosis. However, the mechanism underlying CD47 overexpression has not been elucidated in radioresistant head and neck cancer. The present study demonstrated that decreased Tristetraprolin (TTP) expression induced a sustained overexpression of CD47 using reverse transcription-quantitative PCR and western blotting, and that CD47 overexpression prevented phagocytosis using a phagocytosis assay in a radioresistant HN31R cell line. Subsequently, using TTP transfection, RNA interference, duel-luciferase assay and EMSA, it was revealed that TTP transfection enhanced phagocytosis through degradation of CD47 mRNA by directly binding to CD47 AREs within the CD47 3'UTR. Based on our previous study, methylation-specific PCR and western blotting revealed that DNMT1 was overexpressed in radioresistant HN31R cell line and TTP expression was decreased epigenetically by DMNT1 associated DNA methylation. Overall, these findings provided novel insight into the role of TTP as a biomarker of CD47-positive head and neck cancer patients.

Background and Objectives: Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type is the most common subtype of the ocular adnexal lymphoma. Despite its excellent prognosis, some patients experience partial remission or progressive disease. We aimed to evaluate clinicopathologic differences in the treatment responder group by comparing complete remission (CR) and non-complete remission (non-CR). Materials and Methods: This study retrospectively reviewed 48 patients who were diagnosed with ocular adnexal MALT lymphoma at Ulsan University Hospital between March 2002 and August 2018. Patients who were followed up for less than 6 months were excluded. Histologic and clinical features were analyzed. The patients were divided into two groups: CR and non-CR. Results: Among the 48 patients, 33 achieved CR and 15 achieved non-CR during the median follow-up period of 40.00 months (range, 7–109 months). In univariable analysis, more patients tend to undergo treatment in the CR group, and post-radiotherapy (post-RT) SUVmax, PET and serum lactate dehydrogenase (LDH) levels were higher in the non-CR group (p = 0.043, p = 0.016, and p = 0.042, respectively). In a multivariable analysis, only application of treatment, including radiotherapy or chemotherapy with immunotherapy, was related to CR (odd ratio 7.301, 95% confidence interval 1.273–41.862, p = 0.026). In subgroup analysis according to the site of involvement, none of the variables were significant except for the post-RT SUVmax of PET and level of serum LDH in the non-conjunctiva group (p = 0.026, and p = 0.037, respectively). Seven (14.6%) patients had a recurrence, and those with a recurring site other than the primary site had a higher Ki-67 labeling index, although it was not statistically significant (9.56% vs. 18.00%, p = 0.095). Conclusions: Although belonging to the early stages, the non-CR rate was high in patients with high serum LDH levels, and recurred patients had higher Ki-67. Thus, considering active treatment is recommended in this group of patients.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown cause which leads to alveolar epithelial cell apoptosis followed by basement membrane disruption and accumulation of extracellular matrix, destroying the lung architecture. Oxidative stress is involved in the development of alveolar injury, inflammation, and fibrosis. Oxidative stress-mediated alveolar epithelial cell (AEC) apoptosis is suggested to be a key process in the pathogenesis of IPF. Therefore, the present study investigated whether grape seed proanthocyanidin extract (GSPE) could inhibit the development of pulmonary fibrosis via ameliorating epithelial apoptosis through the inhibition of oxidative stress. We found that GSPE significantly ameliorated the histological changes and the level of collagen deposition in bleomycin (BLM)-induced lungs. Moreover, GSPE attenuated lung inflammation by reducing the total number of cells in bronchoalveolar lavage (BAL) fluid and decreasing the expression of IL-6. We observed that the levels of H2O2 leading to oxidative stress were increased following BLM instillation, which significantly decreased with GSPE treatment both in vivo and in vitro. These findings showed that GSPE attenuated BLM-induced epithelial apoptosis in the mouse lung and A549 alveolar epithelial cell through the inhibition of oxidative stress. Furthermore, GSPE could attenuate mitochondrial-associated cell apoptosis via decreasing the Bax/Bcl-2 ratio. The present study demonstrates that GSPE could ameliorate bleomycin-induced pulmonary fibrosis in mice via inhibition of epithelial apoptosis through the inhibition of oxidative stress.

Long-chain aliphatic amines such as (S,Z)-heptadec-9-en-7-amine and 9-aminoheptadecane were synthesized from ricinoleic acid and oleic acid, respectively, by whole-cell cascade reactions using the combination of an alcohol dehydrogenase (ADH) from Micrococcus luteus, an engineered amine transaminase from Vibrio fluvialis (Vf-ATA), and a photoactivated decarboxylase from Chlorella variabilis NC64A (Cv-FAP) in a one-pot process. In addition, long chain aliphatic esters such as 10-(heptanoyloxy)dec-8-ene and octylnonanoate were prepared from ricinoleic acid and oleic acid, respectively, by using the combination of the ADH, a Baeyer–Villiger monooxygenase variant from Pseudomonas putida KT2440, and the Cv-FAP. The target compounds were produced at rates of up to 37 U g−1 dry cells with conversions up to 90 %. Therefore, this study contributes to the preparation of industrially relevant long-chain aliphatic chiral amines and esters from renewable fatty acid resources.

Background/aim Claudin18.2 (CLDN18.2) is a tight junction protein that has been identified as a promising target in gastric cancer. This study aimed to evaluate the clinical relevance of CLDN18.2 expression in gastric cancer. Patients and methods This study included 367 patients diagnosed with gastric cancer, who underwent curative surgical resection. Immunohistochemical staining for CLDN18.2 was carried out, and expression was scored semi-quantitatively, based on staining intensity and the percentage of staining. Results CLDN18.2 expression was observed in 273 patients (74.4%), and 108 (29.4%) were classified as CLDN18.2-positive by predefined criteria. CLDN18.2 expression was not correlated with age, sex, tumor location, or stage. Expression rates were higher in diffuse-type and HER2-positive tumors. In multivariate survival analysis, CLDN18.2 expression was not associated with survival outcomes. Conclusion Higher expression of CLDN18.2 was observed in diffuse-type and HER2-positive gastric cancers. Meanwhile, CLDN18.2 expression was not associated with survival in patients with gastric cancer.

Background Interpretation of mediastinal biopsy is often challenging even for experienced pathologists especially when a hematolymphoid neoplasm is suspected. Primary mediastinal large B-cell lymphoma (PMLBCL) and classic Hodgkin lymphoma (CHL) represent two major types of mature B-cell lymphomas of the mediastinum. Although PMLBCL and mediastinal CHL share many clinicopathologic characteristics, their treatment strategies and responses are remarkably different. We therefore aimed to find distinctive histologic or protein markers to better differentiate these two lesions. Methods Search for primary mediastinal B-cell lymphomas found 52 consecutive cases from 3 university hospitals of Korea during 2005 to 2012. Among them, 32 cases that were available for additional immunohistochemistry (IHC) assessment were enrolled in this study. These cases consisted of the following: CHL (N = 13), PMLBCL (N = 16), and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL (gray zone lymphoma, N = 3). Along with the clinicopathologic findings, the expression of p63, GATA3 and cyclin E was investigated by IHC in the three categorized lesions mentioned above. Results Most clinical features overlapped between PMLBCL and CHL except for the increased disease progression and mortality found in PMLBCL. In the pathologic review, the presence of epithelioid granuloma favored a diagnosis of CHL, whereas reticulated or alveolar patterns of fibrosis were characteristic of PMLBCL. For protein markers, p63 was predominantly positive in PMLBCL (15/16) compared with CHL (2/13), which indicates that p63 is a marker of the highest diagnostic accuracy when calculated by the area under the ROC curve. GATA3 was expressed in the majority of CHL cases (10/13) compared with PMLBCL (0/16), while the expression of cyclin E was only rarely present in a minor population of PMLBCL. Conclusions P63 expression in tumor cells, even focal expression, and no GATA3 is the most helpful feature in distinguishing PMLBCL from mediastinal CHL.

The aims of this study were to evaluate the diagnostic performance of F-florbetaben PET/CT for detecting amyloid deposits in patients with multiple myeloma (MM) and to identify the optimal PET analysis method.Fourteen patients with MM were prospectively enrolled (6 with amyloidosis, 8 control subjects). Dynamic imaging of the kidneys was performed for 20 minutes, and the retention ratio was obtained. At 90 minutes after injection, PET was performed. All images were assessed qualitatively and quantitatively, and the SUVmax, SUVmean, and SUVratio were obtained. Variables were compared between the amyloidosis group and the control group. Amyloid deposition was confirmed according to international consensus guidelines.Tracer uptake was abnormal in all patients with amyloidosis. The visual detection rate was excellent (100%) in the heart, stomach, and tongue but limited in the kidneys (50%) and poor (0%) in the esophagus, liver, and colon. F-florbetaben PET/CT identified 13 unexpected cases of abnormal uptake, confirming further amyloid deposition. Both spherical and manual volumes of interest showed similar diagnostic performance when evaluating amyloidosis in target organs. There was no significant difference in diagnostic performance between the SUVmax, SUVmean, and SUVratio.F-florbetaben PET/CT can accurately detect systemic amyloid deposits in patients with MM. F-florbetaben PET/CT was particularly useful in the heart, stomach, and tongue but of limited value in the esophagus, liver, and colon. F-florbetaben PET/CT can provide clinical information on organ involvement and could replace pathologic examination for diagnosis of amyloidosis in the future.

EPHA3, a member of the EPH family, is overexpressed in various cancers. We demonstrated previously that EPHA3 is associated with radiation resistance in head and neck cancer via the PTEN/Akt/EMT pathway, the inhibition of EPHA3 significantly enhances the efficacy of radiotherapy in vitro and in vivo. In this study, we investigated the mechanisms of PTEN regulation through EPHA3-related signaling. Increased DNA methyltransferase 1 (DNMT1) and enhancer of zeste homolog 2 (EZH2) levels, along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, correlated with decreased levels of PTEN in radioresistant head and neck cancer cells. Furthermore, PTEN is regulated in two ways: DNMT1-mediated DNA methylation, and EZH2-mediated histone methylation through EPHA3/C-myc signaling. Our results suggest that EPHA3 could display a novel regulatory mechanism for the epigenetic regulation of PTEN in radioresistant head and neck cancer cells.

Recent studies identified germline mutations in HAVCR2 (encoding T-cell immunoglobulin mucin 3) as a genetic factor that predisposes to subcutaneous panniculitis-like T-cell lymphoma (SPTCL). However, the differences between HAVCR2-mutated (HAVCR2MUT) and HAVCR2 wild-type (HAVCR2WT) SPTCLs remain unclear. A nationwide cohort of 53 patients with SPTCL diagnosed at 8 Korean institutions was established. Whole-exome sequencing and RNA-sequencing were performed on 8 patients in the discovery set. In the validation set, targeted gene sequencing or direct sequencing of HAVCR2 was performed. Of 49 patients with available HAVCR2 status, 25 (51.0%) were HAVCR2Y82C. HAVCR2Y82C was associated with younger age (P = .001), development of hemophagocytic lymphohistiocytosis or hemophagocytic lymphohistiocytosis–like systemic illness (P < .001), and short relapse-free survival (RFS) (P = .023). Most mutated genes in SPTCLs were involved in immune responses, epigenetic modifications, and cell signaling. Mutations in UNC13D, PIAS3, and KMT2D were more frequent in HAVCR2WT SPTCLs. At the gene expression level, HAVCR2Y82C SPTCLs were enriched in genes involved in IL6-JAK-STAT3 signaling and in tumor necrosis factor-α signaling via NF-κB. CCR4 was significantly upregulated in HAVCR2WT SPTCLs both at the messenger RNA level and at the protein level. We established a risk stratification system for SPTCL by integrating clinical and histopathological features, including age and HAVCR2 mutation status. This risk stratification system was strongly associated with RFS (P = .031). In conclusion, the HAVCR2Y82C mutation was common in Korean patients with SPTCL and was associated with unique clinicopathological and genetic features. Combining clinicopathological parameters could aid in predicting prognosis for patients with SPTCL.

The molecular features of mantle cell lymphoma (MCL), including its increased incidence, and complex therapies have not been investigated in detail, particularly in East Asian populations. In this study, we performed targeted panel sequencing (TPS) and whole-exome sequencing (WES) to investigate the genetic alterations in Korean MCL patients. We obtained a total of 53 samples from MCL patients from five Korean university hospitals between 2009 and 2016. We identified the recurrently mutated genes such as SYNE1, ATM, KMT2D, CARD11, ANK2, KMT2C, and TP53, which included some known drivers of MCL. The mutational profiles of our cohort indicated genetic heterogeneity. The significantly enriched pathways were mainly involved in gene expression, cell cycle, and programmed cell death. Multivariate analysis revealed that ANK2 mutations impacted the unfavourable overall survival (hazard ratio [HR] 3.126; P = 0.032). Furthermore, TP53 mutations were related to worse progression-free survival (HR 7.813; P = 0.043). Among the recurrently mutated genes with more than 15.0% frequency, discrepancies were found in only 5 genes from 4 patients, suggesting comparability of the TPS to WES in practical laboratory settings. We provide the unbiased genetic landscape that might contribute to MCL pathogenesis and recurrent genes conferring unfavourable outcomes.

BackgroundCentral airway obstruction can be caused by cancer, tracheal intubation, or tuberculosis, among others. If surgery is contraindicated, bronchoscopic therapy may be performed. Bronchoscopic treatment for airway obstruction is continuously evolving. In particular, attempts to overcome the current shortcomings of airway stents (stent migration, mucostasis, and granulation tissue formation) are currently ongoing. To apply a new airway stent to humans, preclinical studies in an appropriate animal model is needed. Canine and porcine tracheas have been used as animal airway stenosis models. However, existing models take a long time to develop (3–8 weeks) and have a disadvantage that the mechanism of stenosis is different from that in humans.PurposeTo establish a new and fast tracheal stenosis model in pigs using a combination of cuff overpressure intubation and electrocautery.MethodsFourteen pigs were divided into three groups: tracheal cautery (TC) group (n = 3), cuff overpressure intubation (COI) group (n = 3), and COI-TC combination group (n = 8). Cuff overpressure (200/400/500 mmHg) was applied using a 9-mm internal diameter endotracheal tube. Tracheal cautery (40/60 watts) was performed using a rigid bronchoscopic electrocoagulator. After intervention, the pigs were observed for 3 weeks and bronchoscopy was performed every 7 days. When the cross-sectional area decreased by > 50%, it was judged that tracheal stenosis was established.ResultsThe time for tracheal stenosis was 14 days in the TC group and 7 days in the COI-TC combination group. In the COI group, no stenosis occurred. In the COI-TC group, electrocautery (40 watts) immediately after intubation for > 1 hour with a cuff pressure of 200 mmHg or more resulted in sufficient tracheal stenosis within 7 days. Moreover, the degree of tracheal stenosis increased in proportion to the cuff pressure and tracheal intubation time.ConclusionsThe combined use of cuff overpressure and electrocautery helped to establish tracheal stenosis in pigs rapidly. This animal model was technically simple and reproducible, and used a mechanism similar to that in human tracheal stenosis. It is expected to help develop new treatments for airway stenosis

Background Small bowel (SB) bleeding accounts for 5% of all gastrointestinal (GI) bleeding cases and 80% of obscure GI bleeding cases. Although angioectasia is the common etiology of SB bleeding, nonsteroidal anti-inflammatory drug (NSAID)-induced SB lesions are also reported as a major cause in studies from Eastern countries. Herein, we assessed the frequency of occurrence of NSAID-induced SB lesions in Korean patients with obscure GI bleeding. Methods We retrospectively analyzed medical records of all consecutive patients aged ≥18 years who underwent capsule endoscopy from March 2018 to February 2019 at Ulsan University Hospital and Kosin University Gospel Hospital. Results Of the 83 subjects (all Korean; mean age ± standard deviation: 59 ± 18 years; age range: 18–84 years; men: n = 52; women: n = 31), 55 (66.2%) had stool with clear blood and 28 (33.8%) had normal stool with iron deficiency anemia. The detection rate of SB bleeding and lesions using capsule endoscopy was 72.3% (60 of 83 patients). A significantly higher frequency (40 of 51) of ulcerative/erosive lesions than other causes was observed in patients with inactive bleeding but visible SB lesions. As a result, NSAID-induced enteropathy accounted for 30.1% of 83 patients with obscure GI bleeding (25 of the all 60 SB bleeding cases). Conclusions Contrary to what is reported for patients in Western countries, this study in Korean patients showed an improved diagnostic yield of capsule endoscopy for obscure GI bleeding and that NSAID-induced enteropathy was the most common etiology of SB bleeding. Aggressive small intestine examination is required for patients with unexplained GI bleeding.

Enzyme-catalyzed esterification of secondary alcohols and multi-hydroxyl compounds is one of the most valuable reactions in organic synthesis. However, it is often difficult to achieve high reaction rates and high regio-selectivities with commonly used enzymes such as lipases and proteases. One of the reasons may include bulky substituents of the secondary alcohols and multi-hydroxyl compounds (e.g., carbohydrates and flavonoids). The stereospecificity pocket of lipases, which is considered as a pocket for the binding of medium substituent, might not accept a large substituent due to steric hindrance. Thereby, this review has focused on the discussion about literature survey and structural feature of the most commonly used lipase (i.e., Candida antarctica lipase B (CAL-B)) and serine-protease (i.e., subtilisin) for acylation of secondary alcohols and complex molecules.

To apply a new airway treatment to humans, preclinical studies in an appropriate animal model is needed. Canine, porcine and leporine tracheas have been employed as animal airway stenosis models using various methods such as chemical caustic agents, laser, and electrocautery. However, existing models take a long time to develop (3-8 weeks) and the mechanism of stenosis is different from that in humans. The aim of the present study was to establish a new and fast tracheal stenosis model in pigs using a combination of cuff overpressure intubation (COI) and electrocautery. Fourteen pigs were divided into three groups: tracheal cautery (TC) group (n=3), COI group (n=3), and COI-TC combination group (n=8). Cuff overpressure (200/400/500 mmHg) was applied using a 9-mm endotracheal tube. Tracheal cautery (40/60 watts) was performed using a rigid bronchoscopic electrocoagulator. After intervention, the pigs were observed for 3 weeks and bronchoscopy was performed every 7 days. When the cross-sectional area decreased by > 50%, it was confirmed that tracheal stenosis was established. The time for tracheal stenosis was 14 days in the TC group and 7 days in the COI-TC combination group. In the COI group, no stenosis occurred. In the COI-TC group, electrocautery (40 watts) immediately after intubation for >1 h with a cuff pressure of 200 mmHg or more resulted in sufficient tracheal stenosis within 7 days. Moreover, the degree of tracheal stenosis increased in proportion to the cuff pressure and tracheal intubation time. The combined use of cuff overpressure and electrocautery helped to establish tracheal stenosis in pigs rapidly.

Background: Small bowel (SB) bleeding accounts for 5% of all gastrointestinal (GI) bleeding cases and 80% of obscure GI bleeding cases. Although angioectasia is the common etiology of SB bleeding, nonsteroidal anti-inflammatory drug (NSAID)-induced SB lesions are also reported as a major cause in studies from Eastern countries. Herein, we assessed the frequency of occurrence of NSAID-induced SB lesions in Korean patients with obscure GI bleeding.Methods: We retrospectively analyzed medical records of all consecutive patients aged ≥18 years that underwent capsule endoscopy from March 2018 to February 2019 at Ulsan University Hospital and Kosin University Gospel Hospital.Results: Of the 83 subjects (all were Korean; mean age ± standard deviation: 59 ± 18 years; age range: 18–84 years; men: n=52; women: n=31), 55 (66.2%) had stools with clear blood and 28 (33.8%) had normal stools with iron deficiency anemia . The detection rate of SB bleeding and lesions using capsule endoscopy was 72.3% (60 of 83 patients). A significantly higher frequency (40 of 51) of ulcerative/erosive lesions than other causes was observed in patients with inactive bleeding but visible SB lesions. As a result, NSAID-induced enteropathy accounted for 41.7% (25 of 60) of all SB bleeding cases.Conclusions: Contrary to what is reported for patients in Western countries, this study in Korean patients showed an improved diagnostic yield of capsule endoscopy for obscure GI bleeding and that NSAID-induced enteropathy was the most common etiology of SB bleeding. Aggressive small intestine examination is required for patients with unexplained GI bleeding.

AIM To provide the overall spectrum of gastrosplenic fistula (GSF) occurring in lymphomas through a systematic review including a patient at our hospital. METHODS A comprehensive literature search was performed in the MEDLINE database to identify studies of GSF occurring in lymphomas. A computerized search of our institutional database was also performed. In all cases, we analyzed the clinicopathologic/radiologic features, treatment and outcome of GSF occurring in lymphomas. RESULTS A literature search identified 25 relevant studies with 26 patients. Our institutional data search added 1 patient. Systematic review of the total 27 cases revealed that GSF occurred mainly in diffuse, large B-cell lymphoma (n = 23), but also in diffuse, histiocytic lymphoma (n = 1), Hodgkin’s lymphoma (n = 2), and NK/T-cell lymphoma (n = 1, our patient). The common clinical presentations are constitutional symptoms (n = 20) and abdominal pain (n = 17), although acute gastrointestinal bleeding (n = 6) and infection symptoms due to splenic abscess (n = 3) are also noted. In all patients, computed tomography scanning was very helpful for diagnosing GSF and for evaluating the lymphoma extent. GSF could occur either post-chemotherapy (n = 10) or spontaneously (n = 17). Surgical resection has been the most common treatment. Once patients have recovered from the acute illness status after undergoing surgery, their long-term outcome has been favorable. CONCLUSION This systematic review provides an overview of GSF occurring in lymphomas, and will be helpful in making physicians aware of this rare disease entity.

Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.

Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.

Background: The association of Invasive tracheobronchial aspergillosis(ITBA) with invasive pulmonary aspergillosis(IPA) is not well-established. We aimed to compare clinical characteristics between patients who exhibited ITBA with IPA and those who exhibited isolated ITBA(iITBA), as well as to evaluate the usefulness of serum or bronchial galactomannan(GM) tests. Methods: A retrospective case-control study, for four years, was conducted at a single center. Fifteen patients were enrolled after confirmation of the presence of ITBA by bronchoscopy-guided biopsy (iITBA=7 vs ITBA+IPA=8). Clinical characteristics and results of serum or bronchial GM test were compared between the two groups. Mortality was assessed through 6-month follow-up data. Results: The ITBA+IPA group showed a higher prevalence of hematologic malignancy (75% vs 14%; p=0.002), greater number of multiple bronchial ulcers (75% vs. 14%; p=0.041), lower platelet counts (63,000/μL vs. 229,000/μL; p=0.001), and significantly higher mortality (63% vs. 0%; p=0.026), relative to those characteristics in the iITBA group. In the ITBA+IPA group, 57% of patients were positive for serum GM test (mean±SEM, 1.61±0.67), whereas all iITBA patients were negative (0.17±0.04; p=0.004). The bronchial GM level was high in both iITBA and ITBA+IPA groups, and did not show a statistical difference (3.13±0.83 vs. 3.45±0.74; p=0.780). Conclusions: Patients with ITBA+IPA had a greater number of hematologic malignancies with lower platelet counts and worse prognoses, compared to those with iITBA. Bronchoscopic findings and bronchial GM test results were more useful than serum GM test results for diagnosing iITBA.

Both gastric adenocarcinoma of fundic gland type (ADC-FG) and carcinoma with lymphoid stroma (lymphoepithelioma-like carcinoma, LELC) are relatively rare. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of LELC. However, the pathogenesis of ADC-FG, as well as the role of EBV in the carcinogenesis of LELC, remain unclear and under debate. The current study presents a case of concurrent ADC-FG and LELC in the stomach in a 69-year-old man. Total gastrectomy was performed, and two separate masses were identified. Upon histological and immunohistochemical examination, the mass located in the lower body was determined to be LELC and the mass in the upper body was diagnosed as ADC-FG. The lesions were characterized by different mucin phenotypes and EBV in situ results. In the lower-body mass, EBV in situ hybridization expression was diffusely strongly positive, but MUC2, MUC5AC, MUC6, and CD10 were all negative. On the other hand, in the upper-body mass, the results were positive for MUC6 but negative for MUC2, MUC5AC, CD10, and EBV by in situ hybridization. The remaining gastric tissue was unremarkable, and perigastric lymph node metastases were absent. Seven months after the gastrectomy, a postoperative computed tomography scan revealed no recurrence or metastasis.

Malignant metastatic melanoma (MM) is the most lethal of all skin cancers, but detailed mechanisms for regulation of melanoma metastasis are not fully understood. Here, we demonstrated that developmentally regulated GTP-binding protein 2 (DRG2) is required for the growth of primary tumors and for metastasis. DRG2 expression was significantly increased in MM compared with primary melanoma (PM) and dysplastic nevi. A correlation between DRG2 expression and poor disease-specific survival in melanoma patients was also identified. Furthermore, inhibition of DRG2 suppressed the binding of Hypoxia-inducible factor 1α to the VEGF-A promoter region, expression of vascular endothelial growth factor (VEGF)-A, and formation of endothelial cell tubes. In experimental mice, DRG2 depletion inhibited the growth of PM and lung metastases and increased survival. These results identify DRG2 as a critical regulator of VEGF-A expression and of growth of PMs and lung metastases.

Curcumin is a yellow-colored ingredient in dietary spice turmeric ( Curcuma longa Linn). This nontoxic polyphenol has antitumor, anti-inflammatory, apoptotic, and antioxidant activities. The ingested curcumin is reduced to multihydrated forms with more potent therapeutic potentials by the curcumin reductase (CurA) from commensal Escherichia coli. In this study, we demonstrated that Vibrio vulnificus CurA ( VvCurA) with 87% sequence similarity to the E. coli CurA exhibits the curcumin-reducing activity through spectrophotometric detection of NADPH oxidation and high performance liquid chromatographic analysis of curcumin consumption and product generation. Afterward, we determined the crystal structures of VvCurA and the VvCurA/NADPH complex, and made the in silico model of the VvCurA/NADPH/curcumin ternary complex through induced fit docking. Based on structural information, active site residues that play critical roles in catalysis have been identified and characterized by mutational and kinetic studies, leading us to propose the reaction mechanism of CurA.

Fatty acids have a low permeability through the cell membrane. Therefore, the intracellular biotransformation of fatty acids can be slow due to supply limitations. The effects of expression level of the fatty acid transporter FadL in Escherichia coli on the biotransformations were investigated. The enhanced expression of FadL led to 5.5-fold increase of the maximum reaction rate Vmax (i.e., 200 μmol/min per g dry cells (200 U/g dry cells)) of the recombinant E. coli expressing a hydratase of Stenotrophomonas maltophilia in the periplasm with respect to hydration of oleic acid. The FadL expression level was also critical for oxidation of 12- and 10- hydroxyoctadecanoic acid by the recombinant E. coli expressing an alcohol dehydrogenase (ADH) of Micrococcus luteus. In addition, the multistep biotransformation of ricinoleic acid into the ester (i.e., (Z)-11-(heptanoyloxy)undec-9-enoic acid) by the recombinant E. coli expressing the ADH of M. luteus and a Baeyer-Villiger monooxygenase of Pseudomonas putida KT2440 was 2-fold increased to 40 U/g dry cells with expression of FadL to an appropriate level. The FadL expression level is one of the critical factors to determine whole-cell biotransformation rates of not only long chain fatty acids but also hydroxy fatty acids. This study may contribute to whole-cell biocatalyst engineering for biotransformation of hydrophobic substances.

Summary The purpose of this study was to examine the prognostic significance of insulin-like growth factor-1 receptor (IGF-1R) expression alone and in relation to the expression of the MET- receptor and the MET-homologous receptor RON, in classical Hodgkin's lymphoma (cHL). Tumour samples from patients with cHL (n = 202; median age 37.5 years) were analysed retrospectively for IGF-R1, MET or RON expression by immunohistochemistry using tissue microarrays. The median follow-up time was 3.7 years (range, 0.1–20 years). Twenty-nine patients (14.3%) expressed IGF-1R protein in Hodgkin/Reed–Sternberg (HRS) cells, which was associated with a better overall survival (OS) (P = 0.036). IGF-1R expression was closely associated with MET receptor expression and low level of lactate dehydrogenase. In patients with cHL receiving doxorubicin, bleomycin, vinblastine and dacarbazine, those expressing IGF-1R showed a trend towards better OS and event-free survival than IGF-1R-negative patients (P = 0.129 and P = 0.115 respectively), but statistical significance was not reached. This study suggests that IGF-1R expression could be associated with better clinical outcome in cHL but is significantly associated with the expression of MET receptor.

Ovarian microcystic stromal tumor (MCST) is a very rare neoplasm; hence, its nomenclature was recently designated as "Distinctive morphologic and immunohistochemical features" in 2009. Its exact origin, etiological genetic alterations, and background are not yet clearly known. Familial adenomatous polyposis (FAP) is an autosomal dominant disease that leads to development of colorectal polyps via germ-line mutations of the APC gene on chromosome 5q21∼22. In this study, we report a 40-year-old female patient who had ovarian MCST and FAP. On sequencing the APC gene in ovarian MSCT, we detected a novel somatic mutation of the APC gene in exon 11, with a heterozygous deletion at nucleotide position c.1540delG (p.Ala514 Profs*9). Mutations of β-catenin (CTNNB1) and FOXL2 were not detected. Although one case demonstrating involvement of Wnt/β-catenin in ovarian MCST associated with FAP has been presented previously, no detailed information was provided. Thus, this is the ovarian MCST with a somatic mutation of APC in a patient with FAP.

We report the findings for 2 patients with a fluid-fluid level seen on endobronchial ultrasound (EBUS) images of bronchogenic cysts. The EBUS images demonstrated a well-circumscribed cyst with a fluid-fluid level showing an anechoic upper part and a relatively hyperechoic lower part. A fluid-fluid level on EBUS imaging of a bronchogenic cyst, which can help confirm the cystic nature of the lesion, has not been previously reported. EBUS-based confirmation of these cysts using fluid-fluid levels may help avoid unnecessary aspiration of the lesions.

The development of biomarkers for the prediction of lymph node metastasis and prognosis is critical for deciding the treatment modality of tongue cancer. The purpose of our study is to investigate the clinical implications of epithelial-mesenchymal transition (EMT) expression in tongue cancer.Historical cohort studyTertiary-care hospital.The study included 95 subjects with tongue cancer who underwent wide excision and neck dissection. According to characteristics of immunohistochemical staining for E-cadherin and vimentin, we classified the tumors as complete EMT phenotype, incomplete EMT phenotype, or epithelial phenotype. The correlation between risk factors and nodal metastasis was assessed, and disease-free survival (DFS) was analyzed.Positive lymph nodes were detected in 46 (48.4%) patients and was found to correlate significantly with depth of invasion ≥ 4 mm and EMT expression on multivariate analysis (P = .030, P = .022, respectively). The mean follow-up period of all patients was 96.3 months (range, 6-149 months). Overall 5-year DFS was 61.7%. On multivariate analysis, the only factors affecting DFS were nodal stage and EMT expression (P = .033, P = .021, respectively).Our study reveals that EMT expression is a significant biomarker for predicting lymph node metastasis and tumor recurrence in tongue cancer. Evaluation of EMT expression in tongue cancer can allow therapy to be offered accordingly.

Recent studies suggest that absolute lymphocyte count, absolute monocyte count and their ratio [lymphocyte/monocyte ratio (LMR)] at diagnosis may predict survival in classical Hodgkin lymphoma (cHL). Here, we investigated the prognostic significance of LMR in cHL patients in relation to age of patients. Subjects included 351 cHL patients (age range from 4 to 84 years, median age 34 years, sex ratio 1.58) who had been followed-up for a median period of 59 months (range, 0.1-245 months). The estimated 5-year overall survival (OS) rate was 86.8%. Subgroup analysis was performed according to patients' age; non-elderly group (

Aims and background Extramedullary hematopoiesis (EMH), a benign condition, is usually observed in patients with hematologic disorders. We report the first case of mass-forming EMH detected on a 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scan in a patient with multiple myeloma (MM). Methods A 58-year-old woman underwent workup for bicytopenia, and was diagnosed with MM based on the results of bone marrow aspiration and serum protein electrophoresis. An 18F-FDG PET/CT scan revealed a paravertebral mass with mild FDG avidity, suggesting a tumorous condition. Results Biopsy was performed to exclude malignancy and the mass was eventually confirmed as EMH. Conclusions Differential diagnosis of a mildly FDG-avid paravertebral mass in MM should include EMH.

We hereby report a case on bronchogenic cyst which is initially non-infected, then becomes infected after bronchoscopic ultrasound (US)-guided transesophageal fine-needle aspiration (FNA). The non-infected bronchogenic cyst appears to be filled with relatively echogenic materials on US, and the aspirate is a whitish jelly-like fluid. Upon contrast-enhanced MRI of the infected bronchogenic cyst, a T1-weighted image shows low signal intensity and a T2-weighted image shows high signal intensity, with no enhancements of the cyst contents, but enhancements of the thickened cystic wall. The patient then undergo video-assisted thoracic surgery 14 days after the FNA. The cystic mass is known to be completely removed, and the aspirate is yellowish and purulent. To understand the image findings that pertain to the gross appearance of the cyst contents will help to diagnose bronchogenic cysts in the future.

Interleukin 23 (IL-23) is an inflammatory cytokine that plays an important role in tumor promotion. Expression of IL-23 is increased in cancer cells and correlates with tumor progression. However, the mechanisms regulating IL-23 expression in cancer cells are still unclear. Here we report that tristetraprolin (TTP), an AU-rich element (ARE)-binding protein, inhibits IL-23 production in CT26 mouse colon cancer cells. Overexpression of TTP decreased the stability of IL-23 mRNA and the expression level of IL-23 in CT26 cells. Conversely, inhibition of TTP by siRNA increased IL-23 production. TTP destabilized a luciferase mRNA reporter containing the IL-23 mRNA 3’UTR, which contains five AREs. Analyses of deletion and point mutants of the IL-23 mRNA 3’UTR demonstrated that the ARE cluster between the third and fifth AREs was responsible for TTP-mediated destabilization of IL-23 mRNA. A RNA electrophoretic mobility shift assay confirmed that TTP binds to this ARE cluster. Taken together, these results demonstrate that TTP acts as a negative regulator of IL-23 gene expression in mouse colon cancer cells and suggest its potential application as a novel therapeutic target to control IL-23-mediated tumor promotion.