Advances in Development of Novel Therapeutic Strategies against Multi-Drug Resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) with multi-drug resistance (MDR) is a major cause of serious healthcare-associated infections, leading to high morbidity and mortality. This opportunistic pathogen is responsible for various infectious diseases, such as those seen in cystic fibrosis, ventilator-associated pneumonia, urinary tract infection, otitis externa, and burn and wound injuries. Due to its relatively large genome, P. aeruginosa has great diversity and can use various molecular mechanisms for antimicrobial resistance. For example, outer membrane permeability can contribute to antimicrobial resistance and is determined by lipopolysaccharide (LPS) and porin proteins. Recent findings on the regulatory interaction between peptidoglycan and LPS synthesis provide additional clues against pathogenic P. aeruginosa. This review focuses on recent advances in antimicrobial agents and inhibitors targeting LPS and porin proteins. In addition, we explore current and emerging treatment strategies for MDR P. aeruginosa, including phages, vaccines, nanoparticles, and their combinatorial therapies. Novel strategies and their corresponding therapeutic agents are urgently needed for combating MDR pathogens.

Dynamic Evolution of SARS-CoV-2 in a Patient on Chemotherapy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved significantly during the pandemic and resulted in daunting numbers of genomic sequences. Tracking SARS-CoV-2 evolution during persistent cases could provide insight into the origins and dynamics of new variants. We report here a case of B-cell acute lymphocytic leukemia on chemotherapy with infection of SARS-CoV-2 for more than two months. Genomic surveillance of his serial SARS-CoV-2-positive specimens revealed two unprecedented large deletions, Δ15-26 and Δ138-145, in the viral spike protein N-terminal domain (NTD) and demonstrated their dynamic shifts in generating these new variants. Located at antigenic supersites, these large deletions are anticipated to dramatically change the spike protein NTD in three-dimensional protein structure prediction, which may lead to immune escape but reduce their viral transmissibility. In summary, we present here a new viral evolutionary trajectory in a patient on chemotherapy.

Commentary on why implementing and standardizing histologic diagnosis of myocarditis is crucial for the clinical setting and patient care.

Histological examination of endomyocardial biopsy or myocardium at autopsy is key to the diagnosis of myocarditis. Among pathologists there is currently extensive variability in routine practice and criteria used to define, diagnose, and report myocarditis as well as to achieve consensus on cases. Two manuscripts emphasizing the need to standardize and implement histopathological diagnostic criteria for myocarditis are reviewed.

Myocarditis and endomyocardial biopsy: achieving consensus diagnosis on 100 cases.

The two histopathology benchmarks used to diagnose myocarditis are the Dallas Criteria, developed in 1984 and the European Society of Cardiology criteria, developed in 2013, which added immunohistochemistry for the detection of CD3+ T cells (lymphocytes) and CD68+ macrophages. Despite their near universal acceptance, the extent to which pathologists use these criteria or their own criteria to consistently render the diagnosis of myocarditis on endomyocardial biopsy (EMB) is unknown. We digitally scanned slides from 100 heart biopsies, including a trichrome stain and immunostaining, that were chosen as representative of myocarditis, non-myocarditis, and borderline myocarditis, as diagnosed per one institution's use of the Dallas Criteria. Eight blinded international cardiovascular experts were asked to render diagnoses and offer a confidence score on each case. No clinical histories were shared. There was full initial agreement across all experts on 37 cases (16 myocarditis and 21 non-myocarditis) and moderate consensus on 35 cases. After individual inquiries and group discussion, consensus was reached on 90 cases. Diagnostic confidence was highest among the myocarditis diagnoses, lowest for borderline cases, and significantly different between the three diagnostic categories (myocarditis, borderline myocarditis, non-myocarditis; P-value=8.49 × 10-57; ANOVA). Diagnosing myocarditis, particularly in cases with limited inflammation and injury, remains a challenge even for experts in the field. Intermediate cases, termed "borderline" in the Dallas Criteria, represent those for which consensus is particularly hard to achieve. To increase consistency for the histopathologic diagnosis of myocarditis, we will need more specifically defined criteria, more granular descriptions of positive and negative features, clarity on how to incorporate immunohistochemistry findings, and improved nomenclature.

The impact of curated educational videos on pathology health literacy for patients with a pancreatic, colorectal, or prostate cancer diagnosis.

Despite patients having increased access to their own electronic health record (EHR) in recent times, patients are often still not considered a primary audience of pathology reports. An alternative to in-person patient education is the use of multimedia programming to enhance health literacy. Curated video presentations designed to explain diagnosis-specific pathology terms were reviewed by a board-certified pathologist and oncologist team and then shown to patients with a primary diagnosis of either pancreatic, colorectal, or prostate cancer in-clinic; these patients then completed a secure electronic survey immediately afterwards. Seventy patients were surveyed, with 91% agreeing or strongly agreeing that the video they watched increased their understanding of the medical terms used in their pathology reports, with a corresponding average Likert score (ALS) of 4.21 (SD = 0.77, CI = ± 0.18). Furthermore, 95% agreed or strongly agreed that the video they watched both enhanced their understanding of the role of the pathologist in diagnosing cancer (ALS = 4.27; SD = 0.65, CI = ± 0.15) and reported they found the video useful (ALS = 4.27; SD = 0.53, CI = ± 0.13). Curated videos such as those utilized in this study have the potential to increase patient health literacy and inform patients of the multidisciplinary nature of cancer diagnosis.

A case of the world's largest renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma is often discovered at an early stage due to the increased use of imaging studies in the current era; therefore, its presentation as a gigantic renal cell carcinoma is rarely encountered. CASE PRESENTATION: A 59-year-old male presented to our hospital due to dizziness, fatigue, and increasing abdominal distension. A computed tomography scan showed an extremely large mass occupying most of the abdomen and pelvis. Surgical resection of the mass was performed. The largely cavitary mass with fibrous capsule was 43 cm and 13.0 kg, and contained a large amount of necrotic tissue. A portion of the left kidney was identified at the periphery of the mass, indicating that the tumor was arising from the left kidney. The final pathologic diagnosis was type 1 papillary renal cell carcinoma. CONCLUSION: To the best of our knowledge, this tumor is the world's largest malignant renal tumor.

Lipid inclusions in cardiac myocytes - a rare case of cardiolipotoxicity.

The heart oxidizes fatty acids for its energy production. The physiological balance between fatty acid uptake and its oxidation prevents lipid accumulation in cardiac myocytes. However, accumulation of lipids due to various processes such as obesity, diabetes, heart failure, myocardial ischemia or infarction can result in damage to the heart tissue, also known as cardiolipotoxicity. We present a unique case of a 69-year-old gentleman with a history of heart failure and ventricular tachycardia. Endomyocardial biopsy to assess for restrictive cardiomyopathy/amyloid showed no evidence of amyloid, significant inflammation or fibrosis, but did show intracellular accumulation of significant amorphous material in most cardiac myocytes. We review the literature regarding the pathogenesis of cardiolipotoxicity, which has no definite cause or treatment yet identified.

Myocarditis: somethings old and something new.

"Since the pathological conditions take place at the cellular level, viral myocarditis and postinfectious autoimmunity can be suggested but not diagnosed clinically. All clinical methods including imaging techniques are misleading if infectious agents are involved. Accurate diagnosis demands simultaneous histologic, immunohistochemical, and molecular biological workup of the tissue. If the primary infectious or immune-mediated causes of the disease are carefully defined by clinical and biopsy-based tools, specific antiviral treatment options in addition to basic symptomatic therapy are available under certain conditions. These may allow a tailored cause-specific treatment that improves symptoms and prognosis of patients with acute and chronic disease." Uwe Kühl; Heinz-Peter SchultheissViral myocarditis.Swiss Medical Weekly. 144():w14010, JAN 2014 DOI:10.4414/smw.2014.14010.

Hypoxia-induced pulmonary hypertension and chronic lung disease: caveolin-1 dysfunction an important underlying feature.

Caveolin-1 (cav-1) has been shown to play a significant role in the pathogenesis of pulmonary hypertension (PH). In the monocrotaline model of PH, the loss of endothelial cav-1 as well as reciprocal activation of proliferative and anti-apoptotic pathways initiate the disease process and facilitate its progression. In order to examine the role of cav-1 in hypoxia-induced PH, we exposed rats and neonatal calves to hypobaric hypoxia and obtained hemodynamic data and assessed the expression of cav-1 and related proteins eNOS, HSP90, PTEN, gp130, PY-STAT3, ß-catenin, and Glut1 in the lung tissue. Chronic hypoxic exposure in rats (48 h-4 weeks) and calves (two weeks) did not alter the expression of cav-1, HSP90, or eNOS. PTEN expression was significantly decreased accompanied by PY-STAT3 activation and increased expression of gp130, Glut1, and ß-catenin in hypoxic animals. We also examined cav-1 expression in the lung sections from steers with chronic hypoxic disease (Brisket disease) and from patients with chronic lung disease who underwent lung biopsy for medical reasons. There was no cav-1 loss in Brisket disease. In chronic lung disease cases, endothelial cav-1 expression was present, albeit with less intense staining in some cases. In conclusion, hypoxia did not alter the cav-1 expression in experimental models. The presence of cav-1, however, did not suppress hypoxia-induced activation of PY-STAT3 and ß catenin, increased gp130 and Glut1 expression, or prevent the PTEN loss, indicating cav-1 dysfunction in hypoxia-induced PH.

Role of Advanced Testing: Invasive Hemodynamics, Endomyocardial Biopsy, and Cardiopulmonary Exercise Testing.

Hypertrophic cardiomyopathy affects 0.5% of the population. Advanced testing is considered, including cardiac catheterization, endomyocardial biopsy, and cardiopulmonary exercise testing. Right and left heart catheterization provides essential hemodynamic data, identifies patients who might benefit from septal reduction therapy, and assesses for comorbidities. Pathologic analysis reveals ventricular hypertrophy, myocardial disarray, and endocardial and interstitial fibrosis. Routine endomyocardial biopsy is not recommended unless other conditions that cause hypertrophy need to be ruled out. Cardiopulmonary exercise testing provides useful physiologic data, allows monitoring of the response to medication and surgical interventions, estimates prognosis, and guides referral for orthotopic heart transplantation.

Genomic Analysis Reveals Distinct Subtypes in Two Rare Cases of Primary Ovarian Lymphoma.

Primary (localized) non-Hodgkin lymphoma (NHL) of the ovary is extremely rare; only a few cases have been reported in the literature. We report two cases of primary ovarian lymphoma (POL), one involving bilateral ovaries in a 15-year-old girl and other involving one ovary in a 5-year-old girl. This report describes detailed clinical, histopathological, and imaging findings, along with the review of literature of primary diffuse large B-cell lymphoma (DLBCL) arising from an ovary. In addition, we describe findings of targeted capture panel sequencing on both tumors and identify the major genetic mutations that are recurrently mutated in pan-cancers. Compared to the genomic mutation features of major subtypes of DLBCL, we distinguish that each POL belongs to distinctive subtypes, GCB (germinal center B-cell subtype) DLBCL and ABC (activated B-cell subtype) DLBCL, respectively. The findings from the genomic analysis may help to understand the pathogenesis of POL and to guide potential targeted therapy in the future.

Single-cell RNA sequencing reveals an altered gene expression pattern as a result of CRISPR/cas9-mediated deletion of Gene 33/Mig6 and chronic exposure to hexavalent chromium in human lung epithelial cells.

Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We recently reported that depletion of this protein promotes lung epithelial cell transformation induced by hexavalent chromium [Cr(VI)]. However, the early molecular events that mediate this process are not clear. In the present study, we used single-cell RNA sequencing to compare gene expression profiles between BEAS-2B lung epithelial cells chronically exposed to a sublethal dose of Cr(VI) with or without CRISPR/cas9-mediated deletion of Gene 33. Our data reveal 83 differentially expressed genes. The most notable changes are genes associated with cell adhesion, oxidative stresses, protein ubiquitination, epithelial-mesenchymal transition/metastasis, and WNT signaling. Up-regulation of some neuro-specific genes is also evident, particularly ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a deubiquitinase and potential biomarker for lung cancer. Gene 33 deletion and/or Cr(VI) exposure did not cause discernable changes in cell morphology. However, Gene 33 deletion led to a modest but significant reduction of cells in the G2/M phase of the cell cycle regardless of Cr(VI) exposure. Gene 33 deletion also significantly reduced cell proliferation. Interestingly, Cr(VI) exposure eliminated the difference in cell proliferation between the two genotypes. Gene 33 deletion also significantly elevated cell migration. Our data indicate that combined Gene 33 deletion and chronic Cr(VI) exposure produces a gene expression pattern and a phenotype resemble those of the transformed lung epithelial cells. Given the known association of UCHL1 with lung cancer, we propose that UCHL1 is an important player in the early stage of lung epithelial cell transformation and tumorigenesis.

Benign and Malignant Brenner Tumors Show an Absence of TERT Promoter Mutations That Are Commonly Present in Urothelial Carcinoma.

Brenner tumors are uncommon ovarian neoplasms, which have morphologic and immunophenotypical features of transitional cell (urothelial) differentiation. The origin of Brenner tumors is perplexing, but they are believed to arise from transitional cell metaplasia occurring within the ovary and/or fallopian tube, although it is controversial whether this metaplasia is truly along transitional cell lines. Recently, TERT promoter mutations have been identified in urothelial carcinoma (UC) with high frequency (approximately 70%), and the current literature suggests a potential diagnostic and/or prognostic role of these mutations in UC. Molecular evidence supporting that Brenner tumors represent neoplasms exhibiting transitional cell differentiation is scant. To explore this further, we investigated a series of 19 Brenner tumors of the ovary (15 benign and 4 malignant) for the presence of TERT promoter mutations after genomic DNA extraction from formalin-fixed paraffin-embedded tissue blocks and standard polymerase chain reaction sequencing. TERT promoter mutations were not identified in any of the cases (0/19). The absence of TERT promoter mutations in Brenner tumors suggests that despite the morphologic and some immunophenotypical resemblance to non-neoplastic and neoplastic transitional epithelium, Brenner tumors may exhibit a molecularly distinct pathogenesis. The findings also may portend diagnostic utility in rare cases wherein it is difficult to distinguish a primary malignant Brenner tumor of the ovary from metastatic UC.

Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association For European Cardiovascular Pathology: II. Noninflammatory degenerative diseases - nomenclature and diagnostic criteria.

Surgical aortic specimens are usually examined in Pathology Departments as a result of treatment of aneurysms or dissections. A number of diseases, genetic syndromes (Marfan syndrome, Loeys-Dietz syndrome, etc.), and vasculopathic aging processes involved in vascular injury can cause both distinct and nonspecific histopathologic changes with degeneration of the media as a common denominator. Terminology for these changes has varied over time leading to confusion and inconsistencies. This consensus document has established a revised, unified nomenclature for the variety of noninflammatory degenerative aortic histopathologies seen in such specimens. Older terms such as cystic medial necrosis and medionecrosis are replaced by more technically accurate terms such as mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation and/or loss, and smooth muscle cell nuclei loss. A straightforward system of grading is presented to gauge the extent of medial degeneration and synoptic reporting tables are provided. Herein we present a standardized nomenclature that is accessible to general pathologists and useful for future publications describing these entities.

Recurrent TERT promoter mutations in urothelial carcinoma and potential clinical applications.

Increased telomerase activity is associated with almost all types of advanced human cancers with unknown molecular mechanism(s). Two recurrent point mutations in the promoter region of telomerase reverse transcriptase (TERT)--the key subunit of telomerase--have recently been identified in melanoma as well as a small sample of bladder cancer cell lines. However, the incidence and clinical-pathological significance of these mutations in urothelial carcinoma have not been well established yet. We collected 86 specimens of urothelial carcinoma including upper and lower urinary tract: high grade and low grade, invasive and noninvasive, and primary and metastatic. We also included some matched benign urothelium and common benign bladder lesions: cystitis, nephrogenic adenoma, and inverted papilloma. In addition, we collected urine samples for urothelial carcinoma workup; blood samples from patients underwent cystectomy with extensive lymphovascular invasion. All specimens were subject to polymerase chain reaction amplification and bidirectional Sanger sequencing for the TERT promoter mutations: C228T and C250T. We found that 64 (74%) of 86 carcinoma samples harbored 1 of the 2 TERT promoter mutations (C228T, n = 54; C250T, n = 10); the incidences were roughly equal regardless of site of origin, histologic grade, and invasive status. All matched benign and benign lesion samples showed wild-type sequence. These TERT promoter mutations are the most common genetic alterations in urothelial carcinoma and are not associated with tumor locations, grade, or invasiveness. Importantly, the feasibility of detecting these mutations in urine samples may provide a novel method to detect urothelial carcinoma in urine.

Novel Respiratory Syncytial Virus-Like Particle Vaccine Composed of the Postfusion and Prefusion Conformations of the F Glycoprotein.

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants and children and represents an important global health burden for the elderly and the immunocompromised. Despite decades of research efforts, no licensed vaccine for RSV is available. We have developed virus-like particle (VLP)-based RSV vaccines assembled with the human metapneumovirus (hMPV) matrix protein (M) as the structural scaffold and the RSV fusion glycoprotein (F) in either the postfusion or prefusion conformation as its prime surface immunogen. Vaccines were composed of postfusion F, prefusion F, or a combination of the two conformations and formulated with a squalene-based oil emulsion as adjuvant. Immunization with these VLP vaccines afforded full protection against RSV infection and prevented detectable viral replication in the mouse lung after challenge. Analyses of lung cytokines and chemokines showed that VLP vaccination mostly induced the production of gamma interferon (IFN-γ), a marker of the Th1-mediated immune response, which is predominantly required for viral protection. Conversely, immunization with a formalin-inactivated RSV (FI-RSV) vaccine induced high levels of inflammatory chemokines and cytokines of the Th2- and Th17-mediated types of immune responses, as well as severe lung inflammation and histopathology. The VLP vaccines showed restricted production of these immune mediators and did not induce severe bronchiolitis or perivascular infiltration as seen with the FI-RSV vaccine. Remarkably, analysis of the serum from immunized mice showed that the VLP vaccine formulated using a combination of postfusion and prefusion F elicited the highest level of neutralizing antibody and enhanced the Th1-mediated immune response.

TFE3-Fusion Variant Analysis Defines Specific Clinicopathologic Associations Among Xp11 Translocation Cancers.

Xp11 translocation cancers include Xp11 translocation renal cell carcinoma (RCC), Xp11 translocation perivascular epithelioid cell tumor (PEComa), and melanotic Xp11 translocation renal cancer. In Xp11 translocation cancers, oncogenic activation of TFE3 is driven by the fusion of TFE3 with a number of different gene partners; however, the impact of individual fusion variant on specific clinicopathologic features of Xp11 translocation cancers has not been well defined. In this study, we analyze 60 Xp11 translocation cancers by fluorescence in situ hybridization using custom bacterial artificial chromosome probes to establish their TFE3 fusion gene partner. In 5 cases RNA sequencing was also used to further characterize the fusion transcripts. The 60 Xp11 translocation cancers included 47 Xp11 translocation RCC, 8 Xp11 translocation PEComas, and 5 melanotic Xp11 translocation renal cancers. A fusion partner was identified in 53/60 (88%) cases, including 18 SFPQ (PSF), 16 PRCC, 12 ASPSCR1 (ASPL), 6 NONO, and 1 DVL2. We provide the first morphologic description of the NONO-TFE3 RCC, which frequently demonstrates subnuclear vacuoles leading to distinctive suprabasal nuclear palisading. Similar subnuclear vacuolization was also characteristic of SFPQ-TFE3 RCC, creating overlapping features with clear cell papillary RCC. We also describe the first RCC with a DVL2-TFE3 gene fusion, in addition to an extrarenal pigmented PEComa with a NONO-TFE3 gene fusion. Furthermore, among neoplasms with the SFPQ-TFE3, NONO-TFE3, DVL2-TFE3, and ASPL-TFE3 gene fusions, the RCCs are almost always PAX8 positive, cathepsin K negative by immunohistochemistry, whereas the mesenchymal counterparts (Xp11 translocation PEComas, melanotic Xp11 translocation renal cancers, and alveolar soft part sarcoma) are PAX8 negative, cathepsin K positive. These findings support the concept that despite an identical gene fusion, the RCCs are distinct from the corresponding mesenchymal neoplasms, perhaps due to the cellular context in which the translocation occurs. We corroborate prior data showing that the PRCC-TFE3 RCCs are the only known Xp11 translocation RCC molecular subtype that are consistently cathepsin K positive. In summary, our data expand further the clinicopathologic features of cancers with specific TFE3 gene fusions and should allow for more meaningful clinicopathologic associations to be drawn.

Hematological disorders and pulmonary hypertension.

Pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate, is known to occur in a number of unrelated systemic diseases. Several hematological disorders such as sickle cell disease, thalassemia and myeloproliferative diseases develop PH which worsens the prognosis. Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction. Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity, activation of proliferative and antiapoptotic pathways leading to vascular remodeling, elevated pulmonary artery pressure, right ventricular hypertrophy and premature death. Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide (NO), limiting its bioavailability, and leading to endothelial dysfunction. In addition, hemolysis releases arginase into the circulation which converts L-arginine to ornithine, thus bypassing NO production. Furthermore, treatments for hematological disorders such as immunosuppressive therapy, splenectomy, bone marrow transplantation, and radiation have been shown to contribute to the development of PH. Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension (PAH). Several studies have reported low iron levels in patients with idiopathic PAH, and iron deficiency is an important risk factor. This article reviews PH associated with hematological disorders and its mechanism; and iron homeostasis and its relevance to PH.

Telomerase reverse transcriptase promoter mutations in glandular lesions of the urinary bladder.

Glandular lesions of the urinary bladder include a broad spectrum of entities ranging from completely benign to primary and secondary malignancies. The accurate diagnosis of these lesions is both important and challenging. Recently, studies suggest that telomerase reverse transcriptase (TERT) promoter mutations could be a biomarker for urothelial carcinoma (UC). We hypothesized that these mutations can distinguish UC with glandular differentiation from nephrogenic adenoma, primary adenocarcinoma of the urinary bladder (PAUB), or secondary malignancies. Twenty-five cases of benign glandular lesions (including nephrogenic adenoma); 29 cases of UC with glandular differentiation; 10 cases of PAUB; and 10 cases each of metastatic colon cancer, prostatic carcinoma, and carcinoma from Mullerian origin were collected. Slides were reviewed and selected to make sure the lesion was at least 10% to 20% of all tissue. Macrodissection was performed in some of cases, and genomic DNA was extracted from the tissue. Telomerase reverse transcriptase promoter mutations were determined by standard polymerase chain reaction sequencing. Twenty-one cases (72%) of UC with glandular differentiation were positive for TERT promoter mutations. However, none of the remaining cases (total 65 cases of benign lesions, PAUB, and metastatic carcinomas) was positive for TERT promoter mutation. Telomerase reverse transcriptase promoter mutations were highly associated with UC including UC with glandular differentiation but not other glandular lesions of bladder. Therefore, in conjunction with morphologic features, Immunohistochemistry stain profile, and clinical information, TERT promoter mutations could distinguish UC with glandular differentiation from other bladder glandular lesions. In addition, lack of TERT promoter mutations in primary adenocarcinoma of bladder suggests that this entity may have different origin or carcinogenesis from those of UC.

Identification of a novel PARP14-TFE3 gene fusion from 10-year-old FFPE tissue by RNA-seq.

Xp11 (TFE3) translocation renal cell carcinoma (RCC) is officially recognized as a distinct subtype of RCC in the 2004 WHO classification. This neoplasm is characterized by several chromosomal translocations between the TFE3-involving Xp11.2 breakpoint and various fusion partners. To date, five partner genes have been identified, that is, PRCC in 1q21, PSF in 1q34, ASPL in 17q25, CLTC in 17q23, and NONO in Xq12; and three additional translocations have been reported with no partner gene being defined: t(X;3)(p11;q23), t(X;10)(p11;q23), and t(X;19)(p11;q13). Here, we report the identification of a novel TFE3 fusion partner, PARP14 in chromosome band3q21. We used RNA-seq on a 10-year-old FFPE (formalin-fixed, paraffin-embedded) tissue sample, which carried t(X;3)(p11;q23) as detected in the original cytogenetic study. The fusion transcript connected the 5'-end of the first two exons of PARP14 to the 3'-end of five exons of TFE3, which was verified by reverse transcription PCR (RT-PCR) and Sanger sequencing. Similar to other TFE3 fusions previously reported, the predicted PARP14-TFE3 product retains the nuclear localization and DNA-binding domains of TFE3. This finding expands the list of TFE3 translocation partner genes and re-emphasizes the essential oncogenic role of TFE3 fusion proteins in this tumor. Our result also clearly demonstrated the feasibility of identifying chromosomal translocation by RNA-seq in clinical FFPE, which are easily accessible and associated with valuable clinical information. © 2015 Wiley Periodicals, Inc.