ABSTRACT
Aim: This study aims to elucidate the involvement of triple-negative breast cancer (TNBC)-derived extracellular vesicles in metastasis. The loss of components in the type 1 interferon (IFN1) signaling pathway has been linked to the promotion of metastasis. However, IFN1 signaling induces immunological dormancy and promotes tumorigenesis. Our hypothesis was that TNBC cells release tumor-derived extracellular vesicles (TEVs) that promote metastasis in an IFN1-independent manner. Methods: Two murine TNBC models and transgenic mice were used to examine the role of IFN1 in TNBC progression to metastasis. Reserpine was employed to determine the effect of TEV education on TNBC progression and overall survival. EVs from cancer cells treated with vehicle and reserpine and from the serum of tumor-bearing mice receiving reserpine were examined to determine changes in EV release and EV content. Results: TNBC cells progress to metastasis in mice lacking the IFN1-induced gene cholesterol-25 hydroxylase (CH25H) or expressing the IFNAR1S526 knock-in that cannot be downregulated. Reserpine suppresses EV release from TNBC cells in vitro and in vivo. Western blot analysis demonstrated reserpine decreased NUPR1 protein levels in EVs. RNAseq analysis demonstrated that endothelial cells lacking CH25H treated with TEVs exhibited increased NUPR1 expression that was decreased by adding reserpine with the TEVs. NUPR1 overexpression upregulated genes that mediate TEV biogenesis and incorporation. Knockdown of NUPR1 with shRNA decreased the release of TEVs. Conclusion: In conclusion, our study suggests that TNBC is driven by aberrant packaging of NUPR1 into TEVs which were transferred into recipient cells to activate pro-metastatic transcription driven by NUPR1.
ABSTRACT
Uropathogenic E. coli (UPEC) is a primary organism responsible for urinary tract infections and a common cause of sepsis. Microbially experienced laboratory mice, generated by cohousing with pet store mice, exhibit increased morbidity and mortality to polymicrobial sepsis or lipopolysaccharide challenge. By contrast, cohoused mice display significant resistance, compared with specific pathogen-free mice, to a monomicrobial sepsis model using UPEC. CD115+ monocytes mediate protection in the cohoused mice, as depletion of these cells leads to increased mortality and UPEC pathogen burden. Further study of the cohoused mice reveals increased TNF-α production by monocytes, a skewing toward Ly6ChiCD115+ "classical" monocytes, and enhanced egress of Ly6ChiCD115+ monocytes from the bone marrow. Analysis of cohoused bone marrow also finds increased frequency and number of myeloid multipotent progenitor cells. These results show that a history of microbial exposure impacts innate immunity in mice, which can have important implications for the preclinical study of sepsis.
Subject(s)
Escherichia coli Infections , Sepsis , Urinary Tract Infections , Uropathogenic Escherichia coli , Mice , Animals , Monocytes , Escherichia coli , Immunity, Innate , Receptor Protein-Tyrosine KinasesABSTRACT
CONTEXT.: Urinary and Male Genital Tumours is the 8th volume of the World Health Organization Classification of Tumours series, 5th edition. Released in hard copy in September 2022, it presents an update to the classification of male genital and urinary tumors in the molecular age. Building upon previous volumes in this series, significant effort has been made to harmonize terminology across organ systems for biologically similar tumors (eg, neuroendocrine tumors). Genomic terminology has been standardized and genetic syndromes covered more comprehensively. This review presents a concise summary of this volume highlighting new entities, notable modifications relative to the 4th edition, and elements of relevance to routine clinical practice. OBJECTIVE.: To provide a comprehensive update on the World Health Organization classification of urinary and male genital tumors, highlighting updated diagnostic criteria and terminology. DATA SOURCES.: The 4th and 5th editions of the World Health Organization Classification of Tumours: Urinary and Male Genital Tumours. CONCLUSIONS.: The World Health Organization has made several changes in the 5th edition of the update on urinary and male genital tumors that pathologists need to be aware of for up-to-date clinical practice.
ABSTRACT
BACKGROUND: The World Health Organization Classification (WHO) of Urinary and Male Genital Tumors has recently been updated to its 5th edition. The new edition presents a comprehensive approach to the classification of urinary and male genital tumors with an incorporation of morphologic, clinical, and genomic data. OBJECTIVE: This review aims to update the new classification of bladder cancer in the 5th edition and to highlight important changes in nomenclatures, diagnostic criteria, and molecular characterization, as compared to the 4th edition. METHODS: The pathologic classification of bladder cancer in the 5th edition of WHO Classification of Urinary and Male Genital Tumours was compared to that in the 4th edition. PubMed was searched using key words, including bladder cancer, WHO 1973, WHO 1998, WHO 2004, WHO 2016, histology, pathology, genomics, and molecular classification in the time frame from 1973 to August of 2022. Other relevant papers were also consulted, resulting in the selection of 81 papers as references. RESULTS: The binary grading of papillary urothelial carcinoma (UC) is practical, but it may be oversimplified and contribute to "grade migration" in recent years. An arbitrary cutoff (5%) has been proposed for bladder cancers with mixed grades. The diagnosis of papillary urothelial neoplasm with low malignant potential has been dramatically reduced in recent years because of overlapping morphology and treatment with low-grade papillary UC. An inverted growth pattern should be distinguished from true (or destructive) stromal invasion in papillary UC. Several methods have been proposed for pT1 tumor substaging, but it is often challenging to substage pT1 tumors in small biopsy specimens. Bladder UC shows a high tendency for divergent differentiation, leading to several distinct histologic subtypes associated with an aggressive clinical behavior. Molecular classification based on the genomic analysis may be a useful tool in the stratification of patients for optimal treatment. CONCLUSIONS: The 5th edition of WHO Classification of Urinary and Male Genital Tumours has made several significant changes in the classification of bladder cancer. It is important to be aware of these changes and to incorporate them into routine clinical practice.
ABSTRACT
As COVID-19 pandemic approaching its third year, more data have shown that obesity and hypertriglyceridemia are the high-risk factors for the major complications such as acute respiratory distress syndrome, thromboembolism, coagulopathy and cytokine storm, which are responsible for the majority of disease severity and mortality. In this review article, we have analyzed the public available clinical reports and laboratory research results of the COVID-19 studies by researchers and clinicians of many nations around the world. Many of these reports covered COVID-19 patients of different ethnic groups. We suggested that obesity and high triglycerides are high risks for severe COVID-19 and death. We also summarized the possible underlying molecular mechanism likely connecting the severe COVID-19 with obesity and hypertriglyceridemia. From public health perspective, we highlight the importance of the healthy diet and lifestyle in fighting against SARS-CoV-2 virus in long period of time.
Subject(s)
COVID-19 , Hypertriglyceridemia , Humans , Pandemics , SARS-CoV-2 , Obesity , Severity of Illness IndexABSTRACT
Although many studies have observed genome-wide host transposon expression alteration during viral infection, the mechanisms of induction and the impact on the host remain unclear. Utilizing recently published influenza A virus (IAV) time series data and ENCODE functional genomics data, we characterized virus induced host differentially expressed transposons (virus-induced-TE) by investigating genome-wide spatial and functional relevance between the virus-induced-TEs and epigenomic markers (e.g. histone modification and chromatin remodelers). We found that a significant fraction of virus-induced-TEs are derived from host enhancer regions, where CHD4 binding and/or H3K27ac occupancy is high or H3K9me3 occupancy is low. By overlapping virus-induced-TEs to human enhancer RNAs (eRNAs), we discovered that a proportion of virus-induced-TEs are either eRNAs or part of enhancer RNAs. Upon further analysis of the eRNA targeted genes, we found that the virus-induced-TE related eRNA targets are overrepresented in differentially expressed host genes of IAV infected samples. Our results suggest that changing chromatin accessibility from repressive to permissive in the transposon docked enhancer regions to regulate host downstream gene expression is potentially one of the virus and host cell interaction mechanisms, where transposons are likely important regulatory genomic elements. Our study provides a new insight into the mechanisms of virus-host interaction and may lead to novel strategies for prevention and therapeutics of IAV and other virus infectious diseases.
Subject(s)
DNA Transposable Elements/physiology , Enhancer Elements, Genetic/physiology , Influenza A virus/genetics , RNA/physiology , Chromatin Assembly and Disassembly/physiology , Gene Expression Regulation , Host Microbial Interactions/genetics , HumansABSTRACT
Laboratory mice comprise an expeditious model for preclinical vaccine testing; however, vaccine immunogenicity in these models often inadequately translates to humans. Reconstituting physiologic microbial experience to specific pathogen-free (SPF) mice induces durable immunological changes that better recapitulate human immunity. We examined whether mice with diverse microbial experience better model human responses post vaccination. We co-housed laboratory mice with pet-store mice, which have varied microbial exposures, and then assessed immune responses to influenza vaccines. Human transcriptional responses to influenza vaccination are better recapitulated in co-housed mice. Although SPF and co-housed mice were comparably susceptible to acute influenza infection, vaccine-induced humoral responses were dampened in co-housed mice, resulting in poor control upon challenge. Additionally, protective heterosubtypic T cell immunity was compromised in co-housed mice. Because SPF mice exaggerated humoral and T cell protection upon influenza vaccination, reconstituting microbial experience in laboratory mice through co-housing may better inform preclinical vaccine testing.
Subject(s)
Immunogenicity, Vaccine , Influenza Vaccines/immunology , Animals , Female , Humans , Immunity, Humoral , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , VaccinationABSTRACT
Label-free high-resolution molecular and cellular imaging strategies for intraoperative use are much needed, but not yet available. To fill this void, we developed an artificial intelligence-augmented molecular vibrational imaging method that integrates label-free and subcellular-resolution coherent anti-stokes Raman scattering (CARS) imaging with real-time quantitative image analysis via deep learning (artificial intelligence-augmented CARS or iCARS). The aim of this study was to evaluate the capability of the iCARS system to identify and differentiate the parathyroid gland and recurrent laryngeal nerve (RLN) from surrounding tissues and detect cancer margins. This goal was successfully met.
ABSTRACT
BACKGROUND: The indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma. METHODS: Patients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label. RESULTS: Between July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator's choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P). CONCLUSION: In this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Immunotherapy/methods , Melanoma/drug therapy , Tryptophan/analogs & derivatives , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Female , Humans , Male , Middle Aged , Tryptophan/pharmacology , Tryptophan/therapeutic useABSTRACT
Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.
Subject(s)
Carcinoma, Giant Cell/diagnosis , Carcinoma, Giant Cell/metabolism , Prostatic Neoplasms/pathology , Urinary Bladder Neoplasms/pathology , Adult , Aged , Biomarkers, Tumor/analysis , Carcinoma, Acinar Cell/pathology , Cell Dedifferentiation , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism , Diagnosis, Differential , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Immunohistochemistry/methods , Male , Middle Aged , Mutation , Neoplasm Grading/methods , Prognosis , Transcription Factors/genetics , Transcription Factors/metabolism , Urothelium/pathologyABSTRACT
The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required for infection of these cells. Importantly, remdesivir treatment effectively inhibited viral replication across cell types, and blunted hyperinflammatory responses. Induction of interferon responses within infected cells was rare and there was significant heterogeneity in the antiviral gene signatures, varying with the burden of infection in each cell. We also found that heavily infected secretory cells expressed abundant IL-6, a potential mediator of COVID-19 pathogenesis.
Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/physiology , Viral Tropism , Adenosine Monophosphate/pharmacology , Alanine/pharmacology , COVID-19/genetics , Epithelium/immunology , Epithelium/virology , Humans , Interferons/genetics , Interferons/immunology , Interleukin-6/genetics , Interleukin-6/immunology , Lung/immunology , Lung/virology , SARS-CoV-2/drug effects , Viral Tropism/drug effects , Virus Replication/drug effects , COVID-19 Drug TreatmentABSTRACT
Genitourinary (GU) cancers are among the most common malignant diseases in men [...].
ABSTRACT
The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required for infection of these cells. Importantly, remdesivir treatment effectively inhibited viral replication across cell types, and blunted hyperinflammatory responses. Induction of interferon responses within infected cells was rare and there was significant heterogeneity in the antiviral gene signatures, varying with the burden of infection in each cell. We also found that heavily infected secretory cells expressed abundant IL-6, a potential mediator of COVID-19 pathogenesis.
ABSTRACT
The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system subdivides prostatic pT3 tumors into pT3a, which includes cases with extraprostatic extension (EPE) and pT3b, which is defined by the presence of seminal vesicle invasion (SVI) with or without EPE. Yet, it is not established whether combined SVI and EPE impart a worse prognosis compared to SVI alone. We studied a cohort of 69 prostatectomy patients with SVI with or without EPE. Patient age at the time of radical prostatectomy was documented and Gleason score and presence or absence of EPE and/or SVI were determined. Biochemical recurrence (BCR) was defined as a PSA rise >0.2 ng/mL. The frequency of BCR was 33.9% in cases with combined EPE and SVI versus 12.5% in cases with SVI alone (relative risk = 2.71). An additional cohort of 88 patients also showed a higher frequency of lymph node metastasis of 29% in patients with combined SVI and EPE at the time of radical prostatectomy versus a 10% frequency of lymph node metastasis in patients with SVI alone (relative risk = 2.9). Based on our data, we propose further subdividing pT3 prostate cancers into three groups: EPE alone (pT3a), SVI alone (pT3b), and combined EPE and SVI (pT3c). This classification system would more accurately identify patients with pT3 prostate cancer who are more likely to experience worse outcomes and provide clinicians with additional information to aid in follow-up and postoperative treatment decisions.
Subject(s)
Adenocarcinoma/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging/methods , Prostatic Neoplasms/pathology , Seminal Vesicles/pathology , Adenocarcinoma/classification , Aged , Aged, 80 and over , Humans , Lymphatic Metastasis/pathology , Male , Middle Aged , Neoplasm Invasiveness/pathology , Prostate-Specific Antigen/blood , Prostatic Neoplasms/classificationABSTRACT
Virus-host cell interactions initiate a host cell-defensive response during virus infection. How transposable elements in the host cell respond to viral stress at the molecular level remains largely unclear. By reanalyzing next generation sequencing data sets from dozens of virus infection studies from the Gene Expression Omnibus database, we found that genome-wide transposon expression up-regulation in host cells occurs near antiviral response genes and exists in all studies regardless of virus, species, and host cell tissue types. Some transposons were found to be up-regulated almost immediately upon infection and before increases in virus replication and significant increases in interferon ß expression. These findings indicate that transposon up-regulation is a common phenomenon during virus infection in human and mouse and that early up-regulated transposons are part of the first wave response during virus infection.
Subject(s)
DNA Transposable Elements/genetics , Host-Pathogen Interactions/genetics , Lymphocytes/virology , Macrophages/virology , Up-Regulation/genetics , Virus Diseases/genetics , Viruses/genetics , A549 Cells , Animals , Databases, Genetic , HEK293 Cells , High-Throughput Nucleotide Sequencing , Humans , Interferon-beta/genetics , Mice , RAW 264.7 Cells , RNA-Seq , Virus Diseases/virology , Virus Replication/geneticsABSTRACT
CONTEXT.: Core biopsy has been increasingly used for clinical decision-making in the management of patients with renal masses. The sensitivity and specificity of histologic diagnoses of renal mass biopsies depend on many factors such as adequate sampling and tissue processing, diagnostic skill and experience, and appropriate use of ancillary techniques. OBJECTIVE.: To review the indications, emphasize the importance of obtaining adequate diagnostic material, and introduce a general diagnostic approach, in conjunction with immunohistochemistry, in diagnosis of renal mass biopsies. DATA SOURCES.: Literature review and personal experiences in daily practice and consultation diagnosis of renal masses in a large tertiary medical center. CONCLUSIONS.: For renal mass biopsies, it is critical to obtain adequate diagnostic material and establish a standard laboratory procedure in working with small biopsy specimens. The key for the diagnosis is to be familiar with different tumor entities with characteristic morphology and to understand the wide spectrum of tumor heterogeneity. By developing a systematic approach, one can categorize the tumor and create a sensible differential diagnosis based on the growth pattern and cellular morphology. Immunohistochemistry is particularly helpful for renal mass biopsy diagnosis in selected situations.
Subject(s)
Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Biopsy, Large-Core Needle , HumansSubject(s)
Heart Neoplasms/surgery , Heart Valve Prosthesis Implantation , Mitral Valve/surgery , Neoplasm Recurrence, Local/surgery , Reoperation , Sarcoma/surgery , Transplantation, Autologous , Adult , Echocardiography, Transesophageal , Female , Heart Neoplasms/diagnostic imaging , Heart Neoplasms/pathology , Heart Valve Prosthesis Implantation/methods , Humans , Magnetic Resonance Imaging , Mitral Valve/diagnostic imaging , Mitral Valve/pathology , Mitral Valve/transplantation , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/pathology , Reoperation/methods , Sarcoma/diagnostic imaging , Sarcoma/pathology , Transplantation, Autologous/methodsABSTRACT
The value of histochemical analysis in the diagnosis of medical renal diseases has long been known, and its use continues currently. Depending on the particular disorder in question, a variety of "special" stains may be applied to renal biopsies. These include the periodic acid-Schiff, Masson trichrome, Jones, von Kossa, Verhoeff-van Gieson, Congo Red, and toluidine blue methods, among others. This review considers the application of such techniques in the assessment of vascular, glomerular, and tubulointerstitial lesions of the kidney.
Subject(s)
Histocytochemistry , Kidney Diseases/pathology , Kidney/pathology , Biopsy , Humans , Predictive Value of Tests , Prognosis , Staining and LabelingABSTRACT
Multilocular cystic renal cell carcinoma has been recently excluded from clear cell renal cell carcinoma (CCRCC) category and re-designated as multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) due to its uniformly good outcomes. While strict distinction between MCRNLMP from predominantly cystic CCRCC (pc-CCRCC) is being emphasized, the significance of extensive true cystic component in CCRCC has not been investigated. Herein, we analyzed 57 MCRNLMP, 69 pc-CCRCC, and 46 non-cystic CCRCC. There were no statistically significant differences between the three subtypes in age, gender, and laterality. ISUP grades were 1 (73%) or 2 (27%) for MCRNLMP; for pc-CCRCC were 1 (31%), 2 (60%), and 3 (9%); and for non-cystic CCRCC were 1 (9%), 2 (52%), 3 (26%), and 4 (13%). MCRNLMP were either pT stage 1 (91%) or 2 (9%), pT stages for pc-CCRCC were 1 (92.5%), 2 (1.5%), and 3 (6%) and for non-cystic CCRCC were 1 (58.7%), 2 (6.5%), and 3 (34.8%). None of MCRNLMP patients developed recurrences or metastases, and only 1 contralateral kidney tumor and 1 metastasis developed in pc-CCRCC. In contrast, 19 patients with non-cystic CCRCC developed metastases (5-year PFS 58%, CI 38.3-73.5%), and 1 patient died of disease. Monosomy 3 was common in both MCRNLMP (3/3) and pc-CCRCC (6/7). This large series of MCRNLMP confirms its indolent behavior, shows that pc-CCRCC has significantly better prognosis than non-cystic CCRCC and may define the lower grade spectrum of CCRCC. We recommend that the presence and extent of CCRCC cystic component should be documented in the pathology report.
Subject(s)
Carcinoma, Renal Cell/secondary , Kidney Neoplasms/pathology , Neoplasms, Cystic, Mucinous, and Serous/secondary , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/therapy , Disease Progression , Female , Humans , In Situ Hybridization, Fluorescence , Kidney Neoplasms/genetics , Kidney Neoplasms/mortality , Kidney Neoplasms/therapy , Male , Mexico , Middle Aged , Neoplasm Grading , Neoplasm Staging , Neoplasms, Cystic, Mucinous, and Serous/genetics , Neoplasms, Cystic, Mucinous, and Serous/mortality , Neoplasms, Cystic, Mucinous, and Serous/therapy , Ploidies , Predictive Value of Tests , Risk Assessment , Risk Factors , Time Factors , United StatesABSTRACT
Persistent müllerian duct syndrome (PMDS) is a form of disordered sex development in which rudimentary müllerian structures are identified in phenotypically and genotypically normal males. It is caused by defects in the anti-müllerian hormone (AMH) system. Since patients with PMDS present with undescended testes, testosterone production by Leydig cells later in life is often decreased. The role of androgens in prostate cancerogenesis is well known. Cryptorchid testes and diminished testosterone levels in post-pubertal life in patients with PMDS play a protective role against prostate cancer, and hence, prostate cancer is a rare event in patients with PMDS. Herein, we present a patient who underwent prostatectomy for high-grade prostatic adenocarcinoma with persistent müllerian structures (such as rudimentary uterus, fallopian tubes, and cervix) identified during surgery. To our knowledge, this is the second case reported in the English language literature where PMDS was associated with prostate cancer.