Telomerase Reverse Transcriptase-Promoter Mutation in Young Patients with Bladder Tumors.

The TERT (Telomerase Reverse Transcriptase) gene promoter mutation is one of the most prevalent mutations in urothelial bladder tumors and this mutation is related to bladder tumor progression. Our purpose was to evaluate the presence of this mutation in a population of patients who were first diagnosed at age ≤ 40 years and to examine its relationship with tumor characteristics and progression. A molecular study was performed to detect the two most prevalent mutations in the TERT promoter (C228T and C250T). The study included 29 patients, with a mean follow-up of 152 months. There were no statistically significant differences in the clinical or tumor characteristics according to the presence or absence of the mutation. Although the mutation group showed poorer recurrence-free survival (RFS), there was no statistically significant difference and there was no difference in progression-free survival by group (p > 0.05). The pTERT mutations in bladder tumor cells occurred less frequently in younger patients than in older patients, a finding that could indicate different mechanisms of carcinogenesis. The trend towards lower RFS in patients with mutated pTERT needs to be confirmed by further studies, given the small number of patients included in these studies due to the low incidence of bladder tumors in this age group.

Different outcomes among patients with intermediate-risk metastastic renal cell carcinoma treated with first-line tyrosine-kinase inhibitors

Introduction Systemic therapy of patients with metastatic renal cell carcinoma (mRCC) has improved in the past years, with the advent of new immunotherapy-based combinations as a standard treatment option for first-line therapy. Nevertheless, particularly in good-risk patients by IMDC criteria, tyrosine-kinase inhibitors (TKI) may remain as an option for some patients. We reviewed our experience with TKI as first-line therapy for mRCC patients, trying to identify subgroups of patients that may still benefit from this strategy. Material and methods All patients with mRCC treated with first-line TKI, and adequate follow-up, in University Hospital La Paz (Madrid, Spain) between 2007 and 2020 were analyzed. Patients treated inside a clinical trial were excluded from this analysis. Results A total of 90 patients treated with first-line TKI were included. Regarding IMDC criteria, 33 patients (36.7%) were good-risk, 41 patients (45.5%) intermediate-risk, and 16 patients (17.8%) poor-risk. With a median follow-up of 49 months, the median overall survival (OS) for good, intermediate, and poor-risk patients was 54, 24, and 16 months (p = 0.004). When intermediate-risk was divided into patients with 1 or 2 risk factors, differences in OS were also statistically significant: patients with 1 risk factor had a median OS of 33 months, while patients with 2 risk factors had a median OS of 16 months, the same as poor-risk patients (p = 0.003). In the multivariate analysis, trying to find out which of the IMDC factors had a more remarkable weight in the prognosis of the patients, both ECOG and hemoglobin levels by themselves were significantly associated with OS. Conclusion In our group of patients, survival outcomes were different among patients with intermediate-risk with 1 or 2 risk factors by IMDC criteria(AU)

Different outcomes among patients with intermediate-risk metastastic renal cell carcinoma treated with first-line tyrosine-kinase inhibitors.

INTRODUCTION: Systemic therapy of patients with metastatic renal cell carcinoma (mRCC) has improved in the past years, with the advent of new immunotherapy-based combinations as a standard treatment option for first-line therapy. Nevertheless, particularly in good-risk patients by IMDC criteria, tyrosine-kinase inhibitors (TKI) may remain as an option for some patients. We reviewed our experience with TKI as first-line therapy for mRCC patients, trying to identify subgroups of patients that may still benefit from this strategy. MATERIAL AND METHODS: All patients with mRCC treated with first-line TKI, and adequate follow-up, in University Hospital La Paz (Madrid, Spain) between 2007 and 2020 were analyzed. Patients treated inside a clinical trial were excluded from this analysis. RESULTS: A total of 90 patients treated with first-line TKI were included. Regarding IMDC criteria, 33 patients (36.7%) were good-risk, 41 patients (45.5%) intermediate-risk, and 16 patients (17.8%) poor-risk. With a median follow-up of 49 months, the median overall survival (OS) for good, intermediate, and poor-risk patients was 54, 24, and 16 months (p = 0.004). When intermediate-risk was divided into patients with 1 or 2 risk factors, differences in OS were also statistically significant: patients with 1 risk factor had a median OS of 33 months, while patients with 2 risk factors had a median OS of 16 months, the same as poor-risk patients (p = 0.003). In the multivariate analysis, trying to find out which of the IMDC factors had a more remarkable weight in the prognosis of the patients, both ECOG and hemoglobin levels by themselves were significantly associated with OS. CONCLUSION: In our group of patients, survival outcomes were different among patients with intermediate-risk with 1 or 2 risk factors by IMDC criteria. These could help select patients that may benefit from first-line treatment with a TKI, particularly in settings with difficult access to novel therapies, such as immunotherapy-based combinations.

Aspectos prácticos sobre la determinación de PD-L1 en el tratamiento de carcinoma urotelial. Consenso del grupo de uropatología de la SEAP / Practical aspects of PD-L1 assessment in the treatment of urothelial carcinoma: Consensus of the uropathology group of the SEAP

La reciente llegada de nuevos fármacos de inmunoterapia para el tratamiento del carcinoma urotelial hace necesario establecer criterios para armonizar la determinación de PD-L1 mediante inmunohistoquímica como factor pronóstico y para la selección de pacientes a tratar. En este escenario, un grupo de uropatólogos de la Sociedad Española de Anatomía Patológica, junto con un oncólogo médico como colaborador externo subespecializado en urooncología, ha elaborado este documento de recomendaciones basadas en la evidencia disponible. En la determinación de PD-L1 son especialmente relevantes la selección de la muestra analizada, su procesamiento, la plataforma de inmunohistoquímica y anticuerpo empleados, así como el algoritmo que se aplique para la lectura. Todos estos aspectos deben indicarse en el informe de resultados, que debería poder ser fácilmente interpretable en un contexto de rápida evolución de terapias inmunológicas.(AU)

The recent addition of novel immunotherapy drugs for the treatment of urothelial carcinoma makes it necessary the establishment of criteria to harmonize the immunohistochemical assessment of PD-L1, both as a prognostic factor and for the selection of patients to be treated. In this scenario, a group of uropathologists from the Spanish Society of Pathological Anatomy, together with a medical oncologist as an external collaborator subspecialized in uro-oncology, have prepared this document of recommendations based on the available evidence. During PD-L1 assessment it is especially relevant the selection of the sample, its processing, the immunohistochemical platform and antibody used, and the algorithm applied in the interpretation of results. All these aspects must be indicated in the results report, which should be easily interpretable in a context of rapid evolution of immunological therapies.(AU)

[Practical aspects of PD-L1 assessment in the treatment of urothelial carcinoma: Consensus of the uropathology group of the SEAP]. / Aspectos prácticos sobre la determinación de PD-L1 en el tratamiento de carcinoma urotelial. Consenso del grupo de uropatología de la SEAP.

The recent addition of novel immunotherapy drugs for the treatment of urothelial carcinoma makes it necessary the establishment of criteria to harmonize the immunohistochemical assessment of PD-L1, both as a prognostic factor and for the selection of patients to be treated. In this scenario, a group of uropathologists from the Spanish Society of Pathological Anatomy, together with a medical oncologist as an external collaborator subspecialized in uro-oncology, have prepared this document of recommendations based on the available evidence. During PD-L1 assessment it is especially relevant the selection of the sample, its processing, the immunohistochemical platform and antibody used, and the algorithm applied in the interpretation of results. All these aspects must be indicated in the results report, which should be easily interpretable in a context of rapid evolution of immunological therapies.

Impact of concurrent tumour events on the prostate cancer outcomes of germline BRCA2 mutation carriers.

BACKGROUND: Several studies have reported the association of germline BRCA2 (gBRCA2) mutations with poor clinical outcomes in prostate cancer (PCa), but the impact of concurrent somatic events on gBRCA2 carriers survival and disease progression is unknown. PATIENTS AND METHODS: To ascertain the role of frequent somatic genomic alterations and histology subtypes in the outcomes of gBRCA2 mutation carriers and non-carriers, we correlated the tumour characteristics and clinical outcomes of 73 gBRCA2 and 127 non-carriers. Fluorescent in-situ hybridisation and next-generation sequencing were used to detect copy number variations in BRCA2, RB1, MYC and PTEN. Presence of intraductal and cribriform subtypes was also assessed. The independent impact of these events on cause-specific survival (CSS), metastasis-free survival and time to castration-resistant disease was assessed using cox-regression models. RESULTS: Somatic BRCA2-RB1 co-deletion (41% versus 12%, p < 0.001) and MYC amplification (53.4% versus 18.8%, p < 0.001) were enriched in gBRCA2 compared to sporadic tumours. Median CSS from diagnosis of PCa was 9.1 versus 17.6 years in gBRCA2 carriers and non-carriers, respectively (HR 2.12; p = 0.002), Median CSS in gBRCA2 carriers increased to 11.3 and 13.4 years in the absence of BRCA2-RB1 deletion or MYC amplification, respectively. Median CSS of non-carriers decreased to 8 and 2.6 years if BRCA2-RB1 deletion or MYC amplification were detected. CONCLUSIONS: gBRCA2-related prostate tumours are enriched for aggressive genomic features, such as BRCA2-RB1 co-deletion and MYC amplification. The presence or absence of these events modify the outcomes of gBRCA2 carriers.

Proteomics Characterization of Clear Cell Renal Cell Carcinoma.

PURPOSE: To explore the tumor proteome of patients diagnosed with localized clear cell renal cancer (ccRCC) and treated with surgery. MATERIAL AND METHODS: A total of 165 FFPE tumor samples from patients diagnosed with ccRCC were analyzed using DIA-proteomics. Proteomics ccRCC subtypes were defined using a consensus cluster algorithm (CCA) and characterized by a functional approach using probabilistic graphical models and survival analyses. RESULTS: We identified and quantified 3091 proteins, including 2026 high-confidence proteins. Two proteomics subtypes of ccRCC (CC1 and CC2) were identified by CC using the high-confidence proteins only. Characterization of molecular differences between CC1 and CC2 was performed in two steps. First, we defined 514 proteins showing differential expression between the two subtypes using a significance analysis of microarrays analysis. Proteins overexpressed in CC1 were mainly related to translation and ribosome, while proteins overexpressed in CC2 were mainly related to focal adhesion and membrane. Second, a functional analysis using probabilistic graphical models was performed. CC1 subtype is characterized by an increased expression of proteins related to glycolysis, mitochondria, translation, adhesion proteins related to cytoskeleton and actin, nucleosome, and spliceosome, while CC2 subtype showed higher expression of proteins involved in focal adhesion, extracellular matrix, and collagen organization. CONCLUSIONS: ccRCC tumors can be classified in two different proteomics subtypes. CC1 and CC2 present specific proteomics profiles, reflecting alterations of different molecular pathways in each subtype. The knowledge generated in this type of studies could help in the development of new drugs targeting subtype-specific deregulated pathways.

Consensus guide on prophylactic gonadectomy in different sex development.

The risk of suffering from gonadal germ cell tumors (GCT) is increased in some patients with different sexual development (DSD), mainly in those with Y chromosome material. This risk, however, varies considerably depending on a multitude of factors that make the decision for prophylactic gonadectomy extremely difficult. In order to make informed recommendations on the convenience of this procedure in cases where there is potential for malignancy, this consensus guide evaluates the latest clinical evidence, which is generally low, and updates the existing knowledge in this field.

Management of Patients with Metastatic Bladder Cancer in the Real-World Setting from the Multidisciplinary Team: Current Opinion of the SOGUG Multidisciplinary Working Group.

Based on the discussion of current state of research of relevant topics of metastatic bladder cancer (mBC) among a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group, a set of recommendations were proposed to overcome the challenges posed by the management of mBC in clinical practice. First-line options in unfit patients for cisplatin are chemotherapy with carboplatin and immunotherapy in PD-L1 positive patients. FDG-PET/CT may be a useful imaging technique in the initial staging or re-staging. In patients with oligometastatic disease, it is important to consider not only the number of metastatic lesions, but also the tumor biology and the clinical course. The combination of stereotactic body radiotherapy and immunotherapy with anti-PD-L1 monoclonal antibodies is under investigation and could improve the results of systemic treatment in patient with oligometastatic disease. Rescue treatment with curative intent could be considered in patients with oligometastatic disease after complete response on FDG-PET/CT. Metastatic disease should be evaluated using the same imaging modality over the course of the disease from diagnosis until rescue treatment. For improving the outcome of patients with mBC, the involvement of a dedicated multidisciplinary team, including urologists, pathologists, oncologists, radiologists and other specialists is of outmost importance in the daily care of these patients.

Blockade of ß2-Adrenergic Receptor Reduces Inflammation and Oxidative Stress in Clear Cell Renal Cell Carcinoma.

Von Hippel-Lindau (VHL) syndrome is a rare inherited cancer disease where the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HBs), CNS-HBs, and clear cell renal cell carcinoma (ccRCC). Since standard therapies in VHL have shown limited response, leaving surgery as the only possible treatment, targeting of the ß2-adrenergic receptor (ADRB2) has shown therapeutic antitumor benefits on VHL-retinal HBs (clinical trial), VHL-CNS HBs, and VHL-ccRCC (in vitro and in vivo). In the present study, we wanted to look deep into the effects of the ADRB2 blockers propranolol and ICI-118,551 on two main aspects of cancer progression: (i) the changes on the inflammatory response of ccRCC cells; and (ii) the modulation on the Warburg effect (glycolytic metabolism), concretely, on the expression of genes involved in the cell reactive oxygen species (ROS) balance and levels. Accordingly, in vitro studies with primary VHL-ccRCC and 786-O cells measuring ROS levels, ROS-expression of detoxifying enzymes, and the expression of p65/NF-κB targets by RT-PCR were carried out. Furthermore, histological analyses of ccRCC samples from heterotopic mouse xenografts were performed. The obtained results show that ADRB2 blockade in ccRCC cells reduces the level of oxidative stress and stabilizes the inflammatory response. Thus, these data further support the idea of targeting ADRB2 as a promising strategy for the treatment of VHL and other non-VHL tumors.

Genomic Landscape of Vinflunine Response in Metastatic Urothelial Cancer.

BACKGROUND AND AIMS: Metastatic urothelial carcinoma (mUC) remains an incurable disease with limited treatment options after platinum-based chemotherapy and immune checkpoint blockade (ICB). Vinflunine has shown a modest increase in overall survival and remains a therapeutic option for chemo- and immunotherapy refractory tumours. However, biomarkers that could identify responding patients to vinflunine and possible alternative therapies after failure to treatment are still missing. In this study, we aimed to identify potential genomic biomarkers of vinflunine response in mUC patient samples and potential management alternatives. METHODS: Formalin-fixed paraffin-embedded samples of mUC patients (n = 23) from three university hospitals in Spain were used for genomic targeted-sequencing and transcriptome (using the Immune Profile panel by NanoString) analyses. Patients who received vinflunine after platinum-based chemotherapy failure were classified in non-responders (NR: progressive disease ≤ 3 months; n= 11) or responders (R: response ≥ 6 months; n = 12). RESULTS: Genomic characterization revealed that the most common alteration, TP53 mutations, had comparable frequency in R (6/12; 50%) and NR (4/11; 36%). Non-synonymous mutations in KTM2C (4/12; 33.3%), PIK3CA (3/12; 25%) and ARID2 (3/12; 25%) were predominantly associated with response. No significant difference was observed in tumour mutational burden (TMB) between R and NR patients. The NR tumours showed increased expression of diverse immune-related genes and pathways, including various interferon gamma-related genes. We also identified increased MAGEA4 expression as a potential biomarker of non-responding tumours to vinflunine treatment. CONCLUSIONS: Our data may help to identify potential genomic biomarkers of response to vinflunine. Moreover, tumours refractory to vinflunine showed immune signatures potentially associated with response to ICB. Extensive validation studies, including longitudinal series, are needed to corroborate these findings.

Inhibition of PKCε induces primordial germ cell reprogramming into pluripotency by HIF1&2 upregulation and histone acetylation.

Historically, primordial germ cells (PGCs) have been a good model to study pluripotency. Despite their low numbers and limited accessibility in the mouse embryo, they can be easily and rapidly reprogrammed at high efficiency with external physicochemical factors and do not require transcription factor transfection. Employing this model to deepen our understanding of cell reprogramming, we specifically aimed to determine the relevance of Ca2+ signal transduction pathway components in the reprogramming process. Our results showed that PGC reprogramming requires a normal extracellular [Ca2+] range, in contrast to neoplastic or transformed cells, which can continue to proliferate in Ca2+-deficient media, differentiating normal reprogramming from neoplastic transformation. Our results also showed that a spike in extracellular [Ca2+] of 1-3 mM can directly reprogram PGC. Intracellular manipulation of Ca2+ signal transduction pathway components revealed that inhibition of classical Ca2+ and diacylglycerol (DAG)-dependent PKCs, or intriguingly, of only the novel DAG-dependent PKC, PKCε, were able to induce reprogramming. PKCε inhibition changed the metabolism of PGCs toward glycolysis, increasing the proportion of inactive mitochondria. This metabolic switch from oxidative phosphorylation to glycolysis is mediated by hypoxia-inducible factors (HIFs), given we found upregulation of both HIF1α and HIF2α in the first 48 hours of culturing. PKCε inhibition did not change the classical pluripotency gene expression of PGCs, Oct4, or Nanog. PKCε inhibition changed the histone acetylation of PGCs, with histones H2B, H3, and H4 becoming acetylated in PKCε-inhibited cultures (markers were H2BacK20, H3acK9, and H4acK5K8, K12, K16), suggesting that reprogramming by PKCε inhibition is mediated by histone acetylation.

[Circumferential calcifications in cromophobe renal cell carcinoma: Description of a clinical case and review of the literature.] / Calcificaciones anormales en tumor renal de células cromófobas: descripción de un caso clínico y revisión de la literatura.

We present a clinical case of an asymptomatic 61-year-old man was found to have a left kidney mass. Ultrasound and CT showed a 6 x 5 cms mass with calcifications. Histologic examination of the radical nephrectomy specimen revealed a chromophobe renal cell carcinoma. The unique feature of this case is the type of calcifications present in a tumor of this category. To our knowledge, were port the first case of chromophobe renal cell carcinoma with peripheral linear calcifications. A literature review onchromophobe renal cell carcinoma with calcifications is performed.

Presentamos el caso de un varón de 61 años diagnosticado de forma incidental de una tumoración renal izquierda. Las imágenes radiológicas obtenidas mediante ecografía y TAC muestran una masa de 6 x 5 cms con calcificaciones circunferenciales y periféricas. El estudio anatomopatológico de la pieza de nefrectomía radical evidencia un carcinoma renal de células cromófobas. La peculiaridad de este caso reside en el tipo de calcificaciones presentes en un tumor de este tipo no habiéndose descrito previamente, en nuestro conocimiento, calcificaciones lineales periféricas como éstas, en carcinoma renal de células cromófobas. Realizamos una revisión de la literatura acerca de las calcificaciones en carcinoma renal de células cromófobas.

Calcificaciones anormales en tumor renal de células cromófobas: descripción de un caso clínico y revisión de la literatura / Abnormal calcifications in a renal chromophobe cell tumor: description of a clinical case and review of the literature

Presentamos el caso de un varón de 61 añosdiagnosticado de forma incidental de una tumoración re-nal izquierda. Las imágenes radiológicas obtenidas me-diante ecografía y TAC muestran una masa de 6 x 5 cmscon calcificaciones circunferenciales y periféricas. El estu-dio anatomopatológico de la pieza de nefrectomía radicalevidencia un carcinoma renal de células cromófobas. Lapeculiaridad de este caso reside en el tipo de calcifica-ciones presentes en un tumor de este tipo no habiéndosedescrito previamente, en nuestro conocimiento, calcifica-ciones lineales periféricas como éstas, en carcinoma renalde células cromófobas. Realizamos una revisión de la lite-ratura acerca de las calcificaciones en carcinoma renal decélulas cromófobas.(AU)

We present a clinical case of an asymptom-atic 61-year-old man was found to have a left kidney mass.Ultrasound and CT showed a 6 x 5 cms mass with calcifi-cations. Histologic examination of the radical nephrectomyspecimen revealed a chromophobe renal cell carcinoma.The unique feature of this case is the type of calcificationspresent in a tumor of this category. To our knowledge, wereport the first case of chromophobe renal cell carcinomawith peripheral linear calcifications. A literature review onchromophobe renal cell carcinoma with calcifications isperformed.(AU)

Histopathological Subtypes and PD-L1 Expression in Primary Urethral Adenocarcinoma: A Series of 5 Cases.

BACKGROUND AND OBJECTIVES: Urethral adenocarcinoma is a rare disease with poor prognosis that can display multiple histologic patterns and has an unclear histogenesis. Radical surgery with extensive periurethral resection is the preferred therapeutic approach. Both chemotherapy and radiotherapy have been used as complementary treatment options. Due to the tendency of these tumors to recur, treatment-associated complications, and the limited choice of therapeutic options, patient management can be difficult. Given the lack of literature regarding immunotherapy in urethral adenocarcinoma, our objective was to explore the expression of programmed death receptor-ligand 1 (PD-L1) throughout the different histological subtypes of primary urethral adenocarcinoma. METHODS: We reviewed all primary urethral adenocarcinomas diagnosed at our hospital between 1965 and 2019, performed immunohistochemical assays on the tissue blocks, classified them according to their histology and origin, and performed PD-L1 (22C3) immunohistochemistry assays in all cases. RESULTS: We found a total of 5 cases of primary urethral adenocarcinoma. All of the patients were women. One of the cases was a cribriform adenocarcinoma, 2 were columnar-mucinous adenocarcinomas, and 2 were clear cell adenocarcinomas. One of the clear cell adenocarcinomas strongly expressed PD-L1. In addition, a profuse inflammatory infiltration constituted by CD3-positive and CD8-positive T lymphocytes within tumor cells was observed in this case. None of the other cases showed PD-L1 expression. CONCLUSIONS: In conclusion, some urethral adenocarcinomas may strongly express PD-L1 and thus could potentially allow the use of immunotherapy in selected cases of advanced or recurrent adenocarcinoma.

Targeting ß2-Adrenergic Receptors Shows Therapeutical Benefits in Clear Cell Renal Cell Carcinoma from Von Hippel-Lindau Disease.

Von Hippel-Lindau (VHL), is a rare autosomal dominant inherited cancer in which the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HB), CNS-HB, and clear cell renal cell carcinoma (ccRCC). ccRCC ranks third in terms of incidence and first in cause of death. Standard systemic therapies for VHL-ccRCC have shown limited response, with recurrent surgeries being the only effective treatment. Targeting of ß2-adrenergic receptor (ADRB) has shown therapeutic antitumor benefits on VHL-retinal HB (clinical trial) and VHL-CNS HB (in vitro). Therefore, the in vitro and in vivo antitumor benefits of propranolol (ADRB-1,2 antagonist) and ICI-118,551 (ADRB-2 antagonist) on VHL-/- ccRCC primary cultures and 786-O tumor cell lines have been addressed. Propranolol and ICI-118,551 activated apoptosis inhibited gene and protein expression of HIF-2α, CAIX, and VEGF, and impaired partially the nuclear internalization of HIF-2α and NFĸB/p65. Moreover, propranolol and ICI-118,551 reduced tumor growth on two in vivo xenografts. Finally, ccRCC patients receiving propranolol as off-label treatment have shown a positive therapeutic response for two years on average. In summary, propranolol and ICI-118,551 have shown antitumor benefits in VHL-derived ccRCC, and since ccRCCs comprise 63% of the total RCCs, targeting ADRB2 becomes a promising drug for VHL and other non-VHL tumors.

Expression profile of microRNAs in the testes of patients with Klinefelter syndrome.

Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy. A distinctive characteristic of KS is oligozoospermia. Despite multiple studies that have described the natural history of the degenerative process of germ cells in patients with KS, the molecular mechanisms that initiate this process are not well characterized. MicroRNA (miRNA)-mediated post-transcriptional control mechanisms have been increasingly recognized as important regulators of spermatogenesis; however, only a few studies have evaluated the role of miRNAs in the gonadal failure of these patients. Here, we describe a differential expression profile for the miRNAs in testicular tissue samples taken from KS patients. We analysed testicular tissue samples from 4 KS patients and 5 control patients (obstructive azoospermia) through next-generation sequencing, which can provide information about the mechanisms involved in the degeneration of germ cells. A distinctive differential expression profile was identified for 166 miRNAs in the KS patients: 66 were upregulated, and 100 were downregulated. An interactome analysis was performed for 7 of the upregulated and the 20 downregulated miRNAs. The results showed that the target genes are involved in the development, proliferation, and differentiation processes of spermatogenesis, which may explain their role in the development of infertility. This is the first report of a miRNA expression profile generated from testicular tissue samples of KS patients.

Fine needle aspiration cytology of polymorphous adenocarcinoma of the salivary glands: A report of 11 patients and review of the literature.

BACKGROUND: Polymorphous adenocarcinoma (PAC) is a rare malignant tumor of the minor salivary glands. It has an infiltrative growth, variable architectural patterns, neurotropism and cellular monomorphism. Approximately 75% of the cases show a specific mutation in the protein kinase D1 (PRKD1) gene. Reflecting the rarity of the tumor and intraoral location, the cytologic experience is limited with few reported series. In this study we analyze our cytologic experience to determine if a preoperative diagnosis is possible. METHODS: A retrospective study of 11 patients with PAC in which a cytologic study was available. A review of the literature was also performed. RESULTS: Our study shows that PAC has relatively constant cytological features. The analysis of the cytological literature although it shows some heterogeneity, also reveals repetitive cytological findings. Smears are cellular with irregular groups some showing pseudopapillary branching morphology. Monolayered clusters and small acinar structures are also present. Most cases have small metachromatic globules embedded within the groups determining a cylindromatous pattern. Tumoral cells are small and uniform with scarce to moderate cytoplasm. Nuclei are round and oval with occasional grooves and small nucleoli. CONCLUSION: PAC has characteristic cytological features that together with its location in minor salivary gland must make us consider it preoperatively. It may resemble basal cell adenoma and epithelial-rich pleomorphic adenoma so we should be cautious in the final diagnosis. Whenever possible, the characteristic cytomorphology of PCA should make us evaluate the mutational status of PRKD1 gene since it may permit a more accurate diagnosis.

Vascular and inflammatory effects of estrogen and anti-androgen therapy in the testis and epididymis of male to female transgender adults.

The volume of ubiquitous chemicals with estrogenic properties is on the rise and some reports relate the increase in hormonal diseases to these compounds. A morphological and immunohistochemical analysis has been performed on 42 bilateral orchiectomy specimens from adult individuals who underwent gender reassignment surgery after receiving crossed-sex hormone therapy to give insight into vascular, inflammatory and epididymal changes following long-term treatment with estrogens and antiandrogens and raise awareness of the consequences of hormone therapy. The present study confirms previously reported findings in testicular parenchyma and epididymis, such as identification of three histological patterns according to lesion severity and cell dedifferentiation, and reports for the first time vascular and inflammatory lesions (atherosclerosis and vasculitis), both on testicle and epididymis. Cross-sex hormone therapy should be provided in specialized units in order to systematize treatments and ensure adequate follow-up.

FNA cytology of postoperative pseudotumoral lesions induced by oxidized cellulose hemostatic agents.

BACKGROUND: The use of topically applied hemostatic substances during surgery has become a common practice. In some cases, the material is not absorbed or induces a granulomatous reaction resulting in a pseudotumoral lesion. With imaging studies, it is not possible to differentiate this from a tumor recurrence or abscess. This study describes the authors' cytologic experience with a large series of pseudotumoral lesions induced by oxidized cellulose, one of the most commonly used hemostatic agents. Almost no cytologic descriptions are available in the medical literature. METHODS: Sixteen patients were evaluated, and the most common sites of fine-needle aspiration (FNA) were the mediastinum and thyroid surgical bed. Other locations were the axilla, neck, vulva, liver, and retroperitoneum. All these lesions appeared after surgical procedures in which oxidized cellulose was used as a topical hemostatic agent. The interval time between surgery and FNA varied from 4 to 46 months with a mean of 15 months. RESULTS: Cytology samples showed very similar findings. In all cases, foreign-body material with a variable granulomatous reaction was present. Oxidized cellulose was seen as laminated inorganic fragments and most often showed an elongated, quadrangular appearance. Amorphous, ill-defined fragments as well as a dense proteinaceous background with phagocytic cells were also present. CONCLUSIONS: The current study demonstrates that FNA cytology is a very useful method for the detection of pseudotumoral lesions induced by hemostatic agents. Pathologists must be familiarized with this finding because cytology permits easy differentiation from tumor recurrence.