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Pituitary neuroendocrine tumors (PitNETs) are common, generally benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNETs can be classified based on the expression pattern of anterior pituitary hormones and three main transcriptions factors (TF), SF1, PIT1 and TPIT that regulate differentiation of adenohypophysial cells. Here, we have extended this classification based on the global transcriptomics landscape using tumor tissue from a well-defined cohort comprising 51 PitNETs of different clinical and histological types. The molecular profiles were compared with current classification schemes based on immunohistochemistry. Our results identified three main clusters of PitNETs that were aligned with the main pituitary TFs expression patterns. Our analyses enabled further identification of specific genes and expression patterns, including both known and unknown genes, that could distinguish the three different classes of PitNETs. We conclude that the current classification of PitNETs based on the expression of SF1, PIT1 and TPIT reflects three distinct subtypes of PitNETs with different underlying biology and partly independent from the expression of corresponding hormones. The transcriptomic analysis reveals several potentially targetable tumor-driving genes with previously unknown role in pituitary tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: The new World Health Organization (WHO) classification system proposed a cell lineage-based classification scheme for pituitary adenomas in which transcription factors (TFs) play a major role as key classifiers. We aimed to evaluate clinical relevance of the new classification system in a clinical setting. Methods: TF staining was retrospectively performed for 153 clinically and histologically well characterized pituitary adenomas. Then, 484 pituitary adenomas were prospectively stained for TFs and then for relevant pituitary hormones. TF and hormone stain-based diagnoses were compared, and differences in clinical manifestations were evaluated. Results: The accuracies of antibodies for three TFs were successfully validated and had an overall matching rate was 89.6%. We identified 50 (10.4%) cases with discrepancies between TF and pituitary hormone stains. Gonadotroph adenomas lacking follicle-stimulating hormone and luteinizing hormone stains account for most discrepancies. Null cell adenomas may be more prevalent than reported and may be clinically more aggressive than gonadotroph adenomas. Conclusion: The new WHO classification is mostly well matched with the traditional classification. However, until the new classification is further validated and interpreted in the context of long-term clinical outcomes, routine histological examination should include full slate of immunostains for pituitary hormones as well as TFs. [ABSTRACT FROM AUTHOR]

Cortexolone 17α‐propionate, also known as clascoterone, is a potent androgen receptor inhibitor intended for the topical treatment of skin diseases associated with androgenic pathway alterations. In nonclinical studies, cortexolone 17α‐propionate was found to have a weak inhibitory effect on human Ether‐à‐go‐go‐Related Gene (hERG) potassium channels, which are vital for normal electrical activity in the heart. When used in a cream formulation, little cortexolone 17α‐propionate is absorbed. However, the solution formulation developed for the treatment of androgenetic alopecia leads to a measurable systemic concentration and accumulation of the antiandrogen. This phase 1 study assessed the effect of cortexolone 17α‐propionate on the QTc interval using concentration‐effect analysis and the effect of a meal on QTc to confirm assay sensitivity. Thirty‐two volunteers were randomly assigned to receive the active drug or a matching vehicle as placebo. Participants were dosed twice daily on days 1 to 3 (225 mg applied topically as a 7.5% solution 12 hours apart) and once on day 4. Pharmacokinetic and electrocardiogram assessments were performed after supratherapeutic doses. Assay sensitivity was successfully confirmed by using the food effect on the QTc interval. The results of this concentration‐QTc analysis demonstrate that cortexolone 17α‐propionate and its metabolite/degradation product had no effect on the QTc interval in the concentration range tested. [ABSTRACT FROM AUTHOR]

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The efficacy of clascoterone cream was demonstrated in two phase three vehicle-controlled clinical trials that enrolled over 1,400 subjects. Its safety profile allowed it to be approved for treating patients as young as 12 years old. During clinical trials, the occurrence of local skin reactions (edema, erythema, pruritus, dryness) was similar to treatment with vehicle alone. All publications describing the clinical development of clascoterone cream (cortexolone 17α-propionate) are reviewed and discussed in relation to with existing topical and systemic therapies for acne vulgaris. Clascoterone 1% cream is a novel first-in-class topical androgen receptor inhibitor for the treatment of acne vulgaris. Topical clascoterone 1% cream represents the first new type of therapy for acne treatment in almost 40 years and may become first-line therapy. [ABSTRACT FROM AUTHOR]

Introduction: Pituitary hyperplasia following primary hypothyroidism in pediatric age group population is considered rare with reports of unnecessary neurosurgical intervention for this medically treatable condition. Given the paucity of information on this topic, it is timely to provide clinicians with a comprehensive summary of available research. Methods: A search of published studies in Pubmed, PsychInfo and Cochrane Database with the terms "pituitary hyperplasia" or "pituitary hypertrophy" and "hypothyroidism" was performed and the results filtered for English language, pediatric (0-18 years) population and CT or MRI confirmed findings. 55 studies met the inclusion criteria. Data for a total of 110 patients with pituitary hyperplasia following primary hypothyroidism were extracted. The study population included 29 males and 81 females (M: F= 0.35:1). Patient age varied from 3 weeks to 18 years with a mean age of 10.22 years. Results: The most common clinical presentations included growth retardation, constipation and features of myxedema which were present in 78, 36 and 18 percent of children included in our review. Neuroimaging showed the mean (SD) pituitary height being 13.48 mm (4.72 mm). All of the patients achieved resolution of their pituitary mass and clinical as well as biochemical abnormalities 1 to 26 months after initiation of thyroid hormone replacement therapy, with an average time interval of 7.22 months. Our review has tried to delve in the pathophysiology as well as clinical, biochemical and radiological aspects of pediatric pituitary hyperplasia secondary to primary hypothyroidism and provide recommendations for treatment and follow-up. This may help anyone concerned gain a substantial knowledge on this topic. [ABSTRACT FROM AUTHOR]

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Objectives: The objective of the study was to determine the risk of subsequent keratitis in prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT). Materials and Methods: Three thousand three hundred and nine patients with PCa were identified using data from Taiwan's National Health Insurance Research Database for 2001 through 2013. Among those patients, 856 treated with ADT comprised the study group, while 856 non-ADT-treated patients matched with 1:1 propensity-score-matched analysis comprised the control group. The demographic characteristics and comorbidities of all the patients were analyzed, and Cox proportional hazards regression was utilized to determine the hazard ratios (HRs) for subsequent keratitis. Results: A total of 157 (9.2%) patients had newly diagnosed keratitis. Compared to the non-ADT-treated patients, the ADT-treated patients had a reduced risk of subsequent keratitis, with an adjusted HR of 0.38 (95% confidence interval: 0.27-0.55; P < 0.001). Conclusion: ADT treatment apparently decreased the risk of subsequent keratitis in the investigated PCa patients, but the clinical significance of this finding should be further assessed in additional studies. [ABSTRACT FROM AUTHOR]

Purpose: Moderate hyperprolactinaemia (2–5 times upper limit of normal) occurring in a patient with a normal pituitary MRI is generally considered to be due to a lesion below the level of detection of the MRI scanner assuming macroprolactin and stress have been excluded. Most patients with mild-to-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We present the rare case of a patient who had prolactin elevation typical of a prolactin-secreting pituitary macroadenoma,with a normal cranial MRI, and in whom the prolactin rose further with dopamine agonist treatment. Subsequent investigations revealed ectopic hyperprolactinaemia to a uterine tumor resembling ovarian sex cord tumor (UTROSCT) which resolved following tumor resection. Although mostly considered to be benign, the UTROSCT recurred with recurrent hyperprolactinaemia and intraabdominal metastases. Methods: We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically. Results: Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT. Conclusions: Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10× ULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs. [ABSTRACT FROM AUTHOR]

The traditional approach to the diagnosis of primary adenohypophyseal cell proliferations uses hormone immunohistochemistry to classify pituitary neuroendocrine tumors (PitNETs). The routine application of immunolocalization of pituitary transcription factors (SF1, PIT1, TPIT, ERα, and recently GATA3) along with adenohypophyseal hormones has taught us critical lessons that are discussed in this communication. We point out that appropriate patient care requires accurate diagnosis and is critical in the era of precision medicine. A misdiagnosis can result in far greater health care costs than the cost of accurate tumor classification and may have other unintended consequences. We provide additional insights about confusing findings in genomic studies, emphasizing that high-quality pathology is essential for strong science and translational research. [ABSTRACT FROM AUTHOR]

Purpose: Earlier findings revealed the damaging effect of visible light on zygotes and gametes. The aim of our study is to eliminate or significantly reduce the potentially harmful effects of light exposure during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and to investigate the effect of light protection on embryo development and implantation.Materials and Methods: To protect sperm cells, oocytes, and embryos from the potential harmful effects of light exposure during laboratory procedures, we created a dark environment for the cells and applied red filters on laboratory lamps and UV or infrared filters in the microscopes in order to eliminate white light exposure of the cells throughout all work stages.Results: The fertilization rate was significantly (p = 0.011) higher in light-protected ICSI cycles. Blastocyst development rates (blastocyst/embryo) were significantly (p < 0.001) higher in light-protected embryos than in those manipulated in conventional light conditions both in IVF (20.9% difference) and ICSI (38.6% difference). Numbers of clinical pregnancies/transfers of ICSI fertilized day 5 blastocysts were also significantly (p = 0.040) higher in light-protected conditions.Conclusions: These data show that light protection has a positive effect on fertilization rate and increases the blastocyst development as well as the number of clinical pregnancies/transfers. Implementation of this light protection method in IVF centers may improve the success rate while maintaining maximal embryo safety. [ABSTRACT FROM AUTHOR]

The classification of tumors of the pituitary gland has seen several changes in recent years. The 4th edition of the World Health Organization Classification of Tumours of Endocrine Organs, published in 2017, saw the introduction of a classification based on cell lineage using immunohistochemistry for both pituitary specific hormones as well as pituitary specific transcription factors. The term "hormone-producing" was thus replaced by "-troph." The other major change was that the entity of "atypical adenoma," which was introduced in the 2004 classification, to identify tumors with a poor prognosis, was removed as it failed to identify aggressive tumors. Instead, assessment of markers of proliferation, clinical parameters, such as invasive status and histological subtypes were recommended to identify tumors with aggressive potential. The diagnostic criteria for pituitary carcinoma, however, remained unchanged and continued to be defined as a tumor of adenohypophyseal cells that metastasize craniospinally or systemically. Null cell adenomas were more clearly defined as tumors that did not show any cell-type differentiation, lacking immunoexpression of hormones as well as transcription factors. Since 2017, the classification has continued to evolve with the identification of aggressive histological variants. There is more recently a proposal to change the terminology from pituitary adenoma to pituitary neuroendocrine tumor (PitNET). This review summarizes the recent advances in the classification of pituitary adenomas. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumours of the adenohypophysis have traditionally been designated as pituitary adenomas to underline their usually indolent growth and lack of metastatic potential. However, they may demonstrate a huge spectrum of growth patterns and endocrine disturbances, some of them significantly affecting health and quality of life. To predict tumour growth, risk of postoperative recurrence and response to medical therapy in patients with pituitary neuroendocrine tumours is challenging. A thorough histopathological and immunohistochemical diagnostic work‐up is an obligatory part of a multidisciplinary effort to precisely define the tumour type and assess prognostic and predictive factors on an individual basis. In this review, we have summarized the current status in the pathology in pituitary neuroendocrine tumours based on the selection of references from the PubMed database. We have presented possible diagnostic approaches according to the current pituitary cell lineage‐based classification. The importance of recognizing histological subtypes with potentially aggressive behaviour and identification of prognostic and predictive tissue biomarkers have been highlighted. Controversies related to particular subtypes of pituitary tumours and a still limited prognostic impact of the current classification indicate the need for further refinement. Multidisciplinary approach including clinical, pathological and molecular genetic characterization will be essential for improved personalized therapy and the search for novel therapeutic targets in patients with pituitary neuroendocrine tumours. [ABSTRACT FROM AUTHOR]

In utero development represents a sensitive window for the induction of mutations. These mutations may subsequently expand clonally to populate entire organs or anatomical structures. Although not all adverse mutations will affect tissue structure or function, there is growing evidence that clonally expanded genetic mosaics contribute to various monogenic and complex diseases, including cancer. We posit that genetic mosaicism is an underestimated potential health problem that is not fully addressed in the current regulatory genotoxicity testing paradigm. Genotoxicity testing focuses exclusively on adult exposures and thus may not capture the complexity of genetic mosaicisms that contribute to human disease. Numerous studies have shown that conversion of genetic damage into mutations during early developmental exposures can result in much higher mutation burdens than equivalent exposures in adults in certain tissues. Therefore, we assert that analysis of genetic effects caused by in utero exposures should be considered in the current regulatory testing paradigm, which is possible by harmonization with current reproductive/developmental toxicology testing strategies. This is particularly important given the recent proposed paradigm change from simple hazard identification to quantitative mutagenicity assessment. Recent developments in sequencing technologies offer practical tools to detect mutations in any tissue or species. In addition to mutation frequency and spectrum, these technologies offer the opportunity to characterize the extent of genetic mosaicism following exposure to mutagens. Such integration of new methods with existing toxicology guideline studies offers the genetic toxicology community a way to modernize their testing paradigm and to improve risk assessment for vulnerable populations. Environ. Mol. Mutagen. 61:55–65, 2020. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. [ABSTRACT FROM AUTHOR]

The diagnostic algorithm and nomenclature of pituitary neuroendocrine tumors have evolved over the past decade, beginning with simpler categorical schemes focused on histomorphologic features and moving to a more sophisticated lineage-specific categorization. This contemporary overview highlights a multimodal approach to pituitary neuroendocrine tumors with a focus on changes in nomenclature, classification, and subclassification; including, brief comments on treatment, and new guidelines for genetic screening, particularly for young patients with such neoplasms., Competing Interests: The authors have no funding or conflicts of interest to disclose, (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: This review explores insights provided by next-generation sequencing (NGS) of pituitary tumors and the clinical implications. Areas covered: Although syndromic forms account for just 5% of pituitary tumours, past Sanger sequencing studies pragmatically focused on them. These studies identified mutations in MEN1, CDKN1B, PRKAR1A, GNAS and SDHx causing Multiple Endocrine Neoplasia-1 (MEN1), MEN4, Carney Complex-1, McCune Albright Syndrome and 3P association syndromes, respectively. Furthermore, linkage analysis of single-nucleotide polymorphisms identified AIP mutations in 20% with familial isolated pituitary adenomas (FIPA). NGS has enabled further investigation of sporadic tumours. Thus, mutations of USP8 and CABLES1 were identified in corticotrophinomas, BRAF in papillary craniopharyngiomas and CTNNB1 in adamantinomatous craniopharyngiomas. NGS also revealed that pituitary tumours occur in the DICER1 syndrome, due to DICER1 mutations, and CDH23 mutations occur in FIPA. These discoveries revealed novel therapeutic targets and studies are underway of BRAF inhibitors for papillary craniopharyngiomas, and EGFR and USP8 inhibitors for corticotrophinomas. Expert opinion: It has become apparent that single-nucleotide variants and small insertion/deletion DNA mutations cannot explain all pituitary tumorigenesis. Integrated and improved analyses including whole-genome sequencing, copy number, and structural variation analyses, RNA sequencing and epigenomic analyses, with improved genomic technologies, are likely to further define the genomic landscape. [ABSTRACT FROM AUTHOR]

Our objective was determining the effects of amniotic fluid (AF) and fetal cord blood (FCB) cotinine concentrations on pregnancy complications and the anthropometric measurements in the newborns whose mothers underwent amniocentesis. This study was conducted as a case-control study, in Turkey. A total of 250 pregnant women with amniocentesis indication were recruited into the study and the cotinine levels in the AF and FCB were determined. A smoking habit did not statistically affect the incidence of pregnancy complications (p>.05). The birth weights of the newborns were negatively correlated with the AF cotinine levels. The incidences of low birth weight, low Apgar scores and RDS were positively correlated with higher levels of cotinine in AF and FCB. It is important for healthcare staff to provide training and consultancy services for the health improvement of pregnant women and the prevention of smoking during pregnancy. Impact statement What is already known on this subject? The pre-pregnancy smoking habit usually continues during the pregnancy. A significant negative correlation was present between the foetal cord blood cotinine levels and the birth weight. What do the results of this study add? The anthropometric measurements of the newborns born from mothers with high AF cotinine levels were lower than newborns born from mothers with low amniotic fluid cotinine levels. Respiratory Distress syndrome is more often determined in newborns born from mothers with high AF cotinine levels. What are the implications of these findings for clinical practice and/or further research? Future studies should be performed to investigate the effects of cigarette smoking on the health problems, the growth characteristics and the neurological development of newborns and infants within the first year of life. [ABSTRACT FROM AUTHOR]

Purpose: Ectopic pituitary adenomas (EPA) are rare tumors thought to arise from embryological remnants along the route of normal pituitary migration. Clinically, these tumors vary in hormonal activity and can exert mass effect based on location and size. Methods: We performed a single-center retrospective analysis of patients with diagnosis of ectopic pituitary adenoma from 2001 to 2018. Results: Five patients were identified with EPA: a 48-year-old woman with suprasellar EPA treated with transsphenoidal removal of the tumor, a 44-year-old woman with cavernous EPA treated with transsphenoidal removal of the tumor, a 48-year-old woman with sphenoid EPA treated with cabergoline, a 45-year-old man with clival EPA treated with cabergoline and transsphenoidal surgical resection, and a 54-year-old man with clival EPA treated with cabergoline therapy. Conclusions: EPA should be considered as a differential diagnosis of juxta-sellar lesions. Appropriate hormonal testing may lead to early diagnosis, avoidance of unnecessary biopsy or surgery, and improved outcomes. [ABSTRACT FROM AUTHOR]

Copyright of Signa is the property of Editorial UNED and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Non-functioning pituitary neuroendocrine tumors do not cause endocrine symptoms related to hypersecretion of adenohypophyseal hormones and are clinically characterized by symptoms due to growing sellar tumor mass. Histopathological classification of this tumor group has always been challenging due to their heterogeneity, limited knowledge on their biology, and diverse methodological problems. We have searched PubMed database for data related to the histopathological classification of non-functioning pituitary tumors and methods for its application. Principles of the classification and grading presented in the recently released 4th edition of the World Health Organization classification of endocrine tumors have been summarized. Based on the expression of anterior pituitary hormones and pituitary specific transcription factors, gonadotroph tumors dominate within the group of clinically non-functioning tumors, followed by corticotroph type; however, other less common types of the non-functioning tumors can be identified. Assessment of tumor cell proliferation is important to identify “high-risk adenomas.” A few subtypes of non-functioning tumors belong to the category of potentially aggressive tumors, independent of the cell proliferation rate. Here, we present up to date criteria for the classification of clinically non-functioning pituitary tumors, offer a diagnostic approach for the routine clinical use, and emphasize a need for inclusion of prognostic and predictive markers in the classification. [ABSTRACT FROM AUTHOR]

Copyright of Genome is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Finasteride is a well-known 5α-reductase inhibitor used for treatment of alopecia and prostate cancer. But the effect of finasteride in regulating melanogenesis is still unclear. In the present study the role of finasteride on melanogenesis was investigated. Finasteride decrease melanin level in melanocyte melan-a cells and B16F10 melanoma cells without inducing cytotoxicity. MC1R (melanocortin 1 receptor) protein expression was also inhibited by finasteride thereby decreasing the expression of adenylate cyclase, MITF (Melanogenesis associated transcription factor), tyrosinases, TRP (tyrosinase-related protein) -1 and -2. Thus our study suggest that finasteride inhibits melanogenesis in melanocyte and melanoma cells by inhibiting MC1R. [ABSTRACT FROM AUTHOR]

The increasing recognition of pituitary disorders and their impact on quality of life and longevity has made understanding of this small gland a subject of paramount importance. Pituitary pathology has seen many significant studies that indicate progress in identification and classification of pituitary lesions, as well as improved management strategies for patients. In this review, we outline six major areas of advances: (i) changes in terminology from 'adenoma' to 'pituitary neuroendocrine tumour'; (ii) reclassification of hormone-negative tumours based on transcription factor expression that defines lineage; (iii) updates in new pathogenetic mechanisms, including those that underlie rare lesions such as X- LAG and pituitary blastoma; (iv) clarification of hypophysitis due to immunotherapy, xanthomatous hypophysitis due to rupture of a Rathke's cleft cyst and IgG4 disease as the cause of inflammatory pseudotumour; (v) the consolidation of pituicytoma variants, including spindle cell oncocytoma and granular cell tumour based on thyroid transcription factor-1 ( TTF-1) reactivity; and (vi) the pathogenetic mechanisms that distinguish papillary from adamantinomatous craniopharyngioma. The remaining challenge is clarification of the pathogenetic mechanisms underlying the development of many of these disorders. [ABSTRACT FROM AUTHOR]

Thyrotropin (TSH)-secreting adenomas (TSHomas) are the rarest form of pituitary adenomas, and most endocrinologists will see few cases in a lifetime, if any. In most cases, the diagnostic approach is complicated and cases may be referred after being presented as a syndrome of inappropriate TSH secretion or as a pituitary mass. This review aims to cover the past, present and possible future diagnostic approaches to TSHomas, including different clinical presentations, laboratory assessment and imaging advances. The differential diagnoses will be discussed, as well as possible coexisting disorders. By evaluating the existing reports and reviews describing this rare condition, this review aims to present a clinically practical suggestion on the diagnosic workup for TSHomas, Major advances and scientific breakthroughs in the imaging area in recent years, facilitating diagnosis of TSHomas, support the belief that future progress within the imaging field will play an important role in providing methods for a more efficient diagnosis of this rare condition. [ABSTRACT FROM AUTHOR]

The 4th edition of the World Health Organization (WHO) classification of endocrine tumors has been recently released. In this new edition, major changes are recommended in several areas of the classification of tumors of the anterior pituitary gland (adenophypophysis). The scope of the present manuscript is to summarize these recommended changes, emphasizing a few significant topics. These changes include the following: (1) a novel approach for classifying pituitary neuroendocrine tumors according to pituitary adenohypophyseal cell lineages; (2) changes to the histological grading of pituitary neuroendocrine tumors with the elimination of the term 'atypical adenoma;' and (3) introduction of new entities like the pituitary blastoma and re-definition of old entities like the null-cell adenoma. This new classification is very practical and mostly based on immunohistochemistry for pituitary hormones, pituitary-specific transcription factors, and other immunohistochemical markers commonly used in pathology practice, not requiring routine ultrastructural analysis of the tumors. Evaluation of tumor proliferation potential, by mitotic count and Ki-67 labeling index, and tumor invasion is strongly recommended on individual case basis to identify clinically aggressive adenomas. In addition, the classification offers the treating clinical team information on tumor prognosis by identifying specific variants of adenomas associated with an elevated risk for recurrence. Changes in the classification of non-neuroendocrine tumors are also proposed, in particular those tumors arising in the posterior pituitary including pituicytoma, granular cell tumor of the posterior pituitary, and spindle cell oncocytoma. These changes endorse those previously published in the 2016 WHO classification of CNS tumors. Other tumors arising in the sellar region are also reviewed in detail including craniopharyngiomas, mesenchymal and stromal tumors, germ cell tumors, and hematopoietic tumors. It is hoped that the 2017 WHO classification of pituitary tumors will establish more biologically and clinically uniform groups of tumors, make it possible for practicing pathologists to better diagnose these tumors, and contribute to our understanding of clinical outcomes for patients harboring pituitary tumors. [ABSTRACT FROM AUTHOR]

Drawing upon a vast array of primary sources, this article focuses on a key period of modern Spanish history: November 1918 – April 1919. In the aftermath of the First World War and spurred on by the Allied victory, demands by Catalonia's political elites for greater autonomy seized the country's agenda. However, the political tussle between the centre and the Catalan elites ended a few months later with their mutual defeat. The upsurge of labour agitation and the hopes of the proletariat generated by the Bolshevik Revolution combined with bourgeois fear resulted in the question of national identity being superseded by bitter class conflict. This article conveys the thesis that these crucial months crystallized the organic crisis of the ruling liberal regime. Indeed, the outcome of these events proved its fragile foundations, dashed hopes for a reformist and negotiated solution, and constituted a dress rehearsal for the military coup of 1923, a clear example of the reactionary backlash which swept across Europe in the interwar years. [ABSTRACT FROM AUTHOR]

This review focuses on discussing the main changes on the upcoming fourth edition of the WHO Classification of Tumors of the Pituitary Gland emphasizing histopathological and molecular genetics aspects of pituitary neuroendocrine (i.e., pituitary adenomas) and some of the non-neuroendocrine tumors involving the pituitary gland. Instead of a formal review, we introduced the highlights of the new WHO classification by answering select questions relevant to practising pathologists. The revised classification of pituitary adenomas, in addition to hormone immunohistochemistry, recognizes the role of other immunohistochemical markers including but not limited to pituitary transcription factors. Recognizing this novel approach, the fourth edition of the WHO classification has abandoned the concept of 'a hormone-producing pituitary adenoma' and adopted a pituitary adenohypophyseal cell lineage designation of the adenomas with subsequent categorization of histological variants according to hormone content and specific histological and immunohistochemical features. This new classification does not require a routine ultrastructural examination of these tumors. The new definition of the Null cell adenoma requires the demonstration of immunonegativity for pituitary transcription factors and adenohypophyseal hormones Moreover, the term of atypical pituitary adenoma is no longer recommended. In addition to the accurate tumor subtyping, assessment of the tumor proliferative potential by mitotic count and Ki-67 index, and other clinical parameters such as tumor invasion, is strongly recommended in individual cases for consideration of clinically aggressive adenomas. This classification also recognizes some subtypes of pituitary neuroendocrine tumors as 'high-risk pituitary adenomas' due to the clinical aggressive behavior; these include the sparsely granulated somatotroph adenoma, the lactotroph adenoma in men, the Crooke's cell adenoma, the silent corticotroph adenoma, and the newly introduced plurihormonal Pit-1-positive adenoma (previously known as silent subtype III pituitary adenoma). An additional novel aspect of the new WHO classification was also the definition of the spectrum of thyroid transcription factor-1 expressing pituitary tumors of the posterior lobe as representing a morphological spectrum of a single nosological entity. These tumors include the pituicytoma, the spindle cell oncocytoma, the granular cell tumor of the neurohypophysis, and the sellar ependymoma. [ABSTRACT FROM AUTHOR]

Investigations on the impact of chemicals on the environment and human health have led to the development of an exposome concept. The exposome refers to the totality of exposures received by a person during life, including exposures to life-style factors, from the prenatal period to death. The exposure to genotoxic chemicals and their reactive metabolites can induce chemical modifications of DNA, such as, for example, DNA adducts, which have been extensively studied and which play a key role in chemically induced carcinogenesis. Development of different methods for the identification of DNA adducts has led to adopting DNA adductomic approaches. The ability to simultaneously detect multiple PAH-derived DNA adducts may allow for the improved assessment of exposure, and offer a mechanistic insight into the carcinogenic process following exposure to PAH mixtures. The major advantage of measuring chemical-specific DNA adducts is the assessment of a biologically effective dose. This review provides information about the occurrence of the polycyclic aromatic hydrocarbons (PAHs) and their influence on human exposure and biological effects, including PAH-derived DNA adduct formation and repair processes. Selected methods used for determination of DNA adducts have been presented. [ABSTRACT FROM AUTHOR]

Background: The somatostatin receptor subtype 2 (sstr2) is expressed on a majority of luminal breast cancers, however SPECT and scintigraphy imaging with agonistic sstr2 probes has been sub-optimal. High affinity antagonists can access more binding sites on the cell surface, resulting in higher tumor uptake and improved sensitivity. We compared the tumor uptake and biodistribution of the antagonist Ga-NODAGA-JR11 with two agonists Ga-DOTA-Tyr-octreotide (Ga-DOTATOC) and Ga-DOTA-Tyr-octreotate (Ga-DOTATATE), in the human, sstr2-positive, luminal breast cancer model: ZR-75-1. Results: Peptides were assayed for binding affinity using a filtration-based competitive assay to sstr2. Ga-DOTATOC and Ga-DOTATATE had excellent affinity (inhibition constant K: 0.9 ± 0.1 nM and 1.4 ± 0.3 nM respectively) compared to Ga-NODAGA-JR11 (25.9 ± 0.2 nM). The number of binding sites on ZR-75-1 cells was determined in vitro by saturation assays. Agonist Ga-DOTATOC bound to 6.64 ± 0.39 × 10 sites/cells, which was 1.5-fold higher than Ga-NODAGA-JR11 and 2.3-fold higher than Ga-DOTATATE. All three Ga-labeled peptides were obtained in good decay-corrected radiochemical yield (61-68%) and were purified by high performance liquid chromatography to ensure high specific activity (137 - 281 MBq/nmol at the end of synthesis). NOD scid gamma mice bearing ZR-75-1 tumors were injected intravenously with the labeled peptides and used for PET/CT imaging and biodistribution at 1 h post-injection. We found that Ga-DOTATOC had the highest tumor uptake (18.4 ± 2.9%ID/g), followed by Ga-DOTATATE (15.2 ± 2.2%ID/g) and Ga-NODAGA-JR11 (12.2 ± 0.8%ID/g). Tumor-to-blood and tumor-to-muscle ratios were also higher for the agonists (>40 and >150 respectively), compared to the antagonist (15.6 ± 2.2 and 45.2 ± 11.6 respectively). Conclusions: The antagonist Ga-NODAGA-JR11 had the lowest tumor uptake and contrast compared to agonists Ga-DOTATOC and Ga-DOTATATE in ZR-75-1 xenografts. The main contributing factor to this result could be the use of an endogenously expressing cell line, which may differ from previously published transfected models in the number of low-affinity, antagonist-specific binding sites. The relative merit of agonists versus antagonists for sstr2 breast cancer imaging warrants further investigation, first in preclinical models with other sstr2-positive breast cancer xenografts, and ultimately in luminal breast cancer patients. [ABSTRACT FROM AUTHOR]

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The article explores the practice of historical research in connection with archival management at the turn of the eighteenth and nineteenth centuries, focusing on revolutionary and imperial France, when the French archives underwent unprecedented alteration. More precisely, it deals with the period 1808-14, when the archives directed by former revolutionary P. C. F. Daunou were merged into a new Palais des Archives and the historical archives of Europe were transported to Paris to form a central imperial repository. The article argues that the management, classification and use of archival documents followed the notion of history as a social science and an analytical empirical discipline put forward by the influential group of the Idéologues in post-Thermidorian France. This resulted in a peculiar way of dealing with the mass of new sources now available in the Archives de l'Empire. Indeed, the practice of historical research in the French archives was linked to a small, yet significant innovation in data management andmaterial culture, namely, the use of filing cards in order to extract facts from documents. The article discusses the distinctive features of archival management and historical research in this transition period in comparison with the supposed "archival revolution" of Romantic historiography. [ABSTRACT FROM AUTHOR]