 We report a case of meningioma with both secretory and lipomatous features in an advanced middle aged female patient with a 3-month history of headaches and convulsions. Radiological findings are revised and compared to other reported cases in the literature.
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 Zusammenfassung Hintergrund
Urologische Tumoren zählen zu den häufigsten malignen Erkrankungen. In den letzten Jahren hat das Wissen um die molekularen Hintergründe und damit auch die potenzielle Zahl an prädiktiven Biomarkern deutlich zugenommen.
Ziel der Arbeit
Ziel der vorliegenden Arbeit ist es, eine Übersicht über aktuelle (molekulare) Entwicklungen und die damit verbundenen prädiktiven Biomarker in der urologischen Onkologie zu geben sowie einen Ausblick auf die kommenden Entwicklungen zu formulieren.
Material und Methoden
Es wurden die aktuelle Literatur und (Studien‑)Datenlage sowie eigene Erfahrungen berücksichtigt und zu Tumoren des ableitenden Harnsystems, der Niere und Prostata zusammengefasst.
Ergebnisse und Diskussion
Die molekularen Subtypen des muskelinvasiven Urothelkarzinoms der Harnblase (MIBC) zeigen eine prädiktive und prognostische Bedeutung mit klinikopathologischem Korrelat. Die Immuntherapie mit Checkpointinhibitoren (CPI) spielt besonders beim Urothelkarzinom, aber auch beim Nierenzellkarzinom und einer Subgruppe des Prostatakarzinoms eine Rolle. Bisher ist dabei lediglich die Erstlinientherapie des Urothelkarzinoms an die PD-L1-Expression gebunden (≥IC2/3, CPS ≥ 10). Weitere prädiktive Marker zur CPI-Therapie sind unter Evaluation, wobei die Wertigkeit der Tumormutationslast (TMB) noch nicht abschließend geklärt ist. Neben weiteren Subgruppen auch der Nierenzellkarzinome stellen Prostatakarzinome mit Veränderungen in den DNA-Reparaturmechanismen eine besondere klinische Gruppe mit speziellen Therapieoptionen dar (PARP-Inhibition, platinhaltige Chemotherapie). Die Vielzahl der potenziell therapierelevanten molekularen Veränderungen und damit verbundenen prädiktiven Marker macht differenzierte Genpanelanalysen sinnvoll, was in der urologischen Pathologie zu einer immer stärkeren Dynamik führt.
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Publication date: Available online 8 May 2019
Source: Pathology - Research and Practice
Author(s): Lina Gu, Meixiang Sang, Juan Li, Fei Liu, Yunyan Wu, Shina Liu, Pengyu Wang, Baoen Shan
Abstract
Objective
To evaluate the clinical characteristics and prognostic significance of MAGE-A11 and transcription factors (SP1, TFCP2 and ZEB1) in patients with esophageal squamous cell carcinoma (ESCC).
Methods
To assess the expression of MAGE-A11 and transcription factors (SP1, TFCP2 and ZEB1) in 121 ESCC samples were respectively detected by immunohistochemical method.
Results
The results showed MAGE-A11 and transcription factors (SP1,TFCP2 and ZEB1) expression were associated with some clinical features in patients, such as pathological differentiation, tumor size, clinical stage, lymph node metastasis and distant metastasis. Kaplan-Meier analysis showed that patients with ESCC having high MAGE-A11 and transcription factors (SP1,TFCP2 and ZEB1) expression had a worse prognosis compared to the patients with low expression. Multivariate Cox proportional hazards regression model revealed that MAGE-A11 expression, TFCP2 expression, lymph node metastasis and distant metastasis were independently associated with ESCC patients’ survival.
Conclusions
High expression of MAGE-A11 and transcription factors (SP1,TFCP2 and ZEB1) in ESCC tissues suggests promoting ESCC progression and poor prognosis, co-expression of MAGE-A11 and transcription factors even worse.
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Publication date: Available online 8 May 2019
Source: Human Pathology
Author(s): Rina Kansal
Summary
The 2016/2017 World Health Organization (WHO2016/2017) classification for acute myeloid leukemia (AML) includes new entities with gene mutations in NPM1 (AML-NPM1mut) and biallelic CEBPA (AML-biCEBPAmut). To retrospectively identify and study these new molecularly-defined WHO2016/2017entities, we reviewed clinicopathologic data and pre-therapy archived pathologic materials at diagnosis for 143 consecutive AML cases {55.2% males, median age 62(range 18–89)y}, and classified all cases by the 2008 WHO (WHO2008) and revised WHO2016/2017 criteria. By WHO2008, cases included 21(15%) with recurrent genetic abnormalities {52.3% males, median age 54(range18–82)y}, 54(38%) with myelodysplasia-related changes (AML-MRC) {M:F = 31:23, median age 65(range 32–84)y}, 3(2%) therapy-related {100% males, median age 66(range 32–84)y}, and 65(45%) not otherwise specified (AML-NOS) {M:F = 34:31, median age 61(range 19–89)y}. 22(15.4%) cases (21 AML-NOS, 1 AML-MRC by WHO2008) reclassified by WHO2016/2017 as AML-NPM1mut showed female predominance (54.5%), and median(range) values: age 60.5(23–84)y, hemoglobin 8.6(5.6–12.9)g/dL, total leucocytes 30.1(2.58–241.84)x109/L, monocytes 1.65(0–49.34)x109/L, neutrophils 1.96(0–29.79)x109/L, platelets 55(11–320)x109/L, blasts {peripheral blood 41%(2–98%), bone marrow 66%(17–97%)}, with myeloblastsCD34neg {17(77%)/21}, cytogeneticsnormal {20(91%)/22}, FLT3-ITDpos {9(41%)/22}, FLT3-ITDnegFLT3-TKDpos {5(23%)/22}, FLT3-ITDnegFLT3-TKDneg {8(36%)/22}, and extramedullary involvement {6(27%)/22}, including 1 novel cutaneous presentation. Notably, presenting features among AML-NPM1mut included those of anemia {22(100%)} and thrombocytopenia {20(91%)/22}. This is also the first report of 4(18%)/22 AML-NPM1mut {including 3(75%)/4 non-smokers} with a family history of leukemia, and one 74-year-old with familial AML-biCEBPAmut. This study validates the application of the WHO2016/2017 classification criteria by retrospectively identifying AML-NPM1mut and AML-biCEBPAmut cases using single-gene molecular analyses. Additional studies are needed to characterize the complete spectrum of WHO2016/2017-defined AML-biCEBPAmut and for familial AML including AML-NPM1mut.
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The ovine developmental model represents the standard in vivo model for studies involving maternofetal physiology, amniotic fluid (AF) research, and fetal cell therapy prior to human clinical use. Although being close to the human fetal anatomy, 2 separate extraembryonic fluid compartments remain during gestation, known as the amnion and the allantois. A clear distinction between AF versus allantoic fluid (AL) is therefore indispensable for correct scientific conclusions with regard to human translation. In the presented study, the biochemical composition of AF and AL was evaluated in ovine gravid uteri postmortem (n = 31) over the entire gestation. Four parameters, consisting of Na+, Cl–, Mg2+, and total protein, have been found to allow for specific discrimination of the 2 fetal fluids at all gestational phases and therefore as potential surrogate parameters for gestational age. In addition, volumetric changes of the developing fetus and the 2 fetal fluid cavities were analyzed by contrast-enhanced computed tomography (n = 12). AF showed a significant, linear volumetric increase over gestation, whereas AL volume maintained relatively static independent of gestational age. These results serve as a basis for future studies by providing surrogate makers enabling a reliable distinction of isolated fetal fluids and contained cells in the ovine developmental model over the entire gestation.
Cells Tissues Organs
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Publication date: Available online 9 May 2019
Source: Pathology - Research and Practice
Author(s): Quentin Le Clef, Thomas Menter, Alexandar Tzankov
Abstract
Unexplained cytopenia is one of the most common indications for performing trephine bone marrow (BM) biopsy (BMB). The histopathological examination in this regard must be seen in the broader context of a multimodal approach in order to reach an as entity-specific as possible diagnosis, considering the medical history, the physical examination, laboratory data, peripheral blood morphology, BM aspiration smear, flow cytometry results and, if indicated, cytogenetics and molecular genetics. The particular irreplaceability of the histopathological work-up and the expectations to the BMB lie especially in the detection of fibrosing and/or focal processes (e.g. localized islets of blasts) and disorders extrinsic to the BM such as e.g. metastases, thrombotic microangiopathies, granulomatous myelitides etc. We propose a systematic combined histopathological pattern-based and blood count-based approach that can be applied in such circumstances to achieve a precise diagnosis or, at least, a clinically useful differential diagnosis, particularly taking into consideration specific morphologic pitfalls and application of ancillary techniques. Constitutional BM failure syndromes will not be profoundly addressed.
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Zusammenfassung
Die Funktion der transplantierten Lunge wird regelmäßig durch Alloimmunreaktionen mit sehr variablen klinischen Verläufen, verschiedenen beteiligten Effektorzellen und -molekülen sowie betroffenen Kompartimenten beeinträchtigt. Die akute zelluläre Abstoßung (ACR) nach Lungentransplantation (LuTx) trägt nicht nur zu einer akuten Transplantatdysfunktion mit erhöhter Mortalität bei, sondern ist neben anderen immunologischen und nichtimmunologischen Faktoren wesentlich an der Entwicklung der chronischen Transplantatdysfunktion („chronic lung allograft dysfunction“, CLAD) beteiligt, welche die Hauptursache für das limitierte Langzeitüberleben nach LuTx darstellt. Neben der ACR wurde analog zur Transplantation anderer solider Organe inzwischen auch bei der LuTx die Bedeutung der antikörpervermittelten (humoralen) Abstoßung (AMR) erkannt. Dabei sind aktuell weder für die ACR noch die AMR spezifische laborchemische, radiologische oder klinische Nachweisverfahren etabliert. Erst durch die synoptische Betrachtung aus morphologischen Verfahren mit histopathologischer Beurteilung einer Lungenbiopsie und mikrobiologischen, virologischen, serologischen sowie funktionellen Befunden wird eine ausreichende Sensitivität und Spezifität in der Abstoßungsdiagnostik erzielt. Im Folgenden werden die derzeit etablierten Kriterien für die morphologische Abstoßungsdiagnostik nach Lungentransplantation unter Berücksichtigung der wichtigsten Differenzialdiagnosen dargestellt.
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Publication date: Available online 9 May 2019
Source: Acta Histochemica
Author(s): Elsayed Metwally, Sameh Mohamed Farouk, Abdel-Hamid Kamel Osman
Abstract
The Cholesterol-synthesizing proteins (HMGCS1 and HMGCS2) are mitochondrial enzymes that believed to catalyze the first reaction of ketogenesis, the process by which energy is provided from fats in the absence of carbohydrates. Typically, astrocytes developed from its progenitor cells in the embryonic optic nerve and enriched with HMGCS1 and 2. However, the detailed histomorphology of camel HMGCS1 and 2 remains to be clearly defined. Here, we investigated the changes that associate with astrocytes differentiation within the developing camel optic nerve. Firstly, we isolated cDNAs encoding HMGCS1 and 2 from the optic nerve. Then, we found that HMGCS1 shared high similarity to human, while HMGCS2 showed a lower similarity and was more diverse. Immunohistochemical studies revealed that distinct correlation of astrocytes differentiation with HMGCS1 and 2 expressions in the developing camel optic nerve. Both encoded proteins were localized throughout the cytoplasm, as well as the nuclei of the astrocytes. In addition, semi-quantitative PCR analysis and western analysis confirmed that both HMGCS1 and 2 were highly expressed in camel optic nerve as well as other tissue, but they were lower in both skeletal and heart muscles. Moreover, various stains such as Sudan black and florescence filipin stains were used to visualize the free cholesterol in the astrocytes, indicating the enzymatic activity of HMGCS1 and 2. Together, our study reported the first comprehensive investigation of the molecular cloning and cellular expression of HMGCS1 and 2 in the optic nerve of dromedary camel.
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Publication date: Available online 9 May 2019
Source: Acta Histochemica
Author(s): Sara Mohamed Naguib Abdel Hafez, Rehab Ahmed Rifaai, Asmaa M.A. Bayoumi
Abstract
Almost all transplanted solid organs are exposed to some degree of ischemia-reperfusion (IR) damage. It is interesting to know that this IR damage affects various remote tissues including the liver and resulted in serious adverse effects. Liver injury triggers different responses of liver tissue especially Kupffer cells (KCs). The goal of this current study is to assess the biochemical and morphological changes of hepatic KCs after the induction of renal ischemia-reperfusion (RIR) and point out their role in remote liver injury after RIR.
Sixteen male Sprague-Dawley rats were randomly divided into two equal groups: Group I; sham group. Group II; renal ischemia reperfusion (IR) group in which rats were exposed to renal ischemia for 45 min followed by renal reperfusion for 48 h. Three rats from each group were subjected to charcoal injection to evaluate KCs activity. Specimens of rat liver from each group were obtained and processed for biochemical, light microscopic and ultramicroscopic examination. The current results showed elevated serum levels of AST and ALT. The liver HGF-α protein expression increased in IR group compared to the sham group. In IR group, numerous charcoal labeled KCs were observed mainly localized around the central vein. Scanning electron micrographs showed complex primary and secondary foot process of the KCs. Ultrastructural study showed KCs with multiple cytoplasmic vacuoles, lysosomes and mitochondria, rough endoplasmic reticulum and ribosomes. Immuno-histochemical study showed more tumor necrosis factor-α (TNF-α) expression in KCs than the sham group. These results collectively demonstrated that renal IR produced biochemical and morphological changes in the liver KCs and theses cells might have a role in the remote liver injury after renal IR. This might be one of the mechanisms through which RIR affects the liver.
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Publication date: Available online 9 May 2019
Source: Acta Histochemica
Author(s): Salvatore Lorenzo Renne, Silvia Redaelli, Biagio Paolini
Abstract
Frozen section examination (FSE) reshaped surgical pathology and is characterized by a high accuracy. Nonetheless pathologists can experience artefacts that can compromise or defer the diagnosis. We compared a commercial system, composed by a cryoembedder and a processor/stainer, to our FSE protocol. Feasibility of diagnosis as well as overall architecture, cytology, and staining, were scored under the following conditions: Traditional (liquid nitrogen freezing and manual staining), Only-Presto (liquid nitrogen freezing and commercial processor/stainer), Only-PrestoCHILL (cryoembedder and manual staining), and PrestoSystem (cryoembedder and processor/stainer). Scores were compared across the different experimental conditions. PrestoSystem had significantly higher scores than Traditional, Only-Presto or Only-PrestoCHILL in all categories (Wilcoxon test; all P-value <.001); similarly, also Only-Presto and Only-PrestoChill had significantly higher scores than Traditional in all categories. Only-PrestoCHILL had significantly higher scores than Only-Presto in Cytology and Architecture. In conclusion the control of pre-analytical variables provided reproducible results, of a higher quality.
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