The neuroendocrine cells can cause a variety of malignancies throughout the human body known as the neuroendocrine tumors (NETs) or carcinoid tumors. The primary testicular carcinoid tumor (PTCT) ...accounts for less than 1% of the testicular neoplasms and for only 0.2% of all carcinoid tumors representing already a very rare neoplastic entity. Here, we present a patient with a history of an exceptionally rare primary testicular carcinoid tumor, staining positive for Cdx-2 along with a literature review.
A 44-year old patient without significant past medical history was diagnosed in September 2009 with primary testicular carcinoid tumor, which was surprisingly staining positively for Cdx-2, too. At the time of the initial diagnosis the tumor was already showing histopathological infiltration of veins. DOTA-TATE-PET/CT imaging and endoscopy studies did not show any signs of distant metastases and in particular no gastrointestinal manifestation following no further medical indication for systemic chemotherapy. The continuous and close follow-up of the patient has reached a total of over 10 years at the time of publication remaining in complete remission.
The diagnosis of primary testicular carcinoid is based on histopathology. The detailed histopathologic assessment of biomarkers based on immunohistochemistry is very important for the classification and the prognosis of the primary testicular carcinoid tumor. Primary testicular carcinoid tumor with Cdx-2 positive stain outlines an exceptionally rare neoplastic entity without a consensus about general follow-up guidelines, requiring close clinical and imaging aftercare and consideration in Cdx-2 positive metastatic tumor of unknown origin.
We investigated the impact of mechanical unloading with a left ventricular assist device (LVAD) on the myocardial proteome.
We collected 11 patient-matched samples of myocardial left ventricular ...tissue of patients with non-ischaemic dilate cardiomyopathy, harvested at time of LVAD implant ('pre-LVAD') and heart transplant ('post-LVAD'). Samples were studied by quantitative proteomics. Further we performed histological assessment of deposited collagens and immune infiltration in both pre- and post-LVAD samples.
A core set of >1700 proteins was identified and quantified at a false discovery rate <1%. The previously established decrease post-LVAD of alpha-1-antichymotrypsin was corroborated. We noted a post-LVAD decrease of matricellular proteins and proteoglycans such as periostin and versican. Also, proteins of the complement system and precursors of cardiac peptide hormones were decreased post-LVAD. An increase post-LVAD was evident for individual proteins linked to the innate immune response, proteins involved in diverse metabolic pathways, and proteins involved in protein synthesis. Histological analysis did not reveal significant alterations post-LVAD of deposited collagens or immune infiltration. The proteomic data further highlighted a pronounced inter-patient heterogeneity with regards to the impact of LVAD therapy on the left ventricular myocardial proteome. Finally, the proteomic data showed differential proteolytic processing in response to LVAD therapy.
Our findings underline a strong impact of LVAD therapy on the left ventricular myocardial proteome. Together with previous studies, protein markers of LVAD therapy such as alpha-1-antichymotrypsin are becoming apparent. Further, matricellular proteins are emerging as important components in response to LVAD therapy.
Congenital extrahepatic portosystemic shunts (CEPS), previously also described as Abernethy malformations, are rare malformations in which the extrahepatic portal system directly communicates with ...the vena cava inferior, thereby bypassing the liver. A hypoplastic portal vein (PV) exists in most cases. CEPS have been associated with the development of liver nodules, ranging from mostly focal nodular hyperplasia (FNH) to hepatic adenoma (HA) and even hepatocellular carcinoma (HCC). Tumor development in CEPS may be due to changes in perfusion pressures, oxygen supply or endocrine imbalances. It is important to rule out CEPS in children with liver tumors, because resection could impede future shunt occlusion procedures, and benign masses may regress after shunt occlusion. Here, we review the case of a 9-years-old male with CEPS and hepatic nuclear Factor 1-alpha (HNF-1-alpha) inactivated HA to raise awareness of this condition and review histopathological changes in the liver of CEPS.
Pathological biopsy protocols require tissue marking dye (TMD) for orientation. In some cases (e.g., close margin), additional immunohistochemical analyses can be necessary. Therefore, the ...correlation between the applied TMD during macroscopy and the examined TMD during microscopy is crucial for the correct orientation, the residual tumour status and the subsequent therapeutic regime. In this context, our group observed colour changes during routine immunohistochemistry. Tissue specimens were marked with various TMD and processed by two different methods. TMD (blue, red, black, yellow and green) obtained from three different providers (A, B and C, and Whiteout/Tipp-Ex
) were used. Immunohistochemistry was performed manually via stepwise omission of reagents to identify the colour changing mechanism. Blue colour from provider A changed during immunohistochemistry into black, when 3,3'-Diaminobenzidine-tetrahydrochloride-dihydrate (DAB) and H
O
was applied as an immunoperoxidase-based terminal colour signal. No other applied reagents, nor tissue texture or processing showed any influence on the colour. The remaining colours from provider A and the other colours did not show any changes during immunohistochemistry. Our results demonstrate an interesting and important pitfall in routine immunohistochemistry-based diagnostics that pathologists should be aware of. Furthermore, the chemical rationale behind the observed misleading colour change is discussed.
Abstract
Background
Chondrogenic tumors are the most frequent primary bone tumors. Malignant chondrogenic tumors represent about one quarter of malignant bone tumors. Benign chondrogenic bone tumors ...are frequent incidental findings at imaging. Radiological parameters may be helpful for identification, characterization, and differential diagnosis.
Methods
Systematic PubMed literature research. Identification and review of studies analyzing and describing imaging characteristics of chondrogenic bone tumors.
Results and conclusions
The 2020 World Health Organization (WHO) classification system differentiates between benign, intermediate (locally aggressive or rarely metastasizing), and malignant chondrogenic tumors. On imaging, typical findings of differentiated chondrogenic tumors are lobulated patterns with a high signal on T2-weighted magnetic resonance imaging (MRI) and ring- and arc-like calcifications on conventional radiography and computed tomography (CT). Depending on the entity, the prevalence of this chondrogenic pattern differs. While high grade tumors may be identified due to aggressive imaging patterns, the differentiation between benign and intermediate grade chondrogenic tumors is challenging, even in an interdisciplinary approach.
Key Points:
The WHO defines benign, intermediate, and malignant chondrogenic bone tumors
Frequent benign tumors: osteochondroma and enchondroma; Frequent malignant tumor: conventional chondrosarcoma
Differentiation between enchondroma versus low-grade chondrosarcoma is challenging for radiologists and pathologists
Pain, deep scalloping, cortical destruction, bone expansion, soft tissue component: favor chondrosarcoma
Potential malignant transformation of osteochondroma: progression after skeletal maturity, cartilage cap thickness (> 2 cm adult; > 3 cm child)
Potentially helpful advanced imaging methods: Dynamic MRI, texture analysis, FDG-PET/CT
Citation Format
Engel H, Herget GW, Füllgraf H et al. Chondrogenic Bone Tumors: The Importance of Imaging Characteristics. Fortschr Röntgenstr 2021; 193: 262 – 274
Zusammenfassung
Hintergrund
Chondrogene Tumoren sind die häufigsten primären Knochentumoren. Maligne chondrogene Tumoren repräsentieren etwa ein Viertel der malignen Knochentumoren. Benigne chondrogene Knochentumoren sind häufige radiologische Zufallsbefunde. Radiologische Parameter können hilfreich sein zur Identifikation, Charakterisierung und Differenzialdiagnostik.
Methode
Systematische Literaturrecherche mittels PubMed. Identifikation und kritische Beurteilung von Studien, welche die Bildgebung chondrogener Knochentumoren analysieren oder beschreiben.
Ergebnisse und Schlussfolgerung
Nach der World-Health-Organization (WHO)-Klassifikation von 2020 werden benigne, intermediäre (lokal aggressiv oder selten metastasierend) und maligne chondrogene Tumoren unterschieden. Das typische radiologische Bild chondrogen differenzierter Tumoren ist gekennzeichnet durch ein lobuliertes Wachstumsmuster mit einem hohen Signal in T2-gewichteten Sequenzen in der Magnetresonanztomografie (MRT) und durch ein meist ring- und bogenförmiges Verkalkungsmuster in der Projektionsradiografie und der Computertomografie (CT). In Abhängigkeit der Entität ist dieses typische Muster unterschiedlich ausgeprägt. Während hochmaligne Tumoren häufig ein eindeutig malignes Wachstumsmuster zeigen, ist die Differenzierung zwischen benignen und intermediären chondrogenen Tumoren auch interdisziplinär schwierig.
Kernaussagen:
Die WHO unterscheidet gutartige, intermediäre und bösartige chondrogene Knochentumoren.
Häufige gutartige Tumoren: Osteochondrom und Enchondrom; häufiger bösartiger Tumor: konventionelles Chondrosarkom.
Differenzierung Enchondrom versus Low-grade-Chondrosarkom ist für Radiologen und Pathologen gleichermaßen schwierig.
Schmerzen, tiefes Scalloping, Kortikalisdestruktion, Knochenexpansion und Weichteilanteil sprechen für ein Chondrosarkom (versus Enchondrom).
Transformationshinweise beim Osteochondrom: Größenprogredienz nach Wachstumsabschluss, Knorpelkappendicke > 2 cm (Erwachsene) bzw. > 3 cm (Kinder).
Neuere, potenziell hilfreiche Bildgebungsmethoden: dynamisches MRT, Texturanalysen und FDG-PET/CT.
Zitierweise
Engel H, Herget GW, Füllgraf H et al. Chondrogenic Bone Tumors: The Importance of Imaging Characteristics. Fortschr Röntgenstr 2021; 193: 262 – 275
To establish a spatially exact co-registration procedure between
multiparametric magnetic resonance imaging (mpMRI) and (immuno)histopathology of soft tissue sarcomas (STS) to identify imaging ...parameters that reflect radiation therapy response of STS.
The mpMRI-Protocol included diffusion-weighted (DWI), intravoxel-incoherent motion (IVIM), and dynamic contrast-enhancing (DCE) imaging. The resection specimen was embedded in 6.5% agarose after initial fixation in formalin. To ensure identical alignment of histopathological sectioning and
imaging, an
MRI scan of the specimen was rigidly co-registered with the
mpMRI. The deviating angulation of the specimen to the
location of the tumor was determined. The agarose block was trimmed accordingly. A second
MRI in a dedicated localizer with a 4 mm grid was performed, which was matched to a custom-built sectioning machine. Microtomy sections were stained with hematoxylin and eosin. Immunohistochemical staining was performed with anti-ALDH1A1 antibodies as a radioresistance and anti-MIB1 antibodies as a proliferation marker. Fusion of the digitized microtomy sections with the
mpMRI was accomplished through nonrigid co-registration to the
mpMRI. Co-registration accuracy was qualitatively assessed by visual assessment and quantitatively evaluated by computing target registration errors (TRE).
The study sample comprised nine tumor sections from three STS patients. Visual assessment after nonrigid co-registration showed a strong morphological correlation of the histopathological specimens with
MRI and
mpMRI after neoadjuvant radiation therapy. Quantitative assessment of the co-registration procedure using TRE analysis of different pairs of pathology and MRI sections revealed highly accurate structural alignment, with a total median TRE of 2.25 mm (histology -
MRI), 2.22 mm (histology -
mpMRI), and 2.02 mm (
MRI -
mpMRI). There was no significant difference between TREs of the different pairs of sections or caudal, middle, and cranial tumor parts, respectively.
Our initial results show a promising approach to obtaining accurate co-registration between histopathology and
MRI for STS. In a larger cohort of patients, the method established here will enable the prospective identification and validation of
imaging biomarkers for radiation therapy response prediction and monitoring in STS patients via precise molecular and cellular correlation.
Several previous studies reported metabolic derangements and an accumulation of metabolic products in the early phase of experimental subarachnoid hemorrhage (SAH), which may contribute to secondary ...brain damage. This may be a result of deranged oxygen utilization due to enzymatic dysfunction in aerobic glucose metabolism. This study was performed to investigate, if pyruvate dehydrogenase enzyme (PDH) is affected in its activity giving further hints for a derangement of oxidative metabolism.
Eighteen male Sprague-Dawley rats were randomly assigned to one of two experimental groups (
= 9): (1) SAH induced by the endovascular filament model and (2) sham-operated controls. Mean arterial blood pressure (MABP), intracranial pressure (ICP), and local cerebral blood flow (LCBF; laser-Doppler flowmetry) were continuously monitored from 30 min before until 3 h after SAH. Thereafter, the animals were sacrificed and PDH activity was measured by ELISA.
PDH activity was significantly reduced in animals subjected to SAH compared to controls.
The results of this study demonstrate for the first time a reduction of PDH activity following SAH, independent of supply of substrates and may be an independent factor contributing to a derangement of oxidative metabolism, failure of oxygen utilization, and secondary brain damage.
Synuclein gamma (SNCG) is under consideration as a potential biomarker in cancer biology. Up to date four different SNCG variants are described. Due to growing evidence suggesting correlations ...between aberrant alternative splicing processes and cancer progression, we investigated the effects of peritumoural conditions on expression pattern of SNCG in endometrial cancer (EC) in vitro. Compared to breast cancer cell lines, mRNA expression levels of all known SNCG isoforms 1-4 are significantly reduced in EC cell lines. We identified a novel alternatively spliced variant of isoform 2 (isoform 2 short) which is found highly expressed in EC cell lines. Hypoxia and acidosis trigger an up-regulation of isoform 2 short. EC cell lines are characterized by low SNCG protein levels under control conditions, but exhibit a significant increase triggered by hypoxia and acidosis. In addition we analysed the potential association between SNCG protein expression and clinico-pathological parameters in human EC samples. Our findings indicate a grade-dependent induction of SNCG protein expression in endometrial cancer. We identified for the first time a novel isoform of SNCG that is found specifically expressed in EC. Our results also strongly indicate the existence of a corresponding protein of isoform 2 short that potentially plays a critical role in EC cancer progression.
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