Vascular Stroma Research Articles

Clear cell stromal tumor of the lung: Report of 3 cases with emphasis on multifocal tumors.

We describe 3 patients with clear cell stromal tumor (CCST) of the lung, all of whom presented with multifocal disease. The patients were 2 men and 1 woman aged 47-58 years (mean, 54 years). Two patients had evidence of autoimmune disease and their pulmonary disease was an incidental finding; one patient presented with non-specific respiratory symptoms. Radiologic imaging revealed multiple pulmonary nodules in all patients. Histologically, the tumors were solid-cystic and composed of cytologically bland, medium-sized ovoid to spindle cells with eosinophilic to clear cytoplasm arranged in a subtle nested pattern. These tumor cells were set in a highly vascularized stroma. Occasional cytologic atypia with multinucleated tumor cells was noted but mitotic activity was low. An infiltrate of mixed inflammatory cells was apparent in all tumors. Immunohistochemical analysis demonstrated diffuse expression of vimentin and TFE3 in all cases. Next generation sequencing revealed the presence of YAP1::TFE3 fusion in 1/1 case. All patients have remained alive albeit with stable or progressive disease, 24-66 months after diagnosis. These cases highlight the existence of multifocal pulmonary CCST and seem to support the notion that multifocality in CCST may be associated with more protracted clinical course. Awareness of the existence of multifocal pattern is important for patient management and prognosis.

A benign tumor of substantial size: Mandibular epithelioid osteoblastoma in a socioeconomically challenged patient

Epithelioid osteoblastoma (EOB) is a rare, benign bone tumor characterized by the proliferation of atypical epithelioid osteoblasts within a vascular stroma. It typically presents as a slow-growing painful mass and requires careful differentiation from more aggressive lesions like osteosarcoma for appropriate management. We present a case of an otherwise healthy 30-year-old man who presented with a mandibular EOB measuring 23 cm × 17 cm x 19 cm, causing significant disfigurement and functional impairment. Surgical management involved radical resection and immediate reconstruction using an osteocutaneous fibula free flap. The case emphasizes the importance of multidisciplinary care, advanced surgical planning, and the impact of socioeconomic factors on healthcare access and outcomes.

Vascular units as advanced living materials for bottom-up engineering of perfusable 3D microvascular networks

The timely establishment of functional neo-vasculature is pivotal for successful tissue development and regeneration, remaining a central challenge in tissue engineering. In this study, we present a novel (micro)vascularization strategy that explores the use of specialized “vascular units” (VUs) as building blocks to initiate blood vessel formation and create perfusable, stroma-embedded 3D microvascular networks from the bottom-up. We demonstrate that VUs composed of endothelial progenitor cells and organ-specific fibroblasts exhibit high angiogenic potential when embedded in fibrin hydrogels. This leads to the formation of VUs-derived capillaries, which fuse with adjacent capillaries to form stable microvascular beds within a supportive, extracellular matrix-rich fibroblastic microenvironment. Using a custom-designed biomimetic fibrin-based vessel-on-chip (VoC), we show that VUs-derived capillaries can inosculate with endothelialized microfluidic channels in the VoC and become perfused. Moreover, VUs can establish capillary bridges between channels, extending the microvascular network throughout the entire device. When VUs and intestinal organoids (IOs) are combined within the VoC, the VUs-derived capillaries and the intestinal fibroblasts progressively reach and envelop the IOs. This promotes the formation of a supportive vascularized stroma around multiple IOs in a single device. These findings underscore the remarkable potential of VUs as building blocks for engineering microvascular networks, with versatile applications spanning from regenerative medicine to advanced in vitro models.

All-aqueous droplets-templated tailorable core-shell alginate microspheres for constructing vascularized intestinal mucosa in vitro models

Recently, in vitro models of intestinal mucosa have become important tools for drug screening and studying the physiology and pathology of the intestine. These models enable the examination of cellular behavior in diseased states or in reaction to alterations in the microenvironment, potentially serving as alternatives to animal models. One of the major challenges in constructing physiologically relevant in vitro models of intestinal mucosa is the creation of three-dimensional microstructures that accurately mimic the integration of intestinal epithelium and vascularized stroma. Here, core–shell alginate (Alg) microspheres were generated to create the compartmentalized extracellular matrix microenvironment needed to simulate the epithelial and vascularized stromal compartments of the intestinal mucosa. We demonstrated that NIH-3T3 and human umbilical vein endothelial cells embedded in the core of the microspheres can proliferate and develop a vascular network, while human colorectal adenocarcinoma cells (Caco-2) can form an epithelial monolayer in the shell. Compared to Caco-2 monolayer encapsulated within the shell, the presence of the vascularized stroma enhances their proliferation and functionality. As such, our core–shell Alg microspheres provide a valuable method for generating in vitro models of vascularized intestinal mucosa with epithelial and vascularized stroma arranged in a spatially relevant manner and demonstrating near-physiological functionality.

Congenital Epulis in a Neonate: A Rare Cause of Oral Cavity Mass

Background: Congenital epulis is a benign tumor of the oral cavity, rarely seen in newborns. Clinical Description: A term, female neonate presented soon after birth with a 5 cm × 3 cm × 2.5 cm, firm, lobulated, noncompressible, nonfluctuant oral cavity mass, arising from the right maxillary alveolar ridge with a pedunculated base. Management and Outcome: The lesion posed an obstacle to the establishment of breastfeeds or paladai feeds along with the potential to compromise the airway for which the mass was excised in toto under general anesthesia. Histopathology revealed a lining of stratified squamous epithelium, large polygonal cells with abundant granular, eosinophilic cytoplasm, and a prominent vascular stroma with no evidence of malignancy suggesting the diagnosis of congenital epulis and immunohistochemistry confirming the same. Conclusion: Congenital epulis are rare tumors of the oral cavity which have excellent results if resected early.

The visual impact of higher-order aberrations in patients with pediatric blepharokeratoconjunctivitis.

To analyze higher-order aberrations (HOAs) and their visual impact in a pediatric blepharokeratoconjunctivitis (PBKC) cohort compared with healthy controls. Prospective case-control study of pediatric patients (≤ 16 years old). Subjects underwent wavefront aberrometry analysis to compare HOAs and their impact on visual quality. A total of 150 eyes from 76 patients were included in the analysis. The PBKC group consisted of 50 eyes and the control group of 100 healthy eyes. Mean age was 10.39 ± 3.81 years for the PBKC group and 10.80 ± 3.61 years for the controls. Mean corrected-distance visual acuity (CDVA) was 0.24 ± 0.21 logMAR in the PBKC group and 0.07 ± 0.1 in the controls (P < 0.001). Mean astigmatism was 1.6 ± 1.98D in the PBKC group vs. 0.67 ± 0.76D in the control group (P = 0.01). Mean RMS of HOAs was 1.05 ± 1.7mm in the PBKC group and 0.41 ± 0.18mm in the controls (P < 0.001). The mean modulation transfer function (MTF) in the PBKC group was significantly lower (16.37 ± 16.32) than controls (30.3 ± 23.57) (P < 0.001). Corneal leukomas, stromal vascularization, peripheral nummular subepithelial scars, and pannus formation are associated with increased HOAs. There was a significant increase in total HOAs of eyes with PBKC compared to healthy controls. Corneal opacity, vascularization, and scarring are associated with increased HOAs. The PBKC eye aberration profile: coma, secondary astigmatism, quadrafoil, and pentafoil, were associated with decreased CDVA and visual quality (PSF and MTF).

Abstract A006: Spatial localization of Caveolin-1 protein in triple negative breast cancer is related to different molecular features

Abstract Background: Triple negative breast cancer (TNBC) is an aggressive and heterogeneous form of breast cancer with few targeted therapies and clinically used biomarkers. Caveolin-1 (CAV1) is a marker of stromal activation and vascularization. Molecular features of the tumor microenvironment (TME), important for tumor metastasis, may improve precision oncology in TNBC. CAV1 protein levels have previously been reported as a potential biomarker in breast cancer depending on their localization. Therefore, we aimed to investigate CAV1 protein levels in malignant and stromal cells of TNBC and their relation to CAV1 gene expression, clinicopathological factors, and molecular features. Methods: Tumor-specific CAV1 protein levels were evaluated with immunohistochemistry in malignant and stromal cells in tumor tissue microarrays from a cohort of 242 TNBC patients (inclusion 2010-2015, Sweden) from SCAN-B (NCT03758976). The protein levels of CAV1 in malignant and stromal cells were dichotomized as ‘strong’ (1) vs ‘negative to moderate’ (0) The CAV1 categories in malignant and stromal cells, respectively, were combined to create a joint CAV1 status with four categories: malignant/stromal cells, 0/0, 0/1, 1/0, and 1/1. Gene expression profiles from massive parallel paired-end sequencing of mRNA (RNA-seq) were available for all the tumors and from which PAM50 category and TNBC subtype were assigned. CAV1 status in malignant and stromal cells in relation to clinicopathological factors was analyzed using Chi-Square test. CAV1 mRNA expression in relation to CAV1 status in malignant and stromal cells was evaluated using Kruskal-Wallis test. Results: CAV1 status could be evaluated in 231/242 tumors. Strong CAV1 staining in malignant cells was associated with higher histological grade but no axillary lymph node involvement (both P &amp;lt;0.007). In contrast, strong CAV1 staining in stromal cells was associated with lower histological grade but axillary lymph node involvement (both P &amp;lt;0.001). Strong CAV1 staining in stromal cells was also associated with higher age at diagnosis (P =0.025). With regards to PAM50 subtypes, CAV1 in malignant cells was positively associated with the basal subtype while CAV1 in malignant cells was positively associated with the HER2 enriched subtype (P &amp;lt;0.001). Depending on localization, CAV1 expression was associated with different TNBCsubtypes. CAV1 in malignant cells was positively associated with the mesenchymal and negatively associated with the immunomodulatory subtype (P &amp;lt;0.001). CAV1 in stromal cells was positively associated with the luminal androgen (LAR) subtype (P &amp;lt;0.001). Neither CAV1 protein levels in malignant cells nor in stromal cells were correlated with CAV1 gene expression in the tumors, and the combined CAV1 status was not associated with CAV1 gene expression. Conclusion: CAV1 protein levels in malignant cells were related to different molecular features of TNBC compared to CAV1 protein levels in stromal cells. The results suggest that depending on localization, CAV1 protein levels function as two distinct biomarkers. Citation Format: Christopher Godina, Somayeh Khazaei, Mattias Belting, Johan Vallon-Christersson, Björn Nodin, Karin Jirström, Karolin Isaksson, Ana Bosch, Helena Jernström. Spatial localization of Caveolin-1 protein in triple negative breast cancer is related to different molecular features [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A006.

Direct Reprogramming of Hepatocytes Into JAK/Stat-Dependent LGR5+ Liver Cells Able to Initiate Intrahepatic Cholangiocarcinoma.

Somatic cells that have been partially reprogrammed by the factors Oct4, Sox2, Klf4, and cMyc (OSKM) have been demonstrated to be potentially tumorigenic in vitro and in vivo due to the acquisition of cancer-associated genomic alterations and the absence of OSKM clearance over time. In the present study, we obtained partially reprogrammed, SSEA1-negative cells by transducing murine hepatocytes with Δ1Δ3-deleted adenoviruses that expressed the 4 OSKM factors. We observed that, under long-term 2D and 3D culture conditions, hepatocytes could be converted into LGR5-positive cells with self-renewal capacity that was dependent on 3 cross-signaling pathways: IL6/Jak/Stat3, LGR5/R-spondin, and Wnt/β-catenin. Following engraftment in syngeneic mice, LGR5-positive cells that expressed the cancer markers CD51, CD166, and CD73 were capable of forming invasive and metastatic tumors reminiscent of intrahepatic cholangiocarcinoma (ICC): they were positive for CK19 and CK7, featured associations of cord-like structures, and contained cuboidal and atypical cells with dissimilar degrees of pleomorphism and mitosis. The LGR5+-derived tumors exhibited a highly vascularized stroma with substantial fibrosis. In addition, we identified pro-angiogenic factors and signaling pathways involved in neo-angiogenesis and vascular development, which represent potential new targets for anti-angiogenic strategies to overcome tumor resistance to current ICC treatments.

Adipose Tissue Dysfunction Determines Lipotoxicity and Triggers the Metabolic Syndrome: Current Challenges and Clinical Perspectives.

The adipose tissue organ is organised as distinct anatomical depots located all along the body axis, and it is constituted of three different types of adipocytes: white, beige and brown, which are integrated with vascular, immune, neural, and extracellular stroma cells. These distinct adipocytes serve different specialised functions. The main function of white adipocytes is to ensure healthy storage of excess nutrients/energy and its rapid mobilisation to supply the demand of energy imposed by physiological cues in other organs, whereas brown and beige adipocytes are designed for heat production through uncoupling lipid oxidation from energy production. The concerted action of the three types of adipocytes/tissues ensures an optimal metabolic status. However, when one or several of these adipose depots become dysfunctional because of sustained lipid/nutrient overload, then insulin resistance and associated metabolic complications ensue. These metabolic alterations close a vicious cycle that negatively affects the adipose tissue functionality and compromises global metabolic homeostasis. Optimising white adipose tissue expandability and ensuring its functional metabolic flexibility and/or promoting brown/beige mediated thermogenic activity are complementary strategies that counteract obesity and its associated lipotoxic metabolic effects. However, the development of these therapeutic approaches requires a deep understanding of adipose tissue in all broad aspects. In this chapter, we will discuss the characteristics of the different adipose tissue depots with respect to origins and precursors recruitment, plasticity, cellular composition, and expandability capacity potential as well as molecular and metabolic characteristic signatures in both physiological and pathophysiological conditions. Current antilipotoxic strategies for future clinical application are also discussed in this chapter.

EFFECT OF HIGH FAT AND CAGED CHICKEN DIET ON OVARIAN HISTOMORPHOLOGY IN FEMALE ALBINO RATS

Background: Consumption of high fat diet, caged chicken meat and sedentary lifestyle have seriously increased the risks of hyperlipidema that leads to increased ovarian weight as well as ovarian stromal changes associated with difficulties in reproduction. This study is designed to compare the effects of high fat and caged chicken diet on histomorphology of ovaries of female albino rats. Methods: This study was conducted in collaboration with National Institute of Health and Anatomy Department of Islamic International Medical College, Islamabad after approval from Ethics Review Committee. The study duration was 12 months from Sep 2021 to Sep 2022, and was performed on 30 albino rats. Control group A was given standard rat diet. Experimental group B was given High Fat Diet (HFD) of 60% fat. Experimental group C was given cubes of caged chicken meat in the raw form. At the end of experiment, animals’ ovaries were collected and weighed. The samples were processed, sectioned in 5 ?m thickness, stained with H&amp;E and observed under light microscope for stromal vascular changes and congestion. Results: The ovarian weight and stromal vascularity significantly increased in caged chicken diet group C compared to control group A and experimental group B. Conclusion: Caged chicken diet is more harmful than HFD in causing ovarian weight gain and ovarian stromal hypervascularity. Pak J Physiol 2023;19(4):23-5

A case report of KIMURA’S DISEASE with nasal septum presentation

Abstract Kimura disease is a rare chronic inflammatory disorder of unknown aetiology, primarily seen in young Asians. The disease is characterised by painless subcutaneous swelling, blood and tissue eosinophilia and raised IgE levels. Kimura’s Disease has three components; cellular component showing lymphoid follicles with germinal centre hyperplasia with inflammatory infiltrate including increased eosinophils, plasma cells, and lymphocytes, surrounded by fibro collagenous and vascular stroma. Kimura disease is a disorder that involves the subcutaneous tissue of the head and neck regions. It is usually associated with regional lymphadenopathy and/or salivary gland involvement.

Different Patterns of Vascularization in Preinvasive States and at the Initial Stages of Invasive Growth of the Neoplasms.

Tissue samples obtained during surgery from 90 patients with malignant neoplasms of various localizations were studied (the presence of precancerous dysplastic alterations and their transition to invasive cancer in the slides were obligatory condition). In addition to traditional histological methods, immunohistochemical reactions for detection of HIF-1α, GLUT1, CAIX, and CD31 were performed. At the precancerous stage including cancer in situ, progressive signs of reduced blood vessel density and hypoxia were observed. At the earliest stages of invasion, hypoxia was compensated by abundant vascularization of the stroma, which was confirmed by disappearance of hypoxia markers in tumor cells and their persistence in the deep layers of the tumor far from blood vessels. At the same time, the ischemic phenotype was preserved in tumor cells even in abundantly vascularized stroma, which can attest to deep metabolic changes in some tumor cells similar to the Warburg effect. Thus, the initial stages of carcinogenesis are associated with reduction of the vascular network up to the complete absence of blood vessels in the cancer in situ. After migration to the vascularized subepithelial stroma, e.g., having started invasion that compensated for hypoxia, the tumor cells no longer expressed markers of hypoxia, except the cells located far from blood vessels. In parallel, neoplastic cell clones that presumably have changed their phenotype and transformed their metabolism similar to the Warburg effect were detected. In the deep layers of the tumors, these cells coexist in different proportions. Analysis of the content of these cells, their alternation, and mutual transformation will be very valuable for estimating the sensitivity of tumor cells to therapeutic measures.

Cell-Cell and Cell-Matrix Interactions at the Presumptive Stem Cell Niche of the Chick Corneal Limbus.

(1) Background: Owing to its ready availability and ease of acquisition, developing chick corneal tissue has long been used for research purposes. Here, we seek to ascertain the three-dimensional microanatomy and spatiotemporal interrelationships of the cells (epithelial and stromal), extracellular matrix, and vasculature at the corneo-scleral limbus as the site of the corneal stem cell niche of the chicken eye. (2) Methods: The limbus of developing (i.e., embryonic days (E) 16 and 18, just prior to hatch) and mature chicken eyes was imaged using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and the volume electron microscopy technique, serial-block face SEM (SBF-SEM), the latter technique allowing us to generate three-dimensional reconstructions from data sets of up to 1000 serial images; (3) Results: Data revealed that miniature limbal undulations of the embryonic basement membrane, akin to Palisades of Vogt (PoV), matured into distinct invaginations of epithelial cells that extended proximally into a vascularized limbal stroma. Basal limbal epithelial cells, moreover, occasionally exhibited a high nuclear:cytoplasmic ratio, which is a characteristic feature of stem cells. SBF-SEM identified direct cell-cell associations between corneal epithelial and stromal cells at the base of structures akin to limbal crypts (LCs), with cord-like projections of extracellular matrix extending from the basal epithelial lamina into the subjacent stroma, where they made direct contact with stomal cells in the immature limbus. (4) Conclusion: Similarities with human tissue suggest that the corneal limbus of the mature chicken eye is likely the site of a corneal stem cell niche. The ability to study embryonic corneas pre-hatch, where we see characteristic niche-like features emerge, thus provides an opportunity to chart the development of the limbal stem cell niche of the cornea.

Fibroblasts mediate endothelium response to angiogenic cues in a newly developed 3D stroma engineered model

Three-dimensional stroma engineered models would enable fundamental and applicative studies of human tissues interaction and remodeling in both physiological and pathological conditions. In this work, we propose a 3D vascularized stroma model to be used as in vitro platform for drug testing. A pullulan/dextran-based porous scaffold containing pre-patterned microchannels of 100 μm diameter is used for co-culturing of fibroblasts within the matrix pores and endothelial cells to form the lumen. Optical clearing of the constructs by hyperhydration allows for in-depth imaging of the model up to 1 mm by lightsheet and confocal microscopy. Our 3D vascularized stroma model allows for higher viability, metabolism and cytokines expression compared to a monocultured vascular model. Stroma-endothelium cross-talk is then investigated by exposing the system to pro and anti-angiogenic molecules. The results highlight the protective role played by fibroblasts on the vasculature, as demonstrated by decreased cytotoxicity, restoration of nitric oxide levels upon challenge, and sustained expression of endothelial markers CD31, vWF and VEGF. Our tissue model provides a 3D engineered platform for in vitro studies of stroma remodeling in angiogenesis-driven events, known to be a leading mechanism in diseased conditions, such as metastatic cancers, retinopathies and ischemia, and to investigate related potential therapies.

Oral solitary fibrous tumors: A collaborative clinicopathologic study of 19 cases.

To report the clinicopathologic features of 19 oral solitary fibrous tumors (SFTs). Clinical data were collected from the records of seven pathology services. All cases were re-evaluated by HE staining and confirmed by immunohistochemistry. The series comprised 11 females (57.9%) and 8 males (42.1%), with a mean age of 47.3 ± 14.7 years (range: 22-71 years) and a 1.3:1 female-to-male ratio. Most tumors affected the buccal mucosa (n = 7; 36.8%) and presented clinically as an asymptomatic solitary submucosal well-circumscribed nodule with coloration similar to the oral mucosa. Morphologically, most SFTs (n = 10; 52.6%) exhibited a classic hybrid pattern characterized by a well-circumscribed proliferation of densely cellular areas alternating with hypocellular areas in a variably collagenous vascular stroma. Remnants of accessory salivary glands were observed in two cases (n = 2; 10.5%). All tumors were positive for STAT6 and CD34 (n = 19; 100%). Outcome information was available from 6 patients (31.6%), with clinical follow-up ranging from 6 to 24 months (mean ± SD, 9.5 ± 6.8 months), and none developed local recurrence. Oral SFTs are rare and often clinically misdiagnosed. Pathologists should consider SFT in the differential diagnosis of oral spindle cell tumors. Accurate diagnosis requires careful morphological evaluation supported by immunohistochemical analysis.

Superb Microvascular Imaging Doppler Technique In The Evaluation Of Ovarian Stromal Vascularity In Women With Polycystic Ovary Syndrome.

To compare the assessment of intra-ovarian stromal vascularity through transabdominal ultrasonography with colour Doppler imaging, power Doppler imaging, colour superb microvascular imaging and monochrome superb microvascular imaging in polycystic ovary syndrome cases. The retrospective cross-sectional study was conducted at the Obstetrics and Gynaecology outpatient department of the Usak Training and Research Hospital, Turkey, from April 11 to June 18, 2018, and comprised grayscale colour Doppler imaging, power Doppler imaging, colour superb microvascular imaging and monochrome superb microvascular imaging of women with polycystic ovary syndrome. The recorded video images were evaluated by three radiologists and rated through consensus decision. Mean values for age, body mass index, follicle stimulating hormone and luteinizing hormone levels, luteinizing hormone-follicle stimulating hormone ratio, Ferriman Gallwey score, and mean ovarian volume of the subjects were evaluated. Data was analysed using Number Cruncher Statistical System. Of the 54 women evaluated, data of 42(77.8%) was included. There were a total of 83 ovaries, as the left ovary of 1(1.2%) patient was not visible. The mean age and body mass index were 24.02±5.8 years and 25.08±4.5kg/m2. Mean follicle stimulating hormone and luteinizing hormone levels were 5.51±1.91 and 7.91±6.13m IU/mL. Luteinizing hormone/follicle stimulating hormone ratio and Ferriman Gallwey score were 1.4±0.8 and 8.67 ±6.94, respectively. The mean ovarian volume was 12.2±3.43 cm3. The detection of vascularity was colour Doppler imaging 0.72±0.97, power Doppler imaging 0.96±1.08, colour superb microvascular imaging 2.47±1.25, and monochrome superb microvascular imaging 2.75±1.31. The techniques were significant for superb microvascular imaging Doppler than conventional Doppler (p<0.001). Hyper- ovarian stromal vascularity, like a 'stellate' sign, was detected in 17(20.5%) of the total 83 ovaries analysed. Transabdominal ultrasonography-colour superb microvascular imaging was found to be more effective in detecting ovarian vascularity than conventional Doppler technique in women with polycystic ovary syndrome.

KDM2B-Rearranged Soft Tissue Sarcomas Expand the Concept of BCOR-Associated Sarcoma

Sarcomas with BCOR genetic alterations (BCOR-associated sarcomas) represent a recently recognized family of soft tissue and bone tumors characterized by BCOR fusion, BCOR internal tandem duplication, or YWHAE::NUTM2B fusion. Histologically, the tumors demonstrate oval to spindle cell proliferation in a variably vascular stroma and overexpression of BCOR and SATB2. Herein, we describe 3 soft tissue sarcomas with KDM2B fusions that phenotypically and epigenetically match BCOR-associated sarcomas. The cases included 1 infant, 1 adolescent, and 1 older patient. All tumors showed histologic findings indistinguishable from those of BCOR-associated sarcomas and were originally diagnosed as such based on the phenotype. However, none of the tumors had BCOR or YWHAE genetic alterations. Instead, targeted RNA sequencing identified in-frame KDM2B::NUTM2B, KDM2B::CREBBP, and KDM2B::DUX4 fusions. KDM2B fusions were validated using reverse-transcription PCR, Sanger sequencing, and in situ hybridization assays. Genome-wide DNA methylation analysis matched all 3 tumors with BCOR-associated sarcomas using the Deutsches Krebsforschungszentrum (DKFZ) classifier and t-distributed stochastic neighbor embedding analysis. One localized tumor showed a flat genome-wide copy number profile, and the patient remained disease-free after treatment. The other tumors showed multiple copy number alterations, including MDM2/CDK4 amplification and/or CDKN2A/B loss, and both tumors metastasized, leading to the patient’s death in one of the cases. When tested using KDM2B immunohistochemistry, all 3 KDM2B-rearranged sarcomas showed diffuse strong staining, and all 13 sarcomas with BCOR genetic alterations also demonstrated diffuse, strong, or weak staining. By contrast, among 72 mimicking tumors, only a subset of synovial sarcomas showed focal or diffuse weak KDM2B expression. In conclusion, our study suggests that KDM2B-rearranged soft tissue sarcomas belong to the BCOR-associated sarcoma family and expand its molecular spectrum. This may be related to the known molecular relationship between KDM2B and BCOR in the polycomb repressive complex 1.1. Immunohistochemical analysis of KDM2B is a potentially valuable diagnostic tool for BCOR-associated sarcomas, including those with KDM2B rearrangement.

Snapshot: Choroid plexus brain barrier

Located in each brain ventricle, choroid plexus (ChP) tissue forms a blood-CSF barrier and produces cerebrospinal fluid (CSF) and other supportive factors. Sheets of ChP epithelial cells enclose a vascularized stroma of mesenchymal, immune, and neuron/glia-like cells. Burgeoning ChP studies are revealing its complex set of functions across the lifespan. To view this SnapShot, open or download the PDF.

Immunohistochemical characterization of clear cell variant of hepatocellular carcinoma in a sheep

The cadaver and viscera of a mature female sheep (Ovis aries) underwent routine abattoir meat inspection. The liver was expanded by an infiltrative neoplastic mass comprising multifocal to coalescing, well-demarcated, pink to white–yellow nodules, up to 25 mm in diameter. An unencapsulated, moderately densely cellular, infiltrative neoplasm was present within the hepatic parenchyma. The neoplastic cells were arranged in solid sheets and acini supported by a moderately fine collagenous vascularized stroma. The neoplastic cells were moderately sized and polygonal, with clearly delineated cell borders and a moderate amount of cytoplasm that was clear or exhibited either globular eosinophilic deposits or fine fibrillar eosinophilic strands. The neoplastic cell nuclei were round and centrally located. The chromatin was lightly stippled and there was frequently a single, prominent, basophilic nucleolus. There were eight mitoses in 10 high-power fields (2.37 mm2). Most of the neoplastic cells had intense cytoplasmic immunolabelling for arginase 1, with frequent concurrent nuclear positivity, and mild to moderately intense punctate cytoplasmic labelling for hepatocyte specific antigen (Hep Par-1). The neoplastic cells did not label with anti-cytokeratin 19 antibody. Based on the histological appearance and the immunolabelling pattern, the neoplasm was diagnosed as the clear cell variant of a hepatocellular carcinoma.

CONSERVATIVE TREATMENT OF ADENOID AMELOBLASTOMA: A CASE REPORT

A 27-year-old female presented painful swelling in the face, on the right mandibular side, 4 months prior to her appointment. Intraoral examination made it possible to observe swelling in the lower mandibular molar vestibule on the right side. Panoramic radiography disclosed a well corticated unilocular radiolucent lesion involving lower mandibular molars on the right side, with root resorption of teeth #46 and #47. Needle aspiration was performed, and a negative result was observed. The total enucleation of the lesion was then performed. The pathological examination revealed a benign odontogenic neoplasm characterized by the presence of infiltrating odontogenic cells arranged in whorls, duct-like structures in a cribriform arrangement, with peripheral palisading ameloblast-like cells, surrounded by a fibrous vascular stroma, with the presence of a moderate inflammatory infiltrate. The histopathological diagnosis was adenoid ameloblastoma. After 8 months, clinical and radiographic follow-up was performed, and a complete bone formation was observed. A 27-year-old female presented painful swelling in the face, on the right mandibular side, 4 months prior to her appointment. Intraoral examination made it possible to observe swelling in the lower mandibular molar vestibule on the right side. Panoramic radiography disclosed a well corticated unilocular radiolucent lesion involving lower mandibular molars on the right side, with root resorption of teeth #46 and #47. Needle aspiration was performed, and a negative result was observed. The total enucleation of the lesion was then performed. The pathological examination revealed a benign odontogenic neoplasm characterized by the presence of infiltrating odontogenic cells arranged in whorls, duct-like structures in a cribriform arrangement, with peripheral palisading ameloblast-like cells, surrounded by a fibrous vascular stroma, with the presence of a moderate inflammatory infiltrate. The histopathological diagnosis was adenoid ameloblastoma. After 8 months, clinical and radiographic follow-up was performed, and a complete bone formation was observed.