Vasculogenic mimicry correlates to presenting symptoms and mortality in uveal melanoma

Abstract Purpose Fluid-conducting extracellular matrix patterns known as vasculogenic mimicry (VM) have been associated with poor prognosis in uveal melanoma and other cancers. We investigate the correlations between VM, presenting symptoms, mortality, and the area density of periodic acid-Schiff positive histological patterns (PAS density). Methods Sixty-nine patients that underwent enucleation for uveal melanoma between 2000 and 2007 were included. Clinicopathological parameters presenting symptoms and outcomes were collected. Histological tumor sections were evaluated for VM and PAS density was quantified with digital image analysis. Results Thirty-four patients (49%) presented with blurred vision. 18 (26%) with a shadow in the visual field, 7 (10%) with photopsia and/or floaters, and 2 (3%) with metamorphopsia. Nine patients (13%) had no symptoms at all. Median follow-up was 16.7 years (SD 2.6). A shadow in the visual field, but no other symptom, was positively correlated with the presence of VM (φ 0.70, p < 0.001) and greater PAS density (p < 0.001). In multivariate regression, retinal detachment (RD), presence of VM, and PAS density ≥ median were independent predictors of a shadow, but not tumor distance to the macula, tumor apical thickness, tumor diameter, or ciliary body engagement. The presence of VM was associated with significantly shorter cumulative disease-specific survival (Wilcoxon p = 0.04), but not PAS density ≥ median, presenting symptoms or RD (p > 0.28). Conclusion Tumors from uveal melanoma patients that report a visual field shadow are likely to display VM and greater PAS density, likely explaining the previously reported association between this symptom and poor prognosis.

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Vasculogenic Mimicry Correlates to Presenting Symptoms and Mortality in Uveal Melanoma

10.21203/rs.3.rs-978191/v1 ◽

2021 ◽

Author(s):

Shiva Sabazade ◽

Viktor Torgny Gill ◽

Christina Herrspiegel ◽

Gustav Stålhammar

Keyword(s):

Visual Field ◽

Uveal Melanoma ◽

Poor Prognosis ◽

Periodic Acid ◽

Vasculogenic Mimicry ◽

Clinicopathological Parameters ◽

Tumor Diameter ◽

Blurred Vision ◽

Periodic Acid Schiff ◽

Presenting Symptoms

Abstract PurposeFluid-conducting extracellular matrix patterns known as vasculogenic mimicry (VM) have been associated with poor prognosis in uveal melanoma and other cancers. We investigate the correlations between VM, presenting symptoms, mortality and the area density of periodic acid-Schiff positive histological patterns (PAS density).MethodsSixty-nine patients that underwent enucleation for uveal melanoma between 2000 and 2007 were included. Clinicopathological parameters, presenting symptoms and outcomes were collected. Histological tumor sections were evaluated for VM and PAS density was quantified with digital image analysis.ResultsThirty-four patients (49 %) presented with blurred vision. 18 (26 %) with a shadow in the visual field, 7 (10 %) with photopsia and/or floaters and 2 (3 %) with metamorphopsia. Nine patients (13 %) had no symptoms at all. Median follow-up was 16.7 years (SD 2.6). A shadow in the visual field, but no other symptom, was positively correlated with the presence of VM (φ 0.70, p<0.001) and greater PAS density (p<0.001). In multivariate regression, retinal detachment (RD), presence of VM and PAS density ≥ median were independent predictors of a shadow, but not tumor distance to the macula, tumor apical thickness, tumor diameter or ciliary body engagement. Presence of VM was associated with significantly shorter cumulative disease-specific survival (Wilcoxon p=0.04), but not PAS density ≥ median, presenting symptoms or RD (p>0.28).ConclusionTumors from uveal melanoma patients that report a visual field shadow are likely to display VM and greater PAS density, likely explaining the previously reported association between this symptom and poor prognosis.

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Alveolar Soft Part Sarcoma

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-488-asps ◽

2007 ◽

Vol 131 (3) ◽

pp. 488-491

Author(s):

Neda Zarrin-Khameh ◽

Kim S. Kaye

Keyword(s):

Poor Prognosis ◽

Soft Part ◽

Periodic Acid ◽

Alveolar Soft Part Sarcoma ◽

Diagnostic Feature ◽

Periodic Acid Schiff ◽

Radiographic Features ◽

Rare Neoplasm ◽

Immunohistochemical Stains

Abstract This article provides an overview of the pathology of alveolar soft part sarcoma, focused on its morphology, special stains useful in diagnosis, and the clinical and radiographic features of the disease. Alveolar soft part sarcoma is a rare neoplasm of unknown histogenesis with poor prognosis. Although there are several immunohistochemical stains available to help reach the diagnosis, the morphology of the tumor should be considered the main diagnostic feature. The periodic acid–Schiff stain is the best single stain that supports the diagnosis.

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Single-cell Transcriptomic Analysis of Eutopic Endometrium and Ectopic Lesions of Adenomyosis

10.21203/rs.3.rs-127243/v1 ◽

2020 ◽

Author(s):

Zhiyong Liu ◽

Zhonghua Sun ◽

Hongyun Liu ◽

Weipin Niu ◽

Xin Wang ◽

...

Keyword(s):

Epithelial Cells ◽

Cell Motility ◽

Single Cell ◽

Periodic Acid ◽

Expression Patterns ◽

Vasculogenic Mimicry ◽

Cell Subpopulation ◽

Periodic Acid Schiff ◽

Eutopic Endometrium ◽

Invasion And Migration

Abstract Background: Adenomyosis (AM) is a common benign chronic gynaecological disorder; however, the precise pathogenesis of adenomyosis is still poorly understood. Single-cell RNA sequencing (scRNA-seq) can uncover rare subpopulations, explore genetic and functional heterogeneity, and reveal the uniqueness of each cell. It provides us a new approach to reveal biological issues from a more detailed and microscopic perspective. Here, we utilize this revolutionary technology to identify the changes of gene expression patterns between ectopic lesions and the eutopic endometrium at the single-cell level and explore a potential novel pathogenesis of AM.Methods: A control endometrium (sample with leiomyoma excluding endometrial disorders, n=1), eutopic endometrium and ectopic lesion (from a patient with adenomyosis, n=1) samples were analysed by scRNA-seq, and additional leiomyoma (n=3) and adenomyosis (n=3) samples were used to confirm colocalization and vasculogenic mimicry (VM) formation. Protein colocalization was visualized by immunofluorescence, and CD34-periodic acid-Schiff (PAS) double staining was used to assess the formation of VM.Results: The scRNA-seq results suggest that cancer-, cell motility- and inflammation- (CMI) associated terms, cell proliferation and angiogenesis play important roles in the progression of AM. Moreover, the colocalization of EPCAM and PECAM1 increased significantly in the ectopic endometrium group (P < 0.05), cell subpopulation with high copy number variation (CNV) levels possessing tumour-like features existed in the ectopic lesion sample, and VNN1- and EPCAM-positive cell subcluster displayed active cell motility in endometrial epithelial cells. Furthermore, the epithelial cells transformed to endothelial cells with the obvious accumulation of vasculogenic mimicry formations (positively stained with PAS but not CD34, P < 0.05) in ectopic lesions.Conclusions: In the present study, our results support the theory of adenomyosis derived from the invasion and migration of the endometrium. Moreover, cell subcluster with high CNV level and tumour-associated characteristics is identified. Furthermore, epithelial-endothelial transition (EET) and the formation of VM in tumours, the latter of which facilitates the blood supply and plays an important role in maintaining cell growth, were also confirmed to occur in AM. These results indicated that the inhibition of EET and VM formation may be a potential strategy for AM management.

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Near-haploid acute lymphoblastic leukemia: a unique subgroup with a poor prognosis?

Blood ◽

10.1182/blood.v58.1.14.bloodjournal58114 ◽

1981 ◽

Vol 58 (1) ◽

pp. 14-19 ◽

Cited By ~ 1

Author(s):

GM Brodeur ◽

DL Williams ◽

AT Look ◽

WP Bowman ◽

DK Kalwinsky

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Dna Content ◽

Poor Prognosis ◽

Lymphoblastic Leukemia ◽

Periodic Acid ◽

Flow Cytometric Analysis ◽

Chromosome 21 ◽

Periodic Acid Schiff ◽

Flow Cytometric ◽

Block Pattern

We describe two adolescent girls with acute lymphoblastic leukemia (ALL) whose leukemia cells were near-haploid. Their lymphoblasts stained in a block pattern with periodic acid Schiff and had “common ALL” surface markers confirmed by indirect immunofluorescence. Each patient had two populations of blasts, one near-haploid and one hyperdiploid, which was an exact doubling of the near-haploid karyotype. The first patient had a predominant population of cells with 26 chromosomes and a few with 52, while the second had a predominance of cells with 56 and a minority with 28. Flow cytometric analysis of DNA content initially detected the minor near-haploid population in the second patient, which was confirmed later by cytogenetic review of the marrow sample. In addition to our two patients, only four patients have been reported with near-haploid ALL. Of these six, five were girls, five were adolescents, and five had short survivals (median, 10 mo). All six had disomy of chromosome 21 with or without disomy for chromosomes 10, 14, 18, or X (four patients each). Thus, near-haploid ALL may represent a unique subgroup of ALL with a poor prognosis. To detect these and other possible subgroups, we have included cytogenetic analysis and flow cytometric analysis of DNA content in our initial evaluation of patients with ALL.

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The Yield of Neuroimaging in Patients Presenting to the Emergency Department With Isolated Neuro-Ophthalmological Complaints

10.21203/rs.3.rs-630811/v1 ◽

2021 ◽

Author(s):

Tharwat El Zahran ◽

Dalia El Hadi ◽

Hala Mostafa ◽

Hana Mansour ◽

Ibrahim Hashim ◽

...

Keyword(s):

Emergency Department ◽

Visual Field ◽

Physical Exam ◽

Blurred Vision ◽

Presenting Symptoms ◽

Pupil Reactivity ◽

Life Threatening ◽

Blurry Vision ◽

Optic Discs ◽

Field Defect

Abstract Background: Neuro-ophthalmological emergencies require prompt assessment and management to avoid vision or life-threatening sequelae. The decision to perform a neuroimaging procedure is currently based on the clinical judgement of the medical team, without defined indications. This study aims to identify presenting symptoms and physical exam findings associated with relative positive findings on neuroimaging studies,Methods: This study was conducted by reviewing the electronic medical records of patients presenting to the Emergency Department (ED) with isolated neuro-ophthalmologic complaints between January 1st, 2013 and September 30th 2019. We collected data on the clinical presentation, neuroimaging procedures and results, consults, and diagnoses.Results: We reviewed the charts of 211 patients of whom 50.7% were females and had a mean age of 41.2 ±21.4 years. Most presented with unilateral eye complaints (53.6%), and the most common symptoms were blurred vision (77.3%) and headaches (42.2%). A total of 126 imaging procedures were performed of which 74.6% were normal, while 25.4% showed relevant abnormal findings. Complaining of blurry vision (p=0.038) or visual field changes (p=0.014) at presentation were associated with having positive findings on imaging. Physical exam findings of a visual field defect (p=0.016), abnormal pupil reactivity (p=0.028), afferent pupillary defect (p=0.018), or abnormal optic disc exam (p=0.009) were also associated with positive findings on imaging.Conclusion: Neuroimaging is more likely to yield positive findings in patients presenting to the ED with blurred vision or changes in visual field and in those found to have visual field irregularities, afferent pupillary defects or abnormal optic discs on physical exam. These findings - when combined with the proper clinical setting - should lower the threshold to proceed with neuroimaging in the emergency department. Based on our results, larger-scale studies might lead to a well-structured algorithm to be followed by ED physicians in decision making.

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Correlations Between Visual Acuity, Presenting Symptoms and Histopathological Findings in Enucleated Eyes with Uveal Melanoma

10.21203/rs.3.rs-952903/v1 ◽

2021 ◽

Author(s):

Elin Asplund ◽

Tony Pansell ◽

Rune Brautaset ◽

Maria Nilsson ◽

Gustav Stålhammar

Keyword(s):

Visual Acuity ◽

Tumor Cell ◽

Uveal Melanoma ◽

Histopathological Examination ◽

Vasculogenic Mimicry ◽

Tumor Thickness ◽

Cell Type ◽

Basal Diameter ◽

Presenting Symptoms ◽

Blurry Vision

Abstract Visual outcomes after treatment of uveal melanoma have been investigated repeatedly. In this paper, we evaluate the correlation between visual acuity (VA) prior to enucleation, presenting symptoms and findings upon histopathological examination of eyes and tumors. Sixty nine patients were included. Their mean best corrected visual acuity (BCVA) prior to enucleation was LogMAR 0.80 (SD 0.70). Patients that reported low VA or blurry vision did not have lower BCVA upon refraction (p=0.34). Patients with low BCVA had tumors with greater apical tumor thickness (p=0.027), basal diameter (p=0.012) and stage (p=0.014). The experience of a shadow in the visual field correlated with presence of vasculogenic mimicry in the tumor (p<0.001). In multivariate Cox regressions with tumor thickness and diameter as covariates, tumor cell type and infiltration of the optic nerve head were associated with increased hazard for melanoma-related mortality (3.2 and 3.6, respectively). We conclude that patients that report low VA do not necessarily have worse BCVA. The latter do however have tumors with larger dimensions, at more advanced stage. A shadow in the VF correlates with presence of vasculogenic mimicry, which is an independent predictor for poor prognosis along with tumor infiltration of the optic disc and tumor cell type.

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Angioarchitecture of Primary Oral Malignant Melanomas

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215540205001116 ◽

2002 ◽

Vol 50 (11) ◽

pp. 1555-1562 ◽

Cited By ~ 10

Author(s):

You-Jin Lee ◽

Noriyuki Nagai ◽

Chong-Huat Siar ◽

Keisuke Nakano ◽

Hitoshi Nagatsuka ◽

...

Keyword(s):

Malignant Tumors ◽

Periodic Acid ◽

Vasculogenic Mimicry ◽

Tumor Vessel ◽

Periodic Acid Schiff ◽

Endothelial Markers ◽

Tumor Microvasculature ◽

Transmission Electron ◽

Oral Malignant Melanoma ◽

Vascular Channels

Angiogenesis is an essential process in the progression of malignant tumors. However, little is known of the angioarchitecture in primary oral malignant melanoma. We sought to determine this by the use of periodic acid-Schiff (PAS) stain, endothelial markers (CD34, CD105) and laminin, and by transmission electron microscopy in two cases. The results demonstrated that endothelium-lined vessels dominated the tumor microvasculature and these stained positively for PAS, laminin, and endothelial markers. Mosaic and tumorlined vessels were infrequently encountered. Most PAS-positive patterned networks and loops ultrastructurally represented intratumor microhemorrhages that probably arose secondary to tumor vessel leakiness. Vascular channels of the vasculogenic mimicry type were rare. They stained for laminin but not for endothelial markers.

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Near-haploid acute lymphoblastic leukemia: a unique subgroup with a poor prognosis?

Blood ◽

10.1182/blood.v58.1.14.14 ◽

1981 ◽

Vol 58 (1) ◽

pp. 14-19 ◽

Cited By ~ 61

Author(s):

GM Brodeur ◽

DL Williams ◽

AT Look ◽

WP Bowman ◽

DK Kalwinsky

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Dna Content ◽

Poor Prognosis ◽

Lymphoblastic Leukemia ◽

Periodic Acid ◽

Flow Cytometric Analysis ◽

Chromosome 21 ◽

Periodic Acid Schiff ◽

Flow Cytometric ◽

Block Pattern

Abstract We describe two adolescent girls with acute lymphoblastic leukemia (ALL) whose leukemia cells were near-haploid. Their lymphoblasts stained in a block pattern with periodic acid Schiff and had “common ALL” surface markers confirmed by indirect immunofluorescence. Each patient had two populations of blasts, one near-haploid and one hyperdiploid, which was an exact doubling of the near-haploid karyotype. The first patient had a predominant population of cells with 26 chromosomes and a few with 52, while the second had a predominance of cells with 56 and a minority with 28. Flow cytometric analysis of DNA content initially detected the minor near-haploid population in the second patient, which was confirmed later by cytogenetic review of the marrow sample. In addition to our two patients, only four patients have been reported with near-haploid ALL. Of these six, five were girls, five were adolescents, and five had short survivals (median, 10 mo). All six had disomy of chromosome 21 with or without disomy for chromosomes 10, 14, 18, or X (four patients each). Thus, near-haploid ALL may represent a unique subgroup of ALL with a poor prognosis. To detect these and other possible subgroups, we have included cytogenetic analysis and flow cytometric analysis of DNA content in our initial evaluation of patients with ALL.

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Metastasis of Uveal Melanoma with Monosomy-3 Is Associated with a Less Glycogenetic Gene Expression Profile and the Dysregulation of Glycogen Storage

Cancers ◽

10.3390/cancers12082101 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2101 ◽

Cited By ~ 1

Author(s):

Siranush Vardanyan ◽

Anton Brosig ◽

Hartmut Merz ◽

Mahdy Ranjbar ◽

Vinodh Kakkassery ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profile ◽

Uveal Melanoma ◽

Expression Profile ◽

Periodic Acid ◽

Glycogen Metabolism ◽

The Cancer Genome Atlas ◽

Prolonged Storage ◽

Periodic Acid Schiff ◽

Monosomy 3

The prolonged storage of glucose as glycogen can promote the quiescence of tumor cells, whereas the accumulation of an aberrant form of glycogen without the primer protein glycogenin can induce the metabolic switch towards a glycolytic phenotype. Here, we analyzed the expression of n = 67 genes involved in glycogen metabolism on the uveal melanoma (UM) cohort of the Cancer Genome Atlas (TCGA) study and validated the differentially expressed genes in an independent cohort. We also evaluated the glycogen levels with regard to the prognostic factors via a differential periodic acid-Schiff (PAS) staining. UMs with monosomy-3 exhibited a less glycogenetic and more insulin-resistant gene expression profile, together with the reduction of glycogen levels, which were associated with the metastases. Expression of glycogenin-1 (Locus: 3q24) was lower in the monosomy-3 tumors, whereas the complementary isoform glycogenin-2 (Locus: Xp22.33) was upregulated in females. Remarkably, glycogen was more abundant in the monosomy-3 tumors of male versus female patients. We therefore provide the first evidence to the dysregulation of glycogen metabolism as a novel factor that may be aggravating the course of UM particularly in males.

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Does Vasculogenic Mimicry Exist in Astrocytoma?

Journal of Histochemistry & Cytochemistry ◽

10.1369/jhc.4a6521.2005 ◽

2005 ◽

Vol 53 (8) ◽

pp. 997-1002 ◽

Cited By ~ 95

Author(s):

Wei-Ying Yue ◽

Zhong-Ping Chen

Keyword(s):

Tumor Cells ◽

Periodic Acid ◽

Vasculogenic Mimicry ◽

World Health ◽

Glial Fibrillary Acid Protein ◽

Melanoma Tumor ◽

Periodic Acid Schiff ◽

Weak Reaction ◽

Positive Pattern ◽

Endothelial Marker

Vasculogenic mimicry (VM) has been observed in melanoma and in some non-melanoma tumor types. It is unknown whether a similar VM phenomenon exists in astrocytoma. The present study was to examine 45 astrocytomas (including World Health Organization grade II 15 cases, grade III 15 cases, and grade IV 15 cases) by CD34 endothelial marker periodic acid-Schiff (PAS) dual staining to see if VM existing in these tumors. The results demonstrated that endothelium-lined vessels dominated the tumor microvasculature and stained positively for PAS, laminin, and endothelial marker. PAS-positive pattern of VM was found in two grade IV astrocytomas. Channels stained positively for PAS, laminin, and negatively for CD34 of the VM entrapped in the tumor tissue. Erythrocytes could be observed in some of these channels. In these networks of PAS-positive pattern, spots of weak reaction for CD34 were observed, suggesting the incorporation of VM channel and normal vessel. Furthermore, in astrocytoma, especially glioblastoma, focus of anaplastic tumor cells appeared with CD34 expression, whereas some tumor cells lost glial fibrillary acid protein expression. It is assumed that genetically deregulated tumor cells in astrocytoma could lose the astrocyte-specific protein and express inappropriate markers not expected in cells of astrocyte lineage. The present results suggest that VM phenomenon exists in some malignant astrocytoma.

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