Pathologic Angiogenesis of Malignant Vascular Sarcomas: Implications for Treatment

2018 ◽  
Vol 36 (2) ◽  
pp. 194-201 ◽  
Author(s):  
Jalal A. Khan ◽  
Robert G. Maki ◽  
Vinod Ravi
Keyword(s):  
Treatment Options ◽  
Growth Factor Receptor ◽  
Kaposi Sarcoma ◽  
Clinical Trial Data ◽  
Epithelioid Hemangioendothelioma ◽  
Vascular Tumors ◽  
Angiogenic Growth Factors ◽  
Notch Pathways ◽  
And Behavior ◽  
Endothelial Growth Factor

Angiosarcoma, epithelioid hemangioendothelioma, and Kaposi sarcoma are classified according to the line of differentiation that these neoplastic cells most closely resemble: the endothelial cell. Although these malignant vascular sarcomas demonstrate immunohistochemical and ultrastructural features typical of this lineage, they vary dramatically in presentation and behavior, reflecting oncologic mechanisms unique to each. Antineoplastic therapies offer significant benefit, but because of the rarity of these cancers, novel therapies are slow to develop, and treatment options for these cancers remain limited. Antiangiogenic approaches that have shown benefit in other malignancies have not fully realized their promise in vascular tumors, suggesting that these tumors do not depend entirely on either angiogenic growth factors or on neighboring endothelia that are affected by these agents. Nonetheless, translational studies have begun to unravel these distinct pathologies, identifying novel translocation products, targets of oncogenic virulence factors, and genomic mutations that hijack angiogenic signaling and drive malignant growth. Concurrently, an elaborate and highly regulated model of angiogenesis and lymphangiogenesis involving vascular endothelial growth factor–receptor tyrosine kinase and TGF-β and Notch pathways has emerged that informs treatment of these tumors as well as cancer in general. This review summarizes the literature on malignant vascular sarcomas in the context of current models of angiogenesis and, in light of recent clinical trial data, could help clinician-scientists generate novel therapeutic approaches.

Pediatric Angiosarcoma of Soft Tissue: A Rare Clinicopathologic Entity

2010 ◽  
Vol 134 (3) ◽  
pp. 481-485 ◽  
Author(s):  
Lobna Ayadi ◽  
Abdelmajid Khabir
Keyword(s):  
Spindle Cell ◽  
Immunohistochemical Study ◽  
Kaposi Sarcoma ◽  
Neck Region ◽  
Epithelioid Hemangioendothelioma ◽  
Vascular Tumors ◽  
Clinical Settings ◽  
Vascular Differentiation ◽  
Head And Neck Region ◽  
Poorly Differentiated

Abstract Angiosarcomas are rare tumors that predominantly affect adults and elderly patients. Although angiosarcomas are well described in a variety of clinical settings, they have been poorly studied in children and little is known about their biology, natural history, or optimal treatment. Childhood angiosarcomas are exceedingly rare. The head and neck region and mediastinum seem to be the preferred locations. Most tumors are high-grade tumors. Vasoformative architecture is not always obvious on light microscopy requiring the benefit of immunohistochemical study. The differential diagnosis includes Kaposi sarcoma, epithelioid hemangioendothelioma, hemangiopericytoma, and spindle cell hemangioendothelioma whose prognosis is different. Complete resection is required for patients with localized tumors. Malignant vascular tumors are rare in children in the first 2 decades of life and when they do occur they seem to be more aggressive than in adults. Pathologic diagnosis is difficult particularly in poorly differentiated angiosarcomas requiring immunohistochemical study to confirm vascular differentiation.

Malignant Vascular Tumors of the Liver in Adults

2018 ◽  
Vol 39 (01) ◽  
pp. 001-012 ◽  
Author(s):  
Jordi Rimola ◽  
Venancio Alves
Keyword(s):  
Differential Diagnosis ◽  
Kaposi Sarcoma ◽  
Epithelioid Hemangioendothelioma ◽  
Vascular Tumors ◽  
Molecular Pathways ◽  
High Grade ◽  
Histological Findings ◽  
Clinical Behavior ◽  
Molecular Assessment ◽  
Tumors Of The Liver

AbstractHepatic angiosarcoma and epithelioid hemangioendothelioma (EHE) might be clinically considered a spectrum since, although more frequently presenting indolent behavior, EHE occasionally evolves to high-grade neoplasms. However, in most circumstances, pathological and immunohistochemical patterns define this differential diagnosis. More recently, molecular pathways for angiosarcoma and for EHE from other organs and from soft tissue have been proved different, paving the way for future morpho-molecular assessment of their hepatic counterpart. The frequency of liver involvement by Kaposi sarcoma in HIV-infected patients is lower nowadays. Histological findings and immunostaining for HHV-8 Ag are characteristic. Hepatic small vessel neoplasms have been recently recognized as important mimickers of angiosarcoma. The criteria for this differential diagnosis and the clinical behavior, up to now considered favorable, must be further studied.

Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2356-2363 ◽  
Author(s):  
Makoto Sugaya ◽  
Takahiro Watanabe ◽  
Aparche Yang ◽  
Matthew F. Starost ◽  
Hisataka Kobayashi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transgenic Mice ◽  
Growth Factor Receptor ◽  
Kaposi Sarcoma ◽  
Lymphatic Drainage ◽  
Vascular Endothelial ◽  
Functional Protein ◽  
Erythematous Skin ◽  
Endothelial Growth Factor

AbstractKaposi sarcoma–associated herpesvirus (KSHV) infects endothelial cells within KS tumors, and these cells express the KSHV latent-cycle gene k-cyclin (kCYC) as well as vascular endothelial growth factor receptor 3 (VEGFR-3), a marker for lymphatic endothelium. To further understand KSHV-mediated pathogenesis, we generated transgenic mice expressing kCYC under the control of the VEGFR-3 promoter. kCYC mRNA and functional protein expression within tissue correlated with VEGFR-3 expression and were most abundantly detected within lung tissue. Clinically, most transgenic mice died within 6 months of age secondary to progressive accumulation of chylous pleural fluid. In skin, edema was detected by magnetic resonance imaging and mice demonstrated persistent erythema of the ears following trauma. Histologically, erythematous skin showed extravasation of erythrocytes and accumulation of erythrocytes within lymphatic lumens. In addition, lymphatic drainage of injected contrast dyes was markedly impaired in transgenic mice. Karyomegaly, a feature observed in kCYC-expressing cells in vitro, was detected in many tissues, and selectively occurred within lymphatic endothelial cells expressing kCYC mRNA by in situ hybridization. In summary, kCYC expression within VEGFR-3+ cells of mice causes marked impairment of lymphatic function. kCYC may contribute to the development of certain clinical and histologic features of KS, including localized edema and retention of extravasated erythrocytes within KS tumors.

scholarly journals Malignant Vascular Tumors of the Head and Neck—Which Type of Therapy Works Best?

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6201
Author(s):  
Susanne Wiegand ◽  
Andreas Dietz ◽  
Gunnar Wichmann
Keyword(s):  
Head And Neck ◽  
Treatment Options ◽  
Age Distribution ◽  
Case Series ◽  
Epithelioid Hemangioendothelioma ◽  
Current Data ◽  
Vascular Tumors ◽  
Retrospective Case ◽  
Standard Medical Therapy ◽  
New Treatment

Malignant vascular tumors of the head and neck are rare neoplasms with variable clinical presentation, wide age distribution, and variable clinical courses. The heterogeneous presentation of angiosarcomas and epithelioid hemangioendothelioma often leads to misdiagnosis and unsuitable treatment. While risk factors for angiosarcomas are previous radiation, chronic lymphedema, and exposure to arsenic, thorium oxide, or vinyl chloride, there are only limited and retrospective data available on prognostic factors in EHE. In both angiosarcomas and EHE, surgery is the mainstay of treatment. There is limited evidence regarding the role of radiotherapy in EHE, although EHE is considered relatively radiosensitive. In angiosarcomas, adjuvant radiotherapy is recommended according to retrospective case series. A standard medical therapy for metastasized malignant vascular tumors is lacking. Chemotherapy, which is effective in angiosarcoma, is mostly ineffective in EHE. Targeted therapy, antiangiogenetic drugs and immunotherapy have been studied as new treatment options. The goal of this review is to summarize the current data regarding malignant vascular tumors along with their diagnosis and management.

scholarly journals Beyond Chemotherapy, PD-1, and HER-2: Novel Targets for Gastric and Esophageal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4322
Author(s):  
Ali Zubair Siddiqui ◽  
Khaldoun Almhanna
Keyword(s):  
Esophageal Cancer ◽  
Growth Factor ◽  
Patient Population ◽  
Treatment Options ◽  
Treatment Algorithm ◽  
Growth Factor Receptor ◽  
Incidence Rates ◽  
Treatment Modalities ◽  
Her 2 ◽  
Endothelial Growth Factor

Together, gastric cancer and esophageal cancer (EC) possess two of the highest incidence rates amongst all cancers. They exhibit poor prognoses in which the 5-year survival rate is dismal. In addition to cytotoxic chemotherapy, treatment efforts have been geared toward targeting human epidermal growth factor receptor 2 (HER-2), vascular endothelial growth factor (VEGF), and programmed death ligand-1 (PD-1). Although ample success has been recorded with these agents, gastric and esophageal cancer remain lethal, and further research into potential treatment alternatives is needed. In this article, we will review some of the targets at the forefront of investigation such as claudin, Dickkopf-related protein 1 (DKK-1), fibroblast growth factor receptor (FGFR), and matrix metalloproteinases (MMPs). These innovative target pathways are in the midst of clinical trials to be implemented in the treatment algorithm for this patient population. Ultimately, exploiting the oncogenic tendencies of these potential biomarkers creates an opportunity for precise treatment and improved prognosis for these cancers. Lastly, research aimed toward reversing PD-1 antibodies resistance by combining it with other novel agents or other treatment modalities is underway in order to expand existing treatment options for this patient population.

Current Treatment Options for HCC: From Pharmacokinetics to Efficacy and Adverse Events in Liver Cirrhosis

2020 ◽  
Vol 21 (11) ◽  
pp. 866-884
Author(s):  
Giovanni Galati ◽  
Antonio Fabio Massimo Vainieri ◽  
Claudia Angela Maria Fulgenzi ◽  
Stefano Di Donato ◽  
Marianna Silletta ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metabolic Pathways ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Current Treatment ◽  
European Medicines Agency ◽  
Multikinase Inhibitor ◽  
Endothelial Growth Factor

Background: Hepatocellular carcinoma (HCC) is among the world’s most common cancers. For over ten years, the only medical treatment for it has been the multikinase inhibitor Sorafenib. Currently, however, other first or second-line therapeutic options have also shown efficacy against HCC, such as multikinase inhibitors (Regorafenib, Lenvatinib, and Cabozantinib), a monoclonal antibody against the vascular endothelial growth factor receptor 2 (Ramucirumab), and immune-checkpoint inhibitors (Nivolumab, Pembrolizumab, Ipilimumab). Aim: The aim of this paper is to review the metabolic pathways of drugs that have been tested for the treatment of HCC and the potential influence of liver failure over those pathways. Methods: The Food and Drug Administration (FDA)’s and European Medicines Agency (EMA)’s datasheets, results from clinical trials and observational studies have been reviewed. Results: This review summarizes the current knowledge regarding targets, metabolic pathways, drug interactions, and adverse events of medical treatments for HCC in cirrhotic patients. Conclusions: The new scenario of systemic HCC therapy includes more active drugs with different metabolic pathways and different liver adverse events. Clinical and pharmacological studies providing more data on the safety of these molecules are urgently needed.

scholarly journals Treatment of Hepatic Epithelioid Hemangioendothelioma: Finding Uses for Thalidomide in a New Era of Medicine

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Matthew P. Soape ◽  
Rashmi Verma ◽  
J. Drew Payne ◽  
Mitchell Wachtel ◽  
Fred Hardwicke ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Liver Biopsy ◽  
Birth Defects ◽  
Epithelioid Hemangioendothelioma ◽  
Vascular Tumors ◽  
Vascular Endothelial ◽  
New Era ◽  
Progression Of Disease ◽  
Endothelial Growth Factor

Hepatic epithelioid hemangioendothelioma (HEH) is extremely rare, occurring in 1 to 2 per 100,000, with chemotherapy options not well defined. Our case involved a 49-year-old female who had hepatic masses and metastasis to the lungs with a liver biopsy revealing HEH. After developing a rash from sorafenib, thalidomide was started with the progression of disease stabilized. Resection is only an option in 10% of the cases; therefore, chemotherapy is the only line of treatment. Newer chemotherapy alternatives are targeting angiogenesis via the vascular endothelial growth factor. Thalidomide was first used as an antiemetic, but, sadly, soon linked to phocomelia birth defects. Given the mechanism of action against angiogenesis, thalidomide has a valid role in vascular tumors. In conclusion, the use of thalidomide as chemotherapy is novel and promising, especially in the setting of a rare vascular liver tumor such as HEH.

scholarly journals Pulmonary sarcomatoid carcinoma: progress, treatment and expectations

2020 ◽  
Vol 12 ◽  
pp. 175883592095020
Author(s):  
Xin Li ◽  
Di Wu ◽  
Hongyu Liu ◽  
Jun Chen
Keyword(s):  
Cell Death ◽  
Growth Factor ◽  
Programmed Cell Death ◽  
Treatment Options ◽  
Sarcomatoid Carcinoma ◽  
Growth Factor Receptor ◽  
Anaplastic Lymphoma ◽  
Epidermal Growth ◽  
Pulmonary Sarcomatoid Carcinoma ◽  
Endothelial Growth Factor

Pulmonary sarcomatoid carcinoma (PSC) is a unique, highly invasive pulmonary malignancy with a poor prognosis, representing 0.1–0.4% of all malignant lung tumors. Because of its highly aggressive character and propensity for frequent metastasis, PSC shows low response rates to traditional treatments such as chemotherapy, radiotherapy, and neoadjuvant therapy. In recent years, considerable progress has been made in gene sequencing, targeted therapies, and immunotherapies. One of the most promising treatment approaches is the selection of mono-targeted or multi-targeted drugs according to tumor gene-mutation sites, such as epidermal growth factor receptor or vascular endothelial growth factor receptor 2 ( EGFR/VEGFR2), anaplastic lymphoma kinase ( ALK), and others. Another approach is the activation of therapeutic anti-tumor immunity via pathways including programmed cell-death protein-1/programmed cell-death ligand-1 ( PD-1/PD-L1), which has been used in individual cases. In this review, we will introduce the clinicopathologic features, molecular typing, and traditional treatments. We will also review the biological characteristics and the latest therapies for PSC. These novel therapies show promise in the management of PSC, and the outcomes of investigative trials will hopefully reveal a variety of treatment options for patients with PSC.

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