Treatment of pulmonary epithelioid hemangioendothelioma with combination chemotherapy: Report of three cases and review of the literature
TL;DR: It is indicated that patients with PEH demonstrated a good partial response to chemotherapy with carboplatin, paclitaxel, bevacizumab, thalidomide and α-interferon, which may hold therapeutic potential for the treatment of this rare disease.
Abstract: No standard therapy for pulmonary epithelioid hemangioendothelioma (PEH) has yet been established due to the rarity of the disease, the lack of clear standards for treatment and the partial-to-complete spontaneous regression. This report describes three cases of PHE manifested as bilateral intrapulmonary masses with an initial diagnosis conducted by thoracoscopic lung biopsy. These patients demonstrated a partial response to combination chemotherapy with carboplatin, paclitaxel, bevacizumab or endostar, and an improvement in clinical status. Furthermore, we reviewed the literature regarding such patients who received chemotherapy and immunotherapy; this indicated that patients with PEH demonstrated a good partial response to chemotherapy with carboplatin, paclitaxel, bevacizumab, thalidomide and α-interferon. Overall, combination chemotherapy regimens may hold therapeutic potential for the treatment of this rare disease.
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TL;DR: This case is the first to report objective, long-lasting response to pazopanib in metastatic pulmonary epithelioid hemangioendothelioma, a rare vascular tumor of borderline or low-grade malignancy.
Abstract: Epithelioid hemangioendothelioma is a rare vascular tumor of borderline or low-grade malignancy. The lungs and liver are the two common primary organs affected. Metastatic disease was reported in more than 100 cases in the literature. However, no firm conclusions can be determined for recommended treatment options. The current case presents a patient with metastatic pulmonary epithelioid hemangioendothelioma to the cervical and mediastinal lymph nodes, lungs and liver that has been treated with pazopanib for more than two years with PET avid complete metabolic response in the mediastinum and lungs, and long-lasting stable disease. Target therapies that block VEGFR have a logical base in this rare malignancy. The current case is the first to report objective, long-lasting response to pazopanib.
51 citations
TL;DR: 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.
Abstract: 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.
38 citations
TL;DR: Understanding TAZ biology and the molecular mechanisms by which it promotes unregulated cell proliferation will yield insights and possibly improved treatments for both EHE as well as much more common cancers.
Abstract: Epithelioid hemangioendothelioma (EHE) is a rare soft-tissue sarcoma involving cells with histologic markers that suggest an endothelial origin Around 90% of EHEs are caused by the fusion of Transcriptional Co-activator with a PDZ-motif (TAZ) with Calmodulin Binding Transcription Activator 1 (CAMTA1), a central nervous system-specific transcription activator The 10% of EHEs that lack the TAZ⁻CAMTA1 fusion instead have a fusion of Yes-associated Protein (YAP) and Transcription Factor E3 (TFE3) genes (YAP-TFE3) YAP and TAZ are well-defined downstream effectors in the Hippo pathway that promote cell growth when translocated to the nucleus The TAZ⁻CAMTA1 fusion transcript is insensitive to the Hippo inhibitory signals that normally prevent this process and thus constitutively activates the TAZ transcriptome In EHE, this causes tumors to form in a variety of organs and tissue types, most commonly the liver, lung, and bone Its clinical course is unpredictable and highly variable TAZ activation is known to contribute to key aspects of the cancer phenotype, including metastasis and fibrosis, and increased expression of TAZ is thought to be causally related to the progression of many cancers, including breast, lung, and liver Therefore, understanding TAZ biology and the molecular mechanisms by which it promotes unregulated cell proliferation will yield insights and possibly improved treatments for both EHE as well as much more common cancers
29 citations
TL;DR: A 44-year-old man with recurrent hemoptysis for approximately 9 years was presented with a new small molecule tyrosine kinase inhibitor that specifically targets VEGFR-2 and showed noticeable symptomatic improvements and positive imaging changes in the first month of treatment, however, the disease progressed in the following month, despite the increased apatinib dose.
16 citations
TL;DR: Although the prognostic factors for PEH have not yet been well established, a better prognosis is usually associated with the multinodular pattern.
Abstract: Pulmonary epithelioid hemangioendothelioma (PEH) is a rare neoplasm of vascular origin. There are three different major imaging patterns identified in thoracic manifestation of epithelioid hemangioendothelioma: (1) multiple pulmonary nodules; (2) multiple pulmonary reticulonodular opacities; and (3) diffuse infiltrative pleural thickening. Radiographically, presence of bilateral multiple nodules is the most common pattern of presentation. The diagnosis is made on the basis of histopathological findings and confirmed by positive immunohistochemistry staining. Although the prognostic factors for PEH have not yet been well established, a better prognosis is usually associated with the multinodular pattern. We report two different imagological presentations of this rare disease, based on two institutional experiences, along with a review of the relevant literature.
16 citations
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TL;DR: It is suggested the term epithelioid hemangioendothelioma be used to designate these biologically “borderline” neoplasms, which may be observed in both benign and malignant vascular lesions.
Abstract: Epithelioid hemangioendothelioma is a unique tumor of adult life which is characterized by an "epithelioid" or "histiocytoid" endothelial cell. Forty-one cases of this rare tumor have been recognized at the Armed Forces Institute of Pathology. They may occur in either superficial or deep soft tissue, and in 26 cases appeared to arise from a vessel, usually a medium-sized or large vein. They are composed of rounded or slightly spindled eosinophilic endothelial cells with rounded nuclei and prominent cytoplasmic vacuolization. The latter feature probably represents primitive lumen formation by a single cell. The cells grown in small nests or cords and only focally line well-formed vascular channels. The pattern of solid growth and the epithelioid appearance of the endothelium frequently leads to the mistaken diagnosis of metastatic carcinoma. The tumor can be distinguished from a carcinoma by the lack of pleomorphism and mitotic activity in most instances and by the presence of focal vascular channels. Ultrastructural study in four cases confirmed the endothelial nature of the tumor in demonstrating cells surrounded by basal lamina, dotted with surface pinocytotic vesicles, and occasionally containing Weibel-Palade bodies. Follow-up information in 31 cases indicated that 20 patients were alive and well following therapy; three developed local recurrences and six metastases. It is suggested the term epithelioid hemangioendothelioma be used to designate these biologically "borderline" neoplasms. The significance of the epithelioid endothelial cell is not entirely clear. Since it may be observed in both benign and malignant vascular lesions, its presence alone does not define a clinicopathologic entity.
1,083 citations
"Treatment of pulmonary epithelioid ..." refers background in this paper
...Immunohistochemical and electron microscopy studies revealed that IVBAT is of endothelial origin, and the tumor was renamed PEH (4-8)....
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Journal Article•
TL;DR: The epithelioid hemangioendothelioma (EHE) as discussed by the authors is a type of cancer characterized by a histiocytoid endothelial cell, which grows in small nests or cords and only focally line well-formed vascular channels.
1,079 citations
TL;DR: The principal clinical, pathologic, and biologic differences among these three lesions of EH of soft tissue, bone, lung, and liver are discussed.
443 citations
"Treatment of pulmonary epithelioid ..." refers background in this paper
...Immunohistochemical and electron microscopy studies revealed that IVBAT is of endothelial origin, and the tumor was renamed PEH (4-8)....
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...The poor prognostic factors of PEH include the presence of respiratory symptoms or pleural effusion revealed by chest radiography on presentation; extensive intravascular, endobronchial or interstitial tumor spreading, hepatic metastases; peripheral lymphadenopathy; the presence of spindle cells in the tumor (4); and, particularly, pleural hemorrhagic effusions and hemoptysis (18)....
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...of vascular endothelial origin, with an intermediate course between hemangioma and conventional angiosarcoma (2-5)....
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...The diagnosis of PEH is conducted on the basis of histological features and is confirmed immunohistochemically (4,16)....
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TL;DR: Twenty cases of an unusual tumor of the lung are described, which is a peculiar sclerosing tumor of endothelial cell origin that presents with multiple small, slowly growing pulmonary nodules.
Abstract: Twenty cases of an unusual tumor of the lung are described. This tumor usually presents with multiple small, slowly growing pulmonary nodules. Many cases are detected incidentally. Eighty percent are women, and 50% are less than 40 years of age. Survival with tumor can be quite long. However, one half the patients have died, usually of progressive pulmonary insufficiency. This is a peculiar sclerosing tumor of endothelial cell origin.
327 citations
"Treatment of pulmonary epithelioid ..." refers background in this paper
...Radiographically, bilateral multiple nodular opacities are the most common presentation (62-65% in a number of studies) (3,13)....
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...of vascular endothelial origin, with an intermediate course between hemangioma and conventional angiosarcoma (2-5)....
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...Regular follow-up with no active therapy has been employed in asymptomatic patients with diffuse lesions (2,3)....
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TL;DR: The results show that the epithelioid vascular tumors EHE and EAS, in addition to staining for the endothelial markers and vimentin, may also express the epithelial marker keratin, important since these tumors may closely resemble carcinomas by routine light microscopy.
224 citations
"Treatment of pulmonary epithelioid ..." refers background in this paper
...Immunohistochemistry for PEH reveals that all tumors display immunoreactivity to some or all of the vascularendothelial markers (CD31, CD34 and factor VIII) (17)....
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...Immunohistologically, the tumor cells were immunoreactive for CD31 and CD34, but negative for cytokeratin, S-100, CD68 and factor VIII....
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...Immunohistochemical analysis revealed that the tumor cells were positive for the endothelial markers, factor-VIII-related antigen and CD34 (Fig....
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...Immunostaining for CD31 was positive in two of our patients, while factor VIII was positive in one patient....
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