Chemotherapy: Open Access

Chemotherapy: Open Access
Open Access

ISSN: 2167-7700

Commentary - (2015) Volume 4, Issue 3

Pulmonary Epithelioid Hemangioendothelioma: Advances in Treatment Options despite a Rare Vascular Tumor

Lilia Bardoscia*, Angela Sardaro, Maria Fonte Petruzzelli, Beatrice Detti and Maurizio Portaluri
Azienda Ospedaliero-Universitaria Policlinico di Bari, Italy
*Corresponding Author: Lilia Bardoscia, Department of Interdisciplinary Medicine, Section of Diagnostic Imaging and Radiotherapy, University Aldo Moro, Bari, Italy, Tel: +8233273 Email:

Abstract

The general issue seems to be that, when bone or pulmonary lesions are small and limited in number, surgical, curative resection (that is amputation, en-bloc resection, wedge resection) achieves good outcomes.

Keywords: Epithelioidhemangioendothelioma, Bone metastases, Radiation therapy, Radiation dose, Pulmonary nodules, Pathological fracture, Chemotherapy

Introduction

We have already discussed about dail and liebow describing pulmonary epithelioid hemangioendothelioma (PEH) as an aggressive bronchoalveolar cell carcinoma with a remarkable propensity to invade adjacent blood vessels and small airways, the following Weiss and Enzinger description of epithelioid hemangioendothelioma (EHE) as a vascular bone and soft tissues tumor showing intermediate malignancy between hemangioma and angiosarcoma, and the final confirmation from Weldon-Linne of a factor-VIII-related antigen onto malignant cells [1]. The recent World Health Organization (WHO 2002) classification has described EHE as lesions that fall into the category of locally aggressive tumors with metastatic potential [2,3]. The etiology of EHE is still a dilemma, as several clonal abnormalities in tumor cells, and different angiogenic stimulators may act as promoters of endothelial cell proliferation [4-8]. A new etiopathogenetic hypothesis suggests a causal relationship between chronic Bartonella infection and the development of this rare vascular tumor: if this was confirmed, it would be plausible that eradicating the bacterial infection or interrupting Bartonella-induced angiogenic and proliferative cell signals could slow the tumor progression and improve patient outcomes [9].

Due to its rarity (EHE represents less than 1% of all vascular tumors), because of EHE clinical presentation is as heterogeneous as its clinical localization can be, there is no standard for treatment and few therapeutic options are available. As the most common presentations are liver alone (21%), liver plus lung (18%), lung alone (12%) and bone alone (14%), the available literature focuses above all on these three directions [10]. The general issue seems to be that, when bone or pulmonary lesions are small and limited in number, surgical, curative resection (that is amputation, en-bloc resection, wedge resection) achieves good outcomes [11,12]. Locally advanced hepatic EHE seems to benefit from transplantation, with good results [13]. However, a complete surgical resection is not usually feasible: Pinet et al. reported a case of an aggressive form of pleural EHE resulting in complete remission after treatment with carboplatin plus etoposide [14], as well as bilateral multicentric PEH seems to respond well to interferon 2α, with some partial spontaneous regression [7]. Nonetheless, when a pathological fracture occurs, a great alternative to plate-and-screws surgical stabilization is radiofrequency ablation: by creating small, carefully controlled, thermal injuries of bone, the extent of resection can be reduced [15]. On the other side, with the aim of controlling residual desease given the recurrence of EHE, radiation therapy (RT) is chosen for localized EHE, while chemotherapy is preferred for widespread disease. In any case, the beneficial effect of both is still not confirmed [14,16-19]. Given the vascular origin of this tumor, the use of antiangiogenetic molecules like thalidomide and lenalidomide reasonably might achieve good outcomes (partial response and several stable diseases), even if using bevacizumab and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) produced higher percentages of progression disease [20]. RT has proven to be ineffective for PEH because of the tumor’s radiobiological characteristics (slow growth of the tumor cells), while a good local control has been obtained in EHE of bone [19,21] Since EHE has been correctly defined, several research groups have dealt with EHE bone irradiation, in order to define the volume and the dose distribution achieving the greatest results for local disease control, together with the greatest tolerance to the treatment and the lowest incidence of side effects [19,21-24]. A 6400 cGy adjuvant RT was also performed against an axillary form of EHE, resulting in the absence of lymph nodes metastases but pleural and pulmonary widespread [18]. In our experience, at our Institute we observed systemic progression of EHE after 4-month-PEG-IFN-α therapy in spite of stable pulmonary disease; then, lumbar pain control with good tolerance and better quality of life at 1-year-follow-up from a symptomatic, normofractionated RT onto the L3-L5 vertebral tract, consolidated outcome through Ifosfamide and Epirubicin chemotherapy soon after RT, and surgical removal of EHE spleen lesions, showing 1-year survival [1].

All this considered, despite the rarity of this vascular tumor and its extremely complex and heterogeneous patterns of presentation, actually we are capable of performing more treatment lines, combined in a multimodal strategy or sequencially adopted, so that we are able to reach good outcomes in most of cases. In this regard, taking into account the EHE radiobiological characteristics, no doubt evidence is all in favour of RT obtaining local pain control with good tolerance and better quality of life at least one-year-follow up. The literature reveals certain discordance about the radiation dose to be used for this purpose, maybe attributable to the very small number of patients and to the limited survival that EHE typically shows. As a result, further studies are needed to answer the question.

Acknowledgments

The authors acknowledge Alison Frank for assisting in revising and editing the English manuscript.

References

  1. Sardaro A, Bardoscia L, Petruzzelli MF, Nikolaou A, Detti B, et al. (2014) Pulmonary epithelioid hemangioendothelioma presenting with vertebral metastases: a case report. Journal of Medical Case Reports 8: 201.
  2. Mertens F, Unni K, Fletcher CDM (2002) Pathology and genetics of Tumors of soft tissue and bone. In: World Health Organization Classification of Tumors. IRAC Press, Lyon, France, p. 155.
  3. Mukherjee S, Mallick J, Pal PC, Chattopadhyay S (2012) Hemangioendothelioma of soft tissue: Cytological dilemma in two unusual sites. Journal of Cytology 29: 89-91.
  4. Budousquie AC, Lawee HJ, Sherman R, Olson S, Magenis RE, et al. (1996) Complex translocation (7;22) identified in an epithelioid hemangioendothelioma. Cancer Genetics 92: 116-121.
  5. Errani C, Zhang L, Sung YS, Hajdu M, Singer S,et al. (2011) A Novel WWTR1-CAMTA1 Gene Fusion is a Consistent Abnormality in Epithelioid Hemangioendothelioma of Different Anatomic Sites. Genes Chromosomes Cancer 50: 644-653.
  6. Antonescu CR, Le Loarer F, Mosquera JM, Sboner A, Zhang L, et al. (2013) Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendotheliom. Genes Chromosomes Cancer 52:775-84.
  7. Radzikowska E, Szczepulska-Wójcik E, Chabowski M, Oniszh K, Langfort R, et al. (2008) Pulmonary epithelioid hemangioendothelioma – interferon 2-alpha treatment – case report. Pneumonologia i Alergologia Polska 76: 281-285.
  8. Gordillo GM, Onat D, Stockinger M, Roy S, Atalay M, et al. (2004) A key angiogenic role of monocyte chemoattractant protein-1 in hemangioendothelioma proliferation. American Journal of Physiology Cell Physiology 4: C866-873.
  9. Mascarelli PE, Iredell JR, Maggi RG, Weinberg G, Breitschwerdt EB (2011) Bartonella Species Bacteremia in Two Patients with Epithelioid Hemangioendothelioma. Journal of Clinical Microbiology 49: 4006-4012
  10. Lau K, Massad M, Pollak C, Rubin C, Yeh J,et al. (2011) Clinical Patterns and Outcome in Epithelioid Hemangioendothelioma With or Without Pulmonary Involvment. Chest 140: 1312-1318.
  11. Kleck CJ, Seidel MJ (2012) Epithelioid Hemangioendothelioma of the Distal Humerus With Pathologic Fracture. Orthopedics 35: e116-e119
  12. Bagan P, Hassan M, Le Pimpec Barthes F, Peyrard S, Souilamas R,et al. (2006) Prognostic Factors and Surgical Indications of Pulmonary Epithelioid Hemangioendothelioma: A Review of the Literature. Annals of Thoracic Surgery 82: 2010-2013.
  13. Kim SJ, Kim YC (2011) Unusual Extrahepatic Metastasis to the Soft Tissue of the Left Cervical Neck Area from Hepatic Epithelioid Hemangioendothelioma. Hepatology 54:1480-1481.
  14. Pinet C, Magnan A, Garbe L, Payan M-J, Vervloet D (1999) Aggressive form of pleural epithelioid hemangioendothelioma: complete response after chemotherapy. European Respiratory Journal 14: 237-238.
  15. Rosenthal DI, Treat ME, Mankin HJ, Rosenberg AE, Jennings CL (2001) Treatment of epithelioid hemangioendothelioma of bone using a novel combined approach. Skeletal Radiology 30: 219-222.
  16. Dail DH, Liebow AA, Gmelich JT, Friedman PJ, Miyai K, et al. (1983) Intravascular, bronchiolar, and alveolar tumor of the lung (IVBAT). An analysis of twenty cases of a peculiar sclerosing endothelial tumor. Cancer 51: 452-464.
  17. Kitaichi M, Nagai S, Nishimura K, Itoh H, Asamoto H, et al. (1998) Pulmonary epithelioid hemangioendothelioma in 21 patients, including three with partial spontaneous regression. European Respiratory Journal 12: 89-96.
  18. Schattenberg T, Kam R, Klopp M, Herpel E, Schnabel PA, et al. (2008) Pulmonary Epithelioid Hemangioendothelioma: Report of Three Cases. Surgery Today 38: 844-849.
  19. van Kasteren MEE, van der Wurff AAM, Palmen FMLHG, Dolman A, Miseré JFMM (1995) Epithelioid hemangioendothelioma of the lung: clinical and pathological pitfalls. European Respiratory Journal 8: 1616-1619.
  20. Gaur S, Torabi A, O’Neill TJ (2012) Activity of Angiogenesis Inhibitors in Metastatic Epithelioid Hemangioendothelioma: A Case Report. Cancer Biology & Medicine 9: 133-136.
  21. Aquilina K, Lim C, Kamel MH, Marks CJ, O’Sullivan MG, et al. (2005) Epithelioid hemangioendothelioma of the spine. Journal of Neurosurgery: Spine 3:393-399.
  22. Gherman CD,Fodor D (2011) Epithelioid hemangioendothelioma of the forearm with radius involvement. Case report. Diagnostic Pathology 6: 120.
  23. Drazin D, Gandhi R, Slodkowska E, Boulos AS (2013) Epithelioid Hemangioendothelioma of the Mastoid: Resection for Recurrence and Adjuvant Radiation with 8-Year Follow up. Case Reports in Surgery 2013: 1-6.
  24. Kabukcuoglu F, Kabukcuoglu Y, Livaoglu A, Ozagari A, Armagan R, et al. (2006) Epithelioid hemangioendothelioma of bone. Acta Orthopaedica et Traumatologica Turcica 400: 324-328.
Citation: Bardoscia L, Sarda A, Petruzzelli M, Detti B, Portaluri M (2015) Pulmonary Epithelioid Hemangioendothelioma: Advances in Treatment Options despite a Rare Vascular Tumor. Chemo Open Access 4:160.

Copyright: © 2015 Bardoscia L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,distribution, and reproduction in any medium, provided the original author and source are credited.
Top