Epithelioid hemangioendothelioma of the anterior mediastinum

Abstract

Epithelioid hemangioendothelioma (EHE) is a very rare vascular neoplasm in the anterior mediastinum. It is considered an intermediate-grade vascular neoplasm between benign hemangioma and highly aggressive angiosarcoma, with the potential for distant metastasis. The management of this disease is dependent on various factors such as the extent of tumor involvement, presence/absence of metastasis, and the general condition of the patient. Surgery is the treatment of choice with/without adjuvant chemo-radiotherapy in resectable disease. This case report presents the successful surgical management of a large invasive EHE in the anterior mediastinum in a 50-year-old woman.

Introduction

Epithelioid hemangioendothelioma (EHE) is an uncommon angiogenic neoplasm developing from vascular endothelial or pre-endothelial cells. Incidence of this tumor in the anterior mediastinum is a rarity. The 5th edition of the World Health Organization (WHO) classification has defined EHE as a malignant vascular neoplasm composed of epithelioid endothelial cells which is distinct from epithelioid angiosarcoma [1]. Herein, we present a case of EHE in the anterior mediastinum, where the tumor was invading surrounding structures, including the pericardium, left phrenic nerve, and left upper lobe of the lung, and causing mild pleural effusion.

Case report

A 50-year-old lady presented with a history of persistent cough for 2 months. An evaluation with contrast-enhanced computed tomography (CECT) of the chest revealed a lesion of 8 × 7 × 5.4 cm in the anterior mediastinum mainly on the left side (Fig. 1). Computed tomography (CT)-guided biopsy raised suspicion of sarcoma. She was further evaluated with a positron emission tomography (PET) scan that revealed a metabolically active large lobulated mass lesion in the anterior mediastinum with infiltration of the left upper lobe of the lung and costal pleura. This mass was also closely abutting mediastinal vascular structures, such as the left main pulmonary artery and superior pulmonary vein, with associated mild left pleural effusion. A multidisciplinary team decided that immediate surgical resection was the most appropriate course of action based on the tumor’s characteristics, location, and the patient’s clinical status. Neo-adjuvant therapy was not deemed necessary for this patient. After a thorough preoperative evaluation, she underwent a left-side diagnostic thoracoscopy followed by radical resection of the mediastinal mass by anterio-lateral thoracotomy. Intraoperatively, this mass was densely stuck to the pericardium, infiltrating the left phrenic nerve and lingular segment of the left upper lobe. Hence, along with the tumor, en-bloc resection of the pericardium, left phrenic nerve, and a wedge of the lingular segment of the left upper lobe was done. Subsequently, the pericardium was reconstructed using a polyglactin 910 mesh, and left diaphragmatic plication was performed using no. 1 polypropylene sutures.

Fig. 1.

A large heterogeneously enhancing lobulated lesion with a central necrotic area in the anterior mediastinum abutting the left main pulmonary artery, superior pulmonary vein

Mediastinal lymph dissection was not performed as the preoperative PET-CT was not showing any suspicious lymph nodes, and the natural behavior of sarcomas to spread hematogenously rather than through lymphocytic pathways. She was extubated on the table. Her postoperative recovery was uneventful and was discharged on the 7th postoperative day. The histopathological examination of the surgical specimen confirmed the diagnosis of EHE, supported by positive immunohistochemical staining for Cluster of Differentiation CD31 and CD34—the vascular markers—and Smooth Muscle Actin (SMA) staining suggestive of smooth muscle fibers. Occasional cells were also positive for CD60 (Fig. 2). As per the tumor, node, metastasis (TNM) staging, the tumor stage was T3/N0/M0. The patient has been in regular follow-up for the last 34 months and is doing well without any local/systemic recurrence.

Fig. 2.

Dilated vascular channels with cords and nests of spherical to spindle epithelioid cells embedded in a myxoid matrix

Discussion

EHE is a rare malignant vascular neoplasm in the anterior mediastinum with a distinct epithelioid appearance arising from vascular endothelial or pre-endothelial cells. The term “epithelioid hemangioendothelioma” was coined by Weiss and Enzinger in 1982. These are locally aggressive tumors with metastatic potential showing its intermediate nature between benign hemangiomas and malignant angiosarcomas [2]. In this study, the patient was diagnosed with locally aggressive EHE invading the pericardium, left phrenic nerve, and left upper lobe of the lung.

The clinical symptoms of mediastinal EHE are nonspecific, mainly such as cough, chest pain, dyspnea, hoarseness of voice, and/or invasion of neighboring structures. EHE is sometimes diagnosed incidentally in imaging investigations performed for other reasons. In case of metastasis, symptoms like pain, mass, hemorrhage, and other abnormalities may appear [3, 4]. In the present case, the patient presented with a persistent cough.

Preoperative misdiagnosis of EHE is common due to its rarity, lack of specific oncological markers, and unclear etiology. No radiological signs are diagnostic. In chest CT, mediastinal EHE typically appears as a well-defined soft tissue mass with peripheral enhancement, or heterogeneous enhancement with/without spotted calcification and fatty foci. Pleural effusion and enlarged lymph nodes in the mediastinum are rare, often leading to misdiagnosis as benign tumors [1, 5]. In the present study, CECT imaging showed a large heterogeneously enhancing lobulated lesion with a central non-necrotic area involving the anterior mediastinum on the left side abutting the left main pulmonary artery, superior pulmonary vein, and compressing the left upper lobe with left mild pleural effusion. Further, in the PET-CT imaging, this mass was metabolically active with maximum standardized uptake value (SUV_max) of 12.3. Histologically, EHE is characterized by cords and nests of spherical to spindle epithelioid cells embedded in a myxoid matrix [6].

In EHE, typically, surgery is the primary treatment aimed at radical complete resection, may be followed by adjuvant radiation therapy to prevent local recurrence [1]. Chemotherapy is the treatment option in cases of distant spread. The exact plan of management should be decided based on the extent of the disease and patient factors [7]. In this study, the index patient successfully underwent surgical resection of the tumor en-masse with the pericardium, left phrenic nerve, and left upper lobe of the lung achieving R0 resection. No adjuvant therapy was given. The mean survival of 4.6 years, ranging from 6 months to 24 years [7], is dependent on various factors such as the extent of tumor spread, location, and response to treatment. In our case, the patient has been in follow-up for 34 months and is doing well.

Conclusion

Although EHE is of rare incidence, it should be considered in the differential diagnosis of anterior mediastinal tumors. They are usually locally aggressive and surgical excision remains the mainstay of treatment.

Author contribution

All authors contributed to patient analysis, surgical treatment, and follow-up evaluation. Dr. Mohan Venkatesh Pulle and Dr. Arvind Kumar conceived and designed the study. Methodological aspects were managed by Dr. Belal Bin Asaf and Dr. Sukhram Bishnoi. Data collection and analysis were overseen by Dr. Harsh Vardhan Puri, Dr. Sumit Bangeria, and Dr. Manan Bharatkumar Parikh. Dr. Mohan Venkatesh Pulle drafted the initial manuscript. Subsequent refinement and editing involved Dr. Arvind Kumar, Dr. Mohan Venkatesh Pulle, Dr. Anmol Bhan, Dr. Sukhram Bishnoi, Dr. Belal Bin Asaf, Dr. Harsh Vardhan Puri, and Dr. Sumit Bangeria. Supervision was provided by Dr. Mohan Venkatesh Pulle and Dr. Arvind Kumar. All authors critically reviewed and approved the final version of the manuscript.

Funding

None.

Data availability

The data that support the findings of this study are available on request from the corresponding author Dr. Arvind Kumar upon reasonable request.

Declarations

Ethical statement

The study was conducted as per the Declaration of Helsinki (as revised in 2008) and as per ethical standards of the Medanta Institutional Ethics Committee which is registered under the Central Licensing Authority (Central Drugs Standard Control Organization) with registration no. ECR/282/Inst/HR/2013/RR-20. The date of ethics committee approval was 27/02/2024.

Informed consent

Written informed consent was obtained from the patient before his involvement in the study. Patient confidentiality was ensured by anonymizing the data before publication unless we obtained explicit consent for data identification.

Conflict of interest

The authors declare no conflict of interest.