Pulmonary Epithelioid Hemangioendothelioma-Mimicking Mesothelioma

Pulmoner epithelioid hemangioendothelioma is a rare and multifocal malignant tumor of vascular origin. Patients are generally asymptomatic. Chest pain, cough, weight loss, hemoptysis, and pleural effusion are seen in symptomatic patients. Moreover, it is more common in women. It is difficult to diagnose the patients based on clinical and radiological findings. Histopathological examination is the gold standard. We here aimed to present our pulmonary epithelioid hemangioendothelioma patient pre-diagnosed with mesothelioma when she was admitted to the hospital with dyspnea and had bilateral multiple nodules and bilateral pleural effusion.

Introduction

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare and low-intermediate grade malignant neoplasm of vascular origin [1,2]. PEH is generally asymptomatic. It is more common in women [3]. They are typically seen as multiple partially well-circumscribed nodules on computed tomography (CT) [4]. It is difficult to diagnose PEH based on clinical and radiological findings alone. Histopathological examination is gold standard for the diagnosis of PEH [5]. We here aimed to present a PEH patient transferred to our department with the diagnosis of mesothelioma.

Case report

A 40-year-old Syrian woman was admitted to the epicenter of a hospital with shortness of breath lasting for about 1 month. After multiple bilateral nodules were monitored on her CT performed at the epicenter the patient pre-diagnosed with mesothelioma was transferred to our department. In her physical examination: BP: 110/50 mm Hg, PR: 110/min, SpO2: 86% and decreased breath sounds were present at the lung bases bilaterally. She had pleural catheter which was placed to left side at the epicenter. The drain output was 100 cc. PFT FEV1: 0.81 24% and FVC: 0.81 21%. Chest x-ray of the patient showed right sinus blunting, mediastinal widening, bilateral nodular opacities and pleural catheter on the left (Figure 1). On PET-CT scan, there were pleural effusion with 1.76 of SUVmax involvement in bilateral hemithorax and large number of nodules measured as 44 mm in diameter and located on the right upper lobe of the lung and a part of which had hypometabolic and necrotic central area (SUVmax: 1.56). Histopathological examination was recommended as mesothelioma was primarily considered based on PET-CT findings. The patient underwent pleural biopsy with right VATS and wedge resection for pulmonary nodules in upper-middle-lower lobes of the lung. In frozen section, a malignant mesenchymal lesion was reported. That is why the patient underwent pleurodesis. In microscopic examination, epithelioid, rarely fusiform tumor cells were monitored in hyaline matrix in some areas. Cytoplasmic vacuoles were monitored in tumor cells (Figures 2,3). Mild to moderate atypia was observed generally. In immunohistochemical examination, diffusely positive reaction for CD31, CD34, WT-1 and FLI-1 and negative reaction for HHV-8, TTF-1 and ALK were showed (Figures 3-5). The patient was diagnosed with PEH based on histopathological and immunohistochemical findings.

Figure 1: Wall thickening of the terminal ileum with adjacent lymphadenopathy in Abdomen and Pelvis CT (with contrast).

Figure 2: Posteroanterior chest X-rays. The chest radiography showed a diffuse nodular pulmonary pattern in both lungs.

Figure 3: Microscopic features. On higher power tumor cells with eosinophilic cytoplasm, typically with erythrocyte-containing lumen structures (H&E 400X).

Figure 4: In immunohistochemical examination, there is a positive reaction with CD31 (100X).

Figure 5: In immunohistochemical examination, there is a positive reaction with CD34 (100X).

Discussion

PEH was first described as a pulmonary intravascular bronchoalveolar tumor in 1975 [6]. Then, the term ‘Epithelioid Hemangioendothelioma’ (EHE) was used by Weiss and Enzinger in 1982 [7]. Weiss and Enzinger described EHE as a new entity between hemangioma and angiosarcoma. According to the latest WHO classification, EHE was described as low to intermediate grade malignant vascular tumor [1]. EHE can arise in different sites including lung, liver and soft tissue. PEH is a rare tumor and generally seen in young adults. It is two times more common in women [3]. Patients are generally asymptomatic. Chest pain, cough, weight loss, hemoptysis and pleural effusion are seen in symptomatic patients. Some clinicians have proposed three main CT patterns in patients with PEH: multiple pulmonary nodules, multiple pulmonary reticulonodular opacities, and diffuse infiltrative pleural thickening [8,9]. Approximately 160 patients with PEH have been reported worldwide until now.

Metastases, primary lung cancer, lymphoid tumors, benign or malignant vascular tumors, infections, sarcoidosis, and mesothelioma should be considered in radiological differential diagnosis. As our patient had both bilateral multiple pulmonary nodules and bilateral pleural effusion mesothelioma was primarily considered.

In a recent study, it has been reported that WWTR1-CAMTA1 fusion was present in most of EHEs and that this fusion was present in most of classical epithelioid hemangioendothelioma regardless of their clinical behaviors [10]. Therefore, they suggested that additional genetic abnormalities could be responsible in driving more aggressive course in EHE. In this study, overall survivals of EHE patients with WWTR1-CAMTA1 fusion and EHE patients with YAP1-TFE3 fusion were compared [10]. According to the results, patients with conventional EHE in whom WWTR1-CAMTA1 fusion was present had a less favorable outcome compared to the ones in whom YAP1-TFE3 fusion was present and the 5-year overall survival rates in these patients were 59% and 86% respectively [10].

There is no standard treatment for PEH as it is rare. Moreover, tumor resection should be considered for the patients who can endure surgery. The rate of 5-year overall survival is approximately 60% in patients who undergo surgery [11]. Chemotherapy is preferred for patients with a disseminated disease, however, radiotherapy has been proved to be ineffective [12,13].

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