A Case of Primary Epithelioid Sarcoma of the Pleura

Background

Epithelioid sarcoma (ES), a malignant tumor with mixed differentiation into both mesenchymal and epithelial cells, was first reported by Enzinger in 1970 [1]. There is wide variation in the 5- year survival rates, ranging from 25% to 78% [2]. It is divided into 2 subtypes: the classic subtype, which occurs distally in the extremities; and the proximal-type subtype, which occurs in the proximal extremities and trunk [3]. The proximal-type subtype has been reported to occur in the perineum, pubis, genitalia, and trunk [4], but only a few cases of ES of pleural origin have been reported. ES in a rare site in which it is difficult to make a definitive diagnosis, but it was reported that ES was characterized by INI-1 deletion in approximately 90% of cases [5].

We experienced a case of proximal-type pleural ES (PES) that grew rapidly. It is difficult to distinguish from malignant pleural mesothelioma (MPM) based on imaging alone, and MPM is relatively difficult to diagnose histologically. Therefore, pathological diagnosis of PES was very difficult because of its low incidence, and the patient died while waiting for diagnosis. However, if a rapidly growing pleural tumor is suspected to be PES, it can be diagnosed by confirming the presence of INI-1 deletion. Herein, we report a rare case of PES and its clinical course.

Case Report

A 64-year-old Asian woman was referred to the respiratory division of our hospital for dyspnea on exertion. Her past medical history was adenocarcinoma of the cervix at the age of 63 years, and concurrent chemoradiotherapy performed 4 months prior to consultation showed partial response. She drank alcohol occasionally and did not have a history of cigarette smoking or illicit substance use.

She had had a cough for a week. Her dyspnea had worsened since the morning and she was referred to the emergency department. Her right respiratory sound was weakened and a chest X-ray showed a massive right pleural effusion. A chest tube was inserted into her right pleural cavity (Figure 1). Chest fluid examination showed low pH (7.00), low glucose (27 mg/dL), high lactate dehydrogenase (1950 U/L), high white blood cells (over the inspection limit), normal carcinoembryonic antigen (2.8 ng/mL), normal hyaluronic acid (234 000 ng/mL), and normal adenosine deaminase (22.8 IU/L). Additionally, cytology revealed malignant cells and culture showed no bacterial infection. Bacterial infection was not proven, but empyema was diagnosed comprehensively based on other examinations. Antibiotics were administered and we repeatedly drained and clamped the pleural effusion at a rate of 1000 mL/day to avoid re-expansion pulmonary edema, but it accumulated daily.

On the 5th hospital day, chest fluid stopped increasing and the chest tube seemed to be occluded. Computed tomography (CT) revealed many encapsulated fluid cavities similar to empyema (Figure 2). At the same time, a rapid thickening of the pleura was also observed, which was considered to be an inflammatory fibrin clot. An additional chest tube was inserted and pleural irrigation and intrapleural fibrinolytic therapy with urokinase were performed for 4 consecutive days; however, her symptoms did not improve. Our division was consulted, and we planned curettage of the cavity and pleurodesis.

We operated on the 14th hospital day. The encapsulated cavity was curetted, and thickened pleura was resected via thoracotomy (Figure 3). Because the resected pleura was thickened, elastic, and hard, like a tumorous lesion rather than inflammatory fibrin tissue, it was submitted for pathological examination. We could not perform pleurodesis because of circulatory instability induced by bleeding. After surgery, she was received a blood transfusion, and her general condition was stabilized until postoperative day (POD) 1. Intraoperative effusion culture showed no bacterial infection. The pathologists reported that most of the resected pleura were tumor lesions but not metastatic adenocarcinomas of the cervix. Based on the report, CT from the neck to the pelvis was performed again, but we observed no clear primary lesion. In addition, no obvious abnormalities were found in a physical examination that included the crown, extremities, and genitals. As we had difficulty in diagnosing her pathologically, we examined immunohistochemical staining of the tumor in stepwise fashion. Accordingly, immunohistological examination was positive for cytokeratin AE1/AE3, vimentin, EMA (partial), CD34 (partial), and β-catenin (membranous and focal cytoplasmic). Staining for INI1, calretinin, TTF-1, chromogranin A, synaptophysin, STAT6, WT1, Melan A, HMB-45, S-100, and NUT were negative. As a result of repeated discussions with 2 pathologists, INI1 negativity was an important decisive factor; finally, we diagnosed ES of the pleura on POD 20 (34th hospital day).

Her right lung was not expanded, despite curettage and manual inflation during surgery. Her respiratory disorder improved temporarily after the operation as the pleural effusion was drained, but her general condition weakened day to day because of extremely rapid tumor progression (Figure 4). She did not wish to receive intubated ventilation after hearing that the respiratory failure caused by the tumor did not improve until treatment was started. On POD7, she developed CO2 narcosis and became unconscious. She regained consciousness with manual mask ventilation, but when she was put on NPPV, she refused to put it on because of discomfort. She stated that if CO2 narcosis redeveloped, she wanted only symptom relief and desired no treatment. We planned to perform anti-tumor treatment immediately after diagnosis; however, CO2 narcosis redeveloped and she died on POD 8 (the 22nd hospital day) because of a respiratory disorder. The family did not provide consent for a pathological autopsy.

Discussion

Epithelioid sarcoma is rare, accounting for less than 1% of soft tissue sarcomas [6]. It is immunohistochemically positive for cytokeratin and vimentin, both mesenchymal and epithelial differentiation are observed, and INI-1 deletion is characteristic. Of the proximal-type, only 2 cases of pleural origin have been reported [7,8]. Previous lung cancer studies reported that the average solid-part tumor volume doubling time is 394~458 days [9,10]. In the present case, the volume of the tumor that had disseminated outside the thorax due to drainage was measured using the SYNAPSE VINCENT 3D volume analyzer (Fuji Medical Systems, Tokyo, Japan). The volume doubling time was calculated by the Schwartz equation [11] as approximately 7 days. This indicates an extremely rapid progression rate. Such a fast progression has not been reported in proximal-type ES and other tumors.

In the present case, it was believed that the marked imaging changes were due to empyema, even though the results of chest fluid aspiration indicated no evidence of bacterial infection. The rapid growth of a tumor causing carcinomatous pleurisy is uncommon; however, in the present case, a diagnosis of carcinomatous pleurisy was made. Therefore, there was an opportunity to suspect a cancerous lesion and a histological examination was performed at the time of surgery. During surgical procedures for typical empyema, cultures are often collected, but histological examination is not common. However, if surgical treatment is to be performed, a histopathological examination should also be performed to ensure accurate diagnosis, especially in cases that appear complicated by neoplastic lesions. In this patient, positive cytology became an indication for tissue diagnosis.

Most tumors growing in the pleura are MPM or metastatic tumors, or rarely a lymphomatous tumor [12]. Differential diagnosis is extremely difficult when none of the above is diagnosed. Additionally, MPM is relatively difficult to diagnose histologically, even immunohistochemically; therefore, MPM is occasionally diagnosed clinically without characteristic findings. On the other hand, this case suggested PES as a possible disease of rapidly growing pleural tumor. The progression of most MPM is not as rapid as PES. Since it is difficult to distinguish PES from MPM based on imaging alone, it is recommended that PES should also be suspected, especially in the presence of a histologically difficult-to-diagnose, rapidly growing pleural tumor. Diagnosis of PES may be possible by examination of INI-1 deletion if it is included in the differential diagnosis.

Conclusions

In cases that appear to be empyema, there is a slight possibility of a rapid growing tumor. Therefore, a histopathological examination should also be performed to ensure accurate diagnosis, especially in patients who seem to be complicated by neoplastic lesions. In addition, if a tumorous lesion is detected and it is neither metastatic nor MPM, PES should be added to the differential diagnosis in the presence of a rapidly growing and histologically difficult-to-diagnose pleural tumor.