An extremely rare case of pulmonary epithelioid hemangioendothelioma

Abstract

Epithelioid emangioendothelioma (EHE) is a rare tumor originating from vascular endothelial cells, which belongs to malignant vascular tumors with low to moderate differentiation and potential metastatic ability and its incidence rate is less than one in a million. We herein report a rare case of EHE of pulmonary origin and a review of the literature concerning the clinical and pathological features of this disease. The patient underwent left upper lobectomy to completely extirpate the lesion by video‐assisted thoracic surgery. Our findings suggest the difficulty of making a diagnosis before surgery and that more cases need to be reported in order to facilitate the preoperative diagnosis of such a rare tumor.

Histological features of EHE: Hematoxylin and eosin (H&E) indicated that the tumor tissue morphology is diverse, showing nodular growth, showing well‐defined eosinophilic nodules, and transparent degeneration or coagulative necrosis similar to amyloidosis or chondroma can be seen in the center. There are many cells around the nodule, and the cell mass located in the mucilaginous chondroid matrix extends into the alveolar cavity, bronchioles, blood vessels, and lymphatic vessel. Part of the alveoli are filled with patches of tumor cells, presenting as papillary or glomerular like hyperplasia, with obvious hyaline degeneration in the interstitium, and relatively normal alveolar septa. Tumor cells have prominent epithelioid features, similar to epithelial cells, tissue cells, or decidual cells, arranged in a nest, cord, or irregular shape. CK7 and TFE‐3 staining was negative. CAMTA‐1, CD34, and CD31 were also positive. (a: CK7, b: TFE‐3, c: CAMTA‐1, d: CD34, e: CD31, f: Hematoxylin and eosin).

INTRODUCTION

Epithelioid hemangioendothelioma (EHE) is a rare tumor originating from vascular endothelial cells, and its incidence rate is less than one in a million. ¹ EHE belongs to malignant vascular tumors with low to moderate differentiation and potential metastatic ability. ² It can occur in multiple organs throughout the body, commonly in the limbs, bones, and liver, with the lungs being a very rare site of occurrence. ³ We herein report a rare case of EHE of pulmonary origin and a review of several studies concerning the clinical and pathological features of this disease.

CASE REPORT

A 55‐year‐old man was admitted to our hospital for assessment of a left upper lobe nodule that was noticed on chest radiography during a routine health check. He had smoked one pack of cigarettes per day for 30 years and had quit smoking for 7 months. He denied the symptoms including the presence of chest pain, hoarseness, cough, and dyspnea. He had no risk factors for immunodeficiency disease or other infections. Physical examination shown normal breath sounds in both chest fields. Laboratory findings were within normal limits. His pulmonary function tests and cardiovascular examination revealed normal performance. The pulmonary function tests showed that FEV1 was 2.16 L and FEV1/FVC was 87.24%. Cardiovascular examination showed that EF was 68%. Plain and chest computed tomography (CT) (Figure 1a,b) showed partial enhancement in the soft tissue, calculated as 1.4 cm × 1.2 cm in size.

FIGURE 1.

Chest computed tomography (CT) of the case. (a) and (b) CT scan showing soft tissue in the left upper lobe, measuring 1.4 × 1.2 cm in size.

As diagnosis was not established through imaging, surgery was scheduled. The patient was subjected to lobectomy by applying a single‐port video‐assisted thoracic surgery (VATS). There was no invasion into the adjacent structures during surgery. After complete resection of the lesion, tissue from the mass was removed with biopsy forceps for quick frozen pathology, which was pathologically diagnosed as epithelioid hemangioendothelioma. Lymph node dissection was performed, with stations 5, 6, 7, 9, 10, 11, and 12 lymph nodes removed. The patient was discharged 3 days after the operation with no complications and has been followed‐up for 5 months without evidence of recurrence.

Hematoxylin and eosin (H&E) indicated that the tumor tissue morphology was diverse, showing nodular growth, well‐defined eosinophilic nodules, and transparent degeneration or coagulative necrosis similar to amyloidosis or chondroma could be seen in the center. There were many cells around the nodule, and the cell mass located in the mucilaginous chondroid matrix extended into the alveolar cavity, bronchioles, blood vessels, and lymphatic vessel. Part of the alveoli were filled with patches of tumor cells, presenting as papillary or glomerular‐like hyperplasia, with obvious hyaline degeneration in the interstitium, and relatively normal alveolar septa. The tumor cells had prominent epithelioid features, similar to epithelial, tissue, or decidual cells, arranged in a nest, cord, or irregular shape (Figure 2f). Immunohistochemically, S‐100, PCK, CK8, Ck7, TTF‐1, P63, HMB45, Syn, CgA, CD56, SMA, PAX8, WT‐1, and TFE‐3 staining was negative. CAMTA‐1, CD34, CD31, and EMA were also positive, and Ki67 index was about 20% (Figure 2a–e).

FIGURE 2.

Histological features. Hematoxylin and eosin (H&E) indicated that the tumor tissue morphology was diverse, showing nodular growth, showing well‐defined eosinophilic nodules, and transparent degeneration or coagulative necrosis similar to amyloidosis or chondroma can be seen in the center. There are many cells around the nodule, and the cell mass located in the mucilaginous chondroid matrix extends into the alveolar cavity, bronchioles, blood vessels and lymphatic vessel. Part of the alveoli are filled with patches of tumor cells, presenting as papillary or glomerular like hyperplasia, with obvious hyaline degeneration in the interstitium, and relatively normal alveolar septa. Tumor cells have prominent epithelioid features, similar to epithelial cells, tissue cells, or decidual cells, arranged in a nest, cord, or irregular shape. CK7 and TFE‐3 staining was negative. CAMTA‐1, CD34 and CD31 were also positive. (a) CK7, (b) TFE‐3, (c) CAMTA‐1, (d) CD34, (e) CD31, (f) H&E.

DISCUSSION

In 1975, Dail and Liebow first described EHE as invasive bronchoalveolar cell carcinoma. ⁴ In 1982, Weiss and Enzinger named it EHE to describe a unique tumor composed of soft tissue endothelial vascular tumors. ⁴ In 2015, the WHO classification of lung tumors classified EHE as low to moderate grade malignant vascular tumors. ⁵

There are currently two possible mechanisms of EHE reported in the literatures. One is related to cell molecular genetics research on EHE, and the occurrence of EHE at the molecular level. It is necessary to stimulate angiogenesis of endothelial cells through monocyte chemoattractant protein‐1 promoting the development of tumors. WWTR1 and CAMTA genes are involved in the development of tumors which play an important role in the exhibition process. ⁶ Another study has confirmed that the occurrence of this disease is related to chronic bartonella infection, which is related to the invasion and induction of Bartonella into red blood cells intradermal infection and at least three Bartonella species induce vascular endothelial factor mediated proliferation, cytoskeleton rearrangement, and inhibit endothelial cell apoptosis by upregulating mitosis and proinflammatory genes. ⁷

EHE tends to occur in middle‐aged women, and the incidence rate is 2–4 times that of men. More than 40% of patients are younger than 30 years old. ⁸ Clinical symptoms include respiratory symptoms such as shortness of breath, dry cough, and hemoptysis, as well as mild chest pain, fatigue, low fever, and anemia, with occasional decrease in body mass. ⁹ In our case, the patient presented without any symptoms.

The radiological diagnosis of EHE is often difficult because of the nonspecific imaging findings. The characteristic CT manifestation is that multiple nodules in both lungs are scattered around the vascular bundle, and small nodules below 5 mm are more common. ² Some studies have also shown that subpleural nodules are more common, with wedge‐shaped or polygonal nodules, and long cords and pleural traction. During follow‐up, the number and volume of nodules will increase gradually. ¹ , ¹⁰

The main manifestation of EHE is a grayish white grayish brown mass, which is distributed seasonally in both lungs and has a slightly tough section. Under the microscope, the tumor tissue is an eosinophilic nodular shape with features such as hyaline degeneration in the central part, and focal areas with calcification and solidification. ⁷ Tumor cells are circular, spindle‐shaped, and some of the cytoplasm of tumor cells will produce vacuoles, where there may be single or multiple red blood cells, vacuolar like nodules the main feature of EHE is the presence of papillary structures in some blood vessels. ¹¹ Mutually related studies have shown that the cells in the tumor margin area are relatively abundant, with epithelioid tumor cells on the surface. It is currently characterized by glomerular like hyperplasia and polypoid hyperplasia, which can fill the dilated alveolar space acidophils can exist in tumor cells. ¹²

Due to the relatively low clinical incidence of EHE and the fact that most studies focus on individual cases, there is a lack of large‐scale data for clinical support, and no relatively accurate and effective treatment plan. If the patient has a single or fewer lesions, surgical resection can be chosen for treatment. However, a single surgical resection cannot alleviate the patient's symptoms, and the patient needs to undergo surgical resection combined with chemotherapy for treatment. The main types of general surgical resection include extended resection and wedge resection, and patients who can undergo surgery have a relatively long overall survival time. ⁵ Other treatments include chemotherapy, radiotherapy, steroids, and low dose interferon has been used in several patients. Very limited clinical trials have been done using chemotherapy and radiotherapy; therefore, the effectiveness of these methods remain unclear. ¹³ In our case, as the mass was in the left upper lobe, we considered lobectomy to extirpate the lesion completely and that extirpation by VATS might be a better option to treat this condition.

In summary, the clinical incidence rate of the disease is not high, but because of the high degree of harm of the disease, it still receives the attention of the majority of clinicians at present. Although there is currently no obvious treatment for this disease, with the further development of relevant research, more standardized, reasonable, and effective treatment methods will definitely be sought in the future when treating EHE. At the same time, a multidisciplinary approach, involving surgeons, radiation oncologists, pulmonologists, and oncologists, is required to optimize the survival and quality of life of patients with lung cancer. ¹⁴

AUTHOR CONTRIBUTIONS

XC was involved in drafting the manuscript. YW and GC was involved in acquisition of data. CS designed and revised the manuscript. All authors have read and approved the final manuscript.

CONFLICT OF INTEREST STATEMENT

The authors have no conflicts of interest to declare.

Chen X, Wang Y, Che G, Shen C. An extremely rare case of pulmonary epithelioid hemangioendothelioma. Thorac Cancer. 2023;14(24):2519–2522. 10.1111/1759-7714.15051

DATA AVAILABILITY STATEMENT

All data for this study are publicly available and are ready for the public from database of hospital.