Lung epithelioid hemangioendothelioma

Abstract

Lung epithelioid hemangioendothelioma (LEHE) is a rare tumor of vascular origin with low to intermediate malignancy. Its diagnosis is confirmed by histopathology study. We report a case of a non-smoker man in his fifties who was diagnosed for LEHE with positive staining for erythroblast transformation-specific-related gene (ERG) and cluster of differentiation 31 (CD31). Our case highlights the importance of a histological diagnosis to avoid misdiagnosis.

Case report

A non-smoker man, in his fifties, consulted for an episode of bronchitis. Chest X-ray showed suspicious left lung mass. Body computed tomography revealed two masses in the left upper lobe invading the mediastinal pleura with discreet infiltration of the mediastinal fat with lymph nodes of the left paratracheal chain. A computed tomography (CT)–guided lung biopsy of the left upper lobe mass was performed, which showed lung localized epithelioid hemangioendothelioma of intermediate grade. Fludeoxyglucose-18 positron emission tomography (FDG PET) scan revealed an uptake in the ventral segment of the left upper lobe measuring 7.5 × 3.87 of the major axis (higher standardized uptake value (SUV) = 5.18) with multiple lymph nodes at the level of the left paratracheal chain (SUV = 2.58) (Fig. 1). The patient underwent tumor resection with mediastinal lymph node dissection. The histopathological study showed epithelioid cell proliferation with characteristic eosinophilic cytoplasmic inclusions (Fig. 2) with positive staining for erythroblast transformation-specific-related gene (ERG) and cluster of differentiation 31 (CD31) (Fig. 3).

Fig. 1.

Fludeoxyglucose-18 positron emission tomography (FDG PET) scan: an uptake in the ventral segment of the culmen

Fig. 2.

Epithelioid cell proliferation with characteristic eosinophilic cytoplasmic inclusions

Fig. 3.

A Positive staining for erythroblast transformation-specific-related gene (ERG). B Positive staining for cluster of differentiation 31 (CD31)

Therefore, it concluded to an intermediate-grade hemangioendothelioma with positive lymph nodes (7 N +/11 N). The tumor was classified as pT4cN2. The postoperative decision was to continue radiological monitoring without systemic treatment or radiotherapy. The patient is in remission after a follow-up of 10 months.

Discussion

The rarity of lung epithelioid hemangioendothelioma (LEHE) and the potential for postoperative “watch and see” are what make our case unique. The first case of epithelioid hemangioendothelioma (EHE) was reported by Dail and Liebow in 1975. They defined it as an aggressive kind of bronchioloalveolar carcinoma that extensively invaded tiny airways and blood vessels [1]. In 50% of cases, a blood vascular origin may be shown [2]. Using WW Domain Containing Transcription Regulator 1 (WWTR1)-Calmodulin Binding Transcription Activator 1 (CAMTA1) breakpoint analysis, it has also been demonstrated that multifocal EHE has a monoclonal origin, meaning that a single initial malignant clone spreads to cause many lesions [3]. There is a wide range in the clinical presentation upon diagnosis. For patients who are fully asymptomatic, the first diagnosis may be incidental. A histopathological study showed epithelioid cells that were arranged in solid nests, cords, or strands. Its cytoplasm was glassy and eosinophilic, frequently containing cytoplasmic vacuoles. LEHE is characterized by positive staining for endothelial differentiation, including Friend leukemia integration 1 (FLI-1), CD31, ERG, and cluster of differentiation 34 (CD34) [2]. Less than 30% of patients show focal cytokeratin immunopositivity [2]. LEHE baseline staging includes whole-body imaging, with brain imaging, using magnetic resonance imaging or CT. Uptake of FDG is typically mild to moderate [3]. Higher standardized uptake value (SUV) lesions appear to be associated with higher progression rates and a lower survival rate.

The treatment of choice for unifocal LEHE is surgery [4]. Systemic therapy, in the context of (neo) adjuvant therapy, is not supported by any data. The initial favored method for patients with asymptomatic metastatic disease that cannot be completely removed with tolerable morbidity is active surveillance. The danger of overtreatment seems to outweigh the harm of starting treatment later in this case. Systemic therapy should be started early in patients with serosal effusion and/or significant systemic symptoms, because these patients typically have a quickly progressing course. Mammalian target of rapamycin inhibitors have been shown to exhibit the strongest clinical activity [4].

There are no well-established pathological or molecular prognostic variables. While there have been conflicting reports on the gene rearrangement subtype’s predictive usefulness, synaptophysin expression has lately been suggested to have a negative prognostic role. The existence of systemic symptoms and the size of the tumor at presentation, as well as metastatic stage, are the only prognostic variables [4].

Author contribution

W.B.K.: idea, writing. M.H. and D.S.: data collection, writing. S.M. and T.B.: pathological study, writing. A.H.: lung surgery. K.C.: revision. A.K.: supervision, revision. W.B.K. is the author guarantor. All the authors reviewed the manuscript.

Funding

None.

Declarations

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and the national research committee of Habib Bourguiba Hospital (08/24) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Patient consent for publication

Consent obtained directly from the patient.

Competing interests

None declared.