A 76-year-old man with hemoptysis and a groin nodule: A case report

Introduction

Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm with clinical behavior that varies from indolent to aggressive. The clinical presentation and anatomical sites of EHE can be variable; however, EHE most commonly affects soft tissue, lung, and liver. ¹ The estimated prevalence is fewer than one in a million individuals, primarily affecting adults and with a slight female predominance.^1,2 The characteristic histological features of EHE include epithelioid cells arranged in cords and nests within a myxohyaline stroma.^1–5 Tumor cells often contain eosinophilic cytoplasm, round nuclei, and cytoplasmic vacuoles, some of which may contain erythrocytes. ¹ Diagnosis of EHE requires immunohistochemical analysis, with tumor cells expressing endothelial markers such as CD34, CD31, podoplanin (D2–40), FLI1, and ERG.^1–3,5 Prognosis depends on the anatomical site of involvement and extent of disease at presentation, with ~21% of cases developing metastases. ¹ Treatment for EHE primarily involves surgical excision, with options for metastatic disease that include chemotherapy, immunotherapy, and targeted therapies. ⁴ Given the variation in clinical manifestations of EHE and its potential for multisystem involvement, recognizing atypical presentations is crucial for timely diagnosis and management.

Case report

A 76-year-old man presented to the emergency department with 9 days of hemoptysis without fever or other systemic symptoms. He had undergone spinal surgery 3 months earlier, complicated by aspiration pneumonia. Prior to admission, bronchoalveolar lavage culture grew Stenotrophomonas maltophilia, sensitive to multiple antibiotics. Computed tomography (CT) showed bilateral multifocal, ill-defined pulmonary nodules with ground-glass halo. The patient deteriorated despite treatment with trimethoprim/sulfamethoxazole, then levofloxacin and imipenem. Over 2 weeks of admission, hemoptysis worsened with increasing oxygen requirements. CT-guided fine needle biopsy showed normal lung parenchyma with hemosiderin-laden macrophages.

An asymptomatic nodule had appeared over his right pubis 5 months earlier (Figure 1) and grown in size to a 3 cm ulcerated tumor. Excisional biopsy revealed a well-defined ulcerated epithelioid vascular tumor with marked nuclear atypia, numerous mitoses, and focal myxoid changes (Figure 2). Immunohistochemistry was positive for AE1/AE3, CD31, and CD34 highlighting branching vascular channels. The tumor was submitted to a soft tissue pathologist, who favored the diagnosis of EHE based on the combination of histologic and immunohistochemistry features.

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Figure 1.

A 3 cm dark purplish-red ulcerated lesion over the right pubis of a 76-year-old man.

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Figure 2.

Histology shows an ulcerated endothelial tumor with epithelioid morphology at 20× magnification. The lesion is well-defined with focal myxoid changes. There is marked nuclear atypia and numerous mitoses. Numerous cells show intracytoplasmic vacuoles, containing red blood cell fragments.

Given the patient’s presentation and the histopathologic findings from the excisional biopsy, a diagnosis of EHE with probable metastatic disease to the lungs was established. The patient declined oncological interventions, opted for palliation, and died 1 month after admission.

Discussion

EHE is a rare vascular tumor with a clinical course that can range from indolent to aggressive. Although EHE can arise in any anatomical location, the lungs, liver, and soft tissues are most commonly involved and multifocal disease is frequently observed. ¹ This case illustrates the diagnostic complexity of EHE, as the patient initially presented with hemoptysis, a groin nodule, and ill-defined pulmonary nodules with ground-glass halo on CT leading to an extensive infectious workup before the ultimate diagnosis of EHE with suspected pulmonary metastases.

EHE can pose a diagnostic challenge due to its overlap with clinically and histologically similar conditions. Key histologic differentials include epithelioid angiosarcoma, which often tends to have a more aggressive course and histologically demonstrates more pronounced cytologic atypia, elevated mitotic activity, solid sheet-like growth, and areas of necrosis^1,2; metastatic amelanotic melanoma, which can mimic EHE but typically expresses melanocytic markers such as S100, Melan-A, HMB-45, and SOX-10 ⁶ ; and metastatic carcinoma, which can be excluded by presence of CD31 positivity. ⁷ Immunohistochemistry, and when appropriate molecular testing, are essential tools to distinguish EHE from these conditions and ensure accurate diagnosis.

Histopathological evaluation of the lesion revealed an epithelioid vascular tumor with nuclear atypia and intracytoplasmic vacuoles containing red blood cell fragments, features characteristic of EHE. ¹ Immunohistochemical staining confirmed endothelial differentiation with positivity for CD31 and CD34, consistent with EHE.^1–3,5 This was confirmed by a soft tissue pathologist who favored the diagnosis of EHE based on the combination of histologic and immunohistochemistry features. The etiology of this disease is still unclear; however, genetic studies have further distinguished two molecular subtypes. The WWTR1–CAMTA1 fusion is present in ~90% of cases, while the less common YAP1–TFE3 fusion is associated with a more distinctive histological pattern and may represent a clinicopathologically unique subset. ¹ These molecular alterations can aid in diagnosis, particularly in cases with ambiguous histological or immunophenotypic features. However, CAMTA1 immunostaining, while associated with EHE, is not exclusively specific and may be expressed in other neoplasms, thus limiting its diagnostic utility. ⁸ In this case, molecular testing for WWTR1–CAMTA1 or YAP1–TFE3 fusion was not pursued, as the patient had declined treatment and was receiving palliative care, and further molecular characterization was not required to guide management.

Prognosis varies significantly depending on anatomical site and extent of disease at presentation. ² Tumors >3 cm and increased mitotic activity (>3 mitoses/10 mm²) are associated with poorer outcomes, with 5-year disease-specific survival rates of 59% compared to 100% in lower-risk cases.^1,9 Although some EHEs exhibit bland cytology, even histologically low-grade tumors can metastasize, underscoring the unpredictable nature of this disease. ¹ In this patient, the rapidly enlarging ulcerated cutaneous tumor, progressive pulmonary disease, and clinical decline suggested an aggressive course.

Management approaches for EHE remain variable, as they are largely guided by findings from case reports, case series, and small trials.^2,4 Surgical excision is the preferred approach for localized disease, whereas systemic therapies may be considered for metastatic or unresectable disease. ² For asymptomatic patients with indolent or stable disease, active surveillance is often appropriate. Systemic treatment for EHE should be considered in patients with significant systemic symptoms or evidence of disease progression, although no standardized therapy currently exists. While conventional chemotherapy has shown limited benefit and should be limited to more rapidly progressing cases, anti-angiogenic agents such as pazopanib, sorafenib, and bevacizumab, as well as mTOR inhibitors (i.e. sirolimus) have demonstrated some retrospective efficacy and are generally preferred in moderately progressive cases.^2,4 However, in patients with advanced disease, pain can be severe and difficult to manage, requiring multimodal strategies, and often the involvement of pain specialists. ² In this case, the patient declined therapy, favoring a palliative approached aligned with their goals of care.

This case underscores the highly variable clinical course of EHE, a rare vascular tumor with potential for aggressive behavior and metastasis. This case highlights that, despite the indolent nature seen in some EHE cases, others may present with widespread disease and a poor prognosis. Early recognition of cutaneous or other atypical lesions, coupled with thorough histopathological and immunohistochemical evaluation, is crucial for diagnosis. Given the variable clinical presentation, diagnosis and management remains challenging. Our case highlights an atypical presentation of EHE with hemoptysis and a solitary groin nodule, underscoring the importance of prompt recognition and intervention.