Primary Pulmonary Angiosarcoma: Case Report and Literature Review

ABSTRACT

Pulmonary angiosarcoma is a rare and aggressive tumour arising from the endothelial cells of the pulmonary vasculature. The average survival from time of diagnosis is 9 months. This cancer presents challenges due to small nodules, pleural effusion, and hemoptysis often being confused for benign diagnosis. We present a case of primary pulmonary angiosarcoma with similar diagnostic challenges and a rapidly declining functional status. Our patient had a non‐diagnostic CT‐guided lung biopsy and iliac crest bone biopsy. Definitive diagnosis was achieved by robotic navigational bronchoscopy of a 2.5 cm left lingula nodule, which identified tumour cells positive for CD31, consistent with epithelioid angiosarcoma. Despite transient improvement with supportive care, the patient's condition deteriorated, culminating in cardiac arrest and death. Our study reviews clinical courses, diagnostic tools, and treatment available for pulmonary angiosarcoma and highlights the importance of robotic biopsy as an earlier diagnostic tool for such aggressive pulmonary cancers.

We present a case of primary pulmonary angiosarcoma with widespread metastatic disease, initially presenting with nonspecific respiratory symptoms and diagnostic uncertainty, ultimately diagnosed via robotic navigational bronchoscopy. This case highlights the challenges in early recognition and the potential role of advanced bronchoscopic techniques in establishing a timely diagnosis.

1. Introduction

Primary pulmonary angiosarcoma is an aggressive tumour of pulmonary endothelial cells, usually affecting nonsmokers with some reported cases in miners and workers exposed to polyvinyl chloride. Exceedingly rare in occurrence, this cancer has been reported to manifest as rapid clinical deterioration, and limited chemotherapy benefits are reported in current evidence.

Radiographic findings are variable and may include solitary or multiple pulmonary nodules, masses, lymphadenopathy, or pleural effusions. Definitive diagnosis requires histopathologic evaluation with immunohistochemical staining demonstrating endothelial markers such as CD31, CD34, and ERG. Due to its rarity, there is limited consensus on optimal diagnostic strategies, and conventional biopsy techniques may be nondiagnostic, particularly in cases with small or difficult‐to‐access lesions.

We present a case of primary pulmonary angiosarcoma with widespread metastatic disease, initially presenting with nonspecific respiratory symptoms and diagnostic uncertainty, ultimately diagnosed via robotic navigational bronchoscopy. This case highlights the challenges in early recognition and the potential role of advanced bronchoscopic techniques in establishing a timely diagnosis.

2. Case Report

We present a case of a 64‐year‐old male who initially presented to our outpatient pulmonology clinic with a two‐month history of cough unrelieved by multiple courses of antibiotics. A chest x‐ray and subsequent CT scan of the chest demonstrated ill‐defined nodular opacities in left lower lobes without evidence of interstitial disease and lymphadenopathy. Initial laboratory workup was notable for leukocytosis. The patient subsequently underwent a CT‐guided biopsy of the left lower lobe nodule, which was nondiagnostic, and a PET scan demonstrating a 3.3 cm left inferior lingular mass with bilateral pulmonary, left skull base, humeral, left iliac, and left femoral metastases. For further diagnostic clarity, an outpatient interventional radiology–guided biopsy of lucent iliac crest lesions revealed carcinoma of unknown origin (Figure 1A). Over the following weeks, he continued to experience cough, fevers up to 102–103°F, and generalized bone pain. The patient experienced progressive clinical decline, including reduced ambulation, generalized weakness, and an estimated 20‐pound weight loss over 2 months. He later presented to our hospital with acute altered mental status. Although he was awake spontaneously, he was disoriented to his surroundings. His Glasgow Coma Scale score remained normal, and laboratory evaluation was notable for hypercalcemia of 14 mg/dL, persistent leukocytosis, and anaemia. A computed tomography scan of the chest revealed several non‐calcified pulmonary nodules along with hilar and mediastinal lymphadenopathy, the largest measuring 2.5 cm in the left hilum (Figure 1B,C).

FIGURE 1.

(A) CTA chest on hospital presentation demonstrating new mediastinal lymphadenopathy (left) and a large left lingular mass without pleural effusions or pneumothorax. (B) Axial (left) and coronal view (right) of CT chest on day four of hospitalization demonstrating scattered nodules and masses throughout the lungs with largest measuring 3.8 cm in the lingula, small left pleural effusion. (C) CT imaging demonstrating nonspecific lucent lesions within the ischium.

MRI brain demonstrated a new 4 mm area of enhancement within the left paramedian cerebellar hemisphere, concerning for a hemorrhagic metastatic lesion; there was no associated cerebral edema or midline shift. Given his rapid clinical deterioration and diagnostic uncertainty regarding primary malignancy after an unsuccessful CT guided lung biopsy of lung mass and IR guided iliac crest biopsy, robotic navigational bronchoscopy was pursued (Figure 2). Following robotic‐assisted ion bronchoscopy of the left lingula, tumour cells positive for CD31 with retained nuclear expression on immunostaining, findings consistent with the epithelioid subtype of primary pulmonary angiosarcoma (Figures 3 and 4). Reanalysis of the previously obtained iliac crest biopsy was subsequently requested with targeted immunohistochemical staining, which revealed CD31 positivity, pancytokeratin negativity, and CD34 negativity, confirming skeletal metastatic disease from the primary pulmonary angiosarcoma rather than a synchronous primary malignancy.

FIGURE 2.

Robotic bronchoscopy images demonstrating localization and sampling of the target lesion.

FIGURE 3.

Lingular and bone biopsy specimens showing markedly atypical neoplastic cells within an inflammatory background. Tumour cells exhibit hyperchromatic nuclei, prominent nucleoli, and moderately abundant amphophilic cytoplasm.

FIGURE 4.

Bone marrow biopsy demonstrating malignant cells positive for CD31 and focally positive for pan‐cytokeratin, and negative for CD34.

The patient experienced temporary improvement in mentation following resolution of hypercalcemia with zoledronic acid and intravenous antibiotics; however, he soon returned to the hospital with worsening generalized weakness and was found to have a white blood cell count of 70,000/μL. Blood cultures, sputum cultures, tuberculosis testing, and viral PCRs were negative; transthoracic echocardiography resulted in normal ejection fraction with mild diastolic dysfunction. His condition further deteriorated, with vasodilatory shock secondary to suspected culture‐negative sepsis; hypoxemia and acute kidney failure requiring intubation and initiation of continuous renal replacement therapy. Repeat chest images showed small pleural effusions and pulmonary nodules. Given clinical decline, increasing vasopressor requirements, and lactic acidosis, multiple goals‐of‐care discussions were held with the family. The patient ultimately suffered ventricular fibrillation cardiac arrest, progressed to asystole, and despite resuscitation efforts, return of spontaneous circulation could not be achieved, and he expired.

3. Discussion

We conducted a comprehensive literature search to identify all reported cases of primary pulmonary angiosarcoma across PubMed/MEDLINE, Embase, and Google Scholar (inception through May 2025), supplemented by manual review of reference lists from identified articles. A total of 1451 records were identified across all databases. After the removal of duplicates and screening of titles and abstracts, 43 full‐text articles were retrieved for detailed review. Following full‐text assessment, cases of angiosarcoma arising from extrapulmonary primary sites, including hepatic and cardiac sources, as well as cases representing secondary or metastatic pulmonary involvement, were excluded. Ultimately, 15 cases of confirmed primary pulmonary angiosarcoma were included in the final synthesis and form the basis of this literature review.

The incidence of primary pulmonary angiosarcoma ranges from 0.001 to 0.030% of all cancers. Among them, the epithelioid type is rare and aggressive, with an average survival of 9 months after diagnosis [1]. In our case, there were multiple diagnostic delays, and time from presentation to the clinic and to death was 6 months. While our patient had no reported exposures, primary pulmonary angiosarcoma is seen after radiation exposure for chest wall tumours and after mastectomy [1, 2]. Other possible carcinogens are thorotrast, polyvinyl chloride, and phenylethyl hydrazine. Some cases have been in patients with tuberculosis and silicosis in copper miners [3]. Epithelioid cancer cases were present in never smokers as well as people with a long history of cigarette exposure [4].

Our patient presented with acute encephalopathy and hypercalcemia, in contrast to more common presentations of hemoptysis, chest pain, and dyspnea. There have also been some reported incidences of Horner's syndrome and hoarseness [5]. Haemorrhage theoretically occurs due to vascular involvement by tumour cells. The epithelioid type of pulmonary angiosarcoma has an insidious onset and is diagnosed at late stages (Table 1). Most patients with non‐specific symptoms undergo several diagnostic tests for benign conditions such as pneumonia, pulmonary tuberculosis, good pastures syndrome, ANCA vasculitis, and pulmonary emboli. Radiological findings of primary pulmonary angiosarcoma could be a solitary endobronchial nodule or multiple bilateral lymphadenopathies with pleural effusions, diffuse pulmonary haemorrhage, or ground‐glass pattern of lung parenchymal inflammation. A CT scan typically shows a solitary nodule or multiple modules with pleural effusions; some cases have had multiple masses with heterogeneous density and irregular contour. Nodules typically range from 0.5 cm to 2 cm and could present with or without ground‐glass opacities. Some cases had pleural thickening on imaging, while upper lobe and lower lobe involvements are equivalent [6]. Our patient's diagnostic imaging revealed a large lingular mass with metastatic lesions to the iliac crest. Our case presented a diagnostic challenge with many benign diagnoses given the small‐sized bilateral pleural effusions and singular mass on the left lingula. Similar to our case, diagnostic delays have been reported due to the techniques used to obtain biopsy samples. The biopsy varies based on the location of the mass and patient characteristics. Due to its rarity, literature lacks comparative analysis of bronchoscopy, CT‐guided biopsy, VATS, or robotic biopsy for epithelioid pulmonary cancers. Existing literature on reported cases suggests that video‐assisted thoracoscopy has the highest diagnostic yield but is associated with a higher risk of bleeding. Cases report diagnosis with VATS after a failed bronchoscopy or in the setting of pneumothorax. Computed tomography‐guided percutaneous biopsy has a good yield if the lesions are peripheral. Robotic‐assisted bronchoscopy offers precision‐based acquisition of samples with minimal procedural complications. Robotic bronchoscopy provides endoscopic vision and navigation path, making it an ideal modality for small tumours. Once the bronchoscope reaches the planned location, it can be locked in that position, providing stability to attain multiple samples as compared to the conventional biopsy. Robotic bronchoscopy has a yield of 80%–90% for pulmonary malignancies and lowest rate of pneumothorax when compared to non‐robotic bronchoscopy, VATS, CT CT‐guided biopsy. It has high yield results even for small nodules with < 1% of major bleeding risk [7].

TABLE 1.

Reported cases of primary pulmonary angiosarcoma and their characteristics.

Author	Year	Symptoms	Size	Nodule site	Mode of resection
Carillo	2012	Hemoptysis	2.5 cm	Apical LLL	CT guided transthoracic
Faiek	2019	Chest pain	N/A	Anterior Mediastinal	Video assisted thoracoscopy
Lin	2023	Coughlhemoptysis	5.5 × 4.8 cm	RUL	Lobectomy
Onyszczuk	2025	Hemoptysis	1.5 cm	Multiple	Autopsy
Ott	1987	Dyspnea	12 cm × l3 cm	Right Hilar Mass	Exploratory Thoracotomy
Ozecelic	2006	Hemoptysis, weight loss	3.5 cm	Posterior Segment (RUL)	Exploratory Thoracotomy
Pavlio	1987	Hemoptysis, Chest Pain	N/A	Right Lung	Pneumectomy
Segal	1988	Dyspnea, Chest Pain	N/A	RightLm1g	Open Lm1g Biopsy
Shirey	2018	Dyspnea	3.4 × 2.7 cm	RUL	Transbronchial FNA
Tahir	2024	Dyspnea, Chest Pain	2.68 cm × 2.61 cm	Right Lung Mass	Thoracotomy
Tochigi	2011	Asymptomatic	2 cm	Right Upper Lobe	Right Upper Lobectomy
Veeraddana	2023	Dyspnea, Chest Pain	N/A	RightLm1g	Video Assisted Thoracoscopy
Wuest	2023	Weight loss, hemoptysis	N/A	Multiple B/L	Video Assisted Thoracoscopy
Yang	2018	Hemoptysis	9.8 cm × 5.5 cm × 7.4 cm	Upper Lobe of Right Lung	FNABiopsy
Yu	2022	Cough, hemoptysis	N/A	Pleural nodule	CT guided lung biopsy

Diagnostic yield is > 90% for lesions ranging from 2 to 3 cm and decreasing to 70% with nodules < 2 cm. In a few reported cases, non‐robotic bronchoscopy was futile due to massive hemoptysis, a frequent presentation of epithelioid pulmonary angiosarcoma. Our patient underwent an inconclusive CT‐guided biopsy of the left lingula and skeletal metastasis at the ileum. Therefore, a decision was made to perform robotic bronchoscopy. Existing literature is limited to diagnosis from lobectomy or video‐assisted thoracoscopic surgery, while bronchoscopy was rarely successful in yielding a diagnostic sample. This is the first reported case of a successful diagnosis of primary pulmonary angiosarcoma diagnosed using a navigational biopsy. While the diagnostic yield of navigational biopsy is non‐inferior when compared to transthoracic needle biopsy, it significantly reduces the risk of iatrogenic pneumothorax [8].

Histopathological sampling and immunostaining are gold standards for the diagnosis of pulmonary angiosarcoma. The varying histological presentation of pulmonary angiosarcoma necessitates the use of immunostaining to confirm the finding. The findings can range from well‐differentiated epithelioid sheet cells to mitosis, a high nucleus‐to‐cytoplasmic ratio, and abundant eosinophilic cytoplasm typical of epithelioid cells interconnected by poorly formed vascular spaces in undifferentiated type angiosarcomas. The epithelioid type has vimentin cells. In a review of 14 cases of PEA factor VIII, it was positive for 13 cases. Additionally, CD31, CD34, FL‐1, and ERG. Found on endothelial cells, CD31 is the most sensitive and specific marker found in most cases. Specifically, with epithelioid types, tissues are strongly positive for vimentin. VWF, CD 31, and CD 34 are also positive in Kaposi sarcoma and can make the diagnosis challenging; in contrast, PEA is also positive for keratin, not found in Kaposi sarcoma.

Owing to the scarcity of cases and limited survival after diagnosis, chemotherapy options are understudied. Doxorubicin, paclitaxel, metastatic lesion, Sintilimab, and apatinib are therapies for metastasis. Variable treatment modalities have been reported, including surgical resection, radiotherapy with and without chemotherapy, and immunotherapy. In one case with a 2 × 2.5 cm size, surgical resection resulted in a 59‐month postoperative survival. Docetaxel and gemcitabine combinations have been used to treat sarcomas, with one case reporting a complete radiological response [9]. Their combination increases the efficacy of gemcitabine in particular, as Docetaxel downregulates bcl‐2 expression and increases cell metabolism and incorporation of the drug in cells [10].

There have also been reported cases of PDL1 expression on some pulmonary angiosarcomas, and these tumours benefited from pembrolizumab infusions, particularly in Stage IV cancers [11]. Another emerging therapy includes an antiangiogenic drug such as bevacizumab. To summarize, while some reported cases have shown response with chemotherapy, early surgical resection remains the first line and mainstay treatment for primary pulmonary angiosarcoma. Literature is scarce, and more evidence is needed to improve diagnostic and treatment standardization in the future.

Patients with primary pulmonary angiosarcoma face a grim prognosis due to the aggressive and rapidly progressive nature of the disease. While one case reported a patient's survival for 15 months, eight others were too frail for chemotherapy [12]. The clinical course can be complicated by severe events, such as diffuse alveolar haemorrhage leading to death [13], or pathological bone fractures [2]. Despite these challenges, there are rare cases of patients achieving partial remission, or even surviving with only a lung wedge resection, without the need for chemotherapy or radiation [14]. In one reported case, a patient with co‐occurring adenocarcinoma of the rectum and prostate recovered with chemotherapy [15]. However, a common outcome is a very short survival period, with one patient reported to have died just 3 months after diagnosis [16].

In conclusion, pulmonary angiosarcoma is an extremely rare and aggressive type of malignancy. Its clinical course is often complicated by diagnostic challenges due to pulmonary lesions being misdiagnosed as an infectious or inflammatory process. Pulmonary angiosarcoma typically manifests as non‐specific small lesions, which can reduce the diagnostic yield of conventional bronchoscopy. Early robotic bronchoscopy is a modality in such cases that can lead to diagnostic accuracy and early initiation of treatment.

Author Contributions

All authors meet criteria for authorship. Both authors contributed to the conception and design of the study, data collection, analysis and interpretation of data, drafting and critical revision of the manuscript, and approved the final version for submission. Both authors agree to be accountable for all aspects of the work.

Consent

The authors declare that written informed consent was obtained for the publication of this manuscript and accompanying images using the consent form provided by the Journal.

Conflicts of Interest

The authors declare no conflicts of interest.

Jawed S. and Sivatej S., “Primary Pulmonary Angiosarcoma: Case Report and Literature Review,” Respirology Case Reports 14, no. 7 (2026): e70668, 10.1002/rcr2.70668.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.