Pulmonary artery intimal sarcoma masquerading as pulmonary embolism during therapeutic apixaban: A case report

Abstract

Pulmonary artery intimal sarcoma (PAIS) is a rare intravascular malignancy that can closely resemble pulmonary embolism (PE). A 65-year-old man receiving therapeutic apixaban for atrial fibrillation presented with 3 weeks of progressive exertional dyspnea. Computed tomography pulmonary angiography showed a large unilateral filling defect in the left main pulmonary artery with occlusion of the left upper- and lower-lobe branches, initially interpreted as PE. However, the D-dimer was low, bilateral lower-extremity ultrasonography showed no deep venous thrombosis, cardiac biomarkers were normal, and echocardiography showed preserved right ventricular size and function without pulmonary hypertension. Contrast-enhanced chest magnetic resonance imaging demonstrated an enhancing lobulated, frond-like proximal pulmonary artery mass with mild arterial expansion and a separate distal nonenhancing component consistent with bland thrombus. Pulmonary thromboendarterectomy with tumor debulking confirmed high-grade PAIS. The patient subsequently received doxorubicin, ifosfamide, and mesna with pembrolizumab followed by proton radiotherapy. This case emphasizes that a unilateral central pulmonary artery filling defect should prompt tumor-directed imaging when the thromboembolic burden is discordant with biomarkers, venous imaging, and right-heart physiology.

1. Introduction

Pulmonary artery intimal sarcoma (PAIS) is a rare malignant tumor arising from the intimal layer of the pulmonary artery. Its clinical presentation overlaps substantially with acute and chronic pulmonary embolism (PE): patients commonly develop progressive dyspnea or chest discomfort, while computed tomography pulmonary angiography (CTPA) demonstrates an intraluminal filling defect. Because thromboembolic disease is far more common, PAIS is frequently treated initially with anticoagulation, and diagnostic delay can narrow the opportunity for surgical resection [1,2].

Certain clinical and imaging findings should prompt reconsideration of PE. These include a unilateral central dominant lesion, expansion of the involved artery, lobulated or frond-like morphology, contrast enhancement, fluorodeoxyglucose uptake, absence of a venous thromboembolic source, and persistence or progression despite adequate anticoagulation [1,3]. We report a patient receiving therapeutic apixaban whose apparent massive left pulmonary artery embolus was ultimately diagnosed as PAIS after contrast-enhanced magnetic resonance imaging (MRI) demonstrated an enhancing tumor with adjacent bland thrombus.

2. Case presentation

2.1. Patient information and clinical course before admission

A 65-year-old man presented in February 2025 with 3 weeks of progressive exertional dyspnea. His history included paroxysmal atrial fibrillation diagnosed in December 2024, hyperlipidemia, class I obesity, positional obstructive sleep apnea, remote coronavirus disease 2019 pneumonia with mild residual dyspnea, recurrent precancerous colonic polyps, and previously excised basal cell carcinomas. A germline multigene cancer panel performed in 2021 had shown no pathogenic variants or variants of uncertain significance. He had no history of venous thromboembolism or known thrombophilia.

After the diagnosis of atrial fibrillation, he began diltiazem and apixaban 5 mg twice daily. Transthoracic echocardiography on December 3, 2024 showed a left ventricular ejection fraction of 62%, normal right ventricular size and function, and an estimated right ventricular systolic pressure of 30 mmHg. A stress echocardiogram later that month was negative for ischemia.

In mid-January 2025, after air travel to a high-altitude destination, he developed progressive dyspnea on exertion. His exercise tolerance declined from 30 to 40 minutes of stationary cycling to dyspnea after walking one city block. He also reported fatigue, occasional dry cough, and mild pleuritic left-sided chest discomfort. He denied symptoms at rest, leg swelling, hemoptysis, or syncope and reported strict adherence to apixaban.

2.2. Initial assessment

At outpatient evaluation on February 10, 2025, oxygen saturation was 97% on room air at rest and decreased to approximately 92% with ambulation. Pulmonary function testing and chest radiography were unrevealing. CTPA demonstrated a large filling defect centered in the left main pulmonary artery, with complete occlusion of the left upper- and lower-lobe pulmonary arteries and sparing of the lingular artery (Fig. 1). Computed tomographic signs interpreted as right-heart strain were present, but there was no pulmonary infarction, pleural or pericardial effusion, thoracic adenopathy, or pulmonary parenchymal abnormality. The patient was referred to the emergency department and treated for presumed PE with an intravenous heparin bolus and infusion; apixaban was held.

Fig. 1.

Initial computed tomography pulmonary angiography. Axial image demonstrates a large unilateral filling defect centered in the left main pulmonary artery, with near-complete obstruction of the left pulmonary arterial branches.

He remained hemodynamically stable with a blood pressure of 147/98 mmHg, heart rate of 65 beats/min, respiratory rate of 16 breaths/min, and oxygen saturation of 99% on room air. Electrocardiography showed sinus rhythm without ischemic changes. Key laboratory findings are shown in Table 1. The D-dimer was 0.29 mg/L fibrinogen-equivalent units despite ongoing symptoms. High-sensitivity troponin T was 10 ng/L and then 9 ng/L, and N-terminal pro-B-type natriuretic peptide was 29 pg/mL and then 34 pg/mL. Bilateral lower-extremity venous ultrasonography showed no deep venous thrombosis. A limited echocardiogram on February 11 showed normal right ventricular size and function, no echocardiographic right-heart strain, no pulmonary hypertension, and a left ventricular ejection fraction of 56%.

Table 1.

Key admission laboratory findings.

Test	Result
White blood cell count	7.0 × 109/L
Hemoglobin	13.3 g/dL
Platelet count	279 × 109/L
Creatinine	0.90 mg/dL
Aspartate/alanine aminotransferase	39/49 U/L
High-sensitivity troponin T	10 then 9 ng/L
N-terminal pro-B-type natriuretic peptide	29 then 34 pg/mL
D-dimer	0.29 mg/L FEU

FEU, fibrinogen-equivalent units.

2.3. Diagnostic reassessment and tumor-directed imaging

The apparent size of the pulmonary arterial obstruction was discordant with the low D-dimer, absence of deep venous thrombosis, normal cardiac biomarkers, preserved right ventricular function, and therapeutic anticoagulation. The differential diagnosis was therefore expanded to include chronic organized thrombus, primary pulmonary artery tumor, and less likely metastatic or inflammatory intravascular disease. Computed tomography of the abdomen and pelvis showed no definite primary malignancy or metastasis.

Contrast-enhanced chest MRI was obtained on February 11. It showed a filling defect in the left main pulmonary artery extending into the left upper- and lower-lobe branches, with mild secondary expansion of the involved artery. The proximal component measured at least 3.3 × 3.7 × 2.5 cm and had a lobulated, frond-like appearance, heterogeneous internal signal, small central cystic spaces, and mild peripheral and subtle central enhancement (Fig. 2). A smoother distal component did not enhance and was favored to represent adjacent bland thrombus. These findings shifted the leading diagnosis from PE to pulmonary artery neoplasm. Because local surgical services were unavailable, the patient was transferred to a tertiary cardiothoracic center while receiving intravenous heparin.

Fig. 2.

Tumor-directed contrast-enhanced magnetic resonance imaging. (A) Axial and (B) coronal images demonstrate a lobulated, frond-like enhancing mass centered in the left main pulmonary artery with mild arterial expansion, favoring neoplasm rather than bland thrombus.

2.4. Management and pathology

Right- and left-heart catheterization on February 13 showed normal right-sided filling pressures and no pulmonary hypertension: right atrial pressure 5 mmHg, pulmonary artery pressure 28/11 mmHg (mean 18 mmHg), pulmonary capillary wedge pressure 9 mmHg, and cardiac index 2.86 L/min/m². Coronary angiography demonstrated multivessel coronary artery disease, including approximately 70% stenoses of the mid-left anterior descending, right coronary, and obtuse marginal arteries.

On February 14, the patient underwent pulmonary thromboendarterectomy with excision and maximal debulking of the pulmonary artery mass, 2-vessel coronary artery bypass grafting using the left internal mammary artery to the left anterior descending artery and a saphenous vein graft to an obtuse marginal branch, and left atrial appendage ligation. The pulmonary artery lesion was invasive, and gross residual tumor remained after maximal debulking. Preliminary intraoperative pathology identified a spindle cell sarcoma.

Final pathology confirmed a high-grade spindle cell sarcoma consistent with PAIS, with marked pleomorphism and brisk mitotic activity. Immunohistochemistry was positive for SATB2. Tumor profiling showed loss of MLH1 and PMS2, consistent with mismatch-repair deficiency; programmed death-ligand 1 expression was 2%; NTRK testing was negative; and MDM2 amplification was absent by fluorescence in situ hybridization. Extended profiling identified a CD164-ALK fusion, amplifications of KIT, PDGFRA, CDK4, and KDR, and TP53 alterations. Staging computed tomography, brain MRI, and postoperative positron emission tomography showed no definite metastatic disease.

2.5. Outcome and follow-up

The postoperative course was complicated by hypoxemic respiratory failure attributed to reperfusion lung injury, vasodilatory shock, atrial fibrillation and flutter, transient acute kidney injury, anemia, transaminitis, and a small pericardial effusion. He was extubated on postoperative day 3, weaned from inhaled nitric oxide by February 19, and ultimately weaned to room air. He was discharged home on March 1, 2025, with apixaban 5 mg twice daily resumed along with aspirin, a statin, and metoprolol.

Adjuvant treatment began in March 2025 with doxorubicin, ifosfamide, and mesna (AIM) plus pembrolizumab, selected in part because of mismatch-repair deficiency. The first cycle caused severe thrombocytopenia and neutropenia requiring platelet transfusion. After 2 initial cycles, he completed 7 weeks of proton radiotherapy on July 10, 2025. Imaging shortly thereafter showed radiation- and checkpoint-inhibitor-associated pneumonitis, which improved with prednisone. Systemic treatment was resumed, and his last documented medical therapy was liposomal doxorubicin plus pembrolizumab in November 2025.

Follow-up CTPA in November 2025 showed no recurrent PE and stable irregularity at the left pulmonary artery resection site without a new intraluminal mass. Post-radiation changes and a small left pleural effusion were present. By April to June 2026, he remained independent in activities of daily living but continued to experience exertional dyspnea, especially on inclines. Echocardiography showed preserved biventricular systolic function and normal estimated pulmonary artery pressure. The pleural effusion remained too small for safe bedside drainage and was managed conservatively. He was referred for cardiopulmonary exercise testing and rehabilitation.

3. Clinical timeline

Date	Event
December 2024	Atrial fibrillation diagnosed; apixaban started. Baseline echocardiogram showed normal right ventricular function and no pulmonary hypertension.
Mid-January 2025	Progressive exertional dyspnea developed after air travel.
February 10, 2025	CTPA interpreted as a large left main pulmonary artery embolus; intravenous heparin started.
February 10-11, 2025	Low D-dimer, no DVT, normal biomarkers, and normal right ventricular function were discordant with massive PE.
February 11, 2025	Contrast-enhanced MRI demonstrated an enhancing pulmonary artery mass with adjacent bland thrombus.
February 14, 2025	Pulmonary thromboendarterectomy and tumor debulking with CABG ×2 and left atrial appendage ligation.
February-March 2025	Pathology confirmed high-grade PAIS; staging showed no definite metastasis.
March-July 2025	AIM plus pembrolizumab followed by proton radiotherapy.
July-November 2025	Treatment-related pneumonitis treated with prednisone; systemic therapy resumed.
November 2025-June 2026	No recurrent intraluminal tumor reported; persistent exertional dyspnea managed with rehabilitation planning.

4. Discussion

PAIS is one of the most challenging mimics of pulmonary thromboembolism because both conditions produce pulmonary arterial filling defects and progressive cardiopulmonary symptoms. In published series and case reports, the initial diagnosis is commonly PE, with weeks or months of anticoagulation before recognition of malignancy [1,2]. The principal educational value of this case is a practical approach to clinical-imaging discordance rather than rarity alone.

Several features argued against routine thromboembolism. The lesion was unilateral, central, and dominant rather than bilateral, multifocal, and branching. Symptoms developed while the patient reported adherence to therapeutic apixaban. The D-dimer remained low despite active symptoms, no lower-extremity DVT was identified, and neither biomarkers nor echocardiography supported meaningful right ventricular pressure overload. Each finding alone is nonspecific, but their combination substantially reduced confidence in a thromboembolic diagnosis. In a hemodynamically stable patient, this discordance justified additional tissue-characterizing imaging rather than immediate thrombolysis or escalation of anticoagulation.

Cross-sectional imaging can help distinguish PAIS from bland thrombus. Tumor-favoring findings include arterial expansion, lobulated or bulging contours, a wall-eclipsing pattern, heterogeneous attenuation or signal, and contrast enhancement [3,4]. Bland thrombus is usually smoother, homogeneous, and nonenhancing. MRI was decisive in this patient because it showed an enhancing frond-like proximal mass and a separate nonenhancing distal thrombus. This distinction also illustrates that tumor and bland thrombus may coexist; identifying a thrombotic component does not exclude an underlying pulmonary artery neoplasm.

Surgery remains the cornerstone of treatment for localized PAIS, both to relieve obstruction and obtain definitive tissue diagnosis. Pulmonary endarterectomy, resection, or debulking is frequently followed by chemotherapy and/or radiotherapy, although evidence is limited to retrospective series and case reports because of the rarity of the disease [2,5]. The molecular profile of intimal sarcoma often includes MDM2, CDK4, and PDGFRA pathway alterations, but heterogeneity is recognized [5]. In this case, CDK4 and PDGFRA were amplified despite absence of MDM2 amplification. Loss of MLH1 and PMS2 informed the decision to include pembrolizumab, although the optimal systemic regimen for PAIS remains undefined.

This report has strengths including contemporaneous multimodality imaging, invasive hemodynamic assessment, surgical pathology, molecular characterization, and follow-up beyond 1 year. Limitations include the single-patient design, incomplete operative margin data, inability to establish the independent contribution of each adjuvant modality, and absence of a formal patient-perspective statement. Nevertheless, the case supports a reproducible diagnostic principle: when the distribution and apparent burden of a pulmonary arterial filling defect do not match the biomarker, venous, echocardiographic, and anticoagulation context, clinicians should reconsider PE and pursue tumor-directed imaging and early surgical consultation.

5. Conclusion

A unilateral central pulmonary artery filling defect should not be assumed to represent thrombus when the clinical and physiologic findings are discordant. In this patient receiving therapeutic apixaban, a low D-dimer, absent DVT, normal cardiac biomarkers, and preserved right ventricular function prompted contrast-enhanced MRI, which differentiated an enhancing pulmonary artery tumor from adjacent bland thrombus. Early recognition allowed surgical diagnosis and multidisciplinary treatment of high-grade PAIS.

Patient perspective

A formal patient-perspective statement was not available for inclusion.

Ethics approval and informed consent

Formal ethics committee approval was not required under institutional policy for this single-patient case report. Written informed consent was obtained from the patient for publication of the clinical information and accompanying images. The original consent form is held by the treating institution.

Data availability

All data relevant to this case are included in the article. Additional patient-level clinical data are not publicly available because of privacy and confidentiality considerations.

Declaration of generative AI and AI-assisted technologies in the manuscript preparation process

During the preparation of this work, the author used ChatGPT (OpenAI) to assist with manuscript organization, language editing, and formatting. The author reviewed and edited all content, verified the clinical information and references, and takes full responsibility for the content of the article. Generative AI was not used to create or alter the submitted clinical images.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

The author declares that there are no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript.