A Comprehensive Insight Into Primary Intimal Sarcoma of the Pulmonary Artery; From Diagnosis to Management: A Case Report and Review of the Literature

ABSTRACT

Primary intimal sarcoma of the pulmonary artery is a rare and aggressive malignancy that presents significant diagnostic and therapeutic challenges due to its nonspecific symptoms and propensity for late detection. This case report aimed to elucidate the diagnostic journey, surgical intervention, and multidisciplinary management of this rare entity. In September 2023, a 42‐year‐old male presented with dyspnea on exertion and retrosternal chest pain, classified as NYHA FC II. Initial investigations, including ECG and lab tests, indicated tachycardia and elevated troponin and NT‐pro‐BNP levels. Transthoracic and transesophageal echocardiography identified a multilobulated mass in the right ventricular outflow tract and main pulmonary artery. Cardiac MRI and CT angiography confirmed a high‐grade pleomorphic spindle cell tumor, leading to surgical resection in October 2023. Histopathology confirmed intimal sarcoma. Postsurgery, the patient underwent chemotherapy and radiotherapy, showing significant clinical improvement and no recurrence on follow‐up PET‐CT. This case highlights the importance of a multidisciplinary approach in diagnosing and managing primary intimal sarcoma of the pulmonary artery, emphasizing the role of advanced imaging, timely surgical intervention, and combined chemotherapy with radiotherapy in improving patient outcomes.

Abbreviations

CK

cytokeratin

CMR

cardiac magnetic resonance

CPB

cardiopulmonary bypass

CPTE

chronic pulmonary thromboembolism

CT

computed tomography

DOE

dyspnea on exertion

EBUS

endobronchial ultrasound

EBUS‐TBNA

endobronchial ultrasound‐guided transbronchial needle aspiration

ECG

electrocardiogram

FDG

fluorodeoxyglucose

IHC

immunohistochemistry

ISPA

intimal sarcoma of the pulmonary artery

LGE

late gadolinium enhancement

LPA

left pulmonary artery

LVEF

left ventricular ejection fraction

MPA

main pulmonary artery

MRI

magnetic resonance imaging

NT‐pro‐BNP

N‐terminal pro B‐type natriuretic peptide

NYHA

New York Heart Association

PA

pulmonary artery

PEA

pulmonary endarterectomy

PET

positron emission tomography

PG

pressure gradient

PS

pulmonic stenosis

PV

pulmonary valve

RPA

right pulmonary artery

RVE

right ventricular enlargement

RVEF

right ventricular ejection fraction

RVOT

right ventricular outflow tract

S4

fourth heart sound

SBRT

stereotactic body radiation therapy

SI

signal intensity

SMA

smooth muscle actin

STIR

short‐tau inversion recovery

STJ

sinotubular junction

T1W

T1‐weighted

T2‐STIR

T2‐weighted short‐tau inversion recovery

TEE

transesophageal echocardiogram

TTE

transthoracic echocardiography

VBG

venous blood gas

VEGFR2

vascular endothelial growth factor receptor 2

WBC

white blood cells

Summary.

• Primary intimal sarcoma of the pulmonary artery, despite its rarity and diagnostic complexity, can be effectively managed through a multidisciplinary approach.

• Early diagnosis, utilizing advanced imaging techniques, combined with prompt surgical resection and adjuvant chemotherapy and radiotherapy, can significantly improve patient outcomes and reduce recurrence risk.

1. Background

Primary intimal sarcoma of the pulmonary artery (ISPA), a rare malignant mesenchymal tumor, challenges the realms of medical comprehension, with a scant 400 documented cases in the literature [1, 2]. Originating from the intimal layer of the vascular wall, this formidable adversary obstructs the lumen, infiltrates the vascular wall, and poses a significant risk of distant metastasis. Its elusive presentation often masquerades as more prevalent pulmonary vascular diseases like chronic pulmonary thromboembolism (CPTE) [1]. Moreover, sophisticated diagnostic tools such as high‐resolution CT scans, color Doppler echocardiography, and molecular testing have revolutionized the identification and differentiation of this rare malignancy [1]. Refined diagnostic criteria, shaped by imaging advancements and molecular insights, guide precise diagnoses. Surgical resection remains the cornerstone of ISPA management, with the extent of resection influencing outcomes [1]. Adjuvant therapies, including radiotherapy and chemotherapy, are areas of ongoing research to complement surgical interventions [3]. The prognosis, while guarded, emphasizes the critical role of early intervention, particularly through surgical resection, in prolonging survival. Here, we present a case report of ISPA and discuss its challenges from diagnosis to treatment.

2. Case Presentation

A 42‐year‐old male presented with exertional dyspnea and retrosternal chest pain, classified as New York Heart Association (NYHA) Functional Class II, in September 2023. The symptoms appeared abruptly a month earlier in August 2023 and only occurred during mild activity. The patient had no prior medical history, cardiovascular risk factors, abnormalities in cholesterol levels, smoking status, obesity, or family history of cardiovascular disease. On physical examination, a systolic ejection murmur was heard at the left upper sternal border, along with a diastolic murmur, an accentuated P2, and a right‐sided S4. ECG showed sinus tachycardia. Laboratory results were normal except for mild elevations in troponin (0.2 ng/mL), NT‐pro‐BNP (1350 pg/mL), and venous blood gas (VBG) indicating mixed respiratory and metabolic acidosis (pH = 7.32, pCO₂ = 5 mmHg, pO₂ = 35 mmHg, HCO₃ = 20 mEq/L).

2.1. Clinical Evaluation

The patient was referred to cardiology, where a transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) revealed a semimobile, multilobulated mass in the right ventricular outflow tract (RVOT), and main pulmonary artery (MPA). The mass extended into the pulmonary valve, causing significant RVOT and pulmonary valve stenosis. Measuring 2.7 × 5.7 cm (axial) and 3.7 cm (coronal), the mass warranted further investigation. The right ventricular ejection fraction (RVEF) was 30%, and the left ventricular ejection fraction (LVEF) was 55% (Figure 1).

FIGURE 1.

Transesophageal Echocardiogram (short axis view) of a 44‐year‐old patient diagnosed with ISPA. This transesophageal echocardiogram reveals a large, multilobular, broad‐based mass (indicated by the arrow) measuring approximately 5.7 × 2.7 cm. The mass demonstrates tissue‐like echotexture with vascularity, originating from the arterial aspect of the pulmonary valve (PV) leaflet. It extends into both the main pulmonary artery (MPA) and right pulmonary artery (RPA), causing significant systolic turbulence in these regions. This flow disturbance contributes to moderate pulmonary stenosis (PS) with a peak gradient of 59 mmHg. Additionally, the left ventricular ejection fraction (LVEF) is moderately preserved at 55%, while the right ventricular ejection fraction (RVEF) is significantly reduced at 30%, indicative of compromised right ventricular function. ISPA, intimal sarcoma of the pulmonary artery; LVEF, left ventricular ejection fraction; MPA, main pulmonary artery; PS, pulmonic stenosis; PV, pulmonary valve; RPA, right pulmonary artery; RVEF, right ventricular ejection fraction.

2.2. Imaging Insights

Multislice spiral computed tomography (CT) angiography with reconstructed views and dynamic contrast medium provided detailed imaging of the mass. It revealed a 30 mm MPA, mild right ventricular enlargement, and an intraluminal filling defect (3.1 $\times$ 6.1 cm) extending from the right MPA to the right pulmonary artery (RPA) and right upper lobar branch. The differential diagnosis included a primary pulmonary artery mass such as sarcoma or a metastatic mass (Figure 2a–c).

FIGURE 2.

Cardiac CT and MRI Imaging of a 44‐year‐old patient diagnosed with ISPA. CT imaging (axial (a), sagittal (b), coronal (c)) reveals an intraluminal filling defect (6.1 $\times$ 3.1 cm) in the right ventricular outflow tract (RVOT), main pulmonary artery (MPA), and extending into the right pulmonary artery (RPA) and right upper lobar branch, involving the pulmonary valve (PV), consistent with intimal sarcoma. The mass causes significant vessel obstruction, potentially leading to pulmonary hypertension and right ventricular (RV) overload. The axial SSFP sequence (c) shows RV enlargement due to pressure overload. The RVOT view (d) reveals a multilobulated mass infiltrating the pulmonary valve, indicating severe RVOT stenosis and mixed tumor composition. On MRI, the lesion is prominently located in the RVOT and extends into the MPA and RPA, including the right upper lobar branch. The mass, approximately 6.1 × 3.1 cm in size, displays a multilobulated structure. T2‐STIR sequences (e) reveal high signal intensity areas, indicating edema and necrosis, while T1‐weighted images (f) highlight viable tumor tissue. The MRI also shows the mass's encasement of the PV, causing severe RVOT stenosis and significant RV enlargement due to pressure overload. CT, computed tomography; ISPA, intimal sarcoma of pulmonary artery; MPA, main pulmonary artery; MRI, magnetic resonance imaging; PV, pulmonary valve; RPA, right pulmonary artery; RV, right ventricle; RVOT, right ventricular outflow tract; SSFP, steady state‐free precession; T1W, T1‐weighted; T2‐STIR, T2 short‐tau inversion recovery.

2.3. Cardiac MRI Confirmation

Cardiac MRI (CMR) further characterized the mass, showing isosignal on T1, hypersignal on STIR, and mild vascularity on perfusion sequences. Late gadolinium enhancement (LGE) images displayed scattered enhancements, along with hypointensity areas suggesting thrombosis or necrosis. The mass encased the pulmonary valve, restricting its movement (Figure 2d–f). Given the potential for metastasis, positron emission tomography (PET)‐CT was performed to assess for hypermetabolic lesions elsewhere, but no metastases were detected.

2.4. Surgical Intervention and Pathological Evaluation

Due to the large multilobulated mass in the RVOT and MPA, which extended into the pulmonary valve and caused significant stenosis, surgery was performed in October 2023 to relieve the patient's symptoms of dyspnea and retrosternal chest pain. A large, jelly‐like tumor (3.0 × 6.2 cm), intricately attached to the pulmonary artery, pulmonary valve, RVOT, left pulmonary artery (LPA), and right pulmonary artery (RPA), was excised. Endarterectomy was performed on the pulmonary artery, RPA, and LPA, followed by careful repair and reconstruction (Figure 3).

FIGURE 3.

Surgical treatment of a 44‐year‐old patient diagnosed with ISPA. The patient underwent surgery to address a large jelly tumor measuring 3.0 × 6.2 cm. The tumor had an extensive base attached to the pulmonary artery (PA), pulmonary valve (PV), right ventricular outflow tract (RVOT), left pulmonary artery (LPA), and right pulmonary artery (RPA). The aorta was transected above the sinotubular junction (STJ). The RPA was fully opened, and an endarterectomy was performed on the PA, RPA, and LPA. The tumor was nearly completely removed, with a small residual portion penetrating the artery in the upper lobe of the right lung. The RPA was repaired using a pericardial patch, with its branches connected to the RPA and LPA via a pulmonary homograft, and the proximal segment was reattached to the RVOT. ISPA, intimal sarcoma of pulmonary artery; LPA, left pulmonary artery; PA, pulmonary artery; PV, pulmonary valve; RPA, right pulmonary artery; RVOT, right ventricular outflow tract; STJ, sinotubular junction.

2.5. Histopathological Findings

Histopathological examination of the resected tumor revealed a cellular spindle cell mass with pleomorphic cells, characterized by hyperchromatic oval‐to‐spindle nuclei and poorly defined pink cytoplasm within a myeloid stroma. Immunohistochemical (IHC) staining was negative for CK, S100, CD34, calretinin, SMA, desmin, myogenin, CD31, and ERG markers. However, Ki‐67 staining showed a 50% proliferation rate in tumor cells. These findings confirmed the diagnosis of a high‐grade pleomorphic spindle cell tumor consistent with intimal sarcoma.

2.6. Oncological Management and Follow‐Up

Chemotherapy began in January 2023, with the patient receiving four cycles of gemcitabine and docetaxel (Taxotere), administered every 3 weeks. Gemcitabine (1000 mg/m²) was given on Days 1 and 8 of each cycle, while docetaxel (75 mg/m²) was given on Day 8. This was followed by 30 sessions of radiotherapy from May 1 to June 14, 2023, totaling 60 Gy.

A multidisciplinary team of oncologists, cardiothoracic surgeons, radiologists, and pathologists provided coordinated care throughout the treatment. Regular follow‐ups were conducted to monitor the patient's recovery and manage potential side effects. In November 2023, a PET‐CT scan, conducted 4 months postsurgery and 1 month after chemotherapy, revealed no hypermetabolic lesions in the pulmonary artery or elsewhere, suggesting no recurrence of the disease.

By May 2024, the patient reported significant clinical improvement, with no signs of shortness of breath or chest pain. Follow‐up evaluations confirmed stable cardiovascular function (LVEF 55%, RVEF 45%), normal levels of troponin and NT‐pro‐BNP, and a normal sinus rhythm on ECG, indicating a successful response to the comprehensive oncological treatment.

3. Discussion

ISPA is a rare and aggressive malignancy, accounting for only 0.001%–0.003% of tumors, with onset ranging from 2 months to 89 years of age, predominantly affecting females [4, 5]. Due to its nonspecific symptoms and imaging similarities to pulmonary embolism, ISPA is frequently misdiagnosed, delaying accurate diagnosis, and significantly impacting treatment outcomes [2, 5]. This section explores innovative treatment approaches and the challenges in managing ISPA.

3.1. Surgical Interventions

Surgical resection of ISPA, combined with pulmonary endarterectomy (PEA) via cardiopulmonary bypass and deep hypothermic circulatory arrest, has been shown to maximize tumor removal in nonmetastatic cases. Despite aggressive surgical measures, the average survival time postsurgery is around 11.6 months, with a high risk of recurrence [6]. However, studies suggest that more extensive surgical resections, including right pneumonectomy and reconstruction, can prevent relapse and improve survival rates, with one case showing disease‐free survival 16 months postsurgery [7].

3.2. Chemotherapy

Traditional chemotherapy regimens, particularly those based on doxorubicin, have shown poor outcomes for ISPA patients. A 2008 study by Penel et al. [8] revealed a median survival of only 8 months among eight patients treated with doxorubicin. Similarly, a 2023 meta‐analysis by Tanaka et al. [9] confirmed that while doxorubicin remains a standard treatment for soft tissue sarcomas, combination therapies have not significantly improved survival. Alternative chemotherapy regimens, such as ifosfamide and epirubicin, have shown tumor regression in select cases, though side effects often limit their use. Newer combinations, such as vinorelbine and cisplatin, have demonstrated promising results in heavily pretreated patients [1].

In our case, we employed a combination of gemcitabine and docetaxel (Taxotere), which resulted in significant clinical and imaging improvement 4 months postchemotherapy. However, due to short‐term follow‐up, long‐term efficacy remains uncertain.

3.3. Adjuvant and Neoadjuvant Radiotherapy

While surgery remains the cornerstone of ISPA treatment, adjuvant radiotherapy has shown promise in controlling tumor progression. For example, a case study by Allen et al. highlighted the use of neoadjuvant radiotherapy to reduce tumor size before surgery, enabling successful tumor removal and disease control [3]. Similarly, Romanowska et al. reported that adjuvant radiotherapy effectively controlled local disease postresection, with no recurrence [10]. In our case, the patient underwent 30 sessions of radiotherapy, delivering a total of 60 Gy, and subsequent PET‐CT scans revealed no hypermetabolic lesions, suggesting successful disease control.

Table 1 provides a survey of various treatment approaches and their outcomes, offering insights into the evolving management of ISPA.

TABLE 1.

Summary of treatment options with their case implication for ISPA.

Treatment option	Case implication
Surgical resection [1, 4, 6]	Complete surgical resection with pulmonary endarterectomy (PEA) is the primary treatment. It may involve extensive reconstructive measures and cardiopulmonary bypass.
Neoadjuvant radiation [3]	Preoperative radiotherapy to improve resectability in cases of borderline resectable tumors.
Adjuvant chemotherapy [1]	Chemotherapy after surgery to reduce the risk of recurrence. Drugs used include doxorubicin, cisplatin, and ifosfamide.
Pazopanib therapy [1]	Use of the tyrosine kinase inhibitor pazopanib for unresectable or recurrent tumors.
Radiotherapy [1]	Postoperative radiotherapy to control local recurrence.
Combination chemotherapy [1]	Use of combination chemotherapy regimens like ifosfamide and epirubicin, or vinorelbine and cisplatin for inoperable or recurrent cases.
Targeted therapy with apatinib [11]	Use of the VEGFR2 inhibitor apatinib for recurrent cases.
Stereotactic body radiation Therapy (SBRT) [12]	Use of SBRT for treating lung metastases and delaying palliative chemotherapy.
Chemotherapy with gemcitabine and docetaxel [3]	Postoperative use of gemcitabine and docetaxel for recurrent cases.
Ex vivo lung autotransplantation [13]	Use of lung autotransplant techniques for the treatment of pulmonary artery sarcoma.

Abbreviations: CPB: cardiopulmonary bypass; PEA: pulmonary endarterectomy; SBRT: stereotactic body radiation therapy; TKI: tyrosine kinase inhibitor; VEGFR2: vascular endothelial growth factor receptor 2.

3.4. Diagnostic Challenges and Misdiagnosis

Accurate diagnosis of intimal sarcoma of the pulmonary artery (ISPA) requires a multimodal imaging approach, utilizing CT, MRI, PET, echocardiography, and endobronchial ultrasound‐guided needle aspiration (EBUS‐NA). Each imaging modality offers distinct advantages, helping to differentiate ISPA from conditions like pulmonary thromboembolism, ultimately guiding appropriate treatment, and improving prognosis [1]. Table 2 includes multiple imaging modalities with their insight through ISPA diagnosis.

TABLE 2.

Different imaging findings and their features in the diagnosis of ISPA.

Imaging insight	Description
CT [14, 15]	Identifies ISPA through features like tumoral impaction, heterogeneous attenuation, and intratumoral vessels. 3D reconstruction helps differentiate ISPA from thromboembolism.
MRI [15, 16]	Provides high spatial resolution and functional assessment. Shows inhomogeneous delayed enhancement, suggesting intermingled thrombi.
PET [17, 18]	FDG‐PET shows hypermetabolism, distinguishing ISPA from thromboembolism. Low cellularity ISPA may show poor FDG uptake.
Echocardiography [14]	Reveals mass‐like lesions in the pulmonary artery, aiding in diagnosis when combined with other imaging modalities.
EBUS [19]	EBUS‐TBNA provides real‐time imaging of lymph nodes and pulmonary arteries, useful for obtaining tissue samples and definitive preoperative diagnosis.

Abbreviations: CT: computed tomography; EBUS: endobronchial ultrasound; EBUS‐TBNA: endobronchial ultrasound‐guided transbronchial needle aspiration; FDG: fluorodeoxyglucose; MRI: magnetic resonance imaging; ISPA: intimal sarcoma of pulmonary artery; PET: positron emission tomography.

The definitive diagnosis is based on histopathological examination following surgical resection. Immunohistochemistry (IHC) is essential, with ISPA tumors often testing positive for markers such as vimentin, smooth muscle actin (SMA), and MDM2. However, differentiating ISPA from other sarcomas, such as leiomyosarcoma, can be challenging in the absence of typical morphologic features [1]. In our case, IHC staining of the surgical sample, including Ki‐67 proliferation activity, confirmed the diagnosis of high‐grade pleomorphic spindle cell intimal sarcoma. Key histological features of ISPA are summarized in Table 3.

TABLE 3.

Histological findings of ISPA with their features description.

Histological features	Description
Sclerosing extracellular matrix [20]	Sclerosing appearance with few spindle/pleomorphic cells, often confused with chronic thromboembolic pulmonary hypertension.
Spindle and pleomorphic cells [20, 21]	The proliferation of atypical spindle and pleomorphic cells within a myxomatous matrix.
Myxoid background [21]	Presence of myxoid matrix in the histological examination.
MDM2 expression [20, 21]	Intense MDM2 expression was observed in tumor cells.
Genetic alterations [21]	Frequent gains and amplifications in the 12q13‐14 region.
Immunohistochemical markers [21]	Strong vimentin expression; focal positivity for alpha‐smooth muscle Actin, CD117, CD68, p53, and bcl2; negative for endothelial markers.
Proliferation index (Ki‐67) [21]	Variable Ki‐67 index ranging from 5% to 80%.
Intimal thickening [22]	Tumor causes arteriosclerosis‐like intimal thickening extending from the main to subsegmental arteries.
Eccentric intimal thickening or recanalization [22]	Observed in distal small arteries due to peripheral tumor emboli or pulmonary hypertension induced by the proximal tumor.
Necrotizing background with low cellularity [18]	Some ISPA cases show low cellularity with a necrotizing background, leading to poor FDG uptake in PET/CT scans.
Cytologic features from EBUS‐TBNA [19, 23]	Pleomorphic malignant spindled cells arranged in loosely cohesive clusters are useful for diagnosis with ancillary studies like immunohistochemistry.

Abbreviations: CT: computed tomography; EBUS‐TBNA: endobronchial ultrasound‐guided transbronchial needle aspiration; FDG: fluorodeoxyglucose; ISPA: intimal sarcoma of pulmonary artery; PET: positron emission tomography.

3.5. Innovative Approaches and Future Directions

Newer targeted therapies, such as apatinib, have shown potential in stabilizing ISPA postsurgery, presenting a promising avenue for future treatment development. In a 2020 case report by Lu & Yin et al. (11), a 44‐year‐old male experienced multiple lesions in the pulmonary trunk, left pulmonary artery, mediastinum, and pericardium, indicating recurrence after tumor resection. Although the patient tolerated apatinib with manageable side effects, he passed away 19 months postsurgery. This case highlights the need for larger clinical trials to establish the safety and efficacy of apatinib for ISPA on a broader scale.

In addition, innovative surgical techniques have been introduced to improve outcomes in ISPA treatment. For instance, Obeso Carillo et al. [24] in 2015 proposed using self‐made stapled bovine pericardial graft conduits for pulmonary artery reconstruction following tumor resection. This method enhances surgical safety and effectiveness by eliminating the need for long‐term anticoagulation and providing excellent biocompatibility and graft durability. However, this technique is technically demanding, requiring advanced surgical expertise. Additionally, it carries the risk of conduit‐related complications, such as stenosis or structural failure, making precise intraoperative management essential for optimal results.

4. Conclusion

We presented a patient with ISPA, referred with dyspnea and retrosternal chest pain. Surgical resection followed by chemotherapy (gemcitabine and docetaxel) and radiotherapy, achieved favorable outcomes with no evidence of disease recurrence on follow‐up PET‐CT, underscoring the significance of comprehensive oncological strategies in managing rare malignancies effectively.

Author Contributions

Azin Alizadehasl: supervision, writing – review and editing. Soroush Najdaghi: conceptualization, resources, software, visualization. Maryam Mohseni Salehi: methodology, project administration, validation. Shahla Meshgi: data curation, investigation. Seyedeh Fatemeh Hosseini Jebelli: resources, validation, writing – original draft. Azam Yalameh Aliabadi: methodology, project administration, writing – original draft. Hoda Hakimian: formal analysis, software, writing – review and editing. Sara Forati: conceptualization, methodology, validation, visualization. Amineh Safavirad: software, writing – review and editing. Delaram Narimani Davani: writing – original draft, writing – review and editing.

Ethics Statement

Informed consent was obtained from the patient for participation and publication of this case report.

Consent

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. All identifying information was removed to ensure privacy. A copy of the written consent is available for review by the Editor of this journal.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

All data generated or analyzed during this study are included in this published article.