A Case Report of Fatal Sinoatrial Node Dysfunction Secondary to Primary Pulmonary Vascular Leiomyosarcoma: Diagnostic Challenges and Imaging Findings

1. Introduction

Pulmonary vascular leiomyosarcoma is an exceedingly rare malignant tumor originating from the smooth muscle cells within the medial layer of elastic arteries. It is classified as a rare subtype of pulmonary artery sarcoma. The disease is highly aggressive and is frequently misdiagnosed as pulmonary embolism due to nonspecific clinical and imaging findings, leading to delays in diagnosis. Although surgical resection is the primary treatment, the overall prognosis remains exceedingly poor. Without treatment, survival is very short, and even after surgery, recurrence and metastasis are common [1]. This tumor falls under the category of primary cardiac sarcomas. Given its extremely low incidence, only a few medical centers have reported individual cases [2], and there have been few updates in the recent literature [3] Owing to its rarity, pulmonary vascular leiomyosarcoma is often clinically mistaken for pulmonary embolism. Current management strategies include surgery, chemotherapy, and radiotherapy; however, these are largely palliative, aimed at prolonging symptom-free survival rather than achieving a cure [4].

2. Case Presentation

A 53-year-old male patient presented to our respiratory department with cough and chest discomfort of unknown cause. Initial non-contrast chest CT soft-tissue window revealed heterogeneous density within the main pulmonary artery and its right branch (Figure 1). To rule out acute pulmonary embolism, CTA was promptly performed, showing filling defects in the main and right pulmonary arteries with local protrusion into the superior vena cava causing significant luminal narrowing, and involvement of the proximal right upper pulmonary artery, suggestive of pulmonary artery sarcoma or leiomyosarcoma (Figure 2). For definitive diagnosis, the patient was transferred to the Department of Thoracic Surgery at Beijing China-Japan Friendship Hospital. Biopsy revealed a grayish-red, hemorrhagic, unencapsulated lesion composed of spindle cells arranged in fascicles or storiform patterns, with abundant cytoplasm, hyperchromatic nuclei, and collagenous stroma. Immunohistochemistry was positive for α-SMA, Vimentin, and Caldesmon, and negative for CK(AE1/AE3), EMA, CD34, S100, and MyoD1. Ki-67 was approximately 10%. Pathology confirmed pulmonary artery spindle cell sarcoma with myogenic differentiation (Figure 3).

After diagnosis, the patient returned to our hospital for chemotherapy and follow-up. Initial PD-1 monotherapy for 3 cycles was switched to PD-1 plus docetaxel and gemcitabine for 6 cycles due to disease progression (Figure 4A,B). Docetaxel monotherapy in cycles 7–8 achieved stable disease (Figure 4C, D). Progression at cycle 9 led to one cycle of PD-1 plus docetaxel and gemcitabine. Early the next year, treatment was adjusted to docetaxel plus bevacizumab for 2 cycles, followed by 1 cycle of docetaxel alone. After 12 cycles, enhanced chest CT showed marked tumor enlargement involving the main, bilateral, and right upper branch pulmonary arteries, and superior vena cava, with mediastinal lymphadenopathy (Figure 4E, F, G). The patient developed bradycardia (38–40 bpm) due to sinus node dysfunction. Isoproterenol infusion and pacemaker implantation were advised but declined. Symptoms improved with supportive care, and the patient was discharged.

Eighty-seven days later, the patient experienced massive hemoptysis and was admitted via emergency service. Chest CT showed significant tumor enlargement, cardiac compression, pericardial effusion, bilateral pulmonary infiltrates, and pleural effusions (Figure 4H, I). With deteriorating condition and conscious conservatism chosen by the family, the patient died of respiratory failure the following morning. Overall survival from diagnosis was 14 months.

3. Discussion

Pulmonary artery sarcoma (PAS), pulmonary vascular leiomyosarcoma, and pulmonary artery intimal sarcoma (PAIS) are often used interchangeably in clinical practice, yet they differ significantly in pathological basis. PAS is a broader category, with the vast majority of cases being intimal sarcomas (i.e., PAIS) originating from the pulmonary artery intima. Microscopically, these often present as undifferentiated sarcomas or show fibroblastic/myofibroblastic differentiation. However, PAS also includes an extremely rare "mural" type—such as pulmonary vascular leiomyosarcoma—which arises not from the intima but from the smooth muscle cells within the medial layer of elastic arteries, differing from PAIS in both origin and histologic features.

Primary pulmonary artery sarcoma was first identified and reported by Mandelstamm in 1923 during an autopsy [3], with an incidence of approximately 0.001%–0.03% [5]. Pulmonary vascular leiomyosarcoma is even rarer, and its incidence lacks statistical data. The disease is often asymptomatic until pulmonary vascular obstruction occurs, unless incidentally detected on routine imaging. Most patients present with symptoms related to pulmonary hypertension and are subsequently diagnosed via imaging studies. According to research by Fumihiro Kashizaki et al. [6], the mean age of PAS patients is 52.6±13.1 years, with a similar gender distribution. The right main pulmonary artery is the most commonly involved site (72.3%, 95% CI 70.9–79.6), consistent with the present case.

Due to overlapping clinical and imaging features with pulmonary embolism, PAS is often misdiagnosed. Laboratory markers such as D-dimer, BNP, CRP, and ESR can be elevated in both conditions and are not useful for differentiation [7]. In this patient, pulmonary embolism could not be ruled out based on non-contrast CT alone. Contrast-enhanced CT has limitations, though an average enhancement of approximately 25 HU may suggest PAS [3], whereas thromboemboli typically do not enhance. MRI is more reliable, as PAS often shows gadolinium enhancement, with the degree of enhancement correlating with tumor differentiation [2]. FDG PET-CT is valuable in differential diagnosis [7] and is often used when CT and MRI are inconclusive. Another middle-aged female patient with pathologically confirmed PAS at our hospital showed invasion of perivascular tissues and other sarcoma-related features on enhanced CT—such indirect signs can help exclude pulmonary embolism at an early stage (Figure 5).

Notably, the present patient developed sinus node dysfunction in the end-stage phase(Figure 6). The sinus node, located at the junction of the superior vena cava and the right atrium, serves as the heart’s primary pacemaker [8]. On enhanced CT prior to death, the PAS had enlarged significantly, invading the superior vena cava and lying in close proximity to the right atrium. Anatomically, although the sinus node is surrounded by a fibrous matrix, it is not completely isolated from the atrial myocardium; its peripheral branches interweave with atrial muscle fibers, facilitating electrical conduction [9]. Given its smooth muscle origin and anatomic proximity, the PAS in this case may have directly invaded the sinus node region, causing myocardial compression and significant pericardial effusion. We speculate that tumor compression of the superior right atrium led to degeneration of perinodal myocardium and fibrous tissue, compounded by preexisting coronary artery disease (the patient had two prior PCI procedures in 2009 and 2010), collectively contributing to sinus node dysfunction. Studies by Moritz C. Wyler von Ballmoos et al. [2] indicate that PAS can cause tachyarrhythmias, conduction abnormalities, pericardial effusion, and tamponade [2]. This patient exhibited atrial flutter during hospitalization, followed by persistent sinus node dysfunction. Atrial flutter may represent the “tachy” phase of tachy-brady syndrome, with sinus node dysfunction serving as a substrate for atrial arrhythmias—the two may form a vicious cycle. Sinus node dysfunction in this case likely hastened the patient’s death.

PAS is rarely curable. Surgical resection—including pulmonary endarterectomy, lobectomy, pneumonectomy, tumor resection with pulmonary artery replacement, or cardiopulmonary transplantation—remains the best option [1], aiming to restore blood flow [10]. To date, chemotherapy and radiotherapy have not shown significant palliative benefit [1]. This patient was inoperable at diagnosis and responded poorly to chemotherapy. PAS is highly aggressive and carries a poor prognosis: median survival is approximately 2 months without surgery and may extend to 10 months post-resection [1].

4. Conclusions

Primary pulmonary vascular leiomyosarcoma is highly aggressive and carries a poor prognosis. As demonstrated in this case, direct local tumor invasion can precipitate critical and life-threatening complications, notably sinoatrial node dysfunction, which significantly accelerates clinical deterioration. Furthermore, the tumor's propensity to masquerade as pulmonary embolism highlights the diagnostic challenges. Because this malignancy responds poorly to current chemotherapy and radiotherapy , early diagnosis and accurate differentiation using multimodal imaging, along with close follow-up, are critical for monitoring disease progression. Ultimately, this report underscores the urgent need for heightened clinical awareness of this rare entity and its atypical complications, as well as the exploration of novel and more effective therapeutic strategies.