Intimal sarcoma of the aortic valve and ascending aorta: a case report

Introduction

Intimal sarcomas are rare tumors that typically affect the major vessels, such as the pulmonary artery and aorta, and largely result in a poor prognosis (1). The symptoms of intimal sarcomas are usually nonspecific, making preoperative diagnosis difficult. As a result, the majority of neoplasms can only be found by histological analysis of the surgical specimen. In this report, we present a patient with an uncommon intimal sarcoma of the aortic valve and ascending aorta with symptoms similar to those seen in nonbacterial thrombotic endocarditis. We present this case in accordance with the CARE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1550/rc).

Case presentation

A 69-year-old female was admitted to Beijing Anzhen Hospital with complaints of chest distress and decreased activity tolerance for nearly one month. The patient had no significant past medical history. Laboratory tests indicated elevated serum levels of interleukin 6 (7.3 pg/mL; normal value: 0–6.4 pg/mL), lactic dehydrogenase (342 U/L; normal value: 120–250 U/L), high-sensitivity troponin I (556 pg/mL; normal value: 0–11.6 pg/mL), and brain natriuretic peptide (1,551 pg/mL; normal value: 0–100 pg/mL) along with mild anemia [hemoglobin (Hb) 105 g/L, normal value: 115–150 g/L; red blood cell (RBC) count 3.6×10¹²/L, normal RBC count: (3.8–5.1)×10¹²/L]. However, the other tests showed no abnormalities, including serum levels of C-reactive protein, anti-streptolysin O, and rheumatoid factor.

Preoperative echocardiogram revealed severe aortic regurgitation (AR) and a mass-like echogenicity on the left coronary leaflet of the aortic valve. The mass appeared to originate from the valve and root of the aorta, with a size of 9.8 mm × 6.6 mm, had an irregular shape and soft texture, and oscillated with the valve leaflets. Additionally, the patient had severe mitral regurgitation, mild tricuspid regurgitation, and mildly reduced left ventricular function, with an ejection fraction of 47%. A computed tomography (CT) scan with contrast-enhanced angiography revealed a low-density area of the aortic root, measuring approximately 6 mm in length (Figure 1).

Figure 1 CT scan with contrast-enhanced angiography before the operation. (A) CT images at the aortic valve level revealed an unclear structure of the aortic valve leaflet. (B) CT scan with contrast-enhanced angiography revealed a low-density area in the aortic valve, measuring approximately 6 mm in length. (C,D) CT composite images of the sagittal and coronal sections of the ascending aorta revealed a low-density area in the aortic valve and the nearby ascending aorta. The arrow in (C) shows the location of the low-density area in the enhanced CT scan with contrast-enhanced angiography. CT, computed tomography.

The patient had no recent history of fever or upper respiratory tract infection. Based on the laboratory tests, the involvement of nonbacterial thrombotic endocarditis in the aortic valve leaflets was considered, and antibiotic therapy was not used before surgery. The patient was given a 7-day regimen of cardiac and diuretic medication to improve cardiac function.

The patient underwent a Bentall procedure through a median sternotomy approach to replace the damaged aortic valve and ascending aorta. She also underwent mitral valve and tricuspid valve repair and coronary artery bypass grafting. The operation was performed under moderate hypothermia (32 ℃). Cardiopulmonary bypass was established with cannulation of the right femoral artery and superior and inferior vena cava. After aortic cross-clamping, a transverse incision of the aortic wall was made, and mass was found on the aortic valve leaflet and the intima of the proximal ascending aorta (Figure S1). To ensure that there was no tissue embolization in the left ventricle or the coronary artery, we meticulously removed all layered material from the aortic valve leaflets and the aortic wall. After resection of the aortic valve leaflet and complete-as-possible removal of the mass on the aortic intima, a St Jude #21 prosthetic vessel with a mechanical valve conduit was used for replacement. The patient was discharged on postoperative day 8 after an uneventful hospital stay.

Pathology of all the specimens (aortic wall, aortic valve and vegetations) was positive for intimal sarcoma. A poorly differentiated spindle cell tumor with nuclear pleomorphism, numerous mitoses, and necrosis microfoci emerging from the intimal surface and infiltrating the aorta wall, including the resected margins, appeared to have heavily invaded the vegetation. Immunohistochemistry with an automated immunostainer and particular antibodies (ZSGB-Biotechnology Co., Ltd., Beijing, China) revealed the following: vimentin(+), MDM2(+), Ki-67(+, index 70%), AE1(–), AE3(–), CD31(+), CD34(+), and ERG(–) (Figure 2). All these findings were consistent with intimal sarcomas.

Figure 2 Routine histological and immunohistochemical examinations. Histologic sections of an aortic intimal sarcoma characterized by highly unusual cells with nuclear pleomorphism and mitoses, along with diffuse vimentin staining and MDM2 positivity. (A) Hematoxylin and eosin staining at 20× original magnification. (B) Hematoxylin and eosin staining at 40× original magnification. (C) Immunoperoxidase staining and hematoxylin counterstaining with a specific antibody against vimentin at 40× original magnification. (D) Immunoperoxidase staining and hematoxylin counterstaining with a specific antibody against MDM2 at 40× original magnification.

Because of the pathology results a ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) was performed to further characterize the lesion and investigate potential dissemination. PET imaging revealed abnormalities at the level of the proximal ascending aorta and aortic valve, attributed to changes caused by surgical procedures. Additionally, potential systemic dissemination was observed in the right adrenal gland and the left humeral head area. Multiple caption areas within the 3A mediastinal zone and right lung hilar were also deemed as lymph node metastasis (Figure S2).

The patient was confirmed to be alive at the time of submission, as verified by the most recent telephone follow-up conducted 13 months post-surgery. However, a computed tomography angiography revealed an occupying lesion in the inferior vena cava one month ago, though it remains unclear whether this is a metastasis of the intimal sarcoma.

All procedures performed in this study were in accordance with the ethical standards of the Beijing Anzhen Hospital Ethics Committee and with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

International multidisciplinary team (iMDT) discussion

Discussion among physicians from Beijing Anzhen Hospital

Most of the cardiac lesions represents secondary location of the primary tumor, those rarely involve the heart (2). A total of approximately 170 cases of aortic sarcoma have been reported to date (1). Typically, intimal sarcomas found in the aorta have been limited to the abdominal tract between the celiac artery and the iliac bifurcation. The descending aorta is involved in 30% of cases, while the involvement of the ascending aorta is rare (3-6). To our knowledge, the case reported here is the first documented instance of the intimal sarcoma affecting the native aortic valve and the root. The patient’s clinical manifestations resembled nonbacterial thrombotic endocarditis of the aortic valve.

Intimal sarcomas are a rare type of malignant tumor that develop quickly and involve an extremely poor prognosis. The average survival for a patient with aortic intimal sarcoma is 11 months (7). Intimal sarcomas of the aorta are often misdiagnosed as nonneoplastic conditions, such as thromboembolism, atheroma, or even intramural hematoma, leading to delayed diagnosis or even postmortem diagnosis (3,4). Immunohistochemical staining is crucial in differential diagnosis between aortic intimal sarcoma and different aortic tumors. Intimal sarcomas are poorly differentiated and often present nonspecifically, while MDM2 is detected in more than 70% of cases. It is critical to distinguish between an intimal sarcoma and two other types of sarcomas: leiomyosarcoma, which is identified by smooth muscle marker staining, and the more common angiosarcoma, which exhibits distinct and diffuse endothelial differentiation (3,5,6,8,9). The diagnosis in this instance was supported by the detection a mesenchymal marker, vimentin, and the lack of epithelial or smooth muscle markers.

It can be challenging to distinguish between aortic intimal tumors, infection, and advanced atherosclerotic disease using CT with contrast-enhanced angiography (10). It is possible that even ¹⁸F-FDG PET may not be able to distinguish a tumor from an infectious lesion. However, magnetic resonance imaging with angiography has recently been advocated as a crucial diagnostic tool for identifying malignant aortic tumors. This method can effectively visualize the degree of tumor involvement in the aortic wall and surrounding tissues, allowing for the differentiation of tumors from the atheromatous illness. Furthermore, it is associated with a lower risk of nephrotoxicity and embolization than are traditional angiography techniques (11-13).

Aortic intimal sarcomas usually present with symptoms caused by the blockage of blood flow to certain organs or extremities due to tumor embolization. More than half of the patients with this condition present dissemination in different organs, such as the bone, lung, liver, lymph nodes, skin, and adrenal glands (14,15). In the present case, postoperative ¹⁸F-FDG PET showed metastasis affecting the right adrenal gland and the left femoral head. Similarly, the treatment of aortic intimal sarcomas depends on the extent of the aortic involvement and whether there is metastatic disease present. It is crucial to completely remove the tumor to improve the patient’s prognosis even in the absence of dissemination. Patients without metastatic disease at the time of diagnosis have a median survival of 20 months, whereas those with metastases have a median survival of only 6 months. However, achieving complete resection through surgery is rare. Although chemotherapy has been reported to be effective in treating those intimal sarcomas, survival still remains poor (14-16).

Several issues concerning the diagnosis and treatment of this patient are discussed below

Question 1: Given the poor prognosis of intimal sarcoma, is it necessary to completely remove the lesion if a rapid paraffin-section pathological diagnosis can be made during the operation?

Expert opinion 1: Dr. David C. Rotzinger

Although surgical resection of cardiac sarcomas is often challenging or sometimes not feasible, it remains the only definitive treatment option for potentially curing the disease. In cases where the tumor is deemed non-resectable—approximately 50% of cases—debulking should still be considered to alleviate functional impairment.

Expert opinion 2: Dr. Tommaso Hinna Danesi

Margin-free resection represents the gold standard in oncologic surgery to achieve better prognosis. Being the intraoperative pathology a time-consuming procedure it can be carried out taking in account the cross clamp time and the ischemic time of the heart since those might widely affect by rapid paraffin-section pathology and might result in poor surgical outcomes. Logistic and total time of the exam should be carefully evaluated especially since a radical vs. partial excision barely improves the life expectancy, but not the mortality.

Expert opinion 3: Dr. Junichi Shimamura

Complete resection can be performed depending on the location of the disease. However, complete resection may not probably improve patient’s prognosis because of aggressive nature of intimal sarcoma.

Question 2: Given the challenges in diagnosing intimal sarcoma, most cases are identified through pathology after surgery. For individuals with metastatic lesions, does the removal of the primary tumor hasten the process of systemic metastasis in intimal sarcoma?

Expert opinion 1: Dr. David C. Rotzinger

The prognosis for intimal sarcoma is generally poor, particularly when the tumor cannot be completely resected with clear margins. Consequently, surgery for metastatic disease is often considered palliative, aimed primarily at symptom relief. Currently, there is limited data on whether removing the primary tumor accelerates metastatic dissemination. However, a review of the literature, which included 142 cases, suggests that radical resection is associated with a longer survival time (16.3 months) compared to other treatments (7.7 months) (17). This finding argues against the notion that surgery accelerates metastatic spread.

Expert opinion 2: Dr. Tommaso Hinna Danesi

Since metastases represent dissemination and might be at different stages/sizes, I am not sure en-bloc resection of the primary lesion will affect the growth of secondary lesions and along them the survival rate.

Expert opinion 3: Dr. Junichi Shimamura

There is a possibility of hasting the process of progression by resecting primary tumor, especially with the use of cardiopulmonary bypass. However, the surgery in this case is justified to improve hemodynamics because of significant AR as well as diagnostic purpose.

Question 3: What is the most effective treatment plan for metastases located outside the heart?

Expert opinion 1: Dr. David C. Rotzinger

A recent literature review indicated that survival improves with radical surgery for metastatic disease, suggesting that, similar to treatment for the primary tumor, aggressive resection remains a key therapeutic approach (17), often in combination with neoadjuvant or adjuvant chemotherapy. In the absence of large cohorts or randomized trials, Xu et al. sought to understand the impact of chemotherapy by reviewing 165 articles and 275 cases of pulmonary artery sarcoma (18). Although different from aortic intimal sarcoma, these findings may offer insights into potential therapeutic strategies, as they suggest that adjuvant and/or neoadjuvant chemotherapy can be beneficial for metastatic disease. Additionally, high-precision radiotherapy, which can be used as an alternative to surgery, is increasingly reported and should be considered in the treatment approach. Multimodal imaging and multidisciplinary discussions are crucial for managing these patients.

Expert opinion 2: Dr. Tommaso Hinna Danesi

En-bloc resection and absence of dissemination seems to be the condition with the best prognosis in terms of life expectancy. Due to delay in diagnosis often the disease is extensive and had already disseminated. Since the tumor is highly resistant to cytotoxic and targeted treatment combination therapy might be an option, although toxicity may represent a limitation. In case reports with extensive vascular and brain dissemination, radiotherapy has been proved to be effective but not curative (19,20).

Expert opinion 3: Dr. Junichi Shimamura

Based on previous literature, anthracycline-based chemotherapy or palliative pazopanib can be an option of metastatic lesions outside the heart.

Conclusions

Intimal sarcomas are an uncommon and extremely aggressive type of primary malignant aortic tumor. Diagnosis might be challenging and requires a high level of suspicion. Standard surgical treatment may include resection of the affected segment followed by interposition graft replacement. Given the poor prognosis even after complete resection, it is essential to rule out metastasis.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1550/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1550/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1550/coif). T.H.D. receives grants or contracts from Edwards Lifesciences consultant and Corcym consultant; and support for attending meetings and/or travel from Scolla Training Center—1^st Brazilian Mics Meeting 2024, AATS Foundation—Asian Valve Symposium 2023, and Endoscopic Cardiac Surgeons Club—1^st annual meeting 2022. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the Beijing Anzhen Hospital Ethics Committee and with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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