Aortic Intimal Sarcoma Diagnosed by Surgical Resection

Abstract

Aortic intimal sarcoma is a rare disease with no established treatment and a poor prognosis. A 70-year-old man who underwent surgery for a mass shadow extending from the ascending aorta to the left common carotid artery on contrast-enhanced computed tomography was diagnosed with intimal sarcoma and underwent postoperative radiotherapy (66 Gy/33 Fr). Three brain metastases were identified after 1.5 months. No recurrence or enlargement was noted for four months following gamma knife radiosurgery and chemotherapy. To our knowledge, this is the first report of gamma knife radiosurgery delaying the progression of aortic intimal sarcoma.

Introduction

Intimal sarcoma, a rare tumor that primarily affects the pulmonary artery and aorta, has extremely high malignant potential (1). Although surgical resection, endarterectomy, bypass, and stenting have been reported to alleviate symptoms (2), the efficacy of perioperative adjuvant chemotherapy and radiotherapy has not been reported, and the treatment methods remain unestablished (3).

We herein report a patient in whom perioperative adjuvant chemotherapy and radiotherapy successfully delayed disease progression and discuss the literature on this subject.

Case report

A 70-year-old man presented to our emergency department with shortness of breath and chest pain. When he visited the hospital, there was a remarkable difference in blood pressure between the right and left arms (right upper arm, 138/63 mmHg; left upper arm, 97/60 mmHg). Blood tests showed a white blood cell count of 16,440 /μL; C-reactive protein, 6.49 mg/dL; hemoglobin, 6.6 g/dL; mean corpuscular volume (MCV), 91 fL; mean corpuscular hemoglobin (MCH), 29.2 pg; mean corpuscular hemoglobin concentration (MCHC), 32.1 g/dL; serum iron, 33 μg/dL; transferrin saturation (TSAT), 20%; unsaturated iron-binding capacity (UIBC), 134 μg/dL; ferritin, 1,930 ng/mL; and D-dimer, ＜0.5 μg/dL (Table). Low serum iron and high ferritin levels were observed, and anemia associated with chronic inflammation was suspected. Upper gastrointestinal endoscopy performed at a later date revealed no disease that could have caused anemia.

Table.

Laboratory Findings of the Patient.

<Complete blood count>				<Biochemistry>
White blood cells	16,440	/μL		C-reactive protein	6.49	mg/dL
Neutrophils	87.9	%		Total protein	7.1	g/dL
Eosinophils	6.4	%		Albumin	3.0	g/dL
Monocytes	3.7	%		Aspartate aminotransferase	14	U/L
Lymphocytes	1.8	%		Alanine aminotransferase	28	U/L
Red blood cells	233×104	/μL		Blood urea nitrogen	17.1	mg/dL
Hemoglobin	6.6	g/dL		Creatinine	1.21	mg/dL
Hematocrit	21.2	%		Sodium	140	mEq/L
Mean corpuscular volume	91	fL		Potassium	4.6	mEq/L
Mean corpuscular hemoglobin	29.2	pg		Serum iron	33	μg/dL
Mean corpuscular hemoglobin concentration	32.1	g/dL		Unsaturated iron-binding capacity	134	μg/dL
Platelets	25.3×104	/μL		Ferritin	1,929.9	ng/mL
				Transferrin saturation	20	%
<Coagulation>
Prothrombin time	11.5	s		<Tumor marker>
Activated partial thromboplastin time	28.8	s		Carcinoembryonic antigen	<1.7	ng/mL
D-dimer	<0.5	μg/dL		Carbohydrate antigen 19-9	<2.1	U/mL

Aortic dissection was suspected, and contrast-enhanced computed tomography (CT) of the thorax and abdomen was performed. There were no findings of aortic dissection, but a mass shadow with poor contrast effect was observed from the ascending aorta to the left common carotid artery (Fig. 1). Aortic wall thrombus was suspected on imaging. Aortic vascular replacement was selected because of the high risk of thrombus recurrence when the thrombus was removed alone. On day 5 after admission, the patient underwent aortic vascular replacement surgery in the ascending arch. On postoperative day 6, histopathology revealed dense proliferation of spindle-shaped cells with atypical nuclei against a background of mucinous matrix with an intimal neck and partial positivity for cluster of differentiation 31 (CD31) and α-smooth muscle actin (αSMA), leading to a diagnosis of intimal sarcoma, a poorly differentiated malignant mesenchymal tumor (Fig. 2).

Figure 1.

Contrast-enhanced computed tomography of the thorax and abdomen on admission showing soft shadows with poor contrast from the ascending aorta to the aortic arch and left common carotid artery (A, B: early phase; C, D: equilibrium phase).

Figure 2.

A pathological examination of the excised specimen showing dense proliferation of spindle-shaped cells in the center of the intima (Hematoxylin and Eosin staining B: ×10, C: ×200). The cells are weakly positive for CD31 (D) and α-SMA (E) and negative for desmin (F) (magnification ×200). α-SMA: alpha smooth muscle actin, CD31: cluster of differentiation 31

A pathological examination did not confirm any negative margins. Postoperative CT showed no evidence of distant metastasis; however, a residual tumor was suspected in the left internal carotid and subclavian arteries (Fig. 3). Therefore, we decided that the patient would undergo radiotherapy for local control.

Figure 3.

Contrast-enhanced CT findings after artificial vascular surgery. The left common carotid artery and left subclavian artery showed poor contrast and findings suggestive of residual tumor. CT: computed tomography

Radiotherapy was chosen for three main reasons: first, the tumor appeared localized on imaging; second, the patient was frail following cardiovascular surgery; and third, despite reviewing the limited available reports, evidence for perioperative chemotherapy was insufficient, and the patient refused this option. After postoperative rest and follow-up, radiotherapy was initiated on postoperative day 45. Despite radiation anesthesia pharyngitis, left mandibular toothache, gingival mucositis, dermatitis, and radiation therapy (66 Gy/33 Fr) were completed, and the patient remained under observation.

However, approximately 1.5 months following radiation therapy, he presented to the emergency department complaining of weakness in his lower extremities and difficulty walking. Imaging tests were performed to investigate the presence of stroke. Magnetic resonance imaging (MRI) of the head revealed three metastatic lesions in the right cerebral hemisphere with cerebral edema, and CT of the head revealed a metastatic lesion with bone destruction in the posterior wall of the left maxillary sinus. He received palliative irradiation (8 Gy once) for posterior wall metastasis of the left maxillary sinus and chemotherapy (gemcitabine and docetaxel) after gamma knife radiosurgery for 3 brain metastases (Fig. 4).

Figure 4.

Head MRI showing three brain metastatic lesions (A1, A2, A3) in the right cerebral hemisphere. Four months after chemotherapy with gamma knife and gemcitabine docetaxel, the lesions had shrunk (B1, B2, B3). MRI: magnetic resonance imaging.

No recurrence or enlargement was observed for approximately 4 months after gamma knife radiosurgery. However, 5 months later, whole-brain irradiation (30 Gy/10 Fr) was performed because the head MRI findings were suspicious for recurrence. The recurrence site was in close proximity to the gamma knife-irradiated area, making reirradiation with the gamma knife difficult. Following the completion of whole-brain irradiation, the patient was unable to resume chemotherapy and died three months later due to a decline in overall health caused by the tumor.

Discussion

Intimal sarcoma, first described by Mandelstamm in 1923, is a rare tumor that arises primarily in the pulmonary artery and aorta (1). It arises from subendothelial pluripotent cells within the intimal lining of the vessel wall and is highly malignant (4). The prognosis is poor, ranging from 5 to 9 months for primary aortic tumors and from 13 to 18 months for primary pulmonary tumors (5). Claudication and arterial embolization are common in aortic intimal sarcomas owing to their bulky intravascular component and friability. More than one-quarter of patients develop claudication, while over one-third experience arterial embolization. Emboli primarily affect areas such as the extremities, kidneys, and abdominal vasculature (4). In many instances, pulmonary artery sarcoma is misinterpreted as an acute or chronic pulmonary thromboembolism, whereas aortic intimal sarcoma is misdiagnosed as protuberant atherosclerotic disease or intimal thrombus.

The most useful imaging modalities for assessing suspected intimal sarcomas include CT angiography, fluorine 18-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET), and MRI (5). CT features favoring neoplasia over benign entities, such as atheroma or thrombus, include marked endoluminal growth, contrast enhancement (although often minimal or absent), aortic wall thickening and/or enhancement, extravascular extension, and nodal or distant metastases (6). Of the few examples in the literature of aortic intimal sarcoma during ¹⁸F-FDG PET, all but one demonstrated metabolic activity (6). In this case, the symptoms included breathlessness and general malaise, likely due to progressive anemia, although these symptoms were nonspecific for aortic intimal sarcoma. Anemia developed gradually, and findings, such as low serum iron, high ferritin, and elevated inflammatory markers, suggested anemia related to chronic inflammation. If contrast-enhanced whole-body CT had been conducted earlier to investigate the cause of chronic inflammation, it might have led to an earlier diagnosis of aortic intimal sarcoma. In addition, when aortic intimal sarcoma is suspected or confirmed, follow-up using ¹⁸F-FDG PET or MRI may be crucial.

The treatment for intimal sarcomas remains unestablished (3). Surgical resection of the tumor is the first-choice treatment in the absence of metastases; however, complete resection is rare (2). If resection is not possible, endarterectomy, bypass, stenting, or local radiotherapy may provide symptomatic relief (2). However, the efficacy of perioperative adjuvant chemotherapy and radiotherapy has not yet been established. In unresectable cases of sarcoma for which individualized treatment has not been established, adriamycin and ifosfamide therapy may be selected if the Eastern Cooperative Oncology Group Performance Status (ECOG PS) is good and tumor shrinkage is expected to provide symptomatic relief. Pazopanib, trabectedin, and eribulin may be considered as second-line therapies for patients who progress following adriamycin-containing regimens (7-10). In the present case, we chose gemcitabine and docetaxel to avoid anthracyclines because of the patient's age (70 years old), ECOG PS (2), and preference for outpatient treatment.

In this case, gamma knife radiosurgery for brain metastases of intimal sarcoma resulted in tumor shrinkage and suppression of recurrence for four months. A search of the Central Journal of Medicine and PubMed did not reveal any cases in which gamma knife surgery was markedly effective for the treatment of intimal sarcoma. Therefore, we hypothesize, based on our findings, that gamma knife radiosurgery may be an option for treating intimal sarcoma.

The authors state that they have no Conflict of Interest (COI).