Calcified nodules in the cervical carotid artery

Abstract

Background:

Calcified nodules (CNs) are a distinct morphological subtype of calcified plaques that cause acute coronary events. However, their clinical relevance in carotid artery disease remains poorly understood.

Case Description:

We report two cases of symptomatic carotid artery stenosis caused by CNs, both successfully treated with carotid endarterectomy (CEA). In both cases, computed tomography angiography (CTA) revealed severely stenotic lesions with bulky calcified plaques protruding into the vascular lumen. Plaque imaging with magnetic resonance imaging and carotid ultrasonography suggested the presence of calcified components. Surgical excision confirmed the diagnosis of CNs through pathological evaluation. Both patients had favorable outcomes with no neurological deficits on discharge. Notably, CNs are rarely reported in the context of carotid artery disease, and preoperative diagnosis remains challenging due to the lack of established imaging criteria. CTA may be a useful non-invasive tool for identifying CNs, as shown in coronary artery studies.

Conclusion:

These cases demonstrate that CNs can cause severe carotid stenosis requiring CEA. CTA may aid in the preoperative identification of CNs, and when CNs are identified on CTA, CEA should be the preferred treatment over carotid artery stenting. Further studies are warranted to clarify the diagnostic criteria and treatment strategies for CNs in carotid disease.

INTRODUCTION

Carotid artery stenosis is a major cause of transient ischemic attack and stroke, leading to considerable patient morbidity and mortality.[1,6] Calcified plaques in the carotid artery play a critical role in the progression and severity of stenosis, often increasing the risk of ischemic events.[8,12] On imaging, calcified lesions are typically identified as high-attenuation areas on computed tomography (CT) and as low-signal intensity on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and time-of-flight (TOF) magnetic resonance imaging (MRI) sequences. These imaging characteristics reflect the absence of mobile water protons and the susceptibility effects associated with calcified tissue.[2] Among calcified plaques, calcified nodules (CNs) represent a distinct morphological subtype characterized by dense protruding calcifications that disrupt the fibrous cap, potentially leading to thrombus formation and contributing to plaque instability and subsequent acute cerebrovascular and coronary events.[3,16]

As a specific subtype of calcified plaques, CNs have attracted attention for their potential role in plaque instability. Studies have indicated that CNs are found in approximately 3% of coronary artery plaques and 5–7% of coronary thrombosis cases, suggesting a substantial role in plaque instability and thrombus formation.[10,15] CNs have been extensively studied in cardiology, particularly in relation to coronary artery disease and acute coronary syndromes. However, research on their role in the context of carotid artery disease is relatively scarce, despite its potential clinical significance.

In this report, we present two cases of symptomatic carotid artery stenosis caused by CNs, confirmed through carotid endarterectomy (CEA) and subsequent pathological diagnosis. These cases detail the diagnostic process, intraoperative challenges, and postoperative outcomes. By presenting these cases, we aim to improve understanding of the clinical characteristics and management strategies for CNs in carotid artery disease, while underscoring the need for further research in this area.

CASE REPORTS

Case 1

An 80-year-old female with a history of hypertension, dyslipidemia, chronic kidney disease, hyperthyroidism, and Crohn’s disease presented with transient amaurosis in her right eye. Ophthalmological examination revealed no abnormalities, and head MRI showed no ischemic lesions. Carotid magnetic resonance angiography (MRA) revealed right internal carotid artery (ICA) stenosis. On presentation at our hospital, the patient was conscious, without any visual impairment, and no other neurological deficits. CT angiography (CTA) revealed a severely stenotic lesion at the C4 vertebral level of the right ICA, with a bulky calcified plaque and an irregular calcified component protruding into the vascular lumen, measured as 70% stenosis according to the North American Symptomatic CEA Trial (NASCET) criteria [Figures 1a and b]. Carotid ultrasonography revealed a peak systolic velocity (PSV) of 242 cm/s and a high-intensity plaque of approximately 30 mm. Plaque imaging using the black-blood method showed low intensity on T1WI, T2WI, and TOF, findings indicative of calcified plaques, which caused transient ocular ischemia. The patient was deemed a suitable candidate for revascularization surgery and was referred to our hospital for the procedure. Considering the presence of a heavily calcified lesion, CEA was performed. Intraoperatively, a protruding calcified lesion was observed in the lumen [Figure 1c], necessitating circumferential dissection. Pathological examination of the excised plaque confirmed the diagnosis of a CN [Figure 2]. The postoperative course was uneventful, and the patient was discharged on postoperative day 12 with a modified Rankin scale (mRS) score of 0. At 8 months after CEA, the patient had no ischemic event, and MRI showed good patency of the ICA.

Figure 1:

Clinical images of Case 1, showing the carotid artery stenosis caused by calcified nodules (CNs) and the surgical findings. (a) Sagittal computed tomography angiography (CTA) image showing bulky calcification of the cervical carotid artery; (b) axial CTA image revealing a calcification protruding into the lumen (white arrowhead); and (c) intraoperative image showing a calcified nodule protruding into the lumen (black arrowheads).

Figure 2:

Pathohistological images of Case 1, showing that the endothelium is disrupted by calcified nodules protruding into the lumen. Asterisk (*) indicates blood vessel lumen. The clot was observed on the calcified nodules (black arrow). (a) Hematoxylin and Eosin staining; (b and c) Elastica–Masson staining on low and high magnification. (c) is magnified image of square box in (b). Scale Bar: (a and b) 2.5 mm on and (c) 250 mm.

Case 2

A 71-year-old male with a history of hypertension, diabetes mellitus, dyslipidemia, chronic obstructive pulmonary disease, gastric cancer, and lung cancer experienced sudden visual impairment in the left eye while driving, leading to a self-accident and subsequent emergency transportation. Head MRI showed no ischemic lesions, and carotid MRA revealed stenosis of the left ICA. An ophthalmological examination revealed no abnormalities, and the patient was diagnosed with transient amaurosis due to left cervical ICA stenosis. On presentation to our hospital, the patient was conscious, without any visual impairment, and no other neurological deficits. CTA revealed a severely stenotic lesion with a bulky calcified plaque at the C5/6 vertebral level of the left ICA and an irregular calcified lesion protruding into the vascular lumen, measured as 90% stenosis according to the NASCET criteria [Figures 3a and b]. Carotid ultrasonography revealed a PSV of 462 cm/s and a high-intensity plaque of approximately 34 mm. Plaque imaging revealed low intensity on T1WI, low-to-intermediate intensity on T2WI, and low-to-intermediate intensity on TOF, findings indicative of calcified plaques. The patient was determined to be a candidate for revascularization surgery and was referred to our hospital for the procedure. Considering the presence of a heavily calcified lesion, CEA was performed. Intraoperatively, a protruding calcified lesion was observed in the lumen [Figure 3c], necessitating circumferential dissection. Pathology of the excised plaque confirmed the diagnosis of CNs [Figure 4]. The postoperative course was uneventful, and the patient was discharged on postoperative day 8 with an mRS score of 0. At 12 months after CEA, the patient had no ischemic events, and MRI showed good patency of the ICA.

Figure 3:

Clinical images of Case 2, showing the carotid artery stenosis caused by calcified nodules (CNs) and the surgical findings. (a) Computed tomography angiography (CTA) image showing bulky calcification at cervical carotid artery; (b) axial CTA image revealing calcification protruding into the lumen (white arrowhead); and (c) intraoperative image showing CN protruding into the lumen (black arrowheads).

Figure 4:

Pathohistological images of Case 2, showing that the endothelium was disrupted by calcified nodules protruding into the lumen. Asterisk (*) indicates blood vessel lumen. The clot is observed on the calcified nodule (black arrow). (a) H and E staining; (b and c) Elastica–Masson staining on low and high magnification. (c) is magnified image of square box in (b). Scale Bar: (a and b) 2.5 mm on and (c) 1 mm.

DISCUSSION

We encountered two cases of carotid artery stenosis with CNs that were treated with CEA. CNs are commonly reported in the cardiovascular field, accounting for approximately 4% of all acute coronary occlusions.[15] Reports on CNs in patients with carotid artery stenosis are scarce, and many aspects of diagnosis, treatment, and clinical significance remain unclear.[5,13] In particular, the preoperative diagnosis of CNs remains challenging, as there are currently no established imaging criteria to reliably differentiate them from other types of calcified plaques. Although low-signal areas on T1WI, T2WI, and TOF MRI sequences may suggest the presence of calcified components, such findings are nonspecific and cannot delineate the protruding nodular morphology characteristic of CNs. Therefore, CTA plays a crucial role in assessing calcified plaque morphology preoperatively, while a definitive diagnosis is typically made through pathological confirmation after surgical resection. Here, we discuss the potential utility of preoperative CTA and clinical features correlated with pathological characteristics.

CTA is a widely used non-invasive modality for evaluating carotid artery stenosis and plaques.[17] Several reports have documented the clinical significance of calcified plaques based on CTA findings, including spotty and bulky calcifications.[4,17] Spotty calcifications, which are small, discrete deposits of calcium within plaques, are associated with an increased risk of ischemic events.[7,8] Studies have shown that spotty calcifications within low-density plaques are correlated with an increased incidence of ischemic stroke.[7,8] Thus, spotty calcifications may serve as markers of plaque vulnerability and higher stroke risk. Bulky calcifications, which are larger and more extensive deposits of calcium, are typically associated with more stable plaques; however, they can still contribute to luminal narrowing and potential ischemic events.[4,7,8,11] CNs typically present as irregular protruding lesions resembling bulky calcifications on CTA. Few studies have reported the proportion of CNs in the calcified plaques of the carotid arteries. Existing studies that evaluated and classified carotid plaques using CTA did not define them as CNs.[5] In the context of coronary artery disease, the gold standards for diagnosing CNs include optical coherence tomography (OCT) and intravascular ultrasound.[9,10] These modalities provide high-resolution images that can be used to accurately identify and characterize calcified lesions. However, these are invasive procedures, and there have been investigations into the potential of using CTA for diagnosing CNs.[14] Sugiura et al. conducted a retrospective analysis of coronary CTA and demonstrated that it can identify CNs with relatively high sensitivity and specificity, comparable to those of OCT. Their analysis also revealed that the CN group had significantly higher coronary artery calcification scores, calcified plaque volume, and maximum calcified plaque area in the target vessel compared to the non-CN group.[14] In the two reported cases, irregular calcified lesions protruding into the vascular lumen were observed, suggesting that CTA could be a useful diagnostic tool for CNs in the carotid artery, similar to its application in the coronary arteries. The detailed imaging provided by CTA facilitates accurate preoperative assessment, which is crucial for planning subsequent surgical interventions.

CNs are dense calcium deposits within atherosclerotic plaques, frequently disrupting the fibrous cap and increasing the risk of rupture.[3,16] Few reports have confirmed the histopathology of CNs in the carotid arteries; however, their clinical characteristics remain poorly understood. In our cases, CNs met the criteria previously established[3,15,16] and were pathologically confirmed, highlighting their rarity in carotid arterial stenosis. A previous report documented the difficulty of performing carotid artery stenting (CAS) in the presence of a CN, ultimately necessitating CEA,[13] which might require an arterial patch graft. As illustrated by the pathological images in our cases, a CN protruding into the arterial lumen can cause stent expansion failure during CAS. Therefore, identifying the CN on preoperative CTA can provide crucial information for selecting an appropriate treatment strategy.

CONCLUSION

Although CNs in carotid artery stenosis are rare, they are clinically significant and present challenges for diagnosis and treatment. We report two cases of carotid artery stenosis with CNs confirmed by CEA and pathological examination, highlighting the clinical significance of CN and emphasizing the potential utility of CTA for preoperative identification to guide revascularization strategy. Further research is needed to better understand the clinical implications and optimal management strategies for CNs in carotid artery disease. When CNs are identified on CTA, CEA should be the preferred treatment over CAS.

Ethical approval:

The research/study was approved by the Institutional Review Board at Kohnan Hospital, number 2023-0118-03, dated January 18, 2023.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

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