https://orcid.org/0009-0003-2319-0599
Abstract
Calcified amorphous tumour (CAT) is a rare lesion that forms at various sites of the heart, including the mitral annulus. Since it is a systemic embolic source, it often requires resection. In contrast, caseous calcification of the mitral annulus (CCMA) usually receives conservative follow-up; however, it is sometimes resected to prevent embolism. Herein, we present a rare case of CCMA-associated CAT with chronic inflammatory cardiomyopathy and comprehensively consider the aetiology of CCMA-associated CAT.
A 52-year-old man with end-stage renal failure requiring haemodialysis underwent annual follow-up echocardiography for aortic valvular dysfunction. Echocardiography revealed a well-defined 22 × 17-mm circular mass on the annulus of the posterior mitral leaflet that had not been detected 2 years previously. Based on imaging characteristics, the mass was suspected to be a CCMA. It had rapidly enlarged and posed a potential risk for embolism; therefore, it was resected concurrently with aortic valve replacement. Although CCMA was suspected based on the intraoperative findings, the histopathological diagnosis was a CAT. Upon histological analysis of the left ventricular myocardial specimen and excised aortic valve, chronic inflammatory cell infiltration was observed; therefore, chronic inflammatory cardiomyopathy was diagnosed.
In this case, the timing of decreased left ventricular systolic function and the arising mass coincided, suggesting that chronic inflammation and immunopathological reactions may have influenced the development of CAT from CCMA. Therefore, the rapid progression of CCMA in the development of CAT should especially be considered in patients with inflammatory cardiac comorbidities.
Caseous calcification of the mitral annulus, a rare variant of mitral annulus calcification, is sometimes accompanied by calcified amorphous tumour (CAT), which is a rare but important embolic source.
Caseous calcification of the mitral annulus is suspected based on the features of imaging studies, whereas CAT is diagnosed histopathologically.
Caseous calcification of the mitral annulus with rapid progression and inflammatory comorbidities should be carefully monitored for arising CAT.
Introduction
Calcified amorphous tumour (CAT) is a rare non-neoplastic lesion with an unclear prevalence. Histologically, it shows calcified areas and amorphous fibrin-like material and is particularly found in the mitral annulus of the heart.1 As CAT occasionally acts as an embolic source, it needs to be resected.1 Conversely, caseous calcification of the mitral annulus (CCMA)—a rare subtype of mitral annulus calcification (MAC), constituting 0.6% of all MAC cases (0.06%–0.07% of the whole population undergoing echocardiography)—is usually followed up on conservatively.2 However, CCMA may also be resected to prevent embolism.2 Recently, CCMA-associated CAT cases have been reported3–6; however, the mechanism by which CAT arises from CCMA was not sufficiently considered.
Herein, we present a rare case of CCMA-associated CAT with chronic inflammatory cardiomyopathy (CICMP) and comprehensively consider its aetiology, including the importance of inflammation.
Summary figure
Case presentation
A 53-year-old male, who initiated dialysis for end-stage renal dysfunction due to diabetic nephropathy or nephrosclerosis at our nephrology department 10 years prior, underwent annual follow-up echocardiography for progressive aortic valve stenosis (AVS) and moderate regurgitation with normal left ventricular (LV) ejection fraction (LVEF). One year before, calcifications suggesting MAC were observed in the posterior mitral annulus, which were not seen two years before. At the latest follow-up, echocardiography revealed a round, smooth-surfaced 22 × 17-mm mass with high echogenicity in the surrounding area and slightly decreased internal brightness on the posterior mitral annular ring of the left atrial side (Figure 1, see Supplementary material online). The patient had no significant symptoms and physical findings, except for systolic murmur.
Echocardiographic images taken (A) 2 years ago, (B) 1 year ago, and (C) at the time of the case presentation. The upper panels show the two-chamber view, while the lower panels show the short-axis view. The images indicate that the circular mass expanded rapidly over the course of 2 years, with high peripheral echogenicity and an echolucent centre at the posterior leaflet of the mitral valve.
Echocardiography also revealed moderate AVS with a transaortic valvular peak flow of 3.76 m/s and moderate aortic valve regurgitation. Mild mitral valve regurgitation but no stenosis was observed. The LV inflow velocity pattern showed a pseudo-normal pattern with 47-mm diameter left atrial enlargement. Serial echocardiography over two years revealed LV enlargement and decreasing LVEF. The LV end-diastolic/end-systolic diameter and LVEF were 50/33 mm and 64%, respectively, 2 years ago; 57/41 mm and 52% 1 year ago; and 59/47 mm and 42% at the latest follow-up.
Considering haemodialysis status, we predicted progression to near-severe AVS, with worsening LV systolic dysfunction, becoming an indication for aortic valve replacement (AVR) in the near future.
Computed tomography (CT) revealed a high-density mass with no contrast enhancement (Figure 2). Magnetic resonance imaging (MRI) showed a well-defined mass of high intensity at the centre, with a hypointense rim on T1 imaging and a devoid signal on T2 (Figure 3). Neoplasms, including myxomas and papillary fibroelastomas, were excluded based on their imaging features. Laboratory findings did not indicate infection, and vegetation with infectious endocarditis was not suspected. Considering end-stage renal dysfunction on haemodialysis and imaging findings, CCMA was suspected. The rapid mass enlargement raised concerns about potential embolism. Consequently, the mass was resected with AVR.
Computed tomography image of the heart in the transverse plane. The arrow shows a high-attenuation mass.
Cardiac magnetic resonance imaging. (A) Intense image with T1 weighted, (B) intense image with T2 weighted. The arrows indicate a mass showing high intensity, with a clear boundary and low-intensity periphery on the T1 image and signal-void centre on the T2 image.
Incision of the left atrium revealed a mass beneath the atrial endocardium in the mitral valve ring (P1–2); creamy substances were observed on the incision of the mass, suggesting CCMA (Figure 4). After thorough tissue removal and debridement, the incision site was sutured by proline. Aortic valve replacement was performed using a 21-mm SJM valve. The weaning from cardiopulmonary bypass was relatively smooth. At discharge, warfarin and aspirin were prescribed, along with bisoprolol for the paroxysmal atrial fibrillation after surgery.
Parts of the resected mass.
No embolic events were observed before or after the surgery.
Histopathological examination revealed scattered granular and nodular calcifications, mostly consisting of inflammatory cell infiltration and vascular proliferation of neutrophils, lymphocytes, foam cells, tissue macrophages, and plasma cells, with partial ossification compatible with CAT (Figure 5A). LV myocardial biopsy to rule out secondary cardiomyopathy and resected aortic valve showed inflammatory cells similar to those observed in CAT (Figure 5B and C). Therefore, CICMP was diagnosed based on decreased wall motion and myocardial fibrosis, with inflammatory cell infiltration > 14 mm2, CD3-positive T cells > 7/mm2, and tenascin C (4C8) negativity.7 However, the cause of CICMP could not be determined.
Histopathological analysis of the specimen using haematoxylin and eosin (HE) staining. (A) CAT: scattered granular and small nodular calcifications are observed, with the inflammatory cells consisting of histiocytes—including neutrophils, lymphocytes, foam cells, and plasma cell infiltrates—accompanied by angiogenesis and partial hyalinization (HE × 4). (B) Myocardium: inflammatory cell infiltration—including CD3-positive T cells ≥ 7/mm², along with fibrosis and myocardial cell dropout—is observed (HE × 4). (C) Aortic valve: many granular and nodular calcifications are observed, accompanied by inflammatory cell infiltration—including neutrophil and fibroblast proliferation—in the surrounding areas. The morphology of the calcifications and surrounding inflammation resembles that of CAT (HE ×4).
Echocardiography 6 months after resection showed no tumour recurrence (see Supplementary material online), no progression of mitral regurgitation, normal function of aortic prosthetic valve, and no improvement of LVEF (41%)
Discussion
We diagnosed a case of CAT, initially considered CCMA, with chronic inflammatory disease before it caused embolism.
Caseous calcification of the mitral annulus is characterized by caseous necrotic material within the calcification.2 However, the mechanism underlying caseous degeneration in CCMA remains unclear. It is often observed in patients with end-stage renal dysfunction, particularly those on haemodialysis, indicating abnormal calcium phosphate metabolism.2 The typical echocardiographic appearance is a circular or crescent-shaped mass with high peripheral echogenicity and an echolucent centre at the posterior leaflet of mitral valve annulus.8 The importance of multimodality imaging is evident in this case and similar cases9,10: on CT images, it appears as a high-attenuation, non-enhancing mass with oval or crescent-shaped calcium deposition.9 On MRI T1-weighted images, CCMA presents as a high-intensity mass with a clear boundary and low-intensity periphery, whereas on T2-weighted images, the interior is signal-void and the periphery appears high-intensity when compared with the myocardium.10 When incised, the mass releases pasty and white caseous substances.2
Caseous calcification of the mitral annulus is a benign, non-neoplastic lesion that required differentiation from cysts, abscesses, thrombi, verrucae, and tumours; asymptomatic CCMA is mostly managed conservatively.2 However, CCMA can cause systemic embolism, leading to fatal outcomes.11,12 Caseous calcification of the mitral annulus undergoes a dynamic transformation over time, including progression or withdrawal2; therefore, predicting the prognosis may be challenging.
Calcified amorphous tumours are non-neoplastic intracavitary masses pathologically diagnosed as calcified nodules in an amorphous fibrinous background with degeneration and focal chronic inflammation.1 They arise from various sites in the heart and take various forms, necessitating differentiation from vegetation and neoplasms.1 Many CAT cases involve systemic embolic events, leading to surgical removal to prevent recurrence and confirm the diagnosis, especially in cases with high mobility.6 Surgical treatment for CAT aims for complete resection; however, in the case of CCMA-associated CAT, the risks associated with complete resection, such as LV rupture due to mitral annulus weakening, should be considered. Therefore, the approach involves incising the mass, completely removing its contents, and covering the incision site. We suggest that echocardiographic follow-up is planned at least within 6 months after surgery.
Endothelial damage, stasis, a hypercoagulable state, abnormal calcification metabolism, and chronic inflammation are potential mechanisms related to CAT.13
In a case of CAT, the time-course of the relationship between inflammatory changes and clinical manifestations was followed using fluorodeoxyglucose-positron emission tomography.14 The degree of inflammation was consistent with CAT progression for 2.5 years, indicating a crucial role of chronic inflammation and profibrotic processes in progression.14
In our case, the timing of decreased LV systolic function—which might be highly related to CICMP—and the arising mass coincided, suggesting that chronic inflammation and immunopathological reactions may have influenced the CAT arising from CCMA.
At six months postoperatively, LV systolic function did not improve, possibly due to CICMP, which generally requires immunosuppressive therapy. We are considering switching from bisoprolol to carvedilol, which has anti-inflammatory effects on the myocardium.14
To our knowledge, this is the first report of CAT arising from CCMA diagnosed before embolic events. Progressive CCMA should be considered during CAT development and possible embolic events, especially in patients with inflammatory comorbidities of the heart.
Lead author biography
Hiroyoshi Yamamoto graduated from the Asahikawa Medical College, Japan in March 1993. After working at Osaka University, Osaka Police Hospital, Osaka National Hospital Organization Medical Center, and Osaka Seamen’s Insurance Hospital, he is currently the Director of the Department of Cardiology and the Department of Diagnostics at Osaka Minato Central Hospital.
Supplementary material
Supplementary material is available at European Heart Journal – Case Reports online.
Acknowledgements
We thank the patient for allowing us to present his case. We would also like to thank Dr Takanori Kawata for attending physician of nephrology and Dr Hiroyuki Nishi for the interpretation of surgical findings. We would like to thank Editage (www.editage.jp) for English language editing.
Consent: The authors confirm that informed written consent was obtained for the submission and publication of this case report, including the accompanying text and images, as per COPE guidelines.
Funding: None declared.
Data availability
In consideration of the privacy of the individual involved in the study, the raw images during the research process will not be made publicly available. However, interested researchers may request access to the data by contacting the corresponding author, adhering to ethical and data policy frameworks.
References
Author notes
Conflict of interest. None declared.
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