A 58-year-old female with good past health presented with an enlarging sternal mass. Computed tomography revealed a 7-cm osteolytic mass in the lower sternum with cortical destruction (Fig 1a and b). Core biopsy revealed metastatic follicular thyroid carcinoma (FTC) with oncocytic cell differentiation. Ultrasound of the thyroid showed a 1-cm calcified right thyroid nodule, and fine needle aspiration cytology suggested an oncocytic cell neoplasm. ¹⁸F-fluorodeoxyglucose positron emission tomography–computed tomography demonstrated avid uptake in the right thyroid lesion, small pulmonary metastases and bone metastases, the largest at the sternum, with small lesions in the right mandible, left scapula and left tenth rib.

As the large sternal metastasis caused severe pain, en bloc resection of the sternal tumour was performed along with the medial ends of the bilateral anterior ribs (Fig 1c and d). The bony resection margin was determined preoperatively using the data from positron emission tomography–computed tomography and virtual planning software (Mimics; Materialise, Leuven, Belgium). Reconstruction was performed with a custom-designed three-dimensional (3D)–printed titanium alloy implant (Ti6Al4V Grade 23; Koln 3D Medical, Hong Kong, China) [Fig 2]. Finite element analysis was performed to optimise the design for implant longevity by eliminating stress risers. The 3D-printed surgical guides ensured precise bone cuts and accurate implant fitting. The total planning and production time was 45 days, and the implant weighed 699 g.

The superior part of the implant was fixed to the native manubrium with eight 3.5-mm orthopaedic angle-stable titanium locking screws (DePuy Synthes, West Chester [PA], US). The undersurface of the implant was porous to allow bone ingrowth, enhancing long-term stability. Laterally, the implant comprised sockets accommodating the native third to fifth rib stumps, which were further secured with non-absorbable No. 2 FiberWire sutures (Arthrex, Naples [FL], US). Inferior to the sixth rib, the conjoint costal cartilage stump was loosely opposed to the implant using sutures passed through pre-formed holes of the implant. A Permacol (Medtronic, Minneapolis [MN], US) mesh was placed over the anterior surface of the implant, above which the muscle flap and skin were closed primarily.

Histopathological examination of the sternal specimen confirmed metastatic FTC with clear margins. The patient made an uneventful recovery and subsequently underwent total thyroidectomy, which demonstrated multifocal FTC with extensive capsular invasion.

Postoperatively, the patient received two courses of radioiodine therapy and continued bisphosphonate treatment with thyroid-stimulating hormone suppression. At 1.5 years after the operation, she had stable disease, was pain-free, and had resumed work and independent daily activities.

To the best of our knowledge, this is the first 3D-printed sternal implant manufactured in Hong Kong using medical-grade titanium alloy powder (TiAl4V Grade 23) by direct metal laser sintering. This custom-made implant represents a novel reconstructive option that provided excellent symptomatic relief. It restored the form and strength of the anterior chest wall while allowing chest wall motion through its rib-socket design. Previous case reports and series on resection of sternal metastases from FTC have utilised alternative reconstructive methods, including pectoralis major flaps, Marlex mesh, Gore-Tex mesh, titanium mesh, and acrylic plates.1

Follicular thyroid carcinoma is the second most common type of well-differentiated thyroid cancer after papillary thyroid carcinoma. Although the presence of distant metastases is a poor prognostic factor, the 5-year disease-specific survival rate for metastatic FTC can be as high as 82.2%.2 Given this considerable life expectancy, balancing oncological with symptomatic relief is essential for optimal management.

Radioactive iodine is less effective in treating bone metastases from differentiated thyroid cancer. Surgical resection of bone metastases has been recommended for patients with solitary lesions with curative intent and for those causing significant morbidity for symptomatic palliation. Furthermore, metastasectomy for maximal tumour debulking may facilitate the effectiveness of radioiodine therapy, as a higher dose can be concentrated in residual malignant cells.1

The custom-made implant and tumour resection plan were based on the patient’s fine-cut computed tomography images. The implant’s central mesh structure was not anatomically identical to the sternum or costal cartilages but still served to protect the mediastinal structures. The mesh design reduced implant weight and allowed soft-tissue ingrowth, theoretically reducing infection risk. Post-processing involved proprietary heat treatment to reduce internal stress and material brittleness, while electropolishing smoothed the surface to reduce fatigue failure.

A 3D-printed polymer rib cage model was made to determine a good fit of the implant, and simulate the implantation process (Fig 2c to e). The lateral parts of the implant connected to the bilateral third to fifth ribs via 2-cm–deep socket design, allowing rib fixture without screws (Fig 2e). This unique design was adopted from the growing orthopaedic implants used in children,3 and enabled free movement of the junctions between the implant and ribs as well as chest wall expansion and contraction during breathing.

In previously reported custom sternal implants, superior fixation was typically achieved using angle-stable screws in the remaining manubrial bone.4 5 Costal fixation methods varied: most designs used rigid screws while others incorporated flexible elements at the rib junction, such as polymer material, spring mechanisms or metal cables and wires, to enhance implant flexibility.6 One case report described two paediatric patients with a partially slidable design, theoretically accommodating chest cavity growth.7 Nonetheless, fatigue failure remains a concern across designs, given the human respiratory cycle of approximately 25 000 breaths per day and over 250 million cycles over a 30-year lifespan. Long-term follow-up of patients with custom sternal prostheses would provide valuable insight into optimal design and fixation methods.

Our design theoretically reduces metallic stress and long-term fatigue risk by preserving motion at the rib-implant junction. Activities of daily living were gradually resumed, and exercise tolerance remained unaffected. The surgery successfully improved our patient’s quality of life, which is vital given the relatively prolonged survival with FTC.

This implant achieved excellent functional outcomes and may serve as a model for reconstruction of large anterior chest wall defects. With technological advancements in 3D printing, similar custom-made implants will be more readily available in the near future, tailored to individual patient needs. This case demonstrates a novel treatment for sternal metastasis. Appropriate patient selection with good premorbid status and reasonable life expectancy is crucial to ensure maximum benefit from such surgery.

All authors contributed to the concept or design, acquisition of data, analysis or interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

This case was presented at the Interesting Case session at the International Surgical Week 2024 held in Kuala Lumpur, Malaysia, 26-29 August 2024.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

This study was approved by the Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster, Hong Kong (Ref No.: UW 25-049). Written informed consent was obtained from the patient for publication of this case report along with the clinical images.

1. Batta R, Njoum Y, Deek R, Awad F, Bakri IA, Maree M. Follicular thyroid carcinoma with sternal metastasis: a case report. Int J Surg Case Rep 2023;109:108625. Crossref

2. Sugino K, Kameyama K, Nagahama M, et al. Follicular thyroid carcinoma with distant metastasis: outcome and prognostic factor. Endocr J 2014;61:273-9. Crossref

3. Fassier F. Fassier–Duval telescopic system: how I do it? J Pediatr Orthop 2017;37 Suppl 2:S48-51. Crossref

4. Dzian A, Živčák J, Penciak R, Hudák R. Implantation of a 3D-printed titanium sternum in a patient with a sternal tumor. World J Surg Oncol 2018;16:7. Crossref

5. Liu C, Sun H, Lin F. The application of three-dimensional custom-made prostheses in chest wall reconstruction after oncologic sternal resection. J Surg Oncol 2024;129:1063-72. Crossref

6. Ramírez O, Torres-SanMiguel CR, Ceccarelli M. Design of a compliant sternum prosthesis for improving respiratory dynamics. Prosthesis 2024;6:561-81. Crossref

7. Anderson CJ, Spruiell MD, Wylie EF, et al. A technique for pediatric chest wall reconstruction using custom-designed titanium implants: description of technique and report of two cases. J Child Orthop 2016;10:49-55. Crossref

A 62-year-old male presented to Shandong Provincial Hospital in China in October 2024 with chest pain. Physical examination was unremarkable, and electrocardiography showed normal sinus rhythm with no ST-segment depression or elevation. The patient had a 5-year history of hypertension, with a maximum systolic blood pressure of 170 mm Hg. Transthoracic echocardiography revealed a small pericardial effusion but no significant structural cardiac abnormalities (Fig a). He was transferred to the cardiac intensive care unit for pain management and symptomatic treatment. On admission, his systolic blood pressure gradually decreased to around 50 mm Hg, and his heart rate increased, with clear signs of pericardial tamponade. Following treatment with vasopressors and fluid resuscitation, his systolic blood pressure rose to 90 to 100 mm Hg and gradually stabilised. Follow-up transthoracic echocardiography revealed a significant increase in pericardial effusion, prompting pericardiocentesis that drained approximately 700 mL of haemorrhagic fluid. Microbial cultures and cytological examination were negative. A subsequent echocardiogram confirmed no recurrence of the pericardial effusion.

Given the patient’s medical history and the initial echocardiographic findings, a preliminary diagnosis of aortic dissection was considered. Nonetheless a comprehensive aortic computed tomography angiography revealed no signs of aortic dissection or intramural haematoma. Maximum intensity projection revealed an irregular, contrastenhancing linear area at the lower right atrium near the right atrial appendage, extending towards the pericardial edge. The contrast density was reduced and the boundary appeared indistinct, with a slightly higher-density area within the pericardium (Fig b). Maximum intensity projection is a high-resolution imaging technique that effectively visualises fine vascular structures and complex anatomical features in small volumes, making it particularly suitable for analysing microvasculature. After multidisciplinary discussions, the progressive pericardial effusion was suspected to be related to an abnormality or mass lesion in the right atrium. A decision was made to proceed with exploratory thoracotomy.

Preoperative transoesophageal echocardiography confirmed the presence of a mass in the right atrial free wall (Fig c). During surgery, a 2.5 × 2.5 cm² mass was found protruding from the free wall of the right atrium, infiltrating the atrial wall. The mass was located approximately 1 cm from the atrioventricular junction and at a sufficient distance from the superior and inferior vena cavae (Fig d-f). The tumour was successfully resected with a safe margin, and the atrial wall defect repaired using a bovine pericardial patch. Postoperative histopathological examination confirmed the diagnosis of cardiac angiosarcoma (Fig g). Follow-up echocardiography revealed normal cardiac chamber structure and function. The patient made an uneventful recovery and was discharged on postoperative day 9 feeling well. Nonetheless, approximately 3 months later, the patient developed pericardial effusion again, suggesting recurrence with possible metastatic progression. The patient did not undergo further treatment.

In clinical practice, chest pain associated with acute pericardial effusion is often considered a potential indication of aortic dissection, as was initially suspected in this case. Nonetheless, routine preoperative assessments for aortic dissection revealed no structural abnormalities in the heart or aorta, leading us to exclude this diagnosis. In establishing a definitive diagnosis, we broadened our differential diagnosis to include other conditions that could cause chest pain with acute pericardial effusion, such as cardiac tumour that is not easily detected in clinical practice. Additionally, we considered whether appropriate diagnostic methods had been used. Hence, we employed more specialised and less commonly used diagnostic techniques such as maximum intensity projection imaging and transoesophageal echocardiography to obtain a clearer understanding of the cardiac structures and reach a definitive diagnosis.

The pathological diagnosis in this patient’s tumour was angiosarcoma. Cardiac angiosarcoma, a rare malignant cardiac tumour, accounts for about 25% to 30% of all primary malignant cardiac tumours.1 Most affected patients are under 65 years of age, and the tumour most frequently originates in the right atrium, often invading adjacent structures.2 Typical clinical manifestations include dyspnoea, pericardial effusion, and chest pain, and these usually appear in the advanced stages of disease, leading to a poor prognosis.3

Patients with chest pain and pericardial effusion are often clinically diagnosed with aortic dissection. Nonetheless, once initial evaluations exclude this diagnosis, it is essential to consider cardiac tumour, a relatively rare condition in clinical practice.

Concept or design: Z Xu, G Zhang.
Acquisition of data: H Yang, X Zhang.
Analysis or interpretation of data: H Yang, X Zhang, Z Chen, F Zhang.
Drafting of the manuscript: H Yang, X Zhang, Z Chen, F Zhang.
Critical revision of the manuscript for important intellectual content: Z Xu, G Zhang.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patient was treated in accordance with the Declaration of Helsinki. The patient was provided with information regarding the study and gave written informed consent for all treatments, procedures, and publication of the case report with the accompanying images prior to participation.

1. Kumari N, Bhandari S, Ishfaq A, et al. Primary cardiac angiosarcoma: a review. Cureus 2023;15:e41947. Crossref

2. Patel SD, Peterson A, Bartczak A, et al. Primary cardiac angiosarcoma—a review. Med Sci Monit 2014;20:103-9. Crossref

3. Chambergo-Michilot D, De la Cruz-Ku G, Sterner RM, Brañez-Condorena A, Guerra-Canchari P, Stulak J. Clinical characteristics, management, and outcomes of patients with primary cardiac angiosarcoma: a systematic review. J Cardiovasc Thorac Res 2023;15:1-8. Crossref

A 61-year-old female with lupus nephritis on peritoneal dialysis presented to our institution in May 2018 with an incidental finding of a right lung nodule on chest X-ray. Subsequent computed tomography of the thorax and positron emission tomography–computed tomography (PET-CT) showed a right lower lobe nodule and two right pleural nodules. Wedge resection of the three lesions confirmed epidermal growth factor receptor (EGFR) exon 19 deletion–positive metastatic adenocarcinoma of the lung with pleural metastases. She had baseline Eastern Cooperative Oncology Group performance status score of 1 and had been on continuous ambulatory peritoneal dialysis for 10 months prior to the cancer diagnosis due to end-stage renal failure secondary to lupus nephritis, with baseline estimated glomerular filtration rate below 5 mL/min/1.73 m² and normal albumin level. Concomitant medications included hydroxychloroquine and prednisolone for lupus.

The patient started on erlotinib 150 mg daily in December 2018 with close monitoring of renal function. Disease control was sustained with best response of stable disease confirmed by serial PET-CT scans performed approximately every 6 months. Erlotinib was well tolerated except for a CTCAE (Common Terminology Criteria for Adverse Events) grade 1 skin reaction manifesting as skin dryness and pruritic maculopapular rash, managed with topical emollients. Nonetheless, after 15 months of treatment, her skin reaction progressed to grade 2, with development of paronychia, blepharitis and increased pruritus. Erlotinib was suspended for 3 weeks. She also experienced grade 2 mucositis with recurrent epistaxis, treated with topical emollients, topical steroids and nasal ointment. Erlotinib was resumed at 100 mg daily after resolution of toxicities and was subsequently well tolerated. Renal function remained stable on continuous ambulatory peritoneal dialysis throughout erlotinib treatment.

In May 2020, following 18 months of erlotinib treatment, PET-CT of the patient revealed disease progression in the pleura, liver, and lymph nodes as well as bone metastases. She was switched to osimertinib 80 mg daily in June 2020 after plasma EGFR mutational analysis revealed a T790M mutation. Treatment was well tolerated with only a grade 1 skin reaction controlled by oral doxycycline and topical emollients. There was an initial biochemical response with carcinoembryonic antigen level decreasing from 246 ng/mL to a nadir of 83.1 ng/mL after 3 months of treatment, but only a mixed response on PET-CT, evidenced by responding lymph node metastases and existing liver metastases, alongside the development of new liver metastases and new collapse of the T4 vertebra with narrowing of the spinal canal. Magnetic resonance imaging showed severe spinal stenosis with radiological cord compression at T4. The orthopaedic team was consulted but the patient declined surgical intervention and was managed conservatively with thoracolumbar orthoses. She had previously received palliative radiotherapy to the same site for pain control. Clinically, she had no limb weakness, sensory changes or sphincter disturbance. With limited options for next-line treatment due to end-stage renal failure, she opted to continue osimertinib.

After a further 9 months of osimertinib treatment, the patient was hospitalised in March 2021 with epigastric pain and newly deranged liver function. She had previously tested negative for hepatitis B surface antigen, with positive anti–hepatitis B antigen, positive anti-hepatitis B antibody, and undetectable hepatitis B virus DNA. The PET-CT confirmed further disease progression with extensive liver metastases, described in the report as almost entirely involving the liver with new hepatomegaly of up to 17 cm. Osimertinib was stopped and the patient succumbed 1 week later to liver failure secondary to liver metastases.

Lung cancer is the most common cancer and the leading cause of cancer-related mortality in Hong Kong.1 Genetic profiling has revolutionised treatment. In Hong Kong, EGFR mutation represents the most common driver mutation, occurring in up to 50% of lung adenocarcinomas among Asians.2 Treatment with EGFR tyrosine kinase inhibitors (TKIs) has demonstrated excellent efficacy and tolerability, extending median survival in patients with metastatic disease to more than 3 years.3 In general, systemic treatment for cancer patients with end-stage renal failure poses particular concerns as renal impairment affects drug excretion as well as absorption and protein binding. Clinical data on the use of EGFR TKIs in patients on dialysis are scarce and largely limited to those on haemodialysis. Hong Kong has adopted a Peritoneal Dialysis First policy since 1985 and has the highest peritoneal dialysis-to-haemodialysis ratio globally.4 This raises specific challenges, as drug elimination by peritoneal dialysis differs from that by haemodialysis. Our case report represents the first in the literature to demonstrate the efficacy and safety of erlotinib and osimertinib in a patient on peritoneal dialysis.

There are no recommendations for dose adjustment when prescribing erlotinib in the presence of renal impairment. Erlotinib is mainly metabolised in the liver by the cytochrome P450 system, primarily CYP3A4 (80%). Renal excretion plays a minor role in its elimination (around 9%).5 Pharmacokinetic analysis in lung cancer patients with chronic renal failure undergoing haemodialysis showed that erlotinib plasma levels were similar before and after dialysis, possibly due to its high protein binding of up to 95%.5 There are no pharmacokinetic data for erlotinib in patients undergoing peritoneal dialysis.

For osimertinib, no dosage adjustment is necessary in mild-to-moderate renal impairment, but it is not recommended for patients with creatinine clearance below 15 mL/min according to the United States Food and Drug Administration labelling.6 Osimertinib is mainly eliminated by hepatic metabolism (68%), with 14% undergoing renal excretion.7 In a pharmacokinetic study of osimertinib in renally impaired patients, parameters were similar between the control group, comprising patients with normal renal function, and two groups stratified by severity of renal impairment (estimated glomerular filtration rates 30-50 mL/min/1.73 m² and <30 mL/min/1.73 m²).7 Nonetheless, a higher incidence and severity of toxicities were observed in the two groups with renally impaired patients.7 For patients on haemodialysis, safety data and clinical outcomes with osimertinib are limited to case reports and small pharmacokinetic studies, which suggest that it can be administered safely. One case report demonstrated that therapeutic drug monitoring may be useful: osimertinib 80 mg daily resulted in grade 3 fatigue in a patient on haemodialysis, but dose adjustment guided by periodic plasma concentration monitoring achieved sustained stable disease for more than a year without recurrence of toxicities.8 Although therapeutic drug monitoring may not be routinely available, careful clinical monitoring for adverse effects during administration of EGFR TKIs in patients with renal impairment is warranted. Drug suspension and dosage adjustments may be undertaken at the clinician’s discretion.

In conclusion, there remains room for exploration regarding the use of EGFR TKIs in patients with end-stage renal failure on peritoneal dialysis. This case demonstrates that both erlotinib and osimertinib exhibited a tolerable safety profile and reasonable treatment efficacy in patients on peritoneal dialysis and may be administered by clinicians with close monitoring.

Both authors contributed to the concept or design, acquisition of data, analysis or interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. Both authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

Both authors have disclosed no conflicts of interest.

The authors are grateful to the patient and their family for their support.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patient was treated in accordance with the Declaration of Helsinki. As the patient is deceased, her elder sister, as next of kin, provided written consent for publication of the case report.

1. Cancer Online Resource Hub. Cancers in Hong Kong: Common cancers in Hong Kong. Lung cancer. Available from: http://www.cancer.gov.hk/en/hong_kong_cancer/common_cancers_in_hong_kong/lung_cancer.html. Accessed 30 Mar 2026.

2. Shi Y, Au JS, Thongprasert S, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non–small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol 2014;9:154–62. Crossref

3. Lin JJ, Cardarella S, Lydon CA, et al. Five-year survival in EGFR-mutant metastatic lung adenocarcinoma treated with EGFR-TKIs. J Thorac Oncol 2016;11:556–65. Crossref

4. Li PK, Lu W, Mak SK, et al. Peritoneal dialysis first policy in Hong Kong for 35 years: global impact. Nephrology (Carlton) 2022;27:787–94. Crossref

5. Togashi Y, Masago K, Fukudo M, et al. Pharmacokinetics of erlotinib and its active metabolite OSI‑420 in patients with non–small cell lung cancer and chronic renal failure who are undergoing hemodialysis. J Thorac Oncol 2010;5:601–5. Crossref

6. United States Food and Drug Administration. Tagrisso (osimertinib) tablet, for oral use: highlights of prescribing information and full prescribing information. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208065s000lbl.pdf. Accessed 30 Mar 2026.

7. Fujiwara Y, Makihara R, Hase T, et al. Pharmacokinetic and dose-finding study of osimertinib in patients with impaired renal function and low body weight. Cancer Sci 2023;114:2087–97. Crossref

8. Tabata K, Aoki M, Miyata R, et al. Successful treatment with osimertinib based on therapeutic drug monitoring in a hemodialysis patient with non–small cell lung cancer: a case report. Case Rep Oncol 2023;16:705–10. Crossref

A 65-year-old male presented to Xinqiao Hospital Army Medical University on 29 November 2023 with a 6-month history of frequent palpitations, fatigue, and reduced exercise tolerance. His heart rate was 114 bpm and blood pressure was 138/87 mm Hg. Auscultation revealed irregular heart sounds and laboratory tests showed an elevated brain natriuretic peptide level (1411.25 pg/mL). An electrocardiogram revealed atrial fibrillation with intraventricular differential conduction (Fig 1a). Transthoracic echocardiography demonstrated enlargement of the left atrium and left ventricle, along with mild mitral and tricuspid valve regurgitation, and slight thickening of the atrial septum (Fig 1b). The patient was diagnosed with heart failure with persistent atrial fibrillation and was initially scheduled for radiofrequency catheter ablation.

Preoperative transoesophageal echocardiography (TEE) revealed a sandwiched foramen ovale under calm breathing conditions, with the depth of the left atrial surface approximately 7.6 mm and the height of the open end around 0.13 mm, while the right atrial surface remained well closed. During the Valsalva manoeuvre, the opening end of the left atrial surface widened while the right atrial surface remained closed, with no evident shunt observed. Additionally, an irregularly shaped webbed structure with compartmented echoes was identified in the middle of the primary septum (Fig 2a and b, Video 1). These findings were confirmed by three-dimensional TEE (3D-TEE), which measured the pouch to be approximately 19.2 × 10.5 × 24.5 mm³, oriented towards the mitral ring. The pouch exhibited a cobweb-like appearance, with its largest opening directed towards the roof, measuring approximately 20.7 × 10.5 mm². Within the pouch, a small polycystic division was observed. Colour Doppler imaging showed low-velocity blood flow within the septal valve but no flow across the atrial septum into the right atrium (Fig 2c, Video 2). Right heart contrast echocardiography confirmed no contrast images in the left atrium for 30 consecutive cardiac cycles following calm breathing and the Valsalva manoeuvre (Fig 2d, Video 3). Additional diagnostic evaluations with computed tomography angiography (Fig 1c) and cardiac magnetic resonance imaging (CMR) [Fig 1d] revealed a band-like abnormality on the left atrial side of the septum without any abnormal shunt. Following a multidisciplinary team discussion, the patient was diagnosed with a variant atrial septal pouch (ASP). After consulting with the patient, the medical team opted to alter the treatment strategy, discontinuing radiofrequency catheter ablation for atrial fibrillation in favour of conservative management. The patient has been followed up for over 1 year and remains in a stable condition with conservative treatment.

An atrial septal anatomical variant known as the ASP was first described by Krishnan and Salazar in 2010.1 It is a pouch-like structure resulting from the incomplete fusion of the primary and secondary septa, with openings into the left, right, or both atria. This patient presented with a left ASP with an accompanying web-like structure that did not involve the secondary septum, as evidenced by the absence of microbubbles during right-heart contrast echocardiography. We hypothesise that this web-like formation may represent a developmental variation of the primary septum, independent of the fusion between the primary and secondary septa. Nonetheless, this remains speculative due to limited research on web-like ASP, and we propose referring to it as a ‘webbed left ASP’.

Left ASP is recognised as a potential risk factor for cardioembolic stroke and blue toe syndrome.2 The pouch’s structure can promote blood stasis, facilitating in situ microthrombus formation and increasing the risk of embolic events.3 In this case, the additional presence of a web-like septal structure may further exacerbate the risk of thrombus formation. A polycystic, web-like septum over the primary septum with multiple floating ends was revealed on the 3D-TEE. The rupture of these delicate reticular structures could potentially result in a stroke. Furthermore, slow blood flow within the septation contributes to a haemodynamic environment prone to thrombus formation.

The atrial septum may receive high-velocity blood flow from the right pulmonary vein, with the contraction of transverse muscular fibres aiding in clearing the blood and reducing thrombus risk. Nonetheless, in conditions such as atrial fibrillation, heart failure, or mitral stenosis, this protective mechanism may fail.4 In the present case, atrial fibrillation impaired this mechanism, increasing the risk of thrombus formation. Given the high embolic risk associated with this complex anatomy, the patient opted for conservative treatment to avoid complications related to atrial septal puncture.

Multi-slice spiral computed tomography, CMR, and TEE are primary diagnostic tools for assessing atrial septal structural variations and thrombi.5 Although multi-slice computed tomography offers high-resolution imaging, it is less effective in patients with irregular heart rhythms, such as atrial fibrillation, due to the potential for image distortion. Detailed 3D morphology can be obtained using CMR, although it has limited resolution for thin structures such as the atrial septum.6 Transoesophageal echocardiography, particularly 3D-TEE, offers superior spatial resolution and is less affected by cardiac rhythm disturbances.7 It enables real-time visualisation of septal anatomy, variations, and haemodynamic flow, making it the ideal tool for diagnosing complex structures such as the webbed left ASP.

The web-like left ASP must be differentiated from bronchogenic atrial septal cysts and hydatid cysts.8 Bronchogenic cysts are benign congenital cystic masses, most commonly located in the mediastinum and lungs, with atrial septal involvement being extremely rare. Ultrasound typically reveals a thin-walled, well-defined anechoic or hypoechoic area, sometimes with internal septations and posterior acoustic enhancement, and no Doppler blood flow signals—features that differ significantly from this case. Hydatid cysts are caused by parasitic infections, usually associated with a history of contact with endemic areas. Their sonographic features and medical history make them relatively easy to identify.

This case highlights a novel variant of the left ASP with a web-like structure. Nonetheless, our understanding of ASP remains limited, and further research and observation are needed. Urgent questions remain regarding risk stratification in ASP, identification of high-risk cases, the need for interventional occlusion or surgical resection, and the optimal treatment approach post-thrombosis. We hope this case enhances understanding of this anatomical variation and informs future research.

Concept or design: G Yang, P He.
Acquisition of data: G Yang, J Yang.
Analysis or interpretation of data: Y Zou, S Xiao, J Yang, N Li.
Drafting of the manuscript: G Yang, P He, Y Zou.
Critical revision of the manuscript for important intellectual content: All authors.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

This study was funded by Sichuan Science and Technology Program (Ref Nos.:2025ZNSFSC1751, 2026YFHZ0039), and North Sichuan Medical College Affiliated Hospital Hospital-level Projects, China (Ref Nos.: 2025LC010, 210930). The funders had no role in the study design, data collection/analysis/interpretation, or manuscript preparation.

The patient was treated in accordance with the Declaration of Helsinki. The patient provided written consent for all treatments, procedures, and consent for publication, including the publication of the accompanying clinical images.

1. Krishnan SC, Salazar M. Septal pouch in the left atrium: a new anatomical entity with potential for embolic complications. JACC Cardiovasc Interv 2010;3:98-104. Crossref

2. Strachinaru M, Castro-Rodriguez J, Verbeet T, Gazagnes MD. The left atrial septal pouch as a risk factor for stroke: a systematic review. Arch Cardiovasc Dis 2017;110:250-8. Crossref

3. Hołda MK, Krawczyk-Ożóg A, Koziej M, et al. Left-sided atrial septal pouch is a risk factor for cryptogenic stroke. J Am Soc Echocardiogr 2018;31:771-6. Crossref

4. Dharshan AC, Joseph J, Goel SK, Tavakoly A, Shenoy MM. Double interatrial septum. Can J Cardiol 2010;26:e63. Crossref

5. Silvestry FE, Cohen MS, Armsby LB, et al. Guidelines for the echocardiographic assessment of atrial septal defect and patent foramen ovale: from the American Society of Echocardiography and Society for Cardiac Angiography and Interventions. J Am Soc Echocardiogr 2015;28:910-58. Crossref

6. Rochitte CE. Cardiovascular magnetic resonance worldwide: a global commitment to cardiovascular care. J Cardiovasc Magn Reson 2025;27:101842. Crossref

7. Gwak SY, Kim K, Lee HJ, et al. Three-dimensional agitated saline contrast transesophageal echocardiography for the diagnosis of patent foramen ovale. Sci Rep 2025;15:29136. Crossref

8. Gross DJ, Briski LM, Wherley EM, Nguyen DM. Bronchogenic cysts: a narrative review. Mediastinum 2023;7:26. Crossref

A primigravida attended our fetal medicine clinic (FMC) in March 2015 at 12 weeks’ gestation for first-trimester (T1) Down syndrome screening. Ultrasound examination revealed an absent nasal bone (NB). A morphology scan at 20 weeks confirmed this finding, along with bilateral non-ossified parietal bones, 11 pairs of ribs, and shortened femur and humerus. Amniocentesis revealed a normal chromosomal microarray. The couple opted for termination of pregnancy at 22 weeks. A computed tomography babygram confirmed the ultrasound findings and also showed bilaterally absent clavicles, hinting at a diagnosis of cleidocranial dysplasia (CCD). Targeted sequencing of the RUNX2 gene on the amniotic fluid sample revealed a de novo heterozygous pathogenic missense variant, c.674G>A (p.Arg225Gln), confirming the diagnosis. Multimodal prenatal and genetic findings were illustrated in Figure 1.

A primigravida attended the FMC in July 2022 at 12 weeks’ gestation for non-invasive prenatal screening (NIPS) for fetal aneuploidy. Ultrasound showed non-ossified skull bones (SB) and reduced spine ossification, but both clavicles were present. A review of the paternal history revealed that he had features of CCD, including the ability to approximate his shoulders, similar to a character in an American drama with diagnosed CCD. Molecular testing for CCD showed a pathogenic nonsense variant in the RUNX2 gene, c.577C>T (p.Arg193Ter), confirming the diagnosis. The fetus was thus suspected to have the same genetic problem. The couple declined invasive genetic testing. Instead, NIPS was performed using a novel technique known as coordinative allele-aware target enrichment sequencing (COATE-seq). This facilitated concomitant screening for chromosomal and monogenic disorders, encompassing 10 aneuploidies, 12 microdeletions and 64 monogenic disorders including RUNX2-related diseases (online supplementary Table 1). Results showed that the fetus was at high risk of having a pathogenic variant in the RUNX2 gene c.577C>T (p.Arg193Ter). Serial ultrasound showed normal SB ossification but with widened sutures, normal spine ossification, and mildly shortened clavicles with a normal S shape. A male infant was delivered at 39 weeks. Skeletal survey showed a persistent metopic suture, widened anterior fontanelle, 11 pairs of ribs, delayed ossification of pubic bones with widely spaced public symphysis, but both clavicles were present. Targeted RUNX2 variant analysis on the cord blood sample validated the presence of the paternal heterozygous pathogenic variant.

In the same patient’s second pregnancy, she attended the FMC at 12 weeks in January 2024 where ultrasound showed hypoplastic clavicles, non-ossified SBs and reduced spine ossification. The NIPS using COATE-seq showed that the fetus was at high risk of having the same pathogenic RUNX2 variant, c.577C>T (p.Arg193Ter). The couple declined invasive confirmatory testing. Serial ultrasound showed non-ossified SBs with widened sutures and fontanelle, a thin NB, very short clavicles with loss of normal S shape, 11 pairs of ribs, and mildly shortened long bones. A female infant was delivered at 38 weeks. Skeletal survey revealed bilateral hypoplastic clavicles and 11 pairs of ribs. Targeted RUNX2 variant analysis of the cord blood sample validated the presence of the paternal heterozygous pathogenic variant, confirming the diagnosis. Imaging and genetic findings are illustrated in Figure 2.

Cleidocranial dysplasia is a rare autosomal dominant skeletal dysplasia characterised by the classic triad of absent or hypoplastic clavicles, delayed ossification of the cranial bones with delayed closure of sutures and fontanelles, and dental abnormalities.1 Approximately two-thirds of cases are caused by RUNX2 gene mutations, with the remaining one-third resulting from copy number variations, translocations, or inversions involving the RUNX2 locus.2 The RUNX2 gene, located on chromosome 6p21, encodes a transcription factor that regulates osteoblast differentiation and chondrocyte maturation.3 Haploinsufficiency of RUNX2 gene leads to delayed intramembranous and endochondral ossification.3 The skull and clavicles, formed by intramembranous ossification, are therefore the most frequently affected.3

Prenatal diagnosis of CCD is rare. Including our three cases, only 22 cases have been reported to date (online supplementary Table 2). Most had affected family members, hinting at the diagnosis. Also, most were diagnosed based on clinical findings, with only 10 cases having a molecular diagnosis of RUNX2 gene defects. This highlights the pivotal role of prenatal ultrasound in identifying the characteristic features, namely, absent or hypoplastic clavicles, absent or inadequate SB ossification with wide fontanelles and sutures, and shortened long bones and absent NB. Among these, clavicular defect is the most characteristic. All three cases in our series had these typical features, detected during the first trimester, with an additional novel finding of 11 pairs of ribs. Nevertheless, the prenatal detection of CCD can be difficult as ultrasound features may be subtle. Although clavicles can be visualised during T1 ultrasound, they are not routinely examined. Conversely, absent NB, a marker for aneuploidy and routinely assessed during T1 nuchal translucency measurement, may be an important clue that prompts further examination of the clavicles and skull. With a positive family history, prenatal detection of inherited CCD by ultrasound may be more feasible. However, this can remain challenging as pathogenic RUNX2 variants exhibit complete penetrance but variable expressivity.1 Within the same family, one affected fetus may present with a subtle phenotype while another may show more pronounced manifestations, as illustrated by the two siblings in Family 2. Therefore, meticulous ultrasound is imperative in pregnancies at risk of CCD.

When CCD is suspected, invasive genetic testing is usually recommended to confirm the diagnosis through targeted RUNX2 variant analysis. However, invasive testing is associated with 0.1% to 0.2% risk of procedure-related fetal loss.4 As CCD rarely results in severe disability, many parents, particularly affected ones, may not consider termination of pregnancy and may choose to avoid invasive testing. In such cases, the new NIPS approach, COATE-seq, provides a viable diagnostic alternative.5 Its performance in high-risk pregnancies has been validated, demonstrating 98.5% sensitivity and 99.3% specificity compared with standard diagnostic methods.6 The two cases in Family 2 represent the first report of prenatal detection of CCD through the identification of a pathogenic RUNX2 variant using this novel technique. These cases highlight the great potential of combining T1 ultrasound with NIPS for early, non-invasive prenatal detection. This powerful non-invasive approach may also be applicable to other autosomal dominant skeletal dysplasia and monogenic disorders.

Concept or design: KW Choy, YH Ting.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: Y Cao, YH Ting.
Critical revision of the manuscript for important intellectual content: Y Cao, YH Ting.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

The authors thank the affected families for participating in and supporting this study.

This study was supported by the National Key Research and Development Program of China (Grant No.: 2023YFC2705603). The funder had no role in study design, data collection/analysis/interpretation or manuscript preparation.

This study was approved by the Joint Chinese University of Hong Kong–New Territories East Cluster Clinical Research Ethics Committee, Hong Kong (Ref No.: 2017.442). Written informed consent was obtained from the families for publication of clinical details and images.

The supplementary material was provided by the authors and some information may not have been peer reviewed. Accepted supplementary material will be published as submitted by the authors, without any editing or formatting. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by the Hong Kong Academy of Medicine and the Hong Kong Medical Association. The Hong Kong Academy of Medicine and the Hong Kong Medical Association disclaim all liability and responsibility arising from any reliance placed on the content.

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