Case 1: PAIS
A 54-year-old woman presented with a two-week history of chest pain. She had no significant past medical history. Routine blood tests, coagulation profiles, and serum tumor markers were within normal limits. Transthoracic echocardiography revealed localized thickening of the right ventricular free wall and multiple hypoechoic nodules on the pulmonary valve, suggestive of a neoplastic process. Computed tomography pulmonary angiography (CTPA) demonstrated soft-tissue density filling defects in the main pulmonary artery and right ventricular outflow tract, accompanied by a small pericardial effusion (Fig.1, E). Acute pulmonary thromboembolism was initially suspected, and therapeutic anticoagulation was initiated but yielded no clinical improvement after one week.
Cardiac magnetic resonance imaging (MRI) with and without contrast showed lesions involving the right ventricular free wall, outflow tract, and main pulmonary artery, with heterogeneous enhancement, compatible with metastatic disease (Fig.1, F-G). Subsequent 18F-FDG PET/CT revealed a mass-like soft-tissue lesion along the course of the pulmonary artery with markedly increased tracer uptake (SUVmax 10.6), as well as multiple hypermetabolic nodules in both lungs and a lesion in the pancreatic tail (SUVmax 8.9), consistent with distant metastases (Fig.1, A-D).
After multidisciplinary team (MDT) discussion and exclusion of contraindications, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed. Cytology revealed malignant spindle cells. Immunohistochemistry was positive for vimentin, MDM2, and CDK4. Fluorescence in situ hybridization (FISH) confirmed MDM2 gene amplification (MDM2/CEP12 ratio = 2.86). The final diagnosis was pulmonary artery intimal sarcoma, staged as cT4N0M1b (stage IV). After discussion with the family, the patient was discharged and referred to a tertiary cancer center for further management and was lost to follow-up.
Case 2: Primary Cardiac Myxoid Sarcoma
A 23-year-old man was referred to our institution after an intracardiac mass was incidentally discovered three days earlier during an evaluation for cholecystitis. His medical history included percutaneous device closure of a secundum atrial septal defect a decade prior. In the days preceding admission, he reported two episodes of transient monocular vision loss (amaurosis fugax). Laboratory tests showed elevated carbohydrate antigen 125 (CA-125), neuron-specific enolase (NSE), and D-dimer levels.
Transthoracic echocardiography demonstrated a large, mobile, heterogeneous mass appearing to arise from the interatrial septum near the occluder device, highly suspicious for a cardiac myxoma. Contrast-enhanced computed tomography (CT) of the chest and abdomen revealed a trans-septal mass involving both atria and ventricles with minimal enhancement, also interpreted as most consistent with myxoma ((Fig.2, F).
18F-FDG PET/CT, however, demonstrated heterogeneous intense uptake within the cardiac mass (SUVmax 6.3 on early imaging, increasing to SUVmax 7.0 on delayed imaging)(Fig.2, A-E), highly suggestive of a malignant process. No extracardiac hypermetabolic lesions were identified.
Following urgent MDT discussion, the patient underwent tumor resection with attempted reconstruction of the interatrial septum. Intraoperatively, a gelatinous, whitish tumor was found extensively infiltrating the interatrial septum and right atrioventricular junction, encasing the occluder device, protruding into the left atrium, and nearly obliterating the tricuspid orifice. Complete resection was impossible, and only palliative debulking could be achieved. Intraoperative frozen section was reported as “consistent with myxoma.”
Permanent histopathology revealed spindle and stellate cells embedded in an abundant myxoid matrix (Fig.2, G). Immunohistochemical staining was positive for CD56, Ki-67 (approximately 40%), focal ALK, and vimentin; MDM2 and CDK4 were negative. The final diagnosis was established as primary cardiac myxoid sarcoma. The postoperative course was uneventful. The patient declined adjuvant therapy and received palliative care only. He died of tumor recurrence and heart failure six months after surgery.
Discuss
The two cases reported herein represent rare sarcomas arising in distinct anatomical compartments of the cardiovascular system, each with unique histopathological features. Their diagnostic and therapeutic courses offer valuable lessons and clinical insights.
The primary teaching point of this report lies in the profound diagnostic challenges posed by these tumors. As illustrated in Case 1, PAIS is frequently misdiagnosed as pulmonary embolism owing to overlapping symptoms and the classic “filling defect” appearance on CTPA. Published series indicate that more than 50%–89% of PAIS patients are initially misdiagnosed, often receiving futile anticoagulation[13, 14]. In Case 2, primary cardiac myxoid sarcoma exhibited striking morphologic overlap with benign cardiac myxoma on both echocardiography and CT, directly contributing to the erroneous intraoperative frozen-section interpretation—a pitfall repeatedly documented in the literature[12, 15].
Against this background, 18F-FDG PET/CT played a decisive role in lesion characterization. Both tumors demonstrated intense FDG avidity (SUVmax 10.6 and 6.3, respectively). Extensive evidence now confirms that benign cardiac myxomas typically exhibit low or mild FDG uptake with mean/median SUVmax values ranging from 2.2 to 4.7[16, 17], while acute or chronic pulmonary thromboemboli show negligible or no significant FDG uptake in the thrombus itself (SUVmax typically <2.5 or comparable to blood pool)[14, 18]. Elevated glucose metabolism thus serves as a reliable discriminator between malignancy and benign/thromboembolic mimics. In Case 1, PET/CT not only established malignancy but also unveiled occult distant metastases, fundamentally altering staging and management. In Case 2, it provided the sole preoperative red flag for malignancy, prompting a more cautious surgical approach despite ultimate reliance on permanent histopathology.
Definitive diagnosis inevitably rests on pathology, and these cases highlight the necessity of a standardized, comprehensive pathologic workflow. Case 1 achieved diagnostic certainty through MDM2 positivity on immunohistochemistry and confirmatory FISH demonstrating MDM2 amplification—now recognized as the molecular hallmark and diagnostic gold standard of PAIS[19, 20].
By contrast, Case 2 proved diagnostically more elusive. Its immunophenotype (CD56+, focal ALK+, MDM2−, CDK4−) lacked specificity and effectively excluded intimal sarcoma, underscoring the molecular heterogeneity of cardiac sarcomas. Diagnosis ultimately hinged on classic morphologic features (abundant myxoid stroma, stellate/spindle cells) combined with a high proliferative index (Ki-67 ≈40%)[12]. This case emphasizes that morphologically ambiguous lesions demand exhaustive pathologic evaluation integrating histology, immunohistochemistry, and, when indicated, broader molecular panels to avert misdiagnosis.
Therapeutically, both cases reflect the shared dilemma of these aggressive sarcomas: achievement of complete (R0) resection is exceptionally difficult. The patient in Case 1 was deemed inoperable owing to distant metastases at presentation, whereas Case 2 permitted only palliative debulking due to extensive infiltration of critical cardiac structures. Contemporary series uniformly identify R0 resection as the most powerful prognostic factor; however, anatomical constraints render it feasible in fewer than 30% of patients, resulting in dismal local control and overall survival [12,13].