An unusual cause of pulmonary edema

Case report

A 79-year-old woman presented after one month of increasing exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. She had a previous thyroid follicular carcinoma and underwent a total thyroidectomy in 2003, with adjuvant radioactive iodine-131 treatment for capsular and vascular invasion. Prior to this, she was diagnosed with primary hyperparathyroidism and underwent a parathyroidectomy in 1973. She had been under surveillance for a monoclonal gammopathy of unknown significance, first diagnosed in 2002. She also suffered from hypertension, hyperlipidemia, vitamin D deficiency, nephrolithiasis, and cholelithiasis. There was no history of cardiac disease. She lived independently and was self-caring. She presented to the emergency department in respiratory distress but hemodynamically stable. Cardiovascular examination revealed an elevated jugular venous pressure and dual heart sounds with no added sounds or murmurs. There were bilateral inspiratory crepitations. She was clinically euthyroid. A 12-lead electrocardiogram confirmed sinus tachycardia with incomplete right bundle branch block. A chest radiograph revealed an increased cardiothoracic ratio, bilateral pleural effusions, and prominent interstitial markings consistent with pulmonary edema. Renal function was mildly impaired (creatinine 81 µmol·L⁻¹, estimated glomerular filtration rate 59 mL·min⁻¹), and the total white cell count was elevated at 14.9 (neutrophilia). B-type natriuretic peptide was elevated at 368 ng·mL⁻¹ (normal <100  ng·mL⁻¹) but cardiac biomarkers were otherwise normal. Her free thyroxine level was 19 pmol·L⁻¹ and thyroid stimulating hormone was 0.2 µmol·L⁻¹, consistent with biochemical hyperthyroidism. Her initial management included diuresis and vasodilator therapy with angiotensin-converting enzyme inhibitors and nitrates. Transthoracic echocardiography revealed a large well-circumscribed left atrial mass (3.5 × 2.0 cm) with a hypoechoic cystic center, arising from the left atrial appendage. The lesion was prolapsing into the mitral valve causing severe functional obstruction with a mean transmitral gradient of 12 mm Hg and associated mild mitral regurgitation (Figure 1(a)). Left ventricular size and systolic function were normal. Pulmonary artery systolic pressure was mildly elevated at 41 mm Hg. Transesophageal echocardiography further defined the variegated cystic mass attached to the left atrial appendage and occluding the mitral valve orifice (Figure 1(b)). Cancer antigen 125 was elevated at 72 kU·L⁻¹ (normal <35 kU·L⁻¹) but other tumor markers were normal. The erythrocyte sedimentation rate was 90 mm·h⁻¹, C-reactive protein was 19 mg·L⁻¹, and serum thyroglobulin was <1.0  µg·L⁻¹. Computed tomography confirmed a lobulated left atrial lesion (50 × 34 mm) expanding the left auricle, with a soft tissue peripheral component. There was no evidence of malignancy elsewhere. A preoperative staging bone scan did not demonstrate any skeletal metastases. There was no obstructive coronary artery disease on coronary angiography. At surgery, a large lobulated tumor was visualized blocking the mitral valve and filling the left atrial appendage. Initial frozen-section analysis revealed malignant cells with necrotic areas. The tumor was adherent to the left atrial wall, and a debulking procedure was undertaken to relieve the valvular obstruction. Intraoperative transesophageal echocardiography confirmed resolution of the mitral stenosis with residual mild-to-moderate regurgitation (Figure 2). Microscopic examination identified highly pleomorphic and bizarre tumor cells described as spindle to epithelioid in appearance along with multinucleated giant cells (Figure 3). Mitotic figures and atypical mitoses were noted. The tumor cells were positive for smooth muscle actin, desmin and cytokeratin MNF116 and negative for CD34, epithelial membrane antigen, cytokeratin AE1/AE3, calretinin, S100 protein, myoD1, myogenin, and thyroid transcription factor 1. The final histologic diagnosis was pleomorphic sarcoma with myoid differentiation. The patient was discharged home after an uneventful postoperative recovery and significant improvement in her symptoms. She was not offered adjuvant radiotherapy or chemotherapy on the basis of incomplete surgical margins and historical prognosis. However, dacarbazine would be considered if she developed further obstructive symptoms. She was readmitted to hospital 3 months later with an episode of paroxysmal atrial fibrillation with rapid ventricular response, and was commenced on sotalol and warfarin. Transthoracic echocardiography showed no valvular obstruction (Figure 4).

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Figure 1.

Transthoracic echocardiography: (a) 2-dimensional image in apical 2-chamber view, showing a tumor mass arising from the left atrial appendage and prolapsing through the mitral valve; (b) mid-esophageal 2-chamber view, showing a tumor mass arising from the left atrial appendage and causing severe valvular obstruction.

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Figure 2.

Intraoperative transesophageal echocardiography post-resection: 2-dimensional image in mid-esophageal 4-chamber view, demonstrating reduced tumor bulk.

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Figure 3.

Highly pleomorphic and bizarre tumor cells with spindle to epithelioid appearance, multinucleated giant tumor cells, and tumor cells positive for smooth muscle actin.

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Figure 4.

Transthoracic echocardiography: 2-dimensional image post-resection.

Discussion

Primary cardiac tumors are a rare occurrence with a frequency of 0.02% based on autopsy data. ¹ Benign tumors account for 75% (50% are benign atrial myxomas) and 25% are malignant (75% are primary cardiac sarcomas). ² The incidence of secondary cardiac neoplasms by metastatic disease or local extension is 20–30 times greater than primary lesions, and they are most commonly associated with carcinoma of the lung, breast, esophagus, lymphoma, leukanemia, and melanoma. ³ Malignant primary cardiac sarcomas are classified by the World Health Organization into angiosarcoma, pleomorphic malignant fibrous histiocytoma, epithelioid hemangioendothelioma, fibrosarcoma, rhabdomyosarcoma, leiomyosarcoma, synovial sarcoma, and liposarcoma. ⁴ Histologic type or degree of differentiation does not appear to correlate with survival. Poor prognostic features include a high degree of cellularity, necrosis, and mitotic activity, corresponding to higher tumor grades. ⁵ In this case, the presence of myoid differentiation in what we believed to be a primary cardiac pleomorphic sarcoma does not conform to the above classification system.

Clinical presentations of cardiac neoplasms depend on the anatomical location, tumor size, and presence of regional extension or metastatic disease. Intracavitary obstruction to blood flow with impairment of ventricular filling (ball-valve effect mimicking mitral or tricuspid stenosis) can result in congestive cardiac failure, pulmonary hypertension, syncope or sudden cardiac death. ² Contrast angiocardiography has been superseded by transthoracic or transesophageal echocardiography for diagnosis of cardiac tumors, with sensitivities of 93.3% and 96.8%, respectively. ⁶ Benign atrial myxomas tend to develop in a characteristic location (fibrovascular stalk/pedicle attachment to the endocardium at the margin of the fossa ovalis) and are heterogenous in appearance. ² Multidetector computed tomography and magnetic resonance imaging can offer further diagnostic information to assist in planning surgical resection or chamber reconstruction. ⁷

Early surgery is the treatment of choice, as for benign atrial myxoma. This is usually curative with a good overall prognosis and low recurrence rate. ⁸ Death from cardiac sarcomas may result from intracardiac obstruction, local infiltration, metastatic disease, or general deterioration. ⁴ Up to 80% of primary cardiac malignancies have been reported to have metastases at the time of diagnosis. ² The mean survival from series in the literature is in the order of 9.6–11 months. Surgical resection is still regarded as the optimal treatment and a survival advantage has been demonstrated with complete excision (where technically feasible) while the role of neoadjuvant or adjuvant chemo- and radiotherapy remains controversial in the absence of randomized clinical trial data. ⁵ Although long-term survival is limited by local or systemic recurrence, palliative resection allows histological confirmation of the diagnosis and provides symptomatic relief.