Identification of a PRKAR1A mutation (c.491_492delTG) in familial cardiac myxoma: A case report.

RATIONALE: Cardiac myxoma is the most common cardiac neoplasm. Currently, there are not many reports on familial cardiac myxoma. Herein, we reported 2 first-degree relatives with left atrial myxoma. PATIENT CONCERNS: A 20-year-old female was admitted in our hospital for lapsing into a coma for 24 hours, and was diagnosed with recurrent left atrial cardiac myxoma. The patient's father also had a history of cardiac myxoma. DIAGNOSIS: The patient was diagnosed with left atrial myxoma using transthoracic echocardiography (TTE). Whole exome sequencing (WES) identified a p.Val164Aspfs (c.491-492delTG) mutation in the cAMP-dependent protein kinase A (PKA) regulatory (R) subunit 1 (PRKAR1A) gene for both the proband and her father, but not in her uncle and brother, who had not shown manifestation of cardiac myxoma by the time of this report. INTERVENTIONS: The myxoma resection was performed following the standard procedure of open chest surgery. OUTCOMES: The tumor was successfully removed along with the tuberculum. The patient recovered well and was discharged home. No recurrence occurred during 1-year follow-up. LESSONS: Our findings suggest that PRKAR1A mutation (c.491_492delTG) may be associated with cardiac myxoma, and genetic counseling and specific locus mutation tests may contribute to assessing the risk of cardiac myxoma.

Predictors of Normalization of Circulating Interleukin-6 after Cardiac Myxoma Resection.

OBJECTIVE: To disclose the relationships between the anatomic features of cardiac myxomas and plasma interleukin (IL)-6 levels. METHODS: Twelve patients undergoing cardiac myxoma resection at The First Hospital of Putian, Teaching Hospital, Fujian Medical University were enrolled into this study. Pre- and postoperative IL-6 levels were determined by an enzyme-linked immunosorbent assay method, and correlations between cardiac myxoma dimension or volume and plasma IL-6 levels were analyzed. C-reactive protein (CRP) levels were also evaluated. RESULTS: IL-6 and CRP levels were significantly decreased one month after cardiac myxoma resection in comparison to preoperative values. IL-6 and CRP levels did not differ between patients with a cardiac myxoma of irregular appearance and those with a myxoma of regular gross appearance, or between patients with a pedicled or a sessile myxoma. Decrement of IL-6 of patients with irregular cardiac myxomas was much higher than that of patients with regular ones, while no intergroup difference was noted in decrement of CRP. A close direct correlation was noted between IL-6 levels and maximal dimension (length) or volume of cardiac myxomas, whereas CRP levels only correlated with maximal dimension of cardiac myxomas. CONCLUSION: Anatomic features of cardiac myxomas (sessile, irregular appearance, maximal dimension, and volume) could be determinants of the patients' circulating IL-6 levels. IL-6 was likely to be a more sensitive biomarker than CRP in predicting the inflammatory status of patients with cardiac myxoma. Sessile and irregular cardiac myxomas might predict more severe inflammatory conditions for their more abundant endothelial cells and IL-6 overproduction.

Predictors of normalization of circulating interleukin-6 after cardiac myxoma resection

Abstract Objective: To disclose the relationships between the anatomic features of cardiac myxomas and plasma interleukin (IL)-6 levels. Methods: Twelve patients undergoing cardiac myxoma resection at The First Hospital of Putian, Teaching Hospital, Fujian Medical University were enrolled into this study. Pre- and postoperative IL-6 levels were determined by an enzyme-linked immunosorbent assay method, and correlations between cardiac myxoma dimension or volume and plasma IL-6 levels were analyzed. C-reactive protein (CRP) levels were also evaluated. Results: IL-6 and CRP levels were significantly decreased one month after cardiac myxoma resection in comparison to preoperative values. IL-6 and CRP levels did not differ between patients with a cardiac myxoma of irregular appearance and those with a myxoma of regular gross appearance, or between patients with a pedicled or a sessile myxoma. Decrement of IL-6 of patients with irregular cardiac myxomas was much higher than that of patients with regular ones, while no intergroup difference was noted in decrement of CRP. A close direct correlation was noted between IL-6 levels and maximal dimension (length) or volume of cardiac myxomas, whereas CRP levels only correlated with maximal dimension of cardiac myxomas. Conclusion: Anatomic features of cardiac myxomas (sessile, irregular appearance, maximal dimension, and volume) could be determinants of the patients' circulating IL-6 levels. IL-6 was likely to be a more sensitive biomarker than CRP in predicting the inflammatory status of patients with cardiac myxoma. Sessile and irregular cardiac myxomas might predict more severe inflammatory conditions for their more abundant endothelial cells and IL-6 overproduction.

A case report of an angiomyxoma in the liver.

Angiomyxomas are uncommon myxoid tumours arising most commonly from the pelvis. A 46-year-old woman with a history of polycystic kidney disease presented asymptomatically for surveillance ultrasonography; changes were noted in the size and morphology of her liver cysts. Subsequent radiological assessment displayed features suspicious of malignancy and a right hemihepatectomy was performed with curative intent. Pathological examination of the resected specimen found histology consistent with an angiomyxoma arising primarily from the liver parenchyma. Follow-up review of the patient has been uneventful with annual imaging showing no evidence of recurrence. Angiomyxomas do not characteristically invade other tissues. However, any liver lesion displaying suspicious features of malignancy should be resected in the absence of disseminated disease.

Atrial myxoma: a rare but well-described cause of increased erythrocyte sedimentation rate and anaemia.

A 56-year-old woman visited her general practitioner 12 months prior with eczema. Blood samples showed anaemia, a haemoglobin level of 105 g/L and a high erythrocyte sedimentation rate (ESR) of 80 mm. Her eczema was diagnosed as discoid lupus erythaematosus but there were no signs of systemic lupus erythaematosus. Extensive investigations were made including testing of serial blood samples, repeated examinations by specialists in dermatology, rheumatology and gynaecology, and several X-rays including CT of the chest and the abdomen, all without finding a reasonable underlying diagnosis. One year later, the patient presented with dyspnoea associated with effort and body position; she was sent for echocardiography, which showed an atrial myxoma filling almost the whole left atrium and affecting the mitral valve. She was treated with urgent surgical removal and now, 6 weeks postsurgery, has fully recovered. She no longer has dyspnoea, her haemoglobin level and ESR have normalised, and the eczema has almost disappeared.

Risk factors for embolism in cardiac myxoma: a retrospective analysis.

BACKGROUND: Myxomas are the most common primary heart tumors and are closely associated with embolic events. Cardiac myxomas typically arise from the interatrial septum at the border of the fossa ovalis in the left atrium. Any other location is considered atypical. Embolism, one of the complications of myxoma, is associated with high morbidity and mortality. The aim of this study was to investigate the risk factors for embolism in patients with cardiac myxoma. MATERIAL AND METHODS: In this retrospective study, a cohort of 162 patients with cardiac myxomas was surgically treated between January 1998 and June 2014 at 3 cardiac centers in China. Preoperative data, including platelet count, sex, age, and the tumor (size, location, surface, and attachment), were compared between embolic and non-embolic groups of patients. RESULTS: No significant differences in vascular risk factors were seen between the 2 groups. However, the percentage of higher platelet count (>300 × 10(9)/L) and mean platelet volume in the embolic group were significantly higher than in the non-embolic group (P=0.0356, and 0.0113, respectively). Irregular surface and atypical location of the myxomas were also independently associated with increased risk of embolic complications. CONCLUSIONS: Tumor location, macroscopic appearance, mean platelet volume, and high platelet count are strong risk factors for embolic events in patients with cardiac myxomas.

Mean platelet volume levels in patients with cardiac myxoma.

Thromboembolic events such as cerebrovascular stroke are common and serious complications in patients with cardiac myxomas (CMs). Previous studies have reported that a high mean platelet volume (MPV) level reflects an activated platelet function and has been proven to be an independent risk factor for thromboembolic events. The aim of this study was to evaluate the relation between MPV level and CM. We compared the MPV levels between patients with CM and control subjects, and also evaluated the differences in the MPV levels in patients with CM before and after a successful surgical treatment. Furthermore, we compared the MPV levels in patients with and without cerebrovascular embolic symptoms. Fifty-one consecutive patients (13 men, 38 women, mean age 51.1 ± 16.9 years) who underwent excision of CM in our hospital in the last 13 years and 50 normal subjects as the control group were included in this study. The patients with CM were divided into two groups according to the presence or absence of cerebrovascular embolic symptoms. The preoperative and postoperative MPV levels of each CM patient was evaluated. MPV levels were found to be significantly higher in patients with CM than in control subjects (9.86 ± 1.30 fL vs. 7.63 ± 0.78 fL, p < 0.001). Moreover, the MPV levels significantly decreased after the surgical removal of CM (9.86 ± 1.30 fL vs. 8.68 ± 1.20 fL, p < 0.001). We also found that the MPV values were significantly higher in patients with neurological embolic events (10.55 ± 1.29 fL vs. 9.59 ± 0.78 fL, p = 0.016). We conclude that increased MPV levels might be considered as a marker of increased thromboembolic risk in patients with CM.

Imaging and intervention of paraneoplastic effect of a right atrial myxoma on factor VII activity levels.

We present the case of a 64-year-old Pakistani man with right atrial myxoma, recently diagnosed with acquired severe factor VII (FVII) deficiency. The patient presented with a history of chronic hiccups and weight loss. Initial evaluation revealed an isolated prolonged prothrombin time, severely reduced FVII activity level, and a giant right atrial myxoma protruding into the right ventricle on computed tomographic thorax and echocardiography. After surgical resection, the patient maintained normal prothrombin time with increased FVII activity level in the immediate 24 hours postoperatively, and a dramatically high level of FVII activity at the 2-month follow-up. We believe that the paraneoplastic effect of myxoma on the FVII activity levels is previously unreported. In addition, we believe that hiccups as a presenting symptom for a myxoma with an atypical origin from the lateral wall of the right atrium has not been reported.

Cardiac myxoma showing extramedullary hematopoiesis in a patient with beta thalassemia.

A 52-year-old woman presented with recurrent episodes of chest pain, shortness of breath, palpitations, and fatigue for three months. Her past medical history was significant for chronic anemia. Physical examination revealed a pansystolic murmur radiating to the left axilla. Her admission workup showed microcytic anemia. Her serum creatinine and iron studies were within normal limits and her hemoglobin electrophoresis pattern was that of beta thalassemia minor. Two-dimensional echocardiography showed a multilobulated mobile mass attached to the mitral annulus at the base of the anterior mitral valve leaflet. The patient underwent surgical resection of the mass. Pathology examination revealed a cardiac myxoma with conspicuous foci of extramedullary hematopoiesis.

Carney complex: pathology and molecular genetics.

Carney complex (CNC) is a unique multiple endocrine neoplasia syndrome (MIM 160980) which is characterized by unusual biochemical features (chronic hypersomatotropinemia and paradoxical responses of cortisol production to glucocorticoids) and multi-tissue involvement. The gene coding for the protein kinase A (PKA) type 1alpha regulatory subunit, PRKAR1A, had been mapped to 17q22-24, one of the genetic loci involved in CNC, and allelic analysis using probes from this chromosomal region revealed consistent changes in CNC tumors. Sequencing of the PRKAR1A gene in over 100 kindreds showed a number of mutations; in almost all cases, the sequence change was predicted to lead to a premature stop codon, and mutant mRNAs were subject to nonsense-mediated mRNA decay. In CNC cells, PKA activity assays showed increased stimulation by cAMP. Few mutations that did not lead to a premature stop codon have been described; they are also associated with increased PKA activity. PRKAR1A has been investigated in sporadic endocrine tumors; it does not appear to be mutated in pituitary adenomas, but both thyroid and adrenal neoplasms have been found to harbor somatic mutations of this gene. Animal models of the disease have been developed. CNC is the first human disease caused by mutations of one of the subunits of the PKA holoenzyme, a critical component of numerous cellular signaling systems. This has wide implications for cAMP involvement in endocrine tumorigenesis.

Multiple cerebral aneurysms as delayed complication of left cardiac myxoma: a case report and review.

Left cardiac myxoma and also consecutive embolization into the brain is well documented, whereas the association of myxomas with multiple fusiform cerebral aneurysms is rare. We analyze 33 previously reported patients and present a case of a 43-year-old woman with multiple cerebral infarctions 2 years after resection of a recurrent myxoma in the left atrium. Cerebral angiography displayed multiple fusiform aneurysms of several cerebral arteries, including a giant aneurysm of the basilar artery. Serum level of interleukin-6 (IL-6) was highly elevated. The clinical, radiological and pathological features of these aneurysms are summarized. The pathogenesis, including the role of IL-6 in the formation of myxomatous aneurysms, is discussed.

[Right atrial myxoma in a patient with antiphospholipid antibodies]. / Mixoma auricular derecho en paciente con anticuerpos antifosfolipídicos positivos.

A 28 year-old asymptomatic male with previously detected elevation of antiphospholipid antibodies (aPL) had a right atrial mass diagnosed by transthoracic echocardiography. Although the morphological characteristics were highly suggestive of myxoma, due to the presence of aPL elevation it had to be differentiated from atrial thrombus. The patient underwent surgery and a 3 x 4 cm mass with its large base attached to the interatrial septum was removed. Histopathological examination confirmed that it was a myxoma. On follow-up, the patient was asymptomatic and antiphospholipid antibodies became undetectable.

Characteristics of cardiac myxoma with constitutional signs: a multicenter study in Japan.

BACKGROUND: A relationship between constitutional signs in patients with cardiac myxoma and interleukin-6 has been noted. However, there is little information about characteristics of cardiac myxomas associated with constitutional signs. HYPOTHESIS: The objective of this study was to clarify the characteristics of myxoma patients who had constitutional signs. METHODS: Questionnaires were sent to cardiology or cardiovascular surgery divisions at university hospitals throughout Japan. Constitutional signs were considered present when a patient had fever, weight loss, or elevations of C-reactive protein or gammaglobulin. In addition, interleukin-6 concentrations were evaluated in some patients. RESULTS: Data were obtained in 249 patients with primary cardiac tumors (204 myxomas, 15 other primary benign tumors, and 30 primary malignant tumors), confirmed histologically between 1993 and 1996. Fever and weight loss were observed in 15 and 6% of patients with myxoma, respectively, while C-reactive protein and gammaglobulin were increased in 39 and 21%, respectively. This amounted to a prevalence of constitutional signs in 49%. All constitutional signs disappeared after tumor resection. Age, gender, tumor site, and frequency of thrombosis did not differ between patients with and without constitutional signs. Tumors associated with constitutional signs were significantly more likely to be large, multiple, or recurrent than those unassociated with constitutional signs. CONCLUSIONS: Constitutional signs are present in about half of patients with myxoma. Large or multicentric tumors are likely to induce constitutional signs, which are reversible upon resection. These might suggest that constitutional signs result when interleukin-6 concentrations exceed a certain threshold.

Interleukin-6 and "complex" cardiac myxoma.

A rare case of "complex" cardiac myxoma is reported. Complex cardiac myxoma manifests with more constitutional signs than the sporadic type. These constitutional signs are known to be associated with the overproduction of interleukin-6 by cardiac myxomas. In our study, immunohistochemical staining of the myxoma for interleukin-6 was strongly positive. The serum interleukin-6 level decreased after surgical removal of the tumor and has remained undetectable for the past 2 years.

Reduced serum T3 level in a patient with nodular goiter and cardiac myxoma.

We report the unusual case of an 87-year-old woman with cardiac myxoma and adenomatous goiter. She exhibited slight elevations of serum interleukin-6 (IL-6), but levels of thyroid hormones such as T3, free T3 and free T4 were all abnormally low. Interleukin-6 may potentiate the alteration of thyroid metabolism.