Familial Myxomas Research Articles

The Question of Relapse of a Cardiac Myxoma: an Unusual Case from Practice

Various studies demonstrate that recurrence of cardiac myxoma (CM) occurs in 2.1–5.3% of cases. In cases of treatment of familial myxoma, the need for reoperations can reach 20–25%. It should be taken into account that among all benign cardiac tumors, CM is detected in up to 80% of cases, and the need for its surgical removal is beyond doubt.
 The aim. To present a case that is of particular interest due to an unusual multiple myxomas lesion of the heart of multi-chamber localization.
 Material and methods. This article presents an unusual case of detecting multiple myxomas of multi-cameral heart lesions 6 years after removal of myxoma of the left atrium of typical localization. The distinguishing feature of the course of the disease lies in the fact that in this case, a careful study of the life history did not reveal the characteristic signs of familial myxomas and Carney complex which is most often characteristic of multi-chamber lesions of the heart by a tumor process. At the same time, during the surgical removal of the myxoma of the left ventricle, the myxomas of the left and right atrium were revealed, which began to grow. A technical feature of the removal of the left ventricular myxoma of the apical localization was the use of video cameras and instruments for thoracoscopic surgery, which greatly facilitated revi-sion and removal of the hard-to-reach neoplasm. Our experience in surgical treatment of CM equals to 868 operations. Wherein, repeated operations performed in 12 patients were due to recurrence or appearance of a tumor in place other than the primary localization.
 Conclusions. CM recurrence is one of infrequent complications in the postoperative period, which, however, requires some vigilance and annual Echo monitoring. In the vast majority of cases, CM was represented by the so-called sporadic myxomas, which are more often localized in the left atrium, and rarely recur. If CM is suspected, it is necessary to exclude the possibility of “myxoma syndrome”, which has the frequency of 0.8%, according to our data. The use of the instruments for thoracoscopic surgery can greatly facilitate the removal of hard-to-reach heart tumors localization.

Sudden death by massive systemic embolism from cardiac myxoma. Role of the clinical autopsy and review of literature

Cardiac myxoma is a rare benign neoplasm of the heart. Historically myxomas were incidental findings during autopsies, however improved imaging techniques made these diagnosis possible in living patients, making the surgical treatment of these neoplasms achievable.Cardiac myxomas may occur both sporadically and in a familial context, often in the clinico-pathological picture of the Carney complex. While familial myxomas occur in the context of well-known genetic mutations, the molecular etiology of sporadically occurring myxomas is still not completely clear.We must note however that many of the patients affected by myxomas are asymptomatic; when symptoms are present they are often nonspecific and hard to decipher, especially when referring to sporadically occurring heart myxomas.In this paper we describe a case of sudden death from the massive embolization of a left atrial cardiac myxoma. We also reviewed all the cases in the literature of sudden death from heart myxoma embolism.An accurate epidemiology of heart myxomas would be the key to outline the best treatment practices and the etiology of sporadic myxomas, nevertheless this target could only be pursued with a deep revaluation of the clinical autopsy as a fundamental diagnostic tool.

On the histogenesis of cardiac myxoma

to investigate the morphological and phenotypic features of cardiac myxoma (CM), to discuss argumentative issues on the sources of its growth. The investigation included 176 sporadic and familial myxomas originating from different cardiac chambers (96% from the atria). The histological, ultrastructural, and immunohistochemical features of the cells and vessels of this tumor were studied. The morphological and phenotypic features of the embryonic endothelium resembling the cells of the primary cardiovascular network were found in the cells and vessels of CM. No signs of other mesenchymal derivatives were detected. The authors anticipate that there is focal cessation of maturation of the embryonic endocardial endothelium and its persistence - hamartia. Postnatal proliferation of embryonic hamartia forms the tumor hamartoma. Differentiated cells may retain the phenotypic (but not morphological) features of closely related cells that have a common precursor. The results of the study have allowed the authors to consider CM to be hamartoma, a monohistioid benign embryonic endocardial endothelioma. Our findings do not exclude the possibility of developing CM from pluripotent mesenchymal cells.

Familial atrial myxoma in three generations: case report

Familial myxomas constitute 7 % of the total myxoma population exhibiting Mendelian autosomal dominant inheritance. We present a rare case of autosomal dominant benign familial myxoma occurring in three generations of the family operated successfully at our institute. A 40-year-old female presented with chest pain and palpitation, was diagnosed with left atrial myxoma, and was operated in 1993. After 2 years of surgery, the patient developed recurrent myxoma, and excision was done in 1995. A 22-year-old son complained of dyspnoea and chest pain. On evaluation, 5.6 × 2.6 cm right atrial myxoma attached to the roof of the right atrium was found, and the patient underwent myxoma excision in 2007. A 3-year-old granddaughter suffered from right hemiplegia. Echocardiography revealed left atrial myxoma 3 cm × 2 cm pedunculated lesion causing diastolic obstruction of mitral inflow. Operated patients in all three generations and other siblings have been genetically screened. On genetic evaluation, all diseased had autosomal dominant single-gene defect or microdeletion. Atrial myxomas presented at earlier age successively and in more aggressive form in these three generations.

EComment. Isolated valvular myxoma

We read with great interest the report by Fernandez et al [1]. They presented a case of a 28-year old male patient with a sessile myxomatous tumour localized on the ventricle aspect of the right and left cusps of the aortic valve. Valve-sparing aortic root reconstruction was impossible, therefore a mechanical aortic valve was implanted. Myxomas are the most common primary cardiac tumours, typically located in the left atrium at the level of the fossa ovalis (three-quarters of these tumours) [2]. Valvular myxomas are extremely rare, atrio-ventricular valves being more involved than the aortic or pulmonary valves. The mitral valve is the most frequently affected structure, followed by the tricuspid, the aortic, and the pulmonary valves [3]. This case provides the possibility to discuss the clinical and pathologic features of valvular myxomas. Myxomas of the aortic valve are usually located at the ventricle side, involving one or two aortic cusps. The mean age at diagnosis is 44 (range 15-72). Ten cases of aortic valve myxomas have been published in the English literature [1, 4, 5], and they all showed a unique feature, that is, an isolated myxoma on the aortic valve. None of these patients presented with Carney's complex, therefore we can conclude that, to date, familial myxomas do not involve aortic valves. Recently, an additional case report was published on the same subject [4]. A 10x8-mm myxoma attached to the non-coronary cusp of the aortic valve from the ventricle side was incidentally found during an echocardiogram. The 72-year old man was operated under cardiopulmonary bypass, the tumour was resected, and the aortic valve was successfully repaired. The postoperative course was uneventful. This is the oldest patient operated on with an aortic valve myxoma. We completely concur with the statement that the main differential diagnosis is made with papillary fibroelastoma, which is generally described as arising from the ventricle aspect of the aortic valve, that a surgical approach should be considered in all these patients, and that echocardiogram follow-up must be recommended [5]. Conflict of interest: none declared.

A New Clonal Chromosomal Aberration (47, XY, +21) in Atrial Myxoma from an Elderly Male Patient

Myxomas are the most common primary cardiac tumors, with an estimated incidence of 0.5 per million per year. Familial myxoma constitutes 10% of all myxomas, among these tumors, one in ten is part of Carney complex - an autosomal dominant syndrome, which are related to some mutations in the PRKAR1A gene. We report a case of 75-year-old man with sporadic cardiac myxoma of a 4-cm large tumor, arising from the left side of the atrial septum and causing a severe left ventricle inflow obstruction. Cytogenetic analysis confirmed by fluorescence in situ hybridization method (FISH), demonstrated a numerical aberration in atrial myxoma cells: 47, XY, +21. Flow cytometry analysis demonstrated that a quarter of tumors cells were hematopoietic progenitor cells (CD34+) and that a similar number were endothelial specific neovascular cells (CD31+). These finding suggest that, hematopoietic progenitor cells may play an important role in the histogenesis of cardiac myxomas and the karyotype aberrations have an impact on sporadic tumor genesis. Nevertheless, genetic screening for sporadic (non-familial) cardiac myxomas is not recommended.

Familial cardiac myxoma with multifocal recurrences: a case report and review of the literature

We report a case of myxoma with multiple recurrences in both the atrium and ventricle in a 26-year-old woman five years after the surgical removal of left atrial myxoma. Her 52-year-old mother had a similar medical history. To our knowledge, this was the first familial case who suffered multifocal cardiac myxoma recurrences without any sign of the myxoma complex. Based on our understanding of the mechanism of recurrence, the approaches to prevent the recurrence, and markers to predict recurrence, we propose that multifocal recurrences, as reported herein, may result from a combination of familial predisposition and multifocal onset. The bi-atrial surgical approach and transesophageal echocardiography are preferred for patients with recurrent cardiac myxomas, especially for those with multiple recurrences and familial myxoma. Immunological and genetic screenings may help to identify family members at risk for developing this disease.

Systemic embolisation as presentation and recurrence of cardiac myxoma two years after surgery.

Primary cardiac tumours are rare when compared with metastatic involvement. The majority of primary cardiac tumours are benign and in adults the majority of these masses are myxomas. The treatment is surgical removal because of the risk of embolisation and/or cardiovascular complications. We describe a female presenting with systemic embolisation and recurrence of cardiac myxoma after surgery. Recurrence of myxoma is rare after surgery in case of solitary tumours but more frequent in patients with familial myxomas in association with the Carney complex. Genetic analysis revealed a mutation in the PRKAR1A gene that has never been described before. (Neth Heart J 2010;18:499502.).

Unidentified Retained Inferior Vena Cava Myxoma Detected by Intra-Operative Trans-Oesophageal Echocardiography

We report a unilateral right atrial familial myxoma with a multicentric nature discovered during cardiac surgery. After the patient was weaned off cardiopulmonary bypass, an inferior vena cava myxoma was discovered with intra-operative trans-oesophageal echocardiogram (TOE) which had been missed preoperatively and during surgery.

Familiar Myxoma with a Positive Genetic Test A case report-

Hyang-Lim Lee, M.D.*, Kook-Yang Park, M.D.*, Kyung-Hee Kim, M.D.**, Seung-Tae Lee, M.D.***, Chang-Seok Ki, M.D.***, Yang-Bin Jeon, M.D.****, Chang-Hyu Choi, M.D.*. Korean J Thorac Cardiovasc Surg 2010;43:67-72. https://doi.org/10.5090/kjtcs.2010.43.1.67

Analysis of GNAS1 and PRKAR1A gene mutations in human cardiac myxomas not associated with multiple endocrine disorders

Cardiac myxomas are rare tumors that usually occur as sporadic lesions or,more rarely, in the familial form,mostly in the context of Carney complex (CNC). The molecular basis for the development of cardiac myxomas is unclear. However, somatic activating mutations in the GNAS1 gene (the gsp oncogene) are detected in the myocardium ofMcCune-Albright syndrome patients while germ-line mutations in the PRKAR1A gene are associated with CNC and familial myxomas. We investigated the presence of activating missense mutations in the GNAS1 gene as well as of inactivating mutations in PRKAR1A in 29 sporadically occurring cardiac myxomas. No gsp and no PRKAR1A mutations were found by direct sequencing of PCR products amplified from tumoral DNA. This is the first study including a large series of sporadic, isolated cardiac myxomas and showing that these cardiac neoplasms do not share the same mutations found in familial forms.

Primary Cardiac Myxomas: Clinical Experience and Surgical Results in 67 Patients

Primary cardiac tumors are rarely seen and have an incidence of 0.3% of all open-cardiac operations. Among those, myxoma is the most common cardiac tumor. There are only a few reports of such tumors from Turkey. We report our experience with 67 patients with primary cardiac myxoma operated on at our institute between December 1990 and October 2006. The study group comprised 22.38% males and 77.61% females with a mean age of 46.29 (+/-18.29) years. The predominant symptoms were dyspnea and palpitation. In addition, 3 patients presented with peripheral embolism with impending limb ischemia that necessitated emergency embolectomy. Echocardiography was generally enough for the demonstration of the myxomas. Two sporadic myxomas (%2.98) and one familial myxomas (1.49%) presented with recurrence. There were three (4.47%) hospital mortalities. Two patients (2.27%), with preoperative decompensation, died after tumor resection, from progressive low cardiac output. One patient, with preoperative massive pulmonary embolus, died two days after operation, from right ventricle insufficient. In conclusion, we herein summarized surgical results with primary cardiac myxomas. Surgical excision of primary cardiac myxomas tends to show excellent results after surgical excision.

The Variations in the Immunologic Features and Interleukin-6 Levels for the Surgical Treatment of Cardiac Myxomas

In this study, we propose the existence of a relationship between cardiac myxomas and the immunologic features or interleukin-6 (IL-6), while also considering the optimal treatment of cardiac myxoma, especially "familial myxoma." In a 19-year period at our hospital, 20 patients underwent 21 operations for cardiac myxomas. The immunologic features and the IL-6 levels were measured pre-operatively in 13 cases and post-operatively in 10 cases. A case of "familial myxoma" was diagnosed based on molecular genetic analyses. No patients died in the hospital. The tumor size correlated with the preoperative IL-6 and/or alpha1-globulin values (P < 0.05). In addition, all of the immunologic features and IL-6 levels normalized by 4 weeks after surgery. "Familial myxoma" demonstrated recurrence without showing increases in either the immunologic features, inflammatory signs, or serum IL-6 levels. Patients with cardiac myxoma should therefore be operated on immediately because the possibility that the tumor size might be large when IL-6 and/or alpha1-globulin values are high. In addition, cases of "familial myxoma" require careful observation and periodic echocardiography after surgery to identify any possible recurrence. Recently, molecular genetic analyses are therefore considered to be an important diagnostic tool for cardiac myxoma, especially "familial myxoma." Our "familial myxoma" case demonstrated a C769T PRKAR1a mutation, which has also been observed in other cases of "familial myxoma."

A rare case of multiple right heart myxomas

Primary tumours of the heart are rare. Myxomas are the most common primary cardiac tumours with an estimated incidence of 0.5 per million population per year. Myxomas are most commonly found in left atrium and are solitary in more than 90% cases. Familial myxomas are rarer and tend to be multiple. We report a rare case of multiple myxomas in the right heart which occurred sporadically, presenting with an episode of pre-syncope.

Exertional Dyspnea in a Soldier

Cardiac myxomas may present with a broad range of clinical features. There is a classic triad of features that includes obstructive cardiac signs, embolic signs, and constitutional manifestations. All patients present with one or more symptoms from this triad, but diagnosis may be elusive due to the nonspecific nature of some of these features. Although myxomas are uncommon and benign, the diagnosis must be considered when signs and symptoms suggest it due to the high associated morbidity and mortality. The size, character, location, and mobility of the tumor determine the type and severity of symptoms. Echocardiography is the most important tool used to establish the diagnosis, but CT and MRI may provide additional information in some cases. Prompt surgical resection of the tumor is the appropriate treatment. The overall prognosis is excellent, but patients should be followed due to the risk of recurrence.

Carney's syndrome: cardiac myxoma and Cushing's syndrome – a case report

Baran Budak, MD Yuksek Ihtisas Hospital Department of Cardiovascular Surgery Ankara/Turkey Sirs: Primary tumors of the heart are rare, most of them are benign and nearly half of them are myxomas [1]. Because of the lack of specific symptoms before the tumor has reached a certain size, their recognition and treatment generally take place in older patients [2]. Although nearly 90% of all myxomas are sporadic, familial myxomas have autosomal domiant transmission and are often present within the construct of a larger syndrome. The “syndrome myxoma” or “Carney’s syndrome” is characterized by both cardiac and noncardiac myxomas, spotty pigmentation, and endocrine overactivity (pituitary, adrenocortical, endocrine testicular tumors) [3, 4]. Case report

Positive genetic test led to an early diagnosis of myxoma in a 4-year-old boy

Less than 10% of cardiac myxomas are familial. These familial cases are related to Carney complex, a multiple neoplasia and lentiginosis syndrome. Mutations in the PRKAR1alpha gene are the cause of Carney complex in most patients. We report a boy, who had PRKAR1alpha gene mutation, and atrial myxoma that was diagnosed in a routine echocardiographic study at the age of four years. Surgical excision of myxoma was performed. This case demonstrates the benefit of screening genetically the kindreds of patients with familial myxomas, and the importance of close follow-up of individuals affected with this mutation irrespective of age.

Caspase-3-dependent apoptosis in cardiac myxoma: not associated with human papillomavirus or Epstein–Barr virus

Cardiac myxoma is the most common tumor of the heart, has a variable clinical presentation and immunohistochemical profile. Viral infections, such as herpes simplex virus, human papillomavirus (HPV), and Epstein–Barr virus (EBV), may play an important role in the causes of cardiac myxoma. This investigation will demonstrate caspase-3-dependent apoptosis in cardiac myxoma without HPV or EBV infection. This study included 15 patients with cardiac myxoma, who were treated with surgical excision of the lesion. Data were collected on detailed clinical parameters. Terminal deoxynucleotidyl transferase nick-end labeling assay, electrophoresis, and caspase-3 immunohistochemical studies were performed to characterize apoptosis. Genechip containing 39 subtypes was used to elucidate HPV; and polymerase chain reaction to detect LMP-1 gene of EBV. The patient population comprised of eight (53%) women and seven (47%) men. The mean age of patient participants was 45 years, with an age range of 30–70 years. All patient cases were sporadic myxomas rather than familial myxomas. The patient presentations included dyspnea (53%), asymptomatic (27%), stroke (7%), chest pain (7%), and fever (7%). All lesions were located in the left atrium. The individual patient cases of myxoma did not differ in location or clinical event in terms of pathological scores, such as vascular proliferation, inflammation, cellularity, hyaline, calcification, or thrombosis. Cardiac myxoma is characterized by apoptosis through caspase-dependent pathway. HPV or EBV was not detected in any of the study patient samples. In conclusion, no viral genomes of HPV or EBV were detected in these 15 patients. This study demonstrates that caspase-3-dependent apoptosis in cardiac myxoma is not dependent on concurrence of previous HPV and/or EBV infection.

Cardiac Myxoma and Myxosarcoma: Clinical Experience and Immunohistochemistry

From January 1978 to February 1999, 120 patients (42 males and 78 females) with cardiac myxoma (115) or myxosarcoma (5) underwent surgical excision or biopsy. There were 5 early postoperative deaths (mortality, 4.2%). Seventy-three survivors were followed up for 0.75 to 20.25 years (mean, 9.42 years); they comprised 4 myxosarcoma patients who all had recurrence or metastasis, and 69 myxoma patients who had no evidence of recurrence or metastasis. Neither familial myxoma nor Carney complex was found. The 5 cases of myxosarcoma and 18 randomly selected cases of myxoma were evaluated for proliferative activity, metastatic potential, and oncogene products by immunohistochemistry. The expression of p53 and Bcl-2 was similar in both groups. Overexpression of proliferating cell nuclear antigen and low expression of nm23 in myxosarcoma are consistent with the high rate of recurrence and metastasis of this tumor. Surgical resection of sporadic myxoma is a safe and effective treatment with satisfactory early and long-term results. However, the prognosis of myxosarcoma is still disappointing. Regular echocardiography and chest radiography or computed tomography are necessary for early detection of recurrence or metastasis of myxosarcoma.

Left ventricular outflow tract obstruction due to valve myxoma

A life-threatening left ventricular outflow tract obstruction developed in a 26-year-old man because of a very uncommon myxoma emerging from the ventricular side of the mitral valve. Immediate surgical treatment was indicated because of high-risk factors reported herein. After transaortic resection of a single myxoma, the progress of this patient has been excellent, especially as a familial myxoma could be excluded.