Cardiac papillary fibroelastoma: Retrospective clinicopathologic study of 17 tumors with resection at a single institution and literature review

Cardiac papillary fibroelastomas (PFEs), which are mainly found in the valves, are rare benign tumors that can cause embolism. Single-center surgical experience in the treatment of this tumor is uncommon.     

Pulmonary valve papillary fibroelastoma. A case report and review of the literature.

Papillary fibroelastomas are rare and benign cardiac tumors that typically affect the cardiac valves. To the best of our knowledge, the English literature contains only 1 case report of pulmonary valve fibroelastoma diagnosed by echocardiogram and confirmed by surgical resection. There is a paucity of pathology literature on this subject. We describe an additional case of pulmonary valve fibroelastoma diagnosed by transesophageal echocardiography and magnetic resonance imaging confirmed by pathologic examination in a patient who also had a thymoma.     

An unusual case of multiple papillary fibroelastoma, review of literature.

Primary neoplasms of the cardiac valves are extremely rare. However, papillary fibroelastoma is the third most common primary tumor of the heart [Ann Thorac Surg 52 (1991) 1127]. These tumors can be found anywhere in the heart, but most commonly involve the cardiac valves [Ann Thorac Surg 52 (1991) 1127; McAllister HA, Fenoglio JJ. Tumors of the cardiovascular system. In: Atlas of tumor pathology, 2nd series, vols. 1-3. Washington (DC): Armed Forces Institute of Pathology; 1978. p. 20-5]. Most papillary fibroelastomas do not cause symptoms and are usually incidental findings by routine echocardiography or at autopsy. However, early diagnosis of this condition is important, since it represents a surgically correctable cause of systemic emboli, stroke, myocardial infarction, and sudden cardiac death [Ann Thorac Surg 52 (1991) 1127; Ann Thorac Surg 68 (1999) 1881; J Am Soc Echocardiogr 9 (1996) 353; Tex Heart Inst J 22 (1995) 327; Tex Heart Inst J 26 (1999) 298]. The echocardiographic findings should be confirmed by histology, since the clinical differential diagnosis includes myxoma, vegetation, thrombi, lipoma, and pseudopapillary fibroelastoma [Tex Heart Inst J 26 (1999) 298; J Am Soc Echocardiogr 11 (1998) 92; J Natl Med Assoc 87 (1995) 68]. Review of the literature reveals that multiple papillary fibroelastomas are extremely rare [Am Heart J 125 (1993) 1443; J Am Soc Echocardiogr 7 (1994) 315; Ann Thorac Surg 48 (1989) 119]. Li Manduri et al. [J Am Soc Echocardiogr 7 (1994) 315] reported multiple masses on the tricuspid valve, the larger of which was 1 cm in diameter. De Virgilio et al. [Ann Thorac Surg 48 (1989) 119] reported a case of multiple 1-cm papillary fibroelastomas located on mitral valve, left ventricular outflow tract, and along septum. We report an unusual case of multiple papillary fibroelastomas in a woman, who initially was admitted because of a shortness of breath and recent cerebrovascular accident.     

Benign cardiac tumors of the pluripotent mesenchyme

Among benign primary cardiac tumors, myxomas and papillary fibroelastomas are the most common. Cardiac myxomas arise from pluripotent mesenchymal cells and are seen as intracardiac, glistening polypoid masses arising most frequently from the interatrial septum in the left atrium. They are composed of stellate to polygonal myxoma cells in a mucopolysaccharide-rich matrix. These tumors can be sporadic or familial. On the other hand, papillary fibroelastomas are sporadic, seen as a mass of delicate papillary fronds ("sea anemone"-like) arising from a slender stalk, commonly located on diseased left-sided valves. They are lined by plump endothelial cells, which rest on stalks composed of mucopolysaccharides enclosing a collagen- and elastin-rich core. Embolism is often the mode of presentation for both of the tumors; myxomas are also associated with obstructive and constitutional symptoms. In contrast, neurogenic tumors (paraganglia or nerve sheath tumors) are exceedingly rare and occur as epicardial and infrequently as intracatdiac masses. The tumors are often incidentally diagnosed by the usual echocardiography, but magnetic resonance imaging is useful for further characterization of the tumors. The tumors are, in general, treated by surgical resection, but may require a little or at times more significant reconstruction. Among these tumors, the myxomas are associated with a higher rate of recurrences.     

Pseudopapillary fibroelastoma of the mitral valve.

Papillary fibroelastomas are well-recognized benign cardiac neoplasms. They are primarily asymptomatic, but occasionally are associated with neurologic and cardiac symptoms. Pseudopapillary fibroelastomas presenting with usual clinical and echocardiographic manifestations of papillary fibroelastoma but lacking characteristic histologic features have not been described previously. This article describes a 42-year-old, previously healthy female admitted with sudden hemiparesis and dysarthria. Symptoms completely resolved within 4 days. Extensive investigations revealed no etiology except for a pedunculated mitral valve mass with echocardiographic appearance suggestive of papillary fibroelastoma. Histologic staining, however, failed to reveal characteristic features of papillary fibroelastoma.     

Papillary fibroelastoma of the endocardium

Six cases of papillary fibroelastoma of the endocardium were presented. All cases appeared as incidental findings at autopsy. Grossly, they were verrucous or tuft-like growths less than 1 cm in size on cardiac valves. Histologically, they consisted of a fibrocollagenous stalk and multiple papillary fronds with typical zonal architecture: central dense hyaline core containing elastic fibers surrounded by a layer of myxoid matrix and covered by hyperplastic endothelial cells. At the surface of papillary fronds there were foci of fibrin deposition. Histogenesis of papillary fibroelastomas is unclear, they are considered variously as primary benign tumours, hamartomas or organized thrombi.     

Papillary fibroelastoma of the heart. A review of 20 cases

After a period during which cardiac papillary fibroelastomas were considered incidental autopsy findings cerebral and coronary arteries embolism proved their aggressiveness. Echocardiography is now able to identify them and surgical resection is rapidly required. Sea anemone like macroscopic pattern is characteristic with finely villous masses, each frond being at microscopical examination formed by a central fibroelastic core surrounded by a myxomatous layer overlied by endothelial cells. Histogenesis remains elusive and we tried to clarify it by immunohistochemical analysis of 8 of the 20 cases studied (10 autopsies, 10 surgical resections). Morphological and immunohistochemical data show that endothelial cells play the most important part in abnormal formations.     

Simultaneous papillary fibroelastomas of the pulmonary and aortic valves

Cardiac papillary fibroelastomas (PFEs) are uncommon valve tumors. Multiple PFEs at the same or different locations in the heart account for less than 10% of patients with PFE. We herein describe a case of an asymptomatic PFE of both pulmonary and aortic valves which was incidentally diagnosed by echocardiography in a 60-year-old woman. Both PFEs were removed surgically without valve replacement. To our knowledge, this combination of lesions has not been previously reported. Even though PFEs are classified as benign cardiac tumors, they can present serious complications, such as embolic episodes, mechanical obstruction or valvular dysfunction. Valve-sparing shave excision of the lesions can be readily accomplished in most instances with good long-term results. All surgically removed valvular lesions should be histopathologically examined to confirm the echocardiographic diagnosis.     

Pathological study of primary cardiac and pericardial tumours in a specialist UK Centre: surgical and autopsy series

BackgroundPrimary cardiac and pericardial tumours are rare with a prevalence of between 0.001% and 0.3%. Thus, general pathologists are not familiar with them. Modern advances in cardiac imaging have increased the number of patients identified with a primary cardiac tumour in its early stage and also improved prognosis. At the Royal Brompton Hospital, London, we did a retrospective study to investigate the pathological features of primary cardiac and pericardial tumours and compared our findings to other cardiac centres.MethodsAll pathologic records at the Royal Brompton Hospital between 1990 and 2008 were reviewed to identify patients with a confirmed diagnosis of primary cardiac tumours. A total of 94 patients with a histological diagnosis of primary cardiac and pericardial tumours were identified and formed the study population.ResultsThe majority (n=67, 71.3%) of cases were benign cardiac tumours. Myxoma was the most common histologic type accounting for 27 cases. Among cases with primary malignant tumours (n=27, 28.7%), unclassified sarcoma (n=11), leiomyosarcoma (n=5), and lymphoma (n=4) were the most common histologic types.ConclusionThis study, primarily from an adult setting (n=78, 83%) demonstrates a large spectrum of cardiac tumours seen in recent cardiologic practice. Myxoma is still the most common tumour but more fibroelastomas are being diagnosed due to increased imaging.     

Heart tumors in children and adults: clinicopathological study of 59 patients from a surgical center.

BACKGROUND: Heart tumors are rare lesions with variegated histological types. Their clinicopathological features could be more comprehensively categorized. METHODS: This is a 19-year retrospective study of 17 infants/toddlers (<2 years of age) and 42 patients aged between 14 and 79 years (mean = 51.5) in a surgical center. RESULTS: Congenital tumors (n = 17; 29%), including rhabdomyomas (n = 9), ventricular fibromas (n = 6), and hemangiomas (n = 1), required surgery mainly because of mass effect. Familial myofibromatosis was the only embolic congenital lesion. Acquired benign tumors (n = 28; 47%) included myxomas (n = 21), fibroelastomas (n = 3), myofibroblastic inflammatory tumors (n = 2), and lipomas (n = 2). Eight (29%) were revealed by systemic embolization. These benign noncongenital tumors were all treated by complete resection, except for an incompletely resected lipoma of the mitral valve. Postoperative arrhythmia (n = 1) and pericardial effusion (n = 3) were the only complications. Primary sarcomas (n = 8; 14%) were mostly vascular tumors (five of eight), and patients with high-grade tumors had a mean survival of 15 months (n = 5). Cardiac metastases (n = 6; 10%) were from carcinomas (n = 3) or sarcomas (n = 3); apart from a necrotic metastasis, all patients died (mean survival of 6 months). CONCLUSIONS: This study shows that, regardless of patients' age, heart tumors can be classified as: (a) congenital lesions, which are spontaneously nonprogressive or regressive lesions possibly requiring surgery mainly because of mass effect; (b) acquired benign tumors, which are lesions requiring surgery often because of embolization risk; and (c) primary and secondary malignant tumors, which are lesions with globally poor prognosis but with some indications for resection.     

Calretinin as a marker for cardiac myxoma. Diagnostic and histogenetic considerations

To study the usefulness of calretinin as an immunohistochemistry marker in the diagnosis of cardiac myxoma (CM) and the origin of myxoma cells, we examined 24 CMs and 9 fetal hearts with immunohistochemical methods on formalin-fixed paraffin-embedded tissues. We compared 24 CMs with 10 mural thrombi, 6 jaw myxomas, and 2 papillary fibroelastomas. Calretinin expression was identified in 100% of CMs and was negative in all cases of mural thrombi, jaw myxoma, and papillary fibroelastoma. Calretinin expression by the neoplastic cells in CM was strong and diffuse and had a cytoplasmic and a nuclear pattern. Calretinin expression in fetal hearts was found in autonomic ganglia cells in the subepicardial tissue of the atria and atrial appendages, along the interatrial and atrioventricular sulci, and in the atrial septum. Results clearly indicate that calretinin can be used as a marker for the diagnosis of CM and that it is a powerful tool for the differential diagnosis, most importantly with mural myxoid thrombi. Furthermore, the positive expression of calretinin by the autonomic neurons in the fetal heart and CM supports the concept that myxoma cells may originate from endocardial sensory nerve tissue.     

Surgical pathology of 104 tricuspid valves (2000–2005) with classic right-sided Ebstein''s malformation

BACKGROUND: Ebstein's anomaly has been described extensively in autopsy material. However, there have been no large surgical pathology series of this malformation. OBJECTIVE: To review clinical and surgical pathologic features of a large number of cases of Ebstein's anomaly from a single institution. METHODS: Review of medical histories, surgical reports, and surgical pathology reports at the Mayo Clinic (2000-2005). RESULTS: Among 104 patients, the mean age was 31 years (2 months-79 years), and 57% were female. Common ECG abnormalities included right bundle branch block (58%), first-degree heart block (31%), preexcitation (18%), and nonspecific intraventricular conduction delay/block (15%). Moreover, 74% had inter-atrial communication, 13% mitral valve prolapse, and 5% bicuspid aortic valve. Clinically, all had tricuspid regurgitation (severe in 74%), and 17% of anterior leaflets were fenestrated. No tricuspid valve was calcified. Surgically, tricuspid tissue was removed during replacement in 99% and repair in 1%. The anterior tricuspid leaflet was resected in 98%, and its length was 0.81-9.3 cm/m2 body surface area (mean, 3.3). Characteristically, leaflets were large and had irregular shapes and numerous short cordal or direct myocardial insertions. One tricuspid valve had two papillary fibroelastomas. None had clinical or pathologic evidence of active or healed endocarditis. CONCLUSIONS: Among patients with Ebstein's malformation, tricuspid valve tissue almost exclusively was removed during valve replacement and represented the anterior leaflet. Valve tissue was generally large, irregularly shaped, and associated with insertion of short cords or myocardial stumps. Interestingly, although appreciably deformed, Ebstein valves were not associated with infective endocarditis.     

Primary diffuse melanoma of the pia mater

A rather rare case of melanoma with a rare primary localization in the pia mater is described. The available literature describes as many as 60 cases of melanomatosis at this site. This case is of certain clinical and morphological interest due to its rare localization and great clinical diagnostic difficulties.     

From Molecules to Behavior: Lessons from the Study of Rare Genetic Disorders

Rare diseases are defined as conditions with a prevalence of less than 1/2,000. To date between 6,000 and 7,000 rare diseases have been identified and many of those have manifestations that include intellectual disability, developmental disorders or other behavioural phenotypes. In this special issue we bring together a range of papers where rare diseases were used as models to delineate specific aspects of learning and memory, or behaviour. In this introductory paper we summarize some of the lessons we can learn from rare diseases. Firstly, we learn that, collectively, rare diseases are not at all rare. As many as 1 in 20 individuals may be affected by a rare disease at some point in their life. Secondly, we learn that rare diseases may share common pathophysiological mechanisms. A discovery in one can therefore have direct relevance to many others. A third lesson is that the study of rare diseases can lead to an understanding of common disorders, as exemplified by the relationship between Trisomy 21 (Down syndrome) and Alzheimer’s disease. A fourth lesson from rare diseases is that the ‘one gene-one functional consequence’ assumption is not correct. Finally, rare diseases have shed new light on the strengths and weaknesses of animal models in the study of behavioural phenotypes.     

Primary mixed mullerian tumor of the vagina--a case report with review of the literature

Malignant mixed mullerian tumor (MMMT) is a rare entity. The commonest site of this tumor in the female genital tract is the uterus followed by cervix. Primary MMMT of vagina is extremely rare. We are reporting this rare entity, with a brief review of the literature, in a 48-year-old perimenopausal female who presented with a history of passage of urine per vagina. On pelvic examination, a polypoidal mass arising from the anterior wall of the vagina was identified. Histopathological examination revealed the biphasic nature of the tumor. Immunohistochemistry confirmed the diagnosis of MMMT of vagina. To conclude, although rare, clinicians, oncologists, and pathologists should identify this malignant tumor for appropriate treatment and management.     

Evolutionary evidence of the effect of rare variants on disease etiology

Gorlov IP, Gorlova OY, Frazier ML, Spitz MR, Amos CI. Evolutionary evidence of the effect of rare variants on disease etiology. The common disease/common variant hypothesis has been popular for describing the genetic architecture of common human diseases for several years. According to the originally stated hypothesis, one or a few common genetic variants with a large effect size control the risk of common diseases. A growing body of evidence, however, suggests that rare single‐nucleotide polymorphisms (SNPs), i.e. those with a minor allele frequency of less than 5%, are also an important component of the genetic architecture of common human diseases. In this study, we analyzed the relevance of rare SNPs to the risk of common diseases from an evolutionary perspective and found that rare SNPs are more likely than common SNPs to be functional and tend to have a stronger effect size than do common SNPs. This observation, and the fact that most of the SNPs in the human genome are rare, suggests that rare SNPs are a crucial element of the genetic architecture of common human diseases. We propose that the next generation of genomic studies should focus on analyzing rare SNPs. Further, targeting patients with a family history of the disease, an extreme phenotype, or early disease onset may facilitate the detection of risk‐associated rare SNPs.     

Simultaneous expression of the rare and common fragile sites on the X chromosome

The fragile X [fra(X)] syndrome is the most common inherited form of X-linked mental retardation and is associated with a rare folate sensitive fragile site on the X chromosome at band Xq27.3. Recently, a common fragile site located at chromosome band Xq27.2 was delineated (Sutherland & Baker 1990). In order to confirm the previous findings and to further investigate the conditions required for induction of both types of fragile sites, we studied the use of four experimental protocols. Samples from a control male, two fra(X) males and a fra(X) carrier female were studied. Both common and rare fragile sites were seen in the samples from the fra(X) subjects. Up to 4% of cells showed both common and rare fragile sites on the same X chromosome at the 500 band level. The rare and common fragile sites on the X chromosome could be clearly distinguished. From 1 to 3% of the control cells exhibited the common fragile site, while none exhibited the rare fragile site. These protocols should be useful in resolving questionable fra(X) syndrome diagnoses.     

Radiation-associated extraskeletal osteosarcoma of the chest wall

Radiation-associated sarcoma is a rare but potential complication of radiation therapy. Most reported cases of osteosarcoma of the chest wall following radiation therapy for breast cancer arise from the chest wall skeletal structures. In contrast, few cases of extraskeletal osteosarcomas have been reported. We report a rare example of an extraskeletal osteosarcoma involving the pectoralis major muscle occurring after radiation therapy for breast cancer. Extraskeletal osteosarcomas are rare soft tissue tumors with a high rate of local recurrence and a poor prognosis.     

Nonchylous idiopathic pleural effusion in the newborn

Congenital isolated pleural effusion is a rare cause of respiratory distress in neonates. It is usually chylous. Herein, we report a rare case of nonchylous congenital idiopathic pleural effusion.     

Polyps of the small intestine

Polyps of the small bowel are rare compared to those of the colorectum. A correct histopathological diagnosis is crucial for the choice of subsequent treatment. This article reviews the most frequently found and some rare but distinct polyps and polyp-like lesions in the small intestine. Adenomas are the most commonly found polyps in the small intestine. Other polypoid lesions include Brunner gland hyperplasia, Brunner gland hamartoma, periampullary myoepithelial hamartoma and pyogenic granuloma. Adenomas are usually found in the distal portion of the duodenum, whereas, Brunner gland hamartoma and inflammatory polyps are noted in the proximal portion of the duodenum. The rare but distinct Peutz–Jeghers polyp and juvenile polyp are reviewed, including the associated hereditary autosomal dominant syndromes (i.e. Peutz–Jeghers and juvenile polyposis syndrome) of which these lesions are the phenotypic hallmarks. Finally, an extremely rare polyposis syndrome with unknown aetiology, i.e. Cronkhite–Canada syndrome, is described with documentation.