Diffuse large B cell lymphoma associated with chronic inflammation arising within atrial myxoma: aggressive histological features but indolent clinical behaviour.

AIMS: Primary cardiac lymphoma (PCL) is a rare neoplasm. PCL is fatal, unless it is diagnosed and treated early. Recently, a small number of cases of diffuse large B cell lymphoma (DLBCL) arising within atrial myxoma have been reported in immunocompetent patients and showed aggressive histological features but an indolent clinical behaviour. METHODS AND RESULTS: We present four unusual cases of Epstein-Barr virus (EBV)-positive DLBCL arising within atrial myxoma with detailed clinical, histological, immunophenotypical and genotypical features in immunocompetent patients, and review the literature for 11 similar cases. All the patients appeared to have morphological features of DLBCL, B lineage immunophenotype, high proliferative index and latency type III of EBV infection. They achieved complete tumour resection without chemotherapy or radiotherapy after surgery and were healthy at 3- and 7-month and 7- and 10-year follow-ups, respectively. CONCLUSIONS: We suggest that this lymphoma should be regarded as a unique DLBCL associated with chronic inflammation (DLBCL-CI) because of an indolent clinical behaviour to avoid excessive or unnecessary treatments. In addition, early accurate diagnosis and complete resection of this tumour are crucial for optimal patient outcome.

Association between herpes simplex virus Types 1 and 2 with cardiac myxoma.

Most cases of atrial myxoma are sporadic, and the exact etiology is unknown. We examined if herpes simplex virus (HSV)-1 and HSV-2 antigens and/or DNA could be detected in a cohort of Iranian patients with cardiac myxomas. From July 2004 to June 2014, among a total of 36,703 patients undergoing open heart surgeries, consecutive patients with cardiac myxoma who were treated by surgical excision at our center included in this study. Of 73 patients studied, 56% were female with a mean age of 54 years (ranging from 23 to 77 years). Seventy-four myxomas were surgically removed from 73 patients, since one patient had two myxomas which were located on both the right atrium and right ventricle. The materials for this analysis were retrospectively gathered from extracted tumors that stored in a pathology bank of tissue paraffin blocks. The formalin fixed paraffin embedded tissue samples were investigated for HSV genomic DNA by both immunohistochemistry (IHC) and polymerase chain reaction (PCR) analysis. In all 74 cases there was no presence of HSV 1 and HSV 2 infection. This suggests that HSV may not play a role in sporadic cardiac myxomas; however, evidence for such association is currently lacking, and further studies are required to determine such a role.

EBV+ diffuse large B-cell lymphoma arising within atrial myxoma in Chinese immunocompetent patient.

The incidence rate of Primary cardiac lymphoma is very low. Primary cardiac lymphoma within myxoma is extremely rare disease. So far, these cases have been reported only eight in the world, which has not reported in Chinese so far. Hence, we reported the unique Chinese case of 52-year-old immunocompetent male with primary Epstein-Barr virus positive diffuse large B-cell lymphoma arising within atrial myxoma, and had no evidence of systemic lymphoma. The patient presented right sided body numbness, arm weakness no incentive and mouth twitch. A transthoracic echocardiogram revealed a large intraatrial mass, attached to the left atrial wall. The mass was removed by open thoracic surgery and subsequently diagnosed as malignant diffuse large B-cell lymphoma with myxoma by histopathology. This was the fourth case of discovered Epstein-Barr virus positive diffuse large B-cell lymphoma in a cardiac myxoma reported so far. The patient has been well by followed up for 5 months without chemotherapy. Now we discuss the importance of histodiagnosis and the proper treatment. Epstein-Barr virus positive diffuse large B-cell lymphoma arising within atrial myxoma is an extraordinary lymphoma for better prognosis, avoiding excessive treatment.

Self-limited effusion large B-cell lymphoma: two cases of effusion lymphoma maintaining remission after drainage alone.

We report two cases of human herpesvirus-8 (HHV-8)-negative large B-cell lymphoma involving pericardial and/or pleural effusion that regressed after drainage alone. Case 1 is a 70-year-old man showing massive pericardial effusion. Cytology of the drained effusion showed monotonous infiltration of CD3-, CD20+, CD79a+, and CD138- large B-cells. Monoclonality was shown by Southern blot analysis. Case 2 is a 70-year-old man with massive pericardial and bilateral pleural effusion. Cytology of pericardial effusion showed infiltration of CD20+, CD45RO-, CD138-, immunoglobulin lambda chain+, and kappa chain- large B cells. In both cases, effusion resolved after drainage and no relapse has been observed. HHV-8 was not demonstrated in either case. Clinical presentation of our two cases resembled primary effusion lymphoma (PEL), but cytomorphology, immunophenotype, and prognosis were clearly distinct from those of PEL. HHV-8-negative effusion lymphomas might include prognostically favorable self-limited tumors that could regress without any cytotoxic therapy.

Incidental Epstein-Barr virus associated atypical lymphoid proliferation arising in a left atrial myxoma: a case of long survival without any postsurgical treatment and review of the literature.

We report a case of left atrial cardiac myxoma harbouring an incidental atypical B-cell lymphoid proliferation. Histology disclosed classic myxoma cells embedded in a mucopolysaccharide-rich matrix and a micronodular atypical lymphoid proliferation under the surface of the mass. Myxoma cells were immunoreactive for calretinin, while lymphoid cells expressed B lineage markers (CD 20+, CD79a), without evidence of clonality. Moreover, they were LMP1 positive; EBNA2 negative; KSHV/HHV8 negative; and, by in situ hybridization, EBER/Epstein-Barr virus (EBV) positive and Kappa and Lambda negative. According to the 2008 WHO schemes, the present case shares close similarities either with diffuse large B-cell lymphomas growing in the context of long-standing chronic inflammation or with primary effusion lymphomas, solid variant, both associated with EBV infection. This is the sixth case of incidental atypical lymphoid proliferation discovered in a cardiac myxoma reported so far. The optimal treatment of such lesions remains undefined, but their clinical course is indolent. After an accurate staging workup, without any postsurgical treatment, the patient we observed has been well with no recurrence of the disease at 6 years of follow-up.

Fibrin-associated large B-cell lymphoma: part of the spectrum of cardiac lymphomas.

Cardiac lymphomas are rare, and the spectrum of pathologic features is not well defined. We encountered an unusual case of cardiac lymphoma residing within a presumed thrombus. To place such cases in context, we reviewed all cardiac lymphomas presenting to a large US cardiovascular medicine referral center during a 30-year period. A total of 14 cardiac lymphomas were identified, and these included 6 primary cardiac lymphomas (PCLs) and 8 lymphomas secondarily involving cardiac structures. Upon review, 3 of the PCLs were confirmed to be diffuse large B-cell lymphoma, not otherwise specified, involving the myocardium. The other 3 cases of PCL lacked myocardial invasion and showed lymphoma cells embedded in fibrin thrombus. Acute inflammation was not evident. These lymphomas presented in immunocompetent male individuals and involved either a prolapsed myxomatous mitral valve, a pseudomyxoma from the left atrium, or a thrombus arising in a synthetic aortic root graft. All 3 consisted of large atypical lymphocytes expressing a nongerminal center B-cell immunophenotype. Two cases were positive for Epstein-Barr virus (latency type III), but none demonstrated human herpes virus-8 latent nuclear antigen. No systemic disease was found at presentation or during follow-up. In our experience, fibrin-associated large B-cell lymphoma arising in the heart represents a substantial proportion of PCL. These lymphomas appear to represent an underrecognized variant of diffuse large B-cell lymphoma with favorable outcome. Further study is needed to understand their natural history.

Primary cardiac diffuse large B-cell lymphoma, non-germinal centre B-cell type in an immunocompetent woman.

Primary cardiac lymphomas are extremely rare and always occur in immunodeficient persons. Here, we report a very rare case of a primary cardiac diffuse large B-cell lymphoma in an immunocompetent 41-year old woman. Echocardiography and computed tomography revealed a mass measuring 74 mm 49 mm in the right atrium. No tumour formations were recognized in other organs. Laboratory data did not reveal immunosuppression, and the human immunodeficiency virus was negative. Histological and immunohistochemical studies showed that the cardiac tumour was diffuse large B-cell lymphoma, non-germinal centre B-cell type. Epstein-Barr Virus-encoded small RNA was negative by in situ hybridization. The patient died 6 months after the operation.

Detection of herplex simplex virus-1 and -2 in cardiac myxomas.

The etiology of sporadic cardiac myxomas remains elusive. The tendency for these lesions to recur following resection, their immunopathological characteristics, along with their histological and molecular profile, may implicate the presence of an infective agent in this type of tumor. In this study, we investigated the presence of herpes simplex virus (HSV) DNA in a cohort of cardiac myxomas in a tertiary referral centre. Twenty-nine formalin-fixed paraffin-embedded (FFPE) sporadic cardiac myxomas were obtained, 17 of which were shown to be informative. These were compared to 19 macroscopically and microscopically normal heart tissue specimens. The detection of HSV-1 and -2 genomic sequences was achieved with the use of a combined nested PCR-Restriction Fragment Length Polymorphism methodology. The presence of HSV-1 and/or -2 DNA was demonstrated in 6 of 17 (35%) informative sporadic cardiac myxomas, whereas no HSV DNA was detected in normal heart tissues (P < 0.01). The existence of HSV-1/2 DNA in sporadic cardiac myxomas, along with its absence from normal heart tissues, reinforces the possibility that HSV infection might be involved in the development of these lesions. Our findings raise the point of anti-HSV medication postsurgically with a potential benefit in reducing the rate of recurrences.

EBV+ diffuse large B-cell lymphoma arising within atrial myxoma. An example of a distinct primary cardiac EBV+ DLBCL of immunocompetent patients.

Cardiac myxoma and diffuse large B-cell lymphoma are uncommon tumors, yet four composite tumors have been reported since 2009. We are reporting on the fifth case providing detailed immunohistochemical and FISH analyses. The lymphoma was present as superficially located nests of large cells with patchy necrosis in the background of a typical atrial myxoma. It displayed features of DLBCL with non-germinal center phenotype, expressed EBER, LMP1, EBNA2 and shared the following features with the previously reported cases: B-cell lineage, high-grade cytology, high proliferation rate, EBV infection in latency type 3 with one tested case and an excellent outcome. The lymphomas arising within myxoma may follow a pathogenic pathway driven by EBV, whose transformation potential is unleashed in the cytokine-rich milieu of a myxoma, presumably accentuating age-related decline of adaptive immunity known as immune senescence. DLBCL arising within atrial myxoma grouped together with EBV+ DLBCL associated with valve prosthesis and with an atrial thrombus differs in the immunocompetent patients from primary cardiac DLBCL, not otherwise specified, in clinical presentation, pathological features and a course of the disease. Distinction between these groups may have important therapeutic consequences.

No association between herpes simplex virus 1 and cardiac myxoma.

PRINCIPLES: Cardiac myxoma is the most commonly diagnosed cardiac tumour. Infection of herpes simplex virus 1 (HSV1) has been postulated to be a factor for this pathologic entity. The aim of the current study was to evaluate the association between HSV 1 and myxoma occurrence. METHODS: Between 1965 and 2005, 70 patients (36 female, mean age: 52.6 years) underwent a resection of myxoma. Selected variables such as hospital mortality and morbidity were studied. A follow-up (FU; mean FU time: 138 ± 83 months) was obtained (76% complete). Immunohistological studies with monoclonal antibodies against HSV type 1 were performed on tumour biopsies of 40 patients. RESULTS: The mean age was 53 ± 16 years (range 23 to 84 years, 51% female). Of the investigated population, 31 (44%) were in New York Heart Association (NYHA) class III-IV. Mitral valve stenosis was identified in 14 patients (20%), and in 25 (36%) patients mitral valve was insufficient. During hospitalisation 3 patients suffered from a transient neurological disorder, and in addition to myxoma resection 18 (25.7%) patients had to undergo an additional intervention. The overall survival rate was 91% at 40 years. There was no early postoperative mortality in follow-up, although 4 patients died and 2 patients had been re-operated on for recurrent myxomas after 2 and 9 years. Immunohistology revealed no positive signals for HSV-1 antigens among the 40 analysed cases. CONCLUSION: Complete surgical resection, septum included, was the treatment of choice and mandatory to prevent relapse. Peri-operative morbidity and mortality over 40 years remained low, and no association between HSV infection and occurrence of cardiac myxoma was found.

Nasopharyngeal carcinoma with pericardial metastasis.

Nasopharyngeal carcinoma (NPC) is prevalent in Taiwan and is characterized by a high frequency of nodal metastasis. The most common organs with distal metastases are the bones, lungs, and liver, with extremely rare cases to the pericardium. Herein, we report a rare case with NPC who presented with dyspnea and orthopnea. Serial studies, including pericardial biopsy, revealed NPC with pericardial metastasis and pericardial effusion. The tumor cells of both the original and metastatic tumors were positive for Epstein-Barr virus by in situ hybridization. This is the first histologically confirmed case of NPC with pericardial metastasis.

Epstein-Barr virus-associated diffuse large B-cell lymphoma arising on cardiac prostheses.

Primary cardiac lymphoma is extremely rare and lymphoma arising in association with prosthetic valves has been described in only 3 case reports. We describe 3 patients with diffuse large B-cell lymphoma (DLBCL) involving prosthetic heart valves and a synthetic tube graft. All 3 specimens showed shallow layering of acellular fibrinous debris over the prosthetic or synthetic materials, with tumor lymphocytes present at the luminal surface. There were frequent mitoses and abundant karyorrhectic debris. All demonstrated a nongerminal center B-cell phenotype. All 3 cases were positive for Epstein-Barr virus, but there was no staining for human herpes virus 8. There was no other evidence of distant disease at the time of diagnosis and no recurrence or dissemination occurred after surgical removal of the prosthesis, though follow-up was limited. On the basis of 2008 World Health Organization diagnostic criteria, we believe these cases should be classified as DLBCL associated with chronic inflammation. However, unlike the characteristically poor prognosis reported in this entity, we hypothesize that the disease resectability in these cardiac sites, in many cases, may allow for a better prognosis than DLBCL with chronic inflammation at other less resectable sites.

Symptomatic metastatic right atrial lymphoma in a patient with AIDS presenting with pulmonary embolization.

Tumors involving the heart are rare, and the majority of them are benign. Secondary lymphoma with localization to the heart is the third most common malignant heart tumor and is more common, by far, than primary cardiac lymphomas. In patients with human immunodeficiency virus, the risk of development of systemic lymphoma is 60 to 200 times higher than in the general population. Symptoms usually consist of chest pain and dyspnea. Patients can also present with obstructive symptoms, based on the location and size of the tumor, and signs such as elevated jugular venous pressure, peripheral edema, ascites, and hepatomegaly. Transthoracic echocardiography is the initial modality of choice for diagnosis of cardiac lymphomas because it is readily available and helps localize the tumor, but transesophageal echocardiography and magnetic resonance imaging remain the best tests for evaluation. Treatment consists primarily of chemotherapy, and anticoagulation can be used in certain cases where embolization of the tumor is likely. This case review describes a 37-year-old man with past medical history significant for herpes zoster and stage 1 syphilis who presented with complaints of weight loss, intermittent fevers, and vague chest pains of 1-month duration.

Herpes simplex virus type 1 infection associated with atrial myxoma.

Some findings suggest an infectious factor in cardiac myxoma and certain histopathological features indicate herpes simplex virus type 1 (HSV-1) infection. We hypothesized that HSV-1 may be involved in the pathogenesis of cardiac myxoma. Paraffin-embedded tissue samples from 17 patients with atrial myxoma were investigated for HSV-1 antigen by immunohistochemistry and viral genomic DNA by nested polymerase chain reaction. The histogenesis and oncogenesis of atrial myxoma were assessed by the expression of calretinin, Ki67, and p53 protein, respectively. Autopsy myocardial samples, including endocardium from 12 patients who died by accident or other conditions, were used for comparison. HSV-1 antigen was detected in atrial myxoma from 12 of 17 patients: 8 of these 12 samples were positive also for HSV-1 DNA. No HSV-1 antigen or DNA was found in tissue from the comparison group. Antigens of HSV-2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus were not found in atrial myxoma. Calretinin was found in myxoma cells of all 17 cases but Ki67 was present only in smooth muscle cells or infiltrating cells in some cases. p53 was not detectable in any myxoma. Most infiltrating cells were cytotoxic T lymphocytes. These data suggest that HSV-1 infection is associated with some cases of sporadic atrial myxoma and that these may result from a chronic inflammatory lesion of endocardium.

Pathogenesis of HIV-associated heart disease.

As longevity increases in HIV-infected individuals after the introduction of highly active antiretroviral therapy regimens, long-term effects such as cardiovascular disease and, more specifically, symptomatic heart failure are emerging as leading health issues. In the present review article, we discuss HIV-associated cardiovascular disease, focusing on etiopathogenetic mechanisms that may play a role in diagnosis, management, and therapy of HIV-associated heart failure in the highly active antiretroviral therapy era.

Incidence of the involvement of the cardiovascular system in HIV infection.

The epidemiology of cardiac complications related to HIV, including cardiomyopathy, increased left ventricular mass, myocarditis, pericardial effusion, endocarditis, and malignancy, are discussed. An increased number of HIV-infected individuals may present with cardiac complications in the next decade as chronic viral infection, co-infections, drug therapy, and immunosuppression affect the heart. Understanding the nature and course of cardiac illness related to HIV infection may allow appropriate monitoring, early intervention and therapy, and will provide a baseline to evaluate the effects of new therapeutic regimens such as highly active antiretroviral therapy on the cardiovascular system.

Human herpesvirus-8-positive body cavity-based lymphoma involving the atria of the heart: a case report.

We describe an unusual case of a body cavity-based lymphoma, otherwise termed primary effusion lymphoma (PEL), involving the atria of the heart of an HIV-seropositive patient. This is the first reported case of the involvement of the heart by this rare lymphoma. This HIV-related lymphoma represents a distinct B-cell malignancy associated with human herpesvirus-8 (HHV-8) infection. It is characterized by involvement of body cavities, with infrequent evidence of organ or bone marrow infiltration. The tumor cells are large, nucleolated with an immunoblastic or anaplastic appearance, positive for activation markers, such as CD30, and negative for B-cell and T-cell immunophenotypic markers. Integration of HHV-8 DNA sequences is considered the hallmark of PEL. The tumor demonstrates frequent association with Epstein-Barr virus (EBV) and uniform absence of c-myc oncogene rearrangement, unlike most other HIV-related lymphomas.