Fibrin-associated diffuse large B-cell lymphoma with plasmacytic differentiation: case report and literature review.

BACKGROUND: Primary cardiac lymphomas are extremely rare entities (< 2% of cardiac tumours) and the most frequent histologic type is diffuse large B-cell lymphoma (DLBCL). Fibrin-associated DLBCL (FA-DLBCL) is a very unusual form of DLBCL associated with chronic inflammation, and only case reports and small series have been described. In the heart, it usually occurs in the context of a cardiac myxoma or cardiac prostheses and it is not bulk forming. These lymphomas frequently present with non-germinal center phenotype and are associated with Epstein-Barr virus (EBV) type III latency. CASE PRESENTATION: We describe a case of FA-DLBCL arising in a cardiac myxoma, with plasmacytic differentiation and type I EBV latency. CONCLUSIONS: Although they are very rare, FA-DLBCLs should be known for their diagnostic difficulty, due to its unspecified clinical manifestations, and for their more favourable prognosis, sometimes even without additional treatment after surgical resection.

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.

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.

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.

An epizootic of subcutaneous tumors associated with subgroup A avian leukosis/sarcoma virus in young layer chickens.

An outbreak of subcutaneous tumors in young layer chickens in a flock in Japan was investigated. Tumors appeared as extensive swelling or bulbous protrusions of the integument and were observed in the head or wing of chickens approximately 9 wk old, with a prevalence of 0.4% (157 of 42,000) in the affected flock. Histologically, two types of tumor were observed: myxoma containing abundant hyaluronic acid and neurofibroma with hyperplasia of the Herbst corpuscles. Ultrastructurally, type C retroviruses, such as viral particles, were found in the tumors. The tumors were specifically stained by immunohistochemistry using monoclonal antibodies against the subgroup A avian leukosis/sarcoma virus (ALSV) and yielded a positive reaction to primers specific for subgroup A ALSV by reverse transcriptase-polymerase chain reaction assay. The virus was isolated from the tumors. Seventeen of 20 clinically normal chickens in the affected flock showed antibodies against ALSV. These results suggest that subcutaneous tumors are associated with subgroup A ALSV infection.

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.