Prognostic Markers in Cardiac Non-Hodgkin Lymphoma: A Retrospective Review

Introduction: Cardiac involvement by Non-Hodgkin lymphoma (NHL) occurs by several distinct mechanisms: primary extra-nodal disease, direct extension, hematogenous or lymphatic spread. While it is not an uncommon autopsy finding, it is rarely deemed to be clinically significant. By contrast, extranodal involvement by NHL is associted with inferior outcomes. Here we performed a retrospective review of 91 published cases of NHL with biopsy-proven cardiac disease to evaluate its clinical significance and impact on outcomes.

Methods: A literature search using Pubmed was performed between 1990 and 2015. Inclusion criteria were biopsy proven lymphoma, age greater than or equal to 18, no history of bone marrow transplant and direct involvement of the pericardium and or myocardium. Survival data was only analyzed from patients without HIV/AIDS. Log-rank (Mantel-Cox) test was used to calculate survival. Age comparisons were calculated using an unpaired t-test with a two-tailed p-value and one-way ANOVA.

Results: Ninety-one cases met inclusion criteria for the review. The mean age was 55 years (range 19-90 years). Patients with Burkitt lymphoma and HIV/AIDS were younger (p=0.016). Of patients with pathological evidence of cardiac involvement, diffuse large B-cell lymphoma (DLBCL) was the most common NHL subtype (52% of cases), followed by T-cell lymphoma (16%), Burkitt Lymphoma (8%) and small lymphocytic lymphoma (SLL, 6%). Chest pain was the most frequent presenting symptom (Table).

Forty-eight patients had primary cardiac lymphoma, which was defined as de novo lymphomatous involvement confined to the myocardium and/or pericardium, 41 patients had secondary disease and two were indeterminate. Patients with primary cardiac lymphoma were older (60 years, 95% CI, 55-59 years, versus 50 years, 95% CI, 47-53 years, p=0.006).

Survival data were available for 54 patients. Of note, ~50% of patients did not receive therapy. Median survival was 3 months for all patients. The median survival of patients with T-cell lymphoma was 2 months, versus 4 months in the B-cell lymphoma subgroup (p=0.20). The median survival of patients with indolent B-cell lymphoma (SLL) was 37.5 months versus 4 months in patients with aggressive lymphoma (DLBCL and Burkitt, p=0.77). We found that female sex was associated with a trend towards improved outcome (median survival of 12 versus 3 months, p=0.63). Furthermore, patients diagnosed with primary (de novo) cardiac lymphomas also had better survival, 4 versus 2 months (p=0.23), possibly reflecting the more aggresive nature of relapsed disease.

On further analysis, patients who were alive one month after diagnosis had a median survival of 18 months versus 3 months for all patients in this cohort (p=0.032). Furthermore, patients with primary B-cell lymphoma had superior survival to patients with T-cell lymphoma and/or secondary disease (median survival not reached vs 2.5 months, p=0.027). We also found that patients who received chemotherapy had a median survival of 18 months versus 1 month for those who did not (p=0.003).

Discussion: Symptomatic cardiac involvement by NHL is rare. While it appears to be more common in DLBCL, it is seen across multiple indolent and aggressive NHL subtypes and is more common in men, typically presenting in the 6^th decade of life. The outcomes of patients with NHL with cardiac involvement are poor, particularly among those with aggressive subtypes. However, patients who are candidates for chemotherapy and who survive beyond one month, particularly those with de novo (primary) cardiac B-cell lymphoma, are more likely to achieve long-term survival. Pathological lymphomatous involvement of cardiac tissue needs to be considered as part of differential diagnosis during work-up of patients with NHL.