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BACKGROUND: Primary cardiac lymphoma (PCL) represents a rare subset of non-Hodgkin lymphoma, characterized
by poor outcomes. The authors aimed to construct a framework of known clinical presentations, diagnostic
features, disease complications, treatment, and outcomes to improve prognostication. METHODS: Individual patient
data were obtained from defined cases of PCL (1949-2009) and systematically analyzed. RESULTS: The authors
report results of a review of 197 cases of PCL, with half of all cases reported since 1995. Survival was affected by 4
factors: immune status, left ventricular involvement, presence of extra-cardiac disease, and arrhythmia. Median
overall survival (OS) for immunocompromised and immunocompetent was 3.5 months (m) and not reached,
respectively (HR 0.29, 95% CI, 0.13-0.68; P .004). LV involvement was uncommon (26%) and associated with
an OS of only 1m, whereas patients free of LV involvement had a median OS of 22m (HR 0.28, 95% CI, 0.12-0.64; P
.002). Patients with extra- cardiac disease had shorter median OS compared with those without (6m vs 22m, HR
0.49, 95% CI, 0.26-0.91; P
.02). Those patients with an arrhythmia of any type had a median OS that was not reached (n 55), whereas those
without rhythm disturbances (n 41) had median OS of 6m (HR 0.51, 95% CI, 0.29-0.91; P .024). Overall
response rate to therapy was 84%, with long-term OS over 40%. CONCLUSIONS: The current study presents the
largest analy- sis of PCL to date. The data demonstrate that PCL is now more frequently diagnosed premortem
and appears to have reasonable response rates. Lack of LV involvement and the presence of arrhythmias are
associated with improved survival. Cancer 2011;117:5819. VC 2010 American Cancer Society.
KEYWORDS: primary cardiac lymphoma, extra nodal lymphoma, non-Hodgkin lymphoma, immunocompromise.
Cardiac involvement of disseminated lymphoma is common, with between 9% and 24% incidence having been
reported on autopsy series,.1-3 Primary cardiac lymphoma (PCL), however, occurs with far lower frequency. Defined as
extranodal lymphoma involving only the heart and/or pericardium, it was first assigned a distinct pathological
categoriza- tion in 1978 on the basis of 4 cases that composed only 0.5% of a series of extranodal lymphomas.4
Applying the same definition, PCL was discovered in only 0.05% of a series of over 12,000 autopsies.5 In 1996, citing
the well recognized difficulty in assessing the precise location of the lymphoid cell(s) at the time of incipient clonal
expansion, the Armed Forces Institute of Pathology broadened the inclusion criteria to include those cases of lymphoma
presenting with cardiac manifestations, particularly if the bulk of disease was found in the heart or pericardium.6-9
A review of primary malignant tumors of the heart published in 1949 attributes the first recognized case to a
1939 report in a German publication.10,11 Since then, accumulated knowledge of PCL has been derived mainly from
isolated case reports, both pre- and postmortem, although series with as many as 9 cases have been published.12
It has been recognized that the incidence of extranodal NHL increased during the latter part of the 20th century
in both the United States and elsewhere.13,14 This has been attributed to multiple possible factors, including improved
diagnostic techniques, increased population of immunosuppressed patients, exposure to environmental toxins, and the
advent of the human immunodeficiency virus (HIV).15 With the discovery of HIV and its role in NHL in the early
1980s, authors began to distinguish reports of PCL vis-a-vis immune status, observing that PCL was more
commonand increasing in incidencein the immunocompromised population.7,16-18 Published reviews to date have
encompassed up to 9 HIV-positive patients and 38-48 immunocompetent patients, where a more recent study
reviewed 68 patients without regard to immune status.12,19-21
Corresponding author: Adam Petrich, MD, Division of Hematology, Department of Oncology, Montefiore Medical Center, 111 E. 210th Street, Bronx, NY 10467;
Fax: (718) 798-7474; apetrich@montefiore.org
1
Department of Oncology, Montefiore Medical Center, Bronx, New York; 2Division of Hematology, Department of Medicine, Montefiore Medical Center, Bronx,
New York; 3Albert Einstein College of Medicine, Bronx, New York; 4Department of Medicine, Jacobi Medical Center, Bronx, New York
DOI: 10.1002/cncr.25444, Received: December 28, 2009; Revised: March 22, 2010; Accepted: April 19, 2010, Published online October 4, 2010 in Wiley Online
Library (wileyonlinelibrary.com)
Cancer
581
February 1, 2011
Cancer
February 1, 581
2011
Original Article
Original Article
premortem and had reported survival data. Otherwise,
unless specified, each percentage presented is of the
entire
197-patient cohort.
RESULTS
Literature Search Results A total of 190 articles
containing case reports were identified. Of these, 13
articles were excluded, as they were not available in
English. Another
11 articles were excluded for the following reasons: a)
reported patients failed to meet either definition of PCL
(as provided above; 6 articles reporting on a total of 14
patients22-27); b) insufficient information was provided
about a given patient to make such a judgment (2
articles reporting on 1 patient each2,28); or c) the
source article could not be located (3 articles with
unknown number of case reports).29-31 This provided a
total of 166 articles, reporting 197 unique cases, for
inclusion in our analysis.
Population
Symptom/Findings
Current
Study
N5197
Ikeda,
200435
N540
Anghel,
200421
N556
Ceresoli,
199720
N548
Dyspnea (%)
Arrhythmia (%)
CHF (%)
Constitutional Complaints (%)c
Chest Pain (%)
Pericardial effusion (%)
Pericardial mass (%)
Tamponade (%)
Peripheral Edema (%)
SVC Syndrome (%)
64
56a
47b
26
24
58d
30d
20b
9
5
50
10
7
NR
NR
NR
37
7
10
2
46
18
28
NR
13
30
NR
NR
26
5
NR
12
52
NR
17
NR
NR
12
NR
8
All values given as percentages of the entire study cohort, unless otherwise specified.
CHF,congestive heart failure; SVC,superior vena cava; NR,not reported.
a
n149.
b
n178.
c
Constitutional complaints include fever, chills, sweats, and weight loss.
d
n183.
abnormalities
were
atrial
arrhythmias
and
atrioventricular
(AV) block, at 23% and 22%, respectively. Interestingly,
20 of 33 reported cases of AV block (61%) were
complete. In addition, 16 patients had either left or
right bundle branch block, and 8 suffered ventricular
arrhythmias.
In keeping with previous reports,35 right heart
involvement was far more common than left heart in
this population. A total of 179 patients had described
chamber involvement (vs pericardial involvement only),
of which
92% had either the right atrium (RA) or right
ventricle (RV) involved. Only 7% of these patients
had left-side involvement in the absence of right-side
involvement. The order of rate of chamber involvement
was RA > RV
> left atrium (LA) > left ventricle (LV). Other
commonly involved structures included the intraatrial septum (41%) and the SVC (25%). Of 183
patients with appro- priate information, 107 had
pericardial effusions (58%),
53 had masses involving the pericardium (30%), and 38
patients had both (21%). Of those with a pericardial
effu- sion, 34% demonstrated tamponade physiology.
Diagnosis
Tissue diagnoses were made in 43% with minimally invasive biopsy techniques 36% at surgery, leaving
autopsy diagnoses accounting for the final 21%. Of
those who underwent surgery, 48% had surgery
performed on an urgent/emergent basis; 56%
underwent partial or com- plete tumor resection at the
time of surgery.
By far, the most common NHL subtype was
diffuse large B-cell lymphoma (DLBCL), with 113
reports. Other reported subtypes constituted fewer
Therapy
Median Overall
Survival, Mo
Type of
Therapy
Received
Not
Received
Chemotherapy
Surgery
Radiation
Chemotherapy & Radiation
30
22
NR
22
0.3
10
10
22a
<.0001
.18
.11
.84
(n105)
(n34)
(n21)
(n19)
(n23)
(n92)
(n104)
(n86)
DISCUSSION
We have here presented the largest review of PCL to
date. We present data that seem to indicate that PCL is
now diagnosed with greater frequency, likely because of
advan- ces in imaging, although other factorssuch as
a larger population of HIV-positive or otherwise
immunosup- pressed patients with longer life
expectancy52 may be contributing to this increase. In
any case, we are unable to substantiate any claim that
incidence is rising in HIV- positive or otherwise
immunosuppressed populations. Our data demonstrate a
fairly even distribution of 23 cases over the years 1981 to
1995 (between zero and 3 reports per year), followed by
another 3 each in 2005, 2006, and
2007. Regardless of trends in overall incidence, it seems
that PCL in these HIV patients, as compared with
their immunocompetent counterparts, more often
reflects only a portion of their lymphomatous
involvement.
Figure 2. Kaplan-Meier survival curves by presence/absence of 4 variables found to significantly impact survival. Kaplan-Meier
survival curves are shown for
presence/absence of
extracardiac disease (Panel A; log
rank P value .024),
immunocompromise; (Panel B; log rank P value .0042), LV involvement (log rank P value .0019), and arrhythmia (log rank P
value .024).
Site of
Lymphoma
No.
Surgery
(%)
Chemotherapy
(%)
RT
(%)
ORR
(CRR) (%)
Median
OS (%)
Gastric55
Breast56
Testes57
CNS58
Cardiac (Current)
312
204
373
378
142
77
49
95
23
28
80
80
75
70
89
19
64
53
88
20
80
93
86
61
79
71
63
48
37
42
(64)
(89)
(71)
(NR)
(59)
(5
(5
(5
(2
(4
y)
y)
y)
y)
y)
ORR, overall response rate (%); CRR, complete response rate (%); OS, overall survival; NR, not reported.
In our analysis of treatment outcomes, chemotherapy appeared to have the greatest effect upon survival,
although it is understood there may have been a
selection bias. Those diagnosed premortem and yet not
receiving chemotherapy likely represented an extremely
moribund subset of the population, with shorter
survival times. Although a similar but weaker bias
may have occurred with other treatment modalities,
there was no significant difference in survival curves for
radiation or surgical resec- tion, compared with those not
receiving these treatments. Our demonstration that
radiation adds little to systemic chemotherapy in terms
of OS is novel. The aggregate of these data regarding
different modalities supports our hy- pothesis that PCL
should be considered a systemic disease, for which
treatment should always include chemotherapy.
We compared our treatment data and those of
reported series of other extranodal lymphomas (Table 3),
each of which, like our cohort of patients, was entirely or
mainly composed of patients with DLBCL subtype.
Chemotherapy was used more often in PCL than in
any other subtype, whereas surgery and radiotherapy
were used comparatively less; surgical rates were on par
with those observed in primary CNS lymphoma, and
rates of radiotherapy similar to those in gastric
lymphoma. Though no formal statistical comparisons
were under- taken, the overall and complete response
rates in PCL seem to approach those seen in primary
lymphomas of the breast, stomach, and testes, and
exceed those in primary CNS lymphoma. Similarly, the
OS rates are indicative of outcomes between primary
CNS and the other 3 types of extranodal lymphoma. It
also bears noting that multiple Kaplan-Meier survival
curves for PCL (Figs. 1 and 2) point to subsets of PCL
patients that are likely cured.
We have provided data in support of 4 adverse
prog- nostic factors: immunocompromise, extracardiac
disease, LV involvement, and the absence of arrhythmia.
The first
2 come as no surprise; immunocompetent patients would
be at an overall greater health risk, and subject to higher
rates of extranodal lymphoma. The presence of LV
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