Original Article

Primary Cardiac Lymphoma

An Analysis of Presentation, Treatment, and Outcome Patterns

Adam Petrich, MD1,2,3; Soung Ick Cho, MD4; and Henny Billett, MD2,3

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
diag-
nostic 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 Primary Cardiac Lymphoma/Petrich et al

We present here an analysis of 197 cases of primary For analyses of factors affecting survival times,
cardiac lymphoma. We have reviewed the cases for multi- patients were included only if they were diagnosed
ple discreet variables in an effort to establish patterns to
these disparate presentations, treatments, and
outcomes to develop a rationale for prognostication in
this disease.

MATERIALS AND METHODS

PubMed searches using the terms primary, extranodal,
cardiac, and lymphoma were used to identify published,
potentially eligible case reports and case series. Works
cited by each of these reports were also evaluated to
iden- tify any cases that may have been missed.
Articles were excluded if 1) the reported patients
failed to meet the current definition of PCL, defined as
cardiac involvement of non-Hodgkin lymphoma,
present upon initial lym- phoma diagnosis, without
evidence of disease elsewhere as evidenced by a lack of
tumor encountered after a) both computed tomography
of the body and bone marrow biopsy, b) autopsy, or c)
an extensive search as reported by the author(s); 2) if
insufficient information was provided to make a
judgment of the diagnosis; or 3) if the source article
could not be located.
Analyses were performed using Excel (Microsoft
Corp, Redmond, Wash), in which all patient data were
tabulated. Variables sought included demographic
information, immune status, clinical presentation, radio-
graphic and other diagnostic characteristics,
disease complications, therapy rendered, therapeutic
response, survival, and cause of death. The year of
estimated diagno- sis for each patient was assessed
according to when the re- spective report was submitted
(or year from publication if submission date not
provided), and subsequently adjust- ing for survival
achieved at the time of report (eg, in the case of a
patient with 5-year survival reported in 1995, the year of
diagnosis was estimated to be 1990). Echocardio-
graphy results were assumed to be transthoracic,
unless otherwise specified. Any response categorization
provided (eg, complete response, refractory disease) was
assumed to be accurate, even if supporting data were
not provided. Where such categorization was not
provided, either a conclusion was drawn from
supporting data or, if these were lacking, it was
considered unknown. Cases that met criteria for an
unconfirmed complete response (CRu) were grouped
with complete responses (CR). All statistical analyses and
graphing were performed using Prism 5.0 (Graphpad
Software, La Jolla, Calif).
 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
Of the 197 patients in our analysis, the male-to-female
ra- tio was 1.94, with a median age of 63. Although
patients ranged in age from 9 to 90 years old, only 5 were
17 years of age or younger. HIV status was not
mentioned for 133 cases (68%), and of the remaining 64
Primary Cardiac Lymphoma/Petrich et al
cases, 26 were HIV- positive (41%). Global immune
status was not mentioned in 119 cases (60%). Apart from
HIV, 2 patients were oth- erwise reported as
immunocompromised. Of these 2, 1 report does not
provide the nature of the immunocom- promise,32
whereas the other patient was on chronic corti- costeroids
and methotrexate for treatment of rheumatoid
arthritis.33 Performance status was given in only 3 instan-
ces, making any assessment of this variable as a
predictor of outcome (including as a component of the
Interna- tional Prognostic Index) impossible.20,34 Half
of all cases included in our analysis were reported
within the last 15 years.
Presentation
Presenting complaints were provided for every patient
included in our analysis (Table 1). Dyspnea was by far
the most common presenting symptom, affecting 64%.
Constitutional complaints and chest pain were the next 2
most common symptoms, at 26% and 24%, respectively.
Ten patients presented with superior vena cava (SVC)
syndrome. Of 178 patients for whom pertinent
informa- tion was reported, 47% were in congestive heart
failure.
In cases where the presenting heart rhythm was
described, 56% (83 of 149) had an arrhythmia other
than sinus tachycardia/bradycardia. The 2 most
common
 Table 1. Presenting Symptoms and Clinical Findings in Primary Cardiac Lymphoma

Symptom/Findings Current Ikeda, Anghel, Ceresoli,

Study 200435 200421 199720
N5197 N540 N556 N548
Dyspnea (%) 64 50 46 NR
Arrhythmia (%) 56a 10 18 12
CHF (%) 47b 7 28 52
Constitutional Complaints (%)c 26 NR NR NR
Chest Pain (%) 24 NR 13 17
Pericardial effusion (%) 58d NR 30 NR
Pericardial mass (%) 30d 37 NR NR
Tamponade (%) 20b 7 NR 12
Peripheral Edema (%) 9 10 26 NR
SVC Syndrome (%) 5 2 5 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 28 cases (15%) reported neither transthoracic (TTE) nor
atrioventricular transesophageal echocardiography (TEE) results, and 13
(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 intra-
atrial 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
The first cases using echocardiography36 and nuclear
imaging37 were both reported for cardiac lymphoma
cases in 1981. This may have dramatically improved the
ability
to detect PCL: 64% of cases (14 of 22) occurring
before or during 1981 were diagnosed only at
autopsy; since then, that figure has dropped to 15%
(27 of 175). Only
of these were reported before 1981. In our series, TTE
had a sensitivity of 73% for right atrial involvement (n
108) and 55% for right ventricular involvement (n
86). Using TEE added to the findings of TTE in 19 of 36
cases (53%).
Pathology
Tissue diagnoses were made in 43% with minimally inva-
sive 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
than 10% each: 13 cases of Burkitt, 10 cases of T-cell
lymphoma,
8 cases of small lymphocytic lymphoma, and 2 cases of
plasmablastic lymphoma. The remainder (51 cases, 26%)
remained unspecified by the authors. These data agree
with the findings of previous authors, who noted
DLBCL as the predominant histology since the early
to mid-
1980s,2,38 irrespective of HIV status.
Tumor dimensions were reported in 81
instances, and, of these, 21 (26%) had disease greater
than 7.5 cm and 7 (9%) greater than 10 cm.
Immunohistochemistry (IHC) was consistent with the
predominance of B-cell disease in those tested; only 3
cases (of 88 reported) were CD-20 negative, of which 2
were T-cell histology and 1 plasmablastic. Values for
KI-67 were reported in 13
instances, with a median value of 80%. Just over 10%
(10 of 98) of patients had bone marrow involvement,
with over half of all reports not including this
information.
It was observed that 112 of 163 patients (68%) met
strict criteria for PCL (see Methods above), with the
remainder of reports lacking sufficient information to
make such a judgment. HIV status seemed to affect the
likelihood of meeting these criteria: only 26% of HIV-
positive patients (5 of 19) were free of extracardiac
lymphoma (ie, met a loose, but not strict chemoradiation, with another 2 patients having
definition of PCL), whereas 76% of HIV-negative
patients (28 of
37) and 74% of those with unknown HIV status (79 of
107) had disease limited to the heart and/or
pericardium at the time of initial diagnosis.
Laboratory Data
These data were most remarkable for elevations in
lactate dehydrogenase (LDH). Sixty-six reports included
LDH values, of which 92% were above their respective
reference ranges, with a mean of 770 IU/L (range 228-
4820 for the elevated levels described). The exact LDH
determinations of patients noted to have normal
levels were not detailed.20,39-42 Anemia affected 27 of
53 patients, with a mean hemoglobin of 11.4 g/dL.
There were too few reports of levels of creatine
phosphokinase (CPK), cardiac-specific enzymes, uric
acid, or erythrocyte sedi- mentation rate (ESR) for
analysis.
Complications
Of all patients included in the analysis, 57% had died
by the time of reporting, and the cause of death was
provided for 71% (80 of 113). The most common
cause of death was heart failure, at 40%. This was
followed by sepsis or other severe infection (26%) and
progression of lym- phoma (23%). Of the 21 cases in
which infection was the cause of death, 12 patients
(57%) had received chemo- therapy, although the link
between treatment and death from infection was
generally not specified. As mentioned above, over half of
all patients with PCL presented with an arrhythmia,
which was fatal in 11% of such cases (9 of
83). Four patients presented with sudden cardiac
death.23,36,43,44
A total of 12 patients presented with embolic
phenomena attributed to PCL, including 7 episodes of
pulmonary embolism (PE) and 4 episodes of cerebrovas-
cular accident (CVA). PE was fatal in 4 instances, CVA
in 1. Although tamponade physiology was noted in 36
cases (see Presentation above), in only 1 of these cases
was it described as fatal.45
Therapy
A total of 142 patients were treated by any modality
(72% of all patients, 91% of those diagnosed premor-
tem). The most common modality was chemotherapy,
which was administered to 89% of those treated.
Surgi- cal resection (either partial or complete) was
undertaken in 28% and radiotherapy performed for
20%, with a median dose of 34.8 Gy (range 15-59
Gy). A total of
23 patients received combined up-front
received both treatments asynchronously. Only 2
patients received radiation with- out any sort of
systemic chemotherapy,46,47 making a substantive
comparison of combination therapy versus radiation
alone impossible. High-dose chemotherapy, followed
by autologous stem cell transplant or allogenic
transplant, was given in 4 patients and 1 patient,
respec- tively. Heart transplant was reported for
another. Based upon the supposition that diagnostic
rates improved with advances in imaging, a parallel
analysis of treat- ment trends was undertaken. This
analysis demonstrated that, before and during 1981
(when echocardiography was first reported as a
diagnostic tool for a case of PCL), only 41% of
patients (9 of 22) were treated by any modality. Since
1981, 79% of all patients (133 of
168) have received treatment (for 7 patients it was
unclear whether treatment was given).
Anthracycline-containing regimens, primarily CHOP,
were given to 89% (97 of 109) of those patients
receiving chemotherapy. The use of rituximab first
occurred in
2001 and, since that year, has been given to 38% of
patients with non-Tcell histology (23 of 61). A
median of 6 cycles of chemotherapy was administered
to the 67 patients for whom such data were reported.
One fatality from tumor lysis syndrome was
reported.48 Taken together with the 12 patients who
had received chemo- therapy and developed sepsis, this
is indicative of a treat- ment-related mortality (TRM)
as high as 10% (13 of
126) for chemotherapy. Management of heart failure
and arrhythmias arising as complications of PCL was
mentioned in only isolated case reports; therefore, no
such data were collected or analyzed.
Response and Survival Patterns
Of the 142 patients treated by any modality, 92 had a
partial (PR) or complete response (CR) documented; 26
reports did not provide response data. This translates to
an overall response rate (ORR) of 79% for cases
with available data and a CR of 59%, which compares
favor- ably to the 38% CR reported in a 2004 review
of 40
Table 2. Therapeutic Management and Overall Survival in
Primary Cardiac Lymphoma
Median Overall
Survival, Mo
Type of Received Not
Therapy Received
Chemotherapy 30 (n105) 0.3 (n23)
Surgery 22 (n34) 10 (n92)
Radiation NR (n21) 10 (n104)
Chemotherapy & Radiation 22 (n19) 22a (n86)
N, number of patients; NR, not reached.
a
For those receiving combination chemotherapy and radiation, the compar-
ator group is those receiving chemotherapy alone, as only 2 patients
received radiation with no chemotherapy.
cases.35 These proportions are lower than the reported
71% CR in a review of cases between 1989 and 2005,
for which the total number of cases in that particular
analysis was not provided.49 Refractory disease as a best
response was documented in only 16 cases, and relapse
following a CR in only 12. The median time to relapse
was 7 months, with none reported beyond 12 months.
Second-line ther- apy was rarely reported, with a 42%
ORR (5 of 12) and 2 instances of CR.50,51, Although
surgical resection and radiation trended toward a
positive impact upon survival, only chemotherapy made
a statistically significant differ- ence (30m vs 0.3m,
P<.0001, Table 2). There was virtu- ally no difference
in survival patterns between those receiving
chemotherapy alone and those receiving com- bined
chemoradiation. This supports a previous assess- ment
of lack of benefit associated with the addition of
radiation therapy to chemotherapy in a smaller group of
patients.20 No effect of histology on overall survival (OS)
could be found; however, as noted, non-DLBCL histo-
logy was rare. Furthermore, subtypes of DLBCL (ie,
germinal center vs nongerminal center) were not
mentioned in any reports.
The median OS of those diagnosed antemortem
was approximately 12 months (Fig. 1). In an effort to
deter- mine predictors of outcome, we analyzed survival
patterns of the 128 patients diagnosed premortem,
for whom survival data was reported. Among them,
those who had extracardiac disease (n 32) had a
reported median OS of 6 months, whereas those
without (ie, those who met strict criteria for PCL, n
74) had a median OS of 22 months (Fig. 2, Panel A;
HR 0.49, 95% CI, 0.26-0.91; log-rank P .024),
with all reports of survival >30 months (n 13)
coming in those without extracardiac disease. Median
OS for those with immunocompromise (including HIV,
n 28) and immunocompetence (n
P
<.0001
.18
.11
.84
Figure 1. Kaplan-Meier survival curve of entire cohort (N
128) of patients for whom antemortem diagnosis was made
and survival data reported.
50) were 3.5 months and not reached, respectively (Fig.
2, Panel B; HR 0.29, 95% CI: 0.13-0.68; log-rank P
.0042). The only chamber whose involvement was found
to affect survival was the LV; the 19 patients with this
chamber involved incurred a median OS of only 1
month, whereas the 103 patients free of LV
involvement had a median OS of 22 months (Fig. 2,
Panel C; HR 0.28, 95% CI: 0.12-0.64; log-rank P .
0024). Those patients with an arrhythmia of any type
(as defined above in Methods) had a median OS of not
reached (n 55), whereas those without rhythm
disturbances (n 41) had median OS of
6 months (Fig. 2, Panel D; HR 0.51, 95% CI: 0.29-0.91;
log-rank P .024).
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).

As noted, our analysis concurs with previous
reports indicating that PCL favors the right side of the
heart. The reason for this phenomenon remains unclear;
however, a possible, novel, anatomic explanation might
be the find- ing that the thoracic duct drains lymph into
the SVC, and subsequently into the right atrium and
ventricle, meaning the right heart would more readily
and frequently be exposed to any pre-existing nodal
lymphoma. This might also explain the finding that
approximately a quarter of PCL patients have SVC
involvement. However, if this hy- pothesis were correct, it
would seem to indicate that PCL is more of an
extranodal complication of what is presumed to be
occult systemic (nodal) lymphoma, and supports the
analysis above that chemotherapy offers opti- mal therapy
for this lymphoma. This would further lead us to posit
that PCL, rather than being primarily cardiac, is simply
a manifestation of occult systemic lymphoma, thus
stripping the strict definition of the disease of sub-
stantive meaning. It nevertheless seems warranted, at
least
currently, to maintain PCL as a diagnostic category. The
cardiac manifestations would almost certainly affect
aspects of care (eg, diagnosis, complications), compared
with cases of systemic lymphoma without significant
cardiac involvement. Moreover, survival rates would be
measurably impacted (Fig. 2A).
In terms of predominance of presenting
symptoms/ findings, our results generally agree with
previous reports (Table 1). An interesting exception is
the much higher incidence of arrhythmia that we here
report. The reason for this discrepancy is unclear, but
may be the result of different inclusion criteria and/or
sample size differen- ces.20,21,35 We considered the
possibility that the high rate of RA involvement might
lead to frequent interference with the function of, or
conduction from, the sinoatrial lymph node.
However, the rates of arrhythmia were virtually
identical: 58% in those with RA involvement (n
101) and 59% in those without RA involvement (n
39).
 Table 3. Therapeutic Modalities for the Treatment of Extranodal Lymphomas

Site of No. Surgery Chemotherapy RT ORR Median

Lymphoma (%) (%) (%) (CRR) (%) OS (%)
Gastric55 312 77 80 19 80 (64) 71 (5 y)
Breast56 204 49 80 64 93 (89) 63 (5 y)
Testes57 373 95 75 53 86 (71) 48 (5 y)
CNS58 378 23 70 88 61 (NR) 37 (2 y)
Cardiac (Current) 142 28 89 20 79 (59) 42 (4 y)

ORR, overall response rate (%); CRR, complete response rate (%); OS, overall survival; NR, not reported.

In our analysis of treatment outcomes, chemother-
apy 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
involvement as a risk factor, although not necessarily
expected, is not particularly surprising. It was subse-
quently noted that 77% of those patients with LV
involve- ment also had right chamber involvement; those
with LV disease may simply be a group with a higher
overall bur- den of cardiac disease, and therefore at
higher overall risk of mortality. It remains curious that
those presenting with rhythm disturbances actually
survived longer than those with normal rhythms,
although there are at least 2 poten- tial explanations: a)
those with arrhythmias more often suffered symptoms
that prompted early presentation; or b) the detection
of arrhythmia upon presentation may have led to
earlier imaging and/or treatment of the affected
population.
We acknowledge that caution must be used in
inter- preting the presented data. Within the
population of patients affected by PCL wide variations
exist, such as the presence and nature of comorbidities,
the sophistication of available diagnostic tools, and even
treatment options. Moreover, when dealing with case
reports as a source of data, there is a bias in favor of
reporting those cases with unique features and a lack of
standardization as to what features should or should not
be reported.
With this in mind, we believe that our data raise
some questions and point out what seem to be trends in
PCL, but fail to definitively answer most issues. Our data
indicate that arrhythmias are much more common in
PCL than previously believed. This is particularly
relevant in terms of further data we have provided
indicating that the presence of arrhythmia may impact
survival. We have shown that response rates approximate
those seen in other types of extranodal lymphoma, but
with inferior overall survival (with the exception of
primary CNS lymphoma). Finally, we would like to note
that PCL, though still rare, is more common than
previously thought. By our analysis of existing reports,
there have been as many as 14 cases in
1 year (in both 1990 and 2006), and an average of over 6
cases per year since 1996. There are certainly others that
go unreported; we have been able to find an additional
3
cases of PCL treated at our own institution (not
reported here) within the last 5 years. In light of the
emerging role of gene expression profiling to sub-
classify DLBCL and clarify prognosis,53,54 comparison
of PCL genotypic ana- lyses might be informative. With
these concerns in mind, it may be worthwhile to create a
registry of PCL patients to better standardize available
data and resolve questions regarding prognosis and
appropriate management.
CONFLICT OF INTEREST DISCLOSURES
The authors made no disclosures.
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