primary cardiac lymphoma: report of two cases occurring in immunocompetent subjects
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Primary Cardiac Lymphoma: Report of Two Cases
Occurring in Immunocompetent Subjects
GABRIEL ANGHELa, VALERIO ZOLIa, NICOLA PETTIa, DANIELE REMOTTIb, MARIANO FECCIAc,PAOLO PINOc and IGNAZIO MAJOLINOa,*
aHematology and Bone Marrow Transplantation Unit, Ospedale ‘‘S. Camillo – Forlanini’’, Rome, Italy; bPathology Service Unit, Ospedale ‘‘S.Camillo – Forlanini’’, Rome, Italy; cCardiology Service Unit, Ospedale ‘‘S. Camillo – Forlanini’’, Rome, Italy
(Received 12 August 2003)
Primary cardiac lymphomas (PCLs), involving solely heart and/or pericardium at presentation, arerare events. They are frequently recognized at autopsy and generally carry a poor prognosis due eitherto a delay in the diagnosis or to infiltration of heart structures. We report here on two patients withlarge B-cell PCL. One is a 52-year-old man who presented with multiple cardiac tumors infiltratingmainly the right atrium and the inter-atrial septum. Diagnosis was established by ultrasound-assistedtransesophageal biopsy of the intra-atrial multilobated tumor mass. He was treated with Rituximab-implemented high-dose sequential (R-HDS) chemotherapy followed by autologous peripheral bloodstem cell transplantation, attaining complete response. He had no evidence of disease 24 months fromonset. The second patient was a 70-year-old woman who presented with pericardial tamponade andlow-output cardiac failure. Despite prompt pericadiocentesis and chemotherapy with cyclopho-sphamide and vincristine, she died 2 weeks later. Postmortem examination revealed large B-celllymphoma proliferation confined to the heart. Whether primitive heart localizations represent anindependent prognostic factor, and what specific measures should be adopted in patients with this rarepresentation is the subject of the present report and review of the literature.
Keywords: Primary cardiac lymphomas; Heart tumors; Echocardiography
INTRODUCTION
Primary cardiac lymphomas (PCLs) are rare malignancies
with isolated, often bulky involvement of the heart and/or
pericardium [1]. PCLs represent about 1 – 5.6% of all
primary cardiac tumors. Cardiac localizations of systemic
non-Hodgkin’s lymphomas (NHLs) are much more
frequent, representing 20 – 28% of secondary cardiac
neoplasias [2 – 4].
In recent years, the increasing number of PCLs reported
in the literature seems to be due, at least in part, to the
increasing incidence of severe immunodeficiency, either
due to HIV infection or to organ transplantation [5 – 13].
In fact, primary lymphomas of the heart are extremely
rare in immunocompetent patients, so that their clinical
and biological behavior is largely unknown.
The majority of patients with PCLs present with
congestive heart failure, hemopericardium with or
without cardiac tamponade, superior vena cava
syndrome, cardiac arrhythmias and nonspecific
electrocardiographic abnormalities. Only a few of
them are asymptomatic [1,4,14,15]. PCLs are envis-
aged as prognostically poor, as most patients go
untreated and diagnosis is frequently made at post-
mortem.
The present report is focused on 2 patients with large
B-cell PCL seen at the Hematology Unit, S. Camillo
Hospital, Rome. One is a 52-year-old man who
presented with multiple cardiac tumors involving right
atrium and inter-atrial septum and only slight pericardial
effusion. He had a complete response with high-dose
sequential chemotherapy supplemented with Rituximab
and also including autologous peripheral blood stem cell
transplantation. The other was a 70-year-old woman
with a pericardial tamponade who died 2 weeks after
diagnosis.
*Corresponding author. Address: Hematology and BMT Unit, Azienda Ospedaliera S.Camillo-Forlamni, Circonvallazione Gianicolense 87, 00152,Roma, Italia. Tel.: +39-6-5870 4418. Fax: +39-6-58704644. E-mail: imajolino@libero.it
Leukemia & Lymphoma, April 2004 Vol. 45 (4), pp. 781–788
ISSN 1042-8194 print/ISSN 1029-2403 online # 2004 Taylor & Francis LtdDOI: 10.1080/10428190310001617259
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PATIENTS AND METHODS
Case 1
A 52-year-old man with hypertension and ischemic heart
disease, presented on June 2001 with dyspnea, cyanosis,
night sweats, diffuse itching and intense fatigue. His heart
rate was 96/min, respiration rate 26/min, and arterial
pressure 140/110 mm Hg. A bilateral ankle significant
edema was present. An initial chest X-ray was normal,
and an electrocardiogram only showed non-specific low-
voltage changes. His hemoglobin was 16 g/dl, hematocrit
50.2%, white blood cell (WBC) count 7.86 109/l with
normal differential, platelet count 1936 109/l. His serum
lactate dehydrogenase (LDH) was 780 U/L (nv: 230 –
460 U/L) and bilirubin 2.3 mg/dl (nv: 0.2 – 1 mg/dl),
mainly unconjugated (1.6 mg/dl). Despite these minor
alterations, CT scan and echocardiography (transthor-
acic, TTE and transesophageal, TEE) showed an
incomplete thrombotic occlusion of inferior vena cava
with multiple cardiac tumors involving the right atrium,
and in part the interatrial septum (Fig. 1). There was a
slight pericardial effusion, and a partial obstruction of the
inferior vena cava and sovrahepatic veins. A slight
abdominal effusion was also present. An echocardiogra-
phy-assisted transesophageal biopsy of the multilobated
tumor mass located in the right atrium showed a
histologic picture of diffuse large B-cell lymphoma
(ECA+, CD2O+). Trephine bone marrow biopsy
and aspiration were negative. The patient was treated
with R-HDS (Rituximab-implemented high-dose sequen-
tial chemotherapy). After an initial debulking with 3
monthly courses of APO (doxorubicin 75 mg/m2, iv, day
1; prednisone 40 mg/m2 orally, day 1 to 21; vincristine
1.4 mg/m2, iv, day 1) the patient received high-dose
cyclophosphamide (HD-CY) 7 g/m2, iv, followed by G-
CSF 5 mcg/kg/day, and high-dose etoposide (HD-VP16)
2 g/m2 plus G-CSF 5 mcg/kg/day. The apheretic
collection of mononuclear cells was attempted at two
time points, the first following HD-CY with the collection
of 0.26 l06/kg CD34+ cells, and the second following
HD-VP16 with the collection of 9.26 106/kg CD34+
cells.
Four doses of Rituximab1 375 mg/m2 each were also
given during this treatment phase. The first and the
second dose were administrated 48 h after HD-CY, and
24 h before the first leukapheresis, respectively. The third
and fourth Rituximab administrations were given 24 h
after the last dose of VP16 and 24 h before the second
planned leukapheresis, respectively. Before the autograft
the patient was considered to be in good partial
remission, with 80% tumor mass reduction. He then
underwent an autologous transplantation with the
previously cryopreserved autologous peripheral stem
cells. BEAM [16] was the preparative regimen. Following
the autograft, he recovered 0.56 l09/l PMN on day +12,
and 506 l09/l platelets on day +10. Two months later,
CT scan and both transthoracic and transesophageal
echocardiography showed complete disappearance of the
lymphoma (Fig. 2). The patient received no further
treatment, and is currently free of disease and in good
clinical condition 16 months from completion of therapy,
24 months from diagnosis.
Case 2
A 70-year-old woman with a history of diabetes,
hypertension, chronic renal failure and hemolytic anemia,
was admitted to our hospital with a picture of heart
failure. During the last few weeks she had developed
worsening dyspnea, fatigue, ankle edema and cyanosis.
On examination she was severely dyspnoic, and appeared
mentally disorientated and cyanotic. Her pulse rate was
94/min, and her blood pressure was 110/60 mmHg. There
were signs of pericardial tamponade and systemic venous
FIGURE 1 Case #1. Transthoracic (a) and transesophageal (b) echocardiography at onset showing a large, multilobated tumoral mass (discontineousline) involving the right atrium, RA (arrow) and the interatrial septum.
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hypertension, with jugular vein distension, and painful
hepatomegaly. Laboratory studies showed hemoglobin
11.4 g/dl, WBC count 5.26 109/l, platelet count
1446 109/l. Blood urea nitrogen was 74 mg/dl
(nv=10 – 50), creatinine 1.6 mg/dl, LDH 1415 U/l
(nv=230 – 460 U/L), total bilirubin=0.89 mg/dl (nv
0.2 – 1). The direct antiglobuline was positive. All other
blood tests, including liver function tests and CPK were
within normal range. However, a chest X-ray showed
marked cardiomegaly and CT scan and a two-dimension
transthoracic echocardiogram showed the presence of 2
multilobated tumors of the right atrium, with abundant
pericardial effusion and signs of cardiac tamponade.
Pericardiocentesis was urgently performed, yielding
1200 ml of effusion fluid. Cytospin preparations were
microscopically examined and showed a large number of
medium and large-sized lymphoid cells of B-cell origin,
characterized by irregular shape and large convoluted
nuclei, most with evident nucleoli. Trephine bone marrow
biopsy was normal. The diagnosis was of primary large-
B-cell lymphoma of the heart. Respiratory distress
improved in the following days, and steroid therapy was
started with i.v. methylprednisolone at the dose of
1.5 mg/kg/day for 15 days. Her condition however
remained critical, and despite chemotherapy with vincris-
tine 1 mg iv, cyclophosphamide 600 mg iv and methyl-
prednisolone 1 mg/kg/day, she died with progressive
cardiac failure 2 weeks from diagnosis. Post-mortem
examination confirmed the diagnosis.
REVIEW OF THE LITERATURE
We performed a medline-based extensive literature review
of primary malignant lymphoma of the heart. We only
considered cases of lymphoma confined to the heart and/
or pericardium, with no bone marrow involvement or
blasts in the peripheral blood, as well as those with a
single and asymptomatic extracardiac disease involve-
ment or minimal loco-regional spread due to massive
cardiac involvement according to the previously
suggested criteria for PCLs [1,17].
We found 68 cases whose characteristics responded to
these criteria [2,4,14,15,17 – 75]. Patients who did not
benefit from modern diagnostic criteria, e.g. ultrasound
imaging evaluation, and/or total body CT scan or
magnetic resonance imaging (MRI), like those reported
before 1980 [14,15,19 – 23] as well as case reports where
essential data were lacking or not available, were not
included in this analysis [17,18,24,28,36 – 38].
Overall we analysed 56 patients reported in the
literature which fulfilled the above mentioned criteria
[2,4,25 – 27,29 – 35,39 – 76]. The male-to-females ratio was
1.6. Median age was 67 years (range 29 – 90). The
reported site involvement at presentation is summarized
in Table I. In the majority of cases (72%) the tumor arose
in the right chambers of the heart, most frequently
involving the right atrium alone (42%), or in concomi-
tance with the right ventricle (28%). Isolate pericardial
effusion was found in 16% of cases, while 7 patients
(14%) presented with a tumoral mass and concomitant
pericardial effusion. The majority (78%) also had
myocardial involvement.
Symptoms at onset are non-specific. Dyspnea was
present in 46.1%, edema in 25.6%, weakness or fatigue
in 20.5%, chest pain or angina in 12.8%, arrhythmia
and palpitations in 17.9%, weight loss, fever or night
sweats in 8%. Superior vena cava syndrome and
congestive heart failure were present at onset in 5%
and 28%, respectively, while cardiac rupture at onset is
an exceptional event [52]. Approximately 3% of patients
were asymptomatic at the initial clinical assessment in
the reports analyzed here.
Imaging technology combined with invasive proce-
dures, as myocardial biopsy during cardiac catheteriza-
tion [26,76], transvenous endomyocardial biopsy or
transthoracic needle biopsy [2,4,49,58,59,69,73] or peri-
cardiocentesis with cytology examination [29,41,54,57 –
FIGURE 2 Case #1. Transthoracic (a) and transesophageal (b) echocardiography showing complete disappearance of the previously describedlymphoma mass involving the right atrium (RA)—arrow.
783PRIMARY CARDIAC LYMPHOMA IN IMMUNOCOMPETENT SUBJECTS
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59,65, our case #2] were the main diagnostic procedures,
especially when patients were not eligible for mediastinal
thoracothomy, due to their critical condition.
Cytology of the pericardial effusion proved diagnostic
in 60% of cases. In some cases, however, highly invasive
procedures were needed, as mediastinal thoracothomy
and subsequent biopsy [4,42,46,48,50,51,57,63 – 65,70,72].
Two-dimensional transthoracic echocardiography
[2,29 – 32,42,46,50,51,58,64,65,69,74, our cases] and
recently transesophageal procedure [4,70,76, our case
#1] with or without subsequent gallium-67 isotope study
[42,58] or CT scan [31,32,44,46,49,51,57 – 59,63 –
65,70,71, our cases], demonstrated their utility in
revealing and accurately characterize the intracardiac
mass, as well in excluding other tumor localizations.
Magnetic resonance imaging (MRI) [2,4,41,49,59,67,69,
72,76] showed the highest sensitivity (88%). There has
been a substantial improvement of diagnosis with the
advent of modern diagnostic techniques. In fact, in the
earliest reports, at a time when these technologies were
not available, diagnosis was frequently made post-
mortem, and often no specific treatment could be
instituted [29,30,32,35,44,45].
From a pathological point of view, the analysis of the
published reports shows a predominance (78%) of
medium and/or large B-cell high grade lymphomas (G
subtype, according to Working Formulation) [2,4,29 –
34,39 – 44,46,53,57,58,64,65,69,74,76] most of them
having a diffuse pattern, while uncleaved small cells
lymphomas [24,45] or immunoblastic cells lymphomas are
exceptionally rare [38].
Information on treatment is available for 52 patients
(Table II). This was chemotherapy (CHT) alone in 27
(52%), CHT plus radiotherapy in 4, CHT combined with
surgery in 2, RT solely (n=3 cases), CHT combined with
RT and surgery (n=1 case). Four patients underwent
surgery, 1 patient was submitted to orthotopic heart
transplantation [48], followed after severe acute rejection
and tumor relapse by concomitant immunosuppression
(cyclosporine) and chemotherapy. One patient (our case
TABLE I Literature review. Disease localizations in immunocompetent patients with PCLs including the 2 cases reported herein (data were
available for 50 patients out of the 56 analyzed)
Involved site Patients Percent of cases References
Right A 21 42 [4,26,28,31,32,40,43,46,50 – 53^,57,61,64,65,69,76], our 2 cases
Right+ left A 1 2 [49]
Right V 1 2 [54]
Left V 2 4 [29,74]
Right V+ left V 3 6 [2,48^^,67]
Right A+right V 14 28 [25,30,44,45,47,54,56,58 – 60,62,63,70,72]
Pericardial effusion* 15* 30 [32,34,35,40,42,43,53,54,59,71,73,74,75], our 2 cases
Abbreviations: A, atrium; V, ventricle; [53]^: the cited author reported 2 cases of PC1s with right atrial involvement; [48]^^ in this patient there was an extensive replace-
ment of myocardium with lymphoma; *in seven patients, pericardial effusion was concomitant to other localizations of the tumoral mass: right atrium (n=5), left ventri-
cle (n=1), and right atrium+right ventricle (n=1).
TABLE II Literature review. Treatment in the immunocompetent patients with PCLs (data were available for 52 patients out of the 56
analyzed)
Treatment
No of
patients AND AWD DD
Median
follow-up (range) References
CHT 27 6 12 9 7 m (0.07 – 144 m) [2,4**,29**,33,34,40,41,53,57**,59,60,
62 – 65,69,71 – 73**,75,76], our case #2**
RT 3 1 – 2 11 m (0.25 – 15 m) [39,42,58**]
CHT+RT 4 3 – 1 26.5 m (11 – 36 m) [42,46,66,67]
Surgery 4 – – 4 1.5 m (0.03 – 7 m) [30**,31,35,50**]
Surgery+CHT 2 – – 2 1 m, 13 m (1 – 13) [55,56]
Surgery+RT+CHT 1 1 – – 3 m [51]
CHT+autologous
PBSCT
1 1 – – 24 m Our case #1
Orthotopic heart
transplantation^
1 – – 1 16 m [48]^
No therapy^^ 9 – – 9** 7 days (3 – 30 days) [25,26,29,32,44,45,54,55]
Abbreviations: CHT, chemotherapy; RT, radiotherapy; PBSCT, peripheral blood stem cell transplantation; AND, alive with no evidence of disease; AWD, alive with
disease; DD, dead for disease progression; m, months; **cases of sudden death (4 30 days from onset); ^patient submitted to heart transplantation, followed by severe
acute rejection and tumor relapse, than treated with concomitant immunosuppression and chemotherapy; ^^patients not submitted to specific treatment, undergoing only
palliative/symptomatic therapy (pericardiocentesis, diuretics, antibiotics etc).
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#1) underwent CHT plus autologous stem cell transplan-
tation. Nine patients did not receive any specific therapy.
Chemotherapy meanly consisted in CHOP or other
anthracyclin containing regimens (n=22 patients),
alkylating agents and/or Vinca alkaloids (n=5 patients),
or other compounds as procarbazine, ifosfamide, metho-
trexate, etoposide, bleomycin, (n=4). Radiotherapy was
administrated alone or in combination with CHT or
surgery (radiation dose 20 – 40 Gy). All patients who did
not undergo any specific therapy (n=9) died within 30
days from diagnosis (range 3 – 30), but it is difficult to say
whether they were not treated due to the severity of
disease or death ensued due to lack of treatment. Among
the 27 patients who were given CHT alone, after a median
follow-up of 7 months (range 0.07 – 144) only 5 were alive
and free of disease. In the other treatment groups,
analysis of outcome is difficult due to the small number
of patients. However, only a few patients were alive and
in complete remission at the time of reporting, a fact that
seems to indicate the superiority of the chemotherapeutic
approach also in this rare variety of malignant
lymphoma.
DISCUSSION
We described here 2 cases of PCLs, the first being a 52-
year-old man who presented with multiple cardiac tumors
infiltrating the right atrium and the interatrial septum,
while the second patient was a 70-year-old woman who
presented with pericardial tamponade and low-output
cardiac failure. Diagnosis of a cardiac tumor was made
both with the help of echocardiogram, as well with CT
scan which confirmed the presence of a tumoral mass. In
patient #1, diagnosis of PCL was established by
transvenous echoguidated biopsy, while in the second
case, pericardiocentesis solely revealed lymphoma cells,
so that diagnosis of malignant lymphoma was possible
even without tissue histology. In the first case, treatment
consisted in Rituximab-implemented high-dose sequential
(R-HDS) chemotherapy followed by autologous periph-
eral blood stem cell transplantation (ABSCT), attaining a
long lasting complete response (24 months from onset). In
the second case, despite prompt pericadiocentesis and
chemotherapy with cyclophosphamide and vincristine,
the patient died 2 weeks from diagnosis. Postmortem
examination revealed B-cell lymphoma proliferation
confined to the heart.
The primitive occurrence of a cardiac tumor within the
heart structures (i.e. heart or pericardium) represents a
rare event. In autopsy series the figure is 0.0017% to
0.25% of total primary cardiac tumors [32,69]. Among
them, PCLs are extremely rare pathologic entities,
representing about 5.6% out off all malignant cardiac
tumors [4]. Although the definition of PCLs includes only
those lymphomas localized to heart and/or pericardium
[1], cases with massive cardiac involvement but minimal
lymphoma dissemination to other sites are worth being
included [17,54], as they probably originate from a
primitive heart localization. Beside those with isolated
heart involvement, we have analyzed as PCLs also tumors
with single asymptomatic extracardiac localization or
minimal locoregional dissemination.
In 1949, Whorten reviewed the 87 malignant neoplasies
out of the 329 cases of primary cardiac tumors previously
collected by Mahaim [14]. Among them, only 3 met the
criteria for a primary cardiac lymphoma. In the next two
decades, only a few authors [1,3,19 – 23] described a limited
number of so-defined reticulum-cell sarcoma of the heart.
The first review of interest is that published by Ceresoli
et al. in 1997 [53]. They analyzed 48 cases with PCLs,
including 8 with minimal extracardiac disease. Diagnostic
procedures mainly used were chest X-rays, TTE, TEE,
MRI and CT scan, combined with invasive procedures as
pericardiocentesis and thoracotomy. Cytology of peri-
cardial effusion was diagnostic in 67% of cases, while
thoracotomy and biopsy yielded a positive result in all.
Among the noninvasive techniques, TEE and MRI
showed a sensitivity 4 90%.
Chim et al. [57] described 2 cases of PCLs and
performed a 21 cases literature review, showing that only
9 patients were diagnosed ante-mortem as follows: 5 by
cytological examination of the pericardial effusion, 2 by
surgical biopsy and 2 by pericardial and myocardial
biopsies during pericardiocentesis respectively. This
stressed the possible role of the cytological examination
in case when open biopsy cannot be proposed because of
the critical clinical conditions. However, one should take
into consideration the scarse sensitivity of this procedure
(approximately 60% according to our analysis).
Percutaneous intracardiac biopsy with combined
fluoroscopic and TEE imaging was the main diagnostic
procedure in the case published by Jurkovich et al. [69]. In
this report, the author stressed the fact that although no
complications have been reported during transvenous
intracardiac tumor biopsy, potential complications as
perforation and cardiac tamponade, arrhytmias, vasova-
gal reactions and pneumothorax may be taken into
account. It also should be considered that TEE is very
useful for characterization of the tumoral intracardiac
masses and combined with fluoroscopy provides an
accurately and safely ultrasound-guided transvenous
biopsy diagnosis.
The cases of PCLs with available data mentioned in the
literature since 1980 were the object of the present review.
In accordance to the published data, PCLs occur more
frequently in male patients and typically in the elderly,
with lesions mainly localized in the heart’s right chambers
(classically in the right atrium) or pericardium, while in a
few cases other sites are involved (left atrium or ventricle,
interatrial or interventricular septum etc.). Clinical
presentation is variable, and in many cases aspecific as
arrythmias, lower edema, congestive heart failure,
pericardial effusion or superior vena cava syndrome. In
most cases, lymphoma cells originate from the B-
lymphocyte lineage, being frequently diffuse, medium or
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large cells high grade lymphomas [77]. Echocardioagraphy
(both transesophageal, as well as transthoracic echocar-
diography), CT scan and MRI are the mainly used
imaging techniques to detect cardiac tumors, but
histologic and immunochemical examination of the
involved tissue, as well as cytologic examination with
cytogenetic studies of pericardial effusion are always
required to confirm diagnosis. Early diagnostic workup,
based upon TEE, MRI or CT scan seems to have a major
contribution in revealing the heart involvement and
confirm the nature of the tumor. In order to exclude the
involvement of the bone marrow a trephine bone marrow
biopsy and aspiration is indicated. In rare cases
thoracotomy may be useful but this approach is highly
invasive and therefore with elevated risk, as death before
appropriate therapy have been occasionally reported
[29,32,44,45,55]. Polymerase chain reaction performed in
the pericardial fluid effusion samples [44,76], may be
useful in confirming the presence of a monoclonal
population lymphoid lineage. Therefore, the availability
of non invasive diagnostic procedures, including imaging
techniques as ultrasound, CT scan, orMRI, made possible
a precoceous diagnosis of PCLs [53,78]. On the other
hand, it should be mentioned that in our literature review,
the number of ante-mortem diagnosis strikingly increased
(31 out of 39), which may suggest that in the last years,
modern diagnostic procedures might have changed
outcome and prognosis of PCLs. Systemic chemotherapy
solely or in combination with irradiation of the tumoral
lesions, as well as surgery, consisting in resection of the
intracardiac tumor or pericardium, are the main ther-
apeutic approaches. Chemotherapy, alone or in associa-
tion with RT, showed at the moment the most relevant
results, as out of 30 patients undergoing CHT solely or
combined with RT, 20 (67%) were alive (8 with no
evidence of disease and 12 in partial remission), some after
more than 3 years since onset [41,71]. The analysis of the
mainly reported complications of the therapeutic
approaches for PCLs reported in the literature stresses
the iatrogenic nature of some of them as: cardiac toxicity
due to chemotherapy, post-radiotherapy pericarditis,
increased incidence of coronaris damage after radio-
therapy. Although a gold standard therapy for cardiac
lymphoma was still not established, and the reported
therapeutic attempts are quite unhomogenous, from the
analyse of the data reported in the literature, surgery did
not seem to have improved the prognosis.
A peculiar role of the sequential high-dose chemother-
apy followed by autologous stem cell transplantation in
the long survival, as might be taken into consideration in
the future especially in those clinically aggressive, large
cell lymphomas. Literature data show that if the disease is
promptly diagnosed at an early stage (with limited
extension), chemotherapy combined or not with radio-
therapy may improve the usually rapidly infaust prog-
nosis [26,30,53].
However, despite modern, early highly sensitive
diagnostic approaches such as transvenously or transoe-
sophageal intracardiac biopsy, cytologic analysis of
pericardial effusion when present including immunophe-
notyping, combined with non specific diagnostic proce-
dures such as electrocardiography, transthoracic 2D-
echocardiogram, computed tomography or magnetic
resonance imaging, [53,69,79,80] which mainly contrib-
uted to make this variety of lymphoma a treatable and
curable disease when promptly diagnosed, the prognosis
of PCLs still remains poor due both to diagnostic delay as
well as of the aggressiveness of this pathological entity.
Acknowledgements
This work was supported in part by a grant from AIRC,
Associazione Italiana per Ia Ricerca Contro il Cancro. Dr
Gabriel Anghel is a fellow of AIRC.
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