Primary testicular lymphoma: a single centre experience
Aim: Primary testicular lymphoma (PTL) is an uncommon and aggressive form of extranodal non-Hodgkin’s lymphoma (NHL). We aimed to analyse the clinicopathological characteristics and outcomes of our PTL cases. Materials and Methods: A review was made of the medical records of 339 NHL patients who wer...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2015
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| Цитувати: | Primary testicular lymphoma: a single centre experience / Y. Kemal, F. Teker, G. Demirag, I. Yucel // Experimental Oncology. — 2015. — Т. 37, № 3. — С. 223-226. — Бібліогр.: 27 назв. — англ. |
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irk-123456789-1455362019-01-23T01:23:59Z Primary testicular lymphoma: a single centre experience Kemal, Y. Teker, F. Demirag, G. Yucel, I. Original contributions Aim: Primary testicular lymphoma (PTL) is an uncommon and aggressive form of extranodal non-Hodgkin’s lymphoma (NHL). We aimed to analyse the clinicopathological characteristics and outcomes of our PTL cases. Materials and Methods: A review was made of the medical records of 339 NHL patients who were treated in the Medical Oncology Department between January 2005 and December 2013. Results: 8 PTL patients were identified from the 339 NHL patients. The average age of the patients was 67.7 ± 7.9 years (range 53–79 years). The mean follow-up time was 24.8 months (range 7–98 months). Inguinal orchiectomy was performed as a diagnostic and initial therapy and all the patients underwent 4–6 cycles of chemoimmunotherapy consisting of cyclophosphamide, doxorubicin, vincristine and prednisone plus rituximab. 4 of 8 patients received intrathecal prophylactic chemotherapy and 6 of 8 patients continued contralateral testis irradiation. Relapse occured in only 1 patient in central nervous system after 6 months who had not received intrathecal prophylaxis. No contralateral testis relapse was observed. Conclusions: Primary testicular NHL is an uncommon entity and we evaluated 8 patients; with one relapse in central nervous system and no relapse in the contralateral testis. Key Words: primary testicular lymphoma, contralateral scrotal irradiation, intratechal chemotherapy. 2015 Article Primary testicular lymphoma: a single centre experience / Y. Kemal, F. Teker, G. Demirag, I. Yucel // Experimental Oncology. — 2015. — Т. 37, № 3. — С. 223-226. — Бібліогр.: 27 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/145536 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions |
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Original contributions Original contributions Kemal, Y. Teker, F. Demirag, G. Yucel, I. Primary testicular lymphoma: a single centre experience Experimental Oncology |
| description |
Aim: Primary testicular lymphoma (PTL) is an uncommon and aggressive form of extranodal non-Hodgkin’s lymphoma (NHL). We aimed to analyse the clinicopathological characteristics and outcomes of our PTL cases. Materials and Methods: A review was made of the medical records of 339 NHL patients who were treated in the Medical Oncology Department between January 2005 and December 2013. Results: 8 PTL patients were identified from the 339 NHL patients. The average age of the patients was 67.7 ± 7.9 years (range 53–79 years). The mean follow-up time was 24.8 months (range 7–98 months). Inguinal orchiectomy was performed as a diagnostic and initial therapy and all the patients underwent 4–6 cycles of chemoimmunotherapy consisting of cyclophosphamide, doxorubicin, vincristine and prednisone plus rituximab. 4 of 8 patients received intrathecal prophylactic chemotherapy and 6 of 8 patients continued contralateral testis irradiation. Relapse occured in only 1 patient in central nervous system after 6 months who had not received intrathecal prophylaxis. No contralateral testis relapse was observed. Conclusions: Primary testicular NHL is an uncommon entity and we evaluated 8 patients; with one relapse in central nervous system and no relapse in the contralateral testis. Key Words: primary testicular lymphoma, contralateral scrotal irradiation, intratechal chemotherapy. |
| format |
Article |
| author |
Kemal, Y. Teker, F. Demirag, G. Yucel, I. |
| author_facet |
Kemal, Y. Teker, F. Demirag, G. Yucel, I. |
| author_sort |
Kemal, Y. |
| title |
Primary testicular lymphoma: a single centre experience |
| title_short |
Primary testicular lymphoma: a single centre experience |
| title_full |
Primary testicular lymphoma: a single centre experience |
| title_fullStr |
Primary testicular lymphoma: a single centre experience |
| title_full_unstemmed |
Primary testicular lymphoma: a single centre experience |
| title_sort |
primary testicular lymphoma: a single centre experience |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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2015 |
| topic_facet |
Original contributions |
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http://dspace.nbuv.gov.ua/handle/123456789/145536 |
| citation_txt |
Primary testicular lymphoma: a single centre experience / Y. Kemal, F. Teker, G. Demirag, I. Yucel // Experimental Oncology. — 2015. — Т. 37, № 3. — С. 223-226. — Бібліогр.: 27 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
AT kemaly primarytesticularlymphomaasinglecentreexperience AT tekerf primarytesticularlymphomaasinglecentreexperience AT demiragg primarytesticularlymphomaasinglecentreexperience AT yuceli primarytesticularlymphomaasinglecentreexperience |
| first_indexed |
2025-07-10T21:54:59Z |
| last_indexed |
2025-07-10T21:54:59Z |
| _version_ |
1837298623511003136 |
| fulltext |
Experimental Oncology 37, 223–226, 2015 (September) 223
PRIMARY TESTICULAR LYMPHOMA: A SINGLE CENTRE EXPERIENCE
Y. Kemal1,*, F. Teker2, G. Demirag2, I. Yucel2
1Department of Medical Oncology, Samsun Education and Research Hospital, Samsun 55100, Turkey
2Department of Medical Oncology, Faculty of Medicine, 19 Mayis University, Samsun 55139, Turkey
Aim: Primary testicular lymphoma (PTL) is an uncommon and aggressive form of extranodal non-Hodgkin’s lymphoma (NHL).
We aimed to analyse the clinicopathological characteristics and outcomes of our PTL cases. Materials and Methods: A review was
made of the medical records of 339 NHL patients who were treated in the Medical Oncology Department between January 2005 and
December 2013. Results: 8 PTL patients were identified from the 339 NHL patients. The average age of the patients was
67.7 ± 7.9 years (range 53–79 years). The mean follow-up time was 24.8 months (range 7–98 months). Inguinal orchiectomy was
performed as a diagnostic and initial therapy and all the patients underwent 4–6 cycles of chemoimmunotherapy consisting of cy-
clophosphamide, doxorubicin, vincristine and prednisone plus rituximab. 4 of 8 patients received intrathecal prophylactic chemo-
therapy and 6 of 8 patients continued contralateral testis irradiation. Relapse occured in only 1 patient in central nervous system
after 6 months who had not received intrathecal prophylaxis. No contralateral testis relapse was observed. Conclusions: Primary
testicular NHL is an uncommon entity and we evaluated 8 patients; with one relapse in central nervous system and no relapse
in the contralateral testis.
Key Words: primary testicular lymphoma, contralateral scrotal irradiation, intratechal chemotherapy.
Non-Hodgkin’s lymphoma (NHL) is a common dise-
ase and nearly 30% of cases occur in extranodal sites.
Primary testicular lymphoma (PTL) is an uncommon and
aggressive form of extranodal NHL [1, 2]. It accounts
for less than 5% of testicular malignancies and 1–2%
of NHL cases, although it is the most common testicular
malignancy in men aged > 60 years [1, 3]. PTL is usually
characterized by the unilateral mass or swelling of testis
and synchronous bilateral involvement at presentation
occurs in 6–10% of patients [4, 5].
Histopathologically, diffuse large B-cell lym-
phoma (DLBCL) is the predominant type in more than
80% of PTL cases [1]. Clinically they do not display
the clear survival plateau of other high-grade lympho-
mas because of the occurrence of late relapses [1,
4, 6]. Relapse presents mostly in extranodal sites,
especially in the central nervous system (CNS) and
contralateral testis [7]. Both these sites are considered
as immunoprivileged sites, owing to the blood-brain
and blood-testis barrier which reduces the penetra-
tion of chemotherapy agents as lymphoma cells may
escape the host T-cell antitumour response [8–10].
PTL is a rare condition and prospective randomised
controlled trials have been difficult to establish,
so standard treatments for PTL have not been well
defined. Orchiectomy is indicated for both diagnostic
and therapeutic purposes but prognosis is considered
to be poor in patients treated with only orchiectomy
and/or radiation [4, 11]. Recently combined modality
treatment with rituximab plus doxorubicin-based che-
motherapy, prophylactic intrathecal chemotherapy,
and scrotal radiotherapy is recommended, but con-
troversies still exist.
In this retrospective study, it was aimed to analyse
the clinicopathological characteristics and outcomes
of 8 PTL cases and discuss the knowledge and experi-
ence gained in this rare but important entity.
PATIENTS AND METHODS
A review was made of the medical records
of 339 NHL patients who were treated in the Medical
Oncology Department between January 2005 and
December 2013. Eight of the 339 patients were PTL. All
PTL patients underwent orchiectomy for pathologi-
cal diagnosis. The Ann Arbor classification system
was used for staging and B symptoms included night
sweats, recurrent fever and unexplained 10% loss
of body weight within 6 months. The international
prognostic index (IPI) score was also determined.
Complete remission (CR) was defined as absence
of disease signs and symptoms one month after
completion of all treatments. The overall survival (OS)
duration was calculated from the time of diagnosis
to the time of death or to the last follow-up. Progres-
sion-free survival (PFS) was measured from the time
of diagnosis to the time of treatment failure, relapse,
or death because of lymphoma. Relapse was defined
as the appearance of a new lesion in a patient with CR.
Statistical analyses were performed with SPSS soft
ware (SPSS 15.0, Chicago, IL). Descriptive analyses
were used for the characteristics of the study popula-
tion. Survival analysis was applied with the Kaplan —
Meier method.
RESULTS
Between January 2005 and December 2013 8 PTL
patients were identified from the 339 NHL patients.
The average age of the patients was 67.7 ± 7.9 years
(range 53–79 years). The mean follow-up time was
24.8 months (range 7–98 months). 4 patients had PTL
Submitted: May 26, 2015.
*Correspondence: E-mail: drturkmen@yahoo.com
Abbreviations used: CHOP — cyclophosphamide, doxorubicin,
vincristine, and prednisone; CNS — central nervous system;
CR — complete remission; DLBCL — diffuse large B-cell lymphoma;
IPI — international prognostic index; NHL — non-Hodgkin’s lympho-
ma; OS — overall survival; PFS — progression-free survival; PTL —
primary testicular lymphoma; R — rituximab; RT — radiotherapy.
Exp Oncol 2015
37, 3, 223–226
224 Experimental Oncology 37, 223–226, 2015 (September)
in the right testicle and 4 patients had PTL in the left
testicle. 6 patients were Ann Arbor stage I or II at the time
of diagnosis and 2 patients were stage III. Only 1 patient
had B symptoms at stage III. Inguinal orchiectomy was
performed as a diagnostic and initial therapy and DLBCL
was confirmed in all 8 patients after histopathological
examination. After orchiectomy, all the patients under-
went 4–6 cycles of chemoimmunotherapy consisting
of cyclophosphamide, doxorubicin, vincristine and
prednisone (CHOP) plus rituximab (R), followed by in-
trathecal prophylactic chemotherapy in 4 of 8 patients
and irradiation of the contralateral testis in 6 of 8 pa-
tients. CR was achieved in 7 patients after R-CHOP
chemotherapy, 1 patient was still undergoing chemo-
therapy during the last follow-up with partial response
(patient # 2) and 1 patient was continuing chemotherapy
and planned contralateral testis irridation (patient # 8).
During the follow-up period, a relapse occured in only
1 patient (patient # 4) in the CNS after 6 months, and
it was determined that he had not received CNS prophy-
laxis. He was treated only with palliative radiotherapy.
No contralateral testis relapse was observed. The pa-
tient characteristics and follow-up data are presented
in Table. Figure shows the OS analysis of the PTL cases.
Table. Epidemiological features, clinicopathological characteristics, type
of management, and outcome of patients with PTL
Pa
tie
nt
n
o
Ag
e,
y
ea
rs
St
ag
e
IP
I
Lo
ca
tio
n
Surgery Chemo-
therapy RT
CN
S
pr
op
hy
la
xis
Re
sp
on
se
Re
la
ps
e
O
S
O
ut
co
m
e,
a
liv
e
1 53 IE 1 Left Orchiectomy 4 × R-CHOP + − CR − 98 +
2 73 IIIEB 4 Left Orchiectomy 4 × R-CHOP − − PR − 7 +
3 63 IIIE 4 Right Orchiectomy 6 × R-CHOP + + CR − 9 +
4 68 IIE 2 Right Orchiectomy 6 × R-CHOP + - CR +(6) 12 −
5 79 IE 1 Right Orchiectomy 4 × R-CHOP + - CR − 15 +
6 66 IIE 1 Right Orchiectomy 6 × R-CHOP + + CR − 36 +
7 74 IIE 1 Left Orchiectomy 6 × R-CHOP + + CR − 14 −
8 66 IE 1 Left Orchiectomy 6 × R-CHOP − − CR − 8 +
Note: R-CHOP — rituximab, cyclophosphamide, doxorubicin, vincristine, and
prednisone; RT — radiotherapy; PR — partial remission.
0 20 40 60 80 100
0.0
0.2
0.4
0.6
0.8
1.0
Months
Fr
ac
tio
n
su
rv
iva
l
Figure. Kaplan — Meier OS curve for PTL patients
DİSCUSSİON
In this study, the clinicopathological characteristics
and outcomes of 8 PTL cases treated at our depart-
ment have been reported. In a recent report, Mertsoylu
et al. [12] evaluated 802 NHL patients and found only
2 cases of PTL in Southern Turkey. In an other study
from South India, Padhi et al. [13] reported 2 PTL pa-
tients among 308 NHL cases. Differently we treated
more PTL patients in our department.
PTL is a rare and aggressive form of extranodal NHL
which accounts for 1–2% of NHL cases in men aged
> 60 years [1, 3]. Although outcomes for patients with
PTL have historically been poor with no plateau in PFS
and OS curves, significant improvements have been
achieved with the addition of radiotherapy (RT) to full-
course anthracycline-based chemotherapy, R and
CNS-directed prophylaxis [14]. Relapses frequently
occur in the contralateral testis and CNS [15]. Both
these sites are considered to be immunoprivileged
sites, where lymphoma cells may escape the host
T-cell antitumour response and chemotherapy may
have reduced efficacy because of the mechanical
blood testis barrier and blood brain barrier [8, 9].
In addition, low levels of p53 expression but high levels
of phosphorylated STAT3 (pSTAT3), overexpression
of pCXCR4, and upregulation of the nuclear factor kB
(NF-kB) pathway were detected in PTL cases by Menter
et al. [16] and they reported that expression of both
CXCR4 and pCXCR4 was predictive of inferior PFS. Pre-
clinical studies have reported that directed metastasis
is mediated by CXCR4 activation and migration toward
CXCR12-expressing target organs [14, 17]. Therefore,
CXCR4 overexpression may predispode extranodal re-
lapse in PTL. Due to the above-mentioned mechanisms
orchiectomy alone is not sufficient even in the early
stages. It has been observed that more than 60% of pa-
tients treated with simple orchiectomy relapsed mostly
in the CNS in the first five years [4, 18].
In the current study, histopathologically all the pa-
tients were DLBCL, which was consistent with other
reports [19–21]. The most common regimen reported
in retrospective studies is R-cyclophosphamide,
doxorubicin, vincristine and prednisolone 3 weekly
(R-CHOP-21) and there are no data to suggest
that any alternative regimen offers a better out-
come [3, 7, 22]. In our study, all the PTL patients
received R-CHOP. R is a monoclonal antibody against
the CD20 antigen expressed on the majority of B-cell
lymphomas which has improved the outcome of both
high- and low-grade B-cell lymphomas in general.
It has also been incorporated into treatment strategies
for PTL over the last decade. However, a retrospec-
tive analysis of 769 patients with testicular lymphoma
from the Surveillance, Epidemiology and End Result
database in the USA did not show any improve-
ments in disease-specific survival after 2000, when
R came into common usage [4]. In a randomized trial
of 399 patients with DLBCL by Feugier et al. [23] the ef-
fect of CHOP plus R (R-CHOP) was compared with that
of CHOP and it was shown that the addition of R did not
reduce the risk of dissemination to the CNS at relapse.
According to the results of these retrospective studies,
the International Extranodal Lymphoma Study Group
(IELSG) reported a prospective phase II trial [24],
in which 53 patients received CHOP-21 plus R followed
by prophylactic irradiation of the contralateral testis
and intrathecal chemotherapy prophylaxis of 4 doses
Experimental Oncology 37, 223–226, 2015 (September) 225
of methotrexate. The patients with stage II disease
also received involved-field RT. After a median follow-
up of 65 months, the 5-year PFS and OS rates were
74% and 85%, respectively. Only 3 cases demonstra-
ted CNS relapse and no cases demonstrated relapse
in the contralateral testis.
In the current series, relapse occured in only 1 pa-
tient in CNS after 6 months who had not received CNS
prophylaxis and he died from his disease 6 months
after this relapse. The second patient died because
of myoardial infarction 14 months after the diagnosis.
Similar to the IELSG study no contralateral testis
relapse was observed in the current study group.
Neither was any CNS relapse observed in those who
received intratechal methotrexate but the current study
population was small and the follow-up period was not
long enough for some patients.
As CNS prophylaxis after anthracycline-based com-
bined chemotherapy and RT, Aviles et al. [25] treated
34 PTL patients with high-dose methotrexate (6 g/m2).
More recently Lokesh et al. [26] reported their PTL
series but none of them received CNS prophylaxis nor
contrlateral testis irradiation so the survival is poor.
In an other new report Ichikawa et al. [27] confirmed
that combined modality treatment suggests a better
PSF similar to our findings.
On the other hand, new potential therapeutic ap-
proaches are necessary because of the poor prognosis
for relapsed patients especially in CNS. If CXCR4 is found
to have a pathophysiologic role in mediating extrano-
dal relapse, development of the CXCR4 inhibitor may
prove attractive as a therapeutic adjuvant to chemo-
therapy. In addition, overactivation of the NF-kB and
STAT3 signalling pathways may be exploited as a tar-
get, but rigorous testing is required in prospective
clinical trials in PTL patients.
In conclusion, PTL is a rare condition and prospec-
tive randomised controlled trials have been difficult
to establish. However, collective international experi-
ence based on a number of retrospective analyses has
led to the evolution of therapeutic protocols that offer
a significantly improved prognosis for PTL. The best
outcome is achieved from combined treatment with
orchiectomy, R-CHOP and CNS prophylaxis with in-
trathecal chemotherapy and irradiation of the contra-
lateral testis. Despite notable improvement in the PFS
and OS, CNS relapse remains a devastating condition.
Ongoing IELSG30 phase II trials with modified CNS
prophylaxis (intrathecal injections of cytarabine) could
yield essential information. In the future, the develop-
ment of biological therapeutic agents should be con-
sidered for this rare but aggressive disease.
ACKNOWLEDGEMENTS
We thank to Dr. Berkhan Topaktas for his advice
on the statistical analyses.
CONFLICT OF INTEREST
The authors report no conflicts of interest.
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