|Year : 2014 | Volume
| Issue : 3 | Page : 231-234
Primary Diffuse large B-Cell lymphoma of testis: A single centre experience and review of literature
Kadabur Nagendrapp Lokesh, Vishwanath Sathyanarayanan, C Lakshmaiah Kuntegowdanahalli, TM Suresh, Lokanatha Dasappa, Govinda Babu K Kanakasetty
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
|Date of Submission||28-Mar-2013|
|Date of Acceptance||25-Sep-2013|
|Date of Web Publication||12-Jun-2014|
OPD-5, Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Dr. MH Marigowda Road, Bangalore - 560 029, Karnataka
| Abstract|| |
Background: Primary testicular lymphoma constitutes 1-2% of Non-Hodgkin's lymphomas affecting elderly men >60 years of age. Most often it is a Diffuse large B cell lymphoma (DLBCL) and treatment involves multimodality approach involving surgery, chemotherapy and radiotherapy. Outcome remains poor in spite of aggressive therapy.
Materials and Methods: We retrospectively reviewed 286 registered cases of DLBCL (aged >14 years) from 2007 to 2011 and found nine primary testicular involvement patients. These cases were analyzed for baseline clinical features, investigations, staging, treatment and outcome.
Results: Median age was 58 (46-76) years. All patients presented with testicular swelling, two had the presence of B symptoms, and three with abdominal lymphadenopathy. Six had stage IE disease and three patients had stage IIE. All patients underwent orchiectomy. Eight patients received combination chemotherapy and six completed three or more cycles. Four achieved complete response, among these three relapsed after 32, 42, 70 months and one was lost to follow up. Two had a progressive disease, among these one died of disease and one alive with disease. Complete follow up was available from five patients and median survival was 36 months (11-78 months).
Conclusion: Primary testicular DLBCL is uncommon, needs multimodality treatment and central nervous system prophylaxis to improve the survival. The outcome needs to be further investigated using biological approaches (Rituximab based) and/or more aggressive management.
Keywords: Diffuse large B cell lymphoma, Non-Hodgkin′s lymphoma, testis
|How to cite this article:|
Lokesh KN, Sathyanarayanan V, Kuntegowdanahalli C L, Suresh T M, Dasappa L, Kanakasetty GK. Primary Diffuse large B-Cell lymphoma of testis: A single centre experience and review of literature. Urol Ann 2014;6:231-4
|How to cite this URL:|
Lokesh KN, Sathyanarayanan V, Kuntegowdanahalli C L, Suresh T M, Dasappa L, Kanakasetty GK. Primary Diffuse large B-Cell lymphoma of testis: A single centre experience and review of literature. Urol Ann [serial online] 2014 [cited 2020 Jan 20];6:231-4. Available from: http://www.urologyannals.com/text.asp?2014/6/3/231/134277
| Introduction|| |
Primary testicular lymphoma (PTL) constitutes 1-2% of Non-Hodgkin's lymphoma (NHL), 4% of extranodal NHL and varying l-10% of testicular neoplasms affecting elderly men greater than 60 years of age, with a grave prognosis. , The most frequent histology is Diffuse large B-cell lymphoma (DLBCL) and has a predilection for extra nodal sites, especially the contra lateral testis and central nervous system (CNS). , The incidence has increased over the last two decades with the emergence of human immune deficiency virus infection.  There is no consensus till date on the treatment of this aggressive neoplasm. Most of them use a multimodality approach involving surgery, anthracycline-based combination chemotherapy, prophylactic intrathecal chemotherapy and cranial/scrotal irradiation. This study has been done to review the clinical, pathological profile and treatment outcome of DLBCL testis at our centre in southern India.
| Materials and methods|| |
We retrospectively reviewed 286 registered cases at our institute, aged >14 years, diagnosed as DLBCL by appropriate tissue/lymph node biopsy confirmed by immunohistochemistry (WHO classification) between January 2007 and December 2011. Of these patients, those with primary involvement of the testis with or without regional lymph nodes were included in the study. The demographic details, clinical details, investigations, treatment and outcome were recorded and analysed.** Cotswold's modification of Ann-Arbor staging was used and International prognostic scoring (IPI) was done. Response was assessed according to standard criteria. Overall survival (OS) was calculated from the date of diagnosis until death (all causes) or last follow-up. Patients were followed-up every 3 months for 2 years and 6 months thereafter. Patients were considered on continuous follow-up if the last visit was within 6 months of data censoring.
| Results|| |
Median age was 58 (46-76) years [Table 1]. Six patients had right testis and three had left testis involvement. All presented with testicular swelling, two had B symptoms and three had abdominal lymphadenopathy. None had Bone marrow or CNS involvement. CD 20 monoclonal antibody was positive in all the patients. Three patients were in low-intermediate and six were in low IPI score. One patient was lost to follow up without treatment. All patients underwent high inguinal orchiectomy. Eight cases received anthracycline-based chemotherapy and six completed three or more cycles. All the patients tolerated chemotherapy without any grade III/IV toxicity. Four patients achieved complete response. Among these, one had nodal relapse at 42 months (died of disease), one was lost to follow up with no disease, and two had CNS relapse at 32 (lost to follow up with disease) and 70 months (alive with disease). Two had progressive disease (one alive with disease and one died of disease). The complete follow up was available from five patients with a median OS of 36 months (11-78 months).
| Discussion|| |
DLBCL is the most common PTL and constitutes around 69-75% of PTL. ,,,, The age at presentation is usually beyond the sixth decade of life. The median age of presentation in our study (58 years) was on par with other Indian study, but early when compared to studies from other countries (70 years). ,,,, Primary DLBCL of testis usually presents with an insidious onset of unilateral painless enlargement of testis. Thirty to forty percent of the patients may present with a hydrocele and shooting pain due to epididymo-orchitis. There is a propensity to involve the opposite testis which can be synchronous or metachronous. B symptoms may be present in upto one-third. ,,, All the patients in our series were presented with painless unilateral testicular enlargement and two had B symptoms. None had involvement of the opposite testis or presented with epididymo-orchitis/hydrocele. Three had retroperitoneal lymph node involvement at presentation.
There is a propensity for involvement of certain extranodal sites especially contra lateral testis, the waldeyer ring, skin, lung, and CNS. , None of the patients in our series had involvement of these sites.
Several variables have been reported as prognostic factors of PTL: Age, B symptoms, performance status (PS), tumour size >9 cm, spermatic cord involvement, elevated LDH, histologic grade, vascular invasion, CNS involvement, Ann-Arbor stage and IPI score. ,,, In our study, median age was 58 years, all were in good ECOG performance status exceptone (PS 2), two had B symptoms, IPI score was 2 in three cases, 1 in four cases and 0 in two cases. None had CSF or CNS involvement. All our patients were in either stage I or II, which is similar to other studies. ,,
In view of small retrospective case series and lack of clinical trials, the treatment of testicular lymphoma has remained a matter of intense discussion and controversy. ,, The treatment can be broadly divided into limited (stage I and II) and advanced stage (stage III and IV). The largest retrospective series [Table 2] of testicular DLBCL patients between 1968 and 1998 was reported by the International Extra nodal Lymphoma Study Group (IELSG).  This study emphasized the high risk of relapse and poor outcome in patients with intermediate to high IPI score, in the absence of prophylactic radiation to the contralateral testis, and treatment with non-anthracycline-based chemotherapy.  Another recent study concluded that only poor ECOG performance status, infiltration of adjacent tissues, and bulky disease as independent prognostic factors.  Earlier with high inguinal orchiectomy alone, OS was 10% at 5 years in stage I primary DLBCL of testis due to dissemination of the disease. , Several Studies showed that addition of anthracycline-based chemotherapy and radiation therapy lead to improvement in outcome and survival. , In spite of multimodality therapy, prognosis of this entity is poor with relapse in nearly half the patients and CNS relapse in 15-20% at 5 years. ,
|Table 2: Summarizing the review of literature with special reference to histology, treatment and outcome|
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The CHOP [Table 1] regimen has been the mainstay of therapy for several decades. Role of rituximab in improving OS is rather controversial in PTL and some authors attribute this improvement in prognosis over the last decade to the use of multimodality therapy, cranial irradiation and intrathecal methotrexate. Earlier, one study showed that the addition of rituximab to anthracycline-based chemotherapy improved outcome in stage I and II PTL.  But in another study, the addition of rituximab to chemotherapy did not prolong the survival of primary testicular DLBCLs. 
CNS relapse remains a major problem; hence, routine CNS prophylaxis is recommended. Over the last two decades, various modalities have been tried including prophylactic cranial irradiation, intrathecal methotrexate and chemotherapy to reduce CNS relapse. Ostronoff et al.,  concluded that all patients with testicular lymphoma should undergo CNS prophylaxis as mentioned above. However, there is no consensus so far on the management/prevention of CNS relapse. One study also emphasized the role of irradiation to contralateral testis as it improved the progression free survival by 34% and OS by 28%. 
In our study, no patient received rituximab in view of financial constraints. Earlier, the role of CNS prophylaxis was controversial as intrathecal therapy does not eliminate CNS relapses; relapses have been observed even after intrathecal therapy and also occur in brain parenchyma.  So our patients did not receive it, but it has been incorporated into our present protocol following these relapses.
A recent phase II trial concluded that combined treatment with rituximab with CHOP, intrathecal methotrexate, and testicular radiotherapy (reduce contralateral testis relapses) is feasible in patients younger than age 80 years and associated with a good outcome in patients with PTL.  However, a longer follow-up is needed to clarify the role of rituximab in PTL. An ongoing prospective study (IELSG-30) will answer the role of intrathecal liposomal cytarabine and systemic intermediate dose methotrexate.
Given the lack of randomized data in this rare disease, treatment options are based only on data available from small retrospective studies. The prognosis remains very poor despite combined modality treatment following orchiectomy. Treatment of relapses at extranodal sites, contralateral testis, and/or CNS needs to be further investigated using new molecular approaches and/or more aggressive management.
To conclude, the PTL is a rare disease and needs high index of suspicion for early diagnosis. Multimodality therapy is recommended for the treatment of stage I-II PTL, which consists of orchiectomy, four to six cycles of anthracycline-based combination chemotherapy with rituximab, radiation to involved lymph nodes and contralateral testis, and CNS prophylaxis. The outcome needs to be further investigated using biological approaches (Rituximab) and/or more aggressive management.
| Acknowledgement|| |
I thank all the staff and students of department of medical oncology, surgical oncology and pathology for their support in preparing this manuscript.
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[Table 1], [Table 2]