Background

Diffuse large B-cellLymphoma of the testisis rare. Itstreatmentdepends on age, patient medical state and patient’spasttreatments. We report the case of a patient with a history of orchiectomy for a testiculartumor of whichhistopathologicalexaminationfound a diffuse large B-celllymphoma. He presentedwith a testicularlumpassociatedwith a hydrocele on the remainingtestis. Wewilldescribeour diagnostic and therapeuticstrategythatwasconsidered in ordertopreserve the testiswhilst meeting the oncologic objectives.

Case presentation

We report the case of a 52-year-old French man withhistory of stage IV diffuse large B-celllymphoma of the right testisafterundergoingorchiectomy of the right testis 10 yearsago. CT scan objectfied an enlargedright lateralaorticlymphnode(4cm in diameter).The patientreceived four cycles of R-CHOP (rituximab, cysclophosphamide, doxorubicin, vincristine and prednisolone) with an evaluationat the end of treatmentthatshowed a completeremission on CT scan. The patient hadsupportedchemotherapyverywell.Subsequently, the patient underwentradiotherapy on all the paraaortic and iliaclymphnodes as well as on the scrotum (30 Gy) with an exta 10 Gy focalized on the right lateralaorticlymphnodes.

Regular clinical and biological monitoring was unremarkable during a period of 10 years until the patient presented a progressive swelling on the left testiswhichhadbeguntwomonthsearlier.

Clinicalexaminationfound a patient in good medical state, a slightlypainfultesticular lump. No other mass wasfoundafter a completephysicalexamwasdone.

An ultrasound scan wasperformedwhichshowed a heterogeneoustesticularhypertrophyassociatedwithhydrocele.

Wewerethereforeconfrontedwiththreepossibilities:

1. TesticularGermcelltumor.
2. B-celllymphoma relapse.
3. « De novo » lymphoma.

Serumtumor markers were all negative.

Given the patient'shistory of orchiectomy and the inability to perform fine-needle aspiration due to the hydrocele and the risk of tumorcelldisseminationcoupledwith the patient'srefusal to undergoorchiectomy on hisremainingtestis,weopted for a surgicaltesticularbiopsywhichrevealed the presence of a diffuse large B- celllymphoma of the testis (DLBCL) expressing BCL2 and BCL6. Biomolecularanalysisusinginterphase  FISHstudiesdetected no rearrangement on the locus of the MYC gene. Cytologyof the hydrocelefluidwasnegative(Figure No : 1, 2, 3).

Giventhesefindingsweperformedtumorstaging:

1. Bonemarrowbiopsy:showed no invasion.
2. Lumbarpuncture:showed an acellularcerebrospinalfluid.
3. PET scan:found a hypermetabolicnecrosisisolated in the lefttesticlewith no other locations. Wehoweverretained the diagnosis of a stage IV diffuse large B celllymphoma of the testis.

The patient receivedchemotherapywith 4 cycles of R-CHOP + 4 therapeuticlumbarpuncturesassociatedwithMethotrexate.

Tumorevaluationat the end of treatmentfound a completeremission on both PET scan and thoraco-abdominal and pelvic CT scan.

Discussion

Primarytesticular non-Hodgkin lymphoma (NHL) isexceptionally rare with an annual incidence of 0.26 / 100,000 [1]; 85% of theselymphomas are diagnosedafter the age of 60 years[2] and veryoftenafterorchiectomy[3].

The peculiarity of our patient alreadyresides in the youngage of discoverywithsignificantdelay of relapse (10 years) whichwaslimited to the testis.

Riskfactors for primarytesticularlymphoma are not wellknown;chronicorchitis, cryptorchidism, trauma or filariasis have been implicated in some cases [4].

Diffuse large B celllymphomais the mostcommonhistological type [4]. The averageage of discoveryisbetween 60 and 69 years[5]. And most publications on testicularlymphomas correspond to isolated cases [1].

The DLBCL isoften in the form of a rapidly progressive unilateraltesticularhypertrophy[6]. Systemicsignsmayassociatefever, anorexia, night sweats and recentweightloss;they are present in about 25 to 41% of cases [1].

Tumor invasion of the scrotum and regionalretroperitoneallymphnodesoftenoccurswiththispathology[6]. Local invasion to the epididymis, spermaticcord and scrotal skin maybeencountered and hydrocelemaybefoundin 40% of cases [6].

Ultrasound shows an intratesticular mass of lowechogenicitycompared to normal testicular tissue or  anenlargedhypoechoictesticle[1].

Stagingisbased on Ann Arbor’sstaging[7]. DLBCL of the testisisknown to extend to the opposite testis, Waldeyer's ring, skin, lungs and central nervous system[2]. Serumlevels of tumor markers in testiculartumors: HCG and alpha-FP are rarelyhigh. However, LDH: a marker for assessingtumor size may have a role to  monitor the response to therapy[6].

On the histologicallevel, tumorcellsoftenpenetrate the tissue spacesdiffusely but usuallywithoutdestroying the basic architecture [6]. They express the markers usuallyfound in B lymphocytes such as CD19, CD20,  CD22 and CD79a but sometimes one or more of these markers maybelacking[8]. Immunohistochemicalstudypermits to distinguishsub-types of testicular DLBCL based on the presence of CD10, BCL6 and MUM-1 and to differentiatebetween germinal center B-cell-like DLBCL and not germinal center B- cell-like. This classification has a prognostic value [5-9].

Tumorstagingsimilar to otherlymphomasincludes a thoraco-abdominal and pelvic CT scan, a PET scan and abonemarrowbiopsy. The practice of lumbarpunctureisrecommended for the significantrisk of extension to the central nervous system [9].

Becauseof the rarity of thisentity, thereis no consensus for treatment[10]. ReportedTherapeuticstrategies for primarytesticularlymphomaassociatesorchiectomywithchemotherapy and / or radiation therapy[3]. Patients canbedividedinto 2 groups by usingAnn Arbor‘sstaging : limited (stages I and II) and advancedtumors (stages III and IV) [6].

In limitedcases;orchiectomyplays a diagnostic role in providingmaterial forhistologicalstudyand a therapeuticrole as wellconsideringthatblood-testisbarrierreduces the effectiveness of systemicchemotherapy[1]. Currently R-CHOP (rituximab, Cysclophosphamide, doxorubicin, vincristine and prednisolone) have showedGoodresults on overallsurvival and progression-free survival[11]. In addition, due to the highrisk of extension to the central nervous system, someauthorsrecommendprophylacticintrathecalchemotherapy[1]. Radiation therapymaybeindicated for prophylaxis in the testis and regionallymphnodes but also in the event of invasion of the retroperitoneallymphnodes[1].

In advanced cases, patients shouldbetreatedaccording to the recommendations of diffuse large B-celllymphoma of lymphnodes. The treatmentisbased on chemotherapycontaininganthracyclineassociatedwithrituximab , scrotal radiotherapy and intrathecalchemotherapy[1].

There is no standard treatment for relapse of DLBCL. But oftenitistreated as a non-Hodgkin aggressivelymphoma[1]. Therapeuticdecisionisinfluenced by age, generalmedical state and treatmentsalreadyadministered[1-6].

The risk of recurrenceishigheven in stage I and II and mayoftenoccurwithin 2 years[6]. The main factors of poorprognosisrecognizedare:age>65 years, a significanttumor mass (> 10 cm), stages III and IV of Ann  Arbor staging, signs of tumoragressivity, a highlevel of LDH and local invasion of the epididymis and spermaticcord[12]. Also, the International Prognostic Index and its components have been frequentlyreported as prognosticfactorsincluding in addition to pre-citeditems:advanced stage, B symptoms, ECOG performance status, Raisedserum b2-microglobulin, hypoalbuminemia, involvement of the lefttestis[13].

Conclusions

Diffuse large B cellLymphomais a rare entity. A carefultumorstagingisrequired to confirmits primitive origin. Throughthis case report, we have shown the importance of anamnesis for diagnosingtesticularlymphoma and opting for a conservative treatment to preserve the testis in a monorchid.

Declarations 

a)Availability of data and material:

All data and materials are available and reproductible.

b)Funding

This studywassupported by the Department of Urology, Hassan II University and the Department of Urology, Robert Boulin Hospital.

c)Ethics Commission

The EthicsCommittee of the Robert Boulin Hospitalapproved the completion of ourstudy.

d)Consent to publish

Writteninformed consent wasobtainedfrom the patient for publication of this case report and anyaccompanying images. A copy of the written consent isavailable for review by the Editor-in-Chief of the journal.

e)Abbreviations

• HOP:rituximab, cysclophosphamide, doxorubicin, vincristine and prednisolone
• CT:Computedtomography
• DLBCL:Diffuse large B-celllymphoma

f)Competinginterests

The authorsdeclarethatthey have no competinginterests.

g)Authors’ contributions

YK was the principal author and major contributor in writing the manuscript. TS, TG, DA, FT, MHF and FJ analyzed and interpreted the patient data and reviewed the literature. Allauthorsread and approved the final manuscript.

Figure No 1:Histologicalappearanceshowing a lymphomatousproliferationcontaininglarge polymorphouscellswithin the testicularparenchyma (x100) (Arrow : lymphomatousproliferation)

Figure No 2:Histologicalappearanceshowing expression of CD20 in immunohistochemistry (x100)

Figure No 3:Histologicalappearanceafterusing the MIB-1 (x100)

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