Primary Testicular Lymphoma

Primary testicular lymphoma constitutes 1-2% of non-Hodgkin’s lymphomas and 5% or lesser of testicular tumours. It has a poorer prognosis than other NHLs. The survival curves do not plateau indication therapy is delaying relapse rather than curing patients. Addition of rituximab has improved survival.

Epidemiology

1. Age: Primary testicular lymphoma is a disease of the elderly with 85% of the patients being older than 60 years. No predisposing factors are known.

2. Testicular Disease: An association between testicular lymphoma and orchitis, testicular trauma and filariasis has been postulated but evidence supporting a role for these diseases in the pathogenesis of testicular lymphomas is lacking.

3. Genetic Predisposition: Testicular DLBCL are more common with HLA-DRB1*15 and HLA-DRB1*12.

4. Follicular Lymphoma: Follicular lymphoma is a disease of children, adolescents and young adults.

Pathology

More than 90% of the patients have diffuse large B cell lymphoma. Primary follicular lymphomas of the testis unlike their nodal counterparts are more common in children, adolescents and young adults. These patients do not have the t(14;18) translocation, are bcl2 negative and do not express p53. They express CD10, CD20 and BCL-6. The cells do not have protection from apoptosis that explains the good outcome of these patients. T cell lymphomas are very rare in the testis.

Clinical Features

Typically primary testicular lymphoma is a disease of the elderly. It usually presents with a unilateral testicular swelling. A hydrocele is present in about 40% of the patients. Contralateral testicular involvement is common and more often is metachronous than synchronous. Waldeyer’s ring is often involved at presentation and should be examined in every patient of testicular lymphoma. Most patients present with localized disease. Fifty to sixty percent present with stage I, 20-30% with stage II and the rest stage III. It is not possible to distinguished from stage IV testicular lymphoma from stage IV extra-testicular lymphoma with testicular involvement.

Recurrences commonly occur in extranodal sites. CNS involvement may present as parenchymal involvement or meningitis. It is common at diagnosis (2-16%). Other common sites of involvement are Waldeyer’s ring, lungs, pleura and soft tissue.

Investigations

Orchiectomy must be performed on all patients. It is best for diagnosis, removes the bulk of tumour and also removes a sanctuary for lymphoma. Testis is a sanctuary site because the blood testis barrier retards penetration of chemotherapy agents. Testicular large B cell lymphomas should be staged with CT scan, PET-CT and a bone marrow trephine biopsy scan as is done in case of other lymphomas.A CSF examination must be done in all patients to diagnose meningeal involvement and ultrasonography of the contralateral testis to detect synchronous testicular disease. Flowcytometery increases the accuracy of diagnosis of CNS involvement. All patients should be tested for HIV.

Staging

Staging for testicular lymphoma is as follows

1. IE Involvement of testis unilateral or bilateral

2. IIE Unilateral or bilateral involvement with regional nodes – para-aortic iliac

3. Advanced III/IV – Unilateral/bilateral disease + distant sites/extanodal diseases

Stage IV disease cannot be distinguished from testicular involvement by lymphoma.

Treatment

The standard treatment of a testicular lymphoma (DLBCL) is orchiectomy, chemotherapy with R-CHOP, intrathecal methotrexate and prophylactic testicular radiation. Younger patients may develop hygonadism following radiation and need monitoring of testosterone levels. R-CHOP 21 with scrotal radiation to the contralateral testis 30gy and intrathecal methotrexate result in a 5 year disease free survival of 74% and overall survival 85% (Vitolo U et al. J Clin Oncol 2011; 29:2766-72) comparable rates for CHOP stage I OS 58%, Stage II OS 46%. There is no plateau in the survival curve and chemotherapy may only delay relapse.

There are too few patients with follicular lymphoma of the testis described to draw conclusions for the efficacy of chemotherapy (CHOP). Some patinets have been treated with chemotherapy while other have achieved success only be orchiectomy.

Prognostic Factors

The poor prognosis factors in testicular large B cell lymphoma include advanced age, poor performance status, systemic disease, tumour bulk more than 9 cm, high LDH. On multivariate analysis low/intermediate IPI score, no B symptoms, antharacycline contain therapy and prophylactic scrotal radiation have been associated with favourable prognosis.