Radiol Oncol 2003; 37(1): 23-7. Malignant lymphomas of the testis Ferhat Berkmen Department of Uro-Oncology, Ankara Oncology Education and Research Hospital, Ankara, Turkey Background. The aim of the study was to analyse 10 patients with malignant lymphomas of the testis, and to discuss the necessity of immunocytochemical staining to confirm the histologic diagnosis and an effective treatment policy. Patients and methods. Ten patients with malignant lymphomas of the testis were reviewed in order to iden-tify and study the incidence, histologic findings, the type of treatment administered and the overall outcome. Results. Testicular malignant lymphomas were identified ten times between 1984 and 1999. Bilateral tu-mours occurred simultaneously in 4 patients, and a metachronous malignancy and testicular relapses de-veloped in 2 patients. Of the remaining patients 4 had unilateral testicular involvement. None had elevated AFP and b-HCG or a history of undecided testis. Eight of patients were younger than 50 years. Five of the lymphomas were high grade, 3 were intermediate and 2 were low grade diffuse non-Hodgkin’s lymphoma. All patients were initially treated with radical orchiectomy and were, according to their clinical stage, treat-ed with chemotherapy and/or radiotherapy. Five of 10 patients were alive with no evidence of disease with follow-up ranging from 9 to 62 months. The remaining 5 patients died between 3 and 42 months respec-tively. Conclusions. Testicular lymphomas are similar to those of testicular germ cell tumours and account for ap-proximately 5% of all testis tumours and represents 1% of all lymphomas. Testicular lymphomas differ from germ cell tumours of the testis by following points: (1) Testicular lymphomas tend to occur in the middle ages, (2) tumour markers AFP and b-HCG are in normal limits, (3) a development in cryptorchid testis is extremely rare, (4) an early systemic therapy is indicated and watchful waiting policy can not be performed, (5) the prognosis is poor. The recognition of histologic diagnosis with immunocytochemical staining for leukocyte common antigen (LCA) is essential and should help the future treatment policy. Key words: testicular neoplasms, lymphoma; germinoma; lymphoma, non-Hodgkin Received 23 August 2000 Accepted 8 August 2002 Correspondence to: Assoc. Prof. Ferhat Berkmen, M.D., Ankara Oncology Education and Research Hospital, Demetevler, Ankara 6200, Turkey; Phone: +312 336 0909 ext. 333; Fax: +312 345 49 79; E-mail: fberkmen@yahoo.com The average incidence of testis tumours is in the range of 2.1 to 2.3 per 100 000 males and remains the most common solid cancer in men between the ages of 20 and 34 years.1-3 24 Berkmen F / Malignant lymphomas of the testis Testicular lymphomas account for approx-imately 5% of testis tumours and constitute the most frequent of all testicular tumours in patients over 50 years of age. The median age of occurrence is about 60 years. Primary lymphoma of the testis rarely occurs in children.4-7 Testicular involvement by lymphoma may be a manifestation of primary extranodal dis-ease, an initial manifestation of clinically no-dal disease or a later manifestation of di-sseminated nodal lymphoma. The most com-mon histologic pattern is a diffuse histiocytic lymphoma and testicular lymphomas are sometimes misdiagnosed as spermatocytic or anaplastic seminomas. The prognosis is poor within one year after the diagnosis if a dis-seminated disease is evident.5,6,9 The aim of this paper was to analyse a group of patients with malignant lymphomas of the testis and to discuss the necessity of performing leukocyte common antigen (LCA) in pathologically reported anaplastic or sper-matocystic seminomas in order to confirm the histologic diagnosis. Patients and methods From 1984 to 1996, 1201 patients, 17 to 73 years of age were treated for a testicular tu-mours in Ankara Oncology Education and Research Hospital. We reviewed medical records of these patients to identify and study lymphomas in the testis with respect to their incidence, histologic findings, the type of treatment administered and the overall out-come. Results Malignant lymphomas of the testis were iden-tified in 10 patients. The information record-ed for each patients included age, date of di-agnosis, initial symptoms and physical find-ings, initial haematologic data, clinical stage, Radiol Oncol 2003; 37(1): 23-7. histology, mode of therapy, response to ther-apy, survival time in months and the patient’s condition to the last date of follow-up. The data are summarised in Table 1. The common clinical presentation was a painless enlargement of the testis. Of 10 pa-tients 7 had generalized constitutional symptoms including anaemia (3 patients), anorexia (6 patients), weakness and weight loss (2 pa-tients). The investigation included a complete blood count, peripheral smears, chest radi-ographs, ultrasonography and/or comput-erised tomography of abdomen, ultrasound of testes, tumour markers AFP and b -HCG. None of patients had elevated AFP and b -HCG. Bilateral tumours were identified in six patients (60 %). The tumours occurred simul-taneously in 4 patients, and metachronous tu-mours plus testicular relapses developed in 2 patients after one and 6 months of the diag-nosis. Initially, all patients were treated with rad-ical orchiectomy. Five of the testicular lymphomas were high grade, 3 were intermediate and 2 were low grade diffuse non-Hodgkin’s lymphoma. Discussion Cancer of the testis accounts for less than 3 % of all malignant tumours in males. Most of these malignancies are of germinal cell ori-gin.1-3 To date, approximately 100 % of germ cell tumours can be cured. The involvement of the testis by lymphomas accounts for almost 5 % of testicular tumours and 50% of patients with bilateral tu-mours have lymphoma.3,7,8,10 Testicular lymphomas differ from germ cell tumours in regard to age, incidence, relation to cryp-torchidism, frequency of bilateral involve-ment, normal tumour marker levels of AFP and b -HCG, and prognosis. Despite reports that the median age of occurrence is about 60 years, in our series the age ranged from 32 to Berkmen F / Malignant lymphomas of the testis 25 73 years with a median of 49. In contrast, 8 of 10 patients were younger than 50 years at di-agnosis. Risk factors, like cryptorchidism, have been reported to range between 7 and 35 % of the total number of patients with tes-ticular germ cell cancer.11-13 In the medical literature, to our knowledge, testicular lymphoma arising in cryptorchid testis was re-ported only once.5 None of our patients had a history of cryptorchidism. In principle, bilateral tumours can occur synchronously or metachronously and bilateral testicular involvement is reported to be a more common feature of malignant lymphomas of the testis than of germ cell tu-mours.14-16 The relative incidence of bilateral testis tumours, reported in the literature from 1981 to 1995, can be calculated as 2.38 %.17-22 Our study doesn’t confirm this, bilateral testis tumours comprise 1.17 %, and lymphoma of the testis comprises 60 % of the total incidence of bilateral testicular carcino-mas. Four of 10 patients had radical inguinal or-chiectomy in different hospitals. Tissue spec-imens of all patients were reviewed in our pathology department to confirm the patho-logic diagnosis, because testicular lymphomas are sometimes pathologically misdi- agnosed as spermatocytic or anaplastic semi-nomas. Our study confirms this in 2 of 10 pa-tients (20 %). There were 2 patients initially misdiagnosed as spermatocytic seminoma. In order not only to prevent misdiagnosis but also for further evaluation and treatment, we recommended to perform immunocytochem-ical staining with LCA if the levels of b -HCG and AFP are normal in the sera, especially in the clinical stages to IIC to IV seminomas. Until several years ago, the traditional treatment for testicular lymphoma was radiation therapy for the localized and regional spread and chemotherapy for distant metas-tasis. To date multiagent chemotherapy, the combined modality treatment has become more frequently used as the initial one.23 Irradiation of contra lateral testicle as a pro-phylactic treatment for patients with testicu-lar lymphoma is controversial.6,24,25 Even though, prophylaxis for the normal opposite testis can be performed safely to the elder pa-tients, the need to preserve testicular func-tion may be vital for young cases. Most previ-ous reports have also indicated a poor prog-nosis for patients with testicular lymphoma, especially in patients with bilateral disease and there were no 5-year survivors. In centres cumulating a sufficient number of cases, even Table 1. Patients’ data presenting with testicular lymphomas Patients Age Laterality Clinical Treatment Disease Status (months) stage free interval (months) 1 32 Right III Chemo 24 Alive with NED 2 38 Right I XRT 11 DD 3 38 Left IV Chemo 42 DD 4 43 Bilateral, M I Chemo+XRT 52 Alive with NED 5 36 Bilateral, M IV Chemo 10 DD 6 48 Bilateral, S I XRT 62 Alive with NED 7 48 Bilateral, S I XRT 18 Alive with NED 8 58 Left IV Chemo 9 Alive with NED 9 70 Bilateral, S IV Chemo 6 DD 10 73 Bilateral, S IV Chemo 3 DD S = simultaneously; M = metachronous; Chemo = chemotherapy; XRT = radiotherapy; NED = no evidence of disease; DD = died of disease Radiol Oncol 2003; 37(1): 23-7. 26 Berkmen F / Malignant lymphomas of the testis in patients with low-stage tumours, a 5-year survival rate has been documented as 30 %.6,12,13,26-29 Thus, even patients whose dis-ease seems to be limited to the testis may have a relatively short survival time. In pa-tients with lymphoma at other sites and who later experience testicular relapses a poor prognostic factor exisists.5,6,9 The reported in-cidence of relapse in the contra lateral testicle is 0 to 35 % for patients with testicular lym-phoma.13,24,26,27,30 Testicular relapse was oc-curred in our 2 cases (20 %). Disease free mean survival times in reported series ranges between 16 months to 30 months.4,6 Five of our cases were alive with no evidence of dis-ease with follow-up ranging from 9 to 62 months. The remaining 5 patients died of dis-seminated disease, with survival ranging 3 -42 months. Even though we treated our pa-tients with combine modality, we did not ob-tain good results. Conclusions Testicular tumours of germ cell origin reach their peak incidence in the age group 20 and 34 years. Malignant lymphomas of the testis account for almost 5% of all testis tumours. The common clinical presentation, initial treatment and the pattern of dissemination of testicular lymphomas are similar to those of testicular germ cell tumours. In contrast, by the following points testicular lymphomas differs from germ cell tumours: (1) Lymphoma of the testis tends to occur in the middle ages; (2) The levels of AFP and b -HCG are in normal limits; (3) Development of tes-ticular lymphoma in cryptorchid testis is ex-tremely rare; (4) In view of aggressive behav-iour, an early systemic chemotherapy is indi-cated and a watchful waiting policy is con-traindicated; (5) Patients with disease appar-ently confined to the testis and who have no clinical evidence of generalised disease 1 year after therapy may or may not have a high probability of cure; (6) Survival is poor espe-cially with bilateral disease, and later experi-encing a testicular relapse. Since testicular lymphomas are sometimes misdiagnosed as spermatocytic and anaplas-tic seminomas, immunocytochemical stain-ing for LCA should be performed in order to confirm the histologic diagnosis. The recogni-tion of histologic diagnosis in testicular lymphoma is essential and should help the future treatment policy. References 1. Morse MJ, Whitmore WF Jr. Neoplasms of the testis. In: Walsh PC, Gittes RF, Perlmutter AD, Stamey TA, eds. Campbell’s urology. Philadelphia: WB Saunders; 1986. p. 1539-44. 2. Davies JM. Testicular cancer in England and Wales: some epidemiological aspects. Lancet 1981; 1(8226): 928-32. 3. Silverberg E, Lubera JA. Cancer statistics, 1989. CA Cancer J Clin 1989; 39(1): 3-20. 4. Richie JP. Neoplasms of the testis. In: Walsh PC, Gittes RF, Perlmutter AD, Stamey TA, eds. Campbell’s urology. 6th Edition. Philadelphia: WB Saunders; 1986. p. 1222-68. 5. Kiely JM, Massey BD Jr, Harrison EG Jr, Utz DC. Lymphoma of the testis. Cancer 1970; 26(4): 847-52. 6. Turner RR, Colby TV, McIntosh FR. Testicular lymphomas: a clinicopathologic study of 35 cases. Cancer 1981; 48(9): 2095-102. 7. Abell MR, Holtz F. Testicular and paratesticular neoplasms in patients 60 years of age and older. Cancer 1968; 21(5): 852-70. 8. Mostofi FK, Price EB Jr. Tumors of the male genital system. In: Atlas of tumor pathology. Fasc 8, se-ries 2. Washington, D.C.: Armed Forces Institute of Pathology; 1973. 9. Paladugu RR, Bearman RM, Rappaport H. Malignant lymphoma with primary manifestation in the gonad: a clinicopathologic study of 38 pa-tients. Cancer 1980; 45(3): 561-71. 10. Ferguson JD. Tumours of the testis. Brit J Urol 1962; 34: 407-21. Radiol Oncol 2003; 37(1): 23-7. Berkmen F / Malignant lymphomas of the testis 27 11. Rosai J. Ackerman’s surgical pathology. 8th Edition. Mosby; 1996. p. 1287-97. 12. Root M, Wang TY, Hescock H, Parker M, Hudson P, Balducci L. Burkitt’s lymphoma of the testicle: report of 2 cases occurring in elderly patients. J Urol 1990; 144(5): 1239-41. 13. Sussman EB, Hajdu SI, Lieberman PH, Whitmore WF. Malignant lymphoma of the testis: a clinico-pathologic study of 37 cases. J Urol 1977; 118(6): 1004-7. 14. Abeshouse BS, Trongson A, Goldfarb M. Bilateral tumors of the testicles. Review of literature and report of case of bilateral simultaneous lymphosar-coma. J Urol 1955; 74: 522-32. 15. Tellem M, Faulk A, Meranze DR. Bilateral malig-nant lymphoma of the testes. Arch Patol 1961; 71: 151-5. 16. Collins DH, Pugh RCB. Classification and fre-quency of testicular tumors. Br J Urol 1964; 36: 1-11. 17. Dieckmann KP, Boeckmann W, Brosig W, Jonas D, Bauer HW. Bilateral testicular germ cell tumors. Report of nine cases and review of the literature. Cancer 1986; 57(6): 1254-8. 18. Montie JE. Carcinoma in situ of the testis and bilateral carcinoma. Urol Clin North Am 1993; 20(1): 127-32. 19. Hoekstra HJ, Wobbes T, Sleyfer DT, Schraffordt Koops H. Bilateral primary germ cell tumors of testis. Urology 1982; 19(2): 152-4. 20. Ware SM, Heyman J, Al-Askari S, Morales P. Bilateral testicular germ cell malignancy. Urology 1982; 19(4): 366-72. 21. Cockburn AG, Vugrin D, Batata M, Hajdu S, Whitmore WF. Second primary germ cell tumors in patients with seminoma of the testis. J Urol 1983; 130(2): 357-9. 22. Strohymeyer T, Hartmann M. Doppelseitige hodentumoren: Fallprasentation und therapiekonzept. Akt Urol 1984; 15: 186-9. 23. Connors JM, Klimo P, Voss N, Fairey RN, Jackson S. Testicular lymphoma: improved outcome with early brief chemotherapy. J Clin Oncol 1988; 6(5): 776-81. 24. Doll DC, Weiss RB. Malignant lymphoma of the testis. Am J Med 1986; 81(3): 515-24. 25. Read G. Lymphomas of the testis-results of treat-ment 1960-77. Clin Radiol 1981; 32(6): 687-92. 26. Duncan PR, Checa F, Gowing NF, McElwain TJ, Peckham MJ. Extranodal non-Hodgkin’s lymphoma presenting in the testicle: a clinical and pathologic study of 24 cases. Cancer 1980; 45(7): 1578-84. 27. Crellin AM, Hudson BV, Bennett MH, Harland S, Hudson GV. Non-Hodgkin’s lymphoma of the testis. Radiother Oncol 1993; 27(2): 99-106. 28. Selli C, Amorosi A, Nesi G, Bartoletti R, De Benedetto A, Cionini L. Asynchronous bilateral non-Hodgkin’s lymphoma of the testis: report of three cases. Urology 1994; 44(6): 930-2. 29. Sasai K, Yamabe H, Tsutsui K, Dodo Y, Ishigaki T, Shibamoto Y, et al. Primary testicular non-Hodgkin’s lymphoma: a clinical study and review of the literature. Am J Clin Oncol 1997; 20(1): 59-62. 30. Jackson SM, Montessori GA. Malignant lymphoma of the testis: review of 17 cases in British Columbia with survival related to pathological subclassification. J Urol 1980; 123(6): 881-3. Radiol Oncol 2003; 37(1): 23-7.