1253Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L Department of Urology, S.B. Ankara Dıskapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey. Can Tuygun, Ufuk Ozturk, Hasan Nedim Goksel Goktug, Kursad Zengin, Nevzat Can Sener, Hasan Bakirtas Evaluation of Frozen Section Results in Patients Who Have Suspected Testicular Masses: A Preliminary Report Corresponding Author: Can Tuygun, MD S.B Ankara Dışkapı Eğitim ve Araştırma Hastanesi, Üroloji Kliniği Sekreterliği, Altındağ, Ankara, Turkey. Tel: +90 312 418 28 78 Fax: +90 312 442 52 24 E-mail: drct36@hotmail.com Received April 2013 Accepted December 2013 Purpose: To report our experience with patients who have suspected testicular masses (STM) managed by ex vivo technique of testicular sparing surgery (TSS) after radical orchiectomy. Materials and Methods: Between 2007-2011 years, 10 patients with STM were evaluated by history, physical examination, testicular ultrasound and serum tumor markers. STM were defined as; no paratesticular lesions, size of the lesion smaller than 20 mm, and no known pres- ence of elevated tumor markers or metastatic disease. The principles of TSS followed by radical orchiectomy were applied to the removed surgical specimen. Excised mass, multiple biop- sies of the adjacent parenchyma and the remaining testis were sent for frozen-section analysis (FSA). Histopathologic sections were re-reviewed for definitive pathologic diagnosis. Results: The mean patient age, mean size and mean length of history of STM were 37 years (25-64), 17.5 mm (10-20) and 6 months (2-12). All STM were palpable and painless. Tu- mor markers were negative in all patients. Six tumors were benign (2 adenomatoid tumor, 1 epididymitis nodosa, 1 leydig cell tumor, 1 sertoli cell tumor, 1 fibrous pseudotumor) and 4 tumors were malignant (3 seminoma, 1 embryonal carcinoma) on definitive pathologic diagno- sis. Excluding one benign lesion, FSA correctly determined 9 lesions and all malignant lesions. Three patients had testicular intraepithelial neoplasia (ones seminoma, ones embryonal carci- noma, ones adenomatoid tumor). Conclusion: Our preliminary report reveals that STM tend to be benign rather than malignant in nature. Also, a careful patient selection and an accurate FSA are crucial points for TSS and it has the potential to become the primary option in selected patients who have testicular lesions instead of the traditional method. Keywords: organ sparing treatments; prognosis; testicular neoplasms; testis; pathology; sur- gery; frozen sections; humans. UROLOGICAL ONCOLOGY 1254 | INTRODUCTION Recently, the extensive use of scrotal ultrasound (US) for diagnosis of various disorders led to more frequently detection of suspected testicular masses (STM) due to the several reasons. First, it sometimes can be difficult to distinguish benign intratesticular lesions from malignant lesions because of the specificity of imaging find- ings of US may decrease.(1) Second, some patient features such as no palpable lesions on examination of testicles, no elevated serum tumor markers, no testicular lesions with a large diameter, no testicular microlithiasis on US exam, no history of cryptorchidism and no past operation history for testicular cancer are also factors to contribute to inconclusive US results.(2,3,4) On the other hand, radical orchiectomy traditionally has been performed for definitive treatment in the presence of a normal contralateral testicle as 90%-95% of primer tes- ticular masses are malignant germ cell tumors.(5,6) In recent clinical studies, it has been reported that the probability of malignancy of STM can be lower than expected, and un- necessary orchiectomies can be prevented by testis-sparing surgery (TSS) using guided Frozen-Section Analysis (FSA) in selected patients with testicular masses.(7,8,9) Despite these exciting reports, clinical problems remain on whether to per- form TSS in patients with STM for following reasons. First, the safety of TSS is completely based on the findings of FSA, if surgical principles are respected. Therefore, misdiagnosis of a malignancy can result in serious problems on the on- cologic outcomes. Second, the data of patients with STM is relatively few in the literature as these cases are rarely en- countered in urological practice. Last, it has been stated by the management guidelines on testicular cancer that TSS is not absolutely indicated in patients with STM.(10) For fea- tures mentioned above, initially, the surgeons should care- fully determine STM cases, and also should be aware of their capability of internal pathological assessment before starting to perform TSS. In this preliminary report, we aimed to pre- sent the first outcomes in our STM cases that were applied TSS with ex vivo approach following radical orchiectomy. MATERIAL AND METHODS Between 2007-2011 years, 10 patients with STM were evalu- ated by history, physical examination, testicular ultrasound and serum tumor markers, preoperatively. STM were con- firmed by two radiologists. Patients with STM were defined as; no paratesticular lesions, size of the lesion smaller than 20 mm, normal tumor markers and no presence of known metastatic disease. Radical orchiectomy was performed and then, the principles of TSS were applied to surgical specimen as in vitro. Excised mass, multiple biopsies of the adjacent parenchyma and the remaining testis were sent for FSA like performing a routine TSS. Histopathologic sections were re- reviewed to confirm the results of FSA. RESULTS The mean patient age was 37 years ,range (25-64), the mean mass size was 17.5 mm ,range (10-20) and the mean sus- pected history 6 months ,range (2-12). All of the testicular masses were palpable and painless. Preoperatively, serum tu- mor markers were negative in all patients. All of the patients with STM were consulted by two radiologists. All patients were undergone radical orchiectomy and then, the principles of TSS were applied to the removed testicle and obtained specimen was sent to FSA (Figure). A benign testicular tumor was found in 6 (2 adenomatoid tumor, 1 epididymitis nodosa, Urological Oncology Figure 1. The macroscopic appearance of excised masses. A) adenomatoid tumor, B) epididymitis nodosa, C) seminoma, D) embryonal carcinoma. 1255Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L 1 leydig cell tumor, 1 sertoli cell tumor, 1 fibrous pseudotu- mor) and a malignant tumor in 4 (3 seminoma, 1 embryonal carcinoma) of the 10 patients on definitive pathology. Com- paring the results of FSA and definitive pathology, excluding one benign lesion, FSA correctly determined 9 lesions and all of the malignant lesions. The results of ultrasound, FSA and definitive pathology of patients were shown in Table. DISCUSSION The results of our study have shown that STM could be benign at a rate of 60% and radical orchiectomy could be avoided by the TSS in these patients. We also noticed that our internal pathologic assessment has a high capability to predict pathological outcomes which FSA results are cor- related with definitive pathologic outcomes in malignant le- sions and nearly all benign lesions. The promising findings of our preliminary study have inspired us to take a step ahead to perform TSS from radical orchiectomy. The long established knowledge states the radical orchiec- tomy as the definitive treatment for all patients with intrat- esticular masses.(5,6) But radical orchiectomy for any STM could be overtreatment as an unexpected ratio of benign tumors has been encountered.(2) Recently, TSS is gradually gaining popularity in preventing unnecessary orchiectomies Suspected Testicular Masses and Frozen Section Analysis | Tuygun et al Table . Characteristics of study subjects. Patients Testicular ultrasonography Excised mass Multiple biopsies Remaining testis Definitive pathology No. 1 Upper-pole, 15 × 10 mm hypoechoic solid Adenomatoid tumor No tumor present No tumor present Adenomatoid tumor No. 2 Middle-pole, 18 × 11 mm hypoechoic solid Embryonal carcinoma No tumor present No tumor present Embryonal carcinoma No. 3 Upper-pole, 16 × 16 mm hypoechoic solid Sex cord stromal tumor No tumor present No tumor present Adenomatoid tumor No. 4 Upper-pole, 20 × 16 mm hyperechoic solid Epididymitis Nodosa No tumor present No tumor present Epididymitis nodosa No. 5 Lower-middle-pole, 20 × 20 mm hypoechoic solid Seminoma No tumor present No tumor present Seminoma No. 6 Lower-middle-pole, 20 × 15 mm hypoechoic solid Sex cord stromal tumor No tumor present No tumor present Leydig cell tumor No. 7 Middle-pole, 15 × 15 mm hyperechoic solid Sex cord stromal tumor No tumor present No tumor present Sertoli cell tumor No. 8 Upper-pole, 16 × 16 mm hyperechoic solid Fibrous pseudotumor No tumor present No tumor present Fibrous pseudotumor No. 9 Middle-pole, 17 × 10 mm hypoechoic solid Seminoma No tumor present No tumor present Seminoma No. 10 Middle pole, 18 × 16 mm hypoechoic solid Seminoma No tumor present No tumor present Seminoma 1256 | REFERENCES 1. Coret A, Leibovitch I, Heyman Z, Goldwasser B, Itzchak Y. Ultrasono- graphic evaluation and clinic correlation of intratesticular lesions: a series of 39 cases. Br J Urol. 1995;76:216-9. 2. Haas GP, Shumaker BP, Cerny JC. The high incidence of benign tes- ticular tumors, J Urol. 1986;1219-20. 3. Kressel K, Schnell D, Thon WF, Heymer B, Hartmann M, Altwein JE. Benign testicular tumors: a case for testis preservation? Eur Urol. 1988;15:200-4. 4. Carmignani L, Gadda F, Gazzano G, et al. High incidence of benign testicular neoplasm diagnosed by ultrasound. J Urol. 2003;170:17-6. 5. Ulbright TM, Amin MB, Young RH. Tumors of the testis, adnexa, spermatic cord and scrotum. Atlas of Tumor Pathology. Third series. Washington: American Registry of Pathology; 1997. 6. Jerome PR, Graeme SS. Neoplasms of the testis. In Campbell’s Urol- ogy, 8th ed. Edited by Walsh PC, Retik AB, Vaughan ED, Wein AJ. Philadelphia: W.B Saunders Co; 2002. vol 4, chapt.81, p. 2876-2919. 7. Robertson GSM. Radical orchiectomy and benign testicular condi- tions. Br J Urol. 1995;82:342-5. 8. Connolly SS, D'Arcy FT, Bredin HC, Callaghan J, Corcoran MO. Value of frozen section analysis with suspected testicular malignancy. Urology. 2006;67:162-5. 9. Passarella M, Usta MF, Bıvalacqua TJ, Hellstrom WJ, Davis R. Testicu- lar-sparing surgery: a reasonable option in selected patients with testicular lesions. BJU Int. 2003;91:337-40. 10. Laguna MP, Pizzacaro G, Klepp O, Algaba F, Kisbenedek L, Leiva O. EAU guidelines on testicular cancer. Eur Urol. 2001;40:102-10. 11. Weissbach L. Organ preserving surgery of malignant germ cell tu- mors. J Urol. 1995;153:90-93. Urological Oncology for patients with STM.(11-14) In these reports, it has been em- phasized that STM can be of benign nature in a consider- able number of patients and TSS can be a better approach than radical orchiectomy. But, clinical trials have provided no strong evidence for the efficacy of TSS in patients with STM as only very few clinical studies have been published. Also, the validity of TSS has still been obscured in the man- agement guideline especially in patients with contralateral “normal” testicle.(10) In the presented report, benign natures of testicular lesions were established by definitive pathology in 6 of 10 patients with STM. Because the limited number of patients included in the study and the surgical technique of TSS has been carried out as ex vivo approach, it is difficult to suggest TSS as the primary treatment choice for all patients with STM. But it has revealed that a curative treatment for 60% of our patients can be established. Defining the enrollment criteria has been one of the corner- stones for TSS candidates with STM. It has been reported that the probability of benign testicular lesions can be increased if the patients have negative tumor markers or/and have a small diameter of lesions especially.(7,8) In fact, Passarella and col- leagues reported that the incidence of benign nature of tes- ticular lesions has increased up to 81% in selected cases.(9) The study consisted of patients who had small, palpable tes- ticular lesions and negative serum tumor markers. Moreover, non-palpable testicular masses -incidentally detected by ul- trasound- in patients with negative tumor markers and small lesions can be reported as better candidates for TSS.(15-17) In those studies, the rates of benign testicular lesions were about 60–100%. For our selection criteria, -all patients have had no paratesticular lesions, size of the lesion smaller than 20 mm, normal tumor markers and no presence of known metastatic disease- the rates of benign testicular lesions were 60%. Another critical point of TSS is FSA and it has a crucial im- portance on decision during the operation whether to keep on with TSS or not. Therefore, an effective communication between surgeons and pathologists is essential to obtain more accurate results and to minimize the number of misdiagno- sis. Fortunately, both specificity and sensitivity of FSA on predicting the definitive diagnosis in STM patients is almost 100%, if the surgical principles were respected (4,18). Our report revealed a relatively high concordance between the frozen-section findings and the definitive histologic results. CONCLUSION Our preliminary report reveals that STM tend to be benign rather than malignant in nature. The selection of patients with STM, the correct application of surgical principles of sparing surgery and the results of FSA are the important aspects for TSS. Also, the surgeons should be aware of the capability of own’s pathology unit before the beginning to perform TSS. We think that TSS may be a potential treatment option for pa- tients with STM in our center instead of radical orchiectomy in the future. CONFLICT OF INTEREST None declared. 1257Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L REFERENCES 1. Coret A, Leibovitch I, Heyman Z, Goldwasser B, Itzchak Y. Ultrasono- graphic evaluation and clinic correlation of intratesticular lesions: a series of 39 cases. Br J Urol. 1995;76:216-9. 2. Haas GP, Shumaker BP, Cerny JC. The high incidence of benign tes- ticular tumors, J Urol. 1986;1219-20. 3. Kressel K, Schnell D, Thon WF, Heymer B, Hartmann M, Altwein JE. Benign testicular tumors: a case for testis preservation? Eur Urol. 1988;15:200-4. 4. Carmignani L, Gadda F, Gazzano G, et al. High incidence of benign testicular neoplasm diagnosed by ultrasound. J Urol. 2003;170:17-6. 5. Ulbright TM, Amin MB, Young RH. Tumors of the testis, adnexa, spermatic cord and scrotum. Atlas of Tumor Pathology. Third series. Washington: American Registry of Pathology; 1997. 6. Jerome PR, Graeme SS. Neoplasms of the testis. In Campbell’s Urol- ogy, 8th ed. Edited by Walsh PC, Retik AB, Vaughan ED, Wein AJ. Philadelphia: W.B Saunders Co; 2002. vol 4, chapt.81, p. 2876-2919. 7. Robertson GSM. Radical orchiectomy and benign testicular condi- tions. Br J Urol. 1995;82:342-5. 8. Connolly SS, D'Arcy FT, Bredin HC, Callaghan J, Corcoran MO. Value of frozen section analysis with suspected testicular malignancy. Urology. 2006;67:162-5. 9. Passarella M, Usta MF, Bıvalacqua TJ, Hellstrom WJ, Davis R. Testicu- lar-sparing surgery: a reasonable option in selected patients with testicular lesions. BJU Int. 2003;91:337-40. 10. Laguna MP, Pizzacaro G, Klepp O, Algaba F, Kisbenedek L, Leiva O. EAU guidelines on testicular cancer. Eur Urol. 2001;40:102-10. 11. Weissbach L. Organ preserving surgery of malignant germ cell tu- mors. J Urol. 1995;153:90-93. 12. Kırkalı Z, Tuzel E, Candan AE, Mungan MU. Testis sparing surgery for the treatment of a sequential bilateral testicular germ cell tumor. Int J Urol. 2001;8:710-2. 13. Heidenreich A, Holtl W, Albrect W, Pont J, Engelmann UH. Testis-pre- serving surgery in bilateral germ cell tumors. Br J Urol. 1997;79:253- 7. 14. Elert A, Olbert P, Hegele A, Barth P, Hofmann R, Heidenreich A. Accu- racy of frozen section examination of testicular tumors of uncertain origin. Eur Urol. 2002;41:290-3. 15. Horstman WG, Haluszka MM, Burkhard TK. Management of tes- ticular masses incidentally discovered by ultrasound. J Urol. 1994;151:1263-5. 16. Sheynkin YR, Sukkarieh T, Lipke M, Cohen HL, Schulsinger DA. Man- agement of nonpalpable testicular tumors. Urology. 2004;63:1163- 7. 17. Comiter CV, Benson CJ, Capelouto CC, et al. Nonpalpable intrates- ticular masses detected sonographically. J Urol. 1995;154:1367-9. 18. Tokuç R, Sakr W, Pontes JE, Haas GP. Accuracy of frozen section ex- amination of testicular tumors. Urology. 1992;40:512-6. Suspected Testicular Masses and Frozen Section Analysis | Tuygun et al