Contralateral biopsies in patients with testicular germ cell tumours: patterns of care in Germany and recent data regarding prevalence and treatment of testicular intra-epithelial neoplasia.

The precursor of testicular germ cell tumours (GCTs), called testicular intra-epithelial neoplasia (TIN/CIS), is safely diagnosed immunohistologically. Testicular biopsy provides a valuable tool for early detection of GCTs in risk groups. Although this knowledge is undisputed, testicular biopsies are utilized poorly. The patterns of care regarding the use of biopsies remain unknown. Uncertainty exists about the prevalence and specific treatment of TIN/CIS. We asked clinical urologists in Germany whether or not they employed contralateral biopsies in GCT patients. We evaluated the prevalence of contralateral TIN/CIS in a retrospective analysis of 780 consecutive GCT patients. All had contralateral double biopsies. Discordance of TIN/CIS findings among biopsy pairs as well as age, histology of the primary tumour and clinical stage was noted. Evaluation of data comprised descriptive statistical methods. To evaluate treatment options for TIN/CIS, we performed a literature search. 52.1% of German urologists always perform the biopsy, 17% do it mostly, 27.3% in select cases, 3.5% never. Curiously, there was a geographic north-south gradient regarding biopsy use. Contralateral TIN/CIS was found in 5%. The median ages of patients with TIN/CIS and those without were 31.8 and 34.9 years respectively (p = 0.02). The discordance rate among biopsy pairs was of 33%. Two-site biopsies provide a 17% gain in diagnostic sensitivity. Local radiotherapy with 20 Gy is the safest treatment of TIN/CIS failing in 2%. Chemotherapy has significantly lower efficacy. Contralateral testicular biopsies in GCT patients are well accepted among German urologists. The prevalence of contralateral TIN/CIS found in this series is in accordance with previous reports. Double biopsies should be the diagnostic standard because of their diagnostic superiority. Local radiotherapy with 20 Gy is the safest way of eradicating TIN/CIS. Failures occur in only 2%, usually many years after irradiation. Cisplatin-based chemotherapy is dose dependent and less effective.

Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: a survey of the German Testicular Cancer Study Group.

BACKGROUND: The treatment of testicular intraepithelial neoplasia (TIN), the progenitor of testicular germ cell tumours (GCTs), is based on little data. PATIENTS AND METHODS: Two hundred and twenty-eight GCT patients with contralateral TIN were retrospectively enrolled. Ten had surveillance, 122 radiotherapy to testis with 18-20 Gy, 30 cisplatin-based chemotherapy (two cycles), 51 chemotherapy (three cycles), and 15 carboplatin. The study end point was a malignant event (ME), defined as detection of TIN upon control biopsy or occurrence of a second GCT. The Secondary end point was hypogonadism during follow-up. RESULTS: Numbers, proportions of ME, and median event-free survival (EFS) times were: radiotherapy N = 3, 2.5%, 11.08 years; chemotherapy (two cycles) N = 15, 50%, 3.0 years; chemotherapy (three cycles) N = 12, 23.5%, 9.83 years; carboplatin N = 10, 66%, 0.9 years; surveillance N = 5, 50%, 7.08 years. EFS is significantly different among the groups. Hypogonadism rates were in radiotherapy patients 30.8%, chemotherapy (two cycles) 13%, chemotherapy (three cycles) 17.8%, carboplatin 40%, surveillance 40%. CONCLUSIONS: Local radiotherapy is highly efficacious in curing TIN. Chemotherapy is significantly less effective and the cure rates are dose-dependent. Though hypogonadism occurs in one-third of patients, radiotherapy with 20 Gy remains the standard management of TIN.

Testicular biopsy for early cancer detection--objectives, technique and controversies.

This review highlights the usefulness of testicular biopsy for early detection of testicular germ cell tumour (GCT). GCT develops through a precursor stage, called testicular intraepithelial neoplasia (TIN; also called intratubular germ cell neoplasia or carcinoma in situ, CIS), which is present many years before invasive malignancy occurs. TIN/CIS is safely detected histologically. TIN is usually widely but non-randomly distributed within the testicle, thus, a biopsy of 3 mm size usually indicates the presence of TIN. Surgically, testicular biopsy should be performed at the cranial pole. Two-site biopsies provide an 18% diagnostic yield over single biopsy. Surgical complications occur in about 2.8%, most of which are managed conservatively. Serial scrotal imaging studies after biopsies revealed significant early changes. Eighteen months thereafter, less than 5% of cases have changes detectable. False-negative biopsies are extremely rare. Biopsy also provides information regarding spermatogenesis. In case of diagnosis of TIN, orchiectomy is rarely required. Low-dose radiotherapy eradicates TIN. In conclusion, testicular biopsy is useful in patients with unilateral GCT to explore the opposite testis, and in patients with retroperitoneal GCT to look for occult testicular primary. Further candidates for biopsy are selected patients with sonographic testicular microlithiasis. Despite its usefulness, the procedure has been implemented in clinical routine only in few countries thus far.

[Concordance of the Gleason score in prostate multibiopsy and definitive histology]. / Die Ubereinstimmung des Gleason-Scores in Prostatabiopsie und definitiver Histologie.

BACKGROUND: Due to an insufficient mean agreement between the Gleason score (GS) revealed from multibiopsy and definitive histology after radical prostatectomy (RP) of merely about 45 %, a modification of the GS including an elimination of GS 2-4 was -accomplished in 2005. The aim of the present study was to evaluate the concordance of GS and WHO grading in biopsy and definitive histology and to -determine parameters influencing the diagnostic accuracy of the biopsy and the prognosis. MATERIALS AND METHODS: Within a 10-year-period before modification of the GS, radical prostatectomy was performed in 856 patients (study group, SG; mean age 64.2 years). The grade of agreement between GS and WHO grading in biopsy and definitive histology was calculated by kappa statistics (kappa) (for the complete and single time -periods). Furthermore, we assessed the univariable and multivariable influence of different preoperatively available parameters on disease-free survival (DFS). The mean follow-up period was 39 months (range: 10-139 months). RESULTS: Undergrading of GS and WHO grading decreased continuously within the three time -periods in favour of a higher agreement regarding the histological results revealed from biopsy and definitive histology. However, we found only a poor to moderate agreement in the complete time period (kappa values of 0.354 for GS and 0.404 for WHO grading) that - with regard to both parameters - was improved by an increased number of biopsy cores taken. PSA value, clinical -tumour stage, number of positive cores (dichotomised at 34 %), annual RP case load (dichotomised at 75), and GS revealed an independent significant influence on DFS. Patients with GS 2-4 in the biopsy exhibited an upgrade to GS > or = 7 in only 5.7 %, and -showed, -independent of the definitive histology, a significantly better prognosis in comparison with patients presenting with a higher GS. CONCLUSIONS: The results of the present study again suggest the independent prognostic impact of the GS revealed from biopsy. However, the concordance with the GS in the definitive histology remains deficient and is improvable by taking a higher number of biopsy cores. Although the elimination of GS 2-4 might be comprehensible for the pathologist's purpose, it results in a considerable loss of pretherapeutic prognostic information.

[Results of the randomised phase III study of the German Testicular Cancer Study Group. Retroperitoneal lymphadenectomy versus one cycle BEP as adjuvant therapy for non-seminomatous testicular tumours in clinical stage I]. / Ergebnisse der randomisierten Phase-III-Studie der "German Testicular Cancer Study Group". Retroperitoneale Lymphadenektomie vs. 1 Zyklus PEB als adjuvante Therapie beim nichtseminomatösen Hodentumor im klinischen Stadium I.

OBJECTIVE: As 30% of non-seminomas in clinical stage I will progress during active surveillance, alternative adjuvant strategies of 2 cycles of bleomycin, etoposid, cisplatin (BEP) or nerve sparing retroperitoneal lymphadenectomy (RPLND) can be offered. The risk of relapse is reduced to 2% and 10%, respectively. Without prognostic markers and with lowered toxicity it is postulated that only one cycle of BEP could significantly reduce the recurrence rate in comparison to RPLND. MATERIALS AND METHODS: Between 1996 and 2005, 382 patients were randomly assigned to receive either RPLND (n=191) or 1 cycle of BEP (n=191). In accordance with the protocol, 174 patients were treated with 1 cycle of BEP and 173 underwent RPLND. The primary study end-point was a reduction of recurrence from 10% after RPLND to a maximum of 3% after 1 cycle of BEP. RESULTS: After a mean follow-up of 4.7 years, there were 2 and 13 recurrences in the according-to-protocol population with chemotherapy and surgery, respectively. The difference between chemotherapy (1.15%) and surgery (7.5%) was statistically significant (p=0.0033). The tumor-specific survival was 100%. CONCLUSION: This largest randomized trial investigating treatment strategies in clinical stage I non-seminomas (AUO AH 01/94) showed the superiority of one cycle BEP over RPLND. The data obtained represent the basis for a reduced chemotherapy.

Optimised surgery (so-called TME surgery) and high-resolution MRI in the planning of treatment of rectal carcinoma.

BACKGROUND: Since November 1998, we have applied the concept of total mesorectal excision (TME) to rectal carcinoma together with a standardised pathological quality assessment. Participation in the European MERCURY study [The MERCURY Study Group Radiology (in press), 2006] required us to establish the indication for neoadjuvant radiochemotherapy on the basis of an magnetic resonance imaging (MRI) scan. The aim of the present retrospective study is to evaluate the quality of the surgery, the efficacy of the MRI and the oncological outcomes achieved. MATERIALS AND METHODS: Between November 2001 and October 2005, 68 out of 109 patients with carcinoma of the rectum were submitted to radical surgery in curative intent and 23/68 (34%) were given neoadjuvant therapy. In an interdisciplinary study group, each patient was evaluated pre-operatively and post-operatively using standardised MRI and histopathological methods. RESULTS: The quality of surgery was established on the basis of the pathological examination of the surgical specimen. The rates of incomplete mesorectal excision, intra-operative tumour cell dissemination and positive circumferential margins were all low at 4%, 7% and 3%, respectively. The effectiveness of MRI proved to be greatest in predicting the tumour status at the circumferential resection margin: in the admittedly limited number of patients it proved possible to correctly predict the tumour status for every patient. The assessment of the anatomic extent of the primary tumour and of the regional lymph node metastasis according to the TNM system, in contrast, was considerably less successful at 73% and 75%, and 37% and 57%, respectively. CONCLUSION: By applying the TME concept and MRI-based therapy planning, excellent results can be achieved and, at the same time, the number of patients requiring neoadjuvant treatment is considerably reduced.

Visual estimation of the tumor volume in prostate cancer: a useful means for predicting biochemical-free survival after radical prostatectomy?

Absolute and relative (ratio absolute tumor volume to gland volume) tumor volumes were visually estimated in 528 prostatectomy specimens. Surveying a mean post-surgical follow-up of 49 months, both parameters were analyzed regarding their aptitude for prognostication. We found relative tumor volumes exceeding 25% to independently predict biochemical recurrence reflected by post-surgical prostate-specific antigen progression, which was also determined to be increased to 28% when absolute tumor volumes exceeded 10 cm(3). However, this cutoff failed to be an independent prognosticator. Because the visual estimation of both parameters can easily be performed, they are felt to be formidable candidates for deriving prognostic information during routine procedures.

[Regression of germ cell tumors after chemotherapy]. / Regression von Keimzelltumoren nach Chemotherapie.

Today the treatment of gonadal germ cell tumors is standardized. The cisplatin containing chemotherapy and the multi-modal therapy strategies have increased the rate of successful treatment enormously. Germ cell tumors are almost always treated surgically. Following the rare, primary chemotherapy, the residual tumor must be classified according to the WHO as accurately as possible. A binding system for the documentation of tumor regression does not exist. The diagnostic retroperitoneal lymphadenectomy is also rare. Here as well, the classification is performed according to the WHO and the TNM classification. The examination of the tissue samples from a retroperitoneal lymphadenectomy after chemotherapy is problematic. The morphology is often bizarre, preparatory and terminological standards do not exist. Is there still vital tumor present then it can most often be diagnosed as a teratoma. In that case a classification takes place as to whether it is "mature" or "immature". If a tissue sample contains other differentiations, the classification is performed in detail according to the WHO classification of germ cell tumors. Sarcomas or carcinomas must be reliably distinguished and classified, as they lead to different therapeutic consequences. The terminology must be defined in a binding manner between both the pathology and the clinic, due to the lack of global definitions.

European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG).

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.

[Endocrine tumors of the testis]. / Endokrine Tumoren des Hodens.

The most characteristic endocrine tumours of the testis are germ cell tumours and sex cord/gonadal stromal tumours. They include the primary carcinoid, the relation of which to teratomas is still unclear. In general, gonadal stromal tumours are rare, however, endocrine activity occurs in at least 10%-20%. Among gonadal stromal tumours, only Leydig cell tumours and Sertoli cell tumours are of practical importance. Endocrine disorders are mostly related to Leydig cell tumours (gynaecomastia, pubertas praecox). Although less frequent than the other gonadal stromal tumours, they can, in principle, occur. The large cell calcifying Sertoli cell tumour occurs in association with other complex disorders (i.e. Peutz-Jeghers syndrome). Valuable markers are: inhibin, calretinin, cytokeratin, melan-A, CD-99, Ki-67, androgen receptor and p53. As the conventional morphology and immunohistological markers frequently overlap, unclear cases should be referred to specialised centres.

False-negative biopsies for the diagnosis of testicular intraepithelial neoplasia (TIN)--an update.

PURPOSE: Testicular intraepithelial neoplasia (TIN; or carcinoma in situ of the testis) is the precursor of testicular germ-cell tumours (GCT). It is detected by conventional surgical biopsy of the testis. To date, only little information is available in regard to the accuracy of the biopsy. False-negative biopsies have been reported only sporadically. PATIENTS AND METHODS: Twenty-one patients who developed a testicular GCT despite a testicular biopsy negative for TIN were analysed clinically and histologically. The median age of the patients is 34 years. The median interval from biopsy to the clinical appearance of GCT is 39 months. Four of the 21 patients had their biopsy done within a previously reported multicentric study (n=1859 cases with negative biopsy including five cases with false-negative biopsy hitherto known). All of the biopsy specimens were re-examined immunohistologically. In 15 cases, the orchiectomy specimens were re-examined for the presence of TIN in the tumour-surrounding tissue. RESULTS: In five cases, TIN was found in the biopsy specimen upon re-examination. In all of the 15 orchiectomy specimens there was evidence of TIN in the tissue adjacent to the tumour. In three biopsy specimens there were microcalcifications in the seminiferous tubules. Severe impairment of the spermatogenesis was observed histologically in only 3 of the 21 patients. The relative proportion of false-negative biopsies is 0.5% (95% confidence intervals (CI): 0.22%; 0.92%). The sensitivity of the biopsy to detect TIN is 0.914 (95% CI: 0.842; 0.959) and the overall accuracy is 0.995 (95% CI: 0.991; 0.9979). A total of 44 false-negative biopsies are reported to date. CONCLUSIONS: False-negative biopsies for TIN do occur but the proportion is only 0.5%. There is no clear-cut clinical nor histological feature associated with false-negative biopsies. However, young age (i.e. <18 years) and intratubular microcalcifications should increase the clinician's and pathologist's vigilance. The majority of false-negative biopsies are caused by the non-random distribution of TIN in the testis while some few cases are caused by technical problems. Two-site biopsies would probably increase the accuracy of the biopsy in high risk cases.

Radiotherapy with 16 Gy may fail to eradicate testicular intraepithelial neoplasia: preliminary communication of a dose-reduction trial of the German Testicular Cancer Study Group.

Low-dose radiotherapy to the testis is effective in eradicating testicular intraepithelial neoplasia (TIN, carcinoma in situ of the testis) at the risk of androgenic deficiency. The present trial was designed to define the lowest dose effective to control TIN assuming a dose-response relation of radiation-induced endocrinological damage. Patients with TIN in a solitary testicle or with bilateral TIN were treated with 18 Gy (14 patients) and 16 Gy (26 patients) (5 x 2 Gy per week). Biopsies to ascertain clearance of TIN were performed after 6 and 24 months. The median time of follow-up is 20.5 months. There were three adverse events. In one patient, relapse of TIN along with microinvasive seminoma was observed 2 years after 16 Gy irradiation. In two other patients, persistent spermatogonia were observed with the 16 and 18 Gy regimen after 6 and 24 months, respectively. All other post-treatment biopsies showed the Sertoli cell-only pattern. These results confirm that TIN is a radiosensitive lesion efficiently controlled in most cases with doses below 20 Gy. However, sporadic failures may occur. A dose of 16 Gy is probably unsafe and should no longer be used. Future investigations should not only focus on total dosage of irradiation but also on fractionation schedules.

Testicular germ cell cancer despite previous local radiotherapy to the testis.

BACKGROUND: Testicular intraepithelial neoplasia (TIN, also carcinoma in situ of the testis) is the uniform precursor of testicular germ cell cancer. Local radiotherapy to the testis with dosages of 18-20 Gy has been found to safely eradicate TIN and germ cells, too. Thus, the general assumption is that the development of invasive germ cell tumours can be prevented by this radiotherapy. PATIENTS AND METHODS: Herein, we report two patients with one-sided testicular tumour and biopsy-proven contralateral TIN. Both of them developed germ cell neoplasms in the remaining testis although local radiotherapy with 20 Gy had been applied to the testis. RESULTS: One patient developed pure seminoma 7 years after completion of radiotherapy, the other developed a combined tumour consisting of embryonal carcinoma and seminoma after 5 years. Treatment consisted of orchiectomy in each of the cases. Histologically, both had TIN in the testicular tissue surrounding the new growths. CONCLUSIONS: Pathogenetically, a small fraction of radioresistent TIN cells overcoming irradiation and progressing to full-blown germ cell cancer in the later course may be the histogenetic clue to explain these unexpected events. Other explanations, though less probable, could be technical radiotherapeutic failure due to targeting problems and a pre-existing radioresistent germ cell tumour in the irradiated testicle.

[Pathology and pathomorphologic diagnosis of germ cell tumors of the testis]. / Pathologie und pathomorphologische Diagnostik von Keimzelltumoren des Hodens.

Testicular germ cell tumors are rare and comprise about 90% of all testis tumors. Genetic factors may play a role in the pathogenesis as can be deduced by a higher family-linked incidence and the p53 gene seems to be important in the development of these tumors which derive from a malignant transformed germ cell. Testicular intraepithelial neoplasia (TIN) may differentiate in two directions, namely into seminomas which comprise nearly 50% of all testicular germ cell tumors and non-seminomas. Since the term "differentiated teratoma" may be misleading, we propose the use of the term "teratoma" only. A preoperative diagnosis by biopsy is not indicated. An exact postoperative diagnosis including all necessary classifications, particularly the WHO and the TNM classifications, requires a very careful preparation of the resected specimen. The histological diagnosis should list all the different types of the WHO classification and the percentage of the tumor should be indicated, at least for embryonal carcinomas. For T categorisation in the TNM classification, the presence of invasion of veins or lymph vessels is important. Documentation, preferably in the form of a standard checklist, is strongly recommended.

Quantity and rigor of qualitative research in four pastoral counseling journals.

Examines the quantity (N = 26) and rigor of qualitative research in The Journal of Pastoral Care, Pastoral Sciences, Journal of Religion and Health, and Pastoral Psychology for 1993-1997. Defines qualitative research using the work of Douglas Sprenkle and Sidney Moon. Uses the eleven criteria developed by Nicholas Mays and Catherine Pope in British Medical Journal for judging rigor. Finds low quantity and mixed quality and discusses implications.

[Management of testicular intraepithelial neoplasia (TIN)--a review based on the principles of evidence-based medicine]. / Therapie der testikulären intraepithelialen Neoplasie (TIN)--eine Ubersicht auf Grundlage der evidenzbasierten Medizin (EBM).

Testicular intraepithelial neoplasia (TIN; also called carcinoma in situ of the testis) is the uniform precursor of testicular germ cell tumors. There is general agreement on the biological significance of TIN, however, the treatment is still a matter of dispute. The present review summarizes the treatment options currently available. In general, the management of TIN has to be adapted to the particular clinical situation of the patient. Eradication of TIN usually implies the loss of fertility. Therefore, fertility aspects should be considered before any kind of treatment is employed. Usually, patients with TIN have only small residual potential of fertility. Nonetheless, individual patients may qualify for sperm banking or cryopreservation of testicular tissue for future sperm extraction (TESE) and assisted fertilization. The most common clinical situation is the case of contralateral TIN in the presence of unilateral testicular cancer. Low dose radiotherapy to the testis with 18 Gy is the standard management option in these patients. The same procedure may be applied to solitary testicles after partial orchiectomy for germ cell tumors. During follow-up, testosterone levels should be evaluated every six months. If chemotherapy is required due to metastatic disease of the primary tumor management of TIN should be deferred. After chemotherapy 30% of TIN cases will persist and approximately 42% will recur in the later course. Repeat biopsy should be done six months after completion of chemotherapy or later. Only in cases with persistent TIN additional radiotherapy should be administered. If one testicle is afflicted with TIN while the other testis is in healthy condition (conceivable in infertility cases or patients with primary extragonadal germ cell tumors), then the TIN-bearing testis should be excised. Radiotherapy is not feasible in these cases because of shielding problems with the healthy testis.

Risk factors for relapse in stage I non-seminomatous germ-cell tumors: preliminary results of the German Multicenter Trial. German Testicular Cancer Study Group.

Risk factor analysis to identify low-risk patients for occult metastatic disease (vascular invasion, percentage embryonal carcinoma, MIB-I proliferation rate) yields reliable results if performed by experts. A correct prediction is possible at the 90% level. Similar accuracy, however, may be achieved if the computed tomography (CT) staging is optimized and the evaluation performed by an experienced investigator. The combination of both methods (biological risk factor analysis and CT staging) may virtually exclude the risk of relapse in a limited number of patients. However, so far, no risk factor that is able to reliably predict occult metastatic disease or relapse in clinical state I patients has been identified in prospective trials. The preliminary results of the current German Multicenter Trial suggest an inferior value of prediction for low-risk patients if risk factor analysis and/or CT staging is performed in non-specialized centers.

False-negative biopsies for testicular intraepithelial neoplasia.

PURPOSE: Testicular intraepithelial neoplasia, also called carcinoma in situ of the testis, is diagnosed by conventional surgical biopsy based on the assumption that testicular intraepithelial neoplasia is randomly distributed throughout the testis. We evaluate the frequency of and possible reasons for false-negative biopsies. MATERIALS AND METHODS: Contralateral testicular biopsy was performed in 1,954 consecutive patients with testicular germ cell tumor. Of the patients 1,859 with a negative biopsy for testicular intraepithelial neoplasia were followed for a median of 6 years. Patients with a second testicular tumor despite previous negative biopsy were evaluated clinically and biopsy specimens were reexamined immunohistologically. RESULTS: Despite negative biopsy 5 patients had a second testis tumor. Testicular intraepithelial neoplasia was detected on reexamination in 2 of the specimens, and mechanical damage to the specimen and technical problems with immunohistochemical staining accounted for the diagnostic failures. The proportion of false-negative biopsies was 0.3% (95% confidence intervals [CI] 0.087 to 0.627). The sensitivity of testicular biopsies to detect testicular intraepithelial neoplasia was 0.95 (95% CI 0.887 to 0.984) and the overall accuracy of the biopsy was 0.997 (95% CI 0.994 to 0.999). To our knowledge 14 cases have been previously reported in the literature, including 2 treated with chemotherapy before testicular biopsy. CONCLUSIONS: The overall proportion of false-negative biopsies for testicular intraepithelial neoplasia is as low as 0.3%. The main reason for diagnostic failure is probably the nonrandom distribution of testicular intraepithelial neoplasia within the testis. Previous chemotherapy and rare technical failures, in particular mechanical damage to the biopsy specimen, may also account for diagnostic failures. Surgical biopsy remains the gold standard for the diagnosis of testicular intraepithelial neoplasia.

[Testicular intraepithelial neoplasms (TIN). An indication for radiotherapy?]. / Die testikuläre intraepitheliale Neoplasie (TIN). Indikation zur Strahlentherapie?

BACKGROUND: Testicular intraepithelial neoplasia (TIN), synonymous for carcinoma in situ of the testis, is a rarely observed preinvasive neoplasia located within the germinative epithelium. According to the current knowledge of the biology of TIN, it is the common precursor of all testicular germ cell neoplasms except spermatocytic seminoma. MATERIAL AND METHODS: This report provides a review of histopathology, epidemiology and diagnostic procedures for TIN and discusses the therapeutic options with particular respect to radiooncological aspects. RESULTS: TIN has a 70% rate of progression to invasive cancer within 7 years. Depending on the individual therapeutic setting surgery, chemotherapy and radiotherapy are alternative treatment modalities. In case of TIN in a single testis or bilateral TIN, local radiotherapy is the standard procedure. With 20 Gy recommended as standard dose in Germany, radiotherapy yields safe eradication of TIN. However, some of the patients show significantly reduced synthesis of testicular androgens. With respect to sporadic reports in the literature, total doses well below 20 Gy might be equally efficient to treat TIN safely. Yet, up to date neither the minimum dose for efficient treatment nor the toxicity profile after consecutive chemo-radiotherapy has been established. CONCLUSIONS: The currently recommended standard dose of 20 Gy in Germany is probably in excess of the minimum dose needed for safe eradication of TIN. Thus, new radiooncological strategies should aim at reducing the total dose of treatment in order to minimize late side effects while maintaining the high efficacy of radiotherapy. This topic is under investigation in a multicenter clinical trial.