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Background: The American Joint Committee on Cancer 8 th edition staging guidelines for testicular cancer established a 3 cm cutoff to subclassify stage T1 seminomas (<3 cm = pT1a and ≥3 cm = pT1b). The efficacy of this cutoff in predicting metastatic disease and impact on treatment patterns have not been studied., Methods: We retrospectively reviewed patients with pT1 testicular seminoma in the National Cancer Database from 2004 to 2016. Receiver operating curves were used to determine the efficacy of the 3 cm tumor cutoff in identifying metastatic disease, and multivariable regression was used to compute the effect of tumor size on the rate of adjuvant therapy among Stage I patients., Results: A total of 10,134 patients with pT1 seminoma were evaluated. The current size cutoff of 3 cm for subclassification did not exhibit high discrimination in identifying metastatic disease (area under receiver operating curve: 0.546). Surveillance has grown as the preferred treatment after orchiectomy -32.1% in 2004 to 81.2% in 2015. However, the rate of adjuvant therapy for pT1, Stage I seminomas associated positively with tumor size even with adjustment for year of diagnosis. For tumors above 3 cm, the odds ratio stabilized around 1.9. By using the 3 cm cutoff to guide adjuvant therapy, up to 85% of T1b patients may be overtreated., Conclusion: The 3 cm cutoff for subclassification of Stage I seminoma does not predict metastatic recurrence but is associated with increased receipt of adjuvant therapy. A 3 cm cutoff and the pT1a/b classification may therefore contribute to overtreatment in many young patients with a long life expectancy for whom minimizing adverse effects should be prioritized., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Seminoma accounts for 30-50% of testicular germ cell tumors (TGCT)-the most common solid malignancy in men aged 15-35 years. The American Joint Committee on Cancer (AJCC) 8th edition (2018) created the subclassifications pT1a (tumor size < 3 cm) and pT1b (≥ 3 cm), despite not being universally recognized. Rete testis invasion (RTI) and tumor size > 4 cm are considered features associated with a higher recurrence risk, but not formally used for staging. The authors propose further understanding the subclassification's potential impact in clinical practice, by summarizing current evidence and reviewing clinical cases in their institutions., Methods: All consecutive cases of seminoma stage I, pT1 treated in two institutions between January 2005 and December 2016 were included. Clinical data were retrieved, and variables were analyzed using SPSS. Relevant literature on the topic was reviewed., Results: Seminoma pT1 was identified in 58 patients. By using newly AJCC criteria, 29 (50%) would have been staged as pT1a and 29 (50%) pT1b. Median age at diagnosis was similar (33 in pT1a vs 32 in pT1b). Median follow-up time 5.8 years. Almost half (45%) of pT1b patients had a tumor size < 4 cm. The majority of either pT1a or pT1b were treated with chemotherapy or radiotherapy, reflecting more intensive approaches in the past. Three retroperitoneal recurrences were recorded (two in pT1a, one in pT1b, all under surveillance protocol); no deaths occurred. RTI and extensive necrosis (EN) were associated with pT1b (P <  0.0001 and P = 0.023, respectively), known adverse biological features., Conclusions: In our population, the exploratory analysis of the newly created AJCC criteria showed no significant difference in recurrence or death, although pT1b was associated with adverse biomarkers, such as RTI and EN, but its clinical relevance remains incompletely understood. Our results confirm an excellent prognosis, regardless of subcategorization, thus a larger population and a longer follow-up time are needed to understand prospectively the impact of the recently updated criteria. We would recommend using the latest AJCC staging system, although the individual risk of relapse, long-term toxicities and patient preferences should be taken into account when considering surveillance or active treatment adjuvant options.

Background: The International Germ Cell Consensus Classification (IGCCC) is the recommended stratification scheme for newly diagnosed metastatic seminoma (mSGCT) and non-seminoma germ cell tumor (mNSGCT) patients. However, a contemporary North-American population-based validation has never been completed and represented our focus., Materials and Methods: We identified mSGCT and mNSGCT patients within the SEER database (2004-2015). The IGCCC criteria were used for stratification into prognostic groups. Kaplan-Meier (KM) derived actuarial 5-year overall survival (OS) rates were calculated. In addition, cumulative incidence plots tested cancer-specific (CSM) and other-cause mortality (OCM) rates., Results: Of 321 mSGCT patients, 190 (59.2%) and 131 (40.8%), respectively, fulfilled good and intermediate prognosis criteria. Of 803 mNSGCT patients, 209 (26.1%), 100 (12.4%), and 494 (61.5%), respectively, fulfilled good, intermediate, and poor prognosis criteria. In mSGCT patients, actuarial KM derived 5-year OS was 87% and 78% for, respectively, good and intermediate prognosis groups (p = 0.02). In cumulative incidence analyses, statistically significant differences were recorded for CSM but not for OCM between good versus intermediate prognosis groups. In mNSGCT patients, actuarial KM derived 5-year OS was 89%, 75% and 60% for, respectively, good, intermediate, and poor prognosis groups (p < 0.001). In cumulative incidence analyses, statistically significant differences were recorded for both CSM and OCM between good, intermediate, and poor prognosis groups., Conclusions: Our findings represent the first population-based validation of the IGCCC in contemporary North-American mSGCT and mNSGCT patients. The recorded OM rates closely replicate those of the original publication, except for better survival of poor prognosis mNSGCT patients.

Recent studies have revealed that feed-forward loops (FFLs) as regulatory motifs have synergistic roles in cellular systems and their disruption may cause diseases including cancer. FFLs may include two regulators such as transcription factors (TFs) and microRNAs (miRNAs). In this study, we extensively investigated TF and miRNA regulation pairs, their FFLs, and TF-miRNA mediated regulatory networks in two major types of testicular germ cell tumors (TGCT): seminoma (SE) and non-seminoma (NSE). Specifically, we identified differentially expressed mRNA genes and miRNAs in 103 tumors using the transcriptomic data from The Cancer Genome Atlas. Next, we determined significantly correlated TF-gene/miRNA and miRNA-gene/TF pairs with regulation direction. Subsequently, we determined 288 and 664 dysregulated TF-miRNA-gene FFLs in SE and NSE, respectively. By constructing dysregulated FFL networks, we found that many hub nodes (12 out of 30 for SE and 8 out of 32 for NSE) in the top ranked FFLs could predict subtype-classification (Random Forest classifier, average accuracy ≥90%). These hub molecules were validated by an independent dataset. Our network analysis pinpointed several SE-specific dysregulated miRNAs (miR-200c-3p, miR-25-3p, and miR-302a-3p) and genes (EPHA2, JUN, KLF4, PLXDC2, RND3, SPI1, and TIMP3) and NSE-specific dysregulated miRNAs (miR-367-3p, miR-519d-3p, and miR-96-5p) and genes (NR2F1 and NR2F2). This study is the first systematic investigation of TF and miRNA regulation and their co-regulation in two major TGCT subtypes.

Germ cell tumors represent 11% of the cancers diagnosed in adolescent males and are the most common solid tumors in adult men between the ages of 20 and 35. Pure seminoma accounts for around 50% of all testicular germ cell tumors. The prognostic classification of the International Germ Cell Cancer Collaborative Group for good-prognosis seminoma includes both nodal disease and pulmonary visceral metastases. In this article, we analyzed recent data on prognosis and outcome of good-prognosis seminoma to revise the traditional classification of the disease and improve tailored treatment.

Background: Older age is a poor prognostic indicator among patients with germ cell tumors. The current study evaluates an age-integrated international germ cell consensus classification (IGCCC) for advanced germ cell tumors., Methods: SEER database (2004-2014) was accessed through SEER*Stat program and both IGCCC and age-integrated IGCCC were calculated based on site of the primary, site of the metastasis and level of tumor markers. Overall survival analyses according to IGCCC and age-integrated IGCCC were conducted through Kaplan-Meier analysis., Results: Overall survival was compared according to IGCCC and age-integrated IGCCC for patients with seminoma and Non-seminomatous germ cell tumors (NSGCTs). P values were significant (P <0.001) for all scenarios. c-index for seminoma for IGCCC was 0.553; c-index for seminoma for age-integrated IGCCC was 0.664;c-index for NSGCTs for IGCCC was 0.729; and c-index for NSGCTs for age-integrated IGCCC was 0.738. A Cox-regression multivariate model of factors affecting cancer-specific survival (adjusted for race and surgical treatment) was conducted. All P values for pair wise comparisons (among different age-integrated IGCCC categories) were significant for both seminoma and NSGCTs (P<0.01)., Conclusion: Compared to traditional IGCCC, age-integrated IGCCC is more discriminatory and the new risk groups introduced within it are prognostically relevant.

Purpose: Testicular cancers are an uncommon and highly curable group of tumors that are typically managed by specialist multidisciplinary teams (MDTs). Although recent guidelines have emphasized the importance of tumor prognostic factors in predicting recurrence and personalizing therapy in early-stage disease, the role of central pathology review in determining these factors is unclear., Patients and Methods: We compared the referral histopathology reports with those obtained after expert central review for all cases reviewed by the UK Thames Valley Cancer Network testicular tumor MDT from August 2004 to September 2012. For cases in which the findings differed, we recorded the effect of the alteration on the estimates of patient prognosis and predicted clinical management using international (European Society of Medical Oncology [ESMO]) and local guidelines., Results: The histopathology reports were altered after central review in 129 of 465 cases (27.7%) referred to the testicular tumor MDT during the study period. These resulted in changes in the estimation of prognosis for 42 patients (9.0% total), with a predicted affect on management according to the ESMO guidelines in 30 cases (6.5%). These proportions were broadly similar for both seminoma and nonseminoma, although the reasons for the discrepancies differed between the 2 (principally errors in categorization of rete testis invasion in seminoma and of lymphovascular invasion in nonseminoma). Changes to the tumor type were uncommon (2 cases)., Conclusion: Central MDT review results in frequent, clinically relevant alterations to testicular tumor histopathology reports for testicular tumors. The results of our study demonstrate the importance of specialist MDTs to inform patient-centered care and ensure best practice in the management of these uncommon cancers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Testicular tumors are the most common genital neoplasms in male dogs, with Leydig cell tumors (LCT), seminomas (SEM), and Sertoli cell tumors (SCT) the most common forms. Human SEM are classified as classical (CSEM) or spermatocytic (SSEM). Intratubular germ cell neoplasia of undifferentiated origin (IGCNU) is another form of human testicular tumor. The aim of this study was to verify that CSEM/SSEM classification is valid in dogs and confirm the existence of canine IGCNU., Results: Testicular tumors were found in 46% of dogs at necropsy and accounted for 7% of tumors biopsied. The median age of dogs with tumors at necropsy was 10.16 years; median age at positive biopsy was 10.24 years. The most common tumors, in decreasing order, were LCT, mixed tumors, SEM and SCT at necropsy, and SEM, SCT, mixed tumors, LCT, peripheral nerve sheath tumor, and teratoma in the biopsy group. IGCNU was found in 3% of testicles at necropsy and in 3% of biopsy samples. Two dogs had testicular tumor metastasis. Expression of c-KIT was most common in SEM and seminomatous components of mixed tumors. PLAP was mostly expressed in IGCNU, SEM, teratoma, and some mixed tumors. Cytokeratin was mainly expressed in SCT. CD30 expression was low in both groups., Conclusions: The high tumor incidence at necropsy can be attributed to older age. Tumor incidence in biopsy samples, dog age, and histological classification were consistent with previous studies. The higher incidence of SEM and SCT in the biopsy group probably resulted from the obvious clinical expression of these tumor types. The low incidence of metastasis confirmed the predominance of benign tumors. Low CD30 expression confirmed the low incidence of testicular embryonal carcinoma. Cytokeratin helps differentiate stromal tumors, especially SCT, from germ cell tumors. Histology and c-KIT and PLAP expression indicate that IGCNU exists in dogs. Expression of c-KIT and PLAP confirmed that CSEM and SSEM classification is valid in dogs.

Background: Spermatocytic seminoma is a rare testicular germ cell tumor of old men. Accounting for 1-4% of all seminomas, spermatocytic seminomas have distinct pathogenesis, histological features, immunohistochemical profile and comparatively benign clinical behavior which distinguishes them from other germ cell tumors, especially classic seminoma., Aims: The purposes of our study were to assess the patient demographics, pathological features and to evaluate the utility of CD 117 immunostain along with other immunohistochemical stains in distinguishing Spermatocytic seminomas from classic seminomas., Material and Methods: All spermatocytic seminomas patients diagnosed during 1992 to 2013 at Section of Histopathology, Department of Pathology and Microbiology, Aga Khan University hospital were included. Patient characteristics, histological details and follow-up data of few patients were available. CD 117 expression was determined by immunohistochemistry., Results: Total 16 cases of Spermatocytic seminomas were reviewed. Median age was 60 years and average tumor size was 10.4 cms. Microscopically, all of the 16 cases showed presence of edema and absence of lymphocytic infiltrate and intratubular germ cell neoplasia. Cytoplasmic glycogen was negative in all 13 cases, PLAP immunostain was negative in all 12 cases, while CD 117 was positive in all 8 cases, where applied., Conclusion: CD 117 is of limited utility in differentiating the spermatocytic seminoma from classic seminoma as it is expressed in significant number of spermatocytic seminomas. However, different histological features, PAS special stain and PLAP immunostain are significantly helpful in distinguishing these two entities.

Increasing rates of testicular germ cells tumors (TGCTs) overtime suggest that environmental factors are involved in disease etiology, but familial risk and genome-wide association studies implicate genetic factors as well. We investigated whether variation in the functional CAG(n) polymorphism in the androgen receptor (AR) gene is associated with TGCT risk, using data from a population-based family study. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association of CAG repeat length and TGCT risk using matched pairs logistic regression. Analyses of 273 TGCT case-mother pairs revealed no association between AR CAG repeat length and overall TGCT risk. However, risk of seminoma was significantly associated with shorter CAG repeat length [CAG 20-21 versus CAG ≤ 19: OR = 0.82 (95% CI: 0.43-1.58), CAG 22-23 versus CAG ≤ 19: OR = 0.39 (95% CI: 0.19-0.83) and CAG ≥ 24 versus CAG ≤ 19: OR = 0.42 (95% CI: 0.20-0.86)], with a highly significant trend over these four categories of decreasing CAG repeat length (P(trend) = 0.0030). This is the first report of a statistically significant association between AR CAG repeat length and seminoma risk, suggesting that increased AR transactivation may be involved in development of seminoma and/or progression of carcinoma in situ/intratubular germ cell neoplasia unclassified to seminoma. This result provides a rationale whereby androgenic environmental compounds could contribute to increases in TGCT incidence, and identifies for the first time a potential biological pathway influencing whether TGCTs achieve seminomatous versus nonseminomatous histology, a clinically and biologically important distinction.

Background: Human seminoma is classified as classical seminoma (SE) and spermatocytic seminoma (SS). Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD) being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels., Methods: Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns) were classified as SE or SS by immunohistochemistry (IHC) using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF) and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS) program was used for various statistical analyses., Results: The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8%) and PLAP-/PAS- SSs were 15/23 (61.2%). All SE cases (8/8, 100%) were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%), 9 diffuse (9/15, 60%), and 4 intratubular/diffuse (4/15, 26.7%) types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion., Conclusion: In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels were a correlated vascular parameter. Although metastasis of canine seminomas has rarely been reported, our results support that canine SE could have high metastatic potential similar to the human counterpart. Further studies are required to clarify the relationship between canine SE and clinical data with metastatic factors.

Necrotic testicular tumors are relatively frequent and can present a significant diagnostic challenge. Because of differing treatments for seminomas versus nonseminomas, accurate diagnosis is critical. Eleven totally (n=9) or almost totally (n=2) necrotic testicular tumors were retrieved from our consult files. The submitting pathologists favored benign processes in 4 cases, Leydig cell tumor in 1, and lymphoma in 1. The cases were evaluated for histologic features and, when material was available, by immunostaining with 7 antibodies: keratin (AE1/AE3), OCT4, placental alkaline phosphatase, alpha-fetoprotein (AFP), CD117, CD30, and S100. Only distinct reactivity in a cellular distribution in the necrotic zone was considered positive; nuclear reactivity alone was scored for OCT4 and membrane reactivity for CD117 and CD30. Mean patient age was 35 years (range 16-63). Mean tumor size was 19 mm (range 7-53). All patients presented with unilateral testicular masses (6 right, 5 left); 2 also had acute pain. The combination of histologic features, immunostains and, in 1 case, serum AFP permitted classification of 8 tumors (4 seminomas, 3 embryonal carcinomas, 1 yolk sac tumor). Three were not classifiable. The necrotic seminomas lacked associated coarse intratubular calcifications and were positive for OCT4 (4/4) and CD117 (3/3) but negative for keratin (0/4) and CD30 (0/4). The necrotic embryonal carcinomas had associated coarse intratubular calcifications and were positive for keratin (2/3), OCT4 (2/2), and CD30 (3/3). OCT4 stained 1 unclassifiable tumor, which lacked other specific markers. We did not find placental alkaline phosphatase, AFP, and S100 stains useful, although S100 did highlight tumor "ghost" cells in 1 case. Other features in most cases included intratubular germ cell neoplasia (6/11), tubular atrophy/hyalinization (10/11), tumor "ghost" cells (10/11), scar (9/11), and inflammation (10/11). Of the 5 patients with available follow-up, 3 were free of disease at 1, 5, and 8 years after orchiectomy (2 necrotic seminomas and 1 germ cell tumor, unclassified). One patient with yolk sac tumor (age 63 y) developed widespread metastases after 15 months and died of disease. The final case was initially misinterpreted as "testicular infarction, no malignancy" and 16 months later the patient developed a large retroperitoneal seminoma. Most totally necrotic testicular tumors can be placed into clinically important groups by assessment for coarse intratubular calcifications and staining reactions for keratin, OCT4, CD117, and CD30.

Objectives: To report the long-term outcome of surveillance for stage I seminoma at a single institution in Japan., Methods: A retrospective review of medical records of 64 patients who underwent orchiectomy between January 1982 and December 2005 was carried out. All of them were managed by surveillance for stage I seminoma., Results: Median follow-up time was 123.8 months. Of the 64 patients, seven developed relapse. Four relapses occurred within the first year after orchiectomy, but three occurred over 4 years after orchiectomy. The actuarial relapse-free rates at 5, 10, and 15 years were 92.1%, 90.0%, and 86.0%, respectively. All patients received salvage chemotherapy at relapse. Four of these seven patients were alive without evidence of disease. One patient died of seminoma and one was alive with this disease. The remaining one patient died of leukemia without secondary relapse of seminoma. T classification was a statistically significant (P = 0.028) risk factor for relapse on univariate analysis. In T1 patients, relapse-free rates at 5, 10, and 15 years were all 97.1%, whereas in T2/T3 patients the corresponding relapse-free rates were 86.4%, 82.1%, and 71.8%, respectively., Conclusions: The relapse-free rate in the present study was similar to previous reports. Late relapse should be considered during surveillance.

Aim: to find out the distribution of germ cell tumor based on age, histopathology, stadium, chemotherapy regimen, and number of cases per year in patients hospitalized in Dharmais National Cancer Hospital during the period of January 2000 to December 2004., Methods: the data were collected from medical record of patients with testicular carcinoma that were treated on inpatient and outpatient basis in Dharmais National Cancer Hospital during the period of January 2000 to December 2004. The data were collected, recorded and analyzed in descriptive manner and presented in tables of distribution and frequency., Results: there were 44 cases testicular carcinoma being analyzed; 40 cases (90.92%) were germ cell tumor, 42.50% aged 21-30 years old; and the most frequent histological type was seminoma (47.50%). About 39.50% of the patients were admitted in stage II of the disease, and 61.59% were put on BEP regimen. Seminoma type was more frequent in >or= 30-year-old age group while on the other hand, non-seminoma was mostly found in

Stage I and IIA/B testicular seminoma represent approximately 45% of all testicular germ cell tumours. Due to the availability of highly efficient salvage treatment, the disease-specific survival in stage I seminoma is approximately 100%, irrespective of the choice of adjuvant treatment. Radiotherapy with 26 Gy to the paraaortic/paracaval lymph nodes yields excellent cure rates of 95 98% with a favourable profile of acute and late toxicity. Likewise, phase-II trials with single-agent carboplatinum systemic treatment have demonstrated a rate of relapse of 3-4% on average. However, carboplatinum chemotherapy has to be regarded as experimental until data of phase-III trials are available. Surveillance in stage I disease is conflicted with a rate of relapse of approximately 20%. However, 80% of the patients will avoid potentially toxic overtreatment by the watch-and-wait policy. In stage IIA/B seminoma, "dogleg" radiotherapy with 30 Gy and 36 Gy, respectively, provides high cure rates of 90-95%. Those patients relapsing will be salvaged in almost 100% of cases. Testicular intraepithelial neoplasia (TIN) is the common precursor lesion of testicular germ cell tumours except for spermatocytic seminoma. In case of TIN in a single testis or bilateral TIN, local radiotherapy with 18 Gy is recommended as standard treatment.

Recurrence pattern of metastatic testicular cancer after the initial treatment was investigated. Seventy-seven patients with metastatic testicular cancer were treated by cisplatin-based chemotherapy. Patients with residual masses after chemotherapy and whose tumor markers were normalized underwent surgical resections. Of the 77 patients, 61 achieved cancer free status and 4 who did not need the study criteria excluded. Recurrences were detected in 12 (21.1%) patients, 2 (7.1%) patients among 28 stage II patients; 10 (34.5%) patients among 29 stage III patients; none (0%) patients among 14 seminoma patients and 12 (27.9%) patients among 43 non-seminoma patients. All recurrences were detected within 17 months (median, 3) after the initial treatment. Of the 12 patients experiencing recurrence, 4 died of cancer. The recurrence rate of the patients in stage III was significantly higher than that in stage II. No recurrence was detected in patients with seminoma. Follow-up studies after treatment should include serum tumor markers and computed tomographic scanning of lung, abdomen and pelvis at defined intervals. Intensive follow-up will be needed especially for the patients in stage III and with non-seminoma. Follow-up within the first two years is especially important in detecting recurrence after chemotherapy.

Purpose: To evaluate the efficacy and toxicity of primary chemotherapy with the schedule E400P in the treatment of patients with early stage II (IIa and IIb) and advanced seminoma of good prognosis according to the international classification (IGCCCG)., Patients and Methods: Sixty-four patients were included. E400P consisted of cisplatin 25 mg/m2/day and etoposide 100 mg/m2/day for four days, every three weeks. Royal Marsden stages were IIab: 53% and IIc-IV: 47%. Twenty-three percent had high BHCG levels, twenty-seven percent had LDH > 2 x N. Sixty-two patients were of good prognosis according to the Medical Research Council classification., Results: Response rate was 98% (69% complete remission, 29% residual disease). After a median follow-up of 34 months, treatment failure was seen in 7 patients (11%). Neutropenia (32%) was the most relevant grade 3-4 toxicity. Other important grade 3-4 side effects were found in less than 5%. Three-year time to treatment failure (TTF) was 89% (95% confidence intervals (CI): 80%-97%) for all patients, 91% (95% CI: 80%-99%) for stages IIa-b, and 87% (95% CI: 74%-99%) for stages IIc-IV. Three-year overall survival (OS) was 97% (95% CI: 93%-99%) for all patients and 95% (95% CI: 85%-99%) for stages IIa-b., Conclusions: E400P was a very active and safe regimen in good-prognosis advanced seminoma, with low toxicity rates. Definitive comparisons of this regimen with radiotherapy in stages IIa-b or with the more standard E500P or BEP, could be of interest.

Testicular seminoma is an uncommon tumor that accounts for approximately 50% of all germ cell testicular tumors. The vast majority of patients present with early-stage disease and almost all patients are cured of their disease. Management is based on disease extent with patients with stage I seminoma having numerous treatment options, varying from surveillance to adjuvant retroperitoneal radiation therapy and prophylactic adjuvant single-agent chemotherapy. Only 20% of patients present with more advanced disease; the majority of those have stage II disease with retroperitoneal lymph node involvement. The standard management is retroperitoneal radiation therapy with chemotherapy being used for patients with bulky disease. Systemic chemotherapy with cisplatin alone or etoposide and cisplatin is the standard approach to advanced and metastatic disease with cure rates approaching 85% to 90%. The goal of treatment is a cure with a minimum of complications. The current controversies include the optimum management of residual retroperitoneal mass (post-radiation therapy or chemotherapy), the management of patients with second testicular or bilateral testicular tumors, the management of testicular intraepithelial neoplasia, and the management of seminoma in immunosuppressed patients.

In order to study the possible biological differences between anaplastic and typical seminoma, the following factors were studied in 11 cases of anaplastic seminoma and 15 cases of typical seminoma: mitotic activity, proliferating cell nuclear antigen (PCNA) expression, immunohistochemical analyses for cytokeratin, vimentin, placental alkaline phosphatase (PLAP), beta-human chorionic gonadotropin (beta-hCG), alpha-fetoprotein (AFP) and c-myc oncoprotein. Anaplastic seminoma was classified according to Mostofi's criteria, which is primarily based on the mitotic activity of the tumor. Mitotic activity was evaluated by both mitotic count and rate. Statistically significant correlations were observed between mitotic count and mitotic rate (R = 0.891), and between the mitotic count and PCNA labeling index (R = 0.792), in both typical and anaplastic seminomas. Immunostaining patterns for cytokeratin, vimentin, PLAP, beta-hCG, AFP and c-myc oncoprotein were not significantly different between typical and anaplastic seminoma. The present data indicated that no apparent clinicopathologic and immunohistochemical parameters discerning anaplastic seminoma from typical seminoma were present, when identifying anaplastic seminoma on the basis of high mitotic count. Anaplastic seminoma may therefore simply represent seminoma with high proliferative activity.

Characterization of the nuclear DNA content (DNA index and DNA histogram type) was carried out in 9 normal testicular tissues and 21 seminomas. Proliferative activity was further determined in the seminomas. Nuclear DNA content was assessed by means of a cell image processor computing the integrated optical density on Feulgen-stained nuclei from formalin-fixed paraffin-embedded materials. The results indicated that the so-called normal testicular tissues exhibited DNA histograms where three cell nuclei populations emerged in varying proportions. These three cell nuclei populations corresponded to haploid, diploid and tetraploid cell nuclei respectively. In contrast, most of the seminomas exhibited monomorphic DNA histogram patterns with a predominance of GO-G1 cell nuclei in the range of the 3c-4c nuclear DNA content. Further studies will be necessary in order to determine whether the DNA histogram has a predictive prognostic value or could be considered as a grading index.