H&E and OCT4/CD34 for the assessment of lympho-vascular invasion in seminoma and embryonal carcinoma.

BACKGROUND: Lymphovascular invasion (LVI) is a relevant prognostic factor in germ cell tumors of the testis (GCTT), and it is included in the pT stage. However, its detection on hematoxylin and eosin (H&E) slides is very challenging, and previous studies reported fair to moderate inter-observer agreement among dedicated uropathologists. In the present study, we tested H&E and a recently developed in-house double staining for OCT4/CD34 to detect LVI in GCTT. METHODS: Nine authors [5 non-uropathologists and 4 uropathologists] independently evaluated 34 consecutive and retrospectively enrolled cases of GCTT. We assessed the inter-observer agreement (Fleiss's Kappa) with both H&E and OCT4/CD34. Besides, we compared the consensus diagnosis on both H&E and OCT4/CD34-stained sections with the original diagnosis to evaluate the pT re-staging (McNemar test) and identify the sources of disagreement. RESULTS: The inter-observer agreement among uropathologists plus non-uropathologists was fair with both H&E (KF=0.398; p < 0.001) and OCT4/CD34 (KF=0.312; p < 0.001). OCT4/CD34 (KF=0.290; p < 0.001) slightly reduces the inter-observer agreement compared to H&E (KF=0.321; p < 0.001) for non-uropathologists; in contrast, OCT4/CD34 (KF=0.293; p < 0.001) significantly reduces the inter-observer agreement compared to H&E (KF=0.529; p < 0.001) for uropathologists, changing it from moderate to fair. Consensus diagnosis with H&E modified the LVI status of the original diagnosis in 8/34 (23.5 %) cases (p: 0.070), with pT re-staging in 2/34 (5.9 %) cases (p: 0.500). Consensus diagnosis with OCT4/CD34 modified the LVI status of the original diagnosis in 8/34 (23.5 %) cases (p: 0.289), with pT re-staging in 3/34 (8.8 %) cases (p: 0.250). The consensus diagnosis with OCT4/CD34 modified the consensus diagnosis with H&E in 8/34 (23.5 %) cases (p: 0.727), and these findings resulted in pT-restaging in 3/34 (8.8 %) cases (p: 0.500). The sources of disagreement among uropathologists were: H&E [artefactual clefts misinterpreted as LVI in 4/6 (66.7 %) cases and true foci of LVI misinterpreted as clusters of histiocytes within the vessels in 2/6 (33.3 %) cases], OCT4/CD34 [artefactual clefts misinterpreted as LVI in 2/8 (25 %) cases, true LVI misinterpreted as artefactual clefts in 2/8 (25 %) cases or floaters in 4/8 (50 %) cases]. CONCLUSIONS: OCT4/CD34 does not improve the inter-observer agreement for the assessment of LVI in OCT4(+) GCTT. Consensus diagnosis with H&E modifies the LVI status in a significant number of cases, resulting in changes of the pT stage in a relatively small subgroup. Consensus diagnosis with OCT4/CD34 provides little additional benefit since it cannot exclude mimickers of LVI such as floaters and artefactual clefts. These results argue against the adoption of this diagnostic tool for the routine assessment of OCT4(+) GCTT.

Primary mediastinal germ cell tumours with high prevalence of somatic malignancy: An experience from a single tertiary care oncology centre.

BACKGROUND: Primary mediastinal germ tumours (PMGCT) constitute, a mere 3-4% of all germ cell tumours (GCT). Although they account for approximately 16% of mediastinal tumours in adults and 19-25% in children as per western literature, there is hardly any large series on PMGCT reported from the Indian subcontinent. DESIGN: We have retrospectively analysed clinicopathological features of 98 cases of PMGCT diagnosed over 10 years (2010-2019) from a tertiary-care oncology centre. RESULTS: The study group (n = 98) comprised predominantly of males (n = 92) (M:F ratio-15:1), with an age range between 3 months to 57 years (median: 25 years). The tumours were predominantly located in the anterior mediastinum (n = 96). Broadly, Non-seminomatous germ cell tumours (NSGCT) were more common (n = 73, 74%) compared to pure seminoma (n = 25, 26%). Mixed NSGCT was the most common histological subtype (n = 30) followed by pure mature teratoma (n = 18), pure Yolk sac tumour (n = 13), mixed seminoma and NSGCT (n = 5), pure immature teratoma (n = 3) and GCT; NOS (n = 4). Interestingly, all female patients had exclusive teratomas. Nine cases revealed secondary somatic malignancy (5 carcinomas and 4 sarcomas). The majority of patients received neoadjuvant chemotherapy (n = 71). Surgical excision was performed in 60 patients. Follow up was available in 68 patients. NSGCT showed a poor prognosis as compared to seminoma (p value = 0.03) and tumours with somatic malignancies had a more aggressive clinical course. CONCLUSION: PMGCT was seen predominantly in young adult males and somatic malignancies were noted in as high as 9% of cases. Patient with somatic malignancy have aggressive clinical course, hence, extensive sampling and careful histopathological evaluation are recommended for the identification and definitive characterization.

Assessment of Prognostic Factors of Racial Disparities in Testicular Germ Cell Tumor Survival in the United States (1992-2015).

OBJECTIVE: Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed. METHODS: The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT. RESULTS: Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality. CONCLUSION: Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.

Testicular self-examination and testicular cancer: a cost-utility analysis.

The United States Preventive Services Task Force (USPSTF) has recommended against testicular self-examinations (TSE) or clinical examination for testicular cancer screening. However, in this recommendation there was no consideration of the significant fiscal cost of treating advanced disease versus evaluation of benign disease. In this study, a cost-utility validation for TSE was performed. The cost of treatment for an advanced-stage testicular tumor (both seminomatous and nonseminomatous) was compared to the cost of six other scenarios involving the clinical assessment of a testicular mass felt during self-examination (four benign and two early-stage malignant). Medicare reimbursements were used as an estimate for a national cost standard. The total treatment cost for an advanced-stage seminoma ($48,877) or nonseminoma ($51,592) equaled the cost of 313-330 benign office visits ($156); 180-190 office visits with scrotal ultrasound ($272); 79-83 office visits with serial scrotal ultrasounds and labs ($621); 6-7 office visits resulting in radical inguinal orchiectomy for benign pathology ($7,686) or 2-3 office visits resulting in treatment and surveillance of an early-stage testicular cancer ($17,283: seminoma, $26,190: nonseminoma). A large number of clinical evaluations based on the TSE for benign disease can be made compared to the cost of one missed advanced-stage tumor. An average of 2.4 to 1 cost benefit ratio was demonstrated for early detected testicular cancer versus advanced-stage disease.

Disparities in stage at diagnosis among adults with testicular germ cell tumors in the National Cancer Data Base.

BACKGROUND: Testicular germ cell tumors (TGCTs) are the most common malignancies among US men between the ages of 20 and 34. Five-year survival has increased since 1970s (95%), but remains below 75% for patients with late-stage disease. Few studies have examined the sociodemographic predictors of late-stage diagnosis, and none have examined the relationship between stage at diagnosis and health insurance among TGCTs. METHODS AND MATERIALS: A total of 48,151 men between the age of 15 and 64 years who were diagnosed with first primary invasive TGCTs from 1998 to 2008 were selected from the National Cancer Data Base. The effect of health insurance, race/ethnicity, ZIP code-based socioeconomic status, and other factors on late-stage diagnosis was examined using histology-stratified multivariate log binomial models to measure relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Overall, 6.6% and 21.2% of seminomas and nonseminomas were diagnosed at late stage, respectively. Uninsured men (seminomas: RR, 1.88, 95% CI, 1.65-2.13; nonseminomas: RR,1.42, 95% CI, 1.32-1.54), Medicaid-insured men (seminomas: RR, 2.99, 95% CI, 2.64-3.38; nonseminomas: RR 2.82, 95% CI, 2.48-3.22), and Medicare-insured men (seminomas: RR, 2.30, 95% CI, 1.91-2.77; nonseminomas: RR 2.02 95% CI, 1.67-2.44) were more likely to be diagnosed at late stage compared with privately insured men. Black men (nonseminomas: RR, 1.43, 95% CI, 1.25-1.64) and Hispanic men (seminomas: RR, 1.34, 95% CI, 1.16-1.55; nonseminomas: RR, 1.22, 95% CI, 1.12-1.33) were significantly more likely to be diagnosed at late stage. Lower socioeconomic status was associated with an increased risk of late-stage diagnosis among both seminomas and nonseminomas. CONCLUSIONS: Sociodemographic covariates, particularly health insurance, race/ethnicity, and socioeconomic status, were predictors of late-stage diagnosis. TGCTs are typically diagnosed among younger men who are less likely to have health insurance. Future efforts should aim to increase health insurance coverage and access to primary care, reduce barriers to care, and promote informed decision making for underserved populations.

What is the value of routine follow-up in stage I seminoma after paraaortic radiotherapy?: an analysis of the German Testicular Cancer Study Group (GTCSG) in 675 prospectively followed patients.

BACKGROUND AND PURPOSE: Routine posttreatment surveillance is recommended after adjuvant radiotherapy for stage I seminoma. However, systematic studies on the value of follow-up in these patients are missing. This report addresses the efficiency of routine follow-up in stage I seminoma with particular reference to the mode of detection of relapse and the costs of posttreatment screening. PATIENTS AND METHODS: All follow-up investigations of a prospectively followed cohort of 675 patients with stage I seminoma treated with PA radiotherapy were analyzed with respect to the first indications of relapse, patterns of recurrence, risk factors of relapse, and cost-efficiency of the different technical examinations of the follow-up schedule over a 10-year period. RESULTS: With a median time to follow-up of 61 months, recurrence was diagnosed by symptoms or physical examination in 14 out of 26 relapsing patients. Among the technical follow-up investigations abdominopelvic imaging had the highest detection rate for relapse, while thoracic imaging and marker analysis were inefficient. Abdominal sonography had the highest cost-efficiency of all technical follow-up investigations, while computed tomography (CT) scans were responsible for approximately 60% of all costs. The authors failed to identify risk factors predictive of relapse after adjuvant irradiation. CONCLUSION: Routine technical investigations during follow-up after PA radiotherapy for stage I seminoma yield only a low detection rate of relapse from cancer. The data presented here provide no evidence for the value of technical follow-up beyond the 3rd year after treatment or routine screening of the chest. Thorough physical examination of the patients should be encouraged. Patients should be informed about potential symptoms indicative of recurrence. Restrictive use of abdominopelvic CT scans will reduce exposure to ionizing radiation and considerably increase the cost-efficiency of follow-up.

A comprehensive systematic review of testicular germ cell tumor surveillance.

BACKGROUND: Testicular cancer is the most common malignancy in men aged 15-34, and its incidence has been increasing over the past half-century. Survival for stage I testis cancer approaches 100% regardless of management strategy which is often dictated by other factors such as perceived morbidity. Advances in treatment have attempted to decrease morbidity and surveillance is thought to achieve this goal. METHODS: An English language literature search of MEDLINE from 1966 to December 2005 and CINAHL from 1982 to December 2005 was conducted using a broad search strategy. Comparative and descriptive original articles on outcomes of seminoma or NSGCT surveillance would be deemed eligible and review articles containing no original data were omitted. One hundred and thirty-eight articles were selected for formal review, during which a database was compiled that documented the first author, publication year, tumor histologic type, study purpose or topic(s), methodology, sample size, median follow-up, and relevant results. RESULTS: Most evidence for the efficacy of surveillance is from descriptive series or non-experimental comparative studies. Relapse occurs in approximately 28% and 17% of surveillance patients in NSGCT and seminoma, respectively, and cause-specific survival is approximately 98% and 100%, respectively. Compliance with surveillance ranges from poor to adequate, however there is no evidence that compliance impacts clinical outcome. Cost analyses have yielded inconsistent results when comparing treatment modalities. There is scant literature on quality of life and psychosocial issues and results are inconsistent. Active surveillance appears to be appropriate and perhaps optimal first line management of clinical stage I seminoma and non-seminomatous germ cell tumors. Further quantitative and qualitative research is warranted to deepen understanding of these issues that may impact treatment decision-making.

Valoración de alfa fetoproteína y gonadotropina coriónica en el diagnóstico de 290 tumores germinales testiculares / Evaluation of alpha-fetoprotein and chorionic-gonadotropin in the diagnosis of 290 testicular germinal tumors

Desde el punto de vista terapéutico y pronóstico, los tumores germinales de testículo se dividen en seminoma puro y no seminoma. El diagnóstico definitivo toma en cuenta la histología, la presentación clínica, y los niveles séricos de alfa fetoproteína (AFP) y fracción beta de gonadotropina coriónica humana (HGC). Objetivo: Correlacionar los valores de AFP y HGC con la variedad histológica y etapa clínica para determinar si cambia el diagnóstico final del tumor. Material y métodos: Se tomó suero en la valoración inicial de 290 pacientes con tumores germinales testiculares determinando niveles de AFP y HGC (ELISA, Quantum II de Abbott). Se revisaron los expedientes para conocer estirpe histológica y estadio clínico. Se consideraron seminomas los tumores con histología de seminoma puro sin elevación de AFP y HGC menor de 500 mUI/ml; los tumores germinales no seminomatosos de testículo (TGNST) presentaron histología de no seminoma o de seminoma con elevación de AFP o HGC mayor de 500 mUI/ml. Resultados: Histológicamente se encontraron 120 seminomas puros y 170 TG-NST. Se reclasificó a 13 casos de seminomas como TGNST ya que 10 presentaron elevación de AFP (tres AFP únicamente y siete AFP más HGC) y tres casos tuvieron elevación de HGC > 500 mUI/ml. La distribución final fue de 107 seminomas y 83 seminomas. Conclusiones: Al analizar los niveles séricos de AFP y HGC con la histopatología se obtiene el diagnóstico definitivo de la estirpe tumoral testicular mejorando la selección del tratamiento