Pathology Of Germ Cell Tumors Research Articles

Characterization of DDX4 Gene Expression in Human Cases with Non-Obstructive Azoospermia and in Sterile and Fertile Mice.

Background:In mammals, spermatogenesis is the main process for male fertility that is initiated by spermatogonial stem cells (SSCs) proliferation. SSCs are unipotent progenitor cells accountable for transferring the genetic information to the following generation by differentiating to haploid cells during spermato-and spermiogenesis. DEAD-box helicase 4 (DDX4) is a specific germ cell marker and its expression pattern is localized to, spermatocytes, and spermatids. The expression in the SSCs on the basement membrane of the seminiferous tubules is low.Methods:Immunohistochemistry (IHC) and Fluidigm reverse transcriptase-polymerase chain reaction (RT-PCR) were used to analyze the expression of DDX4 in testis tissue of fertile and sterile mice and human cases with non-obstructive azoospermia.Results:Our immunohistochemical findings of fertile and busulfan-treated mice showed expression of DDX4 in the basal and luminal compartment of seminiferous tubules of fertile mice whereas no expression was detected in busulfan-treated mice. The immunohistochemical analysis of two human cases with different levels of non-obstructive azoospermia revealed more luminal DDX4 positive cells.Conclusion:Our findings indicate that DDX4 might be a valuable germ cell marker for analyzing the pathology of germ cell tumors and infertility as global urological problems.

917 NOVEL PREDICTORS OF BENIGN PATHOLOGY IN STAGE IA OR IB PATIENTS WITH NON-SEMINOMATOUS TESTICULAR GERM CELL MALIGNANCY UNDERGOING PRIMARY RETROPERITONEAL LYMPH NODE DISSECTION

INTRODUCTION AND OBJECTIVES: There is no consensus on the optimal treatment for Stage I testicular non seminomatous germ cell tumors (T NSGCT), partly due to the inaccuracy of clinical staging methods. Prior reports have demonstrated that the presence of embyronal carcinoma (EC), lymphovascular invasion (LVI), and absence of yolk sac tumor (YST) in the orchiectomy specimen are important risk factors predicting occult metastatic disease. We assessed whether a novel combination of the above factors could predict the presence of benign retroperitoneal pathology. METHODS: We reviewed an institutional database of patients with T NSGCT and included all patients with Stage IA or IB NSGCT who underwent primary RPLND. Logistic regression analysis was used to compare patients with benign pathology versus germ cell tumor (GCT). A combination of significant pathologic factors was used as internal validation to predict the presence of benign or GCT pathology. Significance was determined at p 0.05. No financial funding was obtained. RESULTS: Among 55 patients with Stage IA or IB NSGCT managed with primary RPLND, 44(80%) had benign pathology and 11 (20%) had occult GCT in the retroperitoneum. No specimens revealed retroperitoneal teratoma in this cohort. Predictors of benign pathology were higher preorchiectomy alpha fetoprotein levels (p 0.03), larger percentage of YST (p 0.02), lower embryonal carcinoma to YST (E/Y) ratio (p 0.001), presence of teratoma and absence of LVI in the primary orchiectomy specimen (both p 0.01). Multivariate analysis demonstrated an E/Y ratio 4 to be a strong predictor of benign pathology in the retroperitoneum, with an area under the receiver operating curve of 0.71 0.08 (p 0.04), and a sensitivity and specificity of 37% (16/43) and 100% (12/12), respectively. In combination with absence of LVI, an E/Y ratio 4 had a 100%(10/10) positive predictive value for benign pathology on internal validation. Conversely, presence of LVI and an E/Y ratio of 4 revealed a 64% (7/11) predictive value for GCT. CONCLUSIONS: In our cohort, patients with Stage IA or IB NSGCT who had benign pathology on the primary RPLND had a significantly higher proportion of YST to EC in the preorchiectomy specimen. An E/Y cutoff value of 4 appears to be discriminatory for predicting benign pathology. Emphasis on the proportion of YST in the primary orchiectomy specimen in addition to other previously established risk factors may allow for improved risk stratification.

Pathology of Germ Cell Tumors of the Testis

An increasing incidence of testis tumors has been noted over the second half of the 20th century. Congenital malformation of the male genitalia, prenatal risk factors, nonspecific and specific exposures in adulthood, and male infertility have all been associated with the etiology of germ cell tumors. The histologic classification, pathology, and current concepts of testicular germ cell tumors are reviewed. Germ cell tumors occur at all ages. The tumors are identified as pure form (those of one histologic type) and mixed form (more than one histologic type). Over half of germ cell tumors consist of more than one cell type, requiring appropriate sampling for the correct diagnosis and correlation with the serum tumor markers. Burned-out germ cell tumors may occur in patients with metastatic disease with no gross evidence of a testicular tumor. Appropriate management of testis tumors relies on accurate pathology and classification of these tumors.

Pathology of germ cell tumors in children

Germ cell tumors may be defined as those tumors arising from a primitive germ cell. These tumors have the potential for differentiating along several disparate lines (Figure 1). l-3 The primitive germ cell may proliferate as a pure germ cell tumor, which is variously labeled as seminoma in the testis, dysgerminoma in the ovary, or germinoma in extragonadal sites. Alternatively, the totipotential primitive germ cell may develop as a benign mature teratoma, an immature teratoma of uncertain malignant potential, or a malignant tumor. In children, the malignant tumors are either pure germ cell tumors, embryonal carcinomas, or tumors manifesting extraembryonic features, such as yolk sac tumors and, occasionally, choriocarcinomas. Rarely, a teratoma may contain malignant neural elements. However, teratomas containing malignant epithelial components, such as seen in squamous cell carcinomas or adenocarcinomas, occur only in adults. In children, the malignant potential of malignant germ cell tumors is quite varied. Germinomas are the least aggressive, and teratomas with malignant neural elements (neuroblastoma) are the most aggressive forms of this tumor.4 Yolk sac tumors can usually be controlled by combination chemotherapy. Combination chemotherapy may also be effective in embryonal carcinomas in children, but the numbers are too small for statistical assessment.4.s

Pathology of Germ Cell Tumors of Testis: A Progress Report.

Since the last National Conference on Urological Tumors, there has been major progress in pathology of testicular tumors. An international histological classification of these tumors has been proposed, which is based on the sound principle that pathological examination must specify the exact components that are present in a tumor and give an estimate of relative proportions of each. The WHO classification, using generally accepted principles of tumor typing, has provided a standard method of pathological reporting of these tumors so that results of research from different parts of the world can be compared. The WHO system published in 1977 is readily convertible to the system in use in the American Testicular Tumor Registry. Its convertibility to the Friedman-Moore and Pugh-Cameron Testicular Tumor classifications is limited. Though it is generally believed that embryonal carcinoma can differentiate along extra-embryonic lines to form yolk sac tumor and choriocarcinoma or along embryonic lines to form teratoma, the malignant germ cell itself seems to have the potential to develop along any of these lines without first going through the embryonal carcinoma phase. Seminomas with high mitotic index and seminomas that contain syncytiotrophoblasts appear to have a less favorable prognosis than classic seminomas or spermatocytic seminomas. HCG is readily demonstrable in syncytiotrophoblasts whether alone or forming choriocarcinoma. AFP is demonstrable in yolk sac tumors and in some embryonal carcinomas. Histological demonstration of AFP and HCG can and should be correlated with clinical findings. Such correlation can readily be made with the WHO histological classification of these tumors.

Pathology of Germ Cell Tumors of the Testis

Testicular germ cell tumors form a complex group of interrelated entities. Problems of nomenclature remain, but there does appear to be a close agreement between the major classifications in use. The identification of clinically useful markers for certain germ cell testicular tumors has provided a major impetus in this field. Information gained from the study of these markers has promoted an understanding of the histogenesis of germ cell tumors, has improved standard nomenclature, and has stimulated progress in patient care. Radioimmunoassay techniques are now frequently used to measure beta-human chorionic gonadotrophin and alpha-fetoprotein levels in evaluating the clinical course of patients with nonseminomatous germ cell tumors of the testis. It is hoped that the use of these markers will permit earlier detection of tumor recurrence, prompt treatment, and an improved survival rate. The knowledge of the production of alpha-fetoprotein by the human yolk sac has further refined tumor classification. It is against this general background that we have outlined the standard pathology of germ cell tumors of the testis.