[Testicular germ cell tumors: Histopathological and molecular features]. / Tumeurs germinales du testicule : caractéristiques histopathologiques et moléculaires.

In 2016, the WHO classification of testicular germ cell tumors was revised considering advances in the understanding of their tumorigenesis and molecular features. This restructuring led to a division into two major groups with, on one hand, prepubertal-type tumors, not derived from germ cell neoplasia in situ (GCNIS), and on the other hand, postpubertal-type tumors, GCNIS-derived, which occur in youg men (seminoma and non seminomatous germ cell tumors - embryonal carcinoma, yolk sac tumor, teratoma and choriocarcinoma essentially). The term germ cell neoplasia in situ is consensually accepted as a new terminology for the precursor lesion. In this new classification, the term "spermatocytic seminoma" is replaced by "spermatocytic tumor", reclassified among non-GCNIS-derived tumors. The purpose of this change of nomenclature is to reflect the usually non-aggressive behaviour of this tumor and to avoid any confusion with usual seminoma. The spectrum of trophoblastic tumors continues to expand with the description of new rare entities such as the cystic trophoblastic tumor, the placental site trophoblastic tumor and the epithelioid trophoblastic tumor. This review aims to provide a focus on testicular germ cell tumors highlighting the new immunohistochemical and molecular features responsible for the restructuring of classification. The TNM staging is presented according to the AJCC 8th edition 2017 update.

The utility of microscopic findings and immunohistochemistry in the classification of necrotic testicular tumors: a study of 11 cases.

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.

Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors.

The core embryonic stem cell transcription factors (TFs) OCT3/4 (OCT4), NANOG, and SOX2 have shared as well as nonoverlapping roles in stem cell growth and differentiation. These same TFs are also expressed in various types of human germ cell tumors (GCTs), implicating them in regulation of tumor growth and differentiation. Although NANOG and OCT3/4 are sensitive and specific markers for seminoma and embryonal carcinoma, neither factor aids in the clinically important distinction of seminomatous from nonseminomatous tumors. In contrast, expression profiling data suggest that SOX2 may help with this distinction. To determine if a panel of embryonic stem cell TFs (NANOG, OCT3/4, and SOX2) can facilitate the identification and distinction of seminomatous from nonseminomatous GCTs, we evaluated their expression by immunohistochemistry in primary testicular (n=41) and metastatic retroperitoneal (n=43) GCTs. Our results confirm NANOG and OCT3/4 as sensitive and specific markers for primary seminoma and embryonal carcinoma and demonstrate the novel finding that NANOG is a marker for metastatic GCTs. In addition, SOX2 is expressed in embryonal carcinoma but not pure seminoma and is therefore a useful diagnostic marker for distinguishing seminomatous and nonseminomatous GCTs. In summary, we find that the embryonic stem cell TF signature of seminoma is NANOG+, OCT3/4+, and SOX2-, whereas embryonal carcinoma is NANOG+, OCT3/4+, and SOX2+, and expect these immunohistochemical profiles will facilitate the diagnosis of both primary and metastatic GCTs.

Recent advances in the pathology and classification of ovarian germ cell tumors.

In recent years, our knowledge of ovarian germ cell tumors has increased, and their classification has evolved. The introduction of cisplatin-based chemotherapy and the discovery of tumor markers, including alpha-fetoprotein and human chorionic gonadotropin, have dramatically changed the clinical outlook for most of these patients. In this review, recent advances in the classification and pathology of ovarian germ cell tumors are discussed. Where appropriate, comparisons are made with testicular germ cell tumors. The last section of the article discusses the pathogenesis of germ cell tumors. This review will emphasize the articles written in the last 10 years and those that have significantly advanced our knowledge of germ cell tumors in past decades.

OCT4 is superior to CD30 in the diagnosis of metastatic embryonal carcinomas after chemotherapy.

Correctly diagnosing a metastatic germ cell tumor after chemotherapy may be challenging because of the diverse morphological manifestations of postchemotherapy tumors. Both OCT4 and CD30 are sensitive markers for the identification of primary embryonal carcinomas; however, loss of expression of CD30 (65%) has been reported in metastatic embryonal carcinomas after chemotherapy. The present study was conducted to evaluate the expression patterns of OCT4 and CD30 in postchemotherapy metastatic embryonal carcinomas and to compare their utility as diagnostic tools. Twenty-five cases of metastatic embryonal carcinoma after chemotherapy were immunohistochemically analyzed for CD30, OCT4, and cytokeratin AE1/AE3 expression. The staining intensities and the percentages of positively staining tumor cells were recorded. Nineteen (76%) of 25 cases revealed diffuse, moderate to strong nuclear OCT4 staining in postchemotherapy embryonal carcinomas. Among these 19 OCT4-positive cases, 8 also revealed diffuse and moderate to strong membranous CD30 staining. Seven of these OCT4-positive cases retained focal and weak CD30 expression. The remaining 4 OCT4-positive cases demonstrated a complete loss of CD30 expression. The 19 OCT4-positive cases showed a positive but variable cytokeratin AE1/AE3 expression pattern. Six (24%) of 25 cases were negative for both CD30 and OCT4 but demonstrated diffuse and strong cytokeratin AE1/AE3 staining. OCT4 is a useful diagnostic marker to identify metastatic embryonal carcinomas after chemotherapy, with a better sensitivity than CD30.

Well-differentiated fetal adenocarcinoma of lung.

Well-differentiated fetal adenocarcinoma (WDFA) histologically resembles pulmonary blastoma, and is thought to be a subtype of pulmonary blastoma which has differentiated epithelial features resembling the fetal lung among its epithelial features and sarcomatous features. We recently encountered one patient who underwent surgery for WDFA. This case is reported with a discussion of the literature. A 33-year-old woman had a tumor shadow in the lower lobe of the right lung. The tumor was diagnosed as pulmonary blastoma as a result of echographic biopsy, and right total pneumonectomy was performed. No sarcomatous features were observed on postoperative histological assessment, and the patient was diagnosed as having WDFA. Its prognosis is believed to tend to be better than that of biphasic blastoma, in which sarcomatous features are mingled with epithelial features. However, it is reported that chemotherapy or radiotherapy has seldom been effective. Complete surgical resection is essential for long-term survival.