Mediastinal Germ Cell Tumors: A Review and Update on Pathologic, Clinical, and Molecular Features

Abstract

Mediastinal germ cell tumors (MGCTs) are the most common extragonadal germ cell tumors (GCTs) and most often arise in the anterior mediastinum with a male predilection. MGCTs also have a predilection for patients with Klinefelter syndrome and possibly other genetic conditions. MGCTs, as GCTs at other extragonadal sites, are thought to arise from germ cells improperly retained during migration along the midline during embryogenesis. Similar to their counterparts in the testes, MGCTs are classified into seminomatous and nonseminomatous GCTs. Seminomatous MGCT represents pure seminoma, whereas nonseminomatous MGCTs encompass pure yolk sac tumors, embryonal carcinoma, choriocarcinoma, mature or immature teratoma, and mixed GCTs with any combination of GCT types, including seminoma. Somatictype or hematologic malignancies can also occur in association with a primary MGCT. MGCTs share molecular findings with GCTs at other sites, most commonly the presence of chromosome 12p gains and isochromosome i(12p). Treatment includes neoadjuvant chemotherapy followed by surgical resection of residual tumor, with the exception of benign teratomas, which require only surgical resection without chemotherapy. In this review, we highlight and provide an update on pathologic, clinical, and molecular features of MGCTs. Immunohistochemical profiles of each tumor type, as well as differential diagnostic considerations, are discussed.

Establishment and validation of an individualized nomogram for survival prediction of primary mediastinal germ cell tumors based on the SEER database

“…Laflamme et al reported that postpubertal PMNGCT had the poorer prognosis among GCTs, with a 5-year survival ratio of 45–50% ( 11 ). According to El-Zaatari et al ’s research ( 3 ), the median age at PMS onset was 33 years (range, 18 to 65 years) and the median age at PMNGCT onset was 28 years (range, 12 to 42 years). The occurrence of PMGCT showed a bimodal age distribution, with a first apex at 0–4 years of age, a decline in childhood, and then a second peak at 10–20 years of age.…”

“…They are an uncommon group of tumors that account for just 2–5% of all GCTs. An increment of the short arm of chromosome (i12p) ( 3 ), which frequently results in the creation of an isochromosome, is a famous hallmark of malignant GCTs, both gonadal and extragonadal, and seminoma and non-seminoma. The primary mediastinal germ cell tumors (PMGCT) made up of non-seminomas and seminomas comprise 15% of adult mediastinal carcinomas ( 4 ).…”

Approach to Mediastinal Fine Needle Aspiration Cytology

“…MYST is usually positive for LIN28, SALL4, Glypican-3, AFP, and PLZF, variable for keratins and CD117, but negative for OCT4, CD30, PLAP, Nanog, beta-hCG, and CD10. [60][61][62] Mediastinal embryonal carcinoma (MEC) usually occurs concurrently with other GCT components instead of pure MEC. 55 FNA of MEC component may show clusters of or single large highly atypical epithelioid cells with large round vesicular nuclei and prominent nucleoli (Fig.…”

“…Mediastinal choriocarcinoma is extremely rare 60. FNA of mediastinal choriocarcinoma may show 2 populations of cells: syncytiotrophoblasts and cytotrophoblasts.…”

Oleuropein Counteracts Both the Proliferation and Migration of Intra- and Extragonadal Seminoma Cells

“…Rarely, seminoma occurs outside of the gonads, with the mediastinum being the most common extragonadal location, because of defects from germ cell migration during embryogenesis. Mediastinal seminomas are indistinguishable from gonadal seminomas and are very sensitive to chemotherapy and radiation, as well as testicular seminomas [ 6 ]. Testicular seminoma is practically managed with surgical resection.…”