Disease relevance of MGCT

• Patients with mediastinal germ cell tumors (MGCT) have a high incidence of hematologic malignancies unrelated to cytotoxic chemotherapy [1].
• Serum HCG was raised in three boys with yolk sac tumours, one with a mixed teratoma, and one 14-year-old boy who had a mixed MGCT [2].
• Myelodysplastic syndrome (RARS) with +i(12p) abnormality in a patient 10 months after diagnosis and successful treatment of a mediastinal germ cell tumor (MGCT) [3].
• Endodermal sinus tumor (EST) forms the most common histologic subtype of MGCT [4].
• An association between mediastinal germ cell tumors (MGCT) and hematological malignancies (e.g. acute leukemia, malignant histiocytosis) has been recognized since 1984 [5].

High impact information on MGCT

• We identified six male patients with this syndrome treated at Memorial Sloan-Kettering Cancer Center: in all six, the leukemia was studied immunohistochemically for various hematologic and germ cell antigens; in four, the karyotype of the leukemia was available; in one, the MGCT had also been karyotyped [6].
• A 16-year-old male with probable Klinefelter's syndrome presented simultaneously with acute monocytic leukemia and an MGCT; although the MGCT was not karyotyped, the leukemia showed an i(12p) [6].
• A 19-year-old male developed an acute myeloblastic leukemia 11 months after presenting with an MGCT; karyotypes of the two tumors showed them to be clonally related, both showing an i(12p), a cytogenetic marker of germ cell tumors [6].
• Evidence for a germ cell origin of the acute leukemias in the three other patients was not obtained, although in all three the MGCT and the leukemia occurred simultaneously, supporting an etiologic relationship [6].
• A 23-year-old male developed concurrently an MGCT and acute myelomonocytic leukemia; the leukemia cells coexpressed myelomonocytic antigens (HAM56, My4, My9) and cytokeratin, suggesting dual differentiation, myeloid and germ cell [6].

Chemical compound and disease context of MGCT

• We report on a 21-year-old man with a mediastinal germ cell tumor (MGCT) who developed a myelodysplastic syndrome (MDS) (refractory anemia with ringed sideroblasts, RARS) 10 months after the start of successful treatment with cisplatin, etoposide, ifosfamide, and paclitaxel [3].
• PURPOSE: To determine whether children with localized gonadal malignant germ cell tumors (MGCT) stage II testicular and stages I and II ovarian treated with four cycles of standard-dose cisplatin combined with etoposide and low-dose bleomycin (PEB) have an event-free survival (EFS) of at least 85% without significant toxicity [7].

Biological context of MGCT

• Isochromosome 12p is a specific aberration frequently observed in MGCT [3].
• Although these findings need confirmation from future studies, they suggest a potential influence of in utero exposure to maternal endogenous hormones, parental environmental exposures, and maternal diseases during pregnancy in the development of childhood MGCT [8].
• New findings, not reported previously, include a positive relationship of MGCT risk with birthweight and prolonged breastfeeding, an inverse association between MGCT risk and number of cigarettes smoked by the mother during pregnancy, and a 3.1-fold increased risk (CI = 1.5-6.6) associated with maternal urinary infections during index pregnancy [8].
• Consistent with the findings from studies of adult MGCT, gestational age was associated inversely with risk of MGCT, with a 70 to 75 percent reduction in risk for children born at term compared with those born pre-term [8].
• CONCLUSIONS: Malignant MGCT is a complex tumor of varied histology with frequent coexistence of benign elements [9].

Anatomical context of MGCT

• The United Kingdom Children's Cancer Study Group (UKCCSG) malignant germ cell tumour (MGCT) studies were undertaken to establish standard protocols of investigation, staging, and treatment [2].
• Morphologically identifiable hematologic cells were found within the yolk sac tumor component of the MGCT in four of these patients [1].
• It has been suggested that these leukemic conditions originate from a MGCT progenitor cell capable of undergoing non-germ cell (hematopoietic) differentiation [1].
• The leukemic cells within the MGCT and in the bone marrow had similar morphology, constant expression of the early progenitor cell marker CD34, and variable expression of more mature myeloid, monocytic, erythroid, and megakaryocytic markers [1].
• We identified 14 male germ cell tumor patients (13 of whom had received prior chemotherapy) in whom distinctive neoplasms composed of spindle to stellate cells set in a myxoid to collagenous stroma containing numerous blood vessels developed [10].

Associations of MGCT with chemical compounds

• CONCLUSIONS: The present results reflect the dramatic effectiveness of cisplatin-based chemotherapy for ovarian MGCT and confirm that unilateral oophorectomy can preserve fertility without compromising cure [11].
• In all, 43 patients with IGCCCG intermediate/poor prognosis MGCT were treated with a dose intense regimen alternating bleomycin, vincristine, cisplatin (BOP) with bleomycin, etoposide, cisplatin (BEP) to a maximum of three cycles [12].
• We conducted a phase II clinical trial using ifosfamide (IFX) as a single agent in cisplatin-refractory male germ cell tumor [13].

Other interactions of MGCT

• In our experience CA-125 is an invaluable indicator of the clinical status of the patient and could be a new tumor marker in patients with MGCT [14].
• CONCLUSION: Combination chemotherapy with HDPEB significantly improves EFS for children with high-risk MGCT [15].
• CONCLUSIONS: The present results show positive staining for inhibin/activin subunits in ovarian and testicular MGCT, suggesting a possible role in tumorigenesis with the resultant clinical implication [16].
• The mean tubular diameter (MTD), tubular fertility index (TFI) and mean number of germ cells per tubule (MGCT) were calculated using immunohistochemistry for CD-99, a Sertoli-cell marker, to classify germ cells more accurately [17].
• Human male germ cell tumor resistance to cisplatin is linked to TP53 gene mutation [18].

Analytical, diagnostic and therapeutic context of MGCT

• A retroperitoneal enlarging mass was detected and resected in a 24-year-old nulliparous woman after fertility-preserving surgery and adjuvant chemotherapy for a malignant germ cell tumor (MGCT) of the right ovary [19].
• CONCLUSION: Combination chemotherapy with PEB results in excellent EFS and OS with minimal toxicity in children and adolescents with localized gonadal MGCT [7].
• Patients with MGCT have a significantly increased relative death risk due to a second nongerm cell cancer, even after the introduction of modern treatment principles with overall reduction of radiotherapy [20].
• Immunocytochemistry was helpful in making a definitive diagnosis and suggested that MGCT is a carcinosarcoma like neoplasm [21].
• The dissemination of MGCT resulted in the fatal outcome 81 days after hysterectomy [22].

References