Hematologic Malignancies Associated With Mediastinal Germ Cell Tumors: 10 Years’ Experience at Thailand’s National Pediatric Tertiary Referral Center

Abstract

Mediastinal germ cell tumor (MGCT), which accounts for 1% to 3% of extragonadal germ cell tumors, has unique manifestations; it is associated with several types of hematologic malignancy, particularly myeloid neoplasm. The aim of this study was to report the 10-year incidence, clinical characteristics, and outcomes of MGCT at Thailand's national pediatric tertiary referral center. This retrospective study included patients diagnosed with MGCT at the Department of Pediatrics, Siriraj Hospital during 2005 to 2014. Eight patients (all male) were diagnosed with MGCT. Five of 8 patients were found to have hematologic abnormalities. Three patients were diagnosed with acute myeloid leukemia (AML) (one patient with M1, another having M7, and the other with M0). Another patient had mixed MGCT with mediastinal myeloid sarcoma (MMS). The other patient had malignancy-associated hemophagocytic lymphohistiocytosis syndrome (M-HLH). Isochromosome 12p was detected in 3 patients (AML [2], mixed MGCT/MMS [1]). Four of 5 patients with hematologic abnormalities died of hematologic abnormalities or treatment complication (AML [3], M-HLH [1]). One patient with mixed MGCT/MMS survived with chemotherapy. All patients with AML and MMS were nonseminomatous MGCT and the onset of myeloid malignancies were within 1 year after the diagnosis of MGCT. Associated hematologic malignancies should be suspected in MGCT with abnormal blood count or hematologic symptoms. Isochromosome 12p was the most common cytogenetic finding in MGCT-associated myeloid malignancies patients. Those with nonseminomatous MGCT should have their blood count carefully monitored especially during the first year after the diagnosis of MGCT. Better treatment alternatives for MGCT with associated hematologic malignancies are warranted to ameliorate adverse outcomes.

Clinical Outcomes of Extracranial Germ Cell Tumors: A Single Institute’s Experience

“…Those who had an unresectable tumor received neoadjuvant chemotherapy consisting of cisplatin, etoposide, and bleomycin (PEB) before surgery. 9 Patients with teratoma were treated with surgery solely. However, those children with immature teratoma (IT) either greater than stage II or grade III tumor may have received PEB upon physician discretions.…”

“…Several type of hematologic malignancies, especially acute megakaryoblastic leumemia, were reported in patients with mediastinal GCT. 9,15 Isochromosome 12p might be responsible for the concomitant hematologic malignancies in these patients. 16 Although only one of our patients harbor this abnormal chromosome, we believed that the hematologic malignancies in both of them were related to the mediastinal GCT rather than a secondary malignancy related to cancer treatment since theirs myeloid neoplasms developed very early after the initiation of chemotherapy.…”

Primary Mediastinal and Testicular Germ Cell Tumors in Adolescents and Adults: A Comparison of Genomic Alterations and Clinical Implications

“…Moreover, the hematologic disease frequently carries alterations not typical of the specific type of HM and lacks the canonical aberrations detected in de novo diseases. For example, gain or isochromosome of 12p is an event not detectable in canonical AML [69], but it has been reported in 18 out of 38 HMs associated with MGCTs (approximately 47% of cases) (Table 2) [66,[68][69][70][71][72][73][74]76]. Conversely common alterations, including MLL rearrangements or mutations on genes such as FLT3, NPM1 and others, were not detected in AML coupled with MGCTs [67,69,72,77,78].…”

“…Evidence of a clonal relationship between HM and MGCT was discovered through the identification of molecular alterations shared between the two tumor types (i12p/12p gain, TP53, KRAS and PTEN mutations) (Table 1) [66,[68][69][70][71][72][73][74][75][76][77][78][79][80]. Moreover, the hematologic disease frequently carries alterations not typical of the specific type of HM and lacks the canonical aberrations detected in de novo diseases.…”

А сlinical case report of mediastinal teratoma in an adolescent patient with Klinefelter syndrome

“…Средняя продолжительность жизни таких больных составляет от 1 до 6 месяцев. В данных исследованиях не удалось обнаружить факторы, которые бы предсказывали развитие лейкемии у больных с внегонадными опухолями за исключением их локализации в средостении, наличие компонентов опухоли желточного мешка и/или тератокарциномы в первичной опухоли [16,19,20]. Основываясь на цитогенетических исследованиях, обнаруживших изохромосому 12 в лейкемических клетках, исследователи предполагают, что острый лейкоз и ГКО средостения происходят из одной клетки-предшественницы.…”