The association of hematological malignancies with a mediastinal germ cell tumor (GCT) is very rare. We report one case of a young adult male with primary mediastinal GCT who subsequently developed acute megakaryoblastic leukemia involving isochromosome (12p). A 25-yr-old man had been diagnosed with a mediastinal GCT and underwent surgical resection and adjuvant chemotherapy. At 1 week after the last cycle of chemotherapy, his peripheral blood showed leukocytosis with blasts. A bone marrow study confirmed the acute megakaryoblastic leukemia. A cytogenetic study revealed a complex karyotype with i(12p). Although additional chemotherapy was administered, the patient could not attain remission and died of septic shock. This case was definitely distinct from therapy-related secondary leukemia in terms of clinical, morphologic, and cytogenetic features. To our knowledge, this is the first case report of a patient with mediastinal GCT subsequently developing acute megakaryoblastic leukemia involving i(12p) in Korea.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bleomycin/administration & dosage ; Bone Marrow/pathology ; *Chromosomes, Human, Pair 12 ; Cisplatin/administration & dosage ; Etoposide/administration & dosage ; Humans ; Isochromosomes ; Karyotyping ; Leukemia, Megakaryoblastic, Acute/drug therapy/etiology/*genetics ; Male ; Mediastinal Neoplasms/*diagnosis/drug therapy/surgery ; Neoplasms, Germ Cell and Embryonal/*diagnosis/drug therapy/surgery ; Neoplasms, Second Primary/drug therapy/etiology/*genetics ; Republic of Korea ; Shock, Septic/pathology

BACKGROUND: Therapy-related myeloid neoplasms (t-MN) occur as late complications of cytotoxic therapy. This study reviewed clinical and cytogenetic characteristics of patients with t-MN at a single institution in Korea. METHODS: The study subjects included 39 consecutive patients diagnosed with t-MN. Each subject's clinical history of previous diseases, treatments, and laboratory data was reviewed, including cytogenetics. The primary diagnosis was hematologic malignancy in 14 patients and solid tumor in 25 patients. RESULTS: Therapy-related acute myeloid leukemia (t-AML, 66.7%) was found to be more common than therapy-related myelodysplastic syndrome (t-MDS). Primary hematologic malignancies that were commonly implicated included mature B-cell neoplasm and acute leukemia. Breast cancer was the most common primary solid tumor. The mean time interval from cytotoxic therapy initiation to t-MN detection was 49 months. Chromosomal aberrations were observed in 35 patients, and loss of chromosome 5, 7, or both accounted for 41% of all cases. Balanced rearrangements occurred in 13 patients; these patients showed shorter latency intervals (mean, 38 months) than patients with loss of chromosome 5 or 7 (mean, 61 months). CONCLUSIONS: In this study, we determined the clinical and cytogenetic characteristics of Korean patients with t-MN. Although our results were generally consistent with those of previous reports, we found that t-MN resulting from de novo leukemia was common and that t-AML was more common than t-MDS at presentation. Multi-institutional studies involving a larger number of patients and additional parameters are required to investigate the epidemiology, genetic predisposition, and survival rate of t-MN in Korea.
Adolescent ; Adult ; Aged ; Antineoplastic Agents/*adverse effects/therapeutic use ; Asian Continental Ancestry Group ; Bone Marrow/pathology ; Breast Neoplasms/drug therapy/pathology/radiotherapy ; Child ; Child, Preschool ; Chromosome Aberrations ; Chromosomes, Human, Pair 5 ; Chromosomes, Human, Pair 7 ; Female ; Hematologic Neoplasms/drug therapy/pathology/radiotherapy ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute/*diagnosis/etiology/genetics ; Male ; Middle Aged ; Myelodysplastic Syndromes/*diagnosis/etiology/genetics ; Neoplasms, Second Primary/*diagnosis/etiology/genetics ; Republic of Korea ; Young Adult

Following improvements in therapy for childhood malignancies, the striking increase in survival rate over the past 30 years has led to the increase risk of developing second malignant neoplasms (SMNs). We report a case of colorectal carcinoma as a SMN, following treatment for rhabdomyosarcoma. The patient was diagnosed with rhabdomyosarcoma of the urinary bladder at his age of three years, and developed adenocarcinoma in the colon 13 years later. Histologic examination of the surgical specimen revealed adenocarcinoma involving the rectosigmoid area with radiation colitis in its background. The tumor cells showed strong immunoreactivity for p53 protein, suggesting the role of irradiation and p53 mutation in carcinogenesis. This case emphasizes the need for dose observation in survivors of early childhood malignancies treated with radiation and multiagent chemotherapy.
Adenocarcinoma/pathology ; Adenocarcinoma/genetics ; Adenocarcinoma/etiology+ACo- ; Adolescence ; Antineoplastic Agents, Combined/therapeutic use ; Antineoplastic Agents, Combined/adverse effects+ACo- ; Bladder Neoplasms+ACo-/radiotherapy ; Bladder Neoplasms+ACo-/drug therapy ; Case Report ; Colitis/pathology ; Colitis/etiology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/etiology+ACo- ; Combined Modality Therapy ; Cyclophosphamide/adverse effects ; Cyclophosphamide/administration +ACY- dosage ; Doxorubicin/adverse effects ; Doxorubicin/administration +ACY- dosage ; Genes, p53 ; Human ; Male ; Neoplasm Proteins/analysis ; Neoplasms, Radiation-Induced/pathology ; Neoplasms, Radiation-Induced/genetics ; Neoplasms, Radiation-Induced/etiology+ACo- ; Neoplasms, Second Primary/etiology+ACo- ; Protein p53/analysis ; Radiation Injuries/pathology ; Radiation Injuries/etiology ; Radiotherapy/adverse effects+ACo- ; Rhabdomyosarcoma+ACo-/radiotherapy ; Rhabdomyosarcoma+ACo-/drug therapy ; Sigmoid Neoplasms/pathology ; Sigmoid Neoplasms/genetics ; Sigmoid Neoplasms/etiology ; Time Factors ; Vincristine/adverse effects ; Vincristine/administration +ACY- dosage

Following improvements in therapy for childhood malignancies, the striking increase in survival rate over the past 30 years has led to the increase risk of developing second malignant neoplasms (SMNs). We report a case of colorectal carcinoma as a SMN, following treatment for rhabdomyosarcoma. The patient was diagnosed with rhabdomyosarcoma of the urinary bladder at his age of three years, and developed adenocarcinoma in the colon 13 years later. Histologic examination of the surgical specimen revealed adenocarcinoma involving the rectosigmoid area with radiation colitis in its background. The tumor cells showed strong immunoreactivity for p53 protein, suggesting the role of irradiation and p53 mutation in carcinogenesis. This case emphasizes the need for dose observation in survivors of early childhood malignancies treated with radiation and multiagent chemotherapy.
Adenocarcinoma/pathology ; Adenocarcinoma/genetics ; Adenocarcinoma/etiology+ACo- ; Adolescence ; Antineoplastic Agents, Combined/therapeutic use ; Antineoplastic Agents, Combined/adverse effects+ACo- ; Bladder Neoplasms+ACo-/radiotherapy ; Bladder Neoplasms+ACo-/drug therapy ; Case Report ; Colitis/pathology ; Colitis/etiology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/etiology+ACo- ; Combined Modality Therapy ; Cyclophosphamide/adverse effects ; Cyclophosphamide/administration +ACY- dosage ; Doxorubicin/adverse effects ; Doxorubicin/administration +ACY- dosage ; Genes, p53 ; Human ; Male ; Neoplasm Proteins/analysis ; Neoplasms, Radiation-Induced/pathology ; Neoplasms, Radiation-Induced/genetics ; Neoplasms, Radiation-Induced/etiology+ACo- ; Neoplasms, Second Primary/etiology+ACo- ; Protein p53/analysis ; Radiation Injuries/pathology ; Radiation Injuries/etiology ; Radiotherapy/adverse effects+ACo- ; Rhabdomyosarcoma+ACo-/radiotherapy ; Rhabdomyosarcoma+ACo-/drug therapy ; Sigmoid Neoplasms/pathology ; Sigmoid Neoplasms/genetics ; Sigmoid Neoplasms/etiology ; Time Factors ; Vincristine/adverse effects ; Vincristine/administration +ACY- dosage