PMC4711183_01
FDG-PET/CT showed remarkable FDG uptake in anterior mediastinum (A-C). CT revealed right testicular swelling (D). Head MRI showed multiple parenchymal invasions (E). Mediastinal sections at low (F) and high (G) magnifications showed diffuse infiltration of medium-sized tumor cells with scant cytoplasm and dense chromatin, which was accompanied by nuclear fragmentation. The tumor cells were positive for CD56 (H) and CD99 (I). Testicular mass sections at relapse showed diffuse stromal infiltration of medium- to large-sized atypical cells with no apparent differentiation to neutrophils or monocytes (J and K). The tumor cells were positive for MPO (L) and CD34 (M).
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FDG uptake in the supraclavicular lymph nodes, and a bulky anterior mediastinal tumor (Fig. 1A-C). Fine needle biopsy from the mediastinal tumor was performed. Hematoxylin and eosin-stained mediastinal sections showed diffuse infiltration of medium-sized tumor cells (Fig. 1F and G). Immunohistochemistry demonstrated that the tumor cells were negative for CD1a, CD3, CD8, CD20 and TdT, and positive for CD4, CD43, CD56 (Fig. 1H) and CD99 (Fig. 1I). Because he noticed painless right testicular swelling 10 months after the start of treatment, right orchiectomy was performed for diagnosis (Fig. 1D). Histopathologically, slides of testicular mass sections showed diffuse stromal infiltration of medium- to large-sized atypical cells (Fig. 1J and K). Immunohistochemical analysis revealed that the tumor cells were negative for CD3, CD20, CD68 (PGM1) and TdT, and positive for CD4, CD56, MPO (Fig. 1L) and CD34 (Fig. 1M). However, the patient gradually developed headache, and head magnetic resonance imaging (MRI) detected multiple intraparenchymal masses, which were considered as the invasion of MS (Fig. 1E).
Break-apart FISH analysis revealed FUS gene rearrangement in paraffin-embedded tumor sections both at first presentation (A) and at recurrence (B). RNA was extracted from patient's frozen tissue, YNH-1 cultured cells (from RIKEN Cell Bank, Tsukuba, Japan) as a positive control, and K562 cultured cells as a negative control. RT-PCR analysis of FUS-ERG fusion gene transcripts was performed, and agarose gel electrophoresis showed one major band of 191 bp (Type B) and one minor band of 230 bp (Type A) in the patient (Lane 1) and YNH-1 cells (Lane 2) (C). Sequence of chimeric transcripts showed that exon 7 of the FUS gene located at 16p11 was fused in frame to exon 12 of the ERG gene located at 21q22 (D).
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FUS gene break-apart fluorescent in situ hybridization (FISH) analysis showed split signals in biopsy sections of the mediastinum at initial diagnosis and the testis at recurrence (Fig. 2A and B). Reverse transcriptase polymerase chain reaction (RT-PCR) and direct sequence analysis demonstrated the presence of the FUS-ERG chimeric gene transcript (Fig. 2C and D).