Uterine
leiomyomas, or
fibroids, are very common
smooth muscle tumors. Their potential to metastasize or transform into
leiomyosarcomas is extremely low. Here, we report a patient who underwent
hysterectomy due to a large
leiomyoma and who was diagnosed with pulmonary
tumors seven and nine years later. Histopathological re-evaluation confirmed the cellular
leiomyoma diagnosis for the uterine
tumor, whereas the pulmonary
tumors met the diagnostic criteria of a
leiomyosarcoma. Whole-exome sequencing revealed very similar mutational profiles in all three
tumors, including a somatic homozygous deletion in a rare, but well-established
leiomyoma driver gene FH.
Tumor evolution analysis confirmed the clonal origin of all three
tumors. In addition to mutations shared by all three
tumors, pulmonary
tumors harbored additional alterations affecting e.g. the
cancer-associated genes NRG1 and MYOCD. The second pulmonary
leiomyosarcoma harbored additional changes, including a mutation in FGFR1. In global gene expression profiling, the uterine
tumor showed similar expression patterns as other FH-deficient
leiomyomas. Taken together, this comprehensive molecular data supports the occasional metastatic capability and malignant transformation of uterine
leiomyomas. Further studies are required to confirm whether FH-deficient
tumors and/or
tumors with cellular histopathology have higher malignant potential than other uterine
leiomyomas.