| Autor: |
Odate, Toru, Satomi, Kaishi, Kubo, Takashi, Matsushita, Yuko, Ueno, Toshihide, Kurose, Akira, Shomori, Kohei, Nakai, Tokiko, Watanabe, Reiko, Segawa, Keiko, Ohshika, Shusa, Miyake, Naritomo, Kudo, Sayaka, Shimoi, Tatsunori, Kobayashi, Eisuke, Komiyama, Motokiyo, Yoshimoto, Seiichi, Nakatani, Fumihiko, Kawai, Akira, Yatabe, Yasushi, Kohsaka, Shinji, Ichimura, Koichi, Ichikawa, Hitoshi, Yoshida, Akihiko |
| Zdroj: |
Modern Pathology; 20230101, Issue: Preprints |
| Abstrakt: |
Inflammatory rhabdomyoblastic tumors (IRMTs) are newly recognized skeletal muscle tumors with uncertain malignant potential. We investigated 13 IRMTs using clinicopathological, genetic, and epigenetic methods. The cohort included 7 men and 6 women, aged 23–80 years (median, 50 years), of whom two had neurofibromatosis type 1. Most tumors occurred in the deep soft tissues of the lower limbs, head/neck, trunk wall, and retroperitoneum/pelvis. Two tumors involved the hypopharyngeal submucosa as polypoid masses. Eight tumors showed conventional histology of predominantly spindled cells with nuclear atypia, low mitotic activity, and massive inflammatory infiltrates. Three tumors showed atypical histology, including uniform epithelioid or plump cells and mitotically active histocytes. The remaining 2 tumors demonstrated malignant progression to rhabdomyosarcoma; one had additional IRMT histology and the other was a pure sarcoma. All 11 IRMTs without malignant progression exhibited indolent behavior at a median follow-up of 43 months. One of the 2 patients with IRMTs with malignant progression died of lung metastases. All IRMTs were positive for desmin and PAX7, whereas myogenin and MyoD1 were expressed in a subset of cases. Targeted next-generation sequencing identified pathogenic mutations in NF1(5/8) and TP53(4/8). All TP53mutations co-occurred with NF1mutations. TP53variant allele frequency was much lower than that of NF1in 2 cases. These tumors showed geographic (sub-clonal) strong p53 immunoreactivity, suggesting the secondary emergence of a TP53-mutant clone. DNA methylation-based copy number analysis conducted in 11 tumors revealed characteristic flat patterns with relative gains including chromosomes 5, 18, and/or 20–22 in most cases. Widespread loss of heterozygosity with retained biparental copies of these chromosomes was confirmed in 4 tumors analyzed via allele-specific profiling. Based on unsupervised DNA methylation analysis, none of the 11 tumors tested clustered with existing reference entities but formed a coherent group, although its specificity warrants further study. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
