Botryoid-type embryonal rhabdomyosarcoma: A comprehensive clinicopathologic and molecular appraisal with cross-comparison to its conventional-type counterpart Journal Article
| Authors: | Sharma, A. E.; Dermawan, J. K.; Chiang, S.; Wexler, L. H.; Antonescu, C. R. |
| Article Title: | Botryoid-type embryonal rhabdomyosarcoma: A comprehensive clinicopathologic and molecular appraisal with cross-comparison to its conventional-type counterpart |
| Abstract: | Embryonal rhabdomyosarcoma (ERMS) is the most common subtype of RMS, occurring in soft tissue and visceral sites of young children, and is associated with favorable outcomes. A subset occurs in mucosal-lined luminal structures, displaying a unique grape-like growth termed as "botryoid-type."To further delineate the differences between conventional (cERMS) and botryoid-type (bERMS) RMS, we performed a comparative histologic review and comprehensive molecular profiling of 48 cases (25 bERMS and 23 cERMS). All tumors were subjected to a hybridization capture-based targeted matched tumor-normal DNA NGS assay. The mean age was 17 and 7 years for bERMS and cERMS, respectively. Most bERMS were female with a predilection for the gynecologic tract (75%), while cERMS had a slight male predominance and were preferentially located in abdominopelvic and paratesticular sites (30%, each). All bERMS exhibited an exophytic, bulbous architecture accompanied by a subepithelial "cambium layer."Distinctive germline alterations were detected, with DICER1 (18%) and FH (6%) mutations only in bERMS, and rare TP53, VHL, and APC mutations in cERMS. Similarly, contrasting somatic genomic landscapes were observed, with frequent DICER1 (52%, P∗∗<0.0001) and TP53 (36%, P∗<0.05) alterations exclusively in bERMS. Cartilaginous differentiation was only observed in DICER1-mutated bERMS. All patients had longitudinal follow-up. bERMS patients with somatic/germline DICER1 mutations showed significantly improved recurrence-free survival compared with that of DICER1-wild type patients (P∗<0.05). Moreover, bERMS showed improved disease-specific survival compared with that of cERMS, with 8% versus 30% (P∗<0.05) dead of disease, respectively. In summary, we compare the molecular underpinnings of the largest cohort of bERMS and cERMS with targeted DNA sequencing and long-term follow-up data. Our findings reveal divergent genomic topographies between the 2 groups, with bERMS showing unique germline and somatic abnormalities, including enrichment in DICER1 and TP53 alterations, and a trend towards improved survival. © 2024 Wolters Kluwer Health, Inc. All rights reserved. |
| Keywords: | adolescent; adult; child; clinical article; controlled study; gene mutation; missense mutation; clinical feature; disease course; comparative study; recurrence risk; follow up; germline; tumor volume; cohort analysis; cyclophosphamide; vincristine; wild type; protein p53; irinotecan; dactinomycin; tamoxifen; auditory canal; heterozygosity loss; kaplan meier method; parotid gland; gingiva; nonsense mutation; embryonal rhabdomyosarcoma; uterine cervix; skeletal muscle; bladder; nasopharynx; hybridization; demographics; tp53; high throughput sequencing; proliferation index; dna sequencing; human; male; female; article; dicer1; molecular fingerprinting; dicer1 syndrome; botryoid; cambium |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 48 |
| Issue: | 12 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2024-12-01 |
| Start Page: | 1557 |
| End Page: | 1567 |
| Language: | English |
| DOI: | 10.1097/pas.0000000000002300 |
| PUBMED: | 39210566 |
| PROVIDER: | scopus |
| PMCID: | PMC12117734 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Cristina Antonescu -- Source: Scopus |
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