High-grade transformation of low-grade endometrial stromal sarcomas lacking YWHAE and BCOR genetic abnormalities.
14-3-3 Proteins
/ genetics
Aged
Cell Transformation, Neoplastic
/ genetics
Endometrial Neoplasms
/ genetics
Female
Humans
Middle Aged
Mitotic Index
Neoplasm Grading
Proto-Oncogene Proteins
/ genetics
Repressor Proteins
/ genetics
Retrospective Studies
Sarcoma, Endometrial Stromal
/ genetics
Survival Rate
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
10
02
2020
accepted:
19
03
2020
revised:
19
03
2020
pubmed:
23
4
2020
medline:
21
7
2021
entrez:
23
4
2020
Statut:
ppublish
Résumé
High-grade histologic transformation of low-grade endometrial stromal sarcoma (LGESS) is rare. Here, we describe the clinicopathologic features and gene fusion status of 12 cases (11 primary uterine corpus and 1 primary vaginal), 11 diagnosed prospectively from 2016, and 1 retrospectively collected. Targeted RNA sequencing and/or fluorescence in situ hybridization was employed in all cases. High-grade transformation was seen at the time of initial diagnosis in eight patients and at the time of recurrence in four patients, 4-11 years after initial diagnosis of LGESS. High-grade morphology consisted of generally uniform population of round to epithelioid cells with enlarged nuclei one to two times larger than a lymphocyte, visible nucleoli, and increased mitotic index (range, 6-30; median, 16 per 10 high-power fields); there was often an associated sclerotic and/or myxoid stroma. Estrogen receptor, progesterone receptor, and CD10 expression was absent or significantly decreased (compared with the low-grade component) in the high-grade foci of five tumors. One tumor demonstrated positive (diffuse and strong) cyclin D1 and BCOR staining. p53 staining was wild type in both components of all eight tumors tested. JAZF1-SUZ12 (n = 6), JAZF1-PHF1 (n = 3), EPC1-PHF1, (n = 1), or BRD8-PHF1 (n = 1) fusions were detected in 11 tumors; no fusions were found in one by targeted RNA sequencing. Patients presented with FIGO stages I (n = 4), II (n = 4), III (n = 1), and IV disease (n = 2). Median overall survival calculated from the time of histologic transformation was 22 months (range, 8 months to 8 years) with five patients who died of disease 8-18 months after transformation. High-grade transformation may occur in LGESS with JAZF1 and PHF1 rearrangements at the time of or years after initial diagnosis. Such high-grade transformation is characterized by nuclear enlargement, prominent nucleoli, and increased mitotic index compared with typical LGESS. Histologic high-grade transformation may herald aggressive behavior.
Identifiants
pubmed: 32317704
doi: 10.1038/s41379-020-0535-y
pii: S0893-3952(22)00714-1
pmc: PMC8288077
mid: NIHMS1578682
doi:
Substances chimiques
14-3-3 Proteins
0
BCOR protein, human
0
Proto-Oncogene Proteins
0
Repressor Proteins
0
YWHAE protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1861-1870Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009512
Pays : United States
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