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SMARCA4-deficient Uterine Sarcoma and Undifferentiated Endometrial Carcinoma Are Distinct Clinicopathologic Entities.
- Source :
-
The American journal of surgical pathology [Am J Surg Pathol] 2020 Feb; Vol. 44 (2), pp. 263-270. - Publication Year :
- 2020
-
Abstract
- Undifferentiated and dedifferentiated endometrial carcinomas (UDEC) are aggressive uterine tumors which may show loss of expression of SMARCA4 (BRG1) or SMARCB1 (INI-1). The recently described SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) has a morphology which overlaps with UDEC. In this study, we compared clinical, morphologic, immunohistochemical, and molecular characteristics to identify features which differentiate SDUS from UDEC. Cases of SDUS (n=12) were compared with cases of UDEC (n=84, 55 of which were previously published). Immunohistochemistry was performed for p53, mismatch repair proteins, claudin-4, SMARCA4, and SMARCB1. Targeted molecular profiling was performed on 15 cases. Patients with SDUS were significantly younger than those with UDEC (mean 35.8 vs. 61.2 y, P=0.0001). UDEC and SDUS showed morphologic overlap; however, phyllodiform architecture favored a diagnosis of SDUS (36% vs. 0%, P=0.005), while prominent nuclear pleomorphism was only seen in some cases of UDEC (0% vs. 24%, P=0.15). Compared with SDUS, UDEC more frequently showed TP53 mutations (0% vs. 34%, P=0.03), microsatellite instability (0% vs. 44%, P=0.006), and intact SMARCA4 and SMARCB1 (0% vs. 80%); a panel combining these immunohistochemical markers had a sensitivity of 100% and specificity of 92% in distinguishing SDUS and UDEC. Cases of UDEC had mutations in genes associated with endometrial adenocarcinomas (eg, TP53, PTEN, PIK3CA) and occasionally SMARCA4, while SDUS was characterized solely by inactivating mutations in SMARCA4. Disease-specific survival was shorter in SDUS than UDEC (median survival 9 and 36 mo, P=0.01). In conclusion, SDUS occurs in younger patients than UDEC, has a worse prognosis, and in most cases has a distinct molecular and immunohistochemical profile.
- Subjects :
- Adult
Aged
Aged, 80 and over
Diagnosis, Differential
Endometrial Neoplasms metabolism
Endometrial Neoplasms pathology
Female
Humans
Immunohistochemistry
Middle Aged
Sarcoma metabolism
Sarcoma pathology
Sensitivity and Specificity
Uterine Neoplasms metabolism
Uterine Neoplasms pathology
Biomarkers, Tumor deficiency
DNA Helicases deficiency
Endometrial Neoplasms diagnosis
Nuclear Proteins deficiency
SMARCB1 Protein deficiency
Sarcoma diagnosis
Transcription Factors deficiency
Uterine Neoplasms diagnosis
Subjects
Details
- Language :
- English
- ISSN :
- 1532-0979
- Volume :
- 44
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The American journal of surgical pathology
- Publication Type :
- Academic Journal
- Accession number :
- 31567195
- Full Text :
- https://doi.org/10.1097/PAS.0000000000001375