Atypical uterine polyps show morphologic and molecular overlap with mullerian adenosarcoma but follow a benign clinical course.
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:
01 2022
01 2022
Historique:
received:
30
06
2021
accepted:
29
09
2021
revised:
28
09
2021
pubmed:
23
10
2021
medline:
2
4
2022
entrez:
22
10
2021
Statut:
ppublish
Résumé
A subset of clinically benign uterine polyps shows atypical morphologic features worrisome for, but not diagnostic of, Mullerian adenosarcoma. We report clinicopathologic data for 63 polyps from 58 women with atypical morphologic features including abnormal architecture, abnormal periglandular stroma, stromal atypia, and mitoses >2 per 10 hpf. Four (11%) of 36 women with follow-up tissue sampling had residual/recurrent atypical polyp. Twelve (27%) of 44 women underwent hysterectomy subsequent to a diagnosis of atypical polyp. No patient developed adenosarcoma over median follow-up of 150 months. Twenty-one primary atypical polyps underwent molecular profiling. Five (24%) harbored chr 12q13-15 gain or amplification, 9/20 (45%) harbored chr 6q25.1 gain, and 7/21 (33%) had no significant copy number alterations. Gains of chr 1q, chr 8p12, and chr 10q11.21-23, amplifications of chr 12q24.12-13, chr 15p24.1-26.1, and chr 18q21.33, and loss of chr 7 and chr 11q21 were each seen in a single polyp. Mean tumor mutational burden was 3.1 (range, 0.76-8.365) mutations/Mb. Pathogenic point mutations were identified in 12/20 (60%) primary atypical polyps. We propose the term "atypical uterine polyps" for these lesions, which show biologic overlap with early Mullerian adenosarcoma but lack molecular alterations characteristic of clinically aggressive adenosarcoma and appear to follow a benign clinical course. Conservative management with close clinical follow-up and repeat sampling can be considered for these lesions, when clinically appropriate.
Identifiants
pubmed: 34675347
doi: 10.1038/s41379-021-00946-z
pii: S0893-3952(22)00357-X
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106-116Informations de copyright
© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
Références
Fletcher, J. A., Pinkus, J. L., Lage, J. M., Morton, C. C. & Pinkus, G. S. Clonal 6p21 rearrangement is restricted to the mesenchymal component of an endometrial polyp. Genes Chromosomes Cancer 5, 260–263 (1992).
doi: 10.1002/gcc.2870050315
Caroti, S. & Siliotti, F. Cervical polyps: A colpo-cyto-histological study. Clin. Exp. Obstet. Gynecol. 15, 108–115 (1988).
pubmed: 3402083
Golan, A., Ber, A., Wolman, I. & David, M. P. Cervical polyp: Evaluation of current treatment. Gynecol. Obstet. Invest. 37, 56–58 (1994).
doi: 10.1159/000292522
Van Bogaert, L. J. Clinicopathologic findings in endometrial polyps. Obstet. Gynecol. 71, 771–773 (1988).
pubmed: 3357665
Reslová, T., Tosner, J., Resl, M., Kugler, R. & Vávrová, I. Endometrial polyps. A clinical study of 245 cases. Arch Gynecol. Obstet. 262, 133–139 (1999).
doi: 10.1007/s004040050241
Dal Cin, P. et al. Four cytogenetic subgroups can be identified in endometrial polyps. Cancer Res. 55, 1565–1568 (1995).
pubmed: 7882366
Tallini, G. et al. HMGI-C and HMGI(Y) immunoreactivity correlates with cytogenetic abnormalities in lipomas, pulmonary chondroid hamartomas, endometrial polyps, and uterine leiomyomas and is compatible with rearrangement of the HMGI-C and HMGI(Y) genes. Lab. Invest. 80, 359–369 (2000).
doi: 10.1038/labinvest.3780040
Vanni, R., Marras, S., Andria, M. & Faa, G. Endometrial polyps with predominant stromal component are characterized by a t(6;14)(p21;q24) translocation. Cancer Res. 55, 31–33 (1995).
pubmed: 7805036
Speleman, F. et al. Is t(6;20)(p21;q13) a characteristic chromosome change in endometrial polyps? Genes Chromosomes Cancer 3, 318–319 (1991).
doi: 10.1002/gcc.2870030412
Walter, T. A. et al. inv(12)(p11.2q13) in an endometrial polyp. Cancer Genet. Cytogenet. 41, 99–103 (1989).
doi: 10.1016/0165-4608(89)90113-1
Bol, S. et al. An endometrial polyp with a rearrangement of HMGI-C underlying a complex cytogenetic rearrangement involving chromosomes 2 and 12. Cancer Genet. Cytogenet. 90, 88–90 (1996).
doi: 10.1016/0165-4608(96)00062-3
Vanni, R. et al. Endometrial polyp: another benign tumor characterized by 12q13-q15 changes. Cancer Genet. Cytogenet. 68, 32–33 (1993).
doi: 10.1016/0165-4608(93)90070-3
Hennig, Y., Wanschura, S., Deichert, U., Bartnitzke, S. & Bullerdiek, J. Rearrangements of the high mobility group protein family genes and the molecular genetic origin of uterine leiomyomas and endometrial polyps. Mol. Hum. Reprod. 2, 277–283 (1996).
doi: 10.1093/molehr/2.4.277
Dal Cin, P. et al. Amplification and expression of the HMGIC gene in a benign endometrial polyp. Genes Chromosomes Cancer 22, 95–99 (1998).
doi: 10.1002/(SICI)1098-2264(199806)22:2<95::AID-GCC2>3.0.CO;2-1
Takeda, T. et al. Mutations of RAS genes in endometrial polyps. Oncol Rep. 42, 2303–2308 (2019).
pubmed: 31638232
pmcid: 6826305
Hachisuga, T. et al. K-ras mutation in tamoxifen-related endometrial polyps. Cancer 98, 1890–1897 (2003).
Moore, L. et al. The mutational landscape of normal human endometrial epithelium. Nature 580, 640–646 (2020).
doi: 10.1038/s41586-020-2214-z
Clement, P. B. & Scully, R. E. Mullerian adenosarcoma of the uterus: a clinicopathologic analysis of 100 cases with a review of the literature. Hum. Pathol. 21, 363–381 (1990).
doi: 10.1016/0046-8177(90)90198-E
Gallardo, A. & Prat, J. Mullerian adenosarcoma: a clinicopathologic and immunohistochemical study of 55 cases challenging the existence of adenofibroma. Am. J. Surg. Pathol. 33, 278–288 (2009).
doi: 10.1097/PAS.0b013e318181a80d
Manoharan, M., Azmi, M. A. N., Soosay, G., Mould, T. & Weekes, A. R. Mullerian adenosarcoma of uterine cervix: Report of three cases and review of literature. Gynecol. Oncol. 105, 256–260 (2007).
doi: 10.1016/j.ygyno.2006.12.029
Chin, P.-S., Chia, Y.-N., Lim, Y.-K. & Yam, K.-L. Diagnosis and management of Müllerian adenosarcoma of the uterine cervix. Int. J. Gynaecol. Obstet. 121, 229–232 (2013).
doi: 10.1016/j.ijgo.2012.12.015
Verschraegen, C. F. et al. Clinicopathologic analysis of mullerian adenosarcoma: The M.D. anderson cancer center experience. Oncol. Rep. 5, 939–944 (1998).
pubmed: 9625851
Howitt, B. E. et al. Targeted genomic analysis of Müllerian adenosarcoma. J. Pathol. 235, 37–49 (2015).
doi: 10.1002/path.4442
Brooks, S. E., Zhan, M., Cote, T. & Baquet, C. R. Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999. Gynecol. Oncol. 93, 204–208 (2004).
doi: 10.1016/j.ygyno.2003.12.029
Clement, P. B. Müllerian adenosarcomas of the uterus with sarcomatous overgrowth. A clinicopathological analysis of 10 cases. Am. J. Surg. Pathol. 13, 28–38 (1989).
doi: 10.1097/00000478-198901000-00004
Hodgson, A., Amemiya, Y., Seth, A., Djordjevic, B. & Parra-Herran, C. High-grade müllerian adenosarcoma: Genomic and clinicopathologic characterization of a distinct neoplasm with prevalent TP53 pathway alterations and aggressive behavior. Am. J. Surg. Pathol. 41, 1513–1522 (2017).
doi: 10.1097/PAS.0000000000000907
Piscuoglio, S. et al. Uterine adenosarcomas are mesenchymal neoplasms. J. Pathol. 238, 381–388 (2016).
doi: 10.1002/path.4675
Howitt, B. E., Dal Cin, P., Nucci, M. R. & Quade, B. J. Involvement of chromosome 8 in müllerian adenosarcoma. Int. J. Gynecol. Pathol. 36, 24–30 (2017).
doi: 10.1097/PGP.0000000000000287
Lee, J.-C. et al. Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup. Mod. Pathol. 29, 1070–1082 (2016).
doi: 10.1038/modpathol.2016.99
Ban, Y. et al. Whole-Genome Sequencing and Target Validation Analysis of Müllerian Adenosarcoma: A Tumor With Complex but Specific Genetic Alterations. Front Oncol 10, 538 (2020).
doi: 10.3389/fonc.2020.00538
Kerner, H. & Lichtig, C. Müllerian adenosarcoma presenting as cervical polyps: A report of seven cases and review of the literature. Obstet. Gynecol. 81, 655–659 (1993).
pubmed: 8385764
Zaloudek, C. J. & Norris, H. J. Adenofibroma and adenosarcoma of the uterus: a clinicopathologic study of 35 cases. Cancer 48, 354–366 (1981).
doi: 10.1002/1097-0142(19810715)48:2<354::AID-CNCR2820480222>3.0.CO;2-Q
Howitt, B. E., Quade, B. J. & Nucci, M. R. Uterine polyps with features overlapping with those of Müllerian adenosarcoma: A clinicopathologic analysis of 29 cases emphasizing their likely benign nature. Am. J. Surg. Pathol. 39, 116–126 (2015).
doi: 10.1097/PAS.0000000000000303
Tai, L. H. & Tavassoli, F. A. Endometrial polyps with atypical (bizarre) stromal cells. Am. J. Surg. Pathol. 26, 505–509 (2002).
doi: 10.1097/00000478-200204000-00014
Sholl, L. M. et al. Institutional implementation of clinical tumor profiling on an unselected cancer population. JCI. Insight. 1, e87062 (2016).
doi: 10.1172/jci.insight.87062
Bean, G. R., Anderson, J., Sangoi, A. R., Krings, G. & Garg, K. DICER1 mutations are frequent in müllerian adenosarcomas and are independent of rhabdomyosarcomatous differentiation. Mod. Pathol. 32, 280–289 (2019).
doi: 10.1038/s41379-018-0132-5
Agostini, A. et al. Genomic imbalances are involved in miR-30c and let-7a deregulation in ovarian tumors: implications for HMGA2 expression. Oncotarget. 28, 21554–21560 (2017). 8.
doi: 10.18632/oncotarget.15795
Agostini, A. et al. A novel truncated form of HMGA2 in tumors of the ovaries. Oncol. Lett. 12, 1559–1563 (2016).
doi: 10.3892/ol.2016.4805
Nagaishi, M. et al. High HMGA2 expression without gene rearrangement in meningiomas. Neuropathology 40, 540–545 (2020).
doi: 10.1111/neup.12670
Clement, P. B. & Scully, R. E. Müllerian adenofibroma of the uterus with invasion of myometrium and pelvic veins. Int. J. Gynecol. Pathol. 9, 363–371 (1990).
doi: 10.1097/00004347-199010000-00008