Abstract: Uteri from women undergoing chemoradiotherapy (CRT) may show reactive atypia which may mimic serous endometrial intraepithelial carcinoma (SEIC). We aimed to assess the prevalence and morphological/immunohistochemical features of post-radiotherapy serous-like endometrial changes (PoRSEC) in women undergone CRT for locally advanced cervical cancer, with a focus on the differential diagnosis with SEIC. Consecutive patients with locally advanced cervical cancer undergone CRT between 2011 and 2018 were reviewed. Endometrial histological specimens were assessed for the presence of PoRSEC. Twenty-two cases of SEIC were included for comparison. Immunohistochemistry for p53, p16, and Ki67 was performed. Out of 244 reviewed patients, 36 (14.7%) showed PoRSEC. The degree of nuclear atypia was similar between PoRSECs and SEIC. However, a papillary architecture with areas of confluent papillae was only observed in SEIC. SEIC cases showed a high mitotic activity as opposed to PoRSEC cases. The expression of p53 was aberrant in all SEICs but in none of the PoRSECs; however, 13/36 PoRSECs showed p53 positivity in most tumor cells, potentially mimicking a mutation pattern. A block-type p16 expression was observed in all SEICs and in 16/36 PoRSECs. Mean Ki67 expression was 26.9% in SEIC (range 5-70%) and 8.16% in PoRSEC (range 5-35%). While SEIC showed sharp morphological and immunohistochemical demarcation, PoRSEC were more heterogenous and merged imperceptibly with normal endometrium. In conclusion, PoRSEC may mimic SEIC both morphologically and immunohistochemically. However, a papillary architecture with cytological demarcation is typically observed in SEIC but not in PoRSEC.
Competing Interests: Declarations. Consent to participate: A written consent was obtained from the patient. Data were anonymized. Conflict of interest: The authors declare no competing interests.
(© 2024. The Author(s).)
References: Markovina S, Rendle KA, Cohen AC et al (2022) Improving cervical cancer survival-a multifaceted strategy to sustain progress for this global problem. Cancer 128(23):4074–4084. (PMID: 10.1002/cncr.3448536239006)
Lesack D, Wahab I, Gilks CB (1996) Radiation-induced atypia of endocervical epithelium: a histological, immunohistochemical and cytometric study. Int J Gynecol Pathol 15(3):242–247. (PMID: 10.1097/00004347-199607000-000098811386)
Kim EK, Yoon G, Kim HS (2016) Chemotherapy-induced endometrial pathology: mimicry of malignancy and viral endometritis. Am J Transl Res 8(5):2459–2467. (PMID: 273473554891460)
Wales C, Fadare O (2018) Chemotherapy-associated endometrial atypia: a potential diagnostic pitfall. Int J Surg Pathol 26(3):229–231. (PMID: 10.1177/106689691774155229482404)
Travaglino A, Inzani F, Santoro A et al (2021) Endometrial metaplastic/reactive changes coexistent with endometrial hyperplasia and carcinoma: a morphological and immunohistochemical study. Diagnostics (Basel) 12(1):63. (PMID: 10.3390/diagnostics1201006335054228)
Angelico G, Santoro A, Inzani F et al (2021) An emerging anti-p16 antibody-BC42 clone as an alternative to the current E6H4 for use in the female genital tract pathological diagnosis: our experience and a review on p16ink4a functional significance, role in daily-practice diagnosis, prognostic potential, and technical pitfalls. Diagnostics 11(4):713. (PMID: 10.3390/diagnostics11040713339234278073999)
Nicolae A, Preda O, Nogales FF (2011) Endometrial metaplasias and reactive changes: a spectrum of altered differentiation. J Clin Pathol 64(2):97–106. (PMID: 10.1136/jcp.2010.08555521126963)
Ip PP (2018) Benign endometrial proliferations mimicking malignancies: a review of problematic entities in small biopsy specimens. Virchows Arch 472(6):907–917. (PMID: 10.1007/s00428-018-2314-429445890)
McCluggage WG, McBride HA (2012) Papillary syncytial metaplasia associated with endometrial breakdown exhibits an immunophenotype that overlaps with uterine serous carcinoma. Int J Gynecol Pathol 31(3):206–210. (PMID: 10.1097/PGP.0b013e31823bb1a122498936)
Simon RA, Peng SL, Liu F et al (2011) Tubal metaplasia of the endometrium with cytologic atypia: analysis of p53, Ki-67, TERT, and long-term follow-up. Mod Pathol 24(9):1254–1261. (PMID: 10.1038/modpathol.2011.7821572399)
Travaglino A, Raffone A, Saccone G et al (2019) Endometrial hyperplasia and the risk of coexistent cancer: WHO versus EIN criteria. Histopathology 74(5):676–687. (PMID: 10.1111/his.1377630347477)
Liu D, Chen T, Yu K et al (2022) A 2-tier subdivision of papillary proliferations of the endometrium (PPE) only emphasizing the complexity of papillae precisely predicts the neoplastic risk and reflects the neoplasia-related molecular characteristics-a single-centered analysis of 207 cases. Virchows Arch 481(4):585–593. (PMID: 10.1007/s00428-022-03367-8357968059534819)
Zheng W, Xiang L, Fadare O, Kong B (2011) A proposed model for endometrial serous carcinogenesis. Am J Surg Pathol 35(1):e1–e14. (PMID: 10.1097/PAS.0b013e318202772e21164282)
Köbel M, Ronnett BM, Singh N, Soslow RA, Gilks CB, McCluggage WG (2019) Interpretation of P53 immunohistochemistry in endometrial carcinomas: toward increased reproducibility. Int J Gynecol Pathol. 38 Suppl 1(Iss 1 Suppl 1):S123-S131.
Nafisi H, Ghorab Z, Ismill N et al (2015) Immunophenotypic analysis in Early Müllerian serous carcinogenesis. Int J Gynecol Pathol 34(5):424–436. (PMID: 10.1097/PGP.000000000000017926107560)
No Comments.