Silva invasion pattern can help predict lymph node metastasis risk in endocervical adenocarcinoma. We analysed Silva pattern of invasion and lymphovascular invasion to determine associations with clinical outcomes in stage IA and IB1 endocervical adenocarcinomas. International Federation of Gynecology and Obstetrics (FIGO; 2019 classification) stage IA-IB1 endocervical adenocarcinomas from 15 international institutions were examined for Silva pattern, presence of lymphovascular invasion, and other prognostic parameters. Lymph node metastasis status, local/distant recurrences, and survival data were compared using appropriate statistical tests. Of 399 tumours, 152 (38.1%) were stage IA [IA1, 77 (19.3%); IA2, 75 (18.8%)] and 247 (61.9%) were stage IB1. On multivariate analysis, lymphovascular invasion (p=0.008) and Silva pattern (p<0.001) were significant factors when comparing stage IA versus IB1 endocervical adenocarcinomas. Overall survival was significantly associated with lymph node metastasis (p=0.028); recurrence-free survival was significantly associated with lymphovascular invasion (p=0.002) and stage (1B1 versus 1A) (p=0.002). Five and 10 year overall survival and recurrence-free survival rates were similar among Silva pattern A cases and Silva pattern B cases without lymphovascular invasion (p=0.165 and p=0.171, respectively). Silva pattern and lymphovascular invasion are important prognostic factors in stage IA1-IB1 endocervical adenocarcinomas and can supplement 2019 International Federation of Gynecology and Obstetrics staging. Our binary Silva classification system groups patients into low risk (patterns A and B without lymphovascular invasion) and high risk (pattern B with lymphovascular invasion and pattern C) categories.

Brigham and Women's Hospital Boston MA USA

Department of Human Pathology University of Messina Messina Italy

Department of Pathology 1st Medical Faculty Charles University and General University Hospital Prague Prague Czech Republic

Department of Pathology A C Camargo Cancer Center São Paulo Brazil

Department of Pathology and Laboratory Medicine The University of British Columbia Vancouver BC Canada

Department of Pathology Hospital Garcia de Orta Almada Portugal

Department of Pathology Hospital Universitari de Bellvitge IDIBELL Barcelona Spain

Department of Pathology Jikei University School of Medicine Tokyo Japan

Department of Pathology Memorial Sloan Kettering Cancer Center New York NY USA

Department of Pathology University Hospital of Saint Etienne Saint Priest en Jarez France

Department of Pathology University of Medicine Pharmacy Sciences and Technology Targu Mures Romania

Department of Surgical Oncology A C Camargo Cancer Center São Paulo Brazil

Gynecology Service Department of Surgery Memorial Sloan Kettering Cancer Center New York NY USA; Department of Obstetrics and Gynaecology Weill Cornell Medical College New York NY USA

IRCSS Ospedale Sacro Cuore Don Calabria Negrar Italy

Massachusetts General Hospital Boston MA USA

NOVA Medical School UNL Department of Pathology Instituto Portugues de Oncologia Lisbon Portugal

University of California San Diego La Jolla CA USA

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WHO Classification of Tumours Editorial Board. WHO Classification of Tumours: Female Genital Tumours. 5th ed. Lyon: IARC, 2020.

Stolnicu S, Hoang L, Chiu D, et al. Clinical outcomes of HPV-associated and unassociated endocervical adenocarcinomas categorized by the international endocervical adenocarcinoma criteria and classification (IECC). Am J Surg Pathol 2019; 43: 466–74. PubMed PMC

Stolnicu S, Barsan I, Hoang L, et al. International Endocervical Adenocarcinoma Criteria and Classification (IECC): a new pathogenetic classification for invasive adenocarcinomas of the endocervix. Am J Surg Pathol 2018; 42: 214–26. PubMed PMC

Baalbergen A, Ewing-Graham PC, Hop WC, Struijk P, Helmerhorst TJ. Prognostic factors in adenocarcinoma of the uterine cervix. Gynecol Oncol 2004; 92: 262–7. PubMed

Stolnicu S, Boros M, Hoang L, et al. FIGO 2018 stage IB endocervical adenocarcinomas: an international study of outcomes informed by prognostic biomarkers. Int J Gynecol Cancer 2021; 31: 177–84. PubMed PMC

Diaz De Vivar A, Roma AA, Park KJ, et al. Invasive endocervical adenocarcinoma: proposal for a new pattern-based classification system with significant clinical implications: a multi-institutional study. Int J Gynecol Pathol 2013; 32: 592–601. PubMed

Bhatla N, Berek JS, Cuello Fredes M, et al. Revised FIGO staging for carcinoma of the cervix uteri. Int J Gynaecol Obstet 2019; 145: 129–35. PubMed

Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri. Int J Gynaecol Obstet 2018; 143 (Suppl 2): 22–36. PubMed

Zyla RE, Gien LT, Vicus D, et al. The prognostic role of horizontal and circumferential tumor extent in cervical cancer: implications for the 2019 FIGO staging system. Gynecol Oncol 2020; 158: 266–72. PubMed

National Comprehensive Cancer Network. NCCN Guidelines: Cervical Cancer Version 2.2020. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1426.

Ren H, Almadani N, Pors J, et al. International Endocervical Adenocarcinoma Criteria and Classification (IECC): an independent cohort with clinical and molecular findings. Int J Gynecol Pathol 2021; 40: 533–40. PubMed

Ren H, Pors J, Chow C, et al. Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system compared to p16 immunohistochemistry and HPV RNA in-situ hybridization. J Pathol Transl Med 2020; 54: 480–8. PubMed PMC

Ondic O, Nemcova J, Alaghehbandan R, et al. The newly proposed International Endocervical Adenocarcinoma Criteria and Classification and its relevance to cervical cytology screening assessed in a prospective 2-year study of 118 cases. Cytopathology 2020; 31: 288–91. PubMed

Hodgson A, Olkhov-Mitsel E, Howitt BE, Nucci MR, Parra-Herran C. International Endocervical Adenocarcinoma Criteria and Classification (IECC): correlation with adverse clinicopathological features and patient outcome. J Clin Pathol 2019; 72: 347–53. PubMed

Hodgson A, Park KJ, Djordjevic B, et al. International Endocervical Adenocarcinoma Criteria and Classification: validation and interobserver reproducibility. Am J Surg Pathol 2019; 43: 75–83. PubMed PMC

Park KJ, Cabrero IA, Fadare O, et al. Online training and self-assessment in the histopathologic classification of endocervical adenocarcinoma and diagnosis of pattern of invasion: evaluation of participant performance. Int J Gynecol Pathol 2021; 40 (Suppl 1): S14–23. PubMed PMC

Stolnicu S, Barsan I, Hoang L, et al. Stromal invasion pattern identifies patients at lowest risk of lymph node metastases in HPV-associated endocervical adenocarcinomas but is irrelevant in adenocarcinomas unassociated with HPV. Gynecol Oncol 2018; 150: 56–60. PubMed PMC

Alvarado-Cabrero I, Parra-Herran C, Stolnicu S, Roma A, Oliva E, Malpica A. The Silva pattern-based classification for HPV-associated invasive endocervical adenocarcinoma and the distinction between in situ and invasive adenocarcinoma: relevant issues and recommendations from the International Society of Gynecological Pathologists. Int J Gynecol Pathol 2021; 40 (Suppl 1): S48–65. PubMed PMC

Talia KL, Oliva E, Rabban JT, Singh N, Stolnicu S, McCluggage WG. Grading of endocervical adenocarcinomas: review of the literature and recommendations from the International Society of Gynecological Pathologists. Int J Gynecol Pathol 2021; 40 (Suppl 1): S66–74. PubMed PMC

College of American Pathologists. Protocol for the Examination of Excision Specimens from Patients with Primary Carcinoma of the Uterine Cervix. Version 4.3.0.0. Updated February 2020; cited 24 June 2021. https://documents.cap.org/protocols/cp-femalereproductive-uterinecervix-excision-204300.pdf.

Amin MB, Edge S, Greene F, et al., editors. AJCC Cancer Staging Manual. 8th ed. New York: Springer, 2017.

McCluggage WG, Alvarado-Cabrero I, Duggan MA, et al. Cervical Carcinoma Histopathology Reporting Guide 3rd edition. Sydney: International Collaboration on Cancer Reporting, 2020. https://www.iccr-cancer.org/ICCR/media/Documents/ICCR-cervix-3rd-edn-v1-0-bookmarked-guide.pdf

Roma AA, Fadare O. The pattern is the issue: recent advances in adenocarcinoma of the uterine cervix. Virchows Arch 2018; 472: 897–905. PubMed