The Challenge of Pathological Diagnosis for Precancerous Cervical Lesions

Year 2019, , 39 - 45, 28.04.2019

İlkay Cinar

https://doi.org/10.19127/mbsjohs.521193

Cited By: 2

Abstract

Cervical cancer is the third most common
cancer after breast and colorectal cancers worldwide, and the second most
common gynecological malignancy after endometrial cancer. Cervical cancer screening was first described by
Papanicolaou in 1941 using the PAP smear test. The incidence of invasive
cervical cancer clearly reduced with the common use of PAP smear in developed
countries. The basic methods used for diagnosis of premalignant lesions
of the cervix are determination with colposcopy, biopsy and HPV DNA typing.
Cervical premalignant lesions cannot be observed with the naked eye, other than
exophytic or papillary lesions of condyloma acuminatum. Condyloma acuminatum
are simultaneously LSIL. LSIL and HSIL differentiation cannot be made with
colposcopy. Due to better repeatability and interobserver compliance, the World
Health Organization (WHO) recommends a 2-layer HSIL/LSIL system. In the 3-layer
CIN system, CIN1 is equivalent to LSIL, while CIN3 equivalent is HSIL. The
lesions are frequently encountered in routine biopsies, and in some cases,
differential diagnosis may be difficult. Basal cell hyperplasia, atrophy,
reactive and repair-induced atypia and immature squamous metaplasia may mimic
precancerous lesions. Although histomorphology is gold standard, P16 and Ki-67
are beneficial immunohistochemical ancillary testes. However, it should be kept
in mind that p16 can be positive in LSIL, and negative in HSIL.

Keywords

Cervix, premalignant lesions, pathology

References

• Cuschieri K, Wentzensen N. Human papillomavirus mRNA and p16 detection as biomarkers for the improved diagnosis of cervical neoplasia. Cancer Epidemiol Biomarkers Prev 2008;17: 253645.
• Darragh TM, Colgan TJ, Thomas Cox J, Heller DS, Henry MR, Luff RD, McCalmont T, Nayar R, Palefsky JM, Stoler MH, Wilkinson EJ, Zaino RJ, Wilbur DC; Members of the LAST Project Work Groups. The Lower Anogenital Squamous Terminology Standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Int J Gynecol Pathol. 2013 Jan; 32 (1): 76-115. doi: 10.1097/PGP.0b013e31826916c7. Erratum in: Int J Gynecol Pathol. 2013 Jul; 32 (4): 432. Int J Gynecol Pathol. 2013 Mar; 32 (2): 241.
• Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, Stanley MA.The biology and life-cycle of human papillomaviruses. Vaccine. 2012 Nov 20; 30 Suppl 5: F55-70.
• Edebal Z , Akıncıoğlu E , Kiseli M. Reproducibility of Diagnosis of ASC-US, Reflection of Diagnostic Criteria to Cervical Histopathological Results and Investigation of p16 Antibodies in Cervical Biopsies ASC-US Tanılı Hastalarda Tekrarlanılabilirlik, Tanı Kriterlerinin Servikal Biyopsiye Yansıması ve Servikal Biyopsilerde p16 Antikoru Araştırılması. Acta oncologica turcica. 2017; 50 (1): 50-55.
• Eser SY, Cancer Incidence in Turkey. Karakoç H. Tuncer M (Editör). In: Cancer Control in Turkey, 1. Baskı, Ankara, 776, 2010; 35-50.Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: source, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 2015 Mar 1;136 (5): E 359-86 ). Gültekin M, Boztaş G. Türkiye Kanser İstatistikleri. Ocak 2014
• Gupta M, Basavaraj PK. Histopathological Spectrum of Premalignant and Malignant Lesions of Uterine Cervix . National Journal of Laboratory Medicine. 2018 Jan, Vol-7(1): PO19-PO26.
• Gustinucci D, Passamonti B, Cesarini E, Butera D, Palmieri EA, Bulletti S, Carlani A, Staiano M, D'Amico MR, D'Angelo V, Di Dato E, Martinelli N, Malaspina M, Spita N, Tintori B, Fulciniti F. Role of p16 (INK4a) cytology testing as an adjunct to enhance the diagnostic specificity and accuracy in human papillomaviruspositive women within an organized cervical cancer screening program. Acta Cytol 2012; 56: 506-14.Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, Cheung LC, Raine-Bennett T, Gage JC, Kinney WK. Benchmarking CIN 3+ risk as the basis for incorporating HPV and Pap cotesting into cervical screening and management guidelines. J Low Genit Tract Dis. 2013;17: S28-35.
• Keating JT, Cviko A, Riethdorf S, Riethdorf L Quade BJ, Sun D, Duensing S, Sheets EE, Munger K, Crum CP. Ki-67, cyclin E, and p16INK4 are complimentary surrogate biomarkers for human papilloma virus-related cervical neoplasia. Am J Surg Pathol. 2001 Jul;25(7):884-91.
• Keating JT,Cviko A, Riethdorf S, et al. Ki67, Cyclin E and p16 are complimentary surrogate biomarkers for HPV-related cervical neoplasia. Am Jsurg Pathol. 2001;25:884-891.
• Koss LG, Durfee GR. Unusual patterns of squamous epithelium of the uterine cervix: cytologic and pathologic study of koilocytotic atypia.Ann NY Acad sci.1956 Mar 30;63(6):1245-61.Malpica A, Eucher E. Squomouse lesion of cervix. In:Biopsy interpretation of the uterin cervix and corpus. Wolters kluver,2th edition:2009:16-48.Moore G, Fetterman B, Cox JT, Poitras N, Lorey T, Kinney W, Castle PE.J. Lessons from practice: risk of CIN 3 or cancer associated with an LSIL or HPV-positive ASC-US screening result in women aged 21 to 24. Low Genit Tract Dis. 2010 Apr; 14 (2): 97-102.
• Nayar R, Wilbur DC. The Pap Test and Bethesda 2014. "The reports of my demise have been greatly exaggerated." (after a quotation from Mark Twain). Acta cytol. 2015; 59 (2): 121-32
• Ostor AG. Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol 1993; 12: 186-92.
• Quint KD, de Koning MN, van Doorn LJ, Quint WG, Pirog EC. HPV genotyping and HPV16 variant analysis in glandular and squamous neoplastic lesions of the uterine cervix.Gnecol oncol.2010 May;117(2):297-301.
• Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, Garcia FA, Moriarty AT, Waxman AG, Wilbur DC, Wentzensen N, Downs LS Jr, Spitzer M, Moscicki AB, Franco EL, Stoler MH, Schiffman M, Castle PE, Myers ER; American Cancer Society; American Society for Colposcopy and Cervical Pathology; American Society for Clinical Pathology. American Cancer Society, American Society for Colposcopy and Cervical Pathology and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol. 2012 Apr;137(4):516-42
• Stoler M, Bergeron C, Colgan T:J, Ferenvzy A.S et al. Skuamous cell tumors and precursors,in Kurman RJ,ed: WHO Classification of Tumors of Female Reproductive organs. 4th edition, Lyon, 2014 :172-182.
• Stoler MH, Schiffman M. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA 2001; 285: 1500-1505.
• Stoler MH. Human papillomaviruses and cervical neoplasia: a model for carcinogenesis.Int J Gynecol Pathol. 2000 Jan;19 (1):16-28.Sun M, Shen Y, Ren ML, Dong YM. Meta analysis on the performance of p16/Ki67 dual immunostaining in detecting highgrade cervical intraepithelial neoplasm. J Cancer Res Ther. 2018 Sep;14 (Supplement): S587-S593. doi: 10.4103/0973-1482.183216.
• Tsoumpou I, Arbyn M, Kyrgiou M, Wentzensen N, Koliopoulos G, Martin-Hirsch P, Paraskevaidis E. p16INK4a immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis. Cancer Treat Rev. 2009; 35 (3): 210-20.
• Voltaggio L, Cimino-Mathews A, Bishop JA, Argani P, Cuda JD, Epstein JI, Hruban RH, Netto GJ, Stoler MH, Taube JM, Vang R, Westra WH, Montgomery EA. Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia: A review by organ system. CA Cancer J Clin. 2016 Sep; 66 (5): 408-36.
• Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189 (1):12-19.
• Wentzensen N, von Knebel Doeberitz M. Biomarkers in cervical cancer screening. Dis Markers. 2007; 23 (4): 315-30.
• Wright TC, Ferenczy A. Benign disease of the cervix. İn:Kurman RJ,ed. Blaustein's pathology of The female genital tract. Newyork: Springer-Verlag; 2001:225-252.