The reporting of anal cytology and histology samples: establishing terminology and criteria
Jennifer Margaret Roberts A B and Deborah Ekman A
+ Author Affiliations
- Author Affiliations
A Douglass Hanly Moir Pathology, 14 Giffnock Avenue, Macquarie Park, NSW 2113, Australia.
B Corresponding author. Email: jroberts@dhm.com.au
Sexual Health 9(6) 562-567 https://doi.org/10.1071/SH10140
Submitted: 3 November 2010 Accepted: 7 February 2012 Published: 25 May 2012
Abstract
Our understanding of the human papillomavirus (HPV) related cytomorphology and histopathology of the anal canal is underpinned by our knowledge of HPV infection in the cervix. In this review, we utilise cervical reporting of cytological and histological specimens as a foundation for the development of standardised and evidence-based terminology and criteria for reporting of anal specimens. We advocate use of the Australian Modified Bethesda System 2004 for reporting anal cytology. We propose the use of a two-tiered histological reporting system for noninvasive disease – low-grade and high-grade anal intraepithelial neoplasia. These classification systems reflect current understanding of the biology of HPV and enhance diagnostic reproducibility. Biomarkers such as p16INK4A may prove useful in further improving diagnostic accuracy. Standardisation is important because it will increase the value of the data collected as Australian centres develop programs for screening for anal neoplasia.
Additional keywords: anal canal, anal intraepithelial neoplasia, Australian Modified Bethesda System, human papillomavirus, liquid-based cytology.
References
[1] Darragh TM, Berry JM, Jay N, Palefsky JM. Anal Disease. In Apgar BS, Brotzman GL, Spitzer M, editors. Colposcopy: principles and practice, 2nd ed. Philadelphia: Saunders Elsevier; 2008. pp. 451–81.[2] Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D. GLOBOCAN 2008, cancer incidence and mortality worldwide: IARC CancerBase no. 10. Lyon, France: International Agency for Research on Cancer; 2010. Available online at: http://globocan.iarc.fr [verified February 2012].
[3] Australian Institute of Health and Welfare (AIHW). Cervical screening in Australia 2008–2009. Cancer series no. 61, Cat. no. CAN 57. Canberra: AIHW; 2011.
[4] Schneider V. Symposium part 2: Should the Bethesda System terminology be used in diagnostic surgical pathology? Counterpoint. Int J Gynecol Pathol 2003; 22 13–7.
| Symposium part 2: Should the Bethesda System terminology be used in diagnostic surgical pathology? Counterpoint.Crossref | GoogleScholarGoogle Scholar | 12496691PubMed |
[5] Solomon D, Nayar R. The Bethesda System for reporting cervical cytology. New York: Springer; 2004.
[6] National Health and Medical Research Council (NHMRC). Screening to prevent cervical cancer: guidelines for the management of asymptomatic women with screen detected abnormalities. Canberra: NHMRC; 2005. Available online at: http://www.nhmrc.gov.au/publications/synopses/wh39syn.htm [verified 24 February 2012].
[7] Vajdic CM, Anderson JS, Hillman RJ, Medley G, Grulich AE. Blind sampling is superior to anoscope guided sampling for screening for anal intraepithelial neoplasia. Sex Transm Infect 2005; 81 415–8.
| Blind sampling is superior to anoscope guided sampling for screening for anal intraepithelial neoplasia.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2Mris1altA%3D%3D&md5=130af0e8186b1f1b178cdb0909d2a342CAS | 16199742PubMed |
[8] Chin-Hong PV, Berry JM, Cheng SC, Catania JA, Da Costa M, Darragh TM, et al Comparison of patient- and clinician-collected anal cytology samples to screen for human papillomavirus-associated anal intraepithelial neoplasia in men who have sex with men. Ann Intern Med 2008; 149 300–6.
| 18765699PubMed |
[9] Sherman ME, Friedman HB, Busseniers AE, Kelly WF, Carner TC, Saah AJ. Cytologic diagnosis of anal intraepithelial neoplasia using smears and cytyc thin-preps. Mod Pathol 1995; 8 270–4.
| 1:STN:280:DyaK2Mzkt1yqsQ%3D%3D&md5=7f5f79a878252110df3d1661229dd698CAS | 7617653PubMed |
[10] Darragh TM, Jay N, Tupkelewicz BA, Hogeboom CJ, Holly EA, Palefsky JM. Comparison of conventional cytologic smears and ThinPrep preparations from the anal canal. Acta Cytol 1997; 41 1167–70.
| Comparison of conventional cytologic smears and ThinPrep preparations from the anal canal.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2szptlyqsA%3D%3D&md5=f5345219e22404e8656b52f5dfb97dd9CAS | 9250316PubMed |
[11] Crum CP. Symposium part 1: Should the Bethesda System terminology be used in diagnostic surgical pathology? Point. Int J Gynecol Pathol 2003; 22 5–12.
| Symposium part 1: Should the Bethesda System terminology be used in diagnostic surgical pathology? Point.Crossref | GoogleScholarGoogle Scholar | 12496690PubMed |
[12] Castle PE, Gage JC, Wheeler CM, Schiffman M. The clinical meaning of a cervical intraepithelial neoplasia grade 1 biopsy. Obstet Gynecol 2011; 118 1222–9.
| The clinical meaning of a cervical intraepithelial neoplasia grade 1 biopsy.Crossref | GoogleScholarGoogle Scholar | 22105250PubMed |
[13] Darragh T, Birdsong G, Luff RD, Davey D. Anal–rectal cytology. In Solomon D, Nayar R, editors. The Bethesda System for reporting cervical cytology. New York: Springer; 2004. pp. 169–75.
[14] Linder J. Specimen adequacy. In Wernicke SM, editor. ThinPrep™ Pap test morphology reference atlas. Boxborough: Cytyc; 2003. pp. 11–8.
[15] Mintzer M, Curtis P, Resnick JC, Morrell D. The effect of the quality of Papanicolaou smears on the detection of cytologic abnormalities. Cancer 1999; 87 113–7.
| The effect of the quality of Papanicolaou smears on the detection of cytologic abnormalities.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1Mzht1WltQ%3D%3D&md5=746cb5b72700f074d7d1a0230c12e8f1CAS | 10385441PubMed |
[16] Elias A, Linthorst G, Bekker B, Vooijs PG. The significance of endocervical cells in the diagnosis of cervical epithelial changes. Acta Cytol 1983; 27 225–9.
| 1:STN:280:DyaL3s3ltF2lsg%3D%3D&md5=465f716978d578418eaedd694cc2930bCAS | 6575534PubMed |
[17] Vooijs PG, Elias A, van der Graaf Y, Veling S. Relationship between the diagnosis of epithelial abnormalities and the composition of cervical smears. Acta Cytol 1985; 29 323–8.
| 1:STN:280:DyaL2M3itFamsA%3D%3D&md5=b8432e8ada08c5013d0529013f343964CAS | 3859130PubMed |
[18] Mitchell H, Medley G. Cytological reporting of cervical abnormalities according to endocervical status. Br J Cancer 1993; 67 585–8.
| Cytological reporting of cervical abnormalities according to endocervical status.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3s7ns1OjsQ%3D%3D&md5=3c4b0a8754541c60a0c1b59913296540CAS | 8439508PubMed |
[19] Mitchell H, Medley G. Longitudinal study of women with negative cervical smears according to endocervical status. Lancet 1991; 337 265–7.
| Longitudinal study of women with negative cervical smears according to endocervical status.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3M7gvFCnsQ%3D%3D&md5=c1c600f76777a46ed74144b07d75ac89CAS | 1671112PubMed |
[20] Mitchell HS. Longitudinal analysis of histologic high-grade disease after negative cervical cytology according to endocervical status. Cancer 2001; 93 237–40.
| Longitudinal analysis of histologic high-grade disease after negative cervical cytology according to endocervical status.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3Mvmt1WntQ%3D%3D&md5=e9b7685e1a86186fef7f338153ed2442CAS | 11507695PubMed |
[21] Arain S, Walts AE, Thomas P, Bose S. The anal Pap smear: cytomorphology of squamous intraepithelial lesions. Cytojournal 2005; 2 4
| The anal Pap smear: cytomorphology of squamous intraepithelial lesions.Crossref | GoogleScholarGoogle Scholar | 15715910PubMed |
[22] Bakotic WL, Willis D, Birdsong G, Tadros TS. Anal cytology in an HIV-positive population: a retrospective analysis. Acta Cytol 2005; 49 163–8.
| Anal cytology in an HIV-positive population: a retrospective analysis.Crossref | GoogleScholarGoogle Scholar | 15839621PubMed |
[23] Friedlander MA, Stier E, Lin O. Anorectal cytology as a screening tool for anal squamous lesions: cytologic, anoscopic, and histologic correlation. Cancer 2004; 102 19–26.
| Anorectal cytology as a screening tool for anal squamous lesions: cytologic, anoscopic, and histologic correlation.Crossref | GoogleScholarGoogle Scholar | 14968414PubMed |
[24] Wright TC, Gatscha RM, Luff RD, Prey MU. Epithelial cell abnormalities: squamous. In Solomon D, Nayar R, editors. The Bethesda System for reporting cervical cytology. New York: Springer; 2004. pp. 89–121.
[25] Bean SM, Chhieng DC. Anal–rectal cytology: a review. Diagn Cytopathol 2010; 38 538–46.
| Anal–rectal cytology: a review.Crossref | GoogleScholarGoogle Scholar | 19941374PubMed |
[26] Darragh TM, Winkler B. Anal cancer and cervical cancer screening: key differences. Cancer 2011; 119 5–19.
| Anal cancer and cervical cancer screening: key differences.Crossref | GoogleScholarGoogle Scholar |
[27] Welton ML, Sharkey FE, Kahlenberg MS. The etiology and epidemiology of anal cancer. Surg Oncol Clin N Am 2004; 13 263–75.
| The etiology and epidemiology of anal cancer.Crossref | GoogleScholarGoogle Scholar | 15137956PubMed |
[28] Welton MLR, Bosman F. Chapter 9. Tumours of the anal canal. In Bosman F, Carneiro F, Hruban R, Theise N, editors. WHO Classification of tumours of the digestive system. 4th ed. Lyon: International Agency for Research on Cancer; 2010. pp183–193.
[29] Walts AE, Thomas P, Bose S. Anal cytology: is there a role for reflex HPV DNA testing? Diagn Cytopathol 2005; 33 152–6.
| Anal cytology: is there a role for reflex HPV DNA testing?Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2MvivFGksA%3D%3D&md5=d09a818f2d4eb262b52b5cd2e154b51bCAS | 16078257PubMed |
[30] Fox PA, Seet JE, Stebbing J, Francis N, Barton SE, Strauss S, et al The value of anal cytology and human papillomavirus typing in the detection of anal intraepithelial neoplasia: a review of cases from an anoscopy clinic. Sex Transm Infect 2005; 81 142–6.
| The value of anal cytology and human papillomavirus typing in the detection of anal intraepithelial neoplasia: a review of cases from an anoscopy clinic.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2M7mvVyiuw%3D%3D&md5=8ddbae3f68d70472b12622650082cd79CAS | 15800092PubMed |
[31] Scott H, Khoury J, Moore BA, Weissman S. Routine anal cytology screening for anal squamous intraepithelial lesions in an urban HIV clinic. Sex Transm Dis 2008; 35 197–202.
| Routine anal cytology screening for anal squamous intraepithelial lesions in an urban HIV clinic.Crossref | GoogleScholarGoogle Scholar | 18216727PubMed |
[32] Nathan M, Singh N, Garrett N, Hickey N, Prevost T, Sheaff M. Performance of anal cytology in a clinical setting when measured against histology and high-resolution anoscopy findings. AIDS 2010; 24 373–9.
| Performance of anal cytology in a clinical setting when measured against histology and high-resolution anoscopy findings.Crossref | GoogleScholarGoogle Scholar | 20057313PubMed |
[33] Bean SM, Chhieng DC, Roberson J, Raper JL, Broker TR, Hoesley CJ, et al Anal–rectal cytology: correlation with human papillomavirus status and biopsy diagnoses in a population of HIV-positive patients. J Low Genit Tract Dis 2010; 14 90–6.
| Anal–rectal cytology: correlation with human papillomavirus status and biopsy diagnoses in a population of HIV-positive patients.Crossref | GoogleScholarGoogle Scholar | 20354415PubMed |
[34] Nahas CS, da Silva Filho EV, Segurado AA, Genevcius RF, Gerhard R, Gutierrez EB, et al Screening anal dysplasia in HIV-infected patients: is there an agreement between anal Pap smear and high-resolution anoscopy-guided biopsy? Dis Colon Rectum 2009; 52 1854–60.
| Screening anal dysplasia in HIV-infected patients: is there an agreement between anal Pap smear and high-resolution anoscopy-guided biopsy?Crossref | GoogleScholarGoogle Scholar | 19966632PubMed |
[35] Longacre TA, Kong CS, Welton ML. Diagnostic problems in anal pathology. Adv Anat Pathol 2008; 15 263–78.
| Diagnostic problems in anal pathology.Crossref | GoogleScholarGoogle Scholar | 18724100PubMed |
[36] Berry JM, Palefsky JM, Jay N, Cheng SC, Darragh TM, Chin-Hong PV. Performance characteristics of anal cytology and human papillomavirus testing in patients with high-resolution anoscopy-guided biopsy of high-grade anal intraepithelial neoplasia. Dis Colon Rectum 2009; 52 239–47.
| Performance characteristics of anal cytology and human papillomavirus testing in patients with high-resolution anoscopy-guided biopsy of high-grade anal intraepithelial neoplasia.Crossref | GoogleScholarGoogle Scholar | 19279418PubMed |
[37] Castle PE, Stoler MH, Solomon D, Schiffman M. The relationship of community biopsy-diagnosed cervical intraepithelial neoplasia grade 2 to the quality control pathology-reviewed diagnoses: an ALTS report. Am J Clin Pathol 2007; 127 805–15.
| The relationship of community biopsy-diagnosed cervical intraepithelial neoplasia grade 2 to the quality control pathology-reviewed diagnoses: an ALTS report.Crossref | GoogleScholarGoogle Scholar | 17439841PubMed |
[38] Syrjanen K, Kataja V, Yliskoski M, Chang F, Syrjanen S, Saarikoski S. Natural history of cervical human papillomavirus lesions does not substantiate the biologic relevance of the Bethesda System. Obstetrics and Gynecology 1992; 79 675–82.
| 1:STN:280:DyaK383ivVemsQ%3D%3D&md5=3050374d72337cbdd8ee8f293e2d5d3eCAS | 1314359PubMed |
[39] Lytwyn A, Salit IE, Raboud J, Chapman W, Darragh T, Winkler B, et al Interobserver agreement in the interpretation of anal intraepithelial neoplasia. Cancer 2005; 103 1447–56.
| Interobserver agreement in the interpretation of anal intraepithelial neoplasia.Crossref | GoogleScholarGoogle Scholar | 15726546PubMed |
[40] College of American Pathology, Pathology and Laboratory Quality Center and the ASCCP Consensus Conference. The Lower Anogenital Squamous Terminology Standardization project (the LAST project). Northfield: College of American Pathologists;2012. Available online at: http://www.asccp.org/PracticeManagement/LASTProject/tabid/10967/Default.aspx [verified January 2012].
[41] Oh KY-T, Palefsky J. Diseases of the anus. In Crum CP, Lee KR, editors. Diagnostic gynecologic and obstetric pathology. Philadelphia: Elsevier Saunders; 2006. pp. 199–227.
[42] McCloskey JC, Metcalf C, French MA, Flexman JP, Burke V, Beilin LJ. The frequency of high-grade intraepithelial neoplasia in anal/perianal warts is higher than previously recognized. Int J STD AIDS 2007; 18 538–42.
| The frequency of high-grade intraepithelial neoplasia in anal/perianal warts is higher than previously recognized.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2svmvVeguw%3D%3D&md5=671a1db00dc9da56c13b458ffe42232aCAS | 17686215PubMed |
[43] Pirog EC, Quint KD, Yantiss RK. P16/CDKN2A and Ki-67 enhance the detection of anal intraepithelial neoplasia and condyloma and correlate with human papillomavirus detection by polymerase chain reaction. Am J Surg Pathol 2010; 34 1449–55.
| P16/CDKN2A and Ki-67 enhance the detection of anal intraepithelial neoplasia and condyloma and correlate with human papillomavirus detection by polymerase chain reaction.Crossref | GoogleScholarGoogle Scholar | 20871219PubMed |
[44] Nahas CS, Lin O, Weiser MR, Temple LK, Wong WD, Stier EA. Prevalence of perianal intraepithelial neoplasia in HIV-infected patients referred for high-resolution anoscopy. Dis Colon Rectum 2006; 49 1581–6.
| Prevalence of perianal intraepithelial neoplasia in HIV-infected patients referred for high-resolution anoscopy.Crossref | GoogleScholarGoogle Scholar | 16977374PubMed |
[45] Tsoumpou I, Arbyn M, Kyrgiou M, Wentzensen N, Koliopoulos G, Martin-Hirsch P, et al p16INK4a immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis. Cancer Treat Rev 2009; 35 210–20.
| p16INK4a immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXksVantr0%3D&md5=9a8f4a7415247e4c19268c09aed33531CAS | 19261387PubMed |
[46] Bernard JE, Butler MO, Sandweiss L, Weidner N. Anal intraepithelial neoplasia: correlation of grade with p16INK4a immunohistochemistry and HPV in situ hybridization. Appl Immunohistochem Mol Morphol 2008; 16 215–20.
| Anal intraepithelial neoplasia: correlation of grade with p16INK4a immunohistochemistry and HPV in situ hybridization.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXnsVKrtL4%3D&md5=69c1c7ae79dfbbaf7f35b850b9e0fa9aCAS | 18301250PubMed |
[47] Kreuter A, Jesse M, Potthoff A, Brockmeyer NH, Gambichler T, Stucker M, et al Expression of proliferative biomarkers in anal intraepithelial neoplasia of HIV-positive men. J Am Acad Dermatol 2010; 63 490–8.
| Expression of proliferative biomarkers in anal intraepithelial neoplasia of HIV-positive men.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtVersb3N&md5=5b06ca547a0e00e54477ab2eb28b8b3dCAS | 20006407PubMed |
[48] Bean SM, Eltoum I, Horton DK, Whitlow L, Chhieng DC. Immunohistochemical expression of p16 and Ki-67 correlates with degree of anal intraepithelial neoplasia. Am J Surg Pathol 2007; 31 555–61.
| Immunohistochemical expression of p16 and Ki-67 correlates with degree of anal intraepithelial neoplasia.Crossref | GoogleScholarGoogle Scholar | 17414102PubMed |
[49] Bean SM, Meara RS, Vollmer RT, Conner MG, Crowe DR, Novak L, et al p16 Improves interobserver agreement in diagnosis of anal intraepithelial neoplasia. J Low Genit Tract Dis 2009; 13 145–53.
| p16 Improves interobserver agreement in diagnosis of anal intraepithelial neoplasia.Crossref | GoogleScholarGoogle Scholar | 19550211PubMed |
[50] Walts AE, Lechago J, Bose S. P16 and Ki67 immunostaining is a useful adjunct in the assessment of biopsies for HPV-associated anal intraepithelial neoplasia. Am J Surg Pathol 2006; 30 795–801.
| P16 and Ki67 immunostaining is a useful adjunct in the assessment of biopsies for HPV-associated anal intraepithelial neoplasia.Crossref | GoogleScholarGoogle Scholar | 16819320PubMed |
[51] Scarpini C, White V, Muralidhar B, Patterson A, Hickey N, Singh N, et al Improved screening for anal neoplasia by immunocytochemical detection of minichromosome maintenance proteins. Cancer Epidemiol Biomarkers Prev 2008; 17 2855–64.
| Improved screening for anal neoplasia by immunocytochemical detection of minichromosome maintenance proteins.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1egt7jE&md5=9d3035845152b5af43d2c518dc2d28d2CAS | 18843031PubMed |
[52] Darvishian F, Stier EA, Soslow RA, Lin O. Immunoreactivity of p16 in anal cytology specimens: histologic correlation. Cancer 2006; 108 66–71.
| Immunoreactivity of p16 in anal cytology specimens: histologic correlation.Crossref | GoogleScholarGoogle Scholar | 16404747PubMed |
[53] Tramujas da Costae Silva I, Coelho Ribeiro M, Santos Gimenez F, Dutra Ferreira JR, Galvao RS, Vasco Hargreaves PE, et al Performance of p16INK4a immunocytochemistry as a marker of anal squamous intraepithelial lesions. Cancer Cytopathol. 2011; 119 167–76.
| Performance of p16INK4a immunocytochemistry as a marker of anal squamous intraepithelial lesions.Crossref | GoogleScholarGoogle Scholar |
[54] Meyer JL, Hanlon DW, Andersen BT, Rasmussen OF, Bisgaard K. Evaluation of p16INK4a expression in ThinPrep cervical specimens with the CINtec p16INK4a assay: correlation with biopsy follow-up results. Cancer 2007; 111 83–92.
| Evaluation of p16INK4a expression in ThinPrep cervical specimens with the CINtec p16INK4a assay: correlation with biopsy follow-up results.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXlsVCgsrg%3D&md5=9f22ca8e3538c76dfdf80957877e6b38CAS | 17334990PubMed |
[55] Katz KA, Clarke CA, Bernstein KT, Katz MH, Klausner JD. Is there a proven link between anal cancer screening and reduced morbidity or mortality? Ann Intern Med 2009; 150 283–4.
| 19221387PubMed |
