The value of a transformation zone component in anal cytology to detect HSIL.

BACKGROUND: In a cytology-based screening program intended to prevent anal cancer, the anal transformation zone (TZ) should be adequately sampled because it is the site most susceptible to the development of the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). An adequate TZ component is defined as comprising at least 10 rectal columnar or squamous metaplastic cells. In the current study, the authors examined whether the presence of a TZ component in anal cytology correlated with the detection of histological HSIL. METHODS: In a natural history study of anal human papillomavirus infection in homosexual men, all participants underwent liquid-based cytology and high-resolution anoscopy (HRA) with or without biopsy at each visit. True-negative cytology (negative cytology with non-HSIL biopsy or negative HRA), false-negative cytology (negative cytology with HSIL biopsy), and true-positive cytology (abnormal cytology with HSIL biopsy) were compared with regard to the presence or absence of a TZ component. RESULTS: Of 617 participants, baseline results included 155 true-positive results, 191 true-negative results, and 31 false-negative results. The absence of an adequate TZ component was found to be significantly higher for false-negative (32.3%) than for either true-positive (11.0%; P = .0034) or true-negative (13.1%; P = .0089) results. CONCLUSIONS: Significantly more false-negative cases lacked a TZ component compared with either true-positive or true-negative cases. TZ cells may be an important indicator of sample quality for anal cytology because, unlike cervical sampling, the anal canal is not visualized during cytology sampling. Cancer Cytopathol 2016;124:596-601. © 2016 American Cancer Society.

Papillary Immature Metaplasia of the Anal Canal: A Low-grade Lesion That Can Mimic a High-grade Lesion.

In a natural history study of anal human papillomavirus (HPV) infection and HPV-related lesions among homosexual men in Sydney, Australia, we identified 15 examples of papillary immature metaplasia (PIM) in anal biopsy samples. PIM has previously been described in the cervix, but not in the anal canal. PIM is a form of exophytic low-grade squamous intraepithelial lesion (eLSIL) also known as condyloma. In contrast to the maturing keratinocytes and koilocytosis seen in conventional eLSIL, the slender papillary structures of PIM have a surface population of immature squamous cells. In our anal samples PIM was characterized by close proximity to conventional eLSIL, was negative for p16 (p16) expression, and revealed the presence of a single low-risk HPV genotype (either 6 or 11) in laser capture microdissected lesions. The clinical significance of recognizing PIM lies in preventing misdiagnosis as high-grade squamous intraepithelial lesion, (the presumed precursor to anal cancer), due to the morphologic immaturity of the cell population. In routine practice, awareness of anal canal PIM and p16 immunostaining will prevent this. Further study of the natural history of anal canal PIM is needed.

High reproducibility of histological diagnosis of human papillomavirus-related intraepithelial lesions of the anal canal.

In a natural history study of anal human papillomavirus (HPV) infection and HPV-related lesions, we examined the reproducibility of histological high-grade squamous intraepithelial lesion (HSIL). Three expert anogenital pathologists share the reporting of histological specimens from the Study of the Prevention of Anal Cancer (SPANC), utilising Lower Anogenital Squamous Terminology (LAST) criteria. In total, 194 previously reported biopsies were randomly chosen within diagnostic strata [50 HSIL-anal intraepithelial neoplasia (AIN) 3; 45 HSIL-AIN 2; 49 'flat' low-grade squamous intraepithelial lesion (LSIL); 50 'exophytic' LSIL; and 50 negative for squamous intraepithelial lesion] and reviewed by each of these three pathologists. Consensus was defined as agreement between at least two review diagnoses, using a binary classification of HSIL and non-HSIL, or if consensus was not obtained in this way, it was achieved through a multiheader microscope session by the three pathologists. We found very high agreement between original and consensus diagnoses (Kappa = 0.886) and between each pathologist's review and consensus (Kappas = 0.926, 0.917 and 0.905). Intra-observer agreement for the three pathologists was 0.705, 1.000 and 0.854. This high level of diagnostic reproducibility indicates that the findings of SPANC should be robust and provide reliable information about HPV-related anal canal disease.

Assuring the quality of quality assurance: seeding abnormal slides into the negative Papanicolaou smears that will be rapid rescreened.

BACKGROUND: Rapid rescreening (RR) of negative Papanicolaou smears (PS) is used in many countries as a quality-assurance measure. Seeding of abnormal slides has been suggested as a way to increase the sensitivity of this procedure. Since 2004, the authors have carried out RR with seeding before issuing reports. In this article, they describe their experience. METHODS: Abnormal seeds were sourced from the previous day's high-grade cases, both squamous and glandular. Slides were evaluated for the 'degree of difficulty' (which was defined as the number of fields required to find (fields-to-find [FTF]) the abnormality), relabeled, and redotted to make them indistinguishable from the routine RR work. The number of seeds found/missed, the identity of the screener, the type of seeded abnormality, the degree of difficulty of the seed, and the mapping technique used all were recorded. The cytologists also were surveyed about their views on seeding. RESULTS: Overall, 14.8% of 3082 high-grade seeds were missed during RR. There was no relation between seeds missed and the mapping technique used. However, the difficulty of the seed was relevant to the number missed and ranged from 8.3% when the FTF was <5 to 36% when the FTF was >10 (P = .000). The difference between intraepithelial seeds and invasive seeds was significant for squamous seeds (P = .031) but not for glandular seeds. Glandular seeds also were more likely to be missed than squamous seeds (23.1% vs 14.3%; P = .002). Most cytologists believed that seeding was a good idea and that seeds increased their level of vigilance. CONCLUSIONS: The authors' experience demonstrated that routine seeding is practicable for both conventional and liquid-based slides. With the advent of the human papillomavirus vaccine, abnormalities will become rarer, and seeding will be necessary to maintain the alertness of cytologists.

Comparative sensitivities of ThinPrep and Papanicolaou smear for adenocarcinoma in situ (AIS) and combined AIS/high-grade squamous intraepithelial lesion (HSIL): comparison with HSIL.

BACKGROUND: Despite the historic belief that cytologic screening offers little protection against cervical adenocarcinoma (CAC), there is emerging evidence that, by detecting the precursor lesion, adenocarcinoma in situ (AIS), cervical screening may reduce the incidence of CAC as it has for cervical squamous carcinoma. Because liquid-based cytology is fast replacing the conventional Papanicolaou smear (PS), it is important to establish that it is at least as effective in detecting AIS. METHODS: The authors calculated the sensitivities of PS and ThinPrep (TP) for 100 women with histologic AIS (from 160 PS slides and 60 TP slides), for 94 women with AIS+high-grade squamous intraepithelial lesion (HSIL) (from 151 PS slides and 50 TP slides), and for 558 women with HSIL (from 788 PS slides and 383 TP slides). All smears were taken up to 36 months before the histologic diagnosis. RESULTS: In no category was there a significant difference between PS sensitivity and TP sensitivity. The HSIL category had a significantly higher overall sensitivity than the other categories. However, when sensitivity was defined as cytologic detection of high-grade disease, there was no difference between any of the categories. For the detection of a high-grade glandular lesion, the presence of a concurrent histologic HSIL was associated with reduced sensitivity for the detection of AIS. CONCLUSIONS: The current results indicated that it may prove possible for cervical screening, with either PS or TP, to reduce the incidence of CAC.

A three-armed trial of the ThinPrep Imaging System.

We compared the performance of the ThinPrep (TP) Imaging System (TIS) with manual reading of TP slides (TPM) and with manual reading of the paired conventional Pap smear (PS) in terms of sensitivity for and positive predictive value (PPV) of high-grade disease and productivity. The study consisted of 11,416 routine PS and paired TP slides as well as 103 confirmed abnormal TP slides. In terms of sensitivity for the detection of biopsy-confirmed high-grade disease, overall there was no statistically significant difference between TIS-screened TP (TPI) and TPM (81.1% vs. 86.8%). For the routine cases, TPI was significantly more sensitive than PS (73.4% vs. 57.8%). In terms of PPVs for the cytologic prediction of high-grade disease, there was no statistically, significant difference among TPI, TPM, and PS (75.6%, 73.9%, and 84.6%). For cytologic reports of possible high-grade disease, the PPVs were equivalent for TPI (45.0%) and TPM (37.0%) and there was no significant difference in PPVs between TPI and PS (61.3%). For TP slides, TIS screening showed a 27% productivity gain when compared with manual screening and a 54% productivity gain when compared with manual screening of PS slides. Use of TIS showed productivity benefits when compared with TPM and both productivity and sensitivity benefits over use of PS.

Follow-up of cytologic predictions of endocervical glandular abnormalities: histologic outcomes in 123 cases.

OBJECTIVES: To determine histologic positive predictive values (PPVs) for three categories of cytologic reports of endocervical glandular abnormalities. MATERIALS AND METHODS: We obtained histologic follow-up for 100% of 67 cytologic predictions of adenocarcinoma in situ (AIS) and 82% of 39 predictions of possible AIS (?AIS) made over a 4-year period (1999-2002) and for 25% of 105 atypical endocervical cells (AEC) predictions over a 12-month period (2000). For each category of cytologic report, we determined the histologic yields of high-grade lesions overall and of high-grade glandular lesions. RESULTS: PPVs for predictions of AIS and ?AIS for high-grade lesions overall were 91% and 75% (p = .032), respectively, and those for high-grade glandular lesions were 88% and 72% (p = .046), respectively. For a cytologic report of AEC, of those with histologic follow-up, 9% had a high-grade lesion and 7% had a high-grade glandular lesion. CONCLUSION: Cytology can accurately predict AIS.