Reclassification of atypical immature metaplasia of the uterine cervix by combination of nuclear features on hematoxylin and eosin–stained sections without auxiliary immunohistochemistry

Imai, Yasuo; Fukagawa, Yuichiro; Sugihara, Shiro; Teranishi, Takahide

doi:10.1016/j.humpath.2022.09.002

Cited by 2 publications

(8 citation statements)

References 12 publications

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“…Previously, cellular atypia in Pap smears could only be evaluated by approaches supported by pathological diagnostic results or those of dual IHC for p16 and Ki67. 8,9 However, these approaches only indirectly evaluate cellular findings. As we cannot confirm that the cell cluster being evaluated is identical to that in the lesion, and even if IHC is positive for both p16 and Ki-67, we still cannot confirm if the cell cluster is derived from the lesion.…”

Section: Discussionmentioning

confidence: 99%

“…However, this study provides new evidence that IM with nucleoli and varied nuclear sizes may be caused by CIN2‐derived HPV and are more likely to be CIN2‐derived cell clusters, which require additional management. Previously, cellular atypia in Pap smears could only be evaluated by approaches supported by pathological diagnostic results or those of dual IHC for p16 and Ki67 8,9 . However, these approaches only indirectly evaluate cellular findings.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, nuclear hyperchromasia associated with CIN2/3 seems to be a natural consequence as it is one of the findings that can cytologically indicate ASC‐H or worse. Unfortunately, based on this histological feature, the interobserver reproducibility of a diagnosis of IM is low, and as IHC confirmation of p16 and Ki‐67 is essential for the accurate reclassification of CIN2 or greater, 9 we believe that clearer criteria are needed to distinguish both entities by nuclear enlargement. HPV‐positive IM clusters can be characterized by two criteria for nuclear enlargement: first, they are composed of cells with a nuclear area that is more than twice that of normal intermediate cell nuclei or neutrophils, which is the standard size on Pap smear.…”

Section: Discussionmentioning

confidence: 99%

“…The fact that some smears were actually re‐classified as “atypical squamous cells, cannot exclude HSIL” (ASC‐H) or HSIL means that women who require colposcopy were not immediately referred, which is too serious to dismiss as cytology is susceptible to misinterpretation. Another concern is that if upon Pap smear re‐evaluation, no cells that can be identified as ASC‐H or HSIL are seen in women with CIN2/3 or if dual immunohistochemical staining (IHC) for p16 and Ki67 is negative, 8,9 the cervical cytology result may be considered a sampling error 7,10 . However, this is unavoidable because suspicious cells can only be verified according to whether they match the pathological diagnostic results and whether they are positive for p16 and Ki67 on dual IHC 8,9 …”

Section: Introductionmentioning

confidence: 99%

“…Another concern is that if upon Pap smear re‐evaluation, no cells that can be identified as ASC‐H or HSIL are seen in women with CIN2/3 or if dual immunohistochemical staining (IHC) for p16 and Ki67 is negative, 8,9 the cervical cytology result may be considered a sampling error 7,10 . However, this is unavoidable because suspicious cells can only be verified according to whether they match the pathological diagnostic results and whether they are positive for p16 and Ki67 on dual IHC 8,9 …”

Section: Introductionmentioning

confidence: 99%

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Cytological features of human papillomavirus‐infected immature squamous metaplastic cells from cervical intraepithelial neoplasia grade 2

Okodo,

Okayama,

Teruya

et al. 2023

Journal of Medical Virology

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In reflex cytology, the presence of prominent nucleoli in immature metaplastic squamous cells (IM) may be underdiagnosed due to variations in interpretation. The aim of this study is to identify human papillomaviruses (HPVs) that infect IM clusters in cervical intraepithelial neoplasia 2 (CIN2) on Papanicolaou (Pap) smears to determine the cytological features of lesion‐derived cells. Thirty‐two patients with a simultaneous diagnosis of CIN2 on biopsy and high‐grade squamous intraepithelial lesions (HSIL) on cytology as well as with IM clusters on HSIL smears were included. CIN2 tissues and HSIL and IM clusters on Pap smears were isolated by manual microdissection, and HPV types were identified by PCR‐based genotyping. The nuclear area within the IM clusters was also measured. The median nuclear area of HPV‐negative IM clusters was 48 μm2, with a coefficient of variation (CV) of 0.20; those of HPV‐positive clusters were 66 μm2 and 0.34, respectively. The cut‐off values of the nuclear area and CV for HPV positivity were 62 μm2 and 0.25, respectively. IM clusters composed of cells with a nuclear area of more than twice that of neutrophils or cells with a wide variation in nuclear sizes are likely to be neoplastic cells caused by HPV.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cytological features of human papillomavirus‐infected immature squamous metaplastic cells from cervical intraepithelial neoplasia grade 2

Okodo,

Okayama,

Teruya

et al. 2023

Journal of Medical Virology

View full text Add to dashboard Cite

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Enhancing Cervical Cancer Screening: Review of p16/Ki-67 Dual Staining as a Promising Triage Strategy

Ouh,

Kim,

et al. 2024

Diagnostics

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Cervical cancer, primarily caused by high-risk human papillomavirus (HR-HPV) types 16 and 18, is a major global health concern. Persistent HR-HPV infection can progress from reversible precancerous lesions to invasive cervical cancer, which is driven by the oncogenic activity of human papillomavirus (HPV) genes, particularly E6 and E7. Traditional screening methods, including cytology and HPV testing, have limited sensitivity and specificity. This review explores the application of p16/Ki-67 dual-staining cytology for cervical cancer screening. This advanced immunocytochemical method allows for simultaneously detecting p16 and Ki-67 proteins within cervical epithelial cells, offering a more specific approach for triaging HPV-positive women. Dual staining and traditional methods are compared, demonstrating their high sensitivity and negative predictive value but low specificity. The increased sensitivity of dual staining results in higher detection rates of CIN2+ lesions, which is crucial for preventing cervical cancer progression. However, its low specificity may lead to increased false-positive results and unnecessary biopsies. The implications of integrating dual staining into contemporary screening strategies, particularly considering the evolving landscape of HPV vaccination and changes in HPV genotype prevalence, are also discussed. New guidelines and further research are necessary to elucidate the long-term effects of integrating dual staining into screening protocols.

show abstract

Reclassification of atypical immature metaplasia of the uterine cervix by combination of nuclear features on hematoxylin and eosin–stained sections without auxiliary immunohistochemistry

Cited by 2 publications

References 12 publications

Cytological features of human papillomavirus‐infected immature squamous metaplastic cells from cervical intraepithelial neoplasia grade 2

Cytological features of human papillomavirus‐infected immature squamous metaplastic cells from cervical intraepithelial neoplasia grade 2

Enhancing Cervical Cancer Screening: Review of p16/Ki-67 Dual Staining as a Promising Triage Strategy

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