Differentiated squamous intraepithelial neoplasia associated with squamous cell carcinoma of the anal canal

Wasserman, Jason K.; Bateman, Justin; Kien, T.

doi:10.1111/his.12874

Cited by 17 publications

(10 citation statements)

References 24 publications

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“…The features of disturbed maturation had the second highest level of agreement amongst our pathologists, next in importance only to macronucleoli for dVIN diagnosis. Cobblestone appearance of the epithelium [ 22 ], elongated (± anastomosing) rete ridges and parakeratosis could also be reproducibly identified, and these features should be regarded as important pointers towards the diagnosis of dVIN, especially in cases where nuclear atypia cannot be easily discerned. Spongiotic changes of the epithelium seen in NNED should not be mistaken for the cobblestone appearance, as the latter is always accompanied by evidence of disturbed maturation.…”

Section: Discussionmentioning

confidence: 99%

Differentiated vulvar intraepithelial neoplasia (dVIN): the most helpful histological features and the utility of cytokeratins 13 and 17

et al. 2018

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Differentiated vulvar intraepithelial neoplasia (dVIN) is the precursor lesion of HPV-negative vulvar squamous cell carcinoma (VSCC). The histopathological diagnosis of dVIN can be challenging, as it often resembles vulvar non-neoplastic epithelial disorders (NNED), especially lichen sclerosus (LS). We aimed to establish the most specific and reproducible histological features of dVIN and assessed cytokeratin 13 (CK13) and cytokeratin 17 (CK17) immunohistochemistry as a diagnostic aid. Consecutive cases of dVIN (n = 180) and LS (n = 105) from the period 2010 to 2013 were reviewed using a checklist of histological features. Each feature was recorded as ‘present’ or ‘absent’ and statistical comparison (dVIN vs LS) was made. Interobserver agreement between two pairs of pathologists was assessed for a subset of cases of dVIN (n = 31) and LS and other NNED (n = 23). Immunohistochemistry with CK13, CK17, MIB1 and p53 was performed on dVIN, LS, and other NNED cases. Macronucleoli, features of disturbed maturation and angulated nuclei were significantly more common in dVIN than LS (p < 0.001). We found ‘substantial agreement’ for the diagnosis of dVIN (κ = 0.71). Macronucleoli and deep keratinisation had the highest agreement. In dVIN, the mean percentage of cells staining with CK13 was 15 and with CK17, this was 74. For LS, the mean percentage of cells staining with CK13 was 31, and with CK17, this was 41. By plotting receiver operating characteristic curves (ROC), an area under the curve (AUC) of 0.52 was obtained for CK13, and an AUC of 0.87 was obtained for CK17. The most helpful histological features for diagnosing dVIN were macronucleoli, features of disturbed maturation, and angulated nuclei. Increased CK17 expression may have promise for supporting dVIN diagnosis.Electronic supplementary materialThe online version of this article (10.1007/s00428-018-2436-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Differentiated vulvar intraepithelial neoplasia (dVIN): the most helpful histological features and the utility of cytokeratins 13 and 17

et al. 2018

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“…The two main pathways of progression from AK into iSCC – classical and differentiated – are also present in the anogenital mucosa, where the tumours originated through the CP are related to high‐risk mucosal HPV . Viral proteins E6 and E7 are responsible for p53 and pRB inactivation.…”

Section: Discussionmentioning

confidence: 99%

Epithelial‐to‐mesenchymal transition contributes to invasion in squamous cell carcinomas originated from actinic keratosis through the differentiated pathway, whereas proliferation plays a more significant role in the classical pathway

Sàenz-Sardà

Carrato

Pérez-Roca

et al. 2017

Acad Dermatol Venereol

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Epithelial-mesenchymal transition participates in transformation from AK I into iSCC (differentiated pathway), whereas a higher proliferative capacity facilitates intraepidermal extension in the classical pathway. Podoplanin, which is also involved in tumour invasion, does not seem to play a differential role in either pathway. Finally, the absence of differences in p53 and p16 expressions is at variance with other epithelia where the classical pathway is associated with human papillomavirus infection and can be explained by the fact that both AK pathways share identical mechanisms of actinic oncogenesis.

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“…Nomenclature which has been applied to epithelial tumorigenesis in the skin and other anatomic sites (anogenital and oral) was employed. [17][18][19] Cases in which the AK consisted of atypical keratinocytes confined to the lower one-third of the epidermis near the basalis were classified as having originated through the differentiated pathway. Cases in which the AK shows near full-thickness atypia were classified as having originated through the classical pathway.…”

Section: Methodsmentioning

confidence: 99%

“…As one additional assessment, the tumours were classified based upon the location and the extent of the atypical keratinocytes in the overlying interfollicular tumour. Nomenclature which has been applied to epithelial tumorigenesis in the skin and other anatomic sites (anogenital and oral) was employed . Cases in which the AK consisted of atypical keratinocytes confined to the lower one‐third of the epidermis near the basalis were classified as having originated through the differentiated pathway.…”

Section: Methodsmentioning

confidence: 99%

The depth of follicular extension in actinic keratosis correlates with the depth of invasion in squamous cell carcinoma: implication for clinical treatment

Fernández‐Figueras

Sàenz-Sardà

Vargas

et al. 2018

Acad Dermatol Venereol

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The depth of follicular extension of atypical keratinocytes in an AK correlates with the development of depth of invasion of an associated iSCC, irrespective of the pathway of origin. It is therefore important to note the presence and the depth of follicular extension when diagnosing an AK, as follicular extension likely accounts for a significant proportion of recurrent AK and the development of iSCC following superficial treatment modalities.

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Differentiated squamous intraepithelial neoplasia associated with squamous cell carcinoma of the anal canal

Cited by 17 publications

References 24 publications

Differentiated vulvar intraepithelial neoplasia (dVIN): the most helpful histological features and the utility of cytokeratins 13 and 17

Differentiated vulvar intraepithelial neoplasia (dVIN): the most helpful histological features and the utility of cytokeratins 13 and 17

Epithelial‐to‐mesenchymal transition contributes to invasion in squamous cell carcinomas originated from actinic keratosis through the differentiated pathway, whereas proliferation plays a more significant role in the classical pathway

The depth of follicular extension in actinic keratosis correlates with the depth of invasion in squamous cell carcinoma: implication for clinical treatment

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