Tips and Tricks for Early Diagnosis of Cervico-Vaginal Involvement from Extramammary Paget's Disease of the Vulva: A Referral Center Experience

Abstract

Cervico-vaginal (CV) localization of extra-mammary Paget's disease (EMPD) of the vulva is extremely rare. In order to investigate the incidence risk and the pathognomonic clinical and pathological features of this condition, a retrospective analysis was conducted including 94 women treated for vulvar EMPD at the European Institute of Oncology, Milan, Italy, from October 1997 to May 2020. Overall nine patients developed CV involvement from EMPD, with a cumulative incidence of 2.5% (95% CI: 0.5-8.0%) at 5 years, 6.5% (95% CI: 1.9-15.1%) at 10 years and 14.0% (95% CI: 4.8-27.8%) at 15 years, respectively. All cases except one were firstly detected by abnormal glandular cytology. None reported vaginal bleeding or other suspicious symptoms. The colposcopic findings were heterogeneous and could sometimes be misdiagnosed. Cervical and/or vaginal biopsies were always performed for histopathological diagnosis by identification of Paget cells in the epithelium or stroma. Most patients developed invasive EMPD (5/9) of the cervix and/or vagina and underwent hysterectomy with partial or total colpectomy. CV involvement from EMPD should not be underestimated in women with a long-standing history of vulvar Paget's disease. Liquid-based cytology with immunocytochemistry represents a valuable tool for early diagnosis and should be routinely performed during the required lifelong follow-up.

Keywords: Paget cells; atypical glandular cytology; cervico-vaginal involvement; colposcopic-guided biopsy; vulvar extramammary Paget’s disease (EMPD).

Figure 1

Overall survival of women affected by vulvar EMPD (N = 93).

Figure 2

Cumulative incidence function of cervico-vaginal (CV) localization of vulvar EMPD, considering death as a competing event (N = 93).

Figure 3

Cervical cytology of EMPD: (a,b) liquid-based cytology; (c,d) cell block. Note the (arrow) Paget cells as round or columnar cells with an increased N/C ratio (a, 20×), arranged in small clusters (b, 40×) on liquid-based cytology and highlighted on the cell block (c, 20×) by HER2 expression (d, 20×).

Figure 4

Heterogeneous colposcopic findings in women diagnosed with CV involvement from vulvar EMPD: (a,b) Dense acetowhite epithelium with sharp borders and coarse punctuation: inside the transformation zone of the cervix and in the left vaginal fornix (a); in the middle third of the left vaginal wall (b). (c,d) Micropapillary lesions with ridge sign and coarse punctuation: outside the transformation zone of the cervix (c); in the upper third of the left vaginal wall (d). (e,f) Large papillae with an irregular surface and fragile vessels: in the left vaginal wall (e); in the right and left vaginal walls with a wide extension (f).

Figure 5

Cervical EMPD: (a) intraepithelial and (b) invasive. Note the (arrow) Paget cells, with clear cytoplasm and prominent nucleoli, arranged as single cells or little clusters in the ectocervical epithelium (a) and as gland-like structures in the cervical stroma (b).