Histopathological findings in hysterectomy for cervical stenosis in postmenopausal women: A retrospective case series.

OBJECTIVE: To analyze the histopathological findings in postmenopausal women who underwent hysterectomy for postsurgical cervical stenosis, evaluating the incidental findings of preinvasive or invasive uterine and cervical disease. METHODS: Retrospective case series of postmenopausal women who underwent hysterectomy for postsurgical cervical stenosis at Gynecological Oncology Unit of Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico Aviano-National Cancer Institute from January 2014 to January 2021. RESULTS: During the study period, 36 women underwent hysterectomy for postsurgical cervical stenosis at our institution. Cervical stenosis occurred 10.2 ± 5.6 years from the onset of menopause. In particular, 26 (72.2%) patients underwent a single loop electrosurgical excision procedure or carbon dioxide (CO2)-laser conization before the onset of stenosis. The remaining 10 (27.8%) women had multiple surgical excision before the onset of stenosis. At the final histopathological analysis, 17 (47.2%) patients had a preinvasive or invasive gynecological disease. In particular, 9 cases of cervical disease (including 1 case of endocervical squamous cell carcinoma pT1a) and 6 cases of endometrial hyperplasia emerged. Also, 2 cases of tubo-ovarian diseases were found. CONCLUSIONS: Postsurgical cervical stenosis is a challenging clinical condition, especially in women treated for cervical intraepithelial neoplasia or microinvasive cervical cancer. As shown, cervical stenosis can prevent an adequate gynecological follow-up and a prompt diagnosis of malignancies. Therefore, postmenopausal women with cervical stenosis should be carefully counseled, and hysterectomy could be a reasonable option, especially in those cases in which a conservative approach is not feasible, failed, or is not accepted by the patient.

CIN2 in childbearing-age women: may colposcopy help choosing the proper management?

BACKGROUND: CIN2 is considered a biologically equivocal lesion falling between low- and high-grade cervical dysplasia, but it is often managed with cervical conization as a high-grade lesion. However, since cervical conization can lead to an increased risk of adverse obstetric events, it might be interesting to identify, by colposcopy, a subgroup of women with a low risk of "occult" CIN3 who could be managed with a "wait and see" approach. METHODS: All the women with CIN2 cervical biopsy from 1999 to 2019 were retrospectively identified. Their colposcopic patterns at the time of biopsy and the histopathological findings on the final cone specimen were compared. RESULTS: Among the 354 women with CIN2 biopsy included, the overall CIN3+ lesion rate on final cone specimen was 21.4%. The rate of CIN3 on final specimen was higher in women with G2 colposcopy compared to G1 (27.2% vs. 15.9%, P=0.01). Among women with G1 colposcopy, the rate of CIN3+ lesions was significantly higher in women with fine punctation (P=0.02) while no differences in women with thin acetowhite epithelium or fine mosaic emerged. CONCLUSIONS: In women with CIN2 biopsy, when a G2 pattern or G1 with fine punctation on colposcopy is detected, there is an increased risk of CIN3+ on final histology, therefore an excisional treatment should be preferred. Otherwise, in women with CIN2 biopsy and other G1 patterns on colposcopy, a "wait-and-see" approach could be considered.

Clinical Characteristics and Long-Term Follow-up of Patients Treated for High-Grade Vaginal Intraepithelial Neoplasia: Results From a 20-Year Survey in Italy.

OBJECTIVES: The aim of this survey was to evaluate the different surgical approaches for women with high-grade vaginal intraepithelial neoplasia (HG-VaIN) used in 8 hospitals in central and northern Italy in the last 20 years. In particular, the baseline characteristics of the patients and factors potentially leading to excisional treatment rather than ablation were considered. Moreover, the clinical outcome of patients treated for HG-VaIN (disease persistence or recurrence and progression toward invasive vaginal cancer) was analyzed. MATERIALS AND METHODS: The medical records of all women initially diagnosed with HG-VaIN and subsequently treated in 8 Italian hospitals from January 1996 to December 2016 were analyzed in a multicenter retrospective case series. RESULTS: Among the 226 women included, 116 (51.3%) underwent ablative procedures and 110 underwent excisional surgery (48.7%). An ablative procedure was preferred in cases where multiple lesions were found on colposcopic examinations. Physicians decided more frequently to perform excisional procedures in women with menopausal status, high-grade referral cervical cytology, previous hysterectomy for human papillomavirus-related disease, or VaIN 3 on colposcopic-guided biopsy. CONCLUSIONS: The surgical treatment of HG-VaIN should be tailored according to the clinical characteristics of each woman and each lesion. However, in potentially high-risk cases (VaIN 3, previous hysterectomy for human papillomavirus-related disease, and menopausal women) or in those cases in which an occult invasive disease cannot be ruled out, an excisional approach should be preferred.In any case, long-term follow-up is advisable in women treated for HG-VaIN.

Role of Close Endocervical Margin in Treatment Failure After Cervical Excision for Cervical Intraepithelial Neoplasia: A Retrospective Study.

CONTEXT.­: A significant negative trend in length of cone excision has been observed in recent years, leading to a higher percentage of positive endocervical excision margin and close (<1 mm) negative endocervical margin cases. OBJECTIVE.­: To evaluate the rate of disease persistence and recurrence after cervical excision for cervical intraepithelial neoplasia in relation to a close (<1 mm), negative, or positive endocervical margin. DESIGN.­: We retrospectively analyzed a cohort of patients with cervical intraepithelial neoplasia having a carbon dioxide laser cervical excision performed by the same operator. We evaluated the rate of positive follow-up in relation to the status of endocervical margin. RESULTS.­: We found a higher percentage of positivity at follow-up and recurrence rate between 13 and 24 months in patients with positive margin than for patients with negative or close endocervical margin (P = .005 and P = .006, respectively), with no difference between negative and close margin (7.0% versus 8.3%, P = .89, and 1.2% versus 0%, P = .83, respectively). CONCLUSIONS.­: Women with close and negative endocervical margin presented similar risk of positivity at long-term follow-up, disease persistence, and recurrence between 13 and 24 months, so the histopathologic report of a free endocervical margin less than 1 mm should not categorize the patient as being at increased risk of treatment failure. Therefore, the only information that the pathologist should report is the state of the margin (positive or negative), regardless of the negative endocervical margin length.

Effect of age and cone dimensions on cervical regeneration: an Italian multicentric prospective observational study.

OBJECTIVES: To evaluate cervical regeneration at 6 months following excisional treatment for high-grade cervical intraepithelial neoplasia (CIN), and to investigate the effect of cone dimensions, age of patients and technique of excision on the efficacy of the regeneration process. DESIGN: Prospective observational multicentric study. SETTING: Three tertiary care and research centres. PARTICIPANTS: Among the 197 eligible women of childbearing age, older than 25 years of age, undergoing for the first time a loop electrosurgical excision procedure or carbon dioxide laser cervical excision for a high-grade CIN at the colposcopy-directed cervical punch biopsy, and with a final diagnosis of high-grade CIN, 165 completed the 6-month follow-up and were included in the analysis. PRIMARY OUTCOME MEASURES: The cervical length and volume regeneration (%) after 6 months from procedure were determined by three-dimensional ultrasound, and the correlation of regeneration with cone dimensions, age and excision technique was evaluated. RESULTS: The mean±SD cervical length regeneration at 6 months was 89.5%±6.3% and the mean±SD cervical volume regeneration was 86.3%±13.2%. At the multivariate analysis, a significant and independent inverse correlation between excised cone length and cervical regeneration emerged (r=-0.39, P<0.001). A significantly negative trend in length regeneration at 6 months from procedure with an increasing class of cone length was found (P<0.001). No significant association was found in relation with patient age at the time of procedure or with the technique of excision. CONCLUSIONS: Cervical length regeneration at 6 months from excisional treatments is negatively affected by an increasing cone length but not from the age of the patient or the technique of excision. While still achieving equal clinical efficacy, it is crucial to contain cone dimensions, in order to favour a greater length regeneration, reducing the cervical harm and the potential future obstetric complications.

Colposcopic patterns of vaginal intraepithelial neoplasia: a study from the Italian Society of Colposcopy and Cervico-Vaginal Pathology.

The aim of this study was to evaluate the colposcopic patterns observed in women with a histopathological diagnosis of vaginal intraepithelial neoplasia (VaIN). The medical charts and the colposcopy records of women diagnosed with VaIN from January 1995 to December 2013 were analysed in a multicentre retrospective case series. The abnormal colposcopic patterns observed in women with VaIN1, VaIN2 and VaIN3 were compared. The vascular patterns and micropapillary pattern were considered separately. A grade II abnormal colposcopic pattern was more commonly observed in women with a biopsy diagnosis of VaIN3 rather than with VaIN1 or VaIN2 (P<0.001). Vascular patterns were also more common in women with VaIN3 rather than with VaIN1 or VaIN2 (P<0.001). Moreover, in women with grade I colposcopy, the rate of VaIN3 was significantly higher when a vascular pattern was observed (62.5 vs. 37.5%; P=0.04). The micropapillary pattern was more common in women with grade I colposcopy and it was more frequently observed in women with VaIN1 rather than in those with VaIN2 or VaIN3 (P<0.001). Grade II abnormal colposcopic pattern was more commonly observed in women with VaIN3. Moreover, the detection of vascular patterns appeared to be associated with more severe disease (VaIN3) even in women with grade I colposcopy, whereas the micropapillary pattern should be considered an expression of a less severe disease (VaIN1 and VaIN2).

Cervical Excision Procedure: A Trend of Decreasing Length of Excision Observed in a Multicenter Survey.

OBJECTIVES: The aim of the present study was to observe the trend of length of cone excisions in women treated with cervical excision procedure in five institutions of Central and Northern Italy. MATERIALS AND METHODS: A multicenter retrospective cohort study was conducted on women who underwent a cervical excision procedure between January 2006 and December 2014. The pertinent clinical, histopathological, and sociodemographic characteristics of each woman were collected. In particular, the length of the cone specimen was evaluated and all of the factors that potentially influenced the length of excision were considered. RESULTS: A total of 1482 women who underwent a cervical excision procedure from January 2006 to December 2014 were included. A mean (SD) cone length of 12.9 (5.0) mm was reported, and mostly, a significant decrease during the whole study period emerged. Age (r = 0.1, p = .007) and preoperative diagnosis of glandular lesions (r = 0.1, p < .001) were significantly related to the length of cone excision on multivariate analysis. Compared with the carbon dioxide laser excisional procedure, loop electrosurgical excision procedure showed a negative correlation with the length of excision (r = -0.2, p < .001). CONCLUSIONS: During the study period, a significant decrease in the length of cone excision was observed, probably reflecting the gynecologists' acquired awareness of the increased risk of adverse obstetric outcomes for future pregnancies in the case of wide cone excisions.

Laser Excisional Treatment for Vaginal Intraepithelial Neoplasia to Exclude Invasion: What Is the Risk of Complications?

OBJECTIVE: We undertook a retrospective analysis of the incidence of complications of carbon dioxide (CO2) laser excision for high-grade vaginal intraepithelial neoplasia (HG-VaIN). MATERIALS AND METHODS: Retrospective large case series on 128 CO2 laser excisions for HG-VaIN in 106 women treated at the Department of Gynecologic Oncology, Oncologic Referral Center, Aviano, Italy. These procedures were performed under local anesthesia with a 20-W continuous laser beam focused to a 0.2-mm spot size. Complications were defined as "minor" when limited to vagina, and "major" when surrounding organs were injured or the vaginal vault was opened.To identify possible factors associated with surgical complications, we performed a univariate analysis with the t test for continuous variables and χ or Fisher exact test for qualitative variables as appropriate. RESULTS: The overall rate of complication was 7.8% (10/128); nine of them were vaginal bleeding, and only one (0.8%) was a major complication with vaginal vault perforation.A greater number of previous destructive treatments and of two or more previous laser vaginal excisional treatments was present in patients with complications compared with ones without complications (10% vs 3.9 %, p = .92, and 30% vs 15.2%, p = .44, respectively), although these differences were not statistically significant. A total of 10.5% (6/57) of occult vaginal cancer was detected in women with initial diagnosis of VaIN3 (HG-VaIN) on biopsy. CONCLUSIONS: Carbon dioxide laser excision for HG-VaIN seems to be a safe approach with low rate of complications, probably because of the better accuracy achieved by CO2 laser resections, and permits diagnosis of occult invasive disease.

Multiple preinvasive and invasive HPV-related lesions of the anogenital tract in a female patient with HIV infection: A case report.

RATIONALE: Patients with human immunodeficiency virus (HIV) infection have been shown to be at increased risk for high-risk human papillomavirus (HR-HPV) infection of the anogenital tract. Furthermore, in the last decades, the introduction of highly active antiretroviral therapy (HAART) has increased the longevity of these patients who now live long enough to develop HPV-related cancers; hence, the impact of HPV infection on HIV-positive patients is of increasing concern. PATIENT CONCERNS: We reported the case of an HIV-positive female patient on HAART with a good virological and immunological response and with a long history of HPV-related intraepithelial and invasive lesions of the anogenital tract. DIAGNOSES: From 1996 to 2016, this patient was diagnosed with a high grade cervical intraepithelial neoplasia; a HR-HPV positive inguinal lymph node metastasis from clinically undetectable primary squamous cell carcinoma; a HPV-related vulvar high-grade squamous intraepithelial lesion and an invasive squamous cell carcinoma of the anus. INTERVENTIONS: All the intraepithelial and invasive lesions detected were properly treated, and subsequent follow up visits with gynecologic examination, anoscopy, pap smear and anal cytology were performed. OUTCOMES: After a recurrence of the anal cancer and a subsequent salvage surgery with abdominoperineal resection, at the last available follow up visit no sign of disease recurrence was found. LESSONS: This case stresses the importance of an accurate multidisciplinary follow-up in HIV-positive patients, including not only the routine medical, immunological, and virological evaluation, but also a periodical complete examination of the anogenital tract with cervicovaginal and anal cytology, colposcopy, high resolution anoscopy, and vulvar examination.

Procedures of cervical conization: a national survey among Italian colposcopy units.

BACKGROUND: The recent evolution of surgical techniques, anesthesia and treatment strategies has led to a decrease in the number of cervical conization procedures performed in ordinary hospitalization or with anesthetics other than local infiltration anesthesia of the cervix. Conization should be as least invasive as possible, favor women's compliance and resumption of normal daily activities after surgery. We evaluated various aspects of patient care revolving around conization (technical, healthcare, and administrative aspects) in the clinical practice of 26 Italian colposcopy units. METHODS: A standard multiple-choice questionnaire was used. The retrospective study covered a period of 10 years. RESULTS: The overall number of conization procedures performed over the 10 years' observation period ranged from 20,000 to 37,500. The techniques used were the loop electrosurgical excision procedure in 79.9% of cases, CO2 laser in 16.7%, and the cold-knife biopsy in 3.4%. An outpatient regimen was reported in 62.1% of cases, a day-surgery regimen in 35.2% and an ordinary hospitalization in 2.7%. Local anesthesia, deep sedation and general anesthesia were usually performed in 86.7%, 11.9% and in 1.4% of cases, respectively. The use of prophylactic antibiotics was common only in 8% of cases. The rate of major adverse events recorded over the observed period varied between 0.04% and 0.02% (15,000-29,000 conizations). CONCLUSIONS: The administrative regimen in which conizations are performed is an expression of behaviors of different health authorities and hospitals in relation to the costs that this procedure entails.

Surgical Treatment of Paget Disease of the Vulva: Prognostic Significance of Stromal Invasion and Surgical Margin Status.

OBJECTIVE: The aim of the study was to evaluate the risk of recurrence according to the surgical margin status and the presence of invasion or of superficially invasive carcinoma in patients with extramammary Paget disease (EMPD) of the vulva, who underwent elective surgical treatment. MATERIALS AND METHODS: We performed a retrospective analysis of 27 patients with first diagnosis of extramammary Paget disease of the vulva, who underwent primary and elective surgical treatment from January 1989 to December 2014. A p value of less than .05 was considered statistically significant. Multivariable logistic regression was performed to adjust for confounding factors. RESULTS: We observed invasive disease in 11 cases, with microinvasion in 8 of them. A positive surgical margin was found in 10 patients. During a median follow-up period of 79.5 months, 8 patients (29.6%) showed a first recurrence after a median (range) time of 4.9 (2.3-7.1) years. No significant differences were observed between patients with recurrence and patients without recurrence with respect to age, number of vulvar sectors involved, bilaterality and multifocality, presence of invasion or microinvasion, and surgical margin status. However, during the follow-up period, the presence of invasion was higher (67% vs 41%) in patients with recurrence compared with patients without recurrence. CONCLUSIONS: The rate of recurrence of the disease after therapy is high. Patients should be subjected to a close and long-term follow-up to identify those who must undergo further treatment, especially if they presented with an invasive or even microinvasive disease. A free margin of no greater than 1 to 2 cm might be the most appropriate surgical choice.

Conservative treatment of coexisting microinvasive squamous and adenocarcinoma of the cervix: report of two cases and literature review.

Coexistence of microinvasive squamous cell carcinoma (MISCC) and microinvasive adenocarcinoma (MIAC) of the cervix is a rare phenomenon with very few clinically significant cases described in the literature. While a conservative approach has been studied, and may be effective in MISCC, a lower number of studies that recommend conservative treatment are available for MIAC. We report two cases of synchronous cervix lesions in two separate foci, MISCC and MIAC, who underwent fertility-sparing treatment with long-term follow-up. We describe clinical, histological, and immunohistochemical features of the two cases. The first case is a 41-year-old female with a diagnosis of MIAC of endocervical type, grade 1 differentiation, with a stromal invasion, associated with a separate area of squamous cell carcinoma (International Federation of Gynecology and Obstetrics/TNM stage: pT1a1G1). The second case is a 45-year-old female with a diagnosis of plurifocal MISCC, associated with an MIAC of endocervical type with a stromal invasion (International Federation of Gynecology and Obstetrics/TNM stage: pT1a1G1). After multidisciplinary counseling, both patients accepted conization as definitive treatment. Eleven years after the conization, all tests (Papanicolaou smear, colposcopy, cervical curettage, and hybrid capture 2-human papillomavirus test) planned quarterly in the first year and every 6 months in the subsequent years were negative in both patients. In women affected by stage IA1 squamous cervical cancer coexisting with stage IA1 adenocarcinoma endocervical type, with clear margins, and without lymphovascular space invasion, cervical conization may be considered a fertility-preserving, safe, and definitive therapeutic option.

Vaginal Intraepithelial Neoplasia: Histopathological Upgrading of Lesions and Evidence of Occult Vaginal Cancer.

OBJECTIVE: The aim of this study was to analyze women treated with excisional procedures for vaginal high-grade squamous intraepithelial lesions (HSILs). The histopathological upgrading of the lesions previously detected on vaginal biopsy and the presence of occult invasive vaginal cancer in the specimens excised were investigated, to identify a higher risk subset of women. MATERIALS AND METHODS: A retrospective analysis of the medical records of 86 women with a biopsy histopathologic diagnosis of vaginal HSIL (vaginal intraepithelial neoplasias [VaINs]: VaIN2 and VaIN3) and subsequent excisional therapy, consecutively referred to the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014, was performed. RESULTS: Of the 86 patients, 4 cases (4.6%) of occult vaginal cancer were detected, all of them in women previously diagnosed with VaIN3 on biopsy (4/39 cases, 10.3%). Women with diagnosis of VaIN2 on biopsy showed an upgrading of lesions, with diagnosis of VaIN3 on the final specimen in 5 (10.6%) of 47 cases, with no cases of VAIN2 upgraded to invasive cancer. In 33.3% of the women initially diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus-related disease, a final histopathological upgrading of lesions emerged. Furthermore, tobacco use was significantly related to the histopathological upgrading of lesions previously detected on vaginal biopsy. CONCLUSIONS: Women diagnosed with VaIN3 should be treated with excisional procedures as first-line surgical approach, given the risk of occult invasive disease in 10% of the cases. Women diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus-related cervical diseases should always be carefully evaluated and possibly excised, given the higher risk of histopathological upgrading of lesions and thus the potential risk of occult vaginal cancer. Tobacco users should be considered as high-risk group.

Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

The aim of this study was to analyze the correlation between the first diagnosis of high-grade Vaginal Intraepithelial Neoplasia (HG-VaIN: VaIN 2-VaIN 3) and the cytological abnormalities on the referral pap smear.All the women with histological diagnosis of HG-VaIN consecutively referred to the Gynecological Oncology Unit of the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014 and with a pap smear performed in the 3 months before the diagnosis were considered, and an observational cohort study was performed.A total of 87 women with diagnosis of HG-VaIN were identified. Major cytological abnormalities (HSIL and ASC-H) on the referral pap smear were significantly more frequent than lesser abnormalities (ASC-US and LSIL) in postmenopausal women (64.9% vs 36.7%, P = 0.02) and in women with a previous diagnosis of HPV-related cervical preinvasive or invasive lesions (70.5% vs 39.5%, P = 0.01). Diagnosis of VaIN 3 was preceded by major cytological abnormalities in most of the cases (72.7% vs 27.3%, P < 0.001).The diagnosis of HG-VaIN can be preceded by different abnormalities on referral pap smear. Major abnormalities are usually reported in postmenopausal women and in women with previous cervical HPV-related disease. However, ASC-US or LSIL do not exclude HG-VaIN, especially VaIN2. An accurate examination of the whole vaginal walls (or vaginal vault) must be performed in all the women who underwent colposcopy for an abnormal pap smear, and a biopsy of all suspicious areas is mandatory.

Laser CO2 treatment for vulvar lymphedema secondary to gynecological cancer therapy: A report of two cases and review of the literature.

Vulvar lymphedema is an uncommon and disabling side-effect of pelvic lymphadenectomy and pelvic radiotherapeutic treatment for invasive genital cancer. Lymphorrhea, a complication of lymphedema, may be extremely distressing for patients due to the requirement to wear sanitary towels and as the pain and loss of elasticity of the vulvar skin and mucosa can cause discomfort during coitus. Surgical treatments of lymphorrhea and vulvar lymphedema secondary to gynecological cancer treatments remain controversial and are not currently considered to be the standard therapy. The present study reports two cases of vulvar lymphedema complicated by vulvar lymphorrhea in females who had undergone treatment for cervical and endometrial cancer, respectively; a review of the literature is also included. In the two present cases, vulvar lymphedemas were refractory to standard treatments, including decongestive therapy, manual lymph drainage, elastic bandaging, low-stretch bandaging, exercises and skin care. Laser CO2 excision and vaporization of the whole skin and mucosal tissue of the vulva was successfully performed to treat the lymphorrhea and improve quality of life. Thus, the present two cases indicated that laser CO2 surgery may present an additional therapy for the treatment of genital lymphedema that is refractory to other treatments.

Conservative Treatment of Stage IA1 Adenocarcinoma of the Uterine Cervix during Pregnancy: Case Report and Review of the Literature.

Microinvasive adenocarcinoma (MIAC) of the uterine cervix is rare in pregnancy. Published data on conservative treatment of MIAC both in pregnant and nonpregnant women are scarce. A conservatively treated case of MIAC in a 13-week-pregnant woman after a diagnosis of atypical glandular cells (AGC) on pap smear at the 6th week of pregnancy is presented. The problems of suspected adenocarcinoma in situ (AIS) on biopsy and MIAC on cone biopsy in pregnancy, as well as the risks and benefits of a conservative treatment are discussed. After colposcopic guide laser cervical conization and expression of informed consent the patient underwent followup and vaginal delivery at 40 weeks plus 3 days of gestation. In this case, no obstetric complication has been recorded after the cervical conization, and after a followup of 18 months the patient was alive and free of disease, with negative results as far as pap smear, colposcopy, HPV status, and cervical curettage are concerned. In a stage Ia1 disease of endocervical type, with clear margins and without lymph-vascular space invasion, cervical conization performed during the second trimester may be considered a definitive and safe treatment, at least up to delivery, after expression of informed consent by the woman.