A comprehensive diagnostic approach to differentiate intrauterine arteriovenous malformation in cases of enhanced myometrial vascularity.

PURPOSE: The differentiation between conditions such as uterine arteriovenous malformation, pseudoaneurysm, gestational trophoblastic disease, and retained trophoblastic tissue can be challenging. Ultrasound imaging and Doppler interrogation are the primary diagnostic tools to assess cases of enhanced myometrial vascularity and differentiate intrauterine vascular anomalies. However, some cases remain of difficult differentiation. This study aims to analyze suspected cases and describe their diagnostic management and outcomes. METHODS: We reviewed post-abortion cases that underwent pelvic transvaginal U/S imaging and Doppler examinations due to suspected uterine vascular anomalies. CT scans were performed in cases in which ultrasound did not reach a diagnosis. Simple follow-up, medical or surgical therapy, or embolization of uterine arteries were performed according to the final diagnosis. RESULTS: From 2015 to 2022, we retrieved from electronic ultrasound records 22 cases of suspected vascular malformations. In eight cases, first-line U/S at admission excluded the suspected anomaly. In Five of the remaining 14 patients, uterine vascular anomalies were excluded upon a second-level  U/S based on angio-Doppler imaging and Doppler peak velocity interrogation. Nine cases underwent CT scan, and a digital angiography and embolization were performed in eight of these cases, of whom only two had a documented uterine arteriovenous malformation. CONCLUSION: Our triage proved that only two out of 22 suspected cases had a uterine arteriovenous malformation. This diagnosis is frequently misused in clinical practice. Our data confirm that enhanced myometrial vascularity should be used to encompass the spectrum of possible differential diagnosis. A precise step-by-step diagnostic method is of paramount importance to prevent unnecessary interventions.

Clinical significance of atypical glandular cells on cytology: 10 years' experience of a colposcopic referral center.

INTRODUCTION: 'Atypical glandular cells' (AGC) is an uncommon cytological result of cervical Pap smears which includes a wide of histopathological diagnoses, from benign to premalignant and malignant cervical disorders, endometrial cancer and, occasionally, other genital malignancies. This study aims to provide a comprehensive overview of AGC, assessing risk factors and clinical and histological features in affected patients. MATERIALS AND METHODS: A retrospective analysis was conducted on a cohort of 239 women diagnosed with AGC between 2012 and 2022 at the 'Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders', Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Following AGC detection, patients underwent colposcopy with endocervical sampling and endometrial assessment via pelvic ultrasound. Selective cases also received endometrial biopsies. RESULTS: Among a total of 190 women who underwent both colposcopy and endometrial assessment, 116 (61%) had negative clinical and histopathological findings. The remainder displayed various abnormalities: 36 women (18.9%) were found to have endometrial or cervical polyps, 23 (12.1%) were diagnosed with preinvasive cervical neoplasia, and 21 (10.9%) with invasive cervical or endometrial disease. Menopause, multiparity, and older age were all significantly associated with endometrial cancer, but none of the abovementioned variables were significantly associated with cervical neoplasia. CONCLUSION: Our data confirm that AGC may reveal the presence of a wide range of histopathological conditions. Patients diagnosed with AGC should undergo a careful evaluation including both colposcopy with endocervical sampling and an endometrial assessment.

Weekly Paclitaxel for Pregnancy Associated Breast Cancer.

BACKGROUND: Pregnancy associated breast cancer is the most common cancer diagnosed during pregnancy. When chemotherapy is indicated, although it is more common to use anthracycline-based chemotherapy as a first treatment, we suggest weekly paclitaxel as a valid alternative both in the adjuvant and neoadjuvant setting, as this allows for weekly assessment of maternal-fetal well-being and a quicker maternal and fetal bone marrow recovery in cases of unexpected preterm delivery. PATIENTS AND METHODS: We present a case series of pregnant breast cancer patients treated with weekly paclitaxel between 2016 and 2022. Patient demographics and tumor characteristics, data on management, delivery, and maternal-neonatal outcomes were extrapolated from institutional electronic databases. RESULTS: Eighteen patients underwent weekly paclitaxel for breast cancer during pregnancy (PrBC); 17 were primary diagnoses and 1 was a recurrence. None of the patients had severe adverse reactions to CT. Two cases of preterm prelabour rupture of membranes were reported while in 1 case treatment was stopped due to threatened preterm birth. Two babies were born large for gestational age, 2 were small for gestational age and 2 babies were growth restricted at birth. At a mean follow up of 42.9 months, 1 patient died, 1 patient was diagnosed with disease recurrence and another patient was diagnosed with disease progression. CONCLUSION: Weekly paclitaxel can be safely administered during pregnancy and should be included in the current therapeutic options for PrBC.

Prevalence of high-grade anal intraepithelial neoplasia in immunocompetent women treated for high-grade cervical intraepithelial neoplasia.

BACKGROUND: The aim of the study was to evaluate the prevalence of high-grade anal intraepithelial neoplasia (AIN2-3) among immunocompetent women treated for high-grade cervical intraepithelial neoplasia (CIN2-3). Such knowledge is strongly needed to establish whether a screening program should be recommended in this group of patients. METHODS: This prospective study included a cohort of consecutive women with no known causes of immunosuppression treated with LEEP (loop electrosurgical excision procedure) for a histopathological diagnosis of CIN2-3 in our center between 2019 and 2021. Following the procedure, all patients were invited to undergo anal cytology and anal high-risk HPV-DNA testing (aHPV-DNA). In cases in which one or both tests resulted positive, a high-resolution anoscopy with a biopsy of suspicious lesions was performed. All women also completed a questionnaire on sexual habits. RESULTS: At total of 100 women were enrolled in the study. Among these, eight patients had a concomitant or past diagnosis of anogenital warts, while one patient had received a previous diagnosis of high-grade vaginal intraepithelial neoplasia. Anal Pap smears were positive for low-grade lesions in three patients, while 73 women tested positive for aHPV-DNA. Histological examinations revealed the presence of AIN2-3 lesions in four patients (6.5%; 95% C.I., 1.8 to 15.7%), who subsequently underwent excisional treatment. CONCLUSIONS: Women with a history of high-grade cervical intraepithelial neoplasia have an intermediate risk of developing high-grade anal intraepithelial neoplasia. Future studies are needed in order to assess an ideal screening approach for this condition.

Correlation Between Colposcopic Patterns and Histological Grade of Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

BACKGROUND/AIM: Vaginal intraepithelial neoplasia (VaIN) is a rare human papillomavirus (HPV)- related premalignant condition. VaIN lesions are diagnosed histologically through colposcopy-guided biopsies of suspicious areas, conduced by gynecologists with expertise in lower genital tract diseases. The present study aimed to evaluate the accuracy of colposcopy in the diagnosis of VaIN of any grade. PATIENTS AND METHODS: We conducted a retrospective analysis on a cohort of 149 women diagnosed with low grade (LG)-VaIN (VaIN1) and high grade (HG)-VaIN (VaIN2-3) between 2010 and 2022 at the "Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders", Ospedale Maggiore Policlinico, Milan, Italy. All women had been referred to our center for an abnormal Pap smear or as part of routine follow-up of other HPV-related diseases and had undergone a vaginal biopsy under colposcopic guidance. RESULTS: The distribution of the histological grades of VaIN lesions was the following: 62 women (41.6%) were diagnosed with VaIN1, 51 (34.2%) with VaIN2, and 36 (24.2%) with VaIN3. Grade II (major) abnormal colposcopic patterns were recorded in 71 cases (47.7%) and were more commonly observed in women with VaIN3 (80.6%). However, we found a poor and not statistically significant association between colposcopic and histological grade of VaIN. The sensitivity, specificity, positive predictive value, and negative predictive value of colposcopy for histologically confirmed VaIN were 56.3%, 64.5%, 69% and 51.2%, respectively. The overall diagnostic accuracy of colposcopy was 59.7%. CONCLUSION: Colposcopy-guided biopsy plays an important role in the diagnosis of VaIN and in the distinction between low and high-grade lesions. Our data show that major colposcopic abnormalities moderately correlate with HG-VaIN and that grade I colposcopic findings do not exclude HG-VaIN, especially VaIN2. Targeted biopsies of suspicious vaginal areas must be performed in all women with an abnormal Pap smear.

Immune microenvironment dynamics in breast cancer during pregnancy: impact of gestational age on tumor-infiltrating lymphocytes and prognosis.

Background: Breast cancer during pregnancy (PrBC) is a rare condition known for its aggressive clinical behavior. The presence of tumor-infiltrating lymphocytes (TILs) has been shown to have a significant impact on the prognosis of these patients. Despite some biological characteristics of the tumor that may differ depending on the gestational age, little is known about the dynamics of the immune landscape within the tumor microenvironment (TME) in PrBC. Therefore, in this study, our objective was to gain comprehensive insights into the relationship between gestational age at breast cancer diagnosis and the composition of the TME. Methods: n = 108 PrBC were selected from our institutional registry and categorized based on the gestational age by trimester. For all cases, TILs were profiled according to the International TILs Working Group recommendations, and subtyped by CD4, CD8, and forkhead box P3 (FOXP3) immunohistochemistry. PD-L1 was tested according to the combined positive score (CPS) using the IHC 22C3 pharmDx assay, with a cutoff value of ≥10 for positivity. The statistical approach encompassed Fisher's and Chi-squared tests, with appropriate adjustments for multiple comparisons, logistic regression models, and survival analyses based on the Kaplan-Meier method. Results: The proportion of patients with poorly differentiated (G3) neoplasms increased as the gestational age advanced (first trimester, n = 25, 56.8%; second trimester, n = 27, 69.2%; third trimester, n = 21, 87.5%; p = 0.03). The histologic subtypes as well as the hormone receptor (HR) and HER2 status did not show significant changes across different pregnancy trimesters. In the HR+/HER2- subtype, there was a higher proportion of tumors with high/moderate TILs in the early phases of pregnancy, similar to FOXP3 expression (TILs: first trimester, n = 10, 35.7%; second trimester, n = 2, 10.5%; third trimester, n = 0; p = 0.02; FOXP3: first trimester, n = 10, 40%; second trimester, n = 3, 15.8%; third trimester, n = 0; p = 0.03). The median follow-up for our cohort was 81 months. Patients who relapsed after a breast cancer diagnosis during the first trimester were more frequently PD-L1-negative, unlike those with no disease recurrence (n = 9, 100% vs. n = 9, 56.3%; p = 0.03; hormone therapy and n = 9, 100% vs. n = 7, 53.9%; p = 0.02; chemotherapy). No statistically significant differences were seen among the three trimesters in terms of survival outcome. Conclusion: The TME dynamics of HR+/HER2- PrBC vary based on gestational age, suggesting that immune tolerance expression during later gestational age could explain the increased aggressiveness of tumors diagnosed at that stage.

Fat Grafting in Vulvar Lichen Sclerosus: Long Term Follow-Up.

OBJECTIVE: The rationale for the use of autologous fat grafting in the treatment of vulvar lichen sclerosus (VLS) consists in reduction of inflammation, regeneration of tissues, volume increase, and pain fiber control. The main outcome of this study was the evaluation of patients' satisfaction after treatment. Secondary outcomes included modifications in symptoms, psychosexual wellbeing, vulvar hydration, and histology after surgery. METHODS: Eligible for this study were women aged 18-85 years with a histological diagnosis of VLS who underwent at least one autologous vulvar fat grafting at the authors' center, between 2010 and 2019. In 2021, all women underwent a clinical reevaluation, comprehensive of vulvoscopy, vulvar biopsy, and handing out of validated questionnaires. RESULTS: Overall, 88.7% of patients declared themselves very satisfied/satisfied with the procedure. All symptoms were improved postsurgery; in particular, the difference was statistically significant for pruritus, burning, and dyspareunia ( p < .05). Sexual function was also improved at time of reevaluation, as were depressive and anxiety symptoms ( p < .05). No cases of vulvar intraepithelial neoplasia or cancer occurred during follow-up and vulvar architecture remained stable, although patients reported a significantly reduced need for topical steroids ( p < .0001). Lastly, in postoperative biopsies, inflammatory infiltrate was stable or reduced, and the distribution of elastic fibers was comparable or restored in most patients. CONCLUSIONS: Patient satisfaction with fat grafting is detectable up to 11 years after surgery, and as such, it may represent a valid therapeutic option in selected cases of VLS.

High-grade vaginal intraepithelial neoplasia and recurrence risk: analysis of an Italian regional referral center series.

PURPOSE: The main aim of this study was to investigate the long-term risk of disease recurrence in women treated for high-grade vaginal intraepithelial neoplasia (HG-VaIN). METHODS: We conducted a retrospective analysis on a cohort of 82 women diagnosed with HG-VaIN between 2010 and 2021 at the "Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders", Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. All women underwent either ablative treatment (CO2 laser ablation or electrocoagulation) or cold-knife excision. RESULTS: In our series, the recurrence rate following treatment was 17%. The 5-year cumulative probability of recurrence was 30.4% and the median time to recurrence was 15.5 months. None of the patients progressed to invasive vaginal cancer during follow-up. A concomitant cervical or vulvar intraepithelial lesion was significatively associated with an increased risk of recurrence (p = 0.006). CONCLUSIONS: The results of our study suggest that women with HG-VaIN are at high risk of developing disease recurrence after treatment, especially patients with a concomitant cervical or vulvar intraepithelial lesion. In these women strict monitoring is mandatory to obtain an early identification of recurrence.

Conservative Treatment for Cervical Adenocarcinoma In Situ: Long-Term Results.

OBJECTIVE: This study aimed to evaluate the effectiveness of conservative treatment for cervical adenocarcinoma in situ (AIS). MATERIALS AND METHODS: This is a retrospective study on women with histologically confirmed AIS on cervical loop electrosurgical excision procedure specimen, treated conservatively between 2008 and 2020 in our center, Ospedale Maggiore Policlinico, Milan. The main outcome investigated was the risk of recurrence defined as a subsequent finding of recurrent AIS or invasive adenocarcinoma in a long-term follow-up. The disease-free survival curve was computed using the Kaplan-Meyer method. All patients underwent colposcopy with endocervical curettage and cytology every 6 months for the first 2 years after initial surgery and then annual cytology. RESULTS: Thirty women, aged 26 to 51 years, with histologically proven AIS on excisional specimen with negative margins, negative apex, and negative endocervical curettage were included. The median follow-up was 5.4 years. One woman had a recurrence of AIS after 8 years of follow-up and underwent total hysterectomy. No invasive cervical disease was detected during surveillance. CONCLUSIONS: Women with cervical AIS can be managed conservatively by an excisional procedure, provided that the margins are free and a close and long-term follow-up is guaranteed.

Breast Cancer during Pregnancy as a Special Type of Early-Onset Breast Cancer: Analysis of the Tumor Immune Microenvironment and Risk Profiles.

Breast cancer during pregnancy (PrBC) is a rare tumor with only a little information on its immune landscape. Here, we sought to characterize the cellular composition of the tumor microenvironment (TME) of PrBC and identify its differences from early-onset breast cancer (EOBC) in non-pregnant women. A total of 83 PrBC and 89 EOBC were selected from our Institutional registry and subjected to tumor-infiltrating lymphocytes (TILs) profiling and immunohistochemistry for CD4, CD8, forkhead box P3 (FOXP3), and programmed death-ligand 1 (PD-L1) (clone 22C3). A significantly lower frequency of hormone receptor (HR)-positive tumors was observed in PrBC. The prevalence of low/null PD-L1 and CD8+TILs was higher in PrBC than in the controls, specifically in HR+/HER2- breast cancers. PrBC had a significantly higher risk of relapse and disease-related death, compared to EOBC. The presence of TILs and each TIL subpopulation were significantly associated with disease relapse. Moreover, the death rate was higher in PrBC with CD8+ TILs. The TME of PrBC is characterized by specific patterns of TIL subpopulations with significant biological and prognostic roles. Routine assessment of TILs and TILs subtyping in these patients would be a valid addition to the pathology report that might help identify clinically relevant subsets of women with PrBC.