Andrea Ciavattini

A misleading case of Müllerian anomaly: fibroid degeneration and growth involving nonfunctional, noncommunicating rudimentary horn

To report a rare, misleading fibroid degeneration involving a nonfunctional, noncommunicating horn in a woman with a unicornuate uterus. Although the presence of a functional rudimentary horn may lead to signs and symptoms that recommend its removal, nonfunctional cases are rarely reported, and because of their apparent functional inactivity, the need for their removal has not yet been reported. No previous report showed the possibility of a degenerative process in a nonfunctional rudimentary horn causing patient discomfort. This is a step-by-step narrated video showing a unique case of fibroid degeneration and growth of a nonfunctional, noncommunicating rudimentary horn in a unicornuate uterus (American Society for Reproductive Medicine classification 2021) and its surgical management. University academic hospital. A 48-year-old White nulliparous premenopausal woman was referred to our institution because of abdominal pain and an enlarging adnexal mass. Her personal history showed primary infertility with a previous diagnosis of unicornuate uterus. Given the possibility of ectopic ureters in these occurrences, complete computed tomography was performed, and no genitourinary alterations were found. Preoperative imaging (ultrasound evaluation, computed tomography, and magnetic resonance imaging) provided a provisional diagnosis of a suspicious ovarian fibroma. Considering the patient's age, lack of desire for pregnancy, and volumetric increase in the adnexal mass, a laparoscopic intervention to perform mass removal and prophylactic bilateral salpingectomy was planned. The patient was counseled about the low risk of an underlying malignant transformation. Therefore, the decision to remove the intact mass via a minilaparotomy at the end of the surgery was shared. Once the abdominal cavity was entered, the right unicornuate uterus was found in anatomical continuity with the ipsilateral broad ligament, fallopian tube, and ovary. These structures were wholly attached to the right pelvic wall. On the other side, cranially compared with the right hemiuterus, a roundish myoma-like mass was detected in direct connection with the left broad ligament, fallopian tube, and ovary. In light of a changed intraoperative finding, amputation of the left rudimentary horn and prophylactic bilateral salpingectomy were performed. Showing the fibroid degeneration and growth of a nonfunctional, noncommunicating rudimentary horn in a unicornuate uterus (American Society for Reproductive Medicine classification 2021) treated laparoscopically. Laparoscopic removal of the uterine horn was successful, and no intraoperative and postoperative complications occurred. The patient was in good health at the 6-month follow-up visit. The histopathological examination confirmed the fibroid degeneration and absence of the endometrium. The lack of symptomatic cases of rudimentary nonfunctional horns reported in the literature led gynecologists to consider them a silent Müllerian anomaly. This unique case demonstrates that even nonfunctional rudimentary horns can undergo symptomatic transformation processes requiring surgery. This information may be helpful for more comprehensive counseling of women and for considering the possibility of this occurrence in the diagnostic workup of misleading Müllerian anomalies. With this in mind, surgical treatment can also be better planned as the technical aspects change compared with what is expected for an adnexal pathology.

Diagnosis, treatment and clinical outcomes of extrauterine sites of leiomyomatosis: a systematic review

This review aims to provide a comprehensive description of the clinical presentation, treatment, and histopathological features of extrauterine sites of leiomyomatosis (ESL), such as disseminated peritoneal leiomyomatosis (DPL), parasitic myoma (PM), benign metastatic leiomyoma (BML), and intravascular leiomyoma (IVL). The impact of previous surgery (hysterectomy or myomectomy) on development of intra-abdominal extrauterine leiomyomas (IAELs) and extra-abdominal extrauterine leiomyomas (EAELs) has been evaluated. According to PRISMA guidelines, we searched PubMed, Scopus, and Web of Science databases. Relevant articles were retrieved in full-text format and screened based on predefined inclusion and exclusion criteria. 358 studies (372 cases) are included. Among IAELs, the most common symptom is abdominopelvic pain (63.9% of DPL, and 69.2% of PMs cases, respectively). In contrast, EAELs exhibit heterogeneous clinical presentations; dyspnea is the most common symptom (29.7% of BML, and 29.9% of IVL cases, respectively). 68.8% of DPL, 60% of PM, 89.7% of BML, and 56.4% of IVL patients underwent previous uterine surgery. A significant association ( DPL, PM, BML, and IVL exhibit overlapping characteristics, requiring a multimodal approach that includes imaging, histopathology, and surgical or medical management. Greater awareness among clinicians is needed regarding surgical procedures involving ligation and/or cutting of major uterine vessels, which appear to contribute to the development of EAELs, and morcellation, which tends to promote intraperitoneal metastatic spread.

Molecular Features of HPV-Independent Cervical Cancers

HPV-independent cervical cancers represent a small proportion of these types of cancers, predominantly glandular lesions. It should be noted that some cases may depend on diagnostic problems that lead to false negative cases. However, the most recent classifications distinguish cervical tumors into HPV-associated and HPV-independent cancers. HPV-negative cervical carcinomas (5–11% of all cases) mainly include rare adenocarcinomas (gastric, mesonephric, clear, serous, and endometrioid) and present distinct clinical and molecular features. These tumors usually affect older women and are diagnosed at more advanced stages than HPV-positive tumors, with an overall worse prognosis. This concerning and notably worse prognosis highlights the need for further research and understanding. Unlike HPV-positive carcinomas (which depend on the viral oncogenes E6/E7), HPV-independent tumors accumulate genomic mutations that activate oncogenes and inactivate suppressor genes. Therefore, a comprehensive overview of these aspects can be the key to a better understanding and developing personalized treatments. In the present review, the main mutated genes, the signaling pathways involved, the differences from HPV-positive tumors, the distinctive immunohistochemical markers, and the diagnostic and therapeutic implications are explored in depth.

What is the value of pre-surgical variables in addition to cone dimensions in predicting cone margin status?

Previous studies have shown associations between independent pre-conization variables (e.g. smoking, age, cytological grade, menopause) and positive or negative cone margins. However, it is not clear if these pre-surgical variables add predictive value to cone dimensions in the prediction of cone margin status. This study aimed to compare different models predicting positive ecto- or endocervical margins to assess whether pre-conization variables provide significant added value compared with cone dimensions alone. One hundred and sixty-one consecutive women with high-grade cervical intra-epithelial neoplasia on cone specimens were analysed retrospectively. The sample was divided into women with positive ecto- or endocervical cone margins and women with negative ecto- or endocervical cone margins. Pre-conization clinical features, cone volume and cone length were included among the study variables. Multivariate stepwise regression analysis was used to create different models predicting incomplete cervical excision. The added value of pre-conization predictors was measured with receiver operating characteristic (ROC) curve comparisons. Fifty-seven (35.4 %) women had incomplete cervical excision. Multivariate analysis showed that a positive ectocervical margin was significantly associated with low-grade cervical cytology [odds ratio (OR) = 0.25, 95 % confidence interval (CI) 0.09-0.70] and cone length (OR = 0.69, 95 % CI 0.58-0.82, criterion <9 mm). The area under the curve (AUC) of the combined model for prediction of a positive ectocervical margin was 0.78 (95 % CI 0.70-0.84, p < 0.001). A positive endocervical margin was associated with cone length (OR=0.78, 95 % CI 0.65-0.93, criterion <9 mm) and age (OR=1.07, 95 % CI 1.02-1.11, criterion ≥45 years). The AUC of the combined model for prediction of positive endocervical margin was 0.75 (95 % CI 0.66-0.82, p < 0.001). Comparison of ROC curves showed that the addition of pre-conization variables to cone length did not yield significant predictive results for either ecto- or endocervical cone margins (p = 0.228 and 0.349, respectively). The addition of pre-conization clinical variables to cone dimensions did not improve the prediction of cone margin status significantly in the study cohort. Among cone dimensions, cone length was the best predictor of come margin status.

Role of Age, Comorbidity, and Frailty in the Prediction of Postoperative Complications After Surgery for Vulvar Cancer: A Retrospective Cohort Study with the Development of a Nomogram

Surgery is the cornerstone of vulvar cancer treatment, but it is associated with a significant risk of complications that may impact prognosis, particularly in older patients with multiple comorbidities. The objective of this study was to evaluate the role of age, comorbidities, and frailty in predicting postoperative complications after vulvar cancer surgery and to develop a predictive nomogram. A retrospective cohort study was conducted, including patients who underwent surgery for vulvar cancer at two Italian institutions from January 2018 to December 2023. A logistic regression model for the rate of Clavien-Dindo 2+ 30-days complications was run, considering the age-adjusted Charlson Comorbidity Index (AACCI), body mass index (BMI), and frailty as exposures. Lesion characteristics and surgical procedures were considered as confounders. Among the 225 included patients, 50 (22.2%) had a grade 2+ complication. The predictive score of the nomogram ranged from 44 to 140. The AACCI (0–64 points) and BMI (0–100 points) were independently associated with a risk of complications. A nomogram including the AACCI and BMI predicts the risk of complications for patients undergoing surgery for vulvar cancer. The preoperative determination of the risk of complications enables surgical planning and allows a tailored peri- and postoperative management plan.

Extramammary Paget’s Disease of the Vulva and Concomitant Premalignant/Malignant Vulvar Lesions: A Potential Challenge in Diagnosis and Treatment

The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget’s disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers.

HPV-Negative Adenocarcinomas of the Uterine Cervix: From Molecular Characterization to Clinical Implications

Cervical cancer is the fourth most common cancer in women. It is the leading cause of female deaths in developing countries. Most of these cervical neoplasms are represented by squamous lesions. Cervical adenocarcinoma causes about a quarter of cervical cancers. In contrast to squamous lesions, cervical glandular disease is HPV-negative in about 15–20% of cases. HPV-negative cervical adenocarcinomas typically present in advanced stages at clinical evaluation, resulting in a poorer prognosis. The overall and disease-free survival of glandular lesions is lower than that of squamous lesions. Treatment options require definitive treatments, as fertility-sparing is not recommended. Moreover, the impact of HPV vaccination and primary HPV screening is likely to affect these lesions less; hence, the interest in this challenging topic for clinical practice. An updated review focusing on clinical and molecular characterization, prognostic factors, and therapeutic options may be helpful for properly managing such cervical lesions.

Should attention be paid to the cone depth in the fully visible transformation zone? Retrospective analysis of 517 patients with cervical intraepithelial neoplasia grade 3

AbstractObjectiveThe predictors of positive endocervical margin (EM) and a cone‐depth cutoff value are not established in the fully visible transformation zone (TZ). The present study aimed to assess the independent variables associated with positive EM in women with high‐grade cervical intraepithelial neoplasia (CIN) and fully visible TZ.MethodsThe current investigation was a retrospective study including women with fully visible TZ and CIN 3 cone histology between 2014 and 2019. The sample was divided into women with positive versus those with negative EM. Univariate and multivariate analyses were performed. Finally, receiver operating characteristic curve analysis was also used.ResultsA total of 123 of 517 women (23.8%) showed positive EM at conization. Multivariate analysis found a positive association with type 2 TZ (odds ratio [OR], 2.17 [95% confidence interval (CI), 1.19–3.94]) and lesion extension ≥2 cervical quadrants (OR, 35.57 [95% CI, 17.96–70.45]). Cone depth was inversely related to positive EM (OR, 0.71 [95% CI, 0.63–0.80]). In women with type 2 TZ and lesion extension ≥2 cervical quadrants, the cutoff value was achieved at 8‐mm cone depth (area under the curve, 0.79 [95% CI, 0.67–0.90]).ConclusionIn women with high‐grade CIN and fully visible TZ undergoing conization, the lesion extension and the TZ subtype (1 or 2) should be considered. A no less than 9‐mm cone depth provided a fair predictive value in achieving free EM.

Comparison Of Cytology And Molecular Screening For Detecting Cervical Reactive Cellular Changes In General Population

This study compares the efficacy of cytology (Pap smear) with the molecular screening in their ability to detect reactive cellular changes in the cervix among an open population