The impact of inguinal lymph node micrometastases in patients with vulvar cancer.

PURPOSE: Inguinofemoral metastases are a major determinant of vulvar cancer relapse. Until today, the impact of micrometastases of inguinal nodes on local recurrence rates of patients with vulvar cancer remains unknown. The purpose of this retrospective study is to evaluate the rates of micrometastases in a series of patients with vulvar cancer treated with radical vulvectomy and inguinofemoral LND and to assess the probability of cancer relapse among this specific category. METHODS: We conducted a retrospective observational study on patients with vulvar cancer who attended the gynaecological department of Anticancer Hospital of St. Savvas between January 1989 and January 2007. Ultra-staging of lymph nodes for micrometastases was performed after cutting the remaining specimens with a microtome in multiple slices of 3 µm. Subsequently they were stained with traditional hematoxylin and eosin and CK AE1/AE3 antibodies for immunohistochemichal analysis. RESULTS: Ninety-two patients with primary vulvar malignancies were included in the present retrospective study. Ultrastaging of the lymph nodes revealed micrometastases in five patients (5.4%). Neither the duration of the procedure, nor the number of retrieved lymph nodes was directly associated with the presence of micrometastases. The patients were followed up for more than 5 years. Sixteen recurrences (17.4%) occurred during this period. The presence of micrometastases did not influence the recurrence rate (OR 3.57, 95% CI 0.55-23.36, p = 0.184). CONCLUSION: Ultrastaging of inguinal nodes does not seem to add any benefit in the prediction of local recurrence rates. Future multicenter studies are needed in the field to corroborate our findings.

Leiomyoma of the uterine round ligament: A case report.

Leiomyomas are common benign tumours that can arise in any anatomical structure containing smooth muscle. Their localization in the uterine round ligament is rare, although leiomyomas are the most frequent tumour of this structure. Leiomyomas present as inguinal, labial or intra-abdominal masses, and are often misdiagnosed as hernias or enlarged lymph nodes. The aim of the present study was to describe a rare case of a large intra-abdominal mesenchymal neoplasm arising from the right round ligament of the uterus. A 51-year-old asymptomatic female patient (gravida 3, para 3) presented herself for a routine gynaecological examination. A transvaginal ultrasound examination revealed a solid heterogeneous mass with a maximum diameter of 9 cm localized at the right parametrial space. Further preoperative evaluation using magnetic resonance imaging revealed that the mass contained solid and cystic components, which was suggestive of a mesenchymal neoplasm with possible involvement of the right ovary. Complete excision of the tumour and total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed via laparotomy under general anaesthesia. The intraoperative findings, frozen section biopsies and final histological examination of the tumour established the diagnosis of an intra-abdominal myoma of the right uterine round ligament. The majority of abdominal round ligament myomas are initially asymptomatic. The role of synchronous imaging examinations, such as ultrasonography and magnetic resonance imaging, in the diagnosis of these lesions is crucial.

Paget's disease of the vulva detected in vulvar and vaginal brushing smears: a case report.

UNLABELLED: BACKGROUND; Vulvar Paget's disease comprises only 1-8% of malignant vulvar tumors. It is associated with an underlying carcinoma in 20-30% of cases. Clinically, it manifests as erythematous areas with hyperkeratotic plaques, accompanied by pruritus. Histologically, it is characterized by large, pale cells with mucicarmine-positive cytoplasm, isolated or in aggregates, in the epidermis. CASE: A 75-year-old woman presented with erythematous plaques covering the entire vulvar, vaginal and perianal area and pruritus. Smears were taken from all 3 sites and stained with Papanicolaou stain. Additionally, biopsies were taken from the vulva, vagina and outer borders of the lesion and were stained with hematoxylin-eosin and also for periodic acid-Schiff stain, CK7, CEA, S-100 and CK20. The cytologic examination revealed numerous round to columnar, moderately enlarged atypical cells, dispersed or in loose groups, with abundant clear cytoplasm, vesicular nuclei and prominent nucleoli. The histologic findings confirmed the cytologic diagnosis. No indication of an underlying adenocarcinoma was found. CONCLUSION: Although the histologic examination of a vulvar lesion is necessary in order to confirm the diagnosis of vulvar Paget's disease and rule out the possibility of an underlying invasive adenocarcinoma, the cytologic examination of vulvar smears is useful for alerting the clinician to the possibility of vulvar Paget's disease.

Primary squamous cell carcinoma of the ovary. Review of the literature.

PURPOSE: Primary squamous cell carcinoma (SCC) of the ovary is rare. Most cases arise from a cystic teratoma or less frequently from Brenner tumor or endometriosis. We reviewed 36 cases of primary ovarian SCC reported in the literature including a case diagnosed and treated in our institution. METHODS: Data was collected by using the key-words "primary squamous cell carcinoma" and "ovary" on Google Scholar and PubMed in April 2018. All reviewed cases were analyzed according to diagnosis, surgical approach, adjuvant therapy and outcome. RESULTS: To date 23 articles presenting 36 cases of primary ovarian SCC are reported. Nine patients had stage I, 8 stage II, 11 stage III and 5 stage IV disease, whereas 3 patients had in situ carcinoma. All patients underwent surgery (mainly hysterectomy with bilateral salpingo-oophorectomy). Adjuvant therapy was reported in 24 patients, 15 of which received chemotherapy, 6 radiotherapy and 3 a combination of both. Chemotherapy regimens were similar to the ones used in ovarian carcinoma (more often platinum plus paclitaxel). Follow-up period was in general short and survival varied between 9 days and 14 years, depending on the stage at diagnosis. CONCLUSIONS: Primary ovarian SCC is a rare entity with poor prognosis, compared to serous carcinoma. Treatment is usually extrapolated from classical ovarian carcinoma algorithms, including surgical management combined with adjuvant chemotherapy with or without radiotherapy. Further investigations are needed to define optimal treatment, such as chemotherapy regimens and the role of radiotherapy and lymph node dissection.

Giant condyloma acuminatum-malignant transformation.

Giant condyloma acuminata are associated with malignant transformation in up to 50% of cases, high recurrence rate, and poor prognosis. Treatment strategies have included wide local excision, abdominopelvic resection, and addition of radiotherapy and adjuvant and/or neoadjuvant systemic chemotherapy.

Image analysis and multi-layer perceptron artificial neural networks for the discrimination between benign and malignant endometrial lesions.

BACKGROUND: This study aims to investigate the efficacy of an Artificial Neural Network based on Multi-Layer Perceptron (ANN-MPL) to discriminate between benign and malignant endometrial nuclei and lesions in cytological specimens. METHODS: We collected 416 histologically confirmed liquid-based cytological smears from 168 healthy patients, 152 patients with malignancy, 52 with hyperplasia without atypia, 20 with hyperplasia with atypia, and 24 patients with endometrial polyps. The morphometric characteristics of 90 nuclei per case were analyzed using a custom image analysis system; half of them were used to train the MPL-ANN model, which classified each nucleus as benign or malignant. Data from the remaining 50% of cases were used to evaluate the performance and stability of the ANN. The MLP-ANN for the nuclei classification (numeric and percentage classifiers) and the algorithms for the determination of the optimum threshold values were estimated with in-house developed software for the MATLAB v2011b programming environment; the diagnostic accuracy measures were also calculated. RESULTS: The accuracy of the MPL-ANN model for the classification of endometrial nuclei was 81.33%, while specificity was 88.84% and sensitivity 69.38%. For the case classification based on numeric classifier the overall accuracy was 90.87%, the specificity 93.03% and the sensitivity 87.79%; the indices for the percentage classifier were 95.91%, 93.44%, and 99.42%, respectively. CONCLUSION: Computerized systems based on ANNs can aid the cytological classification of endometrial nuclei and lesions with sufficient sensitivity and specificity. Diagn. Cytopathol. 2017;45:202-211. © 2016 Wiley Periodicals, Inc.

Evaluation Analysis of miRNAs Overexpression in Liquid-Based Cytology Endometrial Samples.

Background: miRNAs have an important role as their deregulation is linked to endometrial cancer. Methods: A custom miScript® miRNA PCR Array was used to investigate for the first time the expression of eight miRNAs in forty-nine histologically confirmed Liquid Based cytology endometrial samples. The expression profile of the same miRNAs was also examined in sixty formalin-fixed tissue samples. Results: Expression of seven miRNAs was significantly higher in malignant samples with three of them (mir-182, mir-141 and mir-205) performing optimally. Conclusion: These results suggest the potential use of this non-invasive method of sampling for miRNA expression studies. Furthermore miRNA overexpression could serve as an ancillary or reflex test for optimal identification of malignant samples especially in morphologically inadequate samples.

A reporting system for endometrial cytology: Cytomorphologic criteria-Implied risk of malignancy.

BACKGROUND: There have been various attempts to assess endometrial lesions on cytological material obtained via direct endometrial sampling. The majority of efforts focus on the description of cytological criteria that lead to classification systems resembling histological reporting formats. These systems have low reproducibility, especially in cases of atypical hyperplasia and well differentiated carcinomas. Moreover, they are not linked to the implied risk of malignancy. METHODS: The material was collected from women examined at the outpatient department of four participating hospitals. We analyzed 866 consecutive, histologically confirmed cases. The sample collection was performed using the EndoGyn device, and processed via Liquid Based Cytology, namely ThinPrep technique. The diagnostic categories and criteria were established by two cytopathologists experienced in endometrial cytology; performance of the proposed reporting format was assessed on the basis of histological outcome; moreover, the implied risk of malignancy was calculated. RESULTS: The proposed six diagnostic categories are as follows: (i) nondiagnostic or unsatisfactory; (ii) without evidence of hyperplasia or malignancy; (iii) atypical cells of endometrium of undetermined significance; (iv) atypical cells of endometrium of low probability for malignancy; (v) atypical cells of endometrium of high probability for malignancy; and (vi) malignant. The risk of malignancy was 1.42% ± 0.98%, 44.44% ± 32.46% (nine cases), 4.30% ± 4.12%, 89.80% ± 8.47%, and 97.81% ± 2.45%, respectively. CONCLUSION: We propose a clinically oriented classification scheme consisting of diagnostic categories with well determined criteria. Each diagnostic category is linked with an implied risk of malignancy; thus, clinicians may decide on patient management and eventually reduce unnecessary interventional diagnostic procedures. Diagn. Cytopathol. 2016;44:888-901. © 2016 Wiley Periodicals, Inc.

A Pyrosequencing Assay for the Quantitative Methylation Analysis of GALR1 in Endometrial Samples: Preliminary Results.

Endometrial cancer is the most common malignancy of the female genital tract while aberrant DNA methylation seems to play a critical role in endometrial carcinogenesis. Galanin's expression has been involved in many cancers. We developed a new pyrosequencing assay that quantifies DNA methylation of galanin's receptor-1 (GALR1). In this study, the preliminary results indicate that pyrosequencing methylation analysis of GALR1 promoter can be a useful ancillary marker to cytology as the histological status can successfully predict. This marker has the potential to lead towards better management of women with endometrial lesions and eventually reduce unnecessary interventions. In addition it can provide early warning for women with negative cytological result.

Classification of endometrial lesions by nuclear morphometry features extracted from liquid-based cytology samples: a system based on logistic regression model.

OBJECTIVE: To investigate the potential of a computerized system for the discrimination of benign from malignant endometrial nuclei and lesions. STUDY DESIGN: A total of 228 histologically confirmed liquid-based cytological smears were collected: 117 within normal limits cases, 66 malignant cases, 37 hyperplasias without atypia, and 8 cases of hyperplasia with atypia. From each case we extracted nuclear morphometric features from about 100 nuclei using a custom image analysis system. Initially we performed feature selection, and subsequently we applied a logistic regression model that classified each nucleus as benign or malignant. Based on the results of the nucleus classification process, we constructed an algorithm to discriminate endometrium cases as benign or malignant. RESULTS: The proposed system had an overall accuracy for the classification of endometrial nuclei equal to 83.02%, specificity of 85.09%, and sensitivity of 77.01%. For the case classification the overall accuracy was 92.98%, specificity was 92.86%, and sensitivity was 93.24%. CONCLUSION: The proposed computerized system can be applied for the classification of endometrial nuclei and lesions as it outperformed the standard cytological diagnosis. This study highlights interesting diagnostic features of endometrial nuclear morphology, and the proposed method can be a useful tool in the everyday practice of the cytological laboratory.

Vaginal primary malignant melanoma: a rare and aggressive tumor.

Vaginal primary malignant melanoma is a rare and very aggressive tumor. It most commonly occurs in postmenopausal women, with a mean age of 57 years. Our patient is an 80-year-old, postmenopausal Greek woman presented with a complaint of abnormal vaginal bleeding. On gynecologic examination there was a pigmented, raised, ulcerated, and irregular lesion 5 × 4.5 cm in the upper third of anterior vaginal wall. She underwent a wide local excision of the lesion. The histopathology revealed vaginal primary malignant melanoma with ulceration and no clear surgical margins. She denied any additional surgical interventions and underwent to postoperative adjuvant radiotherapy. Follow up 5 months after initial diagnosis revealed no evidence of local recurrence or distant metastasis. The prognosis of vaginal primary malignant melanoma is very poor despite treatment modality, because most of the cases are diagnosed at advanced stage. Particularly patients with no clear surgical margins and tumor size >3 cm needed postoperative adjuvant radiotherapy.

E6/E7 mRNA expression of high-risk HPV types in 849 Greek women.

AIM: The goal of this study was to investigate human papillomavirus (HPV) geno typing and high-risk HPV E6/E7 mRNA expression in 849 women. PATIENTS AND METHODS: 849 Cervical samples were obtained from patients attending an outpatient clinic to have their annual gynaecological check-up. All patients underwent a conventional Pap test. The patients were also offered HPV test with the knowledge that it is not part of the screening. RESULTS: Overall prevalence of HPV DNA was 41.3%, while E6/E7 mRNA expression was found in 20.7% of the patients. HPV DNA and E6/E7 mRNA expression were detected in 21.1% and 9.1% of normal cytological samples, respectively, 38.1% and 23.8% of atypical squamous cells of unknown significance, 84.8% and 40.7% of low-grade squamous intraepithelial lesions, and 96.4% and 89.3% of high-grade squamous intraepithelial lesions, respectively. HPV 16 was the most frequent genotype identified. CONCLUSION: E6/E7mRNA detection might be useful as a screening marker for the early prediction of active infections and subsequent progression to severe dysplasia.