Mucosa-Associated Lymphoid Tissue Lymphoma of the Thyroid Gland: A Systematic Review of the Literature.

OBJECTIVE: Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type of the thyroid gland is a rare indolent malignant disease encountered in approximately 0.5% of patients with Hashimoto thyroiditis (HT). The purpose of the present systematic review was to accumulate the current evidence in the field. STUDY DESIGN: We searched the Medline, Scopus, EMBASE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials CENTRAL databases from inception to May 2018. Statistical analysis was performed with SPSS version 22.0. RESULTS: Fourteen case series and 20 case reports were finally included in the present systematic review. Analysis of the patient data included in the published case reports suggested that the age at diagnosis of MALT lymphoma does no differ among males and females (64 [52.5-73] vs. 67 [60.5-72] years, p = 0.442). HT was detected in 60% of patients, whereas coexisting carcinoma was evident in 17% of cases. The incidence of HT and thyroid cancer was comparable among males and females (p = 0.474 and p > 0.999, respectively). Among all patients included in the present systematic review there were two disease relapses and two deaths attributed to the disease. CONCLUSION: MALT lymphoma of the thyroid gland is a rare malignancy with an indolent course. The scarce data available in the literature preclude safe conclusions concerning the mode of treatment and follow-up of these patients. However, the combination of minimally invasive surgery and adjuvant therapy seems feasible. Moreover, an extended follow-up period is recommended.

Gynecological adverse effects of natalizumab administration: Case report and review of the literature.

BACKGROUND: Natalizumab is administered for the treatment of relapsing-remitting multiple sclerosis (RR-MS) with high disease activity.Natalizumab therapy has been associated with adverse effects, such as progressive multifocal leukoencephalopathy, liver damage, nasopharyngitis, urinary tract infection, urticaria, cephalgia, dizziness, fatigue, nausea, fever, rigidity, anxiety and gastroenteritis. OBJECTIVE: To describe a case of a woman with RR-MS who developed recurrent vaginitis on natalizumab administration. METHODS: Case report and review of the literature. RESULTS: The case of a 26-year-old Caucasian woman with RR-MS, who presented with recurrent vaginitis since the initiation of treatment with natalizumab, is reported. The patient had a 4-year history of RR-MS; monotherapy with natalizumab (inj. 300 mg/month) came after one year after the initial diagnosis. Since then, she had a history of persistent gynecological infections; the repeated vaginal cultures revealed a variety of underlying pathogens. The patient underwent numerous treatments with local and systematic antibiotics as well as antifungal agents. After the initiation of probiotics and local hygiene measures, recurrences resolved and the patient remains recurrence-free at one-year follow-up. CONCLUSIONS: Recurrent vaginitis should be taken into account as a possible adverse effect causing discomfort during long-term natalizumab treatment. Simple measures, such as probiotic administration and meticulous local hygiene, can provide adequate relief for such patients.

Ki-67 Expression as a Factor Predicting Recurrence of Ductal Carcinoma In Situ of the Breast: A Systematic Review and Meta-Analysis.

BACKGROUND: Ki-67 is a marker of proliferating cells; in this meta-analysis we aimed to examine whether Ki-67 expression can predict recurrence rates of breast ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible articles were sought in MEDLINE up to April 30, 2017. Random effects (DerSimonian-Laird) models were used for the calculation of pooled relative risk (RR) estimates; meta-regression analysis was also performed. Separate analyses were performed according to Ki-67 expression cutoff levels, invasiveness of recurrence, and adjustment of studies. RESULTS: Ten eligible cohort studies were synthesized; a significant association between Ki-67 expression and DCIS recurrence was noted for the Ki-67 cutoff at 10% (RR = 1.66; 95% confidence interval [CI], 1.14-2.42) as well as the Ki-67 cutoff at 14% (RR = 1.67; 95% CI, 1.01-2.77). Subanalysis on unadjusted (RR = 1.48; 95% CI, 1.06-2.07) and adjusted studies (RR = 2.19; 95% CI, 1.42-3.38) replicated the statistically significant findings. Ki-67 expression predicted the risk of invasive (RR = 1.53; 95% CI, 1.14-2.06) and noninvasive (RR = 1.59; 95% CI, 1.19-2.13) recurrence. CONCLUSION: This meta-analysis highlights Ki-67 expression as a predictor of DCIS recurrence; nevertheless, additional adjusted studies, with adequate follow-up periods, stemming from various world regions seem to be needed on this topic.

Giving Birth After Fertility Sparing Treatment for a Yolk Sac Tumour: Case Report.

Yolk Sac Tumours (YSTs) of the ovary, also called Endodermal Sinus Tumours (ESTs), are the second most common Malignant Ovarian Germ Cell Tumours (MOGCTs), after dysgerminomas. YSTs occur primarily in children and young women. We present a case report of a 20-year-old woman who had been diagnosed with YST (tumour diameter of 29 cm). The patient underwent fertility sparing surgery and was subsequently treated with adjuvant chemotherapy (four cycles of bleomycin, etoposide and cisplatin). Two years after the diagnosis of YST, she successfully gave birth to a healthy girl (birth weight 3,500 g, Apgar score of 9-10 and a spontaneous vaginal delivery). During pregnancy, she had microscopic hematuria and bilateral nephrolithiasis, was ultrasonographically diagnosed. The conception after fertility sparing treatment of YST is possible and the birth of a healthy child is feasible. There are no current guidelines for surveillance of such patients during pregnancy; however, structured pregnancy surveillance in such survivors seems necessary.

Synchronous Endometrial and Ovarian Carcinoma: A Case Series.

Synchronous ovarian and endometrial cancer (SEOC) is a rare instance but it accounts for 50-70% of all synchronous female genital tract tumors. We report three cases of women who were diagnosed with SEOC and underwent surgical staging. All cases were of the endometrioid subtype, grade 1, both in the ovarian and endometrial component. Two of them were stage Ia/Ia, and the third was stage Ib/Ib. More than 2 years after the diagnosis, all patients were alive and recurrence-free. The present report critically discusses the main characteristics, risk factors, and management of patients with SEOCs.

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.

An ovarian mass after breast cancer: Metachronous carcinoma or metastasis? A case report.

INTRODUCTION: Differentiating between primary and secondary ovarian cancer can be a difficult task. In hereditary conditions breast malignancies and primary ovarian cancer often coexist. PRESENTATION OF CASE: We present a 45-year-old patient with an ovarian mass two years after the diagnosis of a lobular, triple negative breast carcinoma. There was concern whether the lesion represented a metachronous ovarian cancer or a metastasis of the lobular carcinoma. The final histological examination showed a metastatic lesion, deriving from the lobular breast carcinoma, as evidenced by the immunohistochemical profile; nevertheless, there were changes in hormonal receptor expression in the metastatic lesion compared to the primary, triple negative tumor. The patient underwent genetic testing for BRCA1 and BRCA2 mutations and was negative. In the adjuvant setting the patient received 6 cycles of chemotherapy with carboplatin and paclitaxel; eighteen months later, the patient remains without disease recurrence. DISCUSSION AND CONCLUSION: This case report highlights the role of imaging, histology and predominantly immunohistochemistry as valuable tools in the assessment of ambiguous ovarian lesions after breast cancer.

Endocervical Carcinogenesis and HPV Vaccination: An Occasional Circumstance or a Gap in the Chain?

As a result of the Human Papillomavirus (HPV) vaccination program, the prevalence of precancerous dysplasia and invasive cervical cancer has substantially decreased. In this brief report, we present a case of a young patient who was diagnosed with in situ adenocarcinoma of the cervix. This 30-year-old female had completed the HPV vaccination after she became sexually active and has been undergoing annual gynecological assessments, including clinical examination and Pap test, all of which had been negative. This year, her Pap test revealed a low grade squamous intraepithelial lesion (LGSIL) and additionally a colposcopy was performed. Given the extent of the lesion and since the colposcopy was inadequate, the patient underwent a type 3 large loop excision of the transformation zone and a curettage of the endocervix under local anesthesia. The pathological diagnosis from cervical biopsy revealed an in situ adenocarcinoma of the endocervix with negative limits. The HPV subtypes 16 and 83 were detected with PCR. After proper consultation she decided to preserve her fertility and to undergo a regular follow-up, postponing hysterectomy after the completion of her family planning. In conclusion, this case report highlights the need for diagnostic surveillance regarding HPV-related cervical cancer even after vaccination.

Vulvar, Perianal and Perineal Cancer After Hidradenitis Suppurativa: A Systematic Review and Pooled Analysis.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that frequently involves the perineal and perianal regions. The association between HS and malignant transformation is a rare but under recognized phenomenon. OBJECTIVE: This systematic review aims to summarize all available cases of vulvar and perianal/perineal cancer emerging in patients with HS, describing clinical and therapeutic particularities of these coexisting conditions in female patients. MATERIALS AND METHODS: This systematic review and pooled analysis was performed in accordance with the PRISMA guidelines; end-of-search date was June 15, 2015. RESULTS: A total of 13 eligible articles were identified; 7 cases of vulvar cancer and 6 cases of perineal/perianal carcinomas in patients with HS were noted. A majority of published cases pertained to rather advanced carcinomas; only occasionally early stage carcinomas were identified. The optimal modifications in the treatment scheme of vulvar, perianal, and perineal cancer in patients with HS have not been established; detailed reporting of recurrence- and survival-related aspects is advised. CONCLUSION: Vulvar, perianal, and perineal cancer represent a rare but serious complication of HS.

Serum inhibin and leptin: Risk factors for pre-eclampsia?

BACKGROUND: Pre-eclampsia and eclampsia are parts of the broader spectrum of hypertensive disorders complicating pregnancy. This study aims to examine the association between serum inhibin and leptin levels and pre-eclampsia. METHODS: This study included 98 consecutive cases of pregnant women with pre-eclampsia, together with their 98 pregnant controls, matched for age, gestational week and time period of delivery. Maternal venous blood samples were obtained within 24h before delivery. In addition to serum inhibin and leptin, birth order, multiple pregnancy, maternal age, maternal overweight/obesity, maternal education, maternal smoking and family history of diabetes/hypertension, were examined as risk factors. Multivariate logistic regression analysis was performed. RESULTS: At the univariate analysis, serum inhibin and leptin levels were significantly higher in cases vs. CONTROLS: Pre-eclampsia occurred more frequently in primiparous women, whereas overweight and obesity were also associated with pre-eclampsia. At the multivariate analysis, higher serum inhibin levels were associated with pre-eclampsia (multivariate OR=1.09, 95%CI: 1.03-1.17, p=0.004, increase per 0.1ng/mL). On the other hand, leptin was not independently associated with the occurrence of pre-eclampsia (multivariate OR=1.02, 95%CI: 0.95-1.09, p=0.631, increase per 10ng/mL). CONCLUSIONS: Elevated serum inhibin levels seem to be associated with pre-eclampsia, reflecting placental dysfunction. Increased serum leptin levels may merely reflect an elevated maternal body mass index, which is a well-known risk factor for pre-eclampsia.

c-met is overexpressed in type I ovarian cancer: Results of an investigative analysis in a cohort of consecutive ovarian cancer patients.

The tyrosine kinase c-met alters signaling cascades such as the BRAF-MAPK and PI3K-PKB pathways. These alterations are involved in the carcinogenesis of type I but not type II ovarian cancer (OC). Therefore, the present study investigated the patterns of c-met expression in a cohort of consecutive patients with OC. c-met expression was determined by immunohistochemical analysis. Differences in c-met overexpression among subgroups of established clinicopathological features, including age, histological subtype, tumor stage, histological grading, post-operative tumor burden and completeness of chemotherapy, were determined by χ2 test. Cox regression analyses were performed to determine the prognostic effect of c-met. Survival rates were estimated using the Kaplan-Meier method. A total of 106 patients were enrolled into the study. c-met was overexpressed in 20.8% of the entire cohort; 35.7% of patients with type I OC and 8.6% of patients with type II OC showed overexpression (P=0.001). However, c-met overexpression was not associated with any other established clinicopathological features (all P-values >0.05). Univariate Cox regression analysis showed that overexpression of c-met was associated neither with progression-free survival (PFS) nor with disease-specific survival (DSS) (P=0.835 and P=0.414, respectively). Kaplan-Meier plots also failed to demonstrate an effect of c-met on the 5-year PFS and DSS rates (P=0.938 and P=0.412, respectively). These findings support the hypotheses that the overexpression of c-met is associated with type I but not type II OC, and that overexpression of c-met does not affect the prognosis of OC.

Office Endometrial Cytological Sampling: Examining Predictors of Strenuousness.

BACKGROUND/AIM: Endometrial cytology is an alternative perspective for the diagnosis of endometrial cancer. The present study examined the potential risk factors for strenuousness in endometrial cytology sampling. PATIENTS AND METHODS: One hundred and eighty-one women who underwent endometrial cytological sampling with the Endogyn curette participated in the study. Strenuousness in obtaining the sample was graded into a five-level scale-score. Various parameters were assessed in association with the strenuousness score. Multivariate ordinal logistic regression analysis was performed. RESULTS: Postmenopausal status (adjusted OR=2.63, 95%CI=1.52-4.56, p=0.001) and previous invasive/surgical procedures in the cervix (adjusted OR=2.15, 95%CI=1.10-4.24, p=0.026) were associated with higher strenuousness score. Participants' age at sampling, phase of menstrual cycle, endometrial thickness, obesity, current hormonal use and reproductive history of women were not significantly associated with the strenuousness of the procedure. CONCLUSION: Increased difficulty during endometrial sampling is noted in postmenopausal women, and in patients with previous surgical procedures in the cervix.

Validation of a two-tier grading system in an unselected, consecutive cohort of serous ovarian cancer patients.

PURPOSE: New insights into the carcinogenesis of ovarian cancer (OC) lead to the definition of low-grade and high-grade serous OC. In this study, we validated the MD Anderson Cancer Center (MDACC) two-tier grading system and compared it with the traditional three-tier grading system as suggested by the International Federation of Gynecology and Obstetrics (FIGO). METHODS: Consecutive patients with serous OC were enrolled. These two grading systems were assessed independently from each other. Kaplan-Meier estimates and Cox-regression analyses were performed to validate and compare their prognostic impact. RESULTS: 143 consecutive patients entered the study. According to the Kaplan-Meier estimates, the MDACC grading system (p = 0.001) predicted the progression free survival (PFS) more precisely than the FIGO system (p = 0.025). The MDACC grading system (p = 0.008) but not the FIGO system (p = 0.329) showed a statistically significant difference in terms of disease specific survival (DSS). Multivariable Cox-regression analyses revealed an independent prognostic impact of the MDACC grading system but not of the FIGO system for PFS (HR 1.570; 95 % CI 1.007-2.449; p = 0.047, and HR 0.712; 95 % CI 0.476-1.066; p = 0.099, respectively). Concerning DSS, the two-tier grading system but not the FIGO system showed a prognostic impact in a univariable Cox-regression analysis (HR 2.152; 95 % CI 1.207-3.835; p = 0.009, and HR 1.258; 95 % CI 0.801-1.975; p = 0.319, respectively). CONCLUSIONS: We were able to validate the MDACC grading system in serous OC. Moreover, this grading system was stronger associated with survival than the FIGO system.

Hormonal receptor status, Ki-67 and HER2 expression: Prognostic value in the recurrence of ductal carcinoma in situ of the breast?

PURPOSE: Local recurrence is considered a major concern in patients diagnosed with ductal carcinoma in situ (DCIS), as its invasive occurrence is associated with high rates of distant disease and mortality. This study aims to assess the possible correlation of hormonal receptor status, Ki-67 and HER2 expression with recurrence rates in women with DCIS, taking also into account the potential prognostic effects of grade and age at diagnosis. METHODS: 230 consecutive patients with DCIS were included in this study. Invasive and non-invasive recurrence events were recorded, as a total. Clinicopathological information, as well as PR positivity, ER positivity, HER2 positivity and ki-67 expression were analyzed. Multivariable Cox regression analysis was performed, examining the risk factors for recurrence. RESULTS: Recurrence was noted in 17.8% of cases; the median follow-up was 44 months. Higher grade (adjusted HR = 1.72, 95%CI: 1.06-2.78), age at diagnosis (adjusted HR = 0.60, 95%CI: 0.43-0.83), Ki-67 expression (adjusted HR = 1.78, 95%CI: 1.11-2.88), and type of administered treatment were independently associated with increased recurrence rates. Recurrence rates were not significantly associated with ER, PR status or HER2 expression. CONCLUSION: In addition to high grade, administered treatment and younger age at diagnosis, high Ki-67 expression seems to be independently associated with increased likelihood of recurrence in patients with DCIS. Future studies with additional molecular markers seem necessary to further improve the identification of high-risk patients for DCIS recurrence.