Uterine Leiomyomas with Specific Histology Features of Two Fumarate Hydratase/Succinate Dehydrogenase-Deficient Tumors: A Double Case Report.

Background and Objectives: Mutations in succinate dehydrogenase (SDH) and fumarate hydratase (FH) give rise to various familial cancer syndromes, with these alterations being characteristic of certain types of histomorphologically specific leiomyomas that hold significant predictive value. Materials and Methods: This study presents two cases of uterine leiomyomas exhibiting rare histomorphological and genetic characteristics, which are crucial for prognosis and further treatment. Results: Distinct histopathological features such as marked nuclear atypia, intracellular eosinophilic globules, and abnormal intratumoral vessels raise suspicion for specific leiomyoma subtypes, which carry predictive significance for additional hereditary cancer syndromes. Immunohistochemical analysis confirmed FH/SDH deficiency in both patients, who underwent careful follow-up. Conclusions: This study describes two cases involving unusual leiomyomas, the histopathological characteristics of which may easily go unrecognized. These features hold predictive significance because their specific mutations point to additional hereditary cancer syndromes, highlighting the need for further examinations.

Cancer during pregnancy: Twenty-two years of experience from a tertiary referral center.

INTRODUCTION: Cancer complicating pregnancy is a rare but potentially life-threatening condition for both the mother and her child. The aim of the present study was to assess the outcomes for mothers and children after pregnancy complicated by malignancy and to investigate which parameters are important for their 1-year survival. MATERIAL AND METHODS: The study included 84 pregnant women diagnosed with malignant tumors during pregnancy from 2001 to 2022. The pregnancy course and outcome, as well as parameters that could influence the survival and condition of the mother and child were evaluated. Mothers and children were followed up for 1 year after delivery to assess their condition/complications and overall survival. RESULTS: Most malignancies were gynecological (31%) or hematological (23.8%) and were diagnosed and surgically treated in the second trimester. Most children (69%) showed adequate growth and development throughout pregnancy but were delivered before term (53.6%) to allow mothers to receive therapy. Adjuvant therapy during pregnancy mostly caused a transitory deterioration of the child's condition, while surgery did not significantly impact the pregnancy course. Deliveries, on average, occurred during the 33.01 ± 6.16 gestational week (range: 20-40) and mostly by cesarean section (76.2%). For mothers, the pregnancy survival rate was 95.2% and survival after 1 year was 87.5%. However, 37.5% of women were still ill and required additional therapy 1 year postpartum. The pregnancy survival rate for children was 94%, whereas the 1-year survival rate was 76.2%. Most children had a favorable condition (alive, adequately growing and developing, and without complications) at birth (81%) as well as at the 1-year follow-up (63.7%). Regression analysis identified the following predictors of favorable 1-year maternal condition: applying therapy during pregnancy, no progression of the malignancy during pregnancy, and delivery at a later gestational week. Predictors of favorable 1-year condition of children were lower histopathological grade of malignancy, surgery as therapy for malignancy, obtaining higher birthweight, and delivery by cesarean section. CONCLUSIONS: If the malignancy is not progressing, pregnancy should be continued as long as possible for the child to obtain adequate birthweight. Both surgery and chemotherapy were safe therapeutic choices, as most pregnancies continued successfully after therapy.

Giant dermatofibrosarcoma protuberans vulvae: rare clinical presentation and literature review.

Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing fibro-cutaneous tumor of low to intermediate grade malignancy. It is characterized by local dermal and subcutaneous infiltration, but also with destructive infiltration of the surrounding tissues (muscle, fascia, and bone). The size of the tumor varies from small nodular to large neglected masses. Males and females are equally affected. The tumor is most often localized in the trunk and the proximal extremities. At a molecular level, more than 90% of all DFSP arise from the translocation of chromosomes 17 and 22. Clinically, it usually occurs in the form of flesh-colored or slightly yellow-brown skin tumor, irregular borders or multinodular appearance. The definitive diagnosis of DFSP is made by biopsy in combination with histological morphology and immunohistochemistry. The standard treatment for DFSP is surgical resection. Radiation treatment is an option for primary inoperable tumors and prior multiple recurrences. There is no consensus about chemotherapy regimens. Imatinib - a tyrosine kinase inhibitor - is approved in Europe for the treatment of inoperable primary tumors, locally inoperable recurrent disease, and metastatic DFSP. The recommended dose is 400-600 mg/daily. DFSP of the vulva is extremely rare, with less than 60 cases reported in the literature. Tumor behavior of DFSP of the vulva does not differ from other DFSP localizations. Spontaneous regressions are common while distant metastases are rare. Multidisciplinary approach requiring wide resection, margin assessment and reconstruction is the therapy of choice.

Utilization of ultrasound as a diagnostic tool in the preoperative assessment of patients with adnexal masses.

PURPOSE: To evaluate the reliability of ultrasound scan (US) findings in the preoperative assessment of the nature of adnexal masses in females. METHODS: After detailed history, a preoperative US examination was performed in all women. Tumor diameter, localization, the presence of solid, cystic and multilocular components, excrescences, metastasis and free fluid were assessed. Doppler scan was done and pulsatility (PI) and resistance indices (RI) were determined. These data were compared with postoperatively obtained histopathological findings and statistically analyzed. RESULTS: The study included 609 women out of which 20.7% had malignant, 73.7% benign, and 5.6% border-line tumors. Patients with malignant tumors were oldest (p<0.001). There were significantly more positive US parameters in malignant than in benign tumors (p<0.001). Also, there were significant differences (p<0.001) between malignant, benign and borderline tumors regarding all examined US and Doppler parameters except tumor multilocularity. RI had sensitivity 75%, specificity 61.2%, positive predictive value (PPV) 42.70% and negative predictive value (NPV) 96.16%. PI had sensitivity 50%, specificity 35.3%, PPV 8.37% and NPV 25.93%. Sensitivity of US characteristics was 94.34%, specificity 30.62%, PPV 22.27% and NPV 96.25%. CONCLUSIONS: US pattern characteristics and Doppler parameters were found to be moderately reliable in discriminating malignant, benign and borderline adnexal tumors. Tumor of solid or mixed consistency, presence of ascites and excrescences were the best predictors of malignancy.

Risk of malignancy index validity assessment in premenopausal and postmenopausal women with adnexal tumors.

OBJECTIVE: The aim of this study was to investigate the validity of the risk of malignancy index (RMI) in premenopausal and postmenopausal patients with adnexal masses. MATERIALS AND METHODS: The study involved all women treated for adnexal tumors throughout an 18-month period in the Clinic for Gynecology and Obstetrics, Clinical Center of Serbia (Belgrade, Serbia). On admission, detailed anamnestic and laboratory data were obtained and an expert ultrasound scan was performed. The RMI was calculated for all patients and the obtained data were related to histopathological findings of the tumors. For statistical analysis, we used descriptive and analytical statistics methods and an SPSS computer program. RESULTS: From a total number of 540 women, 85 women had malignant tumors; 20 women, borderline tumors; and 435 women, benign adnexal tumors. The RMI was reliable in 84.6% of all patients; in 77% of premenopausal patients, and in 81.1% of postmenopausal patients. The sensitivity of the RMI in the overall population was 83.81%; the specificity was 77.24%; the positive predictive value (PPV) was 47.06%, and the negative predictive value (NPV) was 95.18%. In premenopausal women, the RMI sensitivity was 83.87%; specificity, 80.31%; PPV, 28.89%; and NPV, 98.12%. In postmenopausal women the RMI sensitivity was 83.78%; specificity, 68.18%; PPV, 63.92%; and NPV, 74.71%. CONCLUSION: The RMI was a reliable factor for differentiating benign from malignant adnexal masses in premenopausal and postmenopausal patients.

Metastatic malignant ovarian melanoma--a case report.

BACKGROUND: Malignant melanomas of the female reproductive system are rare. These are biologically highly aggressive tumors with poor prognosis. Preoperative establishment of the diagnosis is practically impossible. Therapeutic approach and treatment of patients with metastatic ovarian melanoma are highly dependent on precise histological analysis. CASE REPORT: A woman aged 48 was admitted to the clinic for occasional pains in the lower abdomen and suspected myomatous changes of the uterus. The patient underwent surgery for melanoma on her right arm five years ago. Classic hysterectomy with bilateral adnexectomy with infracolic omentectomy and selective iliac lymphadenectomy were performed. Macroscopic examination revealed an oval tumefaction on the left ovary sized 12.5 x 10 x 3.5 cm of solid structure. Tumor tissue was yellowish-brown colored, of solid structure and mostly localized subcortically with central edema. Microscopic examination showed positive reaction for HMB-45, anti-Melan-A and S-100 protein, but negative immunoreactivity for estrogen and progesterone receptors. Malignant disease caused death after a 4-year follow-up period following gynecological operation. CONCLUSION: The previous diagnosis of skin melanoma is also indicative of metastatic ovarian tumor, while immunohistochemical analyses confirmed the histopathological diagnosis.

Introduction of new Tumor Marker Age Score in clinical practice: Validity evaluation for differentiation benign from malignant adnexal masses.

OBJECTIVE: The aim of the study was to examine several tumor markers and their correlation with pathohistological findings in patients with adnexal masses. METHODS: Study involved 139 patients, 84 of them with benign, 47 with malignant and 8 with borderline adnexal tumor. Levels of CA 125, CA 19-9, CEA and CA 15-3 were obtained preoperatively and assessed regarding the specific pathohistological diagnose and the patient's age. Obtaining these results led us to divide the patient's CA 125 levels with age and by doing that we have attained a new Tumor Marker Age score (TMA score). RESULTS: Patients with malignant adnexal tumors had significantly higher levels of CEA (p<0.05), CA 125, CA 19-9 and CA 15-3 tumor markers (p<0.01), in comparison with patients with benign tumors. TMA score highly statistically correlate with the tumor type (benignant/malignant). CONCLUSIONS: With the increase of tumor marker levels and the patient's age the malignant nature of adnexal tumors is more often. Results of our study highlight the importance of the use of combined tumor markers (at least CA-125 and CA 19-9) in women with adnexal masses. Those levels along with the patient's age and new TMA score could preoperatively predict malignant nature of the tumor.