Folia Medica

Clinical significance of human epididymis protein 4 (HE4), cancer antigen 125 (CA125), the risk of ovarian malignancy algorithm (ROMA), and Copenhagen index (CPH-I) for the diagnosis of endometrial carcinoma

Introduction: Endometrial carcinoma (EC) is the most common gynecological cancer among women, and in more than 90% of cases, the initial manifestation of the disease is postmenopausal bleeding. Unfortunately, despite early diagnosis and treatment, EC often recurs. Among the many serum tumor markers studied, human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) show the most promise as tools for EC diagnosis, prognosis, and monitoring. Aim: The aim of the current study was to evaluate the clinical usefulness of HE4 and CA125, tested either as single markers or in combination by including them in the Risk of Ovarian Malignancy Algorithms (ROMA) and in Copenhagen index (CPH-I). Material and methods: In this retrospective study, 1262 women (74 with confirmed EC) were included. The patients with EC had significantly higher values for HE4, CA125, ROMA, and CPH-I (p<0.001) than the healthy women and patients with benign diseases. The subgroup analysis based on the histological type of EC revealed that the highest markers and algorithms were recorded in type II EC group. Results: The ROC curve analysis showed that the best diagnostic performance for detecting EC among patients with benign diseases was the ROMA index (AUC=0.869; 95% CI: 0.818-0.920), followed by CPH-I (AUC=0.822; 95% CI: 0.757-0.887), and HE4 (AUC=0.816; 95% CI: 0.750-0.881). Tested alone, CA125 presented unsatisfactory results for this purpose. Both algorithms proved to have a correlation with the disease stage and progression better than the markers alone (HR=1.046 vs. HR=1.018). Conclusion: In summary, the ROMA index, CPH-I, and, to a lesser extent, standalone HE4 testing can supplement imaging methods as reliable tools for diagnosing and distinguishing patients with EC from those with benign conditions. They have potential as prognostic markers for advanced disease and could help gynecological oncologists to develop a therapeutic strategy.

Expression of HIF-1α, Ki67, SMA and E-cadherin in endometriosis, endometrial and ovarian carcinoma

Introduction: Endometriosis is a benign gynecological condition that shares many characteristics with cancer cells, including immune evasion, survival, adhesion, invasion, and angiogenesis. The simultaneous investigation of tissue hypoxia, EMT, and proliferative index in endometriosis, endometrial, and ovarian carcinomas may provide new insight into the evolution and progression of gynecological neoplasms. Aim: The aim of our study was to follow the immunohistochemical expression in endometriosis, endometrial and ovarian carcinoma in relation to tissue hypoxia and necrosis, EMT, proliferative index, and fibrosis. Materials and methods: The present study used biopsy samples from 50 patients with endometriosis, endometrial carcinoma, and ovarian carcinoma in search for a correlation between HIF-1α, Ki67, SMA, and E-cadherin expression and various clinicopathological features. Results: We observed heterogeneity and different intensity of immunohistochemical expression in different groups of patients. Immunohistochemical expression was compared with the degree of tumor cell differentiation. Cells of poorly differentiated adenocarcinomas showed a higher proliferative index with Ki67, presence of epithelial-mesenchymal transition with reduced expression of E-cadherin with stronger expression of HIF-1α. Regarding SMA in pelvic and ovarian endometriosis foci, we reported strong diffuse expression in stromal cells with marked fibrosis. Conclusion: Understanding the mechanisms of carcinogenesis and progression of gynecological tumors and endometriosis is important for prognosis, response to therapy, and possibly better treatment of patients.

Rupture of a mature cystic teratoma in a young girl caused by a car accident: an extremely rare case and review of the literature

Mature cystic teratomas (MCT) of the ovary or dermoid cysts are commonly encountered benign ovarian lesions accounting for  approximately 70% of benign tumors and originating from germ cells. A rare case of peritonitis in a 17-year-old female patient caused by traumatic rupture of an MCT of the right ovary is herein presented. A meticulous search of the literature has also been performed. Due to deterioration of patient’s clinical condition, she was urgently led to surgery and intraoperative investigation of the peritoneal cavity revealed an inflamed ruptured ovarian cyst along with extensive peritoneal adhesions and purulent peritoneal fluid. A cyst resec-tion was performed with preservation of the ovary followed by adhesiolysis and meticulous abdominal washing and the patient had an uneventful recovery.  Despite its rarity, traumatic rupture of ovarian cyst should be considered at evaluation of trauma patients with special attention to cases with a discovered or known presence of ovarian cyst.

Synchronous local recurrence and liver metastasis from extragastrointestinal stromal tumor in the rectovaginal septum: a unique case presentation

The rectovaginal septum is a rare location for gastrointestinal stromal tumors (GIST) to occur. The aim of this study was to present a case of synchronous local recurrence of solitary liver metastasis originating from an extra gastrointestinal tumor (E-GIST) of the rectovaginal space. A 55-year-old woman, with a medical history of a resected meningioma, was referred to our department due to a 5 cm solitary liver metastasis located within the left lateral segment. The patient had undergone a transvaginal resection of a low-risk E-GIST 6 months prior without receiving adjuvant chemotherapy. The patient underwent a synchronous laparoscopic left lateral hepatectomy and a transvaginal resection with posterior vaginal wall reconstruction. Her postoperative course was uneventful and was discharged on the fifth postoperative day. The histological examination of the vaginal lesion revealed the development of neoplasm with pathological characteristics consistent with the initial histology expect for a mitotic index exceeding >20%. Liver histology report also included a high-risk GIST with CKIT (+), DOG1 (+), ki67 ≥30%, high mitotic activity and clear resection margins. The patient was referred for adjuvant chemotherapy. E-GISTs are rare neoplasms with low malignant potential. However, these tumors may exhibit metastatic potential and require aggressive treatment.

Attitudes and awareness related to cervical cancer vaccine

Introduction: Cervical cancer causes major morbidity and mortality around the world. This makes prophylactic vaccines a significant tool for preventing the disease. As these vaccines become more widely available, they have the potential to drastically lower the cancer’s prevalence and burden in the future. Aim: The aim of this study was to assess the attitudes toward awareness of the human papillomavirus (HPV) vaccination. Materials and methods: A pilot, cross-sectional, medicosocial survey was conducted using a structured, anonymous online questionnaire, including self-assessment questions on awareness and attitudes towards HPV vaccination. Sixty-four adult female parents of female children participated in the study between June and August 2023. The design and conduct of the study was done with the personal involvement of the researchers. SPSS v. 23.0 was used to analyze the primary statistical information. The results obtained were presented graphically using MS Excel 2010. Results: We found significantly good awareness and negative attitude towards vaccination as prevention against HPV. Conclusion: The present study demonstrated that respondents had a relatively good awareness of cervical cancer, the risk factors associated with the disease, and the virus that causes it. There was a correlation between socio-demographic characteristics and awareness of the study population. The respondents had a certain distrust of the vaccine. The dissatisfaction stemmed from the fact that vaccination was not a substitute for routine cervical screening, was not 100% effective, and did not provide protection against any type of papilloma virus or against pre-existing HPV infections. The low vaccination coverage in Bulgaria leads the authors to believe that our country urgently needs new strategies and approaches in the fight against cervical cancer, through continuous training of medical personnel, inclusion of immunization programs in school health care, and improved health education and awareness of HPV vaccination among adolescent girls and their parents.

Uterine tumor resembling ovarian sex-cord tumor – a rare gynecological neoplasm

Uterine tumor resembling ovarian sex-cord tumor is a rare group of uterine neoplasms with unknown histogenesis and differentiation towards ovarian sex-cord elements. They are benign in nature with low malignancy potential. Diagnosis is based on immunohistochemistry and morphological features, and the distinction from other more malignant differentials is paramount to correctly individualizing treatment. A 47-year-old patient was admitted to the hospital complaining of abdominal pain and abnormal uterine bleeding. Subsequent detection of multiple uterine fibroids by ultrasound study and CT scans lead to a robot-assisted total hysterectomy. Histological studies revealed that one of the fibroids in the myometrium had a morphology resembling an ovarian sex-cord tumor with low Ki-67 proliferative activity. After 12 months of follow-up, no additional treatment was required, and no signs of recurrence or progression were observed. Uterine tumor resembling ovarian sex-cord tumor is a rare gynecological entity with no established treatment protocol. Differentiation between benign and malignant behavior is based on structural features and immunohistochemical expression assessment. This highlights the importance of immunohistochemical staining and morphological analysis to determine the degree of surgical radicality. Minimally invasive approach is feasible and safe, but more experience is needed for further conclusions.

Vaginal Mucosal Melanoma: a Complete Remission after Immunotherapy and '0-7-21' Radiotherapy Regimen (24 Gy/3 fractions/21 days)

We present the case of a patient with vaginal mucosal melanoma who underwent complete remission after immunotherapy and ‘0-7-21’ radiotherapy regimen (24 Gy/3 fractions/21 days). An 80-year-old woman had a biopsy of a voluminous vaginal lesion and received a histological diagnosis of melanoma with angiomatoid aspects. The patient underwent immunotherapy with pembrolizumab 2 mg/kg every 3 weeks and was sent to our attention for planning radiotherapy as the extent of the lesion did not make it susceptible to surgery. Considering the concomitant administration of pembrolizumab, we chose to treat this patient with a modulated intensity radiation therapy technique delivering a hypofractionated dose of 24 Gy in 3 fractions delivered on days 0, 7, and 21. We observed a complete clinical remission of the melanoma 12 months after radiotherapy and she has been alive for 18 months with no clinical signs of local recurrence.

The Conundrum of Prematurity and Pregnancy Outcomes after Fertility Sparing Treatment Modalities for Early Stage Cervical Cancer:  A Systematic Review of the Literature

Advances in modern medicine have allowed patients with early stage cervical cancer (stages Ia - IIai) to preserve their fertility with oncologic efficacy comparable to previous radical treatments. A variety of conservative-fertility sparing procedures, also known as Fertility Sparing Surgeries (FSS) have been proposed. The present review aimed to provide the current evidence on obstetric outcomes and the prematurity rates as well as to discuss the management modalities of these high-risk pregnancies. Our review of the literature included 3042 women with early cervical cancer, of whom 2838 underwent FSS (204 excluded for oncologic reasons). Almost half of these patients attempted to become pregnant and about two thirds of them achieved at least one pregnancy either spontaneously or with the help of Assisted Reproduction Technologies. Data revealed that 63.9% of these pregnancies resulted in live births, whereas 37.6% of them were preterm. The main cause of preterm births in this subpopulation is the postoperative cervical length restriction that consequently leads to cervical incompetence and ascending infections that eventually lead to (clinical or subclinical) chorioamnionitis. Radical operations such as ART, VRT and MIRT presented with higher prematurity rates. The lack of standardized protocols for the management of pregnancies after FSS precluded reaching to firm results with regards to the efficacy of them in achieving favourable obstetrical outcomes. Further large volume studies are warranted with the intent to acquire standardized guidelines for pregnancies achieved after FSS for early stage cervical cancer.

Primary Peritoneal Serous Carcinoma Detected by Abnormal Cervical Smear: a Case Report

Primary peritoneal serous carcinoma (PPSC) is a rare malignancy, the clinical characteristics of which resemble ovarian serous carcinoma. We present a rare case of PPSC detected by an abnormal cervical smear, the first one with an absence of ovarian tissue at the time of the initial diagnosis. A 59-year-old asymptomatic woman presented with glandular atypia on routine Papanicolaou smear. Endocervical and endometrial curettage showed an adenocarcinoma with focal squamous differentiation and uncertain further classification. The patient had a past surgical history of bilateral salpingoophorectomy due to endometriosis. Abdominal MRI depicted omental multinodularity, great amount of ascites and possible endometrial tumor. The patient underwent total hysterectomy, omentectomy and biopsies of implants on Douglass pouch.  Surgical and histological findings were consistent with primary peritoneal serous carcinoma.  Abnormal pap smear could rarely be suggestive of extrauterine malignancies, such as peritoneal cancer.

Giant vulvar polyp in a postmenopausal woman: a rare clinical case

The increased frequency of precancerous lesions and malignant diseases of the vulva is a hallmark of the postmenopausal period. However, the development of fibroepithelial polyps, which are benign neoplasms, is also possible. The exact etiology and pathogenesis remain unclear. These mesenchymal neoplasms are mostly diagnosed in women who received hormone replacement therapy or those who are of reproductive age, with pregnancy being a predisposing factor. We present a clinical case in which surgical treatment was the first choice, and histopathological examination confirmed the diagnosis. The authors report a case of a postmenopausal patient not taking hormone replacement therapy with a single, large, benign, pedunculated fibroepithelial polyp of the vulva (more than 5 cm long) that appeared more than 15 years ago. The polyp was successfully excised, with a good prognosis for the patient. This clinical case emphasizes the accurate clinical diagnosis and the importance of histopathological examination. It illustrates delayed help-seeking in the absence of mandatory prophylaxis.

Primary Bartholin Adenocarcinoma: a Rare Case and Radiotherapy as Definitive Treatment

Primary vulvar adenocarcinoma is a very rare neoplasm, accounting for only 1% of all gynecologic malignancies. Most of the glandular carcinomas originated from the Bartholin’s gland. Because of the rare incidence, the pathogenesis and radiotherapy response are not fully understood. A 47-year-old female from our hospital was diagnosed with primary Bartholin adenocarcinoma and received radiotherapy as definitive treatment. We evaluated the presence of high-risk and low-risk human papillomavirus (HPV) DNA to associate the role of HPV infection, and evaluated its molecular features by the expression of vimentin, p16, estrogen receptor, progesterone receptor, S-100, and Ki 67.