Aggressive Angiomyxoma. A case series of eight years of experience.

BACKGROUND: Aggressive angiomyxoma is a type of mesenchymal tumor occurring predominantly in the pelvic and perineal region. The aim of our study was to reveal our experience with gonadotropin-releasing hormone (GnRH) treatment in patients with angiomyxoma and provide a comprehensive review of management. PATIENTS AND METHODS: This study is a case-series including seven female patients diagnosed with aggressive angiomyxoma from a single institution, between 2012 and 2020. Follow-up after surgery was ranged between 2-45 months with an average of 17.6 months. Resection was performed in all patients without any complications, and five had received GnRH analogue (Goserelin acetate) therapy after surgery. Immunohistochemistry analyses showed positivity for smooth muscle actin and desmin in all cases, while both estrogen receptor (ER) and progesterone receptor (PR) positivity were identified in 6 patients. None of the seven patients had recurrence during follow up period. CONCLUSION: The mean treatment of aggressive angiomyxoma is surgery, and the use of GnHR analogues in cases with positive ER and PR may be effective in preventing recurrence. KEY WORDS: Aggressive Angiomyxoma, Gonadotropin-Releasing Hormone, Soft Tissue Neoplasm.

Tissue Expression of Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Breast Cancers.

Objective: Breast cancer is the most common cancer among women worldwide. Neutrophil gelatinase-associated lipocalin (NGAL) has important roles in immunity, cell proliferation, and carcinogenesis. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein also known as hepatitis A virus cellular receptor 1 and T-cell immunoglobulin and mucin, has restricted expression in immune cells and healthy epithelial cells, but it is up-regulated in several human cancers. The aim of this study was to determine the prognostic values of NGAL and KIM-1 expression in tumor cells and to detect the presence of NGAL-positive neutrophils (PNL) in the tumor microenvironment. Materials and Methods: The expression of NGAL and KIM-1 protein were assessed by immunohistochemical staining in tissue specimens from 412 primary breast cancer cases. Results: In this series, the mean age of the patients was 55.6±12.4 years. In 218 (52.9%) cases, there was NGAL expression in tumor cells. In 104 (25.2%) cases there was KIM-1 expression in tumor cells. NGAL-positive inflammatory cells were seen in tumors of 45 (10.9%) cases. There was no significant relationship between NGAL-positive PNL presence in the tumor microenvironment and other clinicopathological features. However, there was a significant association between the presence of in situ carcinomas and NGAL expression (p = 0.008) and KIM-1 expression (p = 0.020) in tumor cells. Conclusion: This study has demonstrated positivity of NGAL and KIM-1 in breast cancer cells. Considering the development of anti-KIM-1 therapies, the presence of KIM-1 expression may be a new treatment option in breast cancer, especially in in situ component-rich tumors. These findings should be confirmed in larger series.

Effect of tumor size on the accuracy of frozen section in the evaluation of mucinous borderline ovarian tumors.

OBJECTIVE: This study aims to evaluate the accuracy of frozen section (FS) in mucinous borderline ovarian tumors (BOTs) and to examine the factors associated with misdiagnosis. METHODS: In this retrospective study, cases diagnosed as mucinous BOTs by FS or final pathologic (FP) results were studied. The results of FS and FP were compared, and the factors associated with misdiagnosis were analyzed. RESULTS: Seventy-nine cases were examined. The median tumor diameter was 16 (6-50) cm, and 89.9 % of cases had tumors ≥10 cm. The overall agreement ratio between FS and FP was 79.7 %. Over-diagnosis and under-diagnosis rates were 3.8 % and 16.5 %, respectively. The sensitivity and positive predictive values were both 88.7 %. None of the underdiagnosed patients (13 cases) had recurrence during the 100-month median follow-up (9-222). Misdiagnosis was more common in tumors <10 cm (p = 0.025). The under-diagnosis rate for tumors <10 cm was 30.8 %. Tumor size <10 cm was significantly associated with misdiagnosis in univariate and multivariate analyses (Odds ratio {OR} 4.92, 95 % Confidence Interval {CI} (1.08-22.45) p = 0.040; OR 5.17, 95 % CI (1.07-25.05) p = 0.041, respectively). Laterality and preoperative CA 125 levels were not associated with misdiagnosis. CONCLUSION: Tumor size <10 cm is associated with misdiagnosis in mucinous BOTs. Laterality and CA 125 levels do not affect diagnostic accuracy. The evaluation of FS by gynecologic pathologists can help to increase the accuracy of FS.

Utility of the "floating ball sign" in diagnosis of ovarian cystic teratoma.

OBJECTIVE: To evaluate the incidence of the "floating ball" sign in cross-sectional imaging modalities in patients with ovarian teratoma, and to investigate the relationship between the morphologic features of the teratoma and this sign. MATERIALS AND METHODS: Preoperative computed tomography and magnetic resonance imaging studies of 112 women with a pathologic diagnosis of ovarian mature cystic teratoma (MCT) were reviewed for the presence of the floating ball sign. Tumor size, tumor characteristics and the number, size, and characteristics of floating globules were evaluated. RESULTS: In 112 patients (mean age 35.5±16 years, range 5-84 years), 118 ovarian MCTs were diagnosed pathologically. The floating ball sign was demonstrated in cross-sectional imaging in 30 (25.4%) patients. Among 2 of them, MCT was associated with malignancy (squamous cell carcinoma). There was a significant relationship between the floating ball sign, tumor size, and the wall thickness of the tumor (p=0.003 and p=0.018, respectively). In linear regression analysis, a similarly significant relationship was found between the presence of this sign and tumor size and patient age (p=0.003 and p=0.035, respectively). CONCLUSION: The floating ball sign, as a pathognomonic sign for the diagnosis of ovarian teratomas, seems to be more common than is known. Although this sign is almost always seen in MCTs, it may rarely be seen in teratomas with malignant transformation. The relationship of this sign with the characteristics of the tumor can provide an insight into the occurrence of these balls.

Can preoperative magnetic resonance imaging replace intraoperative frozen sectioning in the evaluation of myometrial invasion for early-stage endometrial carcinoma?

OBJECTIVES: To examine the performance of preoperative magnetic resonance imaging (MRI) and intraoperative frozen sectioning in the assessment of myometrial invasion during the early stages of endometrial cancer. MATERIAL AND METHODS: This retrospective study employed data from patients with endometrial cancer who were operated on between January 2013 and November 2018. Patients who underwent preoperative MRI and were of FIGO 2009 stage I were included in the study. Radiological staging and intraoperative staging by frozen sectioning were carried out. The data were analyzed to assess agreement of the overall results concerning myometrial invasion. RESULTS: In total, 222 patients were enrolled. Their mean age was 58.3 ± 8.5 years. The accuracy of MRI for the detection of myometrial invasion was 88.7% and its sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 91.6%, 82.1%, 92.2%, and 80.9%, respectively, with a kappa coefficient of 0.734 (95% confidence interval [CI], 0.684-0.784; p < 0.001). The accuracy of intraoperative frozen sectioning was 94.4%, and its sensitivity, specificity, PPV, and NPV were 97.7%, 85.7%, 94.7%, and 93.4%, respectively, with a kappa coefficient of 0.856 (95% CI, 0.812-0.900; p < 0.001). No significant difference in accuracy was observed between MRI and frozen sectioning (p = 0.057). MRI and frozen sectioning were sensitive for the detection of myometrial invasion, according to receiver operating curve analyses (areas under the curve, 0.869 and 0.917, respectively; p < 0.001). CONCLUSIONS: The assessment of myometrial invasion by preoperative MRI and intraoperative frozen sectioning during the early stages of endometrial carcinoma was highly accurate.

Clinicopathologic evaluation of uterine smooth muscle tumors of uncertain malignant potential (STUMP): A single center experience.

OBJECTIVE: To investigate the clinical outcomes and histopathological features of uterine smooth muscle tumors of uncertain malignant potential (STUMP). METHODS: The study analysed cases diagnosed with uterine STUMP in a tertiary center, between January 2003 and September 2018. We investigated the clinical, operative and histopatholologic data of the cases. Follow-up information and clinical outcomes were also examined. RESULTS: 28 cases with uterine STUMP were studied. The mean age of the patients was 44.5 ± 9.0 years and the median parity was 2 (0-6). The mean tumor diameter was 6.3 cm (range 2-27 cm) and most (78.6%) of the tumors were located intramurally. In 25% of the cases diagnosis was after myomectomy, while in the others diagnosis was after hysterectomy. Of the patients who wanted to preserve the uterus and their fertility and who did not therefore undergo a subsequent hysterectomy, one patient became pregnant without any complication. One case with a history of myomectomy, presented as STUMP. The median follow-up time was 45.4 months (range 5-180). Recurrence occured in one case (3.7%) 33 months after diagnosis. Distant metastasis occurred in the lungs and the pathology of the biopsy was liposarcoma, and the patient died of the disease 62 months after diagnosis. CONCLUSION: Uterine STUMP is a rare condition, and diagnosis can be difficult, often with unusual combinations of findings. Prognosis for the patient is unclear and their is a risk of recurrence with the tumors. To reduce mortality, regular follow-up and a centralised approach are recommended.

The prognostic significance of pdl1 and foxp3 expressions in tumor cells and the tumor microenvironment of ovarian epithelial tumors.

BACKGROUND: The aim of this study is to determine the prognostic values of PDL1 expression in ovarian epithelial tumors and to detect the presence of FOXP3-positive T reg cells in the tumor microenvironment. METHODS: This study included patients with benign, borderline or malignant ovarian serous tumors (n=82), mucinous cancer (n=17) and endometrioid cancer (n=36). FOXP3 and PDL1 were immunohistochemically evaluated and compared with histopathological and clinical prognostic parameters. RESULTS: There was no expression of PDL1 in any tumor cell. However, PDL1-positive inflammatory cells were seen in 10 cases (7.3%) with mucinous carcinoma (n=6), endometrioid carcinoma (n=2), borderline (n=1), and benign (n=1) serous tumors. It was also determined that there was a significant positive correlation between PD-L1 expression in tumor infiltrating cells and survival (P<0.01). In 47 (34.3%) cases, there were FOXP3-positive cells. The number of FOXP3-positive cells was significantly higher in ovarian cancer, especially in serous and endometrioid carcinomas, rather than benign and borderline tumors (P=0.007). But there was no statistically significant association between the survival times and the presence of T regs (P=0.241). CONCLUSIONS: This study demonstrated that the presence of FOXP3 and PDL1-positive regulatory T cells in TILs was associated with mainly malignant tumors. We also found that the presence of PD-L1-positive inflammatory cells has a positive effect on survival.

Tissue expression of human epididymal secretory protein 4 may be useful in the differential diagnosis of uterine cervical tumors.

OBJECTIVES: Human Epididymal Secretory Protein 4 was firstly described as an epididymis-specific protein but more recently it has been demonstrated to be a putative serum tumor marker for different malignancies, especially ovarian epithelial cancers. The aim of this study is to investigate the association between tissue Human Epididymal Secretory Protein 4 expression and the clinicopathological features of uterine cervical tumors. MATERIAL AND METHODS: This retrospective study was designed to evaluate the differences of tissue expressions of Human Epididymal Secretory Protein 4 protein in a spectrum of cervical neoplasms. One hundred and seven patients recently diagnosed as having cervical intraepithelial neoplasm or invasive squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma based on pathology databases. RESULTS: Decreased or negative Human Epididymal Secretory Protein 4 expressions were determined in both normal cervical epithelia and in intraepithelial carcinomas, while increased HE4 expression was observed in invasive tumors. CONCLUSIONS: This study demonstrated that altered expression of Human Epididymal Secretory Protein 4 may involve in tumorigenesis in the uterine cervix. Our findings also suggested the presence of a correlation between Human Epididymal Secretory Protein 4 expression and the invasive potential of uterine tumors. Therefore it may be thought that the tissue expression of HE4 can be used to differentiate high grade intraepithelial tumors from carcinomas.

Intraarticular Giant Size Angiolipoma of the Knee Causing Lateral Patellar Dislocation.

BACKGROUND: Angiolipomas are benign tumors usually seen in patients during their 2nd and 3rd decades. The subcutaneous region of the trunk, neck and extremities are the places where they generally settle. There is only one case report on angiolipoma in the knee joint that was resected by arthroscopic procedure in the English literature. CASE REPORT: We present a case of a giant-size multilobular non-infiltrating angiolipoma, extending outside of the right knee joint and causing lateral patellar dislocation in a thirteen-year-old boy. A large encapsulated mass with fatty and soft-tissue components on magnetic resonance imaging was suggestive of a liposarcoma. However, the diagnosis after the tru-cut biopsy was angiolipoma. The Quadriceps angle was 25°. Complete resection of the tumoral mass and repair of the medial retinaculum were performed with open surgery. Patellofemoral alignment was provided by transferring the tibial tuberosity medially. One year after the surgery, there was no evidence of recurrence. CONCLUSION: Intra-articular angiolipomas are rarely seen masses in the knee joint. To our knowledge, this case report is the first to demonstrate that angiolipoma causes patellar dislocation.

Expression of Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Wilms Tumor.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) and Kidney injury molecule-1 (KIM-1) play important roles in both immunity and cell proliferation. It was reported previously that they are overexpressed in various human cancers. The present study was undertaken to examine the expressions of NGAL and KIM-1 in Wilms Tumors. MATERIAL AND METHOD: Tissue samples of 50 Wilms Tumors were evaluated and underwent immunhistochemical staining for NGAL and KIM-1 protein expressions. The correlations between them, and some clinical prognostic factors such as tumor weight, stage and histological features were also evaluated. RESULTS: Twenty-three (46%) of the cases were male while 27 (54%) were female. The mean age was found to be 3.26±2 years. The average tumor size was 9.16 ± 2.9 cm in diameter and the average weight of the kidney was 478±312 gr. Thirteen (26%) cases were stage I, 18 (36%) cases were stage II, 7 (14%) cases were stage III, and 6 (12%) cases were stage IV. Thirty-nine cases were alive (78%), while 11 cases (22%) were deceased. Mean overall survival time was 68.2±39.5 (2-148) months. NGAL expression was negative in all tumors except the neutrophils within the tumors. KIM-1 expression was positive in 37 tumors (74%), while it was absent in 13 tumors (26%). Using Mann-Whitney U Analysis, KIM-1 expression was found to be associated with the stage of the tumor (p=0.027). CONCLUSION: The preliminary data indicates that KIM-1 expression may be associated with stage in Wilms Tumor. However, further studies are needed to validate these pilot observations and to clarify the functional and mechanistic significance of this relevance.

The evaluation of the caveolin-1 and AT-rich interactive domain 1 alpha expressions in uterine smooth muscle tumors.

OBJECTIVES: This retrospective study was designed to evaluate the importance of tissue expressions of caveolin-1 (Cav-1) and AT-rich interactive domain 1 alpha (ARID-1A) which are known as signal regulator and tumor suppressor in differential diagnosis of uterine smooth muscle tumors (SMTs). MATERIALS AND METHODS: Thirty patients recently diagnosed as uterine SMTs at the Tepecik Training and Research Hospital were identified using pathology databases. Immunohistochemical stains for Cav-1 and ARID-1A were performed. RESULTS: In this series, there were 10 leiomyosarcomas (LMSs), 10 uterine smooth muscle tumors of uncertain malignant potentials (STUMPs), and 10 leiomyomas (LMs). Cav-1 expression located cytoplasmic or perivascular area. Cytoplasmic Cav-1 expression was determined in 5 LMSs and 2 STUMPs while perivascular Cav-1 expression was determined in 9 LMSs and 2 STUMPs. Statistically, it was determined that if the tumor becomes malignant and more invasive, it gains the perivascular Cav-1 expression (P = 0.029). On the other hand, the mean nuclear staining rate for ARID-1A in LMSs (63 ± 23.4%) was higher than both STUMPs (60 ± 18.5%) and LMs (34.5 ± 16.5%). Statistically, it was determined that the expression of ARID-1A was significantly downregulated in LMs when compared with STUMPs and LMSs (P = 0.004). CONCLUSIONS: Our findings were demonstrated that perivascular Cav-1 expression was seen to be a marker for malignancy of uterine SMTs. Similarly, we found to link of ARID-1A expression and the aggressiveness of SMTs. Therefore, it may be suggested that Cav-1 and ARID-1A may act as predictive biomarkers in uterine SMTs.

Optimal cytoreduction, depth of myometrial invasion, and age are independent prognostic factors for survival in women with uterine papillary serous and clear cell carcinomas.

OBJECTIVE: The purpose of this study was to investigate the clinicopathological characteristics, treatment methods, and prognostic factors in women with uterine papillary serous carcinoma (UPSC) and uterine clear-cell carcinoma (UCCC). STUDY DESIGN: All patients who had undergone surgery for UPCS and UCCC between January 1995 and December 2012 were retrospectively reviewed. Patients with missing data, who did not undergo surgical staging and patients with mixed tumor histology were excluded. Multivariate regression models were used to identify the risk factors for overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 49 UPSC and 22 UCCC women were included. The majority of the patients were at stage I [IA, 22 (31%) and IB, 18 (25.4%)]. Stages II, III, and IV were identified in 9 (12.7%), 13 (18.3%), and 9 (12.7%) of cases, respectively. Optimal cytoreduction was achieved in 71.8% of cases. Recurrences occurred in 16 patients (22.5%). The 5-year OS rates were 67% for UPSC; 76% for UCCC; 68% for both histology, respectively. Multivariate analysis pointed out that age>67 years (odds ratio (OR): 3.85, p = 0.009 and OR: 3.35, p = 0.014), >50% myometrial invasion (MI) (OR: 2.87, p = 0.037 and OR: 2.46, p = 0.046) and optimal cytoreduction (OR: 3.26, p = 0.006 and OR: 2.77, p = 0.015) were the independent prognostic factors for both PFS and OS. CONCLUSIONS: Our study demonstrated that optimal cytoreduction, >50% MI, and age >67 years are the most significant factors affecting survival in women with UPSC and UCCC.

Differences in the ARID-1 alpha expressions in squamous and adenosquamous carcinomas of uterine cervix.

AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene involved in chromatin remodeling which encodes ARID1A (BAF250a) protein. Recent studies have shown the loss of ARID1A expression in several types of tumors. This retrospective study was designed to evaluate the differences in tissue expressions of ARID1A in a spectrum of cervical neoplasms. Cervical intraepithelial neoplasms, invasive squamous or adenosquamous carcinomas were identified in 100 patients recently diagnosed as cervical neoplasms based on pathology databases. In this series, there were 29 low- and 29 high-grade cervical intraepithelial neoplasms, 27 squamous cell carcinomas, and 15 adenosquamous carcinomas. Mean age of the patients was 47.8 ± 13 years (20-80 years). It was determined that the expression of ARID1A was statistically significantly down-regulated in adenosquamous carcinomas when compared with non-invasive or invasive squamous cell carcinomas (p = 0.015). Lower levels of the ARID1A expression were detected in cases with adenosquamous carcinomas (60%), low- or high-grade squamous intraepithelial lesion (SIL) (31%), and squamous cell carcinomas (18.5%). Our findings have demonstrated the presence of a correlation between ARID1A expression and adenomatous differentiation of uterine squamous cell carcinomas. Therefore, ARID1A gene may suggestively have a role in the pathogenesis of cervical adenosquamous carcinomas.

Expression of caveolin-1 in peritumoral stroma is associated with histological grade in ovarian serous tumors.

BACKGROUND: Previous studies have demonstrated that Caveolin-1 (Cav-1) can ambiguously behave as tumor suppressor or tumor promoter in different neoplasms, depending on cancer type. Some findings have also revealed that cell proliferation, migration and invasion were attenuated by the knockdown of Caveolin-1 expressions. However, the functional and prognostic significance of Caveolin-1 in most tumors remains to be fully elucidated. OBJECTIVES: The aim of the study was to investigate a possible association between tissue Caveolin-1 expression and the clinicopathologic features of ovarian serous tumors. MATERIAL AND METHODS: Caveolin-1 expression was studied in a total of 82 formalin-fixed, paraffin-embedded specimens of ovarian serous tumors and its association with different clinicopathologic parameters was evaluated. RESULTS: The study included 36 (43.9%) benign, 12 (14.6%) borderline and 34 (41.5%) malignant serous tumors. Mean patient age was 43.9 ± 14.4 years (17-72 years). Statistical analysis revealed that if the tumor becomes more aggressive and invasive, it losses the stromal Caveolin-1 expression (p = 0.001). Also, parallel changes between stromal and perivascular Caveolin-1 expressions were observed. CONCLUSIONS: Our findings demonstrated a link between Caveolin-1 expression and the aggressiveness of ovarian cancer. Therefore, it seems safe to suggest that Cav-1 may act as a differential diagnostic biomarker in ovarian serous tumors.

A case of bladder endometriosis that became symptomatic during the third trimester.

BACKGROUND: The urinary tract endometriosis is observed in 1-2% of the patients and in 90% of these cases, there are endometriotic nodules in the bladder. With respect to knowledge, it is generally believed that pregnancy cures endometriosis. However in this case, symptoms developed during the third trimester of pregnancy. CASE REPORT: We report a case of 31 year old, 30 week pregnant woman with a vegetative mass with 33 × 33 × 21 mm dimensions and irregular borders on the posterior wall of the bladder. After the cesarean section, the vegetative and superiorly localized mass on the internal wall of the bladder was excised with partial bladder excision. The patient had no other apparent findings of pelvic endometriosis at operation but the pathology result indicated endometriosis. CONCLUSION: Although this case shows that endometriosis may become symptomatic during pregnancy, it has to be underlined that it cannot be discerned whether it is consequent to progress of the disease or to pregnancy-mediated modifications of a pre-existing lesion.

Is mucinous adenocarcinoma of the endometrium a risk factor for lymph node involvement? A multicenter case-control study.

PURPOSE: The purpose of this multicenter case-control study was to compare the demographic and clinical characteristics of patients with mucinous adenocarcinoma of the endometrium (MAE) and endometrioid endometrial carcinoma (EEC). METHODS: A retrospective review of two cancer registry databases in Turkey was conducted to identify patients diagnosed with MAE between January 1996 and December 2012. Each patient was matched with a control EEC patient by age and tumor grade. Cases and controls were compared in terms of known risk factors for lymph node metastasis, disease-free survival (DFS), and overall survival (OS). RESULTS: The analysis included 112 patients with MAE and 112 with EEC. No significant difference in baseline characteristics was evident between the two groups. Lymphovascular space invasion, deep myometrial invasion, cervical involvement, and tumor diameter did not differ significantly between the mucinous and endometrioid cases. Multivariate analysis confirmed that only mucinous histology (OR 2.2, 95 % CI 1.1-4.5; P = 0.02) was an independent predictor of lymph node involvement. Although the median DFS and OS tended to be better in the endometrioid group, the differences were not statistically significant. Routine appendectomy was performed in 52 (46.2 %) patients with MAE. No mucinous tumor of the appendix was identified. CONCLUSION: Routine appendectomy is not necessary when the appendix is grossly normal at the time of surgery for MAE. Although the DFS and OS of EEC and MAE patients were similar, the risk of nodal metastasis in MAE patients was greater than that in ECC patients, and we thus suggest to perform retroperitoneal lymphadenectomy (both pelvic and para-aortic) for patients with MAE during the initial operation.

A pitfall in transrectal prostate biopsy: malakoplakia evaluation of two cases based on the literature review.

Malakoplakia is a rarely seen inflammatory condition that is considered to develop secondary to a chronic Escherichia coli infection. Although malakoplakia usually affects the genitourinary tract, it may also be observed in the colon, stomach, lungs, liver, bones, uterus, and skin. Malakoplakia of the genitourinary system usually involves the bladder, whereas it may also affect the prostate along with the bladder. Malakoplakia of the prostate is very rare, and it may be clinically mistaken for prostatic malignancies. Definitive diagnosis is only possible through histopathological examination. This study elaborates on two patients who presented to our hospital in 2013 with high PSA levels. The primary clinical consideration was prostate carcinoma. However, these two cases were diagnosed as malakoplakia based on the results of histopathological analysis of the transrectal prostate biopsy specimen.