The Clinicopathological Study of 21 Cases With Uterine Smooth Muscle Tumors of Uncertain Malignant Potential: Centralized Review Can Purify the Diagnosis.

OBJECTIVE: The objective of this study was to investigate the clinicopathological features and factors associated with recurrence in patients with uterine smooth muscle tumor of uncertain malignant potential (STUMP). METHODS: Forty-six cases diagnosed between 2000 and 2014 from 2 tertiary centers underwent blind slide review. Initial diagnosis included smooth muscle tumors with equivocal diagnosis, STUMPs, and cases that were named as leiomyosarcomas (LMS) or low-grade LMS despite not fulfilling the Stanford criteria. RESULTS: In total, 21 patients with a final diagnosis of STUMP were available. Fifteen (68.1%) of 22 patients with an initial diagnosis of STUMP, 4 (22.2%) of 18 cases with an equivocal smooth muscle tumor diagnosis, and 2 (33.3%) of 6 cases with an initial diagnosis of LMS were interpreted as STUMP after slide review. The mean age at diagnosis was 43 years (range, 20-64 years). The mean follow-up time was 65.9 months (range, 10-154 months). Four patients (19.0%) developed recurrent disease. Recurrent tumors were LMS in 3 patients (75%). One patient (4.8%) with recurrence succumbed to disease. There was no difference in patients' age (P = 1.0) or type of initial surgery (uterus conserving versus hysterectomy) (P = 0.57) between patients who recurred and did not recur. CONCLUSIONS: Uterine STUMPs can harbor significant uncertainty regarding the original diagnosis and clinical outcomes. Recurred cases may have an aggressive clinical course associated with multiple relapses and death. Uterine mesenchymal tumors other than ordinary myomas and overt sarcomas deserve a second opinion in centers with experience because the real diagnosis may vary significantly.

Diagnostic and Treatment Reproducibility of Cervical Intraepithelial Neoplasia / Squamous Intraepithelial Lesion and Factors Affecting the Diagnosis.

OBJECTIVE: Inter-observer differences in the diagnosis of HPV related cervical lesions are problematic and response of gynecologists to these diagnostic entities is non-standardized. This study evaluated the diagnostic reproducibility of "cervical intraepithelial neoplasia" (CIN) and "squamous intraepithelial lesion" (SIL) diagnoses. MATERIAL AND METHOD: 19 pathologists evaluated 66 cases once using H&E slides and once with immunohistochemical studies (p16, Ki-67 and Pro-ExC). Management response to diagnoses was evaluated amongst 12 gynecologists. Pathologists and gynecologists were also given a questionnaire about how additional information like smear results and age modify diagnosis and management. RESULTS: We show moderate interobserver diagnostic reproducibility amongst pathologists. The overall kappa value was 0.50 and 0.59 using the CIN and SIL classifications respectively. Impact of immunohistochemical evaluation on interpretation of cases differed and there was lack of statistically significant improvement of interobserver diagnostic reproducibility with the addition of immunohistochemistry. We saw that choice of treatment methods amongst gynecologists varied and overall concordance was only fair to moderate. The CIN2 diagnostic category was seen to have the lowest percentage agreement amongst both pathologists and gynecologists. We showed that pathologists had diagnostic "styles" and gynecologists had management "styles". CONCLUSION: In summary each pathologist had different diagnostic tendencies which were affected not only by histopathology and marker studies, but also by the patient management tendencies of the gynecologist that the pathologist worked with. The two-tiered modified Bethesda system improved diagnostic agreement. We concluded that immunohistochemistry should be used only to resolve problems in select cases and not for every case.

Therapy Modalities, Prognostic Factors, and Outcome of the Primary Cervical Carcinosarcoma: Meta-analysis of Extremely Rare Tumor of Cervix.

OBJECTIVE: The aim of this study was to evaluate the prognostic factors, treatment options, and survival outcomes of primary carcinosarcomas of the uterine cervix. METHODS: An electronic search of the literature was conducted from 1951 to February 2017 to identify articles on primary cervical carcinosarcoma. After comprehensive evaluation of case series and case reports, 81 cases were included in the study. RESULTS: The most common clinical FIGO (International Federation of Gynecology and Obstetrics) stage was IB at 53% of cases. Median follow-up time was 15 months (range, 1.75-156 months). Two-year disease-free survival (DFS) and overall survival (OS) of the entire cohort were 49% and 60%, respectively. Both 2-year DFS and OS were significantly higher in patients with stage I than in those with stage II disease or greater (73% vs 22%, P = 0.000 and 82% vs 33%, P = 0.000, respectively). Two-year OS was 17% for patients who received primary radiotherapy, whereas it was 68% for those who underwent only surgery (P = 0.003). Surgery followed by adjuvant radiotherapy with or without chemotherapy was significantly associated with improved DFS and OS compared with primary radiotherapy. Two-year DFS was 63% in patients who underwent primary surgery, whereas it was 100% in patients treated with primary surgery followed by adjuvant radiotherapy with chemotherapy (P = 0.030). Stage alone was an independent prognostic factor for risk of both recurrence and death (hazard ratios, 9.8 [P = 0.004] and 14 [P = 0.018], respectively). CONCLUSIONS: In due course of presentation, the tumor stage has a great importance because it is the only independent factor for prognosis. Surgery followed by adjuvant radiotherapy with or without chemotherapy seems to be related with better OS and DFS.

Frozen section in borderline ovarian tumors: is it reliable?

OBJECTIVE: We reported the concordance of frozen/section (FS) diagnosis of borderline ovarian tumor (BOT) and identified the factors associated with the concordance. STUDY DESIGN: FS results of the patients with a final diagnosis of BOT operated between 1990 and 2012 were analyzed. The FS results were reported as benign, rule out borderline tumor, borderline tumor, at least borderline tumor and malign tumor intraoperatively. The concordance of FS diagnosis was determined by comparing the FS result with the final pathological diagnosis. We accepted the FS concordant with the final pathology when the FS result was borderline tumor or at least borderline tumor, since we managed these patients in a similar way intraoperatively. Data regarding histological subtype, tumor size, age of the patients, menopausal status, presence of bilateral disease, preoperative Ca-125 level and the final diagnosis were evaluated. RESULTS: FS results of 145 patients were analyzed. The concordance of FS analysis for the total group, for the ones with serous and mucinous BOT were 79%, 92% and 62%, respectively. Totally, 29 patients (20%) weren't staged intraoperatively due to inaccurate FS result. Mucinous histology and larger tumor size were associated with lower concordance of FS. Concordance wasn't associated with type of surgery (conservative vs radical), menopausal status, laterality of the tumor, age of the patients and Ca-125 level of the patients. CONCLUSION: The high discrepancy rate of FS, especially in mucinous and larger tumors should be kept in mind during intraoperative decision-making based on FS analysis for BOT.

Prediction of staging with preoperative parameters and frozen/section in patients with a preoperative diagnosis of grade 1 endometrioid tumor in endometrial cancer.

OBJECTIVE: To investigate the likelihood of the detection of the necessity of staging preoperatively with the use of clinical parameters and frozen/section (FS). MATERIAL AND METHODS: 219 patients were included who were operated on between 1996 and 2010 with a diagnosis of grade 1 endometrioid adenocarcinoma in probe curettage. RESULTS: Among the clinical characteristics, only age and body mass index (BMI) predicted staging preoperatively. The probability of staging increased as age increased and BMI decreased. The concordance between preoperative diagnosis and FS was 89.5%. The diagnosis was upgraded at postoperative evaluation for 13 patients (5.9%), and downgraded for 2 patients (0.9%) compared with FS. The wrong diagnosis regarding grade, the depth of myometrial invasion DMI, tumour type and cervical invasion in FS was clinically significant and affected the decision of staging in 10 patients. In conclusion, only 7 patients (3.2%) who acquired staging surgery were missed in FS. CONCLUSION: It was shown that preoperative clinical parameters could not effectively predict the patients who should be staged. FS predicted the lymphatic involvement with high accuracy. The patient with a preoperative diagnosis of grade 1 endometrium cancer should be operated upon in centres where FS is utilised and oncologic staging surgery can be performed.

Staining characteristics of p16INK4a: is there a correlation with lesion grade or high-risk human papilloma virus positivity?

AIM: The aims of this study were to evaluate the efficiency of p16INK4a in showing cervical lesions and to determine any relationship between lesion grade and high-risk human papilloma virus (HR-HPV) infection and p16INK4a staining characteristics. METHODS: Immunohistochemical analysis of p16INK4a was performed on 13 low-grade squamous intraepithelial lesions (LSIL), 22 high-grade squamous intraepithelial lesions (HSIL), 23 squamous cell carcinoma (SCC) and 25 normal tissue samples. The distribution, staining pattern and intensity of p16INK4a expression were assessed and correlated with HR-HPV positivity determined by real-time polymerase chain reaction. RESULTS: All HSIL and SCC cases, but only 46.2% of LSIL cases, were positive for p16INK4a. Although positive staining of p16INK4a in showing HR-HPV-positive lesions was statistically significant (P=0.000), we could not find a significant correlation for distribution (P=0.319), staining pattern (P=0.057) or intensity (P=0.057) of p16INK4a in showing HR-HPV in cervical epithelium. These parameters were correlated only with the increasing grade of the lesion (P=0.000). CONCLUSIONS: p16INK4a is a highly sensitive marker of cervical intraepithelial neoplasia and cervical cancer. There is a good correlation between p16INK4a expression and cervical lesion grade and HR-HPV positivity. The distribution, staining pattern and intensity of this marker are significantly correlated with the increasing grade of cervical lesions, suggesting that diffuse distribution, full thickness staining pattern and strong intensity of this marker are highly supportive of HSIL and cervical cancer, while focal distribution, scattered/basal staining pattern and weak intensity suggest LSIL. However, these parameters are not correlated with HR-HPV status in cervical lesions.

Ligneous inflammation of the cervix: a case report.

BACKGROUND: Ligneous change of the genital tract is a very rare condition and may result in infertility. CASE: A 27-year-old woman presented with primary infertility and ligneous changes of the genital tract. Cervical and endometrial samples revealed subepithelial deposition of dense, amorphous, eosinophilic material associated with intensive inflammatory cell infiltration. Plasminogen functional activity was 16%. CONCLUSION: The clinician must be aware of the systemic nature of this disorder and the multisystem complications.

Expression of hepatocyte growth factor/scatter factor receptor in IUGR fetuses' placentas: an immunohistochemical analysis.

OBJECTIVE: We aimed to evaluate the expression sta tus of c-met, receptor for the hepatocyte growth factor (HGF), in the placentas of intrauterine growth retardation (IUGR) fetuses. MATERIALS AND METHODS: Placentas were obtained during delivery from both third trimester normal and IUGR complicated pregnancies. Ultrasonographic estimation of fetal birth weight has been done and placentas of those under the fifth percentile for their gestational ages were enrolled in the study group. Eighteen fetuses with IUGR and 6 uncomplicated pregnancies were subjected to the study. Histological sections from placentas were immunohistochemically evaluated for the expression status of c-met. RESULTS: Seventeen of the eighteen patients (94.4%) in the study group were found to have overexpression of the c-met while this figure was only 16.7% (1/6) in the control group (p < 0.0001). There was a strong statistically significant difference between the two groups regarding degree of c-met expression. CONCLUSION: Our present findings suggest that c-met is an important cell membrane receptor in human placenta. Deregulation of the interaction between HGF and its receptor c-met during placentation may be the cause responsible for the growth retardation of the fetus due to the impaired placental functions.

Fertility and recurrence results of conservative surgery for borderline ovarian tumors.

OBJECTIVES: To evaluate the fertility and recurrence outcomes in women treated with fertility-sparing surgery for borderline ovarian tumors. METHODS: A total of 142 patients with borderline ovarian tumors managed surgically from 1993 to 2004 were identified from gynecologic oncology and pathology files of SSK Ankara Maternity and Women's Health Teaching Hospital. Sixty-two of those patients who had conservative surgery were eligible for the study. Information was acquired by retrospective medical record review and patient interview. RESULTS: The observed recurrence rates after radical and fertility-sparing surgery were 0.0% and 6.5%, respectively. Four patients from the conservative surgery group developed recurrence, in contrast to none of the patients from the non-conservative surgery group. No disease-related deaths occurred in any group. In the conservatively managed group, ten women had successful pregnancies, with a total of 10 live births and 3 abortions. The mean duration of follow-up for the conservative surgery group was 44.3 months (range, 3-128). CONCLUSION: Fertility-sparing surgery for borderline ovarian tumors should be considered for women in the reproductive age group who desire preservation of fertility. Recurrence is noted significantly more often after this type of treatment and close follow-up is needed to detect recurrent disease.

Is frozen-section diagnosis a reliable guide in surgical treatment of stage I endometrial carcinoma?

Frozen-section diagnoses and paraffin-section diagnoses were compared in 154 patients in stage I endometrial adenocarcinoma. In 134 (87%) of the 154 patients (p < 0.001), a corresponding depth of myometrial invasion was found, and in 132 (85.7%) patients the same tumor grade was established (p < 0.001). Frozen-section diagnosis of stage I endometrial adenocarcinoma is reliable for estimation of the extent of disease and accurately identifies patients who require surgical staging.

The organochlorine pesticide residues and antioxidant enzyme activities in human breast tumors: is there any association?

The levels of some organochlorine pesticides (OCP)s (hexachlorobenzene, HCB, alpha-hexachlorocyclohexane, alpha-HCH, beta-HCH, gamma-HCH, heptachlorepoxide, HE, bis (4-chlorophenyl)-1,1-dichloroethene, p.p'DDE, bis (4-chlorophenyl)-1,1,1-trichloroethane, p.p' DDT and total DDT (E-DDT) and antioxidant enzyme activities namely Cu, Zn superoxide dismutase (SOD), catalase (CAT), selenium-dependent glutathione peroxidase (Se-GSH-Px), total glutathione peroxidase (T-GSH-Px), selenium independent glutathione peroxidase (GSH-Px II), glutathione reductase (GRd), level of reduced glutathione (GSH) and lipid peroxidation (LP), glutathione S-transferase (GST) activity toward several substrates including 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EAA), 1,2-epoxy-3-(p-nitrophenoxy)-propane (ENPP) were measured in tumor and surrounding tumor free tissues of 24 female breast cancer patients and was evaluated whether there exist any association between the levels of OCPs and antioxidants. The mean levels of GSH, alpha-BHC, gamma-BHC and HE, and activities of SOD, Se-GSH-Px, T-GSH-Px, GSH-Px II,GRd, GST CDNB, and GST DCNB were significantly higher in tumors than in controls. In tumors, significant correlations were noted between: SOD and y-BHC; Se-GSH-Px and gamma-BHC; T-GSH-Px and gamma-BHC; GSH-Px II and alpha-BHC, gamma-BHC; GSH and alpha-BHC, gamma-BHC, HE; GRd and alpha-BHC; CDNB GST and alpha-BHC, gamma-BHC. These results show that free-radical mediated oxidative stress is, at least partly, associated with some of these OCP residues in human breast tumors.