Reproducibility determination of WHO classification of endometrial hyperplasia/well differentiated adenocarcinoma and comparison with computerized morphometric data in curettage specimens in Iran

<p>Abstract</p> <p>Background</p> <p>Management of endometrial precancerous lesions has been of much debate due to inconsistencies in their classification, natural history and histologic diagnosis. Endometrial hyperplasia constitutes a wide range of histomorphologic features associated with high intra and interobserver diagnostic variability.</p> <p>Although traditional microscopic diagnosis is by far the most applicable method and the gold standard for histomorphologic diagnosis, digitized image analysis has been used as a powerful adjunct to maximize the histologic data retrieval and to add some detailed objective criteria for correct diagnosis in difficult cases.</p> <p>Methods</p> <p>A series of 100 endometrial curettage specimens with diagnosis of endometrial hyperplasia or well differentiated adenocarcinoma were blindly reviewed by 5 pathologists; their intra and interobserver reproducibility determined and further compared to the objective morphometric data i.e. D-score and volume percent of stroma (VPS).</p> <p>Results</p> <p>The results were assessed using the weighted kappa statistics. Mean intraobserver kappa value was 0.8690 (99.44% agreement). Mean interobserver kappa values by diagnostic category were: simple hyperplasia without atypia: 0.7441; complex hyperplasia without atypia: 0.3379; atypical hyperplasia: 0.3473, and well-differentiated endometrioid carcinoma: 0.6428; with a kappa value of 0.5372 for all cases combined.</p> <p>Interobserver agreement was in substantial rate for simple hyperplasia (SH) and well differentiated adenocarcinoma (WDA) but was in fair limit for complex hyperplasia (CH) and atypical hyperplasia (AH). Intraobserver agreement was almost perfect. The specimens were divided in two groups according to the computerized morphometric analysis: Endometrial Hyperplasia (EH) ( D Score ≥ 1 or VPS ≥ 55%) and Endometrial Intraepithelial Neoplasia (EIN) (D-Score < 1 or VPS < 55%). Morphometric findings were closely compatible with routine WHO classification made by one expert pathologist; however; diagnosis of (CH) and (AH) made by other pathologists were not concordant with morphometric data.</p> <p>Conclusion</p> <p>It may be necessary to make some revisions in WHO classification for endometrial hyperplasia and precancerous lesions.</p

Endocervical and metaplastic cells: comparison of endocervical and metaplastic cell number in papanicolaou smears with and without squamous intraepithelial lesion

Objective: To compare, with a retrospective study, endocervical and metaplastic cell number to identify the cytology of squamous intraepithelial lesion (SIL) of the cervix. Study Design: Cytology files from March 2000 to March 2003 were reevaluated, and those with SIL were identified. Results: In 8,743 cervicovaginal smears were found 70 (0.8%) SIL smears (39 low grade, 31 high grade) and 140 randomly selected smears without squamous or glandular abnormalities that were not atrophic or unsatisfactory. Endocervical and metaplastic cells counted in these smears and then classified into 5 groups were compared with each other. Conclusion: Women with smears containing endocervical cells are not at greater risk for SIL than those with smears lacking these cells. Women with smears containing metaplastic cells are more likely to have SIL than those without metaplastic cells. In addition, high grade lesions are more likely in smears containing more metaplastic cell

Comparison of radiological and pathological results in gestational trophoblastic diseases

Background: Gestational trophoblastic disease (GTD) is a heterogenous group of neoplastic lesions that is derived from placental trophoblastic epithelium. According to World Health Organization (WHO) classification they include: Hydatidiform mole (complete and partial), invasive mole, choriocarcinoma and placental site trophoblastic tumor. Hydatidiform mole is the most common and the diagnosis is achieved by pre-evacuation ultrasonographic evaluation, laboratory tests and finally histological assessment as gold standard. Since these disorders show varying potential for local invasion and metastasis, the accurate diagnosis, follow up and recommendations given to patients may differ.Methods: Consecutive cases with diagnosis of GTD from archive of pathology department of women (Mirza Kochak Khan) hospital were reviewed in whom results of clinical presentation and pre-evacuation ultrasound examination were documented. There were overall 220 cases for which the following clinical features were determined: gravidity, parity, history of previous abortion and gestational trophoblastic disease, the clinical symptoms such as vaginal bleeding and hypertension. Finally concordance between pre-evacuation ultrasonographic and histological diagnosis by kappa test is calculated.Results: Out of 220 cases with clinically gestational trophoblastic disease diagnosis, 197 cases were confirmed by histological diagnosis. The concluding histological diagnosis includes: 98 cases of complete mole (CM), 84 partial mole (PM), 4 invasive mole and 11 cases of choriocarcinoma. Outside 98 cases with histological diagnosis CM only in 4 cases misdiagnosed by ultrasonoghraphy (4.1%) and high degree of concordance between ultrasonography and histological diagnosis is seen.Conclusion: Ultrasonographic examination accompanied with clinical examination, beside histological assessment as gold standard have high efficacy in diagnosing  complete mole. This study did not show this finding for partial mole

Altered PTEN expression; a diagnostic marker for differentiating normal, hyperplastic and neoplastic endometrium

Abstract Background Different molecular alterations have been described in endometrioid endometrial carcinoma (EECA). Among them the most frequently altered is loss of the PTEN protein, a tumor suppressor gene. The purpose of this study was to evaluate the expression pattern of PTEN gene in normal, hyperplastic and neoplastic endometrium. Methods In a study in a referral gynecologic hospital in Tehran, Iran, immunohistochemical (IHC) evaluation of PTEN was performed on 87 consecutive specimens to the following three groups; group A- normal proliferative endometrium(n = 29); group B- hyperplastic endometrium [including simple hyperplasia without atypia(n = 21) and complex hyperplasia with atypia (n = 8)] and group C- EECA(n = 29). Immunostaining of cells was analyzed by arbitrary quantitative methods according to both slide's area staining and intensity of color reaction. Results PTEN immunoreactivity was present in all normal proliferative endometrium, all simple hyperplasia, 75% of atypical complex hyperplasia and in 48% of EECA (P &lt; 0.001). The intensity of PTEN reaction was significantly higher in group with proliferative endometrium than hyperplastic endometrium and EECA (P &lt; 0.001). Conclusion PTEN expression was significantly higher in cyclical endometrium than in atypical hyperplasia and endometrioid carcinoma.</p

A new grading system “two-tier” in clasification of ovarian serous carcinoma and evaluation of P53 gene expression by immunohistochemical staining

Background: Recently the use of “two tier" grading system in which ovarian serous carcinoma was classified as low-grade or high-grade in comparing to preceding system has improved authority in prognosis and survival. This approach is simplistic, reproducible, and based on biologic evidence. In this study, we reclassified ovarian serous carcinoma by a new two-tier system for grading and then evaluation of P53 expression in these tumors by immunohistochemistry method. Methods: We retrospectively reviewed 32 cases of ovarian serous carcinoma with previous diagnosis of well differentiated (eight cases) and moderate to poorly differentiated serous carcinoma (24 cases) and according "two tier" grading system in low-grade vs. high-grade serous carcinoma reclassified. Subsequntly all cases immunostained by P53 marker. Also clinical data related to survival of patients (with or without recurrence of tumor and death) and paraclinical findings such as presurgical blood serum level of CA125 are gathered. Results: Out of total eight patients with previously diagnosis; well diferentiated serous carcinoma and of 24 patients with moderate to poorly differentiated serous carcinoma reclassified as low-grade and high-grade ovarian serous carcinoma respectively and a statistically significant difference was found between two groups. (P<0.005) Also of total 24 cases with high grade serous carcinoma, in 12 cases (54%) P53 immunostaining was detected but in non of all low grade serous carcinoma was seen. All 8 low grade serous carcinoma were alive without recurrence of tumor. In 10 and 12 out of 24 cases with high grade serous carcinoma recurrence of tumor and death were seen respectively. Conclusion: Since the presence of P53 negative expression in all of low-grade serous carcinoma by immunostaining and low-grade serous carcinoma accounts for small pupulation of all ovarian serous carcinoma and also few cases in our study, we did not find significant differences between P53 expression and survival in two low-grade vs high-grade serous carcinoma groups

Twin Pregnancy with Hydatidiform Mole and Coexisting Fetus: Report of Three Cases and Review of Literature

A twin pregnancy with a coexisting complete hydatidiform mole and a healthy fetus (CMCF) is rare. Here we report three cases of CMCF with different clinical courses but similar outcome without a surviving neonate. Two women required uterine evacuation before 20 weeks of gestational age because of vaginal bleeding and medical complications and the other patient underwent termination of her pregnancy at 24 weeks of gestation due to severe pre-eclampsia. The pathologic diagnosis of complete hydatidiform mole was confirmed in each case and the chromosome complement was 46XX in two molar gestations and 46XY in one gestation. One of the three women required chemotherapy for treatment of low-risk gestational trophoblastic disease. The hCG level was normalized after 4 cycles and the patient was free of disease at 1 year follow-up. Review of the literature discussing the diagnostic tools, clinical features, management and outcome of pregnancies with CMCF are presented

Association of Neo Angiogenesis by CD34 Expression and Clinicopathologic Features in Squamous Cell Carcinoma of Cervix

Tumor angiogenesis is one of the most important factors in tumor progression. In this study, the angiogenesis of cervical squamous cell carcinoma (SCC) and its association with prognostic factors was assessed by using CD34 immunostaining marker. The microvessel density in 40 patients with cervical SCC was studied in three areas of the tumor; stromal and peripheral tumor area (combined) central stromal tumor area and peripheral tumor area and the relationship of microvascular density and survival was also evaluated. The count of CD34 is correlated with younger age, the presence of perineural invasion and metastasis to lymph nodes. High peripheral tumor angiogenesis is also correlated with lower disease-free tumor survival. According to the findings of the present study, CD34 expression, especially in peripheral tumor areas, can be used as a prognostic marker in cervical SCC