scholarly journals What Is New on Ovarian Carcinoma: Integrated Morphologic and Molecular Analysis Following the New 2020 World Health Organization Classification of Female Genital Tumors

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 697
Author(s):  
Antonio De Leo ◽  
Donatella Santini ◽  
Claudio Ceccarelli ◽  
Giacomo Santandrea ◽  
Andrea Palicelli ◽  
...  

Ovarian carcinomas represent a heterogeneous group of neoplasms consisting of separate entities with distinct risk factors, precursor lesions, pathogenesis, patterns of spread, molecular profiles, clinical course, response to chemotherapy, and outcomes. The histologic subtype and the related molecular features are essential for individualized clinical decision-making. The fifth edition of the World Health Organization classification of tumors of the female genital tract divides ovarian carcinomas into at least five main and distinct types of ovarian carcinomas: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, clear cell carcinoma, and mucinous carcinoma. Molecular pathology has improved the knowledge of genomic landscape of ovarian carcinomas identifying peculiar alterations for every histologic subtype. It is well-known that high-grade and low-grade serous carcinomas are separate entities with entirely different morphologic and molecular characteristics. TP53 and BRCA mutations are typical of high-grade serous carcinoma, whereas BRAF and KRAS mutations frequently occur in low-grade serous carcinoma. Endometrioid and clear cell carcinomas are frequently associated with endometriosis. Endometrioid tumors are characterized by β-catenin alterations, microsatellite instability, and PTEN and POLE mutations, while ARID1A mutations occur in both endometrioid and clear cell carcinomas. Mucinous carcinomas are uncommon tumors associated with copy-number loss of CDKN2A and KRAS alterations and metastasis from other sites should always be considered in the differential diagnosis.

2018 ◽  
Vol 6 (4) ◽  
pp. 85 ◽  
Author(s):  
Ugo Testa ◽  
Germana Castelli ◽  
Elvira Pelosi

Brain tumors are highly heterogeneous and have been classified by the World Health Organization in various histological and molecular subtypes. Gliomas have been classified as ranging from low-grade astrocytomas and oligodendrogliomas to high-grade astrocytomas or glioblastomas. These tumors are characterized by a peculiar pattern of genetic alterations. Pediatric high-grade gliomas are histologically indistinguishable from adult glioblastomas, but they are considered distinct from adult glioblastomas because they possess a different spectrum of driver mutations (genes encoding histones H3.3 and H3.1). Medulloblastomas, the most frequent pediatric brain tumors, are considered to be of embryonic derivation and are currently subdivided into distinct subgroups depending on histological features and genetic profiling. There is emerging evidence that brain tumors are maintained by a special neural or glial stem cell-like population that self-renews and gives rise to differentiated progeny. In many instances, the prognosis of the majority of brain tumors remains negative and there is hope that the new acquisition of information on the molecular and cellular bases of these tumors will be translated in the development of new, more active treatments.


2015 ◽  
Vol 25 (7) ◽  
pp. 1201-1207 ◽  
Author(s):  
Esther Louise Moss ◽  
Tim Evans ◽  
Philippa Pearmain ◽  
Sarah Askew ◽  
Kavita Singh ◽  
...  

IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.


Author(s):  
Nisha Singla ◽  
Sarita Nibhoria ◽  
Kanwardeep Kaur Tiwana ◽  
Prince Gupta

Introduction: The ovaries are the primary female reproductive organs and endocrine glands. Ovarian carcinoma has often been called as the silent killer because the symptoms may develop so late that the chances of cure are very poor. According to World Health Organisation (WHO) ovarian tumours are classified based upon their most probable tissue of origin: surface epithelial (65%), germ cell (15%), sex cord-stromal (10%), metastases (5%) and miscellaneous. The malignant surface epithelial tumours are further classified by cell type into serous, mucinous, endometrioid, clear cell, brenner, seromucinous and undifferentiated carcinoma. The most widely used tumour marker in ovarian carcinoma is CA-125 which is considered as gold standard. Aim : To find the utility of serum CA-125 levels in histopathological variants of malignant surface epithelial tumours, degree of differentiation and their distribution according to clinical data pertaining to age, parity, history of use of oral contraceptive pills/ovulation inducing drugs and family history of carcinoma ovary/breast or colon. Materials and Methods: A prospective study (cohort study) was done at Guru Gobind Singh Medical College and Hospital, Faridkot over a period of 1.5 year (April 2017-oct 2018) on 50 ovarian masses which were diagnosed as ovarian carcinoma. Data was represented as frequencies and percentages for categorical variables and as means and standard deviations for continuous variables. Analysis was done using Statistical Package for Social Sciences (SPSS) v 20.0.0. Results: Serous carcinoma (80%) topped among all the histological variants. Serous high grade carcinoma was more common than serous low grade carcinoma. Maximum rise of serum CA-125 levels were seen in serous carcinoma. Among serous carcinomas, mean serum CA-125 levels were more in high grade serous carcinoma than low grade serous carcinoma and the results were statistically significant. conclusion: Serum CA-125 level is a great tool for diagnosis, follow-up and prognosis of ovarian carcinomas.


2001 ◽  
Vol 125 (5) ◽  
pp. 646-651 ◽  
Author(s):  
Stephen J. Cina ◽  
Kristen J. Lancaster-Weiss ◽  
Kristen Lecksell ◽  
Jonathan I. Epstein

Abstract Objective.—The present study examines p53 and Ki-67 staining patterns of the diagnostic entities included within the new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms. Design.—We retrospectively studied 151 bladder biopsies from 81 patients with the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12); low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB-1). Two hundred cells from each lesion were visually counted, and the percentage of positive cells was tabulated without knowledge of the WHO/ISUP diagnosis. Results.—In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder, 29% of the benign urothelial cells were p53 positive. In papillary lesions, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high-grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary neoplasm of LMP. Conclusions.—An increased proliferative index as demonstrated by immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma but may be seen in benign-appearing urothelium, suggesting a “field effect” with occult molecular aberration.


2018 ◽  
Vol 27 (3) ◽  
pp. 225-230
Author(s):  
Cléciton Braga Tavares ◽  
Francisca Das Chagas Sheyla Almeida Gomes Braga ◽  
Emerson Brandão Sousa ◽  
José Nazareno Pearce de Oliveira Brito

Objective. This review aims to carry out a survey on the importance of Ki67 in the astrocytomas study. Methods. A search in the electronic database of Medline via PubMed and using MESH terms was carried out. Articles were published between January 2005 and December 2015. All studies were analyzed by two experienced researchers, using inclusion and exclusion criteria for the selection of studies. Results. Five studies showed an association between cell proliferation and survival time. Four articles mentioned as cut-off point for survival a Ki67 of 10% and a fifth article a Ki67 of 14.3. A study showed an association between therapeutic failure and Ki67. Four studies have made the association between Ki67 and World Health Organization classification. Conclusion. High levels of Ki67 are associated to high grade astrocytomas and lower survival time.


Author(s):  
Tamer M. Abdel Dayem ◽  
Amira M. Badawy

Background: Epithelial ovarian cancers (EOCs) are the most common cause of death from gynaecological malignancy. Serous ovarian carcinomas represent (68%) of Epithelial ovarian cancers, they are further divided into low-grade (type I) and high-grade (type II) serous ovarian carcinomas. There has been increasing evidence that fallopian tubes are considered the most important site of origin of pelvic high grade serous carcinoma. Salpingectomy is thought to be effective in reducing ovarian cancer risk in the future and prolonging average life expectancy, however, there are some concerns regarding ovarian function after elective salpingectomy in premenopausal women. The current study was carried out to assess the effect of salpingectomy on ovarian function in premenopausal women.Methods: 60 premenopausal cases were recruited and subjected to open abdominal hysterectomy without oophorectomy (for benign indications). Included cases were below 45 years, with documented active ovarian functions. Cases with genital malignancy, ovarian gross pathology and suspected or known ovarian failure were excluded. Cases were randomly allocated to one of two groups; group-A (where salpingectomy was performed), and group-B (where salpingectomy was not done). For all patients, ovarian functions were assessed prior operation, and at one and three months after operation using serum anti-Mullarian hormone (AMH) as well as early follicular antral follicular count (AFC), serum follicle stimulating hormone (FSH) and serum oestradiol (E2).Results: The mean pre-operative AFC, AMH, FSH, and E2 levels showed no significant changes after operation at one and three months postoperative follow up in both studied groups, denoting preserved ovarian function in both groups.Conclusions: Prophylactic salpingectomy is a safe and simple procedure that has no effect on ovarian reserve or function when performed in premenopausal women.


2010 ◽  
Vol 134 (8) ◽  
pp. 1160-1163
Author(s):  
Hiroshi Miyamoto ◽  
Fadi Brimo ◽  
Luciana Schultz ◽  
Huihui Ye ◽  
Jeremy S. Miller ◽  
...  

Abstract Context.—Few large cohort studies have addressed outcome in patients with noninvasive low-grade papillary urothelial carcinoma (LG-UrCa) following implementation of the 2004 World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification. Objective.—To evaluate our cohort of LG-UrCa cases classified according to 2004 WHO/ISUP to reassess outcome and interobserver agreement. Design.—Files were searched for all patients diagnosed with LG-UrCa between 1998 and 2008. All sections were reevaluated for accuracy of classification. Results.—A total of 112 cases initially diagnosed as LG-UrCa were identified. Of those, 8 of 55 cases (15%) initially diagnosed by nonurologic pathologists were reclassified as high-grade papillary urothelial carcinoma and were excluded. The mean length of follow-up was 40.1 months (range, 2–113 months). Tumor recurrence was encountered in 56 of 104 patients (53.8%), including 37 (35.6%) with LG-UrCa or lower-grade tumors and 19 (18.3%) with high-grade papillary urothelial carcinoma. Of the 19 patients demonstrating grade progression, 7 (37%) also developed stage progression (invasive carcinoma, n  =  5; metastatic carcinoma, n  =  2). Seven patients eventually underwent radical cystectomy. None of the 104 patients died of bladder cancer. The mean number of recurrence episodes was 3.11. The mean durations of time to first recurrence and time to grade progression were 13.9 months and 25.1 months, respectively. The mean size of initial tumors was 1.73 cm. There was no significant correlation between tumor size, patient age, sex, or smoking history and the likelihood for recurrence or grade progression. A significantly higher rate of recurrence was seen in patients with multiple tumors at initial diagnosis (P  =  .04). Conclusions.—A tendency to underdiagnose high-grade papillary urothelial carcinoma continues to exist. More than half (53.8%) of patients with LG-UrCa developed recurrence, with an 18.3% incidence of grade progression and a 6.7% incidence of stage progression. Patients with multiple initial tumors had significantly higher risk of developing recurrence.


2013 ◽  
Vol 13 (2) ◽  
pp. 84-86
Author(s):  
Arvids Jakovlevs ◽  
Andrejs Vanags ◽  
Janis Gardovskis ◽  
Ilze Strumfa

Abstract Rhabdoid meningioma (RM) is a rare type of meningioma. It is classified as a grade III tumour (anaplastic meningioma) in the recent World Health Organization (WHO) classification of the tumours of the central nervous system (CNS). Here we describe a unique case of RM lacking any features of malignancy. Few cases of low-grade RMs are described in the literature in contrast with the grading of this entity in WHO classification.


2021 ◽  
Author(s):  
Chang Gok Woo

Abstract Background: Nestin, a type VI intermediate filament, is expressed in neuroepithelial cells during embryogenesis and has been expressed in various human tumors. Recent studies have reported that expression is associated with poor prognosis in brain tumors, but the results are inconclusive. In this study, we evaluated usefulness of Nestin expression using immunohistochemistry as a diagnostic and prognostic biomarker for IDH mutation and the new World Health Organization (WHO) classification.Methods: To investigate Nestin expression, immunohistochemistry was performed on 92 adult brain gliomas using tissue microarrays. We further analyzed the clinical characteristics and survival outcomes according to Nestin expression and examined its correlation with another glioma biomarker, IDH mutation.Results: Sixty patients (65.2%) were Nestin-positive (weak and strong). Nestin expression and intensity were significantly correlated with age, location, diagnosis, and IDH mutations. Old age and high-grade gliomas showed a higher frequency and stronger intensity of Nestin expression than those of young age and with low-grade gliomas (p<0.001). Gliomas with IDH mutations that are located in the frontal lobe showed no expression or had weak positivity. Multivariate analysis demonstrated that Nestin expression (weak, hazard ratio [HR] 5.39, p=0.036; strong, HR 8.43, p=0.007) and IDH wildtype (HR 7.63; p=.001) were significant independent prognostic factors. Moreover, patients with tumors expressing Nestin showed shorter survival (p<0.001).Conclusions: Nestin expression exhibits high intensity in high-grade gliomas and is a useful diagnostic marker. High expression and level of Nestin were significantly correlated with worse survival and was considered a significant marker of poor prognosis in new WHO classification, independent of IDH mutation.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Masafumi Koshiyama ◽  
Noriomi Matsumura ◽  
Ikuo Konishi

Type I ovarian tumors, where precursor lesions in the ovary have clearly been described, include endometrioid, clear cell, mucinous, low grade serous, and transitional cell carcinomas, while type II tumors, where such lesions have not been described clearly and tumors may developde novofrom the tubal and/or ovarian surface epithelium, comprise high grade serous carcinomas, undifferentiated carcinomas, and carcinosarcomas. The carcinogenesis of endometrioid and clear cell carcinoma (CCC) arising from endometriotic cysts is significantly influenced by the free iron concentration, which is associated with cancer development through the induction of persistent oxidative stress. A subset of mucinous carcinomas develop in association with ovarian teratomas; however, the majority of these tumors do not harbor any teratomatous component. Other theories of their origin include mucinous metaplasia of surface epithelial inclusions, endometriosis, and Brenner tumors. Low grade serous carcinomas are thought to evolve in a stepwise fashion from benign serous cystadenoma to a serous borderline tumor (SBT). With regard to high grade serous carcinoma, the serous tubal intraepithelial carcinomas (STICs) of the junction of the fallopian tube epithelium with the mesothelium of the tubal serosa, termed the “tubal peritoneal junction” (TPJ), undergo malignant transformation due to their location, and metastasize to the nearby ovary and surrounding pelvic peritoneum. Other theories of their origin include the ovarian hilum cells.


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