Frequency of "incidental" serous tubal intraepithelial carcinoma (STIC) in women without a history of or genetic risk factor for high-grade serous carcinoma: A six-year study.
Universal Screening for Mismatch-Repair Deficiency in Endometrial Cancers to Identify Patients With Lynch Syndrome and Lynch-like Syndrome.
International journal of gynecological pathology
2017; 36 (2): 115-127
Objective The purpose of this study was to determine the prevalence of incidentally discovered serous tubal intraepithelial carcinoma in women without a genetic risk for or history of high grade serous carcinoma (HGSC) in the gynecologic tract.All pathology reports at our institution that included bilateral salpingectomies from January 2006-December 2011 were examined in women >50years old in which the entire tube or the distal one-third was examined histologically with the complete (proximal and distal fallopian tube) or modified (distal one third of the tube) SEE-FIM protocol. Cases were divided into: Group 1, a history of or known risk factors (BRCA1 or BRCA2 mutations) for HGSC and Group 2, those without these attributes for whom a STIC would be unexpected (incidental). Women undergoing unspecified "risk-reducing" procedures were included in Group 1.Of 4051 identified total, 2268 had complete examination of the distal fallopian tube and were age 50 or above. Of these, 1747 were in group 2. Two STICs were identified (0.1%), one associated with a grade 2 endometrial endometrioid adenocarcinoma and one with a low-grade ovarian serous carcinoma in the setting of a serous borderline tumor.Incidental STICs in women over age 50 are uncommon. However, the significance of lesser tubal atypias (0.3% in this study), risk of STIC in women with no epithelial pathology and the risk imposed by coexisting endometrioid neoplasia are unclear and require further study.
View details for DOI 10.1016/j.ygyno.2017.04.015
View details for PubMedID 28479065
Identification and Characterization of 2 Testicular Germ Cell Markers, Glut3 and CyclinA2
APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
2013; 21 (5): 401-407
Although consensus has yet to be reached on universal mismatch-repair (MMR) protein immunohistochemical (IHC) screening for Lynch syndrome (LS) in endometrial cancer (EC), an increasing number of institutions have adopted universal screening protocols similar to those used for colorectal carcinoma. Here we describe our institution's experience with a prospective universal screening protocol in which all ECs resected over a period of 19 months (n=242) were screened for MLH1, PMS2, MSH2, and MSH6 deficiencies using IHC, followed by MLH1 promoter methylation testing when appropriate. When consent was obtained, tumor samples underwent next-generation sequencing. A total of 11 unmethylated MMR-deficient cases (4.5% of cohort) were identified through IHC screening. Germline testing was performed in 10 cases and confirmed LS in 4 patients (1.7% of cohort). Of our 4 confirmed LS cases, 1 did not meet traditional LS screening criteria (eg, age below 50 y, Revised Bethesda criteria). In addition, universal screening identified 6 germline-negative MMR-deficient nonmethylated cases, 4 of which occurred in women older than 50. Although our next-generation sequencing data suggest somatic mutations in 4 of these cases, it is possible that these cases may represent cases of "Lynch-like syndrome." We conclude that a subset of LS cases could be missed using traditional screening guidelines. The value of screening for Lynch-like syndrome has yet to be determined. Although the cost-effectiveness of universal screening in EC has yet to be elucidated, we conclude that universal IHC screening is currently a reasonable, and arguably superior, approach to screening for LS.
View details for DOI 10.1097/PGP.0000000000000312
View details for PubMedID 27556954
Testicular germ cell tumors (TGCT) are the most common type of testicular tumor and encompass different histologic types that greatly influence treatment and prognosis. Immunohistochemical studies may be required for accurate classification, particularly when these tumors present at extragonadal sites, and to aid in distinguishing histologic types. Traditional markers for identifying and distinguishing TGCT include PLAP, CD117, AFP, and CD30. More recently, the addition of OCT3/4 and SALL4 has increased sensitivity for immunohistochemical detection of germ cell tumors. We examined gene expression data from a previously published microarray study that compared normal testis mRNA expression to various TGCT. We also performed a search of the literature to identify less well-characterized markers. Glut3 and cyclinA2 showed promise as TGCT markers. Therefore, we evaluated expression of glut3 and cyclinA2 by immunohistochemistry using tissue microarrays (TMAs). Of 66 seminomas included in the TMA, 64 (97%) showed positive nuclear staining for cyclinA2 and 58 (88%) were strongly positive. Strong positive staining for cyclinA2 was also seen in the spermatocytic seminoma. All 20 of the embryonal carcinomas stained positively with cyclinA2, and 19 (95%) displayed strong nuclear staining for cyclinA2. Twenty of the 20 embryonal carcinomas stained for glut3 in a strong membranous pattern. Of 8 yolk sac tumors, 100% stained with glut3. We also evaluated glut3 and cyclinA2 staining on a general TMA containing 486 samples representing 156 different tumors. CyclinA2 stained a number of other tumor types, but the majority of these were weak or focal staining. Glut3 was rarely positive in other tumors; interestingly, most of these were of ovarian origin. We conclude that glut3 is a sensitive (96%) and specific (92%) marker for embryonal carcinomas and yolk sac tumors. Although cyclinA2 is a sensitive marker of seminomas and embryonal carcinomas (98%), its specificity is lower if focal and weak staining of nongerm cell tumors is considered positive. The sensitivity and specificity of glut3 are comparable with that seen for SALL4.
View details for DOI 10.1097/PAI.0b013e31827b505f
View details for Web of Science ID 000324837800004
View details for PubMedID 23343953