Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare uterine neoplasms characterized by pure or predominant epithelial-like patterns that share morphologic, immunohistochemical, and ...ultrastructural features with ovarian sex cord tumors. FOXL2 immunoexpression has recently been found in sex cord stromal tumors of the ovary, including granulosa cell tumors, Sertoli-Leydig cell tumors, thecomas, and fibromas, but mutations have been identified mostly in adult granulosa cell tumors. In this study, we investigated FOXL2 mutation status and protein expression in UTROSCTs. Mutational analysis using a TaqMan real-time polymerase chain reaction-based allelic discrimination assay was performed on formalin-fixed, paraffin-embedded tissue from 15 UTROSCTs. FOXL2 mutation was absent in all tumors. FOXL2 immunoexpression was tested in all 15 tumors. Intensity of staining was scored as weak, moderate, or strong. Percentage of tumor cells with nuclear staining was recorded as follows: 0 (negative); 1+ (1% to 25%); 2+ (26% to 50%); 3+ (51% to 75%); and 4+ (76% to 100%). Nuclear expression of FOXL2 was present in 6 of 15 (40%) UTROSCTs. One tumor demonstrated strong 4+ staining. Moderate expression was seen in 3 cases, including 2 and 1 showing 2+ and 1+ staining, respectively. Weak expression was observed in 2 tumors demonstrating 3+ and 1+ staining. Although UTROSCTs show overlapping morphologic, immunohistochemical, and ultrastructural features with sex cord stromal tumors of the ovary, they do not harbor FOXL2 mutation despite focal immunoreactivity in a subset of these tumors.
The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual ...differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk.
We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. Anti-Mullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (OR
). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics.
Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (OR
: 1.07 (0.99-1.17)), or with any of the examined subgroups.
Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.
Cytopathology (CYP) fellowship training is a critical component of maintaining a skilled group of cytopathologists. For years, the recruitment process for CYP fellowship programs has remained ...unchanged, with individual programs outlining their own requirements and timeline, and applicants bearing the cost of travel and dealing with the variable processes outlined by individual programs. However, there has been renewed interest in analyzing the recruitment process for CYP fellowships to look for areas of potential improvement and uniformity.
With the goal of gauging the interest of CYP fellowship program directors (PDs) in a more unified approach to recruitment or a formal match process, the ASC Cytopathology Program Directors Committee (CPDC) surveyed PDs via SurveyMonkey and organized special webinars with polling over a 4-year time frame (2017-2021), and examined Qualtrics survey data collected by the American Board of Pathology (ABPath) in 2020.
The response rate for PDs was greatest in a formal survey by the ABPath (66 respondents; 71% of PDs) conducted in 2020, and lower for an ASC survey in 2021 (61 respondents, 66% of PDs) and 2017 (19 respondents; 21% of PDs) and two recent ASC webinars (10 and 26 respondents; 11% and 28% of PDs). Support for a fellowship match process varied from 29% to 77%, respondent uncertainty ranged from 13% to 50%, and a lack of support ranged from 10% to 60%. In aggregate, approximately 56% of respondents would be in favor of a more standardized process. Recently, after hearing about other fellowships experimenting with a standardized process, the interest in a unified approach doubled from approximately 29% to 60%, and the percentage of PDs with uncertainty decreased from 50% to 26%. In the most recent follow up survey, interest reached the highest level of 77% among PDs.
Herein we present several years of feedback from the CYP fellowship PD community regarding a more standardized approach to CYP fellowship recruitment, culminating in the latest survey with 77% of CYP fellowship PDs expressing interest. Thus, details about what a unified timeframe may look like for CYP fellowships is presented to show how this may improve the recruitment process for the mutual benefit for programs and applicants.
•With the recent move to virtual interviews during the COVID-19 pandemic, the emerging need for an equitable selection process, and the momentum provided by other subspecialties moving toward to unified timeframe, there has been renewed interest in analyzing the recruitment process for CYP fellowships to look for areas of potential improvement and uniformity.•In various surveys and webinar polling, support for a fellowship match process varied from 29%-77%, respondent uncertainty ranged from 13%-50%, and a lack of support ranged from 10%-60%. In aggregate, approximately 55.6% of PD respondents would be in favor of a more standardized process. Recently, after hearing about other fellowships using a standardized process, the interest in a unified approach doubled from approximately 29% to 60%, and then a follow-up survey achieved the greatest interest level of 77%.•Given the problems with the current process and interest among over half of the CYP fellowship PDs in a more standardized approach, details about what a unified timeframe may look like for CYP fellowships is presented to show how this may improve the recruitment process for the mutual benefit for programs and applicants.
An international panel recently recommended reclassification of non-invasive follicular variant of papillary thyroid carcinoma (PTC) to non-invasive follicular thyroid neoplasm with papillary-like ...nuclear features (NIFTP). NIFTPs have little or no risk of recurrence and can be treated with lobectomy alone. Preoperative distinction of NIFTP from PTC will help avoid overtreatment.
All thyroid tumors with a histologic diagnosis of PTC and preceding diagnostic cytology (n = 299) over a 5-year period were identified. Cases meeting criteria for NIFTP were reclassified as such. All NIFTP cases with available cytology (n = 6) and a similar number of randomly selected invasive follicular variant of papillary thyroid carcinoma (IFVPTC; n = 9) and classic PTC (cPTC, n = 11) were evaluated for 18 cytologic features.
A total of 35 (12%) lesions were reclassified as NIFTP, 194 (65%) were cPTC, and 70 (23%) were IFVPTC. The NIFTPs had a preceding cytologic interpretation of benign (31%), atypia of undetermined significance (34%), follicular neoplasm (9%), suspicious for malignancy (12%), or malignant (14%). Cytologically, NIFTP was distinguished from cPTC by absence of any architectural features in all 6 cases, and by absence of pseudoinclusions (P < 0.001) and multinucleated giant cells (P = 0.027) in nearly all. Nuclear pseudoinclusions (P = 0.001), marginal micronucleoli (P = 0.018), irregular branching sheets (P = 0.025), and linear arrangement (P = 0.025) favored IFVPTC over NIFTP.
NIFTPs were originally assigned to a variety of cytologic categories. There are several cytologic differences between NIFTP and cPTC or IFVPTC. Our findings support restricting the definitive diagnosis of PTC to cases with architectural features of PTC and/or intranuclear pseudoinclusions.
Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging.
To determine diagnostic concordance for biopsy-proven low-grade squamous intraepithelial lesion ...(LSIL) and high-grade squamous intraepithelial lesion (HSIL) Papanicolaou test slides in the College of American Pathologists PAP Education program.
We analyzed 121 059 responses from 4251 LSIL and HSIL slides for the interval 2004 to 2013 using a nonlinear mixed-model fit for reference diagnosis, preparation type, and participant type. We evaluated interactions between the reference diagnosis and the other 2 factors in addition to a repeated-measures component to adjust for slide-specific performance.
There was a statistically significant difference between misclassification of LSIL (2.4%; 1384 of 57 664) and HSIL (4.4%; 2762 of 63 395). There was no performance difference between pathologists and cytotechnologists for LSIL, but cytotechnologists had a significantly higher HSIL misclassification rate than pathologists (5.5%; 1437 of 27 534 versus 4.0%; 1032 of 25 630; P = .01), and both were more likely to misrepresent HSIL as LSIL ( P < .001) than the reverse. ThinPrep LSIL slides were more likely to be misclassified as HSIL (2.4%; 920 of 38 582) than SurePath LSIL slides (1.5%; 198 of 13 196), but conventional slides were the most likely to be misclassified in both categories (4.5%; 266 of 5886 for LSIL, and 6.5%; 573 of 8825 for HSIL).
More participants undercalled HSIL as LSIL (false-negative) than overcalled LSIL as HSIL (false-positive) in the PAP Education program, with conventional slides more likely to be misclassified than ThinPrep or SurePath slides. Pathologists and cytotechnologists classify LSIL equally well, but cytotechnologists are significantly more likely to undercall HSIL as LSIL than are pathologists.
Introduction In concert with the 2014 update to the Bethesda System for Reporting Cervical Cytology, a Web-based image interobserver study was performed to evaluate concordance with the “expert ...panel” interpretation, as was done during the Bethesda 2001 update. The aim was to identify cytomorphologic features and Bethesda reporting categories that represent sources of poor interobserver agreement and see how the trends compared to the first Bethesda Interobserver Reproducibility Study (BIRST). Materials and methods Participants were recruited online through national and international cytopathology professional societies. Study participants evaluated 84 previously unpublished web images chosen from the third Bethesda Atlas image set, prior to the release of the atlas. These images spanned all reporting categories and included typical and borderline cytomorphology. Demographic information was collected on level of training, practice patterns, and experience of the participants. Participation was restricted to those correctly answering 2 basic cytopathology questions, ensuring minimal knowledge of gynecologic cytopathology. Results A total of 1290 unique individuals attempted access to this Web-based study and 833 correctly answered the two qualifying questions. Of these, 518 respondents completed the survey. Participant origin included: 59% United States, 41% international; 48% cytotechnologists, 41% pathologists, 5% fellows, and 6% other. Practice types were: 39% academic institutions, 29% private hospitals, and 16% commercial laboratories. Overall, the mean participant agreement with the exact Bethesda panel interpretation was 62.8%. The best agreement was found for negative for intraepithelial lesion or malignancy (NILM; 74%) and low-grade squamous intraepithelial lesion (LSIL; 86%) categories. Squamous cell carcinoma (SCC) (63%), high-grade squamous intraepithelial lesion (HSIL; 60%), atypical squamous cells of undetermined significance (ASC-US; 62%) and atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H; 60%) showed slightly lower concordance with the panel interpretations. Cervical glandular lesions were more problematic (33%). Anal samples performed similarly to their gynecologic counterparts. There was similar diagnostic agreement across participant certifications and practice type (academic versus non-academic). Performance was higher for United States and other North America–based participants ( P = 0.0104). This significance may be attributed to a language bias, as the survey was only offered in English. Conclusions Similar to the BIRST-1 study conducted in 2001, the most important factor for diagnostic agreement by cytotechnologists, pathologists, and trainees was the a priori difficulty of an image rather than participant training, certification, or experience. Participants showed better general diagnostic agreement with the expert panel interpretations of the material in BIRST-2 than in BIRST-1. Agreement was highest for Bethesda categories of NILM, LSIL, HSIL, and SCC. Concordance for even the borderline ASC-US and ASC-H categories exhibited remarkable improvement in the BIRST-2.
The histopathologic distinction between typical carcinoid (TC) and atypical carcinoid (AC) of the lung is based largely on mitotic index. Ki-67 may aid in separation of these tumors, as well as the ...distinction from large cell neuroendocrine carcinoma (LCNEC).
We identified 55 surgically resected primary neuroendocrine lung tumors (39 TC, 7 AC, 9 LCNEC) based on mitotic rate and histologic features. Ki-67 proliferative index based on automated image analysis, tumor necrosis, nodal metastases, local or distant recurrence, and survival were compared across groups.
The mean mitotic count and Ki-67 index for TC, AC, and LCNEC were 0.1 and 2.3%, 3.4 and 16.8%, and 56.1 and 81.3% respectively. The Ki-67 index did not overlap among groups, with ranges of 0-6.7% for TC, 9.9-25.7% for AC, and 63.2-91.9% for LCNEC. Nodal metastases were identified in 4/39 (10%) TC, 2/7 (22%) AC, and 2/8 (25%) LCNEC. There was no survival difference between TC and AC, but there was a significant survival difference between LCNEC and TC and AC combined (p<0.001). There was a step-wise increase in disease free survival with tumor grade: no TC recurred, 2/7 AC recurred or progressed (median interval 35.5 months), and all LCNEC recurred or progressed (median interval 10.1 months). No patient with TC or AC died of disease, compared to 7/8 LCNEC with follow-up data.
We conclude that Ki-67 index is a useful diagnostic marker for neuroendocrine tumors, with 7% a divider between AC and TC, and 50% a divider between LCNEC and AC. LCNEC is biologically different from AC and TC, with a much more aggressive course, and a high Ki-67 index.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_174.
The nature of the distinctive ovarian lesion often associated with sclerosing peritonitis, initially considered a variant of luteinized thecoma in the paper describing this phenomenon, remains ...uncertain, as does its long-term prognosis. We describe the features of 27 cases, including immunohistochemical analysis of 13 cases. Sclerosing peritonitis was documented in 25 cases. Patients ranged in age from 10 months to 85 years, and typically presented with abdominal distension and pain with ascites and sometimes bowel obstruction. The ovarian lesions, clinically bilateral in 24 cases, ranged from 2 to 31 cm and often had a striking cerebriform aspect. Microscopically, mitotically active spindle cells with weakly luteinized cells, variable edema, and entrapped follicles were typical. The spindle cells were focally positive with calretinin in 2 cases, CD56 in 2, AE1/3 in 4, smooth muscle actin in 12, and desmin in 8 cases, and negative with alpha-inhibin, epithelial membrane antigen, beta-catenin, CD34, and transforming growth factor-beta, with focal nuclear positivity for estrogen receptor in 5 and progesterone receptor in 11 cases. Luteinized cells were positive with alpha-inhibin, calretinin, and/or CD56. The peritoneal lesions were strongly positive with AE1/3 and exhibited focal weak or moderate positivity with estrogen receptor or progesterone receptor in 4 of 8 cases each. Follow-up in 20 cases (mean: 5.9 y) disclosed no evidence of spread of the ovarian lesion, but 3 patients died of sclerosing peritonitis. The findings fail to allow definitive classification of the ovarian lesions, and we prefer at present to retain their current designation as a subtype of luteinized thecoma, but to allow for the possibility of a non-neoplastic nature, feel it reasonable to have the designation "thecomatosis" as a parenthetical alternative. We have documented for the first time that sclerosing peritonitis is not invariably associated with the distinctive ovarian pathology present in these cases.
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