Jenkins, Sarah M.

AbstractMeningeal solitary fibrous tumors (SFT) are rare and have a high frequency of local recurrence and distant metastasis. In a cohort of 126 patients (57 female, 69 male; mean age at surgery 53.0 years) with pathologically confirmed meningeal SFTs with extended clinical follow‐up (median 9.9 years; range 15 days–43 years), we performed extensive molecular characterization including genome‐wide DNA methylation profiling (n = 80) and targeted TERT promoter mutation testing (n = 98). Associations were examined with NAB2::STAT6 fusion status (n = 101 cases; 51 = ex5‐7::ex16‐17, 26 = ex4::ex2‐3; 12 = ex2‐3::exANY/other and 12 = no fusion) and placed in the context of 2021 Central Nervous System (CNS) WHO grade. NAB2::STAT6 fusion breakpoints (fusion type) were significantly associated with metastasis‐free survival (MFS) (p = 0.03) and, on multivariate analysis, disease‐specific survival (DSS) when adjusting for CNS WHO grade (p = 0.03). DNA methylation profiling revealed three distinct clusters: Cluster 1 (n = 38), Cluster 2 (n = 22), and Cluster 3 (n = 20). Methylation clusters were significantly associated with fusion type (p < 0.001), with Cluster 2 harboring ex4::ex2‐3 fusion in 16 (of 20; 80.0%), nearly all TERT promoter mutations (7 of 8; 87.5%), and predominantly an “SFT” histologic phenotype (15 of 22; 68.2%). Clusters 1 and 3 were less distinct, both dominated by tumors having ex5‐7::ex16‐17 fusion (respectively, 25 of 33; 75.8%, and 12 of 18; 66.7%) and with variable histological phenotypes. Methylation clusters were significantly associated with MFS (p = 0.027), but not overall survival (OS). In summary, NAB2::STAT6 fusion type was significantly associated with MFS and DSS, suggesting that tumors with an ex5::ex16‐17 fusion may have inferior patient outcomes. Methylation clusters were significantly associated with fusion type, TERT promoter mutation status, histologic phenotype, and MFS.

Pleural epithelioid mesothelioma (PEM) is divided into low and high grades based on nuclear atypia, mitoses, and necrosis in the tumor. Assessing mitoses and nuclear atypia tend to be labor-intensive with limited reproducibility. Ki-67 proliferation index was shown to be a prognostic factor in PEM, but its performance has not been directly correlated with tumor grade or mitotic score. This study evaluated the potential of Ki-67 index as a surrogate of tumor grade. We also compared the predictability of mitoses and Ki-67 index for overall survival (OS). Ninety-six PEM samples from 85 patients were identified from the surgical pathology file during 2000-2021 at our institution, and all glass slides were reviewed by 2 pulmonary pathologists to confirm the diagnosis and assign the tumor grade. Digital image analysis (DIA) was done for Ki-67 index. The agreement on tumor grading between 2 reviewers was moderate (kappa value = 0.47). The correlation between mitotic count (average count by 2 reviewers) and Ki-67 index was 0.65. The areas under the curve for predicting tumor grade by mitotic score and Ki-67 index were 0.84 and 0.74 (reviewer 1) and 0.85 and 0.81 (reviewer 2), respectively. High Ki-67 index and mitoses were significantly associated with poor OS (P=0.03 and 0.0005, using 30% and 10/2 mm2 as cutoffs, respectively). In conclusion, Ki-67 index by DIA was associated with tumor grade as well as mitotic count, and its predictability for OS was comparable to that of mitotic score, thus being a potential surrogate for tumor grade.

Abstract INTRODUCTION Disparities in breast cancer (BC) screening are observed between Hispanic and non-Hispanic White women and stronger amongst Hispanic women with under- and uninsured statuses.1-2 Risk-based screening has been recommended by professional societies, including American Cancer Society, starting at age 30 and may be an important strategy for reducing disparities.3 The purpose of the study was to characterize whether women had been told their personal risk of BC and to identify differences in characteristics of patients informed of their personal risk. METHODS This is a cross-sectional analysis of data from a supplemental self-reported survey to an NIH-funded randomized trial conducted at a large Federally Qualified Health Center (FQHC) in Arizona (R01 MD09682-05). The survey was sent to a randomized 600 of the 1,356 participants. Between November 2022 and April 2023, 177 women completed the survey (response rate 29.5%). Participants were asked if a doctor or other healthcare provider had ever talked to them about their personal risk for BC. Differences between those who recalled being told their personal risk for BC and those who did not were assessed using Fisher exact test. RESULTS Overall, 66.3% were 50 years or older, 81.8% who speak primarily Spanish, and 64.8% of respondents had less than a high school education. Also, 22.4% reported a family history of BC, 27.4% have been previously recalled for additional imaging, 10.8% have had a history of prior breast biopsy, 59.9% stated having a regular provider, and 53.1% were found to have dense breast category C or D at screening visit. 40% did not report having a regular doctor although all participants received care at an FQHC. 30.5% of respondents stated that a healthcare professional had ever talked to them about their personal risk for BC. There was a trend toward women with a main doctor being more likely to recall being told their personal risk for BC as compared to those without a main doctor (38.5% vs 22.5%, p=0.06). CONCLUSIONS In this cohort of primarily Spanish-speaking Hispanic women who have had mammography screening and written report of their breast density, about a third of respondents recall being informed of their personal BC risk. These observations need to be confirmed in a larger population with greater response rate, but these results suggest that there is a cohort of patients who need different approaches for conveying risk. REFERENCES 1. Jadav, S., Rajan, S. S., Abughosh, S., & Sansgiry, S. S. (2015). The Role of Socioeconomic Status and Health Care Access in Breast Cancer Screening Compliance Among Hispanics. Journal of Public Health Management and Practice, 21(5), 467–476. https://www.jstor.org/stable/48517175 2. American Cancer Society. (2017). Breast cancer facts & figures 2017-2018. Atlanta, GA: American Cancer Society, Inc. 3. ACS Breast Cancer Screening Guidelines. (2022, January 14). https://www.cancer.org/cancer/types/breast-cancer/screening-tests-and-early-detection/american-cancer-society-recommendations-for-the-early-detection-of-breast-cancer.htm Citation Format: Jhenitza P. Raygoza Tapia, Sarah M. Jenkins, Jennifer L. Ridgeway, Aaron D. Norman, Crystal R. Gonzalez, Valentina Hernandez, Bhavika K. Patel, Celine M. Vachon, Jessica D. Austin. Communicating breast cancer risk to Spanish-speaking Hispanic women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C126.

Objective A follow-up of women 50 years or older with concomitant positive high-risk human papillomavirus (HPV) genotypes other than 16 and 18 (hrHPVO) and negative Pap test (NILMPap) was conducted to better understand the implications of hrHPVO positivity on potential risk of developing significant high-grade lesions. Material and Methods A retrospective review of 2014 cytology data of patients with co-testing (Pap test and HPV DNA) identified 85 women 50 years or older with NILMPap and hrHPVO+. Results Most patients (63) had repeat co-testing on next follow-up. Of these, 41 patients with persistent hrHPVO+ status, 3 developed cervical intraepithelial neoplasia 2 (CIN2), and 1 CIN3. Nineteen patients were followed with biopsies. Of these, 7 biopsies were abnormal, 5 of which showed low-grade (CIN1) and 2 high-grade (CIN3) histology; none progressed on further follow-up. Three patients were followed with Pap test only, all had NILMPap, and none progressed on further follow-up. In summary, of the 85 patients, 26 developed abnormal histology during follow-up, 6 of whom had high-grade histology (CIN2 and CIN3, 3 each). The 5-year risk of CIN1+ in this cohort was 43.8% and for CIN2+ was 12.3%. The risk of abnormal histology did not differ significantly by prior history of Pap tests, histology, and/or HPV results. Conclusions A persistent positivity for hrHPVO indicated higher likelihood to develop a lesion, and this risk was not reduced for patients 50 and older compared with the published screening population risk.

AimsGiant cell arteritis (GCA) is a systemic vasculitis affecting medium and large arteries in patients aged over 50 years. Involvement of temporal arteries (TA) can lead to complications such as blindness and stroke. While the diagnostic gold standard is temporal artery biopsy (TAB), comorbidities and age‐related changes can make interpretation of such specimens difficult. This study aims to establish a baseline of TA changes in subjects without GCA to facilitate the interpretation of TAB.Methods and resultsBilateral TA specimens were collected from 100 consecutive eligible postmortem examinations. Subjects were divided into four age groups and specimens semiquantitatively evaluated for eccentric intimal fibroplasia, disruption and calcification of the internal elastic lamina (IEL), medial attenuation and degree of lymphocytic inflammation of the peri‐adventitia, adventitia, media and intima. The individual scores of intimal fibroplasia, IEL disruption and medial attenuation were added to yield a ‘combined score (CS)’. Seventy‐eight 78 decedents were included in the final analysis following exclusion of 22 individuals for either lack of clinical information or inability to collect TA tissue. A total of 128 temporal artery specimens (50 bilateral from individual decedents, 28 unilateral) were available for examination. Intimal proliferation, IEL loss, IEL calcification and CS increased with age in a statistically significant fashion. Comparison of the oldest age group with the others showed statistically significant differences, although this was not uniformly preserved in comparison between the three youngest groups.ConclusionSenescent arterial changes and healed GCA exhibit histological similarity and such changes increase proportionally with age. The CS demonstrates significant association with age overall and represents a potential avenue for development to ‘normalise’ TA biopsies from older individuals.