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Supplemental material is available for this article. Keywords: Mammography, Breast, Machine Learning © RSNA, 2023

A variety of organisms have been shown to have altered physiology or developed pathology due to gene transfer, but mammals have never been shown to do so. Here, we show that circulating tumor DNA (ct) can promote cell-specific horizontal gene transfer (HGT) between human cancer cells and explain the mechanisms behind this phenomenon. Once ctDNA enters the host cell, it migrates to the nucleus and integrates into the cell’s genome, thereby transferring its genetic information. We determine that retrotransposons of the ERVL, SINE, and LINE families are necessary for cell targeting and the integration of ctDNA into host DNA. Using chemically synthesized retrotransposons, we found that AluSp and MER11C reproduced multiple myeloma’s (MM) ctDNA’s cell targeting and integration into MM cells. We also discovered that ctDNA might, as a result of HGT, influence the treatment response of multiple myeloma and pancreatic cancer models. Overall, this is the first study to show that retrotransposon-directed HGT can promote genetic material transfer in cancer. There is, however, a broader impact of our findings than just cancer since cell-free DNA has also been found in physiological and other pathological conditions as well. Furthermore, with the discovery of transposons-mediated tissue-specific targeting, a new avenue for the delivery of genes and therapies will emerge.

OBJECTIVE The aim of the study was to describe the incidence and correlates of atypical glandular cell (AGC) Pap tests in a low socioeconomic status, underserved population. MATERIALS AND METHODS Medical records of patients with AGC Pap tests at a single institution were reviewed from January 2013 to August 2019. Baseline characteristics were extracted including age, body mass index, birth control, abnormal uterine bleeding, and human papillomavirus (HPV). All colposcopy and endometrial biopsies were classified into negative/low-risk (polyps, tubular metaplasia, microglandular hyperplasia, cervical intraepithelial neoplasia 1) and high-risk (HR) lesions (cervical intraepithelial neoplasia 2/3, adenocarcinoma in situ, endometrial hyperplasia, cervical cancer, endometrial cancer). Logistic regression identified significant associations. Sixty-eight randomly selected AGC cytology slides from the cohort and 32 non-AGC slides outside the cohort were blindly reviewed by 6 pathologists. Fleiss κ interrater agreement was assessed. RESULTS Seven hundred forty patients with AGC Pap tests were identified (0.8% of all Pap tests performed during this time). After excluding for incomplete data, 478 patients were included. Sixty-three patients had HR lesions (13.3%). Patients with HR lesions had increased odds of abnormal uterine bleeding (odds ratio = 4.32, p < .001) and HPV positivity (odds ratio = 10.89, p < .001) when compared with patients with low-risk lesions. The κ agreement was 0.21 for all cases and 0.18 for AGC alone. CONCLUSIONS This population falls within the national averages for AGC Pap tests. There was an increased risk of HR lesions in patients with abnormal uterine bleeding and HPV positivity. The rate of HR lesions among AGC Pap tests was at the lower end of values in the literature. After blinded pathologist review, interobserver κ agreement was low for AGC Pap tests.

Objective Morphologic diagnosis and grading of anal squamous intraepithelial lesions (ASILs) are challenging. In this study, we investigated interobserver variability and p16 utility in accurately grading anal SIL. Materials and methods Six pathologists evaluated the degree of SIL on hematoxylin and eosin slides from 146 anal biopsies, followed by the review of both p16 and hematoxylin and eosin slides in cases where p16 was previously performed. κ was calculated in the following 4 ways: (A) 4-tiered diagnosis (negative for SIL [NSIL], anal intraepithelial neoplasia [AIN 1, AIN 2, AIN 3]); (B) 3-tiered diagnosis (NSIL and AIN 1 [pooled], AIN 2, AIN 3); (A) 3-tiered diagnosis (NSIL, low-grade SIL, high-grade SIL [HSIL]); and (D) 2-tiered diagnosis (no HSIL, HSIL). Results There is only moderate agreement with a 4-tiered diagnosis with or without p16 (κ = 0.48-0.57). There is substantial agreement when AIN 2 and AIN 3 are pooled as HSIL in cases with or without p16 review (κ = 0.71-0.78). There is almost perfect agreement with a 2-tiered diagnosis of negative for HSIL and HSIL both in cases where p16 was used and where p16 was not required, with the best agreement for a 2-tiered diagnosis with concurrent p16 review. Conclusions This study highlights the importance of a judicious use of p16 for diagnosis. When there is no need for p16 by the Lower Anogenital Squamous Terminology guidelines, interobserver agreement was substantial to almost perfect with a 2-tiered diagnosis. However, when its use is indicated but it is not performed or reviewed, the agreement is much lower even with a 2-tiered diagnosis. Rational use of p16 will ensure diagnostic accuracy and the best possible patient care.

Purpose:An unmet need in low-resource countries is an automated breast cancer detection assay to prioritize women who should undergo core breast biopsy and pathologic review. Therefore, we sought to identify and validate a panel of methylated DNA markers to discriminate between cancer and benign breast lesions using cells obtained by fine-needle aspiration (FNA).Experimental Design: Two case–control studies were conducted comparing cancer and benign breast tissue identified from clinical repositories in the United States, China, and South Africa for marker selection/training (N = 226) and testing (N = 246). Twenty-five methylated markers were assayed by Quantitative Multiplex-Methylation-Specific PCR (QM-MSP) to select and test a cancer-specific panel. Next, a pilot study was conducted on archival FNAs (49 benign, 24 invasive) from women with mammographically suspicious lesions using a newly developed, 5-hour, quantitative, automated cartridge system. We calculated sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) compared with histopathology for the marker panel.Results:In the discovery cohort, 10 of 25 markers were selected that were highly methylated in breast cancer compared with benign tissues by QM-MSP. In the independent test cohort, this panel yielded an AUC of 0.937 (95% CI = 0.900–0.970). In the FNA pilot, we achieved an AUC of 0.960 (95% CI = 0.883–1.0) using the automated cartridge system.Conclusions:We developed and piloted a fast and accurate methylation marker–based automated cartridge system to detect breast cancer in FNA samples. This quick ancillary test has the potential to prioritize cancer over benign tissues for expedited pathologic evaluation in poorly resourced countries.

Objectives We describe the experience of a busy metropolitan medical examiner’s office in the United States and share our navigation of the COVID-19 autopsy decision-making process. We describe key gross and microscopic findings that, with appropriate laboratory testing, should direct a pathologist towards a COVID-19-related cause of death. Material and methods We performed a retrospective review of 258 suspected and/or confirmed COVID-19 associated deaths that occurred between March 5, 2020, and March 4, 2021. Results A total of 62 cases due to fatal COVID-19 infection were identified; autopsy findings included diffuse alveolar damage, acute bronchopneumonia and lobar pneumonia, and pulmonary thromboemboli. Nine additional decedents had a nasopharyngeal swab positive for SARS CoV-2 and a cause of death unrelated to COVID-19 infection. Forty-seven cases with COVID-19-like symptoms showed no laboratory or histopathologic evidence of COVID-19 infection; the most common causes of death in this group were hypertensive or atherosclerotic cardiovascular disease, complications of chronic alcoholism, and pulmonary thromboemboli unrelated to infection. Conclusions The clinical findings associated with COVID-19 infection are not specific; a broad differential diagnosis should be embraced when decedents present with cough or shortness of breath. An autopsy may be indicated to identify a cause of death unrelated to COVID-19 infection.

Ovarian sex cord-stromal tumors are uncommon tumors and clinically differ from epithelial tumors. They occur across a wide age range and patients often present with hormone-related symptoms. Most are associated with an indolent clinical course. Sex cord-stromal tumors are classified into 3 main categories: pure stromal tumors, pure sex cord tumors, and mixed sex cord-stromal tumors. The rarity, overlapping histomorphology and immunoprofile of various sex cord-stromal tumors often contributes to diagnostic difficulties. This article describes the various types of ovarian sex cord-stromal tumors and includes practical approaches to differential diagnoses and updates in classification.

OBJECTIVE Anal cancer rates are increasing among HIV-infected persons. Although an efficacious human papillomavirus (HPV) vaccine is available, HPV vaccination rates remain low. Therefore, providers perform anal cancer screening, but there is no consensus on the optimal methods or timing of screening. This study was performed to determine the prevalence of and factors associated with anal squamous intraepithelial lesions in sexually active HIV-infected young men who have sex with men and transgender women. MATERIALS AND METHODS We performed a single-center, retrospective study of sexually active HIV-infected young men who have sex with men and transgender women aged 13 to 24 years at an HIV clinic in Atlanta GA from 2009 to 2016. We used analysis of variance and χ tests of independence to evaluate bivariate associations and identify demographic, behavioral, and clinical risk factors. RESULTS Of 314 subjects with a mean (SD) age of 20.4 (2.1) years at initial anal cytology testing, 5% had completed the HPV vaccine series at or before the time that cytology was obtained. Ninety-five percent of the anal cytology tests obtained were abnormal, and 72 (29%) of those subjects returned for diagnostic testing either by intraoperative biopsy or high-resolution anoscopy. Fifty-seven percent of those who underwent biopsy had histologic high-grade squamous intraepithelial lesions including 2 cases of carcinoma in situ. A history of greater than 20 lifetime sexual partners was associated with abnormal histology (probability < 0.001, p = .017). CONCLUSIONS Our study highlights the value of early, standardized screening to avoid missing anal dysplasia or cancer, particularly in unvaccinated persons with high numbers of sexual partners.

Human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies and are often excluded from cancer immunotherapy regimens. To evaluate the immune competence of this cancer patient population, we evaluated HLA class I antigen presenting machinery (APM) component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(−) head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(−) controls diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers in the United States were identified. HLA class I APM component, PD-1, and PD-L1 expression were analyzed by immunohistochemical staining with monoclonal antibodies (mAbs). Clinical data was abstracted from the medical records. There was no significant difference between the cases and controls in LMP2, TAP1, HLA-A and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p = .004, p = .026, and p = .006, respectively) but not in the HIV(−) controls. In addition, HLA-A expression was significantly associated with PD-L1 expression in the HIV(+) HNC cases only (p = .029). HIV-infected individuals diagnosed with HNC do not have any detectable defects in HLA class I APM component expression and in PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit from the recently FDA-approved immune checkpoint blockade therapy.

Endocytosis of VE-cadherin in response to the Kaposi sarcoma E3 ubiquitin ligase K5 is dependent on two membrane-proximal lysine residues but independent of a constitutive endocytosis motif. p120-catenin blocks endocytosis mediated by both motifs, demonstrating that p120 is a master regulator of multiple context-dependent endocytic signals., Vascular endothelial (VE)-cadherin undergoes constitutive internalization driven by a unique endocytic motif that also serves as a p120-catenin (p120) binding site. p120 binding masks the motif, stabilizing the cadherin at cell junctions. This mechanism allows constitutive VE-cadherin endocytosis and recycling to contribute to adherens junction dynamics without resulting in junction disassembly. Here we identify an additional motif that drives VE-cadherin endocytosis and pathological junction disassembly associated with the endothelial-derived tumor Kaposi sarcoma. Human herpesvirus 8, which causes Kaposi sarcoma, expresses the MARCH family ubiquitin ligase K5. We report that K5 targets two membrane-proximal VE-cadherin lysine residues for ubiquitination, driving endocytosis and down-regulation of the cadherin. K5-induced VE-cadherin endocytosis does not require the constitutive endocytic motif. However, K5-induced VE-cadherin endocytosis is associated with displacement of p120 from the cadherin, and p120 protects VE-cadherin from K5. Thus multiple context-dependent signals drive VE-cadherin endocytosis, but p120 binding to the cadherin juxtamembrane domain acts as a master regulator guarding cadherin stability.

OBJECTIVES/GOALS: Cervical cancer is the fourth most common cancer among women worldwide, with approximately 570,000 newly diagnosed cases and 311,000 related deaths among women in 2018.In the United States, approximately 13,000 new cases of cervical cancer are diagnosed annually with approximately 4,000 women dying each year from cervical cancer. Nearly all cervical cancer is caused by oncogenic strains of the human papillomavirus (HPV). Prevention strategies to reduce cervical cancer after HPV exposure entail treatment of cervical dysplasia at the premalignant state, specifically low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL), along with the eventual clearance of HPV.The most common treatment for persistent LSIL or HSIL is the loop electrical excisional procedure (LEEP). This procedure is unfortunately not widely available in resource-limited countries and is associated with potential significant morbidities, including decreased fertility, preterm birth, premature rupture of membranes and cervical incompetence. Despite undergoing standard of care treatment, in certain high-risk populations, specifically HIV-infected women, there is a higher rate of premalignant HPV-related cervical disease persistence, progression and recurrence.There is a paramount need for novel nonsurgical treatments to stabilize or treat precancerous lesions of the cervix and to decrease the persistence of HPV infection. Medical treatment with the natural herb curcumin may allow subjects to receive treatment of cervical lesions without undergoing a surgical procedure.Curcumin is a major active component extracted from turmeric with anti-inflammatory, anti-infectious, and anti-cancer properties.Topical intravaginal curcumin has the promise of delivering this drug directly to the site of disease, ensuring adequate concentrations at the site of disease while avoiding systemic side effects. This proposed study will determine if there are higher rates of HPV clearance after curcumin administration among women with and without HIV who have premalignant HPV-related cervical disease, specifically LSIL or recently treated (with a LEEP) HSIL. METHODS/STUDY POPULATION: We are proposing a prospective double-blind randomized control trial to investigate the utility of topical intra-vaginal curcumin in increasing rates of HPV clearance and mitigating the high rates of disease recurrence in women with and without HIV. A sample of approximately 200 women with and without HIV who have biopsy-proven LSIL or recently treated HSIL will be randomized to one of two arms: 2000 mg of curcumin powder in capsules or placebo inserted intravaginally at bedtime once weekly for 20 weeks (excluding the time of menses). Cervical cytology and HPV testing will be performed at baseline and 6 months post-randomization. If a participant has abnormal cytology or a positive high-risk HPV test 6 months post-randomization, they will be scheduled to undergo a colposcopy with biopsies of all suspicious cervical lesions. If biopsy results are HSIL or greater, subjects will be referred back to routine clinical treatment, which may include a LEEP. Clinicians performing the colposcopies and the study participants will be blinded since the placebo has the same appearance as the curcumin capsules. At the end of the study, study participants will be offered the opportunity to participate in 2-3 hour focus groups to discuss acceptability of the product as a treatment for premalignant HPV-related cervical disease until data saturation is achieved. Power and sample size calculations are based on the primary outcome of interest, which is clearance of HPV at 6 months. Basu et al (2013) documented HPV clearance in as many as 80% of subjects with topical curcumin. To account for an expected lower success rate in HIV-infected women, who will also be included in the study, we intend to power our study to determine a more conservative 20% improvement in clearance rate at 6 months with curcumin treatment, assuming an expected clearance rate of HPV in HIV-infected women of 25%. In order to detect a 20% difference of HPV clearance among those treated with intravaginal curcumin vs. placebo at 6 months, about 80 patients per arm would achieve 80% power at the 5% significance level. To account for up to 20% loss to follow-up or discontinuation, the total sample size in each arm would be 100 subjects with a total of approximately 200 subjects enrolled in both arms. RESULTS/ANTICIPATED RESULTS: We are currently in the process of collecting data for this study. We hypothesize that intravaginal curcumin will have a 20% higher rate of HPV clearance at 6 months as compared to placebo. Primary outcome measures will include clearance of HPV at 6 months in curcumin vs. placebo. Secondary outcomes measures will include recurrence of disease by either cytologic or histologic abnormality requiring further surveillance or treatment at 6 months. We also hypothesize that intravaginal curcumin administered once weekly at bedtime for 20 weeks will be safe, acceptable, and well tolerated. This is based off of previous findings from the Phase 1 trial of intravaginal curcumin that we performed. During this Phase 1 trial, we explored daily intravaginal administration of 2000 mg of curcumin to further understand curcumin’s tolerability. Our focus group participants displayed an overwhelming consensus that daily administration affected quality of life, specifically due to the yellow-colored vaginal discharge from the medication. Study participants expressed that once or twice weekly administration was more tolerable and feasible. Our proposed study would therefore test the tolerability and effects of weekly curcumin administration and its ability to clear HPV infection. The primary outcome measure will be the proportion of study participants who discontinue treatment for any reason (acceptability) and the proportion of study participants who discontinue treatment due to adverse effects (tolerability). DISCUSSION/SIGNIFICANCE OF IMPACT: Non-surgical treatments that decrease the morbidity and risk of progression of premalignant HPV-related cervical disease are greatly needed, especially in low-resource settings and among women experiencing barriers to care and/or at high risk for disease progression. Medical treatment with the natural herb curcumin is an emerging strategy that may allow subjects to receive treatment of cervical lesions without undergoing a surgical procedure.Several preclinical and clinical studies have shown curcumin’s ability to reduce tumors and precancerous lesions in animal and human cancer cells. Curcumin can suppress the activation of transcription factor NF-κB and the expression and activity of VEGF and p16INK4a, biomarkers known to be elevated in premalignant HPV-related cervical disease.Studies have also shown that curcumin alters HPV-associated molecular pathways in cancer cells, suppressing cervical cancer growth by inhibiting the transcription of oncoproteins HPV16 and HPV18 (designated as E6 and E7) and restoring p53 and retinoblastoma function. Our proposed study would therefore test the tolerability and effects of weekly curcumin administration and its ability to clear HPV infection. Our results will generate novel data as to what is an acceptable and well-tolerated dosing regimen of intravaginal curcumin, which would be crucial in designing further curcumin intervention studies. The results of our proposal will explore the effect of intravaginal curcumin as a standalone and adjuvant therapy to a LEEP among women with premalignant HPV-related cervical disease. The potential to not just excise diseased tissue, but to directly augment the clearance of the causative agent HPV, would have profound long-term ramifications in resource-limited settings and among women experiencing barriers to care and/or at high risk for disease progression.

Objective: We aimed to evaluate the sensitivity of fine needle aspiration (FNA) for the diagnosis of Hodgkin’s lymphoma (HL) in HIV-infected patients. Study Design: An electronic search was conducted to retrospectively identify patients diagnosed with HL who underwent FNA followed by confirmatory biopsy. FNAs were categorized as negative, atypical/suspicious/positive, or nondiagnostic. Diagnostic sensitivity in HIV+ and HIV– patients was statistically compared via Fisher’s exact test, with a p value Results: Thirty-six patients meeting inclusion criteria were identified (24 HIV– and 12 HIV+). Average age was 36.0 ± 11.5 and 36.5 ± 7.4 years (means ± SD) in HIV– and HIV+ patients, respectively. The male-to-female ratio was 1.4:1 in HIV– patients versus 3:1 in HIV+ patients. Among these 36 patients, a total of 42 FNAs were performed. Overall sensitivity of FNA was 66.7% (95% confidence interval: 52.4–80.9%). When stratified by HIV status, a statistically significant difference in FNA sensitivity was detected, as sen­sitivity was 84.6% (70.8–98.4%) in HIV– patients versus only 37.5% (13.8–61.2%) in HIV+ patients (p =0.003). Conclusion: The diagnostic sensitivity of FNA biopsy was significantly attenuated in the HIV+ cohort. In HIV-infected patients presenting with lymphadenopathy, increased clinical suspicion of HL is critical to avoid misdiagnosis.

Background Anal cancer rates have increased, particularly in human immunodeficiency virus (HIV)–infected (HIV+) women. We assessed factors associated with anal precancer in HIV+ and at-risk HIV-negative women from the Atlanta Women’s Interagency HIV Study cohort. Methods All participants underwent high-resolution anoscopy and anal cytology and had anal and cervical samples collected. Specimens were tested for 37 human papillomavirus (HPV) types and for FAM19A4 and microRNA124-2 promoter methylation. Binary logistic regression and multivariate analysis were conducted with histologic anal high-grade squamous intraepithelial lesion (A-HSIL) as the dependent variable. Results Seventy-five women were enrolled: 52 (69%) were HIV+ with three-fourths having undetectable viral load; 64 (86%) were black; mean age was 49 ± 8 years. Forty-nine (65%) anal cytology samples were abnormal, and 38 (51%) of anal samples were positive for at least 1 of 13 high-risk HPV (hrHPV) types. Thirteen (18%) anal biopsies identified A-HSIL. Hypermethylation of FAM19A4 and/or microRNA124-2 was found in 69 (95%) anal samples and 19 (26%) cervical samples. In multivariate analyses, the odds of having A-HSIL were >6 times higher in women with anal hrHPV (adjusted odds ratio [aOR], 6.08 [95% confidence interval {CI}, 1.27–29.18], P = .02) and with positive cervical methylation (aOR, 6.49 [95% CI, 1.66–25.35], P = .007), but not significantly higher in women with positive anal methylation. Conclusions Anal hrHPV and promoter hypermethylation in the cervix show promise as biomarkers for anal cancer screening in HIV+ and at-risk HIV-negative women. Greater understanding of gene silencing by promoter hypermethylation in anal carcinogenesis is needed.

Introduction Human papillomavirus (HPV) and anal carcinoma are prevalent in high-risk patients including human immunodeficiency virus (HIV)-positive patients. There are currently no clear guidelines for screening, however. We assessed anal cytology specimens and HPV testing at an inner-city hospital by correlating anal cytology with anal biopsy (bx), and evaluated if results differed with traditional proctoscopy (TP) or high-resolution anoscopy (HRA). Materials and methods 209 anal cytology and subsequent biopsies taken during the period 2003-2014 from 152 male patients were reviewed. Demographic data for age, sex, HIV, HPV, cytology, histology, and the method of biopsy were analyzed. Results All specimens were followed by a biopsy within a period of 6 months. Ninety-seven percent of patients were HIV-positive and 43% had AIDS. Lesions most diagnosed on cytology were low-grade squamous intraepithelial lesion (LSIL) (52%) and atypical squamous cells of undetermined significance (ASC-US) (21.5%). Lesions most diagnosed on bx were anal intraepithelial neoplasia (AIN) grade 2-3 (52%) and AIN grade 1 (37%). Almost all ASC-US cases tested for HPV were positive (97%). There was cytology histology correlation in 48% of LSIL and 83% of high-grade squamous intraepithelial lesions. Anal cytology had 97% sensitivity in detecting AIN and carcinoma and a positive predictive value of 96%. There was no difference in rate of detection of AIN 1and AIN 2-3 on bx using TP versus HRA. Conclusion Screening in high-risk patients detected almost all high- and low-grade squamous intraepithelial lesions, however, anal cytology alone could not predict the degree of dysplasia. It may be prudent to perform anal bx in all atypical anal cytology. Clear guidelines are needed for screening of a high risk population.

Spatial genetic heterogeneity is a characteristic phenomenon that influences multiple myeloma's (MM) phenotype and drug sensitivity (Rasche L. et al and Bolli N et al.). Hence, the branch model of tumor evolution is not sufficient to explain the disorganized architecture observed in MM. In this study, we investigated whether MM ctDNA horizontal gene transfer (HGT) affect tumor genetic architecture and drug sensitivity, resembling what is seen in prokaryotes, and elucidated the mechanisms involved in the mobilization of genetic material from one cell to another. We identified that plasma from patients with MM transmits drug sensitivity or resistance to cells in culture. This transmission of drug sensitivity is mediated by ctDNA transfer of oncogenes to a host cell. Importantly, in vitro and in vivo demonstrated that ctDNA mainly targets cells resembling the cell of origin (tropism). Karyotype spreads and whole genome sequencing demonstrated that once patients ctDNA encounters host cells, it migrates into the nucleus where it ultimately integrates into the cell's genome. Integration to the genome was confirmed to be targeted to myeloma cells. Further sequencing analysis of multiple MM samples identified ctDNA tropism and integration is dependent on the 5' and 3' end presence of transposable elements (TE), particularly of the MIR and ALUsq family. These results were further validated by TE mediated delivery of GFP into MM cells in vitro and HSVTK in tumors of mouse xenografts. In conclusion, this data indicates for the first time that TE mediates MM ctDNA HGT into homologous tumor cells shaping the hierarchical architecture of tumor clones and affecting tumor response to treatment. Therapeutically, this unique quality of ctDNA can be exploited for targeted gene therapeutic approaches in MM and potentially other cancers. Disclosures Bernal-Mizrachi: Kodikas Therapeutic Solutions, Inc: Equity Ownership; TAKEDA: Research Funding; Winship Cancer Institute: Employment, Patents & Royalties.

The incidence of anal cancer is increased in HIV-infected patients compared with the general population. Risk factors associated with the anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), have not been extensively studied in an urban black population with late-stage HIV disease. We performed a retrospective chart review of HIV-infected men at the Grady Ponce de Leon Center HIV Clinic (Atlanta, GA) referred for high-resolution anoscopy (HRA), a procedure where anal tissue is examined under magnification and abnormal areas are biopsied. Between December 2013 and September 2015, 147 men underwent HRA: 72% were black, and 94% were men who have sex with men. CD4 count closest to time of HRA was a median 325 cells/mm(3) (interquartile range 203–473), and 69% had an undetectable HIV viral load. Ninety-four percent had abnormal anal cytology [80% atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (LSIL) and 20% atypical squamous cells, cannot exclude HSIL/HSIL], and 97% had abnormal histology (35% LSIL, 65% HSIL). Statistically significant variables associated with HSIL included number of biopsies [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.13–2.14] and having ≥1 high-grade anal cytology in the last 12 months (OR 3.76, 95% CI 1.38–10.23). No significant association was found between HSIL and CD4, HIV viral load, or recent sexually transmitted infection. In this population, the burden of anal HSIL was extremely high, regardless of most recent anal cytology result. In newly diagnosed HIV-infected men with no history of anal cancer screening, performing HRA as primary anal cancer screening instead of cytology appears to be a viable option.

Background We examined the prognostic value of a panel of biomarkers in patients with squamous cell carcinoma of the head and neck (SCCHN) who were human immunodeficiency virus (HIV) positive (HIV-positive head and neck cancer) and HIV negative (HIV-negative head and neck cancer). Methods Tissue microarrays (TMAs) were constructed using tumors from 41 disease site-matched and age-matched HIV-positive head and neck cancer cases and 44 HIV-negative head and neck cancer controls. Expression of tumor biomarkers was assessed by immunohistochemistry (IHC) and correlations examined with clinical variables. Results Expression levels of the studied oncogenic and inflammatory tumor biomarkers were not differentially regulated by HIV status. Among patients with HIV-positive head and neck cancer, laryngeal disease site (P = .003) and Clavien-Dindo classification IV (CD4) counts

A 47-year-old man with HIV infection presented 10 years after initial secondary syphilis diagnosis and treatment for routine follow-up. His HIV was well controlled on antiretroviral therapy. Rapid plasma reagin was 1:1, and TP-PA was reactive. Physical examination revealed a wide pulse pressure, a systolic murmur, and an early diastolic decrescendo murmur. Echocardiogram revealed moderate to severe aortic regurgitation, and subsequent computed tomography angiogram showed a 6.8-cm fusiform aneurysm of the proximal ascending aorta. Aortic valve and ascending hemiarch replacement were performed. Pathology showed adventitial inflammation with plasma cells, gumma-like amorphous areas surrounded by histiocytes, and giant cells with calcified plaques. Cardiovascular syphilis, while rare, remains a relevant cause of aortic aneurysm, even in previously treated patients. The physical exam can be critical in identifying this potentially fatal complication.

There have been several updates recently on the classification of uterine tumors. Endometrial carcinomas have traditionally been divided into 2 types, but some are difficult to classify and do not fit readily into either of the currently recognized categories. The Cancer Genome Atlas Research Network has recently defined 4 new categories of endometrial cancer on the basis of mutational spectra, copy number alteration, and microsatellite instability, which might provide independent prognostic information beyond established risk factors. The Society of Gynecologic Oncology, moreover, now recommends systematic screening of every patient with endometrial cancer for Lynch syndrome. The new definition of high-grade endometrial stromal sarcoma disregards the number of mitotic figures as a primary diagnostic criterion and instead specifies moderate atypia still resembling stromal origin but lacking the pleomorphism of undifferentiated uterine sarcoma; these tumors also harbor a JAZF1-SUZ12 gene rearrangement. Mitotic count, atypia, and coagulative necrosis are the main histologic criteria that define leiomyosarcoma. Determining the type of necrosis can be very challenging in patients receiving various treatment modalities for symptomatic fibroids before myomectomy, since key histologic features of ischemic-type necrosis are often absent. Ancillary stains including p16, p53, MIB-1, trichrome, and reticulin may be helpful in tumors harboring necrosis that is difficult to classify. Minimally invasive gynecologic surgeries have introduced histologic artifacts that complicate the diagnosis. It is essential to recognize these as procedure-related artifacts to avoid upstaging tumors and triggering unnecessary adjuvant treatment.

People living with HIV/AIDS (PLWHA) are at a higher risk of developing non-Hodgkin lymphoma (NHL). The influence of combined antiretrovirals (cART) on the presentation, treatment, and outcomes of HIV-associated NHL (HIV-NHL) warrants further investigation. We performed a retrospective analysis of PLWHA diagnosed with NHL who received care at the Infectious Diseases Ponce de Leon Center in Atlanta, Georgia, from January 1, 2004 to December 31, 2010. Thirty-five patients with HIV-NHL were identified. Among these patients, 7 had Burkitt lymphoma (BL), 20 had diffuse large B cell lymphoma (DLBCL), 7 had plasmablastic lymphoma (PL), and 1 had primary effusion lymphoma (PEL). The majority of patients (82.9%) presented with advanced disease, and 63% were not on ART at diagnosis. Despite having good performance status at presentation, the majority of patients presented with high International Prognostic Index (IPI) scores. There were differences between the histologic subtypes of NHL in regard to treatment, complications, and outcomes. The median CD4 lymphocyte count at diagnosis was 110 cells/mm(3) for patients with DLBCL [interquartile range (IQR): 66, 203], 165 cells/mm(3) for Burkitt lymphoma (IQR: 36, 199), and 98 cells/mm(3) for plasmablastic lymphoma (IQR: 34, 214). Overall, patients completed 67% of planned chemotherapy cycles. Common causes for chemotherapy termination were persistent myelosuppression (18.2%), social factors (22.7%), and disease progression (36.4%). Social factors included lack of transportation, substance abuse, unstable housing, and poor adherence. Two-year overall survival was 40% for all HIV-NHL. Half of the patients with DLBCL (n=10), 42% of patients with PL (n=3), and only 14.3% of patients with BL (n=1) were alive at 2 years. Among the overall survivors at 2 years, 85.7% had CD4200 cells/mm(3) and 78.6% had undetectable HIV viral loads (VL) at that time.

Hepatoid adenocarcinoma (HAC) is a rare type of extrahepatic cancer, with pathologic features largely indistinguishable from hepatocellular carcinoma. Thirty cases of HAC have been described. The majority of HAC cases arise in the lung. Extrapulmonary HAC occurs in the stomach [1], and cases have been reported in the mediastinum, esophagus, gallbladder, pancreas, ampulla of Vater, renal pelvis, bladder, endometrium, ovary, and testicle [2–5]. In addition to the pathologic similarities to hepatocellular cancer, a large proportion of HACs produce AFP, and plasma levels may be very high [6]. Alpha-fetoprotein (AFP) was first detected in the serum of a patient with a primary liver tumor in 1965 [7] and has since been used as a tumor indicator for either primary liver or yolk sac tumors [8,9]. Certain gastrointestinal tumors such as gastric, rectal, and pancreatic carcinomas as well as lung cancer also secrete AFP [10–12]. We are reporting the second female case of pulmonary HAC who presented with elevated AFP and was treated with lobectomy and 3 cycles of adjuvant platinum-doublet chemotherapy. Case Presentation

Objectives: To explore the diagnosis of hematolymphoid malignancies of the liver (hepatic lymphoma [HeL]) by image-guided fine-needle aspiration (FNA), which can often be difficult due to a low index of suspicion and nonspecific patient presentations, especially in the rare cases where the liver is the only site of disease (primary HeL [PHeL]). Understanding the clinical setting in which such lesions arise, as well as the cytomorphologic findings, may assist cytopathologists in making an accurate diagnosis and triaging samples for ancillary studies. Methods: In this retrospective study of 32 patients with HeL, the largest such study to our knowledge, we review the clinical and diagnostic features of HeL. Results: HeL and especially PHeL most commonly show a diffuse large B-cell lymphoma phenotype and have a poor prognosis (median survival of seven months). PHeL is strongly associated with human immunodeficiency virus infection (12/16 patients). Conclusions: Image-guided FNA with immediate evaluation is a reliable means to obtain diagnostic material and triage for ancillary tests.

Introduction: Plasmablastic lymphoma (PL) is an aggressive variant of lymphoma, with strong association with HIV. Despite significant improvements in the survival of other lymphomas, PL has a short overall survival (14 months). The association with Epstein-Barr virus (EBV) infection and MYC chromosomal translocations are defining features of PL. However, the genetic causes and the role of specific mutation in PL are largely unknown. This limitation hinders the design of therapeutic approaches aimed to improve PL survival. Therefore, we performed a comprehensive analysis of the genetic landscape in PL. Methodology: Whole exon sequencing of 52 de novo PL tumors from HIV+ patients and matched normal tissues (15%) using high throughput sequencing on the Illumina platform. Of these 52 patient samples, 10 tumor and 4 normal control samples were removed due to poor sequencing quality. Mapping and variant calls were performed using BWA and Varscan softwares. Variants call filtering criteria include: exon location, minimum coverage of 5%, and onside T-test P value ≤ of 0.01 or 0.02). For immunohistochemistry, we use p-TAK1 Thr184-187 (Cell signaling) and p-BTK Tyr551(Termofisher) antibodies. Results: Analysis of exome sequencing data identified 1562 recurrent somatic mutations (p-value ≤0.01) in 711 genes, including 304 mutations previously identified in cancer driving genes. The most common recurrent pathways affected within the top 2000 gene mutations with p≤0.02 comprised mainly of NF-κB signaling followed by immune response (antigen presentation by MHC class II and the alternative and lectin induced complement pathways), reverse signaling by Ephrin B, mTOR/PTEN and EGFR/RAS pathways. Based on the lack of canonical NF-κB activation previously reported (Chapman J et al. Leukemia 2015; 29: 2270-2273) and the important role of MYD88-p100 signaling pathway in B cell differentiation into plasmablast (Guo et al. Oncogene 2016. 36(29):4224-4232), we investigated the status of p100 signaling in PL using a published gene expression dataset (Chapman J. et al Leukemia 2015). Our analysis demonstrated that most PL (70%) manifest constitutive p100 signaling. Therefore, we focused on mutations in genes involved in the NF-κB activation. Mutations in the NF-κB pathway were identified in all the analyzed cases with an average of 4 mutated genes in each tumor. Consistent with the previously reported downregulation in RNA expression of genes implicated in the BCR and canonical NF-κB signaling, we found deleterious mutations in genes in the BCR pathway that have been previously reported in lymphomas, including MATL1, FYN and SYK (24%, 16% and 15%, respectively). In contrast, we found frequent gene mutations in the MYD88-PI3P pathway that never have been reported in lymphomas, including SHIP2, DOCK8, PLCG2 in 50%, 39% and 37% of the cases, respectively. These findings are of relevance, as this mutations are expected to results in increased MYD88/TAK1 and BTK signaling (Shinners NP et al J. Imm. 2007, 179 (6) 3872-3880) and can be targeted by specific inhibitors. To evaluate the status of phosphorylation of TAK1 and BTK in these tumors, we performed immunohistochemistry analysis in 15 PL, demonstrating high levels of phosphorylation of these proteins in all tumors analyzed. Conclusion: To our knowledge, this is the first in-depth analysis of PL genome. Our data provide the most comprehensive genetic portrait of PL, provides potential genetic causes of this disease and identify potential druggable targets that deserve further clinical exploration. Disclosures Flowers: National Cancer Institute: Research Funding; Millennium/Takeda: Research Funding; Eastern Cooperative Oncology Group: Research Funding; OptumRx: Consultancy; Denovo Biopharma: Consultancy; Genentech/Roche: Research Funding; V Foundation: Research Funding; Abbvie: Consultancy, Research Funding; Acerta: Research Funding; Celgene: Research Funding; Pharmacyclics/ Janssen: Consultancy; Spectrum: Consultancy; Burroughs Wellcome Fund: Research Funding; Bayer: Consultancy; Karyopharm: Consultancy; Gilead: Research Funding; Genentech/Roche: Consultancy; Pharmacyclics: Research Funding; Janssen Pharmaceutical: Research Funding; Abbvie: Research Funding; BeiGene: Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy. Lossos:Affimed: Research Funding. Bernal-Mizrachi:Takeda Pharmaceutical Company: Research Funding; Kodikaz Therapeutic Solutions: Consultancy, Equity Ownership.

Objectives: To assess the association between Rosai-Dorfman disease (RDD) and IgG4-related disease (IgG4-RD). Methods: We studied the number of IgG4-positive plasma cells and the IgG4/IgG ratio in 32 biopsy specimens (13 nodal, 19 extranodal) from 29 patients with RDD and compared the findings with those in IgG4-RD of the pancreas and reactive lymph nodes. We also assessed the number of FOXP3-positive regulatory T cells (Tregs) since they were reported to be increased in IgG4-RD. Results: We found that RDD cases had much lower numbers of IgG4-positive plasma cells and lower IgG4/IgG ratios compared with IgG4-RD but were similar to reactive lymph nodes. Furthermore, RDD had lower numbers of FOXP3-positive Tregs than did IgG4-RD. There were no significant differences in the number of IgG4-positive plasma cells and the IgG4/IgG ratio between the nodal and extranodal RDD cases. Conclusions: Our study suggests that RDD does not belong in the spectrum of IgG4-RD.

Diffuse large B-cell lymphoma (DLBCL) has been categorized into two molecular subtypes that have prognostic significance, namely germinal center B-cell like (GCB) and activated B-cell like (ABC). Although ABC-DLBCL has been associated with NF-κB activation, the relationships between activation of specific NF-κB signals and DLBCL phenotype remain unclear. Application of novel gene expression classifiers identified two new DLBCL categories characterized by selective p100 (NF-κB2) and p105 (NF-κB1) signaling. Interestingly, our molecular studies showed that p105 signaling is predominantly associated with GCB subtype and histone mutations. Conversely, most tumors with p100 signaling displayed ABC phenotype and harbored ABC-associated mutations in genes such as MYD88 and PIM1. In vitro, MYD88 L265P mutation promoted p100 signaling through TAK1/IKKα and GSK3/Fbxw7a pathways, suggesting a novel role for this protein as an upstream regulator of p100. p100 signaling was engaged during activation of normal B cells, suggesting p100's role in ABC phenotype development. Additionally, silencing p100 in ABC-DLBCL cells resulted in a GCB-like phenotype, with suppression of Blimp, IRF4 and XBP1 and upregulation of BCL6, whereas introduction of p52 or p100 into GC cells resulted in differentiation toward an ABC-like phenotype. Together, these findings identify specific roles for p100 and p105 signaling in defining DLBCL molecular subtypes and posit MYD88/p100 signaling as a regulator for B-cell activation.

The locoregional recurrence (LRR) rate after mastectomy is reported to be similar with immediate reconstruction. We aimed to identify characteristics of LRR after transverse rectus abdominis myocutaneous (TRAM) reconstruction.We retrospectively reviewed patients undergoing immediate TRAM reconstruction for breast cancer who were diagnosed with LRR.We identified 18 LRR (4.6 %) in 18 of 390 patients who underwent immediate TRAM reconstructions for breast cancer from 1998 to 2008. The median follow-up was 69.2 months. The mean age at time of mastectomy was 49.5 years. All LRR were detected by physical examination. The LRR occurred in the TRAM subcutaneous tissue (n = 9), five in the ipsilateral axillary lymph node and four in the supraclavicular lymph node. Of the 18 patients who developed LRR, 14 (77.7 %) presented with stage 0-1-2 and 4 (22.2 %) with stage 3 disease at the time of the original mastectomy. The average time for a LRR to present was 35.8 months after initial mastectomy and reconstruction. For patients who initially presented with stage 3 disease, the average time to LRR was shorter (22.9 months). Nine patients (50.0 %) were found to have metastatic disease at the time of the LRR, and 6 (33.3 %) died of disease.All TRAM LRR were detected by routine physical examination by the patient or the surgeon. Our findings suggest that routine history and clinical breast examination of the breast reconstructed with a TRAM flap along with patient self-awareness are reliable in the diagnosis of LRR.

Background Clinical management of papillary breast lesions (PBLs) remains controversial. The objective of this study was to identify pathologic and radiologic predictors of malignancy from a large cohort of PBLs diagnosed on core-needle biopsy (CNB). Study Design Retrospective review of the institutional pathology database identified all PBLs diagnosed from 2001 to 2009 and surgically excised within 6 months of diagnosis. PBLs were divided into intraductal papilloma (IDP) and IDP associated with atypical ductal or lobular hyperplasia (ADH/ALH). Surgical pathology of all lesions was reviewed and upgrade was defined as a change to a lesion of greater clinical significance, including ALH, ADH, lobular, or ductal carcinoma in situ (LCIS or DCIS), and invasive ducal carcinoma (IDC). Results We identified 276 patients (mean age 56 years; range 23 to 88 years) with PBLs on CNB. Seventy-nine patients (28.6%) upgraded to a lesion of greater clinical significance. Of the 234 (84.7%) had IDP only, 42 (17.9%) upgraded to ADH, and 21 (8.9%) to DCIS or IDC. Of the 42 (15.3%) patients with associated ADH or ALH on CNB, 16 (38.0%) upgraded to DCIS or IDC. The majority of patients (n = 173, 62.6%) had no breast symptoms. All patients had an abnormal mammogram and/or ultrasound that prompted the CNB. Among all clinical and radiographic variables analyzed, older age alone was predictive of upgrade. Conclusions Frequent upgrade to a high-risk lesion or cancer is observed with IDPs diagnosed on CNB without adequate identifiable clinical and radiographic risk factors. Surgical excision should be performed for all IDPs to delineate subsequent clinical management.

Delays in treatment for breast cancer can lead to poorer patient outcome. We analyzed time to treatment among female patients receiving breast-conserving surgery in two different hospital settings, public versus private. Retrospective chart review revealed 270 patients diagnosed during 2004–2008. Three consecutive time intervals were defined (Initial abnormal imaging [I] to core biopsy [II] to surgery /pathology staging [III] to oncology evaluation for adjuvant treatment). Multivariate analyses investigated hospital type and demographic factors. Overall median treatment time was 83 days, Interval II accounting for the longest (43 days). Only 55% of patients received the entire spectrum of care within 90 days; for each consecutive 30-day interval, percentages varied dramatically: 80.7%, 31.1%, and 68.9%.Public hospital patients experienced longer overall time to treatment than private patients (94 versus 77 days, p

Uterine papillary serous carcinoma (UPSC) represents 10% of endometrial carcinomas. Significant number of patients initially present with extrauterine disease. The role of adjuvant treatment in low stage, especially polyp-confined UPSC is controversial. This multi-institutional study evaluated the significance of positive pelvic washing (PW) and adjuvant treatment on disease recurrence in a setting of endometrial polyp-confined UPSC. Surgical pathology files from 3 institutions were searched for cases of endometrial polyp-confined UPSC. Following histologic review, cases were clinically staged as Stage I, without myoinvasion or lymphovascular invasion. Clinicopathologic characteristics, results of PW, and type of adjuvant therapy were recorded. Statistical analysis using the Kaplan-Meier method for survival and Fisher exact test were performed. Thirty-three patients were included in the study. All patients were diagnosed with polyp-confined UPSC. The size of the polyp ranged from 0.3 to 4.3 cm. PW was positive for tumor cells in 8/33 (24%) patients. Twenty-two patients (66.6%) received some type of adjuvant treatment. Six patients (18%) developed recurrent disease. There was no significant difference in disease-free survival in the patients receiving adjuvant treatment versus not (P=0.375). However, there was significant association (P=0.0013) between positive PW and disease recurrence. Data are conflicting whether positive PW affects prognosis in low-stage endometrial carcinomas. Our study showed that in UPSC, malignant cells can be present in PW without lymphovascular invasion or myoinvasion and may have negative prognostic implication. Our data also reflect the controversies in the role of adjuvant treatment in endometrium-confined UPSC.

BACKGROUND: African American (AA) women experience higher breast cancer mortality than white (W) women. These differences persist even among estrogen receptor (ER)-positive breast cancers. The 21-gene recurrence score (RS) predicts recurrence in patients with ER-positive/lymph node-negative breast cancer according to RS score—low risk (RS, 0-18), intermediate risk (RS, 19-31), and high risk (RS, >31). The high-risk group is most likely to benefit from chemotherapy, to achieve minimal benefit from hormonal therapy, and to exhibit lower ER levels (intrinsically luminal B cancers). In the current study, the authors investigated racial differences in RS testing, scores, treatment, and outcome. METHODS: Tumor registry data from 3 Atlanta hospitals identified women who were diagnosed with breast cancers during 2005 through 2009. Medical record abstraction provided information on RS and other tumor/treatment factors. Statistical analyses used chi-square/exact tests and logistic regression. RESULTS: Of 2186 patients, including 1192 AA women and 992 W women, 853 women had stage I or II, ER-positive/lymph node-negative disease and, thus, were eligible for RS testing (AA = 372 [31.2%]; W = 481 [48.5%]; P < .0001); and 272 women (31.8%) received testing (AA = 76 [20.4%]; W = 196 [40.7%]; P < .0001). Tumors were distributed into the following groups according to risk: low risk (n = 133), medium risk (n = 113), and high risk (n = 26). The mean RS did not differ by race, but risk groups did (low-risk group: 46.1% vs 50% for AA women and W women, respectively; high-risk group: 15.8% vs 7.1%, respectively; P = .043). In multivariate analyses, AA race (odds ratio, 3.6) was associated independently with high risk scores. CONCLUSIONS: AA women were half as likely as W women to receive 21-gene RS testing but were 2-fold more likely to be categorized as high risk. The current data suggested that testing guidelines are not applied equivalently, testing bias may attenuate racial differences in RS, and disparate outcomes may be explained in part by differences in RS, although compliance and pharmacogenomics also may play a role. Cancer 2012;. © 2011 American Cancer Society.

BACKGROUND: African American (AA) women experience higher breast cancer mortality than white (W) women, partly attributable to their development of poor prognosis tumors and differences in access and treatment. However mortality differences persist among estrogen receptor positive (ER+) breast cancers, despite similar stage and treatment. The 21-gene recurrence score (RS) assay (Oncotype DX) is used to determine optimal individualized treatment in patients with ER+, node negative (N-) breast cancer. Results are reported on a continuum and also trichotomized into 3 RS groups: low(0-18), intermediate(19-31) and high(>31), the latter most likely benefitting from chemotherapy, achieving less benefit with hormonal therapy, and exhibiting lower ER levels (intrinsically categorized as luminal B cancers). We investigated differences between AA and W women in RS, treatment, and outcome. METHODS: Tumor registry data from three Atlanta hospitals identified female invasive breast cancers of AA or W descent diagnosed during 2005-2009. Additional medical record abstraction obtained information on RS, treatment, and outcome. Statistical analyses employed chi-square, fisher exact, t-tests, and multivariate logistic regression. RESULTS: Of 1987 cases (AA=1110, W=877), 773 were identified as Stage I-II, ER+N-, thus eligible for RS testing [AA=350(45.3%), W=423 (54.7%), P Neither mean RS (AA=20.4, W=18.5, p=0.287) nor risk groups (Low=51.1% vs 54.5%, Medium=34.0% vs 38.2%, and High=14.9% vs 7.3% for AA and W women respectively, p=0.333) significantly differed by race. However, AA women were more likely than W women to be diagnosed under age 50 (40.4% vs 23.5%, p=0.036) with higher prevalence of tumors of larger size (Mean = 2.0 cm vs 1.6cm, p=0.038) and Grade III (23.4% vs 8.1%, p=0.0.026), and stage II disease (38.3%% vs 23.6%, p=0.057). Only grade and tumor size were associated with RS in multivariate analyses. After median follow-up of 20 months (range 1-55), 5 women recurred (2AA, 3W); 2 low, 2 intermediate, and 1 high risk. Chemotherapy was received by 40 women (Low=7, Medium=19, High=14) and did not differ by race (AA=31.9%, W=20.3%, p=0.156). Hormonal therapy was received by 80.5% of W and 63.8% AA women (p=0.027). DISCUSSION: AA women were less likely than W women to be diagnosed with ER+N-breast cancers and to receive RS testing if diagnosed. Of those tested, RS scores did not significantly differ by race. However, AA women tended to have poorer prognostic factors. Our data suggest that testing guidelines are not equivalently applied, that selection bias in testing could be attenuating any real racial differences in RS, and that disparate outcomes could partly be explained by treatment differences, treatment effectiveness e.g. endocrine agent metabolism, compliance, as well as differences in prognostic factors; all areas requiring future exploration. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-13.

In April 2007, the National Quality Forum (NQF) endorsed the first nationally recognized hospital-based performance measures for stage I, II, and III breast cancer. The purpose of this study was to document compliance with the 3 NQF breast quality indicators during 2 time intervals in a metropolitan public hospital.Tumor registry and medical records were used to identify patient demographics and treatments before (2005-2006) and after (2008) implementations in 2007 as a result of the NQF audit. Program changes included: hiring a dedicated medical oncology nurse practitioner, requiring the radiation oncology case manager to attend weekly multidisciplinary conferences, educating Patient Navigators of the importance of multimodal care, and providing support groups for patients addressing importance of completion of all treatment options.A total of 213 female patients were diagnosed with and treated for stage I, II, or III breast cancer in 2005-2006 and 2008. Of these, 189 (89%) were African American (AA) women. Also, 70 patients of 86 (81.3%) received radiation therapy, 60 of 77 (77.9%) received or were considered for adjuvant chemotherapy, and 124 of 144 (86.1%) for hormonal therapy according to NQF indicators. After 2007, patients receiving radiation therapy increased from 75.8 to 95.8%. Patients receiving or considered for adjuvant chemotherapy or hormonal therapy increased from 73.7 to 93.7% and from 84.1 to 90.0%, respectively.NQF breast cancer indicators provided a mechanism to improve compliance of multimodal treatment in our center. Raising awareness of these indicators in the multidisciplinary conference, hiring dedicated personnel, and educating patients has led to major improvements in breast cancer care.

Background Anal cancer rates have increased in HIV+ women. Factors associated with anal cancer precursor high-grade squamous intraepithelial lesions (HSIL) in HIV+ and at-risk-HIV- women were assessed. Methods HIV+ and HIV- women from the Atlanta WIHS cohort were enrolled in a cross-sectional pilot study. All anal (AS) and cervical (CS) swab samples were analyzed for HPV-genotyping (Linear-Array® HPV-Genotyping Test, LA-HPVGT) and FAM19A4 and microRNA-124-2 promoter methylation. All women underwent high resolution anoscopy with biopsy of suspicious lesions and anal cytology (AC) collection. Logistic regression was conducted with anal HSIL histology (A-HSIL) as the dependent variable. Results 75 women were enrolled: 52(69%) were HIV+ with 3/4 having undetectable viral load, 64(86%) Black, with mean age 49. 44(59%) AC samples were ASCUS/+hrHPV or higher, 38(51%) of all AS were +hrHPV by LA-HPVGT.13 anal biopsies were confirmed A-HSIL. 69(95%) AS and 19(26%) CS tested positive for hypermethylation, respectively. A-HSIL model included ASCUS/+hrHPV or greater on AC and cervical hypermethylation as covariates (Table 1). AS hypermethylation was not associated with A-HSIL. Conclusions Our results suggest AC with hrHPV testing and/or cervical gene promoter hypermethylation measurements as promising non-invasive screening strategies for A-HSIL in both HIV+ and HIV- women. Lack of association between AS hypermethylation and A-HSIL may reflect characteristics of the anal milieu and warrants further investigation.

Margin status is an important prognostic factor for local recurrence after breast-conserving surgery (BCS) in patients with breast malignancy. It is unclear whether the removal of additional tumor cavity margins reduces the reoperation rate and is cosmetically acceptable. This study compares the reoperation rates, volume of breast excised in cm3, and number of pathology slides examined in two groups of patients who underwent BCS with or without four or five additional margins (BCS + M). We retrospectively analyzed 320 patients who underwent BCS or BCS + M for stage 0-I-II breast cancer from 2004 to 2007. We classified the margins as negative (≥1 mm), close (