Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells.

The exchange of genes between cells is known to play an important physiological and pathological role in many organisms. We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer between human cancer cells and explain part of the mechanisms behind this phenomenon. As ctDNA migrates into the nucleus, genetic information is transferred. Cell targeting and ctDNA integration require ERVL, SINE or LINE DNA sequences. Chemically manufactured AluSp and MER11C sequences replicated multiple myeloma (MM) ctDNA cell targeting and integration. Additionally, we found that ctDNA may alter the treatment response of MM and pancreatic cancer models. This study shows that retrotransposon DNA sequences promote cancer gene transfer. However, because cell-free DNA has been detected in physiological and other pathological conditions, our findings have a broader impact than just cancer. Furthermore, the discovery that transposon DNA sequences mediate tissue-specific targeting will open up a new avenue for the delivery of genes and therapies.

An Alternative to Cytology in Triaging Cisgender Men and Transgender Women With HIV for High-Resolution Anoscopy.

OBJECTIVES: To evaluate high-risk human papillomavirus testing (hrHPV) as an alternative for anal cytology in screening for high-grade anal neoplasia (AIN2-3) among males with HIV. To identify predictive risk factors for AIN2-3 and develop a clinical tool to triage males with HIV for high-resolution anoscopy (HRA) without cytology. DESIGN: Retrospective cohort study of 199 adult cisgender men and transgender women with HIV referred to an anal neoplasia clinic in the Southeastern United States between January 2018 and March 2021. METHODS: Each subject underwent cytology, hrHPV, and HRA. Clinical and sociodemographic risk factors were collected for each subject. Significant risk factors for AIN2-3 were identified using logistic regression, and a triage tool incorporating these factors was developed. Screening test characteristics were calculated for cytology with and without adjunct hrHPV, hrHPV alone, and the triage tool. RESULTS: In multivariate analysis, significant predictors of AIN2-3 were hrHPV positivity (odds ratio [OR] = 11.98, CI = 5.58-25.69) and low CD4 count (OR = 2.70, CI = 1.20-6.11). There was no significant difference in positive or negative predictive values among the tool, stand-alone hrHPV, and anal cytology with adjunct hrHPV. Sensitivity and specificity were not significantly different for stand-alone or adjunctive hrHPV testing. Compared with cytology, stand-alone hrHPV and the novel triage tool reduced unnecessary HRA referrals by 65% and 30%, respectively. CONCLUSIONS: Stand-alone hrHPV would have missed 11 of 74 AIN2-3 and generated 74 fewer unnecessary HRAs than current cytology-based screening patterns, which led to 115 unnecessary HRAs in our cohort. We propose triaging those with low CD4 count, hrHPV positivity, and/or smoking history for HRA.

Programmed Death Ligand-1 (PD-L1) Expression in Cervical Squamous Cell Carcinoma: Does it Correlate With Outcomes?

Cervical cancer is one of the most common gynecological malignancies. Upregulation of programmed death ligand-1 (PD-L1), an immunoregulatory protein, is associated with an adverse outcomes in several malignancies. Most studies evaluating PD-L1 expression in cervical squamous cell carcinoma (CSCC) lack data on outcomes. In this study, we correlate PD-L1 expression with clinicopathologic factors and clinical outcomes in invasive CSCC. Seventy-three cases of CSCC from 2010 to 2018 were immunostained for PD-L1. A combined positive score (CPS) of ≥1 and ≥10 was correlated with age, stage, and survival outcomes. Kaplan-Meier curves for progression-free survival and overall survival were plotted and compared using the log-rank test. Cox regression analysis was performed to identify significant prognostic factors (2-tailed P <0.05 was considered statistically significant). With CPS ≥1 or ≥10 as the cut-off, PD-L1 was positive in 52/73 (71.2%) and 23/73 (31.5%) of cases, respectively. PD-L1 positive patients present at a higher stage of disease, especially those with CPS ≥10. With CPS of ≥10 as the cut-off, the 5-yr progression-free survival and 5-yr overall survival were significantly lower ( P = 0.034 and 0.012, respectively). Only stage was statistically significant for worse overall survival on multivariate analysis. PD-L1 positive patients present at a higher stage of disease, and stage is an independent prognostic indicator for adverse outcomes in CSCC. This study highlights the potential of PD-L1 targeted therapy in patients with CSCC.

Multiplatform analyses reveal distinct drivers of systemic pathogenesis in adult versus pediatric severe acute COVID-19.

The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers of COVID-19 severity, yet the mechanisms underlying these processes remain elusive. Here we show alterations in fluid shear stress-responsive pathways in critically ill COVID-19 adults as compared to non-COVID critically ill adults using a multiomics approach. Mechanistic in-vitro studies, using microvasculature-on-chip devices, reveal that plasma from critically ill COVID-19 adults induces fibrinogen-dependent red blood cell aggregation that mechanically damages the microvascular glycocalyx. This mechanism appears unique to COVID-19, as plasma from non-COVID sepsis patients demonstrates greater red blood cell membrane stiffness but induces less significant alterations in overall blood rheology. Multiomics analyses in pediatric patients with acute COVID-19 or the post-infectious multi-inflammatory syndrome in children (MIS-C) demonstrate little overlap in plasma cytokine and metabolite changes compared to adult COVID-19 patients. Instead, pediatric acute COVID-19 and MIS-C patients show alterations strongly associated with cytokine upregulation. These findings link high fibrinogen and red blood cell aggregation with endotheliopathy in adult COVID-19 patients and highlight differences in the key mediators of pathogenesis between adult and pediatric populations.

The EMory BrEast imaging Dataset (EMBED): A Racially Diverse, Granular Dataset of 3.4 Million Screening and Diagnostic Mammographic Images.

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

Human papillomavirus 16/18/45 are not the most frequent genotypes in African American women: analysis in cervical Papanicolaou smears of women in an inner-city hospital.

INTRODUCTION: Cervical cancer is considered the most common human papillomavirus (HPV)-associated disease in women. Primary and secondary prevention methods have been established through Pap tests, HPV molecular testing, and vaccines. Although the most common high-risk HPV (HR-HPV) genotypes in the United States are 16, 18, and 45, there is reported ethnic disparity in the distribution of these genotypes. MATERIALS AND METHODS: Data analysis of HPV genotype results on cervical pap tests in our institution between late 2018 and early 2020 was performed. The distribution of HPV genotypes in each Bethesda category was evaluated. RESULTS: A total of 13,160 smears were evaluated; 75.5% were from African American women. Of those tested for HR-HPV (10,060), 1412 (14%) were HR-HPV positive. In all diagnostic categories of the Bethesda classification system, non-16/18/45 HR-HPV genotypes were more prevalent, ranging from 60.8% even in high-grade squamous intraepithelial lesion to 90.4% in negative for intraepithelial lesion or malignancy. CONCLUSIONS: In this study with a predominantly African American population, non-16/18/45 HR-HPV genotypes were prevalent in the majority (60.8%) of high-grade squamous intraepithelial lesion cases. Ethnic variability should be considered when deciding which HPV genotypes to integrate into the HPV vaccine.

Is it COVID-19? The value of medicolegal autopsies during the first year of the COVID-19 pandemic.

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 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. Forty-seven cases with COVID-19-like symptoms showed no laboratory or histopathologic evidence of SARS-CoV-2 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 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.

Programmed Death Ligand-1 Expression Is Associated With Poorer Survival in Anal Squamous Cell Carcinoma.

CONTEXT.­: Upregulation of programmed death ligand-1 (PD-L1), an immunoregulatory protein, is associated with an adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in invasive anal squamous cell carcinoma (ASCC). OBJECTIVE.­: To assess PD-L1 expression in patients with ASCC and correlate it with clinicopathologic factors and clinical outcomes. DESIGN.­: Fifty-one cases of ASCC were immunostained for PD-L1. PD-L1 expression by combined positive score and tumor proportion score was correlated with age, sex, HIV status, HIV viral load, CD4 count, stage, and outcomes. Kaplan-Meier curves for overall survival were plotted and compared using the log-rank test. Cox regression analysis was performed to identify significant prognostic factors (2-tailed P < .05 was considered statistically significant). RESULTS.­: PD-L1 was positive in 24 of 51 cases (47%) by combined positive score and in 18 of 51 (35%) by tumor proportion score. The median cancer-specific survival and 5-year overall survival were significantly lower in PD-L1+ patients. Age, sex, HIV status, HIV viral load, stage, and cancer progression were not significantly different between the 2 groups. CD4 count of more than 200/µL was significantly higher in PD-L1+ patients. PD-L1+ status remained statistically significant for worse overall survival on multivariate analysis. CONCLUSIONS.­: PD-L1+ status is an independent adverse prognostic factor for overall survival in ASCC. This study highlights the potential of PD-L1 targeted therapy in better management of ASCC.

Do High Rates of Atypical Glandular Cells Correlate With Higher Incidence of Disease in a Large Safety Net Hospital.

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.

Pilot Study of Markers for High-grade Anal Dysplasia in a Southern Cohort From the Women's Interagency Human Immunodeficiency Virus Study.

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.

Diagnosing Anal Squamous Intraepithelial Lesions With and Without p16: An Interobserver Variability Study.

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.

DNA Methylation Markers for Breast Cancer Detection in the Developing World.

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.

Cytodiagnostic Sensitivity of Fine Needle Aspiration Biopsy for Hodgkin's Lymphoma Is Decreased in Patients with Human Immunodeficiency Virus Infection.

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 <0.05 considered significant. 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 sen-sitivity 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.

Practical Review of Ovarian Sex Cord-Stromal Tumors.

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.

Prevalence of Anal Squamous Intraepithelial Lesions in HIV-1-Infected Young Men Who Have Sex With Men and Transwomen.

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.

Factors Associated with High-Grade Anal Intraepithelial Lesion in HIV-Positive Men in a Southern U.S. City.

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/mm3 (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.

HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers.

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.

Asymptomatic Cardiovascular Syphilis With Aortic Regurgitation Requiring Surgical Repair in an HIV-Infected Patient.

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.

Prognostic biomarkers in patients with human immunodeficiency virus-positive disease with head and neck squamous cell carcinoma.

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 <200 cells/µL (P = .01) were associated with poor prognosis. Multivariate analysis showed that p16 positivity was associated with improved overall survival (OS; P < .001) whereas increased expression of transforming growth factor-beta (TGF-ß) was associated with poor clinical outcome (P = .001). CONCLUSION: Disease site has significant effect on the expression of biomarkers. Expression of tumor TGF-ß could be a valuable addition to the conventional risk stratification equation for improving head and neck cancer disease management strategies.