National pilot of entrustable professional activities in pathology residency training.

Entrustable professional activities (EPAs) are observable clinical skills and/or procedures that have been introduced into medical education at the student and resident levels in most specialties to determine readiness to advance into residency or independent practice, respectively. This publication describes the process and outcomes of a pilot study looking at the feasibility of using two anatomic pathology and two clinical pathology EPAs in pathology residency in 6 pathology residency programs that volunteered for the study. Faculty development on EPAs and their assessment was provided to pilot program faculty, and EPA assessment tools were developed and used by the pilot programs. Pre- and post-study surveys were given to participating residents, faculty, and program directors to gauge baseline practices and to gather feedback on the EPA implementation experience. Results demonstrated overall good feasibility in implementing EPAs. Faculty acceptance of EPAs varied and was less than that of program directors. Residents reported a significant increase in the frequency with which faculty provided formative assessments that included specific examples of performance and specific ways to improve, as well as increased frequency with which faculty provided summative assessments that included specific ways to improve. EPAs offered the most benefit in setting clear expectations for performance of each task, for providing more specific feedback to residents, and in increasing Program director's understanding of resident strengths abilities and weaknesses.

Prioritizing the Interview in Selecting Resident Applicants: Behavioral Interviews to Determine Goodness of Fit.

From our initial screening of applications, we assess that the 10% to 15% of applicants whom we will interview are all academically qualified to complete our residency training program. This initial screening to select applicants to interview includes a personality assessment provided by the personal statement, Dean's letter, and letters of recommendation that, taken together, begin our evaluation of the applicant's cultural fit for our program. While the numerical scoring ranks applicants preinterview, the final ranking into best fit categories is determined solely on the interview day at a consensus conference by faculty and residents. We analyzed data of 819 applicants from 2005 to 2017. Most candidates were US medical graduates (62.5%) with 23.7% international medical graduates, 11.7% Doctors of Osteopathic Medicine (DO), and 2.1% Caribbean medical graduates. Given that personality assessment began with application review, there was excellent correlation between the preinterview composite score and the final categorical ranking in all 4 categories. For most comparisons, higher scores and categorical rankings were associated with applicants subsequently working in academia versus private practice. We found no problem in using our 3-step process employing virtual interviews during the COVID pandemic.

Inflammatory reaction to BioGlue™ masquerading as recurrence in patients with endometrial cancer: A report of two cases.

•BioGlue™, a glutaraldehyde-based vessel sealant, can cause a foreign body reaction.•Vessel sealants may be used for IVC repair during endometrial cancer staging.•Foreign body reaction to BioGlue™ may look like a cancer recurrence on imaging.•It is important to note prior use of vessel sealants in assessing paraaortic recurrence.

A comparison of screening tests for detection of high-grade cervical abnormalities in women living with HIV from Cameroon.

BACKGROUND: Women living with human immunodeficiency virus (WLWH), especially those living in low- and middle-income countries (LMIC), are at increased risk of cervical cancer. The optimal cervical-cancer screening strategy for WLWH has not been determined. We therefore conducted a pilot study of screening methods in WLWH living in Limbe, Cameroon. METHODS: Five-hundred sixty-six WLWH, aged 25-59 years, were enrolled. After self-collecting a cervicovaginal specimen, they underwent a pelvic exam, during which a provider also collected a cervical specimen and visual inspection after acetic acid (VIA) was performed. Both self- and provider-collected specimens were tested for high-risk HPV by the Xpert HPV Test (Cepheid, Sunnyvale, CA, USA), with the residual of the latter used for liquid-based cytology. Women testing HPV positive on either specimen and/or VIA positive were referred to colposcopy and biopsies. However, because of poor attendence for follow-up colposcopy for the screen positives due to civil strife and technical issues with biopsies, high-grade cytology and/or clinical diagnosis of cancer was used as the primary high-grade cervical abnormality endpoint. Clinical performances for high-grade cervical abnormality of HPV testing and VIA for screening WLWH, and the most carcinogenic HPV genotypes and/or VIA to triage high-risk HPV-positive WLWH, were evaluated. RESULTS: Four-hundred eighty-seven (86.0%) WLWH had results for HPV testing on both specimen, VIA, and cytology and were included in the analysis. Forty-nine (10.1%) had a high-grade cervical abnormality. HPV testing on provider- and self-collected specimens was more sensitive than VIA (95.9 and 91.8% vs. 43.8%, respectively, p < 0.01 for both comparisons) for identifying women with high-grade cervical abnormalities. HPV testing on provider- and self-collected specimens was less specific than VIA (57.5 and 51.6% vs. 89.7%, respectively, p < 0.01 for both comparisons) for identifying women with high-grade cervical abnormalities; HPV testing on provider-collected specimens was more specific than on self-collected specimens (p < 0.01). Among HPV-positive women, HPV16/18/45 detection or VIA positivity had a sensitivity and positive predictive value of 73.5 and 29.0%, respectively, for provider-collected specimens and 68.8 and 22.9%, respectively, for self-collected specimens for high-grade cervical abnormalities. CONCLUSIONS: HPV testing was more sensitive but less specific than VIA for detection of high-grade cervical abnormality in WLWH. Improved triage methods for HPV-positive WLWH are needed. TRIAL REGISTRATION: NCT04401670 (clinicaltrials.gov); retrospectively registered on May 26, 2020.

Cervical human papillomavirus DNA detection in women living with HIV and HIV-uninfected women living in Limbe, Cameroon.

BACKGROUND: There are limited data on cervical HPV prevalence in Cameroon and none from its Anglophone region. We investigated cervical HPV prevalence in HIV-uninfected (HIV[-]) and HIV-infected (WLWH) women living in the region. METHODS: A convenience sample of consecutively recruited HIV[-] women (n = 295) and women living with HIV (WLWH) (n = 560) attending the Limbé Regional Hospital were enrolled into a cervical screening study. Women underwent screening that included HPV testing of self-collected and provider-collected specimens. We calculated the HPV prevalence by HIV status, overall and stratified by age, and among WLWH, stratified by CD4 counts. We compared the concordance for the detection of HPV between self- and provider-collected specimens. RESULTS: Crude HPV prevalence was 21.69 % (95 % confidence interval [95 %CI] = 17.21-26.48 %) for HIV[-] women and 46.43 % (95 %CI = 42.24-50.66 %) for WLWH (p < 0.001). Among WLWH, older age (ptrend = 0.01) and higher CD4 counts (ptrend = 0.007) were associated with lower HPV prevalence. There was a good-to-excellent agreement for HPV detection between specimens, and self-collected were more likely than provider-collected specimens to test HPV positive, for all women and stratified by HIV status. CONCLUSIONS: HIV-related immunosuppression was a risk factor for HPV prevalence in this population. HPV testing of self-collected specimens appeared to be less specific than HPV testing of provider-collected specimens.

Training the Next Generation of Pathologists: A Novel Residency Program Curriculum at Montefiore Medical Center/Albert Einstein College of Medicine.

Pathology residency training is currently a time-intensive process, frequently extending up to 6 years in duration as residents complete 1 or 2 fellowships following graduation. Innovative training curricula may help address the impending changes in the health-care landscape, particularly future shortfalls in pathology staffing and changing health-care models that incorporate more work within interdisciplinary teams. Montefiore has created a novel residency training program aimed at accelerating the acquisition of competency in pathology, preparing residents for independent practice at the completion of residency training, and providing residents with the requisite adaptability and consultative skills to excel wherever they choose to practice. We describe the implementation of this novel pathology residency training curriculum at Montefiore Medical Center/Albert Einstein College of Medicine and the perception of residents in both the old curriculum and the new curriculum.

Protocol for the study of cervical cancer screening technologies in HIV-infected women living in Rwanda.

INTRODUCTION: The optimal method(s) for screening HIV-infected women, especially for those living in sub-Saharan Africa, for cervical precancer and early cancer has yet to be established. METHODS AND ANALYSIS: A convenience sample of >5000 Rwandan women, ages 30-54 years and living with HIV infection, is being consented and enroled into a cross-sectional study of cervical cancer screening strategies. Participants are completing an administered short risk factor questionnaire and being screened for high-risk human papillomavirus (hrHPV) using the Xpert HPV assay (Cepheid, Sunnyvale, California, USA), unaided visual inspection after acetic acid (VIA) and aided VIA using the Enhanced Visual Assessment (EVA) system (Mobile ODT, Tel Aviv, Israel). Women positive for hrHPV and/or by unaided VIA undergo colposcopy, which includes the collection of two cervical specimens prior to undergoing a four-quadrant microbiopsy protocol. The colposcopy-collected specimens are being tested by dual immunocytochemical staining for p16INK4a and Ki-67 (CINtec PLUS Cytology, Ventana, Tucson, Arizona, USA) and for E6 or E7 oncoprotein for 8 hrHPV genotypes (HPV16, 18, 31, 33, 35, 45, 52 and 58) using the next-generation AV Avantage hrHPV E6/E7 test (Arbor Vita Corporation, Freemont, California, USA). Women with a local pathology diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) or pathology review diagnosis of CIN grade three or more severe (CIN3+) will receive treatment. Clinical performance and cost-effectiveness (eg, sensitivity, specificity and predictive values) of different screening strategies and algorithms will be evaluated. ETHICS AND DISSEMINATION: The protocol was approved by local and institutional review boards for human subjects research. At the completion of the study, results will be disseminated to the scientific community through peer-reviewed publication and to the Rwandan stakeholders through an external advisory panel.

RNA-seq Identification of RACGAP1 as a Metastatic Driver in Uterine Carcinosarcoma.

PURPOSE: Uterine carcinosarcoma is a rare aggressive malignancy frequently presenting at advanced stage of disease with extrauterine metastases. Median survival is less than 2 years due to high relapse rates after surgery and poor response to chemotherapy or radiotherapy. The goal of this study was to identify novel therapeutic targets. EXPERIMENTAL DESIGN: We applied RNA-seq analysis to prospectively collected uterine carcinosarcoma tumor samples from patients undergoing primary surgical resection and for comparison, normal endometrial tissues from postmenopausal women undergoing hysterectomy for benign indications. Functional assays were done in primary carcinosarcoma cell lines developed from patients and in established cell lines, as well as a cell line-derived xenograft model. Validation was done by analysis of an independent cohort of patients with uterine carcinosarcoma from The Cancer Genome Atlas (TCGA). RESULTS: Rac GTPase-activating protein 1 (RACGAP1) was identified to be highly upregulated in uterine carcinosarcoma. Functional assays showed that RACGAP1 mediates motility and invasion via regulation of STAT3 phosphorylation and survivin expression. RACGAP1 depletion or survivin inhibition abrogated motility and invasiveness of carcinosarcoma cells, while RACGAP1 overexpression conferred invasiveness to endometrial adenocarcinoma cells. In the TCGA cohort, RACGAP1 expression correlated with survivin expression and extrauterine spread of disease. CONCLUSIONS: The RACGAP1-STAT3-survivin signaling pathway is required for the invasive phenotype of uterine carcinosarcoma and is a newly identified therapeutic target in this lethal disease. Clin Cancer Res; 22(18); 4676-86. ©2016 AACR.

Onboarding for Pathology Residency Programs-The Montefiore Experience.

Onboarding is a system frequently used in the corporate world as a means of orienting incoming employees to their duties and inculcating the workplace values. The program aims to facilitate transition into new work roles and improve employee retention rates. At Montefiore, we have instituted an onboarding curriculum that is given to new anatomic and clinical pathology residents about a month prior to the start of residency. The program includes an introductory video series of basic histology and a series of anatomic and clinical case studies illustrating basic laboratory principles. This didactic content is tagged to learning objectives and short self-assessment modules. In addition, content related to the work ethos at Montefiore and the role of the core competencies and milestones in residency education are included. Finally, a broader component of the onboarding gives the incoming residents a social welcome to our area, including key information about living in the area surrounding Montefiore. The program has been well received by our residents for whom the content has helped to boost confidence when starting. We feel that the program is helpful in ensuring that all incoming residents start having received the same baseline didactic content. Transmitting this didactic content via onboarding allows our residents to begin the work of learning pathology immediately, rather than spending the first weeks of residency covering remedial content such as basic histology. Such a program may be useful to other pathology residencies, most of whom have residents from a range of backgrounds and whose prior exposure to pathology may be limited.

A team-based approach to autopsy education: integrating anatomic and clinical pathology at the rotation level.

CONTEXT: Pathology residency training programs should aim to teach residents to think beyond the compartmentalized data of specific rotations and synthesize data in order to understand the whole clinical picture when interacting with clinicians. OBJECTIVE: To test a collaborative autopsy procedure at Montefiore Medical Center (Bronx, New York), linking residents and attending physicians from anatomic and clinical pathology in the autopsy process from the initial chart review to the final report. Residents consult with clinical pathology colleagues regarding key clinical laboratory findings during the autopsy. This new procedure serves multiple functions: creating a team-based, mutually beneficial educational experience; actively teaching consultative skills; and facilitating more in-depth analysis of the clinical laboratory findings in autopsies. DESIGN: An initial trial of the team-based autopsy system was done from November 2010 to December 2012. Residents were then surveyed via questionnaire to evaluate the frequency and perceived usefulness of clinical pathology autopsy consultations. RESULTS: Senior residents were the most frequent users of clinical pathology autopsy consultation. The most frequently consulted services were microbiology and chemistry. Eighty-nine percent of the residents found the clinical pathology consultation to be useful in arriving at a final diagnosis and clinicopathologic correlation. CONCLUSION: The team-based autopsy is a novel approach to integration of anatomic and clinical pathology curricula at the rotation level. Residents using this approach develop a more holistic approach to pathology, better preparing them for meaningful consultative interaction with clinicians. This paradigm shift in training positions us to better serve in our increasing role as arbiters of outcomes measures in accountable care organizations.

Hemoglobin parameters from diffuse reflectance data.

Tissue vasculature is altered when cancer develops. Consequently, noninvasive methods of monitoring blood vessel size, density, and oxygenation would be valuable. Simple spectroscopy employing fiber optic probes to measure backscattering can potentially determine hemoglobin parameters. However, heterogeneity of blood distribution, the dependence of the tissue-volume-sampled on scattering and absorption, and the potential compression of tissue all hinder the accurate determination of hemoglobin parameters. We address each of these issues. A simple derivation of a correction factor for the absorption coefficient, µa, is presented. This correction factor depends not only on the vessel size, as others have shown, but also on the density of blood vessels. Monte Carlo simulations were used to determine the dependence of an effective pathlength of light through tissue which is parameterized as a ninth-order polynomial function of µa. The hemoglobin bands of backscattering spectra of cervical tissue are fit using these expressions to obtain effective blood vessel size and density, tissue hemoglobin concentration, and oxygenation. Hemoglobin concentration and vessel density were found to depend on the pressure applied during in vivo acquisition of the spectra. It is also shown that determined vessel size depends on the blood hemoglobin concentration used.

Pseudoepitheliomatous hyperplasia mimicking vulvar cancer in a patient with AIDS.

BACKGROUND: Pseudoepitheliomatous hyperplasia (PEH) clinically and histologically mimics squamous cell carcinoma (SCC), specifically in patients with HIV and AIDS. CASE: A 51-year-old G3P2 with AIDS and history of vulvar cancer presented with large bilateral exophytic lesions on the vulva, grossly appearing neoplastic. Initial biopsies of the lesions were interpreted as vulvar SCC. After resolution with empiric treatment with acyclovir for possible herpes simplex virus type 2 outbreak, additional slides were reviewed, and cells with viral inclusions were identified, making the final diagnosis PEH in association with herpes simplex virus type 2 infection. CONCLUSIONS: Although PEH is infrequently encountered, PEH should be considered in the differential diagnosis of vulvar lesions. A multidisciplinary approach including the gynecologist, pathologist, and infectious disease specialists can optimize patient outcome.

Insulin-like growth factor 2 expression modulates Taxol resistance and is a candidate biomarker for reduced disease-free survival in ovarian cancer.

PURPOSE: This study was undertaken to examine the role of the insulin-like growth factor (IGF) signaling pathway in the response of ovarian cancer cells to Taxol and to evaluate the significance of this pathway in human epithelial ovarian tumors. EXPERIMENTAL DESIGN: The effect of Taxol treatment on AKT activation in A2780 ovarian carcinoma cells was evaluated using antibodies specific for phospho-AKT. To study the drug-resistant phenotype, we developed a Taxol-resistant cell line, HEY-T30, derived from HEY ovarian carcinoma cells. IGF2 expression was measured by real-time PCR. A type 1 IGF receptor (IGF1R) inhibitor, NVP-AEW541, and IGF2 small interfering RNA were used to evaluate the effect of IGF pathway inhibition on proliferation and Taxol sensitivity. IGF2 protein expression was evaluated by immunohistochemistry in 115 epithelial ovarian tumors and analyzed in relation to clinical/pathologic factors using the chi(2) or Fisher's exact tests. The influence of IGF2 expression on survival was studied with Cox regression. RESULTS: Taxol-induced AKT phosphorylation required IGF1R tyrosine kinase activity and was associated with upregulation of IGF2. Resistant cells had higher IGF2 expression compared with sensitive cells, and IGF pathway inhibition restored sensitivity to Taxol. High IGF2 tumor expression correlated with advanced stage (P < 0.001) and tumor grade (P < 0.01) and reduced disease-free survival (P < 0.05). CONCLUSIONS: IGF2 modulates Taxol resistance, and tumor IGF2 expression is a candidate prognostic biomarker in epithelial ovarian tumors. IGF pathway inhibition sensitizes drug-resistant ovarian carcinoma cells to Taxol. Such novel findings suggest that IGF2 represents a therapeutic target in ovarian cancer, particularly in the setting of Taxol resistance.

Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma.

BACKGROUND: Half of the patients with head and neck squamous cell carcinoma (HNSCC) can be expected to fail therapy, indicating that more aggressive treatment is warranted for this group. We have developed a novel risk model that can become a basis for developing new treatment paradigms. Here we report on the performance of our model in a new multicenter cohort. DESIGN: Eligible patients from 3 institutions (Montefiore Medical Center, University of Manitoba, and New York University Medical Center) were identified and pathology slides from their resection specimens were reviewed by Margaret Brandwein-Gensler; risk category was assigned as previously published. Kaplan-Meier analysis was performed for disease progression and survival. Cox proportional hazards regression was performed, adjusted for potential confounders. A teaching module was also developed; attending pathologists were asked to score coded slides after a lecture and multiheaded microscope teaching session. Agreement was assessed by calculating Cohen unweighted kappa coefficients. RESULT: The validation cohort consisted of 305 patients, from the above institutions, with 311 primary HNSCC of the oral cavity, oropharynx, and larynx. The median follow-up period for all patients was 27 months. Risk category predicts time to disease progression (P=0.0005), locoregional recurrence (P=0.013), and overall survival (P=0.0000) by Kaplan-Meier analysis. High-risk status is significantly associated with decreased time to disease progression, adjusted for clinical confounders (P=0.015, hazard ratio 2.32, 95% confidence interval 1.18-4.58) compared with collapsed intermediate and low-risk groups. We also demonstrate substantial interrater agreement (kappa=0.64), and very good rater agreement when compared with the standard (kappa=0.87). CONCLUSIONS: We demonstrate significant predictive performance of the risk model in a new cohort of patients with primary HNSCC, adjusted for confounders. Our training experience also supports the feasibility of adapting the risk model in clinical practice.

Extragenital adenosarcoma: a case report, review of the literature, and management discussion.

BACKGROUND: Müllerian adenosarcoma is a rare mixed epithelial-mesenchymal tumor. An extragenital site of origin and sarcomatous overgrowth are associated with aggressive clinical behavior. CASE: We present a rare case of extragenital adenosarcoma with sarcomatous overgrowth and coexistent endometriosis. She was treated with initial cytoreductive surgery and chemotherapy. She underwent a second surgery for management of a high-grade bowel obstruction, due to pathologically confirmed recurrent intraperitoneal adenosarcoma. A complete clinical response was achieved with liposomal doxorubicin, and the patient remains disease-free eighteen months after completion of chemotherapy. CONCLUSION: Liposomal doxorubicin appears to be an active agent for the treatment of adenosarcoma with sarcomatous overgrowth. In addition, we conclude from our review of all reported cases of extragenital adenosarcoma that concurrent endometriosis may represent a favorable prognostic factor.