PLAG1-Rearranged Uterine Sarcomas: A Study of 11 Cases Showing a Wide Phenotypical Spectrum Not Limited to Myxoid Leiomyosarcoma-like Morphology.

PLAG1 gene fusions were recently identified in a subset of uterine myxoid leiomyosarcomas (M-LMS). However, we have encountered cases of PLAG1-rearranged uterine sarcomas (PLAG1-US) lacking M-LMS-like morphology and/or any expression of smooth muscle markers. To better characterize their clinicopathological features, we performed a multi-institutional search which yielded 11 cases. The patients ranged in age from 34-72 years (mean: 57). All tumors arose in the uterine corpus, ranging in size from 6.5-32 cm (mean: 15). The most common stage at presentation was pT1b (n=6), three cases had stage pT1 (unspecified) and one case each presented in stage pT2a and pT3b. Most were treated only by hysterectomy with adnexectomy. The follow-up (range: 7-71 months; median: 39 months) was available for 7 patients. Three cases (7-21 months of follow-up) had no evidence of disease. Three out of 4 remaining patients died of disease within 55-71 months, while the last developed peritoneal spread and was transferred for palliative care at 39 months. Morphologically, the tumors showed a high inter- and intratumoral heterogeneity. M-LMS-like and epithelioid LMS-like morphology was present in 3 and 5 primary tumors, respectively, the rest mostly presented as non-descript ovoid/spindle cell sarcomas. Unusual morphological findings included prominently hyalinized stroma (n=3), adipocytic differentiation with areas mimicking myxoid liposarcoma (n=2), osteosarcomatous differentiation (n=1) and undifferentiated pleomorphic sarcoma-like areas (n=1). The mitotic activity ranged from 3-24 mitoses/10 high-power fields (mean: 9), 3/10 cases showed necrosis. In 3/11 cases, no expression of SMA, h-caldesmon or desmin was noted, whereas 5/5 cases expressed PLAG1. By RNA-sequencing, the following fusion partners were identified: PUM1, CHCHD7 (each n=2), C15orf29, CD44, MYOCD, FRMD6, PTK2 and TRPS1 (each n=1). One case only showed PLAG1 gene break by FISH. Our study documents a much broader morphological spectrum of PLAG1-US than previously reported, encompassing but not limited to M-LMS-like morphology with occasional heterologous (particularly adipocytic) differentiation. Since it is currently difficult to precisely define their line of differentiation, for the time being, we suggest using a descriptive name PLAG1-rearranged uterine sarcoma.

Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.

Assessment Question Characteristics Predict Medical Student Performance in General Pathology.

CONTEXT.­: Evaluation of medical curricula includes appraisal of student assessments in order to encourage deeper learning approaches. General pathology is our institution's 4-week, first-year course covering universal disease concepts (inflammation, neoplasia, etc). OBJECTIVE.­: To compare types of assessment questions and determine which characteristics may predict student scores, degree of difficulty, and item discrimination. DESIGN.­: Item-level analysis was employed to categorize questions along the following variables: type (multiple choice question or matching answer), presence of clinical vignette (if so, whether simple or complex), presence of specimen image, information depth (simple recall or interpretation), knowledge density (first or second order), Bloom taxonomy level (1-3), and, for the final, subject familiarity (repeated concept and, if so, whether verbatim). RESULTS.­: Assessments comprised 3 quizzes and 1 final exam (total 125 questions), scored during a 3-year period, (total 417 students) for a total 52 125 graded attempts. Overall, 44 890 attempts (86.1%) were correct. In multivariate analysis, question type emerged as the most significant predictor of student performance, degree of difficulty, and item discrimination, with multiple choice questions being significantly associated with lower mean scores (P = .004) and higher degree of difficulty (P = .02), but also, paradoxically, poorer discrimination (P = .002). The presence of a specimen image was significantly associated with better discrimination (P = .04), and questions requiring data interpretation (versus simple recall) were significantly associated with lower mean scores (P = .003) and a higher degree of difficulty (P = .046). CONCLUSIONS.­: Assessments in medical education should comprise combinations of questions with various characteristics in order to encourage better student performance, but also obtain optimal degrees of difficulty and levels of item discrimination.

Outcomes of Remote Pathology Instruction in Student Performance and Course Evaluation.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted undergraduate medical education, including preclinical class-based courses, by requiring social distancing and essentially eliminating in-person teaching. The aim of this study was to compare student performance and satisfaction before and after implementation of remote instruction in a first-year introductory pathology course. Assessments (3 quizzes, 1 practical exam, and 1 final) were compared between courses given before (January 2020) and during (January 2021) the COVID-19 pandemic, in terms of mean scores, degree of difficulty, and item discrimination, both overall and across different question types. Students' evaluations of the course (Likert scale-based) were also compared between the 2 years. Significantly higher mean scores were observed during remote instruction (compared to the prior, in-person year) on verbatim-repeated questions (94.9 ± 8.8 vs 89.4 ± 12.2; P = .002) and on questions incorporating a gross specimen image (88.4 ± 7.5 vs 84.4 ± 10.3; P = .007). The percentage of questions that were determined to be moderate/hard in degree of difficulty and good/very good in item discrimination remained similar between the 2 time periods. In the practical examination, students performed significantly better during remote instruction on questions without specimen images (96.5 ± 7.0 vs 91.2 ± 15.2; P = .004). Finally, course evaluation metrics improved, with students giving a higher mean rating value in each measured end point of course quality during the year of remote instruction. In conclusion, student performance and course satisfaction generally improved with remote instruction, suggesting that the changes implemented, and their consequences, should perhaps inform future curriculum improvements.

Systematic review of cognitive behavior therapy to improve mental health of women living with HIV.

Psychological distress is highly prevalent in people living with HIV. Cognitive behavior therapy (CBT) has been associated with improved mental health outcomes in HIV-infected men who have sex with men (MSM); however, little is known of its effect in women living with HIV/AIDS (WLHA). We review current literature on CBT and its effects on depression, anxiety, stress and mental health quality of life (QOL) in WLHA. We undertook a systematic review of the literature indexed in PubMed, Medline, Psychiatry Online and ScienceDirect. Of the 273 relevant studies discovered, 158 contained duplicate data, and 105 studies did not meet the inclusion and exclusion criteria, yielding 10 studies for analysis. Data were independently extracted by each researcher, with differences resolved through discussion and consensus. For WLHA, CBT substantially improved QOL, symptoms of depression and stress, but appeared to have less impact on anxiety. Three of the six studies measuring depression outcomes showed statistically significant decreases in depression. Three of three studies measuring mental health QOL, and three of three studies measuring stress also demonstrated statistically significant improvement. Two of two studies measuring anxiety did not show statistically significant change. CBT is a promising therapy for WLHA. CBT may reduce psychological distress, improving symptoms of depression, stress and QOL. There is a need for additional, better standardized studies that examine CBT for WLHA.

HPV-positive Squamous Cell Carcinoma of the Larynx, Oral Cavity, and Hypopharynx: Clinicopathologic Characterization With Recognition of a Novel Warty Variant.

Human papillomavirus (HPV) is a principal driver for most oropharyngeal squamous cell carcinomas (OPSCCs), where it is strongly associated with improved survival. HPV is much less frequently detected in squamous cell carcinomas arising in nonoropharyngeal sites (non-OPSCCs), and its pathogenic role and prognostic value in these tumors is unclear. We evaluated the clinicopathologic features of 52 non-OPSCCs considered HPV-positive based upon p16 immunohistochemistry and direct HPV detection using RNA in situ hybridization (ISH), DNA ISH, or real-time DNA polymerase chain reaction. The HPV-positive non-OPSCCs were from the larynx (n=27), oral cavity (n=21), and hypopharynx (n=4). While most cases (n=34, 65%) showed classic histologic features of HPV-positive OPSCC, including endophytic growth, minimal keratinization, and hyperchromatic nuclei without koilocytic changes, a subset (n=13, 25%) were characterized by exophytic growth, exuberant surface hyperkeratosis and parakeratosis, marked nuclear pleomorphism, and prominent koilocytic atypia. These antithetical features were highly reminiscent of the warty variant of HPV-positive squamous cell carcinoma described in anogenital sites. Compared with tumors without warty features, the warty tumors presented at lower stage and were not associated with lymph node metastasis, local recurrence, or distant spread (4 y disease-free survival of 100% vs. 66%, P=0.069). The presence of transcriptionally active HPV as detected by RNA ISH suggests a pathogenic role for HPV in these nonoropharyngeal sites. While most HPV-positive non-OPSCCs are morphologically similar to their tonsillar counterparts, this study highlights a previously unrecognized warty variant that may be associated with a highly favorable clinical outcome.