Detecting Cholangiocarcinoma in the Setting of Primary Sclerosing Cholangitis: Is Biliary Tract Fluorescence In Situ Hybridization Helpful?

INTRODUCTION/OBJECTIVE: Biliary brushing cytology (BB) to detect cholangiocarcinoma (CCA) is integral in the surveillance of patients with primary sclerosing cholangitis (PSC). Since reactive changes can mimic carcinoma, indeterminant results are frequent. Fluorescence in situ hybridization (FISH) using the UroVysion probe set has been advocated to enhance the detection of CCA. This study evaluates the performance of FISH for detecting CCA in patients with and without PSC. MATERIALS AND METHODS: A query of our pathology database for atypical and suspicious BB with concurrent FISH results was performed from 2014 to 2021. FISH (using UroVysion probe set containing centromere enumeration probes to chromosomes 3, 7, and 17) was positive if at least 5 cells demonstrated polysomy. Electronic medical records were reviewed to identify patients with PSC and CCA. CCA was confirmed by pathology or clinical impression. RESULTS: Of the 65 patients (103 BB) in the PSC cohort, 59 patients (94 BB) without CCA and 6 patients (9 BB) with CCA were identified. 33 non-PSC patients (41 BB) with CCA were included for comparison. Positive FISH was highest in non-PSC patients with CCA (10/41 BB, 24%). Positive FISH was seen in both PSC with (1/9 BB, 11%) and without (2/94 BB, 2%) CCA. CONCLUSIONS: FISH positivity was lower than expected and was positive in PSC patients without CCA. These results question the clinical utility of FISH for CCA surveillance in PSC patients.

An Approach to Nonurothelial Malignancies of the Urinary Bladder in Urine Cytology.

Urine cytology is an economical and convenient method of triaging patients who present with urinary symptoms as well as surveying those who have previously been diagnosed with urothelial carcinoma for recurrent or persistent disease. While the vast majority of malignancies diagnosed in urine cytology are urothelial carcinomas, it is important to recognize nonurothelial elements to inform patient prognosis and raise the possibility of involvement by a urothelial carcinoma variant, nonurothelial malignancy of the bladder, or a nonbladder primary, which may alter patient management pathways. As such, becoming familiar with morphologic features of nonurothelial malignancies in urine cytology as well as their related clinical risk factors, radiologic and cystoscopic features, differential diagnostic considerations, and the utility and pitfalls of ancillary tests can facilitate optimal patient care.

Online learning developments in undergraduate medical education in response to the COVID-19 pandemic: A BEME systematic review: BEME Guide No. 69.

BACKGROUND: The COVID-19 pandemic spurred an abrupt transition away from in-person educational activities. This systematic review investigated the pivot to online learning for nonclinical undergraduate medical education (UGME) activities and explored descriptions of educational offerings deployed, their impact, and lessons learned. METHODS: The authors systematically searched four online databases and conducted a manual electronic search of MedEdPublish up to December 21, 2020. Two authors independently screened titles, abstracts and full texts, performed data extraction and assessed risk of bias. A third author resolved discrepancies. Findings were reported in accordance with the STORIES (STructured apprOach to the Reporting in healthcare education of Evidence Synthesis) statement and BEME guidance. RESULTS: Fifty-six articles were included. The majority (n = 41) described the rapid transition of existing offerings to online formats, whereas fewer (n = 15) described novel activities. The majority (n = 27) included a combination of synchronous and asynchronous components. Didactics (n = 40) and small groups (n = 26) were the most common instructional methods. Teachers largely integrated technology to replace and amplify rather than transform learning, though learner engagement was often interactive. Thematic analysis revealed unique challenges of online learning, as well as exemplary practices. The quality of study designs and reporting was modest, with underpinning theory at highest risk of bias. Virtually all studies (n = 54) assessed reaction/satisfaction, fewer than half (n = 23) assessed changes in attitudes, knowledge or skills, and none assessed behavioral, organizational or patient outcomes. CONCLUSIONS: UGME educators successfully transitioned face-to-face instructional methods online and implemented novel solutions during the COVID-19 pandemic. Although technology's potential to transform teaching is not yet fully realized, the use of synchronous and asynchronous formats encouraged virtual engagement, while offering flexible, self-directed learning. As we transition from emergency remote learning to a post-pandemic world, educators must underpin new developments with theory, report additional outcomes and provide details that support replication.

An update on developments in medical education in response to the COVID-19 pandemic: A BEME scoping review: BEME Guide No. 64.

BACKGROUND: COVID-19 has fundamentally altered how education is delivered. Gordon et al. previously conducted a review of medical education developments in response to COVID-19; however, the field has rapidly evolved in the ensuing months. This scoping review aims to map the extent, range and nature of subsequent developments, summarizing the expanding evidence base and identifying areas for future research. METHODS: The authors followed the five stages of a scoping review outlined by Arskey and O'Malley. Four online databases and MedEdPublish were searched. Two authors independently screened titles, abstracts and full texts. Included articles described developments in medical education deployed in response to COVID-19 and reported outcomes. Data extraction was completed by two authors and synthesized into a variety of maps and charts. RESULTS: One hundred twenty-seven articles were included: 104 were from North America, Asia and Europe; 51 were undergraduate, 41 graduate, 22 continuing medical education, and 13 mixed; 35 were implemented by universities, 75 by academic hospitals, and 17 by organizations or collaborations. The focus of developments included pivoting to online learning (n = 58), simulation (n = 24), assessment (n = 11), well-being (n = 8), telehealth (n = 5), clinical service reconfigurations (n = 4), interviews (n = 4), service provision (n = 2), faculty development (n = 2) and other (n = 9). The most common Kirkpatrick outcome reported was Level 1, however, a number of studies reported 2a or 2b. A few described Levels 3, 4a, 4b or other outcomes (e.g. quality improvement). CONCLUSIONS: This scoping review mapped the available literature on developments in medical education in response to COVID-19, summarizing developments and outcomes to serve as a guide for future work. The review highlighted areas of relative strength, as well as several gaps. Numerous articles have been written about remote learning and simulation and these areas are ripe for full systematic reviews. Telehealth, interviews and faculty development were lacking and need urgent attention.

Clinicopathological characterisation of renal cell carcinoma in young adults: a contemporary update and review of literature.

AIMS: Renal cell carcinomas are relatively rare in children and young adults. While well characterised in adults, the morphological and molecular characterisation of these tumours in young patients is relatively lacking. The objective of this study was to explore the spectrum of renal cell carcinoma (RCC) subtypes in children and young adults and to determine their clinico-pathological, immunohistochemical and molecular characteristics by evaluating a large retrospective cohort of renal cell carcinoma patients age 30 years or younger. METHODS AND RESULTS: Sixty-eight cases with confirmed diagnosis of renal cell carcinoma at age 30 years or younger were identified at our institution. Clear cell carcinoma accounted for the most common subtype seen in this age group. Translocation renal cell carcinoma and rare familial syndrome subtypes such as succinate dehydrogenase deficient renal cell carcinoma and tuberous sclerosis complex-associated renal cell carcinoma were found relatively more frequently in this cohort. Despite applying the 2016 WHO classification criteria, a high proportion of the tumours in our series remained unclassified. CONCLUSIONS: Our results suggest that renal cell carcinoma in children and young adults is a relatively rare disease that shares many histological similarities to renal cell carcinoma occurring in adults and yet demonstrate some unique clinical-pathological differences. Microphthalmia-associated transcription (MiT) family translocation RCC and rare familial syndrome subtypes are relatively more frequent in the paediatric and adolescent age groups than in adults. Clear cell RCC still accounted for the most common subtype seen in this age group. MiT family translocation RCC patients presented with advanced stage disease and had poor clinical outcomes. The large and heterogeneous subgroup of unclassified renal cell carcinoma contains phenotypically distinct tumours with further potential for future subcategories in the renal cell carcinoma classification.

An Updated Contextual Approach to Mesothelial Proliferations in Pleural Effusion Cytology Leveraging Morphology, Ancillary Studies, and Novel Biomarkers.

CONTEXT.­: Pleural effusions are common cytologic specimens that can be leveraged to make diagnoses of malignancy that drive appropriate patient management. However, the overlap in morphologic features of reactive mesothelial proliferations, mesotheliomas, and adenocarcinomas can create diagnostic pitfalls in the cytologic evaluation of pleural fluids. OBJECTIVE.­: To review the morphologic spectrum of benign and malignant mesothelial proliferations in pleural effusions, as well as relevant clinicoradiologic contexts and ancillary tests. DATA SOURCES.­: Existing scientific and clinical literature as of January 2023. CONCLUSIONS.­: We can leverage the knowledge of several overlapping morphologic features, clinicoradiologic scenarios, and immunohistochemical studies to enhance the diagnostic accuracy of pleural effusion cytology to appropriately delineate cases of adenocarcinoma, reactive mesothelial proliferation, and mesothelioma. Earlier diagnosis through cytology, particularly in cases of mesothelioma, may positively impact patient treatment options and prognosis.

The "Pathology Passport": a redesign of the pathology elective experience to enhance medical student engagement and understanding of pathology as a clinical practice.

Given the trend of condensed preclinical curricula in medical schools nationwide, creating meaningful pathology learning experiences within the clinical and post-clinical curricula is important to both enhance student understanding of how pathology integrates into daily healthcare delivery and spark potential career interest in the field. While pathology electives are a common modality for medical students to explore pathology, they frequently render students passive observers of daily clinical workflows (often in grossing and sign-out rooms of surgical pathology). This can have a negative impact on student engagement with their pathology clinical teams and on their satisfaction with the pathology elective experience. As such, we aim to describe our institutional experience in creating a new pathology elective structure, the "Pathology Passport," which leverages intentional student engagement with existing pathology workflows and introduces a means of criterion-based grading. Data collected from student pre- and post-elective surveys demonstrate the elective's positive impact on students' perceived understanding of pathology and their overall learning experience. We hope that our resources can be leveraged at other institutions and even other non-pathology clerkship/elective rotations to promote active engagement of students in clinical workflows while providing clear expectations for grading.

Telecytology versus conventional rapid on-site evaluation for endobronchial ultrasound-guided fine needle aspiration: a single institution's experience.

INTRODUCTION: Telecytology (TC) has the advantage of allowing cytopathologists to remotely support multiple sites rapid on-site evaluation (ROSE) concurrently and represents a potential solution for an increased clinical demand for ROSE. In this study, we share our comparative experience of using TC versus conventional (in-person) ROSE for endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA). MATERIALS AND METHODS: We evaluated 475 consecutive cases of EBUS-FNA that underwent TC-ROSE from May 2020 to August 2021 along with 475 consecutive cases which had conventional ROSE from November 2019 to August 2021 at the University of Michigan. Concordant rates of preliminary and final diagnoses were calculated and compared between TC and conventional methods. RESULTS: While there was no significant difference in preliminary diagnostic rates of nondiagnostic, benign, atypical, and malignant categories between the TC and conventional cohorts, a significantly lower proportion of TC cases received a preliminary suspicious for malignancy diagnosis (2%) compared to the conventional group (4%) (P = 0.03). The concordance rate of preliminary and final diagnoses in TC and conventional ROSE was 96% and 94%, respectively. The average total number of passes per procedure did not differ significantly between TC and conventional ROSE (4.9 versus 4.7). While a relatively higher number of TC-ROSE cases collected dedicated passes compared with conventional ROSE (49% versus 40%), the difference was not statistically significant. CONCLUSIONS: The performance of TC-ROSE for EBUS-FNA is comparable to that of conventional ROSE with similar performance metrics and therefore can be used as a feasible substitute.

Performance of fluorescence in situ hybridization in biliary brushings with equivocal cytology: an institutional experience.

INTRODUCTION: Biliary brushing (BB) cytology has a sensitivity of 15%-65% and specificity approaching 100% for detecting malignancy. Fluorescence in-situ hybridization (FISH) using the UroVysion probe set has been advocated to enhance the detection of malignancies with reported sensitivity of 43%-84%. We sought to evaluate the performance of FISH in BB with equivocal cytology at our institution. MATERIALS AND METHODS: Patients with atypical and suspicious BB with concurrent diagnostic FISH performed at our institution from 2014 to 2021 were identified through a query of our pathology database. FISH (using UroVysion probe set containing centromere enumeration probes to chromosomes 3, 7, and 17) was positive if at least 5 cells demonstrated polysomy. Electronic medical records were reviewed for pathology results and outcomes. Patients were classified malignant if they had positive pathology or documented clinical impression of malignancy and benign if they had negative pathology and/or documented benign clinical course for at least 12 months. RESULTS: We identified 254 equivocal BB (238 atypical/16 suspicious) with concurrent FISH results from 191 patients (105 benign, 86 malignant). 12% (22/191) of patients were FISH positive. Twenty-four percent (21/86) of patients with malignancy had positive FISH but were nonspecific for pancreaticobiliary/ampullary adenocarcinomas. Almost all positive FISH were associated with malignancy (21/22; 95%). There was 1 positive FISH in a patient with primary sclerosing cholangitis who had a benign outcome. CONCLUSIONS: The small number of positive FISH results in BB with equivocal cytology raises the question of the optimal criteria for malignancy. Using only polysomy could result in lower sensitivity.

Comparative expression of TRPS1, GATA3, SOX10, mammaglobin, and GCDFP-15 in effusion specimens with breast carcinoma.

BACKGROUND: Traditional immunohistochemistry (IHC) for breast carcinomas has shown low detection rates of metastatic breast carcinoma (MBC) in effusions. Although GATA3 has enhanced diagnostic accuracy in this realm, its limited utility in detecting triple-negative breast carcinoma (TNBC) has been highlighted. TRPS1 has been introduced as a potentially sensitive and specific marker in detecting MBC on histologic samples. We investigate the utility of TRPS1 as a marker for MBC in effusion specimens and compare its performance to SOX10, GATA3, mammaglobin (MG), and GCDFP-15. METHODS: A database search identified malignant effusions involved by MBC between 2013 and 2021. Cases from unique patients with sufficient cellularity were evaluated for TRPS1, GATA3, SOX10, MG, and GCDFP-15 IHC. The intensity and extent of tumor cells (TC) were scored by two pathologists. Any discrepancies were jointly reviewed for consensus. RESULTS: GATA3 showed the highest rate of positivity (98.2%), followed by TRPS1 (89.5%), MG (43.9%), GCDFP-15 (21.1%), and SOX10 (3.5%). All GATA3-positive cases showed intermediate to high expression. Comparatively, TRPS1 showed more variability in staining extent and intensity. In 13 (22.8%) cases, TRPS1 showed extensive background staining of inflammatory and mesothelial cells. Of six TNBCs, GATA3, and TRPS1 were positive in six (100%) and four (66.7%) cases, respectively. CONCLUSIONS: While TRPS1 shows a lower detection rate for MBC than GATA-3, using a combination of these markers can enhance effusion cytology's performance in detecting MBC. However, variability in TRPS1 staining intensity and high background TRPS1 staining of inflammatory and mesothelial cells can increase difficulty in its evaluation.

A rare entity: Ganglioneuroma of the prostate.

Ganglioneuromas are benign tumors arising from the neural crest. Histologically, they are composed of mature Schwann cells and ganglion cells admixed with fibrous tissue. While they frequently are seen in the abdomen and mediastinum, rare reports have highlighted their occurrences in the genitourinary system. The only prior reported prostatic ganglioneuroma arose in a patient with a history of neurofibromatosis type 1. In this report, we highlight the first reported prostatic ganglioneuroma without a known genetic linkage.

Performance of Afirma genomic sequencing classifier and histopathological outcome in Bethesda category III thyroid nodules: Initial versus repeat fine-needle aspiration.

BACKGROUND: There is limited data comparing the performance of Afirma Genomic Sequencing Classifier (GSC) in thyroid nodules carrying an initial versus a repeat diagnosis of atypia of undetermined significance (AUS). This study reported an institutional experience in this regard. MATERIALS AND METHODS: This retrospective study included consecutive thyroid nodules that had an initial or a repeat AUS diagnosis and had a subsequent GSC diagnostic result (benign or suspicious) from 2017 to 2021. All nodules were followed by surgical intervention or by clinical and/or ultrasound monitoring. GSC's benign call rate (BCR), rate of histology-proven malignancy associated with a suspicious GSC result, and diagnostic parameters of GSC were calculated and compared between the two cohorts (initial versus repeat AUS). Statistical significance was defined with a p-value of <.05 for all analysis. RESULTS: A total of 202 cases fulfilled inclusion criteria, including 67 and 135 thyroid nodules with an initial and a repeat AUS diagnosis, respectively. BCR was 67% and 66% in initial and repeat AUS cohorts, respectively. Rate of histology-proven malignancy associated with a suspicious GSC result were 22% and 24% in initial and repeat AUS cohorts, respectively. Compared with the repeat AUS cohort, the initial AUS cohort showed slightly lower sensitivity (83% vs. 100%), specificity (70% vs. 73%), PPV (23% vs. 24%), NPV (98% vs. 100%), and diagnostic accuracy (72% vs. 75%). Nevertheless, these differences did not reach statistical significance. CONCLUSION: GSC demonstrated comparable performance in thyroid nodules with a repeat AUS diagnosis versus nodules with an initial AUS diagnosis.

Pathology Rotations Embedded Within Surgery Clerkships Can Shift Student Perspectives About Pathology.

Purpose: Medical school curricula have focused more on early clinical exposure with compressed didactic curricula, raising questions on how pathology can be effectively integrated into clinically relevant medical education. This study highlights how a required 1-week pathology rotation embedded within a surgery clerkship can impact students' knowledge base and perspectives of pathology. Methods: One hundred ninety-two medical students rotated through a newly designed mandatory 1-week pathology rotation during surgery clerkship. Post-rotation feedback and survey data from students were collected to evaluate their perspectives of pathology. Pathology residents and faculty were surveyed about changes on workflow imposed by the new rotation. Results: Eighty percent of student respondents agreed the rotation improved understanding of pathology workflow and its integration into the larger picture of healthcare delivery. 62% and 66% reported the rotation had a positive impact on their perspectives of pathology and pathologists, respectively. However, a significant number pathology resident respondents noted that integration of students into clinical activities either slightly (42%) or significantly (5%) decreased their own learning. Both pathology faculty and residents also noted medical student presence either slightly (19% and 37%, respectively) or significantly (63% and 58%, respectively) decreased workflow efficiency. Conclusions: Integration of pathology rotations into surgical clerkships is a viable strategy to remedy decreased pathology contact and education due to curricular restructuring that condenses preclinical time while offering medical students a more integrated and practical perspective of pathology as a field. It is essential for pathology departments to prioritize and actively participate in both preclinical and clinical curricular development. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01569-y.

Performance of Afirma genomic sequencing classifier and histopathological outcome are associated with patterns of atypia in Bethesda category III thyroid nodules.

BACKGROUND: Data on Afirma's genomic sequencing classifier (GSC) performance in atypia of undetermined significance (AUS) subcategories is limited. This study investigated GSC performance in AUS nodules with architectural atypia (AUS-A), cytological atypia (AUS-C), architectural and cytological atypia (AUS-AC), and predominantly Hürthle cells (AUS-HC). METHODS: This study retrieved consecutive thyroid nodules having a recurrent cytologic diagnosis of AUS with qualifiers and a concurrent GSC diagnostic result. All nodules were followed by either surgical intervention or clinical and/or ultrasound monitoring (≥6 months). GSC benign call rate (BCR), rate of histology-proven malignancy, and diagnostic parameters of GSC were calculated for individual AUS subcategories. Statistical analysis was performed using the Fisher exact test. RESULTS: A total of 135 AUS nodules fulfilled inclusion criteria, including 79 AUS-A, 9 AUS-C, 29 AUS-AC, and 18 AUS-HC. BCR was 72.2%, 66.7%, 44.8%, and 77.8% in AUS-A, AUS-C, AUS-AC, and AUS-HC, respectively. AUS-A showed a greater BCR than AUS-AC (p < .05). All GSC-benign nodules were considered benign on clinical or surgical follow-up. Among GSC-suspicious nodules, histology-proven malignancies represented 4.5% of AUS-A, 0% of AUS-C, 56.3% of AUS-AC, and 25.0% of AUS-HC cases. AUS-AC demonstrated a higher malignant rate compared with AUS-A (p < .05). GSC offers 100% NPV and a wide range (5%-56%) of PPV across all AUS subcategories. AUS-AC demonstrated a greater PPV compared with AUS-A (p < .05). CONCLUSION: BCR of GSC and malignant rates associated with suspicious GSC may differ in various AUS subcategories. GSC-suspicious nodules with both architectural and cytologic atypia are more likely to be malignant. These findings may improve clinical triage and/or management of patients with AUS thyroid nodules.

A Study of Thyroid Fine Needle Aspiration of Follicular Adenoma in the "Atypia of Undetermined Significance" Bethesda Category Using Digital Image Analysis.

BACKGROUND: Originally designed for computerized image analysis, ThinPrep is underutilized in that role outside gynecological cytology. It can be used to address the inter/intra-observer variability in the evaluation of thyroid fine needle aspiration (TFNA) biopsy and help pathologists to gain additional insight into thyroid cytomorphology. METHODS: We designed and validated a feature engineering and supervised machine learning-based digital image analysis method using ImageJ and Python scikit-learn . The method was trained and validated from 400 low power (100x) and 400 high power (400x) images generated from 40 TFNA cases. RESULT: The area under the curve (AUC) for receiver operating characteristics (ROC) is 0.75 (0.74-0.82) for model based from low-power images and 0.74 (0.69-0.79) for the model based from high-power images. Cytomorphologic features were synthesized using feature engineering and when performed in isolation, they achieved AUC of 0.71 (0.64-0.77) for chromatin, 0.70 (0.64-0.73) for cellularity, 0.65 (0.60-0.69) for cytoarchitecture, 0.57 (0.51-0.61) for nuclear size, and 0.63 (0.57-0.68) for nuclear shape. CONCLUSION: Our study proves that ThinPrep is an excellent preparation method for digital image analysis of thyroid cytomorphology. It can be used to quantitatively harvest morphologic information for diagnostic purpose.

Comparison of Diagnostic Rates and Concordance with Subsequent Surgical Resections between Conventional Smear and ThinPrep Preparations versus ThinPrep Only in Thyroid Fine Needle Aspiration (T-FNA) Specimens.

BACKGROUND: Thyroid fine needle aspiration (T-FNA) is a mainstay in management of thyroid nodules. However, the preparation of T-FNA specimens varies across institutions. Prior studies have compared diagnostic rates between different specimen preparations of T-FNA specimens and their associated advantages and disadvantages. However, few have compared the rates of all diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) between liquid-based preparations (LBPs) and a combination of LBP and conventional smear (CS) preparations. Our study compares TBSRTC diagnostic rates between these 2 cohorts and correlates cytologic diagnoses with subsequent thyroid resections to evaluate rates of neoplasia (RON) and malignancy (ROM). METHODS: 584 consecutive thyroid FNA specimens were collected and stratified by preparation type (ThinPrep [TP] vs. CS & TP). Diagnostic rates for each TBSRTC diagnostic category were calculated. The institution's electronic medical records database was searched for histologic diagnoses of previously sampled thyroid nodules to evaluate the RON and ROM. RESULTS: Of 584 thyroid FNA specimens, 73 (12.5%) and 511 (87.5%) were evaluated by TP only and CS & TP, respectively, reflecting the predominance of rapid on-site evaluation (ROSE) with CS for T-FNAs at our institution. Of the TP only and CS & TP cohorts, 29 (39.7%) and 98 (19.2%) had subsequent resections, respectively. The frequency of non-diagnostic cases was lower in the CS & TP cohort (12.7% vs. 26%). While the diagnostic rate of follicular lesion of undetermined significance was similar for both cohorts, SFN categorization was only utilized in the CS & TP cohort (1.5% vs. 0%). Although RON and ROM were similar between cohorts in many of the TBSRTC categories, there was a higher RON associated with non-diagnostic specimens in the TP only cohort when the denominator included all non-diagnostic cases. CONCLUSION: The combination of CS and LBP may potentially decrease the non-diagnostic rate of T-FNA specimens as well as the number of passes required for diagnosis, particularly with ROSE. Evaluation of morphologic features highlighted in conventional smears may facilitate diagnostic categorization in the "suspicious for follicular neoplasm" category.

Cellular engagement and interaction in the tumor microenvironment predict non-response to PD-1/PD-L1 inhibitors in metastatic non-small cell lung cancer.

Immune checkpoint inhibitors (ICI) with anti-PD-1/PD-L1 agents have improved the survival of patients with metastatic non-small cell lung cancer (mNSCLC). Tumor PD-L1 expression is an imperfect biomarker as it does not capture the complex interactions between constituents of the tumor microenvironment (TME). Using multiplex fluorescent immunohistochemistry (mfIHC), we modeled the TME to study the influence of cellular distribution and engagement on response to ICI in mNSCLC. We performed mfIHC on pretreatment tissue from patients with mNSCLC who received ICI. We used primary antibodies against CD3, CD8, CD163, PD-L1, pancytokeratin, and FOXP3; simple and complex phenotyping as well as spatial analyses was performed. We analyzed 68 distinct samples from 52 patients with mNSCLC. Patients were 39-79 years old (median 67); 44% were male and 75% had adenocarcinoma histology. The most used ICI was atezolizumab (48%). The percentage of PD-L1 positive epithelial tumor cells (EC), degree of cytotoxic T lymphocyte (CTL) engagement with EC, and degree of CTL engagement with helper T lymphocytes (HTL) were significantly lower in non-responders versus responders (p = 0.0163, p = 0.0026 and p = 0.0006, respectively). The combination of these 3 characteristics generated the best sensitivity and specificity to predict non-response to ICI and was also associated with shortened overall survival (p = 0.0271). The combination of low CTL engagement with EC and HTL along with low expression of EC PD-L1 represents a state of impaired endogenous immune reactivity. Together, they more precisely identified non-responders to ICI compared to PD-L1 alone and illustrate the importance of cellular interactions in the TME.

Increasing Medical Student Exposure to Pathology by Creating an Integrated Rotation During Surgery Clerkship.

Following a nationwide trend, the University of Michigan Medical School has restructured its curriculum to facilitate integration of basic science curricula and early inclusion of clinical experiences, resulting in a truncation of a 19-month didactic-based preclinical curriculum to 13 months. Because preclinical didactic and lab sessions formed the bulk of pathology contact hours, the curriculum overhaul significantly reduced student exposure to pathologists. This reduction in exposure may decrease student understanding of how pathology integrates into the larger picture of healthcare delivery and could also decrease the pipeline of students interested in pursuing pathology as a career choice. To ameliorate these concerns, a mandatory 1-week rotation through the Pathology Department was integrated into the surgery clerkship. This brief report outlines the process of creating a new, unique pathology rotation for surgery clerkship students that includes observation in autopsy and surgical pathology sign-out, small group sessions focused on foundational concepts in microbiology, chemistry, and transfusion medicine, and access to online case-based modules. Available qualitative student feedback indicates that students appreciate how this rotation granted them a "behind the scenes" look at pathology but also noted that the fast pace of clinical sign-out sessions and length of small group sessions were suboptimal for student learning. This feedback and future survey data will serve as a platform on which curricular improvements can be made to enhance the learning environment for both learners and educators.

Diagnosis and categorization of malignant effusions: A 6-year review from a single academic institution.

BACKGROUND: Cytologic detection of malignant cells in pleural, peritoneal, or pericardial effusion most likely indicates advanced stage of malignant disease. There are a few studies updating the categorization of malignant effusions. METHODS: The electronic pathology database was searched to identify consecutive cases of malignant effusion during a 6-year period. Patient age and gender, origins of known malignancy, and cytologic diagnoses were recorded and summarized. RESULTS: A total of 1059 specimens included 561 (53%) pleural, 441 (41.6%) peritoneal, and 57 (5.4%) pericardial fluids. Most of the pleural (516, 92.0%), peritoneal (418, 94.8%), and pericardial (53, 93.0%) specimens were derived from patients with a single known malignancy. More common origins involving pleural fluid were lung (152, 27.1%) followed by breast (103, 18.4%) and gastrointestinal tract (76, 13.5%). The most common etiology for women and men was breast (102, 30.8%) and lung (67, 36.2%), respectively. More common origins involving peritoneal fluid were gastrointestinal (158, 35.8%) and gynecologic (156, 35.4%) tracts, and breast (46, 10.4%). The most common etiology for women and men was Mullerian (156, 55.5%) and gastrointestinal tract (94, 68.6%), respectively. Most common origins involving the pericardial fluid were breast (20, 37.7%) and lung (17, 29.8%). Breast and lung were the most common etiology for women (20, 57.1%) and men (8, 44.4%), respectively. CONCLUSIONS: Breast and lung remain to be the most common origin of both malignant pleural and pericardial effusion for women and men, respectively. The most common origin involving peritoneal effusion is Mullerian for women and gastrointestinal tract for men.