Aubry, Marie‐Christine

Context.— A monthly pathology journal club has met for 24 years. It was established to help members stay apprised of the literature relevant to diagnostic pulmonary pathology. Objective.— To assess whether the journal club met its goal and to report on opportunities identified for improvement. Design.— To determine whether articles chosen for discussion as opposed to notation were more significant, Scopus citation indices for article types reviewed from January 2007 to November 2023 were compared. A survey of current faculty was undertaken to determine if the club was meeting expectations and to identify improvement opportunities. Results.— Articles from January 2007 to November 2023 included 858 discussed and 3385 noted. Mean (SD) citation count was 103.0 (409.80) for discussion and 64.9 (259.77) for notation articles ( P < .001). The citation count was noticeably right skewed, as articles with high citation counts inflated the mean. Members were mostly satisfied with the way the journal club was structured and managed. Members most valued the summary of the articles, followed by the live discussion. Opportunities for improvement included decreasing the number of journals scanned, decreasing detail in summaries, and using generative artificial intelligence (AI) to facilitate summary generation. A pilot using AI anecdotally reduced preparatory time, but the human-edited summary included more specific context, critical commentary, and enhanced take-home messages, providing a more nuanced analysis. Conclusions.— The journal club met its initial goal. Opportunities for improvement have been identified including the use of generative AI to facilitate article summarization.

Context.— Cardiac and pulmonary allograft recipients represent a unique population, frequently interacting with support groups and exhibiting intense curiosity about their pathology. Like other solid organ transplant patients, they have enduring and frequent interaction with the laboratory for routine allograft surveillance. Objective.— To address patient requests to understand what happens to their explanted organ and to better understand their disease while simultaneously improving awareness of pathologists’ roles in their continuing care. Design.— At routine follow-up appointments, transplant nurse coordinators offer each allograft recipient the opportunity to interact with a pathologist in our “ On My Path ” program. Organ viewing occurs in a private setting, in a specialized room. Relevant pathology is discussed, and questions are answered, with documentation in the medical record. The patient is subsequently gifted a 3-dimensional model of their explanted organ. Transplant coordinators were surveyed for their feedback on the experience. Results.— One hundred fifty-eight interactions have been documented (2017–2022) at our institution, including patients who underwent cardiac transplant (96, 61%), single or bilateral lung transplant (54, 34%), or combination lung and heart transplant (8, 5%). Transplant coordinators reported an increase in patient understanding of their disease and emotional closure related to the disease through the On My Path program. Conclusions.— Pathologists providing direct patient care is a feasible model that addresses currently unmet desires of the transplant population to better understand their pathology. Providing a 3-dimensional model helps to empower patients and drives satisfaction. These interactions also improve awareness about pathology as a discipline and its importance in the continued care of transplant recipients.

Primary pulmonary myxoid sarcoma (PPMS) and thoracic angiomatoid fibrous histiocytoma (AFH) are rare neoplasms with EWSR1 fusions and overlapping morphology. Both tumor types often show epithelial membrane antigen expression, but AFH characteristically co-expresses desmin. We encountered a case of PPMS with the unexpected finding of patchy, strong anaplastic lymphoma kinase (ALK) (previously reported in AFH) and synaptophysin expression. We evaluated a cohort of PPMS and thoracic AFH with systematic morphologic comparison and surveyed for aberrant expression of ALK and synaptophysin. Medical records and slides were reviewed for 16 molecularly confirmed cases of PPMS (n=5) and thoracic AFH (n=11). Each case was scored for morphologic characteristics typical of PPMS and/or AFH. ALK, synaptophysin, chromogranin, desmin, and epithelial membrane antigen immunostains were performed on cases with available tissue. AFH and PPMS cases showed similar age at presentation and long-term tumor behavior. Almost all cases of PPMS and AFH had a fibrous pseudocapsule and lymphoid rim. All PPMS had myxoid stroma and reticular growth pattern, but these features were also present in a subset of AFH. Synaptophysin expression was present in 6 of 11 AFH and 1 of 5 PPMS; all tested cases were negative for chromogranin (n=15). One case of AFH and 1 case of PPMS showed focally strong coexpression of synaptophysin and ALK. AFH and PPMS show considerable clinicopathologic overlap. When supportive, the immunohistochemical findings described may aid in diagnosis before molecular confirmation. PPMS and AFH may be morphologic variants of the same clinicopathologic entity, which can show more immunophenotypic variability than previously reported.

Context.— Respiratory infections complicate lung transplantation and increase the risk of allograft dysfunction. Allograft lungs may have different susceptibilities to infection than native lungs, potentially leading to different disease severity in lungs of single lung transplant recipients (SLTRs). Objective.— To study whether infections affect allograft and native lungs differently in SLTRs but similarly in double LTRs (DLTRs). Design.— Using an institutional database of LTRs, medical records were searched, chest computed tomography studies were systematically reviewed, and histopathologic features were recorded per lung lobe and graded semiquantitatively. A multilobar-histopathology score (MLHS) including histopathologic data from each lung and a bilateral ratio (MLHSratio) comparing histopathologies between both lungs were calculated in SLTRs and compared to DLTRs. Results.— Six SLTRs died of infection involving the lungs. All allografts showed multifocal histopathologic evidence of infection, but at least 1 lobe of the native lung was uninvolved. In 4 of 5 DLTRs, histopathologic evidence of infection was seen in all lung lobes. On computed tomography, multifocal ground-glass and/or nodular opacities were found in a bilateral distribution in all DLTRs but in only 2 of 6 SLTRs. In SLTRs, the MLHSAllograft was higher than MLHSNative (P = .02). The MLHSratio values of SLTR and DLTR were significantly different (P &lt; .001). Conclusions.— Allograft and native lungs appear to harbor different susceptibilities to infections. The results are important for the management of LTRs.

AimsGiant cell arteritis (GCA) is a systemic vasculitis affecting medium and large arteries in patients aged over 50 years. Involvement of temporal arteries (TA) can lead to complications such as blindness and stroke. While the diagnostic gold standard is temporal artery biopsy (TAB), comorbidities and age‐related changes can make interpretation of such specimens difficult. This study aims to establish a baseline of TA changes in subjects without GCA to facilitate the interpretation of TAB.Methods and resultsBilateral TA specimens were collected from 100 consecutive eligible postmortem examinations. Subjects were divided into four age groups and specimens semiquantitatively evaluated for eccentric intimal fibroplasia, disruption and calcification of the internal elastic lamina (IEL), medial attenuation and degree of lymphocytic inflammation of the peri‐adventitia, adventitia, media and intima. The individual scores of intimal fibroplasia, IEL disruption and medial attenuation were added to yield a ‘combined score (CS)’. Seventy‐eight 78 decedents were included in the final analysis following exclusion of 22 individuals for either lack of clinical information or inability to collect TA tissue. A total of 128 temporal artery specimens (50 bilateral from individual decedents, 28 unilateral) were available for examination. Intimal proliferation, IEL loss, IEL calcification and CS increased with age in a statistically significant fashion. Comparison of the oldest age group with the others showed statistically significant differences, although this was not uniformly preserved in comparison between the three youngest groups.ConclusionSenescent arterial changes and healed GCA exhibit histological similarity and such changes increase proportionally with age. The CS demonstrates significant association with age overall and represents a potential avenue for development to ‘normalise’ TA biopsies from older individuals.

Abstract B-cell activation is increasingly linked to numerous fibrotic lung diseases, and it is well known that aggregates of lymphocytes form in the lung of many of these patients. Activation of B-cells by pattern recognition receptors (PRRs) drives the release of inflammatory cytokines, chemokines, and metalloproteases important in the pathophysiology of pulmonary fibrosis. However, the specific mechanisms of B-cell activation in patients with idiopathic pulmonary fibrosis (IPF) are poorly understood. Herein, we have demonstrated that B-cell activation by microbial antigens contributes to the inflammatory and profibrotic milieu seen in patients with IPF. B-cell stimulation by CpG and β-glucan via PRRs resulted in activation of mTOR-dependent and independent pathways. Moreover, we showed that the B-cell–secreted inflammatory milieu is specific to the inducing antigen and causes differential fibroblast migration and activation. B-cell responses to infectious agents and subsequent B-cell–mediated fibroblast activation are modifiable by antifibrotics, but each seems to exert a specific and different effect. These results suggest that, upon PRR activation by microbial antigens, B-cells can contribute to the inflammatory and fibrotic changes seen in patients with IPF, and antifibrotics are able to at least partially reverse these responses.

Abstract Context. —Not uncommonly, a surgical pathologist will be requested to review excised material, with a clinical diagnosis of cancer, in which no malignancy can be identified. Often, sampling may be the issue. However, different nonneoplastic processes may mimic cancer clinically and not be recognized histologically. These are commonly referred to as pseudoneoplasms and can involve the lung, pleura, and mediastinum. Objective. —To review the most commonly encountered pseudoneoplasms of the thoracic cavity in surgical pathology and discuss the main differential diagnosis. Data Sources. —Literature and personal review of cases with focus on inflammatory pseudotumors of the lung, organizing pneumonia, nodular lymphoid hyperplasia, apical cap, round atelectasis, and sclerosing mediastinitis with its pulmonary counterpart, hyalinizing granuloma. Conclusions. —When reviewing specimens that appear nondiagnostic for malignancy, it is important to consider one of these pseudoneoplasms in the differential diagnosis as they may explain the clinical and radiologic information.

Abstract Context. —Diffuse pulmonary hemorrhage is an uncommon presenting manifestation of angiosarcoma. Objective. —To review the clinical, radiologic, and pathologic findings of patients with metastatic angiosarcoma who presented with diffuse pulmonary hemorrhage. Design. —Patients fulfilling inclusion criteria were identified from the consultation files. Clinical and radiologic data were obtained from referring pathologists. Histologic slides were reviewed in all patients. Results. —Our patients included 6 men and 1 woman, aged 31 to 73 years; 4 patients were younger than 40 years. Six patients presented with hemoptysis, and all had diffuse abnormalities on radiographic studies. Clinical considerations prior to biopsy included pulmonary hemorrhage syndrome (n = 2), acute respiratory failure (n = 1), and infection (n = 1). Metastatic disease was included in the differential diagnosis in only 1 patient. None had a diagnosis of malignancy prior to lung biopsy. All biopsies showed hemorrhage associated with atypical epithelioid and spindle cells, forming anastomosing vascular channels, distributed along and within lymphatics and arteries. Neoplastic cells were immunoreactive for factor VIII–related protein or CD31 in all cases for which special stains were available. Three patients with complete follow-up died of their disease. Primary sites were discovered in all 3 patients who underwent autopsy examination. Two tumors arose in the heart and 1 in the pelvic soft tissues. One additional patient had a likely primary site identified in the right atrium by cardiac ultrasound and was subsequently lost to follow-up. Conclusion. —Angiosarcoma should be included in the differential diagnosis of diffuse pulmonary hemorrhage, especially in young adults.

e19013 Background: Mutation profiling to assess for potentially druggable mutations in NSCLC is being offered at an increasing number of cancer centers throughout North America and internationally. Although data continue to accumulate for the potential value of mutation testing in designing chemotherapeutic regimens, the treatment impact of obtaining information beyond assessment of EGFR and ALK status remains unclear. How best to obtain and clinically utilize these data, including information from exome and whole genome sequencing, also remains unclear. Methods: Patients were reviewed electronically in a multidisciplinary conference regarding indications for testing and results of mutation profiling from various methods, including the mass-spec based LungCarta test, targeted NexGen sequencing, exome, and whole genome sequencing. Outcomes of the multidisciplinary review were communicated back to treating physicians. Results: Mutation testing was performed on 200 patients using a variety of approaches. The majority (>150) were surgically resected stage I and II tumors. Mutations in at least 1 major cancer driver gene, including EGFR, KRAS, MET, BRAF and PIK3CA, were found in 47% of all patients tested. EGFR mutations were present in 14.8% of patients tested, KRAS 21.3%, BRAF 2.6%, PIK3CA 3.2%, and MET 4.5%. A total of 8 patients underwent either exome or whole genome sequencing. A limited number of patients (<10) had mutation results that impacted treatment decisions from this cohort. Conclusions: Mutation profiling can influence treatment decisions in NSCLC, but at a low frequency. The role of exome and or whole genome sequencing for patients with NSCLC is evolving and remains undefined.

11119 Background: Evaluation of prognostic factors in carcinoid tumors of the lung is limited due to the rarity of disease. This study assessed Ki-67 expression and other clinical variables as prognostic factors in 262 patients. Methods: A systematic search of Mayo Clinic lung cancer epidemiology and tumor registry databases from 1997 to 2009 identified 449 consecutive patients, with 262 having available tissue blocks [40 atypical carcinoids (AC) and 222 typical carcinoids (TC)]. Clinical data were collected by chart review. Tissue blocks were reviewed by 1/3 pathologists using WHO criteria. Tumors were tested for the Ki-67 index using digital image analysis (tumor tracing) by two operators. The association and predictive value of the factors with recurrence-free and overall survival (RFS and OS) were explored using univariable Cox proportional Hazards model and concordance (c) index. Results: Age, stage, smoking history, lymph node (LN) involvement and Ki-67 index were significant prognostic factors for RFS and OS. Median follow-up on alive-patients is 5 years (range: 0.006-5). Median percentage of Ki-67 index of AC and TC were 1.61% and 0.56% (P<0.0001), respectively. Patients with Ki-67 ≥ 1% had significantly worse RFS (HR=3.69, P<0.0001) and OS (HR=3.69, P=0.0007) compared with Ki-67 < 1% group. The c-index of Ki-67 (0.65) was comparable to the pathologic distinction between AC and TC (0.62 for original diagnosis and 0.63 for central-reviewed diagnosis). Conclusions: Ki-67 index cutoff value of 1% is a valuable prognostic biomarker for pulmonary carcinoids based on this large cohort. Our data also provide strong evidence for clinical variables such as age, stage, smoking history, and LN involvement as clinical prognostic factors in pulmonary carcinoids. A prognostic calculator incorporating Ki-67 and clinical variables is under development. [Table: see text]