Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides.

Cancer diagnosis and management depend upon the extraction of complex information from microscopy images by pathologists, which requires time-consuming expert interpretation prone to human bias. Supervised deep learning approaches have proven powerful, but are inherently limited by the cost and quality of annotations used for training. Therefore, we present Histomorphological Phenotype Learning, a self-supervised methodology requiring no labels and operating via the automatic discovery of discriminatory features in image tiles. Tiles are grouped into morphologically similar clusters which constitute an atlas of histomorphological phenotypes (HP-Atlas), revealing trajectories from benign to malignant tissue via inflammatory and reactive phenotypes. These clusters have distinct features which can be identified using orthogonal methods, linking histologic, molecular and clinical phenotypes. Applied to lung cancer, we show that they align closely with patient survival, with histopathologically recognised tumor types and growth patterns, and with transcriptomic measures of immunophenotype. These properties are maintained in a multi-cancer study.

Diseases Involving the Lung Peribronchovascular Region: A CT Imaging Pathologic Classification.

TOPIC IMPORTANCE: Chest CT imaging holds a major role in the diagnosis of lung diseases, many of which affect the peribronchovascular region. Identification and categorization of peribronchovascular abnormalities on CT imaging can assist in formulating a differential diagnosis and directing further diagnostic evaluation. REVIEW FINDINGS: The peribronchovascular region of the lung encompasses the pulmonary arteries, airways, and lung interstitium. Understanding disease processes associated with structures of the peribronchovascular region and their appearances on CT imaging aids in prompt diagnosis. This article reviews current knowledge in anatomic and pathologic features of the lung interstitium composed of intercommunicating prelymphatic spaces, lymphatics, collagen bundles, lymph nodes, and bronchial arteries; diffuse lung diseases that present in a peribronchovascular distribution; and an approach to classifying diseases according to patterns of imaging presentations. Lung peribronchovascular diseases can appear on CT imaging as diffuse thickening, fibrosis, masses or masslike consolidation, ground-glass or air space consolidation, and cysts, acknowledging some disease may have multiple presentations. SUMMARY: A category approach to peribronchovascular diseases on CT imaging can be integrated with clinical features as part of a multidisciplinary approach for disease diagnosis.

Updates on lung adenocarcinoma: invasive size, grading and STAS.

Advancements in the classification of lung adenocarcinoma have resulted in significant changes in pathological reporting. The eighth edition of the tumour-node-metastasis (TNM) staging guidelines calls for the use of invasive size in staging in place of total tumour size. This shift improves prognostic stratification and requires a more nuanced approach to tumour measurements in challenging situations. Similarly, the adoption of new grading criteria based on the predominant and highest-grade pattern proposed by the International Association for the Study of Lung Cancer (IASLC) shows improved prognostication, and therefore clinical utility, relative to previous grading systems. Spread through airspaces (STAS) is a form of tumour invasion involving tumour cells spreading through the airspaces, which has been highly researched in recent years. This review discusses updates in pathological T staging, adenocarcinoma grading and STAS and illustrates the utility and limitations of current concepts in lung adenocarcinoma.

Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma.

Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-immune cells, and cell type-specific profiling in monocytes further improved outcome predictions. Additional analyses of tumor-adjacent transcriptomic data from The Cancer Genome Atlas validated the association of the inflammatory signature with worse outcomes across cancers. Collectively, our study suggests that molecular profiling of tumor-adjacent tissue can identify patients at high risk for disease progression.

Correlation of Programmed Death-Ligand 1 Expression With Lung Adenocarcinoma Histologic and Molecular Subgroups in Primary and Metastatic Sites.

Programmed death-ligand 1 (PD-L1) expression in terms of the tumor proportion score (TPS) is the main predictive biomarker approved for immunotherapy against lung nonsmall cell carcinoma. Although some studies have explored the associations between histology and PD-L1 expression in pulmonary adenocarcinoma, they have been limited in sample size and/or extent of examined histologic variables, which may have resulted in conflicting information. In this observational retrospective study, we identified primary and metastatic lung adenocarcinoma cases in the span of 5 years and tabulated the detailed histopathologic features, including pathological stage, tumor growth pattern, tumor grade, lymphovascular and pleural invasion, molecular alterations, and the associated PD-L1 expression for each case. Statistical analyses were performed to detect associations between PD-L1 and these features. Among 1658 cases, 643 were primary tumor resections, 751 were primary tumor biopsies, and 264 were metastatic site biopsies or resections. Higher TPS significantly correlated with high-grade growth patterns, grade 3 tumors, higher T and N stage, presence of lymphovascular invasion, and presence of MET and TP53 alterations, whereas lower TPS correlated with lower-grade tumors and presence of EGFR alterations. There was no difference in PD-L1 expression in matched primary and metastases, although higher TPS was observed in metastatic tumors due to the presence of high-grade patterns in these specimens. TPS showed a strong association with a histologic pattern. Higher-grade tumors had higher TPS, which is also associated with more aggressive histologic features. Tumor grade should be kept in mind when selecting cases and blocks for PD-L1 testing.

Histopathology of the Mitral Valve Residual Leaflet in Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: Mitral valve (MV) elongation is a primary hypertrophic cardiomyopathy (HCM) phenotype and contributes to obstruction. The residual MV leaflet that protrudes past the coaptation point is especially susceptible to flow-drag and systolic anterior motion. Histopathological features of MVs in obstructive hypertrophic cardiomyopathy (OHCM), and of residual leaflets specifically, are unknown. OBJECTIVES: The purpose of this study was to characterize gross, structural, and cellular histopathologic features of MV residual leaflets in OHCM. On a cellular-level, we assessed for developmental dysregulation of epicardium-derived cell (EPDC) differentiation, adaptive endocardial-to-mesenchymal transition and valvular interstitial cell proliferation, and genetically-driven persistence of cardiomyocytes in the valve. METHODS: Structural and immunohistochemical staining were performed on 22 residual leaflets excised as ancillary procedures during myectomy, and compared with 11 control leaflets from deceased patients with normal hearts. Structural components were assessed with hematoxylin and eosin, trichrome, and elastic stains. We stained for EPDCs, EPDC paracrine signaling, valvular interstitial cells, endocardial-to-mesenchymal transition, and cardiomyocytes. RESULTS: The residual leaflet was always at A2 segment and attached by slack, elongated and curlicued, myxoid chords. MV residual leaflets in OHCM were structurally disorganized, with expanded spongiosa and increased, fragmented elastic fibers compared with control leading edges. The internal collagenous fibrosa was attenuated and there was collagenous tissue overlying valve surfaces in HCM, with an overall trend toward decreased leaflet thickness (1.09 vs 1.47 mm, P = 0.08). No markers of primary cellular processes were identified. CONCLUSIONS: MV residual leaflets in HCM were characterized by histologic findings that were likely secondary to chronic hemodynamic stress and may further increase susceptibility to systolic anterior motion.

Extensive fibrosis in mediastinal seminoma is a diagnostic pitfall in small biopsies: two case reports.

Background: In mediastinal biopsies that show fibrosis, the differential diagnosis includes fibrosing mediastinitis, immunoglobulin G subclass 4-related disease, Hodgkin lymphoma, as well as reactive fibrotic and inflammatory changes adjacent to other processes including neoplasms. Cases Description: We report two cases of incidentally detected mediastinal seminoma that contained extensive areas of paucicellular fibrosis, which precluded accurate preoperative biopsy diagnosis. The fibrosis consisted of mildly inflamed, densely scarred tissue with thin dilated vessels, and was present to a significant extent that is suggestive of spontaneous regression. These features are not currently described in the World Health Organization Classification of Thoracic Tumors. In both patients, needle and open biopsies sampled only the fibrotic areas of the tumors, and the final diagnosis was not achieved until surgical excision was performed. After surgery, both patients received chemotherapy, and were alive without evidence of disease at 3.4 years and 1 year post-operatively, respectively. Tumor fibrosis composed approximately 95% and 50% of each patient's tumor, respectively. In one of the patients, correlation of the needle biopsy position with the positron emission tomography (PET) scan revealed that the biopsy needle had sampled a non-metabolically active portion of the tumor. Conclusions: While pathologic spontaneous regression is well-described in gonadal germ cell tumors, it is not well-reported in extragonadal locations. Prospective knowledge of this diagnostic pitfall and targeting PET-avid regions of the tumor may increase the diagnostic yield and help to avoid non-indicated surgical interventions.

The contribution of amyloid deposition in the aortic valve to calcification and aortic stenosis.

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits associated with CAVD, which could allow the use of antisense oligonucleotides and/or isotype gene therapies for the prevention and/or treatment of CAVD.

Pre-transplant immune cell function assay as a predictor of early cardiac allograft rejection.

INTRODUCTION: ImmuKnow, an immune cell function assay that quantifies overall immune system activity can assist in post-transplant immunosuppression adjustment. However, the utility of pre-transplant ImmuKnow results representing a patient's baseline immune system activity is unknown. This study sought to assess if pre-transplant ImmuKnow results are predictive of rejection at the time of first biopsy in our cardiac transplant population. METHODS: This is a single center, retrospective observational study of consecutive patients from January 1, 2018 to October 1, 2020 who underwent orthotopic cardiac transplantation at NYU Langone Health. Patients were excluded if a pre-transplant ImmuKnow assay was not performed. ImmuKnow results were categorized according to clinical interpretation ranges (low, moderate, and high activity), and patients were divided into two groups: a low activity group versus a combined moderate-high activity group. Pre-transplant clinical characteristics, induction immunosuppression use, early postoperative tacrolimus levels, and first endomyocardial biopsy results were collected for all patients. Rates of clinically significant early rejection (defined as rejection ≥ 1R/1B) were compared between pre-transplant ImmuKnow groups. RESULTS: Of 110 patients who underwent cardiac transplant, 81 had pre-transplant ImmuKnow results. The low ImmuKnow activity group was comprised of 15 patients, and 66 patients were in the combined moderate-high group. Baseline characteristics were similar between groups. Early rejection occurred in 0 (0%) patients with low pre-transplant ImmuKnow levels. Among the moderate- high pre-transplant ImmuKnow group, 16 (24.2%) patients experienced early rejection (P = .033). The mean ImmuKnow level in the non-rejection group was the 364.9 ng/ml of ATP compared to 499.3 ng/ml of ATP for those with rejection (P = .020). CONCLUSION: Patients with low pre-transplant ImmuKnow levels had lower risk of early rejection when compared with patients with moderate or high levels. Our study suggests a possible utility in performing pre-transplant ImmuKnow to identify patients at-risk for early rejection who may benefit from intensified upfront immunosuppression as well as to recognize those where slower calcineurin inhibitor initiation may be appropriate.

Rho Kinase Expression in Giant Cell Arteritis: Validating Phosphorylated Ezrin/Radixin/Moesin Intensity Score to Increase Sensitivity of Temporal Artery Biopsy.

OBJECTIVE: Aberrant Rho-associated protein kinase (ROCK) activity is implicated in several vascular and immunologic disorders. We previously demonstrated increased ROCK activity in histopathologically negative temporal artery biopsies (TABs) in subjects with clinical giant cell arteritis (GCA) compared to those without GCA. This current study aimed to examine ROCK activity in a larger cohort of biopsy-negative GCA subjects and to validate the prior findings. METHODS: Based on clinical data 6 months after TAB, subjects were categorized into 2 groups: biopsy-negative GCA and controls without GCA. Paraffin-embedded TABs were stained for phosphorylated ezrin/radixin/ moesin (pERM), a surrogate of ROCK activity, and scored by 2 pathologists blinded to clinical diagnosis using a previously derived scoring system measuring staining intensity in 3 areas of the vessel. RESULTS: Thirty-six subjects with biopsy-negative GCA and 43 controls were analyzed. The mean (SD) pERM intensity score in non-GCA subjects was 3.9 (1.4), compared to 5.0 (1.4) in those with GCA (P = 0.002). Using the predetermined cut-off of 4 to define high pERM intensity, subjects with GCA were significantly more likely to have a high pERM intensity score compared to non-GCA (odds ratio 3.67, 95% CI 1.19-11.36; P = 0.02. The sensitivity of high pERM intensity score for diagnosis of GCA in histologically negative TABs was 86% (95% CI 70-95). CONCLUSION: In this well-characterized cohort, those with biopsy-negative GCA had significantly higher pERM intensity scores compared to subjects without GCA. pERM staining has diagnostic significance in enhancing the sensitivity of TAB and may help to define the clinically important group of biopsy-negative GCA.

Expression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non-small cell lung cancer.

Most patients with non-small cell lung cancer (NSCLC) do not achieve durable clinical responses from immune checkpoint inhibitors, suggesting the existence of additional resistance mechanisms. Nicotinamide adenine dinucleotide (NAD)-induced cell death (NICD) of P2X7 receptor (P2X7R)-expressing T cells regulates immune homeostasis in inflamed tissues. This process is mediated by mono-adenosine 5'-diphosphate (ADP)-ribosyltransferases (ARTs). We found an association between membranous expression of ART1 on tumor cells and reduced CD8 T cell infiltration. Specifically, we observed a reduction in the P2X7R+ CD8 T cell subset in human lung adenocarcinomas. In vitro, P2X7R+ CD8 T cells were susceptible to ART1-mediated ADP-ribosylation and NICD, which was exacerbated upon blockade of the NAD+-degrading ADP-ribosyl cyclase CD38. Last, in murine NSCLC and melanoma models, we demonstrate that genetic and antibody-mediated ART1 inhibition slowed tumor growth in a CD8 T cell-dependent manner. This was associated with increased infiltration of activated P2X7R+CD8 T cells into tumors. In conclusion, we describe ART1-mediated NICD as a mechanism of immune resistance in NSCLC and provide preclinical evidence that antibody-mediated targeting of ART1 can improve tumor control, supporting pursuit of this approach in clinical studies.

Pulmonary Pathology of End-Stage COVID-19 Disease in Explanted Lungs and Outcomes After Lung Transplantation.

OBJECTIVES: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop end-stage lung disease requiring lung transplantation. We report the clinical course, pulmonary pathology with radiographic correlation, and outcomes after lung transplantation in three patients who developed chronic respiratory failure due to postacute sequelae of SARS-CoV-2 infection. METHODS: A retrospective histologic evaluation of explanted lungs due to coronavirus disease 2019 was performed. RESULTS: None of the patients had known prior pulmonary disease. The major pathologic findings in the lung explants were proliferative and fibrotic phases of diffuse alveolar damage, interstitial capillary neoangiogenesis, and mononuclear inflammation, specifically macrophages, with varying numbers of T and B lymphocytes. The fibrosis varied from early collagen deposition to more pronounced interstitial collagen deposition; however, pulmonary remodeling with honeycomb change was not present. Other findings included peribronchiolar metaplasia, microvascular thrombosis, recanalized thrombi in muscular arteries, and pleural adhesions. No patients had either recurrence of SARS-CoV-2 infection or allograft rejection following transplant at this time. CONCLUSIONS: The major pathologic findings in the lung explants of patients with SARS-CoV-2 infection suggest ongoing fibrosis, prominent macrophage infiltration, neoangiogenesis, and microvascular thrombosis. Characterization of pathologic findings could help develop novel management strategies.

Presentation, Diagnosis and Management of Innominate Artery Thromboembolism.

PURPOSE: Acute thromboembolic disease of the innominate artery (IA) poses a unique set of therapeutic challenges, owing to its contribution to both the cerebral and upper extremity circulation, and risks of distal embolization via the carotid and subclavian arteries, respectively. Herein, we present a 74-year-old female who presents with acute IA thrombus treated successfully with right axillary and common carotid exposure and aspiration catheter-directed mechanical thrombectomy (CDT). Furthermore, an emerging use of CDT and its application in acute thromboembolism are outlined. CASE REPORT: A 74-year-old female with history of right lung transplant for pulmonary fibrosis with severe pulmonary hypertension, and stage IIIA left lung adenocarcinoma status post left lower lobectomy undergoing adjuvant chemotherapy presented with acute IA thrombus and right-sided stroke. She was treated successfully with right axillary and common carotid exposure and aspiration CDT. Computed tomography angiography performed 1 month postoperatively confirmed patent IA with no evidence of residual or recurrent thrombus. CONCLUSION: There are currently no standard guidelines on the management of acute IA thromboembolism, with mostly individual cases reported in the literature describing this rare entity. Nevertheless, this unique clinical entity mandates expeditious diagnostic and therapeutic approaches in order to avoid permanent neurologic deficits from distal embolization. Our case demonstrates that aspiration CDT may be an effective treatment modality for patients with acute IA thrombus.

Histologic assessment of lower extremity deep vein thrombus from patients undergoing percutaneous mechanical thrombectomy.

BACKGROUND: Histologic analyses of deep vein thrombi (DVTs) have used autopsy samples and animal models. To the best of our knowledge, no previous study has reported on thrombus composition after percutaneous mechanical extraction. Because elements of chronicity and organization render thrombus resistant to anticoagulation and thrombolysis, a better understanding of clot evolution could inform therapy. METHODS: We performed a histologic evaluation of DVTs from consecutive patients who had undergone mechanical thrombectomy for extensive iliofemoral DVTs using the Clottriever/Flowtriever device (Inari Medical, Irvine, Calif). The DVTs were scored using a semiquantitative method according to the degree of fibrosis (collagen deposition on trichrome staining) and organization (endothelial growth with capillaries and fibroblastic penetration). RESULTS: Twenty-three specimens were available for analysis, with 20 presenting as acute DVT (≤14 days from symptom onset). Of the 23 patients, 11 (48%) had had >5% fibrosis (ie, collagen deposition) and 14 (61%) had had >5% organization (ie, endothelial growth, capillaries, fibroblasts). Four patients with acute DVT had had ≥25% organized thrombus and two had had ≥25% collagen deposition. Of the 20 patients with acute DVT, 40% had had >5% fibrosis and 55% had had >5% organization. The acuity of DVT did not correlate with the amount of fibrosis or organizing scores. CONCLUSIONS: A large proportion of patients with acute DVT will have histologic elements of chronicity and fibrosis. A better understanding of the relationship between such elements and the response to anticoagulant agents and fibrinolytic drugs could inform our approach to therapy.

Assessment of the feasibility of frozen sections for the detection of spread through air spaces (STAS) in pulmonary adenocarcinoma.

Spread through air spaces (STAS) is reportedly associated with worse prognosis in sublobar resections of lung adenocarcinoma. Recently, it was proposed that STAS detected on frozen sections can be an indication for lobectomy instead of sublobar resection. We undertook this study to evaluate the reliability of STAS assessment on frozen sections compared to permanent sections, as well as the associations among STAS, tumor grade, and recurrence-free survival (RFS) after sublobar resection. A total of 163 stage I lung adenocarcinoma resections with frozen sections were identified retrospectively. For each case, and for frozen and permanent sections separately, the presence or absence of STAS, as well as the tumor grade, were recorded. Compared to permanent sections, STAS detection on frozen sections had low sensitivity (55%), low positive predictive value (48%), and fair agreement (K = 0.34), whereas there was higher specificity (80%) and negative predictive value (85%). Accuracy was 74%. Tumor grade assessment on frozen sections showed higher sensitivity (77%), positive predictive value (90%), agreement (K = 0.72), specificity (94%), and accuracy (87%), and the same negative predictive value (85%). High-grade histology on frozen sections was associated with shorter RFS (p = 0.02), whereas STAS on frozen sections was not (p = 0.47). Our results suggest that the intraoperative detection of STAS has low sensitivity and positive predictive value. False-positive results may lead to overtreatment of patients with lung cancer. The determination of tumor grade on frozen sections offers better sensitivity and specificity, plus it is associated with RFS, whereas STAS on frozen sections is not. Further study is needed to explore the utility of assessing tumor grade on frozen sections.

Cardiogenic shock complicating multisystem inflammatory syndrome following COVID-19 infection: a case report.

BACKGROUND: With the high prevalence of COVID-19 infections worldwide, the multisystem inflammatory syndrome in adults (MIS-A) is becoming an increasingly recognized entity. This syndrome presents in patients several weeks after infection with COVID-19 and is associated with thrombosis, elevated inflammatory markers, hemodynamic compromise and cardiac dysfunction. Treatment is often with steroids and intravenous immunoglobulin (IVIg). The pathologic basis of myocardial injury in MIS-A, however, is not well characterized. In our case report, we obtained endomyocardial biopsy that revealed a pattern of myocardial injury similar to that found in COVID-19 cardiac specimens. CASE PRESENTATION: A 26-year-old male presented with fevers, chills, headache, nausea, vomiting, and diarrhea 5 weeks after his COVID-19 infection. His SARS-CoV-2 PCR was negative and IgG was positive, consistent with prior infection. He was found to be in cardiogenic shock with biventricular failure, requiring inotropes and diuretics. Given concern for acute fulminant myocarditis, an endomyocardial biopsy (EMB) was performed, showing an inflammatory infiltrate consisting predominantly of interstitial macrophages with scant T lymphocytes. The histologic pattern was similar to that of cardiac specimens from COVID-19 patients, helping rule out myocarditis as the prevailing diagnosis. His case was complicated by persistent hypoxemia, and a computed tomography scan revealed pulmonary emboli. He received IVIg, steroids, and anticoagulation with rapid recovery of biventricular function. CONCLUSIONS: MIS-A should be considered as the diagnosis in patients presenting several weeks after COVID-19 infection with severe inflammation and multi-organ involvement. In our case, EMB facilitated identification of MIS-A and guided therapy. The patient's biventricular function recovered with IVIg and steroids.

CUL4high Lung Adenocarcinomas Are Dependent on the CUL4-p21 Ubiquitin Signaling for Proliferation and Survival.

Cullin (CUL) 4A and 4B ubiquitin ligases are often highly accumulated in human malignant neoplasms and are believed to possess oncogenic properties. However, the underlying mechanisms by which CUL4A and CUL4B promote pulmonary tumorigenesis remain largely elusive. This study reports that CUL4A and CUL4B are highly expressed in patients with non-small cell lung cancer (NSCLC), and their high expression is associated with disease progression, chemotherapy resistance, and poor survival in adenocarcinomas. Depletion of CUL4A (CUL4Ak/d) or CUL4B (CUL4Bk/d) leads to cell cycle arrest at G1 and loss of proliferation and viability of NSCLC cells in culture and in a lung cancer xenograft model, suggesting that CUL4A and 4B are oncoproteins required for tumor maintenance of certain NSCLCs. Mechanistically, increased accumulation of the cell cycle-dependent kinase inhibitor p21/Cip1/WAF1 was observed in lung cancer cells on CUL4 silencing. Knockdown of p21 rescued the G1 arrest of CUL4Ak/d or CUL4Bk/d NSCLC cells, and allowed proliferation to resume. These findings reveal that p21 is the primary downstream effector of lung adenocarcinoma dependence on CUL4, highlight the notion that not all substrates respond equally to abrogation of the CUL4 ubiquitin ligase in NSCLCs, and imply that CUL4Ahigh/CUL4Bhigh may serve as a prognostic marker and therapeutic target for patients with NSCLC.

A novel approach to percutaneous aortic thrombectomy.

Aortic mural thrombus in the absence of underlying aortic disease is rare and results in a risk of distant arterial embolization that can result in limb loss or other end organ damage. Current management involves open surgery, anticoagulation, and systemic thrombolysis; however, each carries inherent risks. We report the case of aortic thrombus with distal emboli in two patients, a 56-year-old man and a 68-year-old man, neither with underlying aortic pathology and both presenting with limb threatening ischemia. We performed percutaneous mechanical thrombectomy using the FlowTriever System (Inari Medical, Irvine, Calif) with successful removal of the aortic thrombus in both patients.