Supplementary Table S7: Lung cancers characteristics diagnosed during the active phase of the LEAP study based on the selection method for inclusion criteria: NLST criteria vs broadened criteria (≥ 20 pack-years, ≥ 50 years old, one additional lung cancer risk factor)

Supplementary Figure S1: Map of participating study centers

Supplementary Table S4: LDCT screening results in the LEAP cohort by centers

Supplementary Table S5: Characteristics of screen-detected lung cancers and during follow-up in the LEAP cohort

Supplementary Table S2: Management procedures for positive screening tests within the LEAP cohort, all sites.

Supplementary Table S8: Comparison of lung cancer incidence between the LEAP cohort and the NLST, stratified by age at enrollment, sex, pack-year cigarette use and race.

BACKGROUND:Blood-based biomarkers could improve the effectiveness of lung cancer screening (LCS) with low-dose CT (LDCT) through more accurate lung cancer risk stratification and nodule malignancy risk assessment. The Lung Cancer, Early Detection, Assessment of Risk, and Prevention (LEAP) study aims to establish a reference set to validate promising cancer biomarkers in the context of LCS. METHODS:This prospective international cohort study (United States, France, and Spain) enrolled individuals with elevated risk of developing lung cancer based on National Comprehensive Cancer Network Guidelines into an LCS program. Participants underwent three annual rounds of LDCT-LCS, with blood specimens collected at each time point. Questionnaires and medical chart reviews were utilized to determine participants' cancers status. RESULTS:Between 2014 and 2019, 2,841 participants were enrolled who underwent LDCT: 2,841 at baseline, 2,097 at year 1 (74%), and 1,779 at year 2 (63%). Rates at baseline, year 1, and year 2 were positive scans (13%, 7.5%, and 7.5%, respectively), false positives (12%, 6.8%, and 6.9%, respectively), and screen-detected lung cancer (0.9%, 0.9%, and 0.7%, respectively). After 5 years of follow-up, 74 lung cancer cases were detected: 55% stage I, 11% stage II, 16% stage III, and 12% stage IV. The LEAP biobank collected 6,586 blood specimens, including 126 (lung) and 201 (other) prediagnostic samples within 5 years of diagnosis. CONCLUSIONS:The LEAP cohort provides a resource with a longitudinal database of participant data, LDCT imaging, and matched blood specimens for biomarker validation, aiming to address unmet clinical needs in LCS. IMPACT:LEAP provides longitudinal biospecimens linked with clinical follow-up and LDCT imaging for biomarker validation in the context of imaging findings and lung cancer diagnosis.

Context.-The need for appropriate specimen use for ancillary testing has become more commonplace in the practice of pathology. This, coupled with improvements in technology, often provides less invasive methods of testing, but presents new challenges to appropriate specimen collection and handling of these small specimens, including thoracic small biopsy and cytology samples. Objective.-To develop a clinical practice guideline including recommendations on how to obtain, handle, and process thoracic small biopsy and cytology tissue specimens for diagnostic testing and ancillary studies. Methods.-The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Core needle biopsy, touch preparation, fine-needle aspiration, and effusion specimens with thoracic diseases including malignancy, granulomatous process/sarcoidosis, and infection (eg, tuberculosis) were deemed within scope. Ancillary studies included immunohistochemistry and immunocytochemistry, fluorescence in situ hybridization, mutational analysis, flow cytometry, cytogenetics, and microbiologic studies routinely performed in the clinical pathology laboratory. The use of rapid on-site evaluation was also covered. Results.-Sixteen guideline statements were developed to assist clinicians and pathologists in collecting and processing thoracic small biopsy and cytology tissue samples. Conclusions.-Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation helpful in appropriate triage, handling, and processing of specimens.

CONTEXT.—The need for appropriate specimen use for ancillary testing has become more commonplace in the practice of pathology. This, coupled with improvements in technology, often provides less invasive methods of testing, but presents new challenges to appropriate specimen collection and handling of these small specimens, including thoracic small biopsy and cytology samples.OBJECTIVE.—To develop a clinical practice guideline including recommendations on how to obtain, handle, and process thoracic small biopsy and cytology tissue specimens for diagnostic testing and ancillary studies.METHODS.—The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Core needle biopsy, touch preparation, fine-needle aspiration, and effusion specimens with thoracic diseases including malignancy, granulomatous process/sarcoidosis, and infection (eg, tuberculosis) were deemed within scope. Ancillary studies included immunohistochemistry and immunocytochemistry, fluorescence in situ hybridization, mutational analysis, flow cytometry, cytogenetics, and microbiologic studies routinely performed in the clinical pathology laboratory. The use of rapid on-site evaluation was also covered.RESULTS.—Sixteen guideline statements were developed to assist clinicians and pathologists in collecting and processing thoracic small biopsy and cytology tissue samples.CONCLUSIONS.—Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation remains helpful in appropriate triage, handling, and processing of specimens.

Radiation-associated sarcomas are rare and aggressive types of sarcomas that can occur after exposure to ionizing radiation. We examine a case of radiation-associated undifferentiated/unclassified soft-tissue sarcoma with primary disease in the chest wall. The optimal treatment of these patients is surgical resection if possible; however, the role of chemotherapy has not been well defined. The patient described herein had a central tumor in the chest wall. Since many of these patients have borderline resectable tumors, the use of neoadjuvant chemotherapy may be helpful to downstage the tumors for possible surgical resection. In this case, doxorubicin plus ifosfamide chemotherapy was employed with a favorable therapeutic effect prior to being resected. To our knowledge this is the first report of greater than 90% necrosis in a patient with radiation-associated undifferentiated/unclassified soft-tissue sarcoma treated with chemotherapy for a borderline resectable mass.

Procedure Appropriateness Category Relative Radiation Level Radiography chest Usually Appropriate ☢ CT chest with IV contrast May Be Appropriate ☢☢☢ CT chest without IV contrast May Be Appropriate ☢☢☢ MRI chest without and with IV contrast Usually Not Appropriate O MRI chest without IV contrast Usually Not Appropriate O CT chest without and with IV contrast Usually Not Appropriate ☢☢☢ FDG-PET/CT skull base to mid-thigh Usually Not Appropriate ☢☢☢☢

OBJECTIVE The U.S. Preventive Services Task Force recommendation and Centers for Medicare & Medicaid Services coverage decision have created a favorable environment for implementation of clinical population-wide lung cancer screening. The purpose of this article is to describe effective recruitment methods for clinical lung cancer screening programs, with a focus on addressing barriers to screening for socioeconomically disadvantaged communities. CONCLUSION Large-scale recruitment of high-risk individuals into screening programs across the country is essential to significantly decrease the mortality associated with lung cancer. Recruitment strategies must also be tailored to minority and underserved communities, because they are at the highest risk for developing lung cancer.

We report the first case of calcifying fibrous pseudotumor (CFPT) to arise in the posterior mediastinum with encapsulation of the thoracic duct. This exceedingly rare lesion was incidentally discovered in an asymptomatic young woman and treated with surgical resection, requiring ligation and excision of the thoracic duct. There has been no evidence of tumor recurrence or postoperative complication.

PURPOSE OF REVIEW:Necrotizing sarcoid granulomatosis (NSG) is rare. Its various clinical and histological presentations are ambiguous and confusing. Although sometimes limited only to the lungs, other organ systems can be involved. The disease affects primarily women in their late forties but has been documented in children.RECENT FINDINGS:There are two schools of thought regarding the taxonomical position of NSG. Some believe that it is an independent entity, whereas others argue that it is just another manifestation of sarcoidosis. This article will review the available, current and evidence-based information about clinical and basic science aspects of NSG.SUMMARY:Diagnosis of NSG is perplexing; its pathogenesis is a dilemma. The disease is frequently confused with other processes including malignancy, Wegener's granulomatosis, hypersensitivity pneumonitis, sarcoidosis and lymphoid granulomatosis. Its symptoms are nonspecific and a histology finding of necrotizing granuloma has many causes. Although no specific management tool or strategies are advocated, steroids, surgical resection of localized disease or sometimes watchful waiting are recommended.

Purpose of review Cardiac involvement in sarcoidosis is not always associated with a wide spread of disease, but when present, has been linked with a relatively poor prognosis. This review will delve into new genetic associations, recently reported clinical manifestations and complementary radiographic tools that aid with diagnosis and follow-up. Recent findings Clinical manifestations, diagnosis and management remain an intricate maze. Genetic predisposition and associations that include HLA class II molecules and polymorphisms in tumor necrosis factor-α have been reported due in part to weakened arguments suggesting autoimmune disorders or dysregulation. In addition, further symptomatologies have been reported that assist with diagnosis. Radiographic tools including Microvolt T wave alternans, cardiovascular magnetic resonance, late gadolinium enhancement and cardiac assist devices, recently being used, are shedding some light on the diagnostic challenges. Summary Cardiac involvement in sarcoidosis remains a challenging dilemma, relying on a combination of clinical findings and imaging abnormalities because no single diagnostic test has yet emerged with a high degree of specificity and sensitivity. Given its life-threatening nature, prompt establishment of a diagnosis, an aggressive management strategy and devices to prolong life should be pursued.