Intrathoracic Lymph Node Microcalcifications are Associated With a High Prevalence of Malignancy and Anaplastic Lymphoma Kinase Rearrangement: The "Calce" Study.


Journal

Journal of bronchology & interventional pulmonology
ISSN: 1948-8270
Titre abrégé: J Bronchology Interv Pulmonol
Pays: United States
ID NLM: 101496866

Informations de publication

Date de publication:
01 Jul 2024
Historique:
received: 14 12 2023
accepted: 20 05 2024
medline: 1 7 2024
pubmed: 1 7 2024
entrez: 1 7 2024
Statut: epublish

Résumé

Microcalcifications are acknowledged as a malignancy risk factor in multiple cancers. However, the prevalence and association of intrathoracic lymph node (ILN) calcifications with malignancy remain unexplored. In this cross-sectional study, we enrolled patients with known/suspected malignancy and an indication for endosonography for diagnosis or ILN staging. We assessed the prevalence and pattern of calcified ILNs and the prevalence of malignancy in ILNs with and without calcifications. In addition, we evaluated the genomic profile and PD-L1 expression in lung cancer patients, stratifying them based on the presence or absence of ILN calcifications. A total of 571 ILNs were sampled in 352 patients. Calcifications were detected in 85 (24.1%) patients and in 94 (16.5%) ILNs, with microcalcifications (78/94, 83%) being the predominant type. Compared with ILNs without calcifications (214/477, 44.9%), the prevalence of malignancy was higher in ILNs with microcalcifications (73/78, 93.6%; P<0.0001) but not in those with macrocalcifications (7/16, 43.7%; P=0.93). In patients with lung cancer, the high prevalence of metastatic involvement in ILNs displaying microcalcifications was independent of lymph node size (< or >1 cm) and the clinical stage (advanced disease; cN2/N3 disease; cN0/N1 disease). The anaplastic lymphoma kinase (ALK) rearrangement was significantly more prevalent in patients with than in those without calcified ILNs (17.4% vs. 1.7%, P<0.001), and all of them exhibited microcalcifications. ILN microcalcifications are common in patients undergoing endosonography for suspected malignancy, and they are associated with a high prevalence of metastatic involvement and ALK rearrangement.

Sections du résumé

BACKGROUND BACKGROUND
Microcalcifications are acknowledged as a malignancy risk factor in multiple cancers. However, the prevalence and association of intrathoracic lymph node (ILN) calcifications with malignancy remain unexplored.
METHODS METHODS
In this cross-sectional study, we enrolled patients with known/suspected malignancy and an indication for endosonography for diagnosis or ILN staging. We assessed the prevalence and pattern of calcified ILNs and the prevalence of malignancy in ILNs with and without calcifications. In addition, we evaluated the genomic profile and PD-L1 expression in lung cancer patients, stratifying them based on the presence or absence of ILN calcifications.
RESULTS RESULTS
A total of 571 ILNs were sampled in 352 patients. Calcifications were detected in 85 (24.1%) patients and in 94 (16.5%) ILNs, with microcalcifications (78/94, 83%) being the predominant type. Compared with ILNs without calcifications (214/477, 44.9%), the prevalence of malignancy was higher in ILNs with microcalcifications (73/78, 93.6%; P<0.0001) but not in those with macrocalcifications (7/16, 43.7%; P=0.93). In patients with lung cancer, the high prevalence of metastatic involvement in ILNs displaying microcalcifications was independent of lymph node size (< or >1 cm) and the clinical stage (advanced disease; cN2/N3 disease; cN0/N1 disease). The anaplastic lymphoma kinase (ALK) rearrangement was significantly more prevalent in patients with than in those without calcified ILNs (17.4% vs. 1.7%, P<0.001), and all of them exhibited microcalcifications.
CONCLUSION CONCLUSIONS
ILN microcalcifications are common in patients undergoing endosonography for suspected malignancy, and they are associated with a high prevalence of metastatic involvement and ALK rearrangement.

Identifiants

pubmed: 38946295
doi: 10.1097/LBR.0000000000000973
pii: 01436970-202407010-00010
pii:
doi:

Substances chimiques

Anaplastic Lymphoma Kinase EC 2.7.10.1
ALK protein, human EC 2.7.10.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure: The authors declare no conflict of interest.

Références

Vidavsky N, Kunitake JAMR, Estroff L. Multiple pathways for pathological calcification in the human body. Adv Healthc Mater. 2021;10:e2001271.
Bonfiglio R, Granaglia A, Giocondo R, et al. Molecular aspects and prognostic significance of microcalcifications in human pathology: a narrative review. Int J Mol Sci. 2021;22:120.
D’Orsi C, Sickles E, Mendelson E, et al. ACR BI-RADS Atlas, Breast Imaging Reporting and Data System, 5th ed. American College of Radiology; 2013.
Eghtedari M, Chong A, Rakow-Penner R, et al. Current status and future of BI-RADS in multimodality imaging, from the AJR special series on radiology reporting and data system. Am J Roentgenol. 2021;2016:860–873.
Cen D, Xu L, Zhang S, et al. BI-RADS 3–5 microcalcifications: prediction of lymph node metastasis of breast cancer. Oncotarget. 2017;8:30190–30198.
Haugen BR, Alexander EK, Bible KC, et al. 2015 ATA management guidelines for adult patients with thyroid nodules and differentiated thyroid carcinoma. Thyroid. 2016;26:1–133.
Perros P, Boelaert K, Colley S, et al. British Thyroid Association Guidelines for the management of thyroid carcinoma. Clin Endocrinol. 2014;81(suppl 1):1–122.
Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules—2016 update. Endocr Pract. 2016;22:622–639.
Frates MC, Benson CB, Charboneau JW, et al. Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Radiology. 2005;237:794–800.
Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167–1214.
Tot T, Gere M, Hofmeyer S, et al. The clinical value of detecting microcalcifications on a mammogram. Semin Canc Biol. 2021;72:165–174.
Kim H, Jang SJ, Chung DH, et al. A comprehensive comparative analysis of the histomorphological features of ALK-rearranged lung adenocarcinoma based on driver oncogene mutations: frequent expression of epithelial-mesenchymal transition markers than other genotype. PLoS One. 2013;8:e76999.
Fujiwara T, Yasufuku K, Nakajima T, et al. The utility of sonographic features during endobronchial ultrasound-guided transbronchial needle aspiration for lymph node staging in patients with lung cancer: a standard endobronchial ultrasound image classification system. Chest. 2010;138:641–647.
Hylton DA, Turner J, Shargall Y, et al. Ultrasonographic characteristics of lymph nodes as predictors of malignancy during endobronchial ultrasound (EBUS): a systematic review. Lung Cancer. 2018;126:97–105.
Evison M, Morris J, Martin J, et al. Nodal staging in lung cancer: a risk stratification model for lymph nodes classified as negative by EBUS-TBNA. J Thorac Oncol. 2015;10:126–133.
Hylton DA, Turner S, Kidane B, et al. The Canada Lymph Node Score for prediction of malignancy in mediastinal lymph nodes during endobronchial ultrasound. J Thorac Cardiovasc Surg. 2020;159:2499–2507.
Wang Memoli JS, El-Bayoumi E, Pastis NJ, et al. Using endobronchial ultrasound features to predict lymph node metastasis in patients with lung cancer. Chest. 2011;140:1550–1556.
Schmid-Bindert G, Jiang H, Kähler G, et al. Predicting malignancy in mediastinal lymph nodes by endobronchial ultrasound: a new ultrasound scoring system. Respirology. 2012;17:1190–1198.
Shafiek H, Fiorentino F, Peralta AD, et al. Real-time prediction of mediastinal lymph node malignancy by endobronchial ultrasound. Arch Bronconeumol. 2014;50:228–234.
Verhoeven RLJ, Leoncini F, Slotman J, et al. Accuracy and reproducibility of endoscopic ultrasound B-mode features for observer-based lymph nodal malignancy prediction. Respiration. 2021;100:1088–1096.
Morishita M, Uchimura K, Furuse H, et al. Predicting malignant lymph nodes using a novel scoring system based on multi-endobronchial ultrasound features. Cancers. 2022;14:5355.
Gogia P, Insaf TZ, McNulty W, et al. Endobronchial ultrasound: morphological predictors of benign disease. ERJ Open Res. 2016;2:00053-2015.
Sun J, Zhi X, Chen J, et al. Endobronchial ultrasound multimodal imaging for the diagnosis of intrathoracic lymph nodes. Respiration. 2021;100:898–908.
Alici IO, Demirci NY, Yilmaz A, et al. The sonographic features of malignant mediastinal lymph nodes and a proposal for an algorithmic approach for sampling during endobronchial ultrasound. Clin Respir J. 2016;10:606–613.
Ayub I, Mohan A, Madan K, et al. Identification of specific EBUS sonographic characteristics for predicting benign mediastinal lymph nodes. Clin Respir J. 2016;12:681–690.
Wang L, Wu W, Teng J, et al. Sonographic features of endobronchial ultrasonography predict intrathoracic lymph node metastasis in lung cancer. Ann Thorac Surg. 2015;100:1203–1210.
Trisolini R, Cancellieri A, Livi V, et al. Pulmonary adenocarcinoma with psammoma bodies is associated with a specific endobronchial ultrasound pattern and a high prevalence of actionable driver mutations. Lung Cancer. 2020;147:204–208.
Tahvildari AM, Pain L, Kong CS, et al. Sonographic-pathologic correlation for puctate echogenic reflectors in papillary thyroid carcinoma. J Ultrasound Med. 2016;35:1645–1652.
Nakanishi K, Nakagawa K, Asakura K, et al. Is calcification in the regional lymph nodes a benign feature in patients with lung cancer? World J Surg. 2019;43:1850–1856.
Shweihat YR, Samant RS, Joshi M, et al. Endobronchial ultrasound-guided transbronchial needle aspiration in a geographical region with endemic histoplasmosis infection. J Bronchol Intervent Pulmonol. 2010;17:295–300.
Kim YK, Lee KS, Kim B-T, et al. Mediastinal nodal staging of non-small cell lung cancer using integrated 18FDG PET/CT in a tuberculosis-endemic country. Diagnostic efficacy in 674 patients. Cancer. 2007;109:1068–1077.
Das DK. Psammoma body; a product of dystrophic calcification or of a biologically active process that aims at limiting the growth and spread of tumor? Diagn Cytopathol. 2009;37:534–541.
Miyake A, Okudela K, Matsumura M, et al. Update on the potential significance of psammoma bodies in lung adenocarcinoma from a modern perspective. Histopathology. 2018;72:609–618.
Izumi M, Suzumura T, Ogawa K, et al. Differences in molecular epidemiology of lung cancer among ethnicities (Asian vs. Caucasian). J Thorac Dis. 2020;12:3776–3784.

Auteurs

Fausto Leoncini (F)

Interventional Pulmonology Division, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome.

Giovanni Sotgiu (G)

Clinical Epidemiology and Medical Statistics Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari.

Alessandra Cancellieri (A)

Pathology Division.

Mariangela Puci (M)

Clinical Epidemiology and Medical Statistics Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari.

Stefania Cortese (S)

Pulmonology Division, Fondazione Policlinico Universitario A. Gemelli IRCCS.

Vanina Livi (V)

Interventional Pulmonology Division, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome.

Jacopo Simonetti (J)

Pulmonology Division, Fondazione Policlinico Universitario A. Gemelli IRCCS.

Daniela Paioli (D)

Interventional Pulmonology Division, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome.

Daniele Magnini (D)

Interventional Pulmonology Division, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome.

Federico Cappuzzo (F)

Medical Oncology Division, IRCCS Regina Elena National Cancer Institute.

Emilio Bria (E)

Thoracic Oncology Division, Comprehensive Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Rocco Trisolini (R)

Interventional Pulmonology Division, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH