Caracterización de tumores primarios de tiroides con arquitectura folicular y cambios nucleares similares a los del carcinoma papilar en pacientes del hospital universitario nacional, 2020-2023
| dc.contributor.advisor | Olaya Morales, Natalia | |
| dc.contributor.author | Quijano Turizo, Jose Miguel | |
| dc.contributor.educationalvalidator | Tarquino Gonzalez Jonathan Steve | |
| dc.coverage.city | Bogotá | |
| dc.coverage.country | Colombia | |
| dc.coverage.temporal | 2020-2023 | |
| dc.date.accessioned | 2026-02-05T18:44:18Z | |
| dc.date.available | 2026-02-05T18:44:18Z | |
| dc.date.issued | 2025 | |
| dc.description | ilustraciones a color, diagramas, fotografías | spa |
| dc.description.abstract | Introducción: Diferenciar entre neoplasias tiroideas con arquitectura folicular y cambios nucleares similares a los del carcinoma papilar puede resultar complejo. Objetivo: Caracterizar tumores primarios de tiroides bien diferenciados con arquitectura folicular y score nuclear ≥2, describiendo sus perfiles demográficos y morfológicos, determinando los rasgos nucleares por histopatología convencional y analizando cuantitativamente las características nucleares usando herramientas de patología digital. Métodos: Estudio observacional analítico, retrospectivo, de corte transversal en pacientes del Hospital Universitario Nacional de Colombia (2020–2023). Se realizó el análisis digital de 921 microfotografías y se segmentaron 88.501 núcleos de células foliculares tiroideas, incluyendo control de tejido tiroideo benigno y PTC clásico, mediante QuPath y StarDist. Posteriormente se realizaron comparaciones mediante U de Mann–Whitney y Kruskal–Wallis con Dunn-Bonferroni. Resultados y conclusiones: Los diagnósticos más frecuentes de la cohorte analizada fueron NIFTP y PTCfi. Las neoplasias malignas correspondieron a pacientes con una edad promedio más alta y tumores de menor tamaño. NIFTP se asoció a categorías Bethesda III–IV, mientras que el PTCfi con Bethesda V–VI. Los NIFTP evidenciaron predominantemente un score nuclear de 2, mientras que las neoplasias malignas (IEFVPTC y PTCfi) un score nuclear de 3. Las pseudoinclusiones fueron mucho más frecuentes en el PTCfi. Se identificaron diferencias significativas en la circularidad y la textura nuclear entre las neoplasias con arquitectura folicular y una puntuación nuclear ≥2. Las neoplasias de bajo riesgo (NIFTP, WDT-UMP) mostraron núcleos más circulares, con mayor entropía y contraste que los de las neoplasias malignas (IEFVPTC y PTCfi). (Texto tomado de la fuente) | spa |
| dc.description.abstract | Introduction: Differentiating thyroid neoplasms with follicular architecture and nuclear changes resembling those of papillary carcinoma remains challenging. Objective: This study aimed to characterize well-differentiated primary thyroid tumors with follicular architecture and nuclear score ≥2 by describing their demographic and morphologic profiles, determining nuclear features through conventional histopathology, and quantitatively analyzing digital nuclear characteristics using digital pathology. Methods: An observational, analytical, retrospective, cross-sectional study was conducted in patients at the National University Hospital of Colombia (2020–2023). Digital analysis of 921 microphotographs was performed, segmenting 88,501 nuclei of thyroid follicular cells, including controls of benign thyroid tissue and classic papillary thyroid carcinoma (PTC), using QuPath and StarDist. Statistical comparisons were performed using the Mann–Whitney U and Kruskal–Wallis tests with Dunn–Bonferroni correction. Results and conclusions: The most frequent diagnoses in the analyzed cohort were NIFTP and PTCfi. Malignant neoplasms occurred in patients with a higher mean age and smaller tumor size. NIFTP was associated with Bethesda categories III–IV, whereas PTCfi was associated with Bethesda V–VI. NIFTP predominantly exhibited a nuclear score of 2, while malignant neoplasms (IEFVPTC and PTCfi) showed a nuclear score of 3. Pseudoinclusions were markedly more frequent in PTCfi. Significant differences were identified in nuclear circularity and texture among neoplasms with follicular architecture and nuclear score ≥2. Low-risk neoplasms (NIFTP, WDT-UMP) displayed more circular nuclei with higher entropy and contrast than malignant neoplasms (IEFVPTC and PTCfi). | eng |
| dc.description.degreelevel | Especialidades Médicas | |
| dc.description.degreename | Especialista en Patología Anatómica y Clínica | |
| dc.description.methods | observacional analítico. | |
| dc.description.notes | . | |
| dc.description.technicalinfo | . | |
| dc.format.extent | 108 páginas | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.instname | Universidad Nacional de Colombia | spa |
| dc.identifier.reponame | Repositorio Institucional Universidad Nacional de Colombia | spa |
| dc.identifier.repourl | https://repositorio.unal.edu.co/ | spa |
| dc.identifier.uri | https://repositorio.unal.edu.co/handle/unal/89403 | |
| dc.language.iso | spa | |
| dc.publisher | Universidad Nacional de Colombia | |
| dc.publisher.branch | Universidad Nacional de Colombia - Sede Bogotá | |
| dc.publisher.faculty | Facultad de Medicina | |
| dc.publisher.place | Bogotá, Colombia | |
| dc.publisher.program | Bogotá - Medicina - Especialidad en Patología Anatómica y Clínica | |
| dc.relation.references | Tallini, G., Tuttle, R. M., & Ghossein, R. A. (2016). The History of the Follicular Variant of Papillary Thyroid Carcinoma. In The Journal of Clinical Endocrinology & Metabolism (Vol. 102, Issue 1, pp. 15–22). The Endocrine Society. https://doi.org/10.1210/jc.2016-2976 | |
| dc.relation.references | Kholová, I., Haaga, E., Ludvik, J., Kalfert, D., & Ludvikova, M. (2022). Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Tumour Entity with a Short History. A Review on Challenges in Our Microscopes, Molecular and Ultrasonographic Profile. Diagnostics, 12(2), 250. https://doi.org/10.3390/diagnostics12020250 | |
| dc.relation.references | Williams, E. D. (2000). Guest Editorial: Two Proposals Regarding the Terminology of Thyroid Tumors. International Journal of Surgical Pathology, 8(3), 181–183. doi:10.1177/10668969000080030 | |
| dc.relation.references | Nikiforov, Y. E., Seethala, R. R., Tallini, G., Baloch, Z. W., Basolo, F., Thompson, L. D. R., Barletta, J. A., Wenig, B. M., Al Ghuzlan, A., Kakudo, K., Giordano, T. J., Alves, V. A.,Khanafshar, E., Asa, S. L., El-Naggar, A. K., Gooding, W. E., Hodak, S. P., Lloyd, R. V., Maytal, G., … Ghossein, R. A. (2016). Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma. In JAMA Oncology (Vol. 2, Issue 8, p. 1023). American Medical Association (AMA). https://doi.org/10.1001/jamaoncol.2016.0386 | |
| dc.relation.references | R. Lloyd, R. Osamura, G. Kloppel, J. Rosai. WHO classification of tumours of endocrine organs, 4th edn. (International Agency for Research on Cancer, Lyon, France, 2017) | |
| dc.relation.references | Basolo, F., Macerola, E., Poma, A.M. et al. The 5th edition of WHO classification of tumors of endocrine organs: changes in the diagnosis of follicular-derived thyroid carcinoma. Endocrine 80, 470–476 (2023). https://doi.org/10.1007/s12020-023-03336-4 | |
| dc.relation.references | WHO Classification of Tumours Editorial Board. Endocrine and neuroendocrine tumours. Lyon (France): International Agency for Research on Cancer; 2022. (WHO classification of tumours series, 5th ed.; vol. 10). | |
| dc.relation.references | Jung CK, Bychkov A, Kakudo K. Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach. Endocrinol Metab (Seoul). 2022;37(5):703-718. doi:10.3803/EnM.2022.1553 | |
| dc.relation.references | Seethala, R., Baloch, Z., Barletta, J. et al. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a review for pathologists. Mod Pathol 31, 39–55 (2018). https://doi.org/10.1038/modpathol.2017.130 | |
| dc.relation.references | Alves, V., Kakudo, K., LiVolsi , V., Lloyd, R., Nikiforov, Y., Nosé, V., … Thompson, L. (2018). Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP): Achieving Better Agreement By Refining Diagnostic Criteria. Clinics, 73. doi:10.6061/clinics/2018/e576 | |
| dc.relation.references | Kim, C., Agarwal, S., Bychkov, A., Hang, J.-F., Harahap, A. S., Hirokawa, M., Kakudo,K., Keelawat, S., Liu, C.-Y., Liu, Z., Nguyen, T. P.-X., Rana, C., Vuong, H. G., Zhu, Y., & Jung, C. K. (2024). Differentiating BRAF V600E- and RAS-like alterations in encapsulated follicular patterned tumors through histologic features: a validation study.In Virchows Archiv (Vol. 484, Issue 4, pp. 645–656). Springer Science and Business Media LLC. https://doi.org/10.1007/s00428-024-03761-4 | |
| dc.relation.references | Jung, C. K., Bychkov, A., Song, D. E., Kim, J.-H., Zhu, Y., Liu, Z., Keelawat, S., Lai, C.-R., Hirokawa, M., Kameyama, K., & Kakudo, K. (2021). Molecular Correlates and Nuclear Features of Encapsulated Follicular-Patterned Thyroid Neoplasms. In Endocrinology and Metabolism (Vol. 36, Issue 1, pp. 123–133). Korean Endocrine Society. https://doi.org/10.3803/enm.2020.860 | |
| dc.relation.references | Ramos, H. E., Vale, J., Lopes, S., Marques, A., Pinheiro, J., de Lima Beltrão, F. E., Rodrigues, G., Rende, P. R. F., Hecht, F., & Eloy, C. (2022). Nuclear score evaluation in follicular-patterned thyroid lesions using optical and digital environments. In Endocrine (Vol. 77, Issue 3, pp. 486–492). Springer Science and Business Media LLC. https://doi.org/10.1007/s12020-022-03104-w | |
| dc.relation.references | Ali, S. Z., & VanderLaan, P. A. (2023). The Bethesda System for reporting thyroid cytopathology definitions, criteria, and explanatory notes. Springer International Publishing. | |
| dc.relation.references | Fu, G., Polyakova, O., Chazen, R. S., Freeman, J. L., & Witterick, I. J. (2021). Diagnostic Value of Galectin-3 in Distinguishing Invasive Encapsulated Carcinoma from Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features (NIFTP). In Cancers (Vol. 13, Issue 12, p. 2988). MDPI AG. https://doi.org/10.3390/cancers13122988 | |
| dc.relation.references | V, T., Venugopal, L., Ravikumar, K., & Rajendran, D. (2023). DIAGNOSTIC ROLE OF GALECTIN-3 EXPRESSION IN BENIGN FOLLICULAR PATTERNED THYROID LESIONS, NON-INVASIVE FOLLICULAR THYROID NEOPLASM WITH PAPILLARY-LIKE NUCLEAR FEATURES (NIFTP), AND INFILTRATIVE FOLLICULAR VARIANT PAPILLARY THYROID CARCINOMA (IFVPTC). In Asian Journal of Pharmaceutical and Clinical Research (pp. 91–94). Innovare Academic Sciences Pvt Ltd. https://doi.org/10.22159/ajpcr.2023.v16i6.47696 | |
| dc.relation.references | . Acquaviva G, de Biase D, Diquigiovanni C, Argento CM, De Leo A, Bonora E, Rhoden KJ, Pession A, Tallini G. BRAF Exon 15 Mutations in Papillary Carcinoma and Adjacent Thyroid Parenchyma: A Search for the Early Molecular Events Associated with Tumor Development. Cancers (Basel). 2020 Feb 12;12(2):430. doi: 10.3390/cancers12020430. PMID: 32059434; PMCID: PMC7072486. | |
| dc.relation.references | Baloch, Z.W., Asa, S.L., Barletta, J.A. et al. Overview of the 2022 WHO Classification of Thyroid Neoplasms. Endocr Pathol 33, 27–63 (2022). https://doi.org/10.1007/s12022-022-09707-3 | |
| dc.relation.references | Kim, M., Jeon, M. J., Oh, H.-S., Park, S., Kim, T. Y., Shong, Y. K., Song, D. E. (2018). BRAF and RAS Mutational Status in Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features and Invasive Subtype of Encapsulated Follicular Variant of Papillary Thyroid Carcinoma in Korea. Thyroid, 28(4), 504–510. doi:10.1089/thy.2017.0382 | |
| dc.relation.references | Afkhami, M., Karunamurthy, A., Chiosea, S., Nikiforova, M. N., Seethala, R., Nikiforov, Y. E., & Coyne, C. (2016). Histopathologic and Clinical Characterization of Thyroid Tumors Carrying theBRAFK601EMutation. Thyroid, 26(2), 242–247. doi:10.1089/thy.2015.0227 | |
| dc.relation.references | De Leo, A.; Serban, D.; Maloberti, T.; Sanza, V.; Coluccelli, S.; Altimari, A.; Gruppioni, E.; Chiarucci, F.; Corradini, A.G.; Repaci, A.; et al. Expanding the Spectrum of BRAF Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre. Int. J. Mol. Sci. 2023, 24, 4057. https://doi.org/ 10.3390/ijms24044057 | |
| dc.relation.references | Lee, H. S., Lee, J.-W., Park, J. H., Kim, W.-S., Han, H. S., & Lee, S. E. (2019). Comprehensive analysis for diagnosis of preoperative non-invasive follicular thyroid neoplasm with papillary-like nuclear features. In P. Soares (Ed.), PLOS ONE (Vol. 14, Issue 7, p. e0218046). Public Library of Science (PLoS). https://doi.org/10.1371/journal.pone.0218046 | |
| dc.relation.references | Rana, C., Vuong, H. G., Nguyen, T. Q., Nguyen, H. C., Jung, C. K., Kakudo, K., & Bychkov, A. (2021). The Incidence of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Meta-Analysis Assessing Worldwide Impact of the Reclassification. In Thyroid. Mary Ann Liebert Inc. https://doi.org/10.1089/thy.2021.0158 | |
| dc.relation.references | Barrero Flórez, F. (2022). Cáncer de tiroides: características clinicopatológicas en una serie de casos del Hospital Universitario Nacional 2017-2020. Universidad Nacional de Colombia. | |
| dc.relation.references | Hung, Y. P., & Barletta, J. A. (2017). A user’s guide to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Histopathology, 72(1), 53–69. doi:10.1111/his.13363 | |
| dc.relation.references | Chu, Y.-H., & Sadow, P. M. (2020). Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): Diagnostic Updates and Molecular Advances. Seminars in Diagnostic Pathology. doi:10.1053/j.semdp.2020.06.001 | |
| dc.relation.references | . Hahn SY, Shin JH, Oh YL, Kim TH, Lim Y, Choi JS. Role of Ultrasound in Predicting Tumor Invasiveness in Follicular Variant of Papillary Thyroid Carcinoma. Thyroid. 2017 Sep;27(9):1177-1184. doi: 10.1089/thy.2016.0677. Epub 2017 Aug 7. PMID: 28699414. | |
| dc.relation.references | Raufeisen, J., Xie, K., Hörst, F., Braunschweig, T., Li, J., Kleesiek, J., Röhrig, R., Egger, J., Leibe, B., Hölzle, F., Hermans, A., & Puladi, B. (2024). Cyto R-CNN and CytoNuke Dataset: Towards reliable whole-cell segmentation in bright-field histological images. In Computer Methods and Programs in Biomedicine (Vol. 252, p. 108215). Elsevier BV. https://doi.org/10.1016/j.cmpb.2024.108215 | |
| dc.relation.references | Bongiovanni, M., Giovanella, L., Romanelli, F., & Trimboli, P. (2019). Cytological Diagnoses Associated with Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features According to the Bethesda System for Reporting Thyroid Cytopathology: A Systematic Review and Meta-Analysis. In Thyroid (Vol. 29, Issue 2, pp. 222–228). Mary Ann Liebert Inc. https://doi.org/10.1089/thy.2018.0394 | |
| dc.relation.references | Nishigami, K., Liu, Z., Taniguchi, E., Koike, E., Ozaki, T., Mori, I., & Kakudo, K. (2012). Cytological features of well-differentiated tumors of uncertain malignant potential: Indeterminate cytology and WDT-UMP. Endocrine Journal, 59(6), 483–487. doi:10.1507/endocrj.ej11-0261 | |
| dc.relation.references | Deniz MS, Özdemir D, İmga NN, Başer H, Çuhacı Seyrek FN, Altınboğa AA, Topaloğlu O, Ersoy R, Çakır B. Investigation of pre-operative demographic, biochemical, sonographic and cytopathological findings in low-risk thyroid neoplasms. Clin Endocrinol (Oxf). 2023 Nov;99(5):502-510. doi: 10.1111/cen.14965. | |
| dc.relation.references | Bychkov, A., Jung, C.K., Liu, Z. et al. Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features in Asian Practice: Perspectives for Surgical Pathology and Cytopathology. Endocr Pathol 29, 276–288 (2018). https://doi.org/10.1007/s12022-018-9519-6 | |
| dc.relation.references | Raufeisen, J., Xie, K., Hörst, F., Braunschweig, T., Li, J., Kleesiek, J., Röhrig, R., Egger, J., Leibe, B., Hölzle, F., Hermans, A., & Puladi, B. (2024). Cyto R-CNN and CytoNuke Dataset: Towards reliable whole-cell segmentation in bright-field histological images. In Computer Methods and Programs in Biomedicine (Vol. 252, p. 108215). Elsevier BV. https://doi.org/10.1016/j.cmpb.2024.108215 | |
| dc.relation.references | Bankhead, P., Loughrey, M. B., Fernández, J. A., Dombrowski, Y., McArt, D. G., Dunne,P. D., McQuaid, S., Gray, R. T., Murray, L. J., Coleman, H. G., James, J. A., Salto-Tellez, M., & Hamilton, P. W. (2017). QuPath: Open source software for digital pathology image analysis. In Scientific Reports (Vol. 7, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1038/s41598-017-17204-5 | |
| dc.relation.references | Kim, M. J., Won, J.-K., Jung, K. C., Kim, J., Cho, S. W., Park, D. J., & Park, Y. J. (2018). Clinical Characteristics of Subtypes of Follicular Variant Papillary Thyroid Carcinoma. Thyroid, 28(3), 311–318. doi:10.1089/thy.2016.0671 | |
| dc.relation.references | Mohan, U., Sunny, S.P., Mendonca, P. et al. Systematic Review and Meta-Analysis to Identify the Immunocytochemical Markers Effective in Delineating Benign from Malignant Thyroid Lesions in FNAC Samples. Endocr Pathol 33, 243–256 (2022). https://doi.org/10.1007/s12022-022-09721-5 | |
| dc.relation.references | Schmidt, U., Weigert, M., Broaddus, C., & Myers, G. (2018). Cell Detection with Star-Convex Polygons. In Medical Image Computing and Computer Assisted Intervention – MICCAI 2018 (pp. 265–273). Springer International Publishing. https://doi.org/10.1007/978-3-030-00934-2_30 | |
| dc.relation.references | Saito, A., Numata, Y., Hamada, T., Horisawa, T., Cosatto, E., Graf, H.-P., Kuroda, M., & Yamamoto, Y. (2016). A novel method for morphological pleomorphism and heterogeneity quantitative measurement: Named cell feature level co-occurrence matrix. In Journal of Pathology Informatics (Vol. 7, Issue 1, p. 36). Elsevier BV. https://doi.org/10.4103/2153-3539.189699 | |
| dc.relation.references | . L’Imperio, V., Coelho, V., Cazzaniga, G., Papetti, D. M., Del Carro, F., Capitoli, G., Marino, M., Ceku, J., Fusco, N., Ivanova, M., Gianatti, A., Nobile, M. S., Galimberti, S., Besozzi, D., & Pagni, F. (2024). Machine Learning Streamlines the Morphometric Characterization and Multiclass Segmentation of Nuclei in Different Follicular Thyroid Lesions: Everything in a NUTSHELL. Modern Pathology, 37(12), 100608. https://doi.org/10.1016/j.modpat.2024.100608 | |
| dc.relation.references | Bhuyan, G., & Rabha, A. (2024). Can the analysis of chromatin texture and nuclear fractal dimensions serve as effective means to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features from other malignancies with follicular pattern in the thyroid?: a study. Ultrastructural Pathology, 48(4), 310–316. https://doi.org/10.1080/01913123.2024.2362758 | |
| dc.rights.accessrights | info:eu-repo/semantics/openAccess | |
| dc.rights.license | Reconocimiento 4.0 Internacional | |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| dc.subject.ddc | 610 - Medicina y salud::616 - Enfermedades | |
| dc.subject.ddc | 610 - Medicina y salud::615 - Farmacología y terapéutica | |
| dc.subject.decs | Neoplasias Primarias Múltiples | spa |
| dc.subject.decs | Neoplasms, Multiple Primary | eng |
| dc.subject.decs | Cáncer Papilar Tiroideo | spa |
| dc.subject.decs | Thyroid Cancer, Papillary | eng |
| dc.subject.decs | Pathology, Clinical | eng |
| dc.subject.decs | Células Epiteliales Tiroideas | spa |
| dc.subject.decs | Thyroid Epithelial Cells | eng |
| dc.subject.decs | Patología Clínica | spa |
| dc.subject.proposal | NIFTP | spa |
| dc.subject.proposal | WDT-UMP | spa |
| dc.subject.proposal | IEFVPTC | spa |
| dc.subject.proposal | PTC | spa |
| dc.subject.proposal | Patología digital | spa |
| dc.subject.proposal | Haralick | eng |
| dc.subject.proposal | Digital pathology | eng |
| dc.title | Caracterización de tumores primarios de tiroides con arquitectura folicular y cambios nucleares similares a los del carcinoma papilar en pacientes del hospital universitario nacional, 2020-2023 | spa |
| dc.title.translated | Characterization of primary thyroid tumors with follicular architecture and nuclear changes similar to those of papillary carcinoma in patients at the National University Hospital, 2020–2023 | eng |
| dc.type | Trabajo de grado - Especialidad Médica | |
| dc.type.coar | http://purl.org/coar/resource_type/c_bdcc | |
| dc.type.coarversion | http://purl.org/coar/version/c_ab4af688f83e57aa | |
| dc.type.content | Text | |
| dc.type.driver | info:eu-repo/semantics/masterThesis | |
| dc.type.redcol | http://purl.org/redcol/resource_type/TM | |
| dc.type.version | info:eu-repo/semantics/acceptedVersion | |
| dcterms.audience.professionaldevelopment | Estudiantes | |
| dcterms.audience.professionaldevelopment | Investigadores | |
| dcterms.audience.professionaldevelopment | Maestros | |
| dcterms.audience.professionaldevelopment | Público general | |
| oaire.accessrights | http://purl.org/coar/access_right/c_abf2 |
Archivos
Bloque original
1 - 1 de 1
Cargando...
- Nombre:
- TRABAJO GRADO JMQT EVALUADORES _AS_FB FINAL REPOSITORIO.pdf
- Tamaño:
- 47.78 MB
- Formato:
- Adobe Portable Document Format
- Descripción:
- Tesis de Especialidad Médica en Patología Anatómica y Clínica
Bloque de licencias
1 - 1 de 1
Cargando...
- Nombre:
- license.txt
- Tamaño:
- 5.74 KB
- Formato:
- Item-specific license agreed upon to submission
- Descripción:

