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Histopathological Characterization and Development of Objective Diagnostic Criteria in Mycosis Fungoides

Received: 12 September 2024     Accepted: 18 October 2024     Published: 13 November 2024
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Abstract

Background: Mycosis Fungoides is a subtype of Cutaneous T Cell Lymphomas, often difficult to diagnose in its early stages due to its histopathological resemblance to inflammatory dermatoses. Objectives: To refine and enhance the diagnostic criteria for Mycosis Fungoides by utilizing digital scanning and analysis systems for the quantitative evaluation of immunohistochemical markers. Methods: A retrospective longitudinal observational descriptive study based on the reevaluation and comparison of diagnostic criteria (histological and immunohistochemical) of patients with a clinical suspicion of MF, creating two groups: patients whose diagnosis, despite requiring numerous biopsies, was finally Mycosis Fungoides (MF Group), and patients who, despite clinical suspicion, always had a diagnosis of Inflammatory Dermatoses (Control Group). The study was conducted on 62 patients with clinical suspicion of MF who underwent punch biopsies between 2000 and 2022 at Severo Ochoa University Hospital. Histological and immunohistochemical markers (CD2, CD3, CD4, CD5, CD7, CD8, TOX) were assessed using APERIO AT2 LEICA BIOSYSTEMS scanner and CIVAGENIUS software, ensuring objective and reproducible results. Results: Basal epidermotropism, lymphocytic atypia, and peri-lymphocytic halo showed strong associations with MF diagnosis. Significant differences were observed in the CD3/CD8 and CD5/CD8 ratios between Mycosis Fungoides and Inflammatory Dermatoses groups. High TOX antibody expression correlated with early-stage MF diagnosis. These findings suggest the potential of combining marker ratios and TOX expression with digital analysis to improve diagnostic accuracy. Conclusions: Digital scanning and automated analysis systems significantly enhance the precision and efficiency of Mycosis Fungoides diagnosis. Implementing these methods in routine practice can reduce diagnostic delays and improve patient outcomes by differentiating Mycosis Fungoides from similar dermatological conditions more effectively.

Published in International Journal of Clinical and Experimental Medical Sciences (Volume 10, Issue 4)
DOI 10.11648/j.ijcems.20241004.12
Page(s) 48-59
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Mycosis Fungoides, Tox Antibody, Inflammatory Dermatoses, Epidermotropism, Algorithm, Immunohistochemical Markers

References
[1] Vowels BR, Lessin SR, Cassin M, Jaworsky C, Benoit B, Wolfe JT, et al. Th2 Cytokine mRNA Expression in Skin in Cutaneous T-Cell Lymphoma. Journal of Investigative Dermatology. 1994; 103(5): 669-73.
[2] Choi J, Goh G, Walradt T, Hong BS, Bunick CG, Chen K, et al. Genomic landscape of cutaneous T cell lymphoma. Nat Genet. 2015; 47(9): 1011-9.
[3] Prasad A, Rabionet R, Espinet B, Zapata L, Puiggros A, Melero C, et al. Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome. J Invest Dermatol. 2016; 136(7): 1490-9.
[4] Sekulic A, Liang WS, Tembe W, Izatt T, Kruglyak S, Kiefer JA, et al. Personalized treatment of Sézary syndrome by targeting a novel CTLA4:CD28 fusion. Mol Genet Genomic Med. 2015; 3(2): 130-6.
[5] Pérez C, González-Rincón J, Onaindia A, Almaráz C, García-Díaz N, Pisonero H, et al. Mutated JAK kinases and deregulated STAT activity are potential therapeutic targets in cutaneous T-cell lymphoma. Haematologica. 2015; 100(11): e450-453.
[6] Park J, Yang J, Wenzel AT, Ramachandran A, Lee WJ, Daniels JC, et al. Genomic analysis of 220 CTCLs identifies a novel recurrent gain-of-function alteration in RLTPR (p.Q575E). Blood. 2017; 130(12): 1430-40.
[7] Bastidas Torres AN, Cats D, Mei H, Szuhai K, Willemze R, Vermeer MH, et al. Genomic analysis reveals recurrent deletion of JAK-STAT signaling inhibitors HNRNPK and SOCS1 in mycosis fungoides. Genes Chromosomes Cancer. 2018; 57(12): 653-64.
[8] Kirsch IR, Watanabe R, O’Malley JT, Williamson DW, Scott LL, Elco CP, et al. TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL. Sci TranslMed. 2015; 7(308): 308ra158.
[9] Massard C, Michiels S, Ferté C, Le Deley MC, Lacroix L, Hollebecque A, et al. High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial. Cancer Discov. 2017; 7(6): 586-95.
[10] Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part I. Diagnosis: clinical and histopathologic features and new molecular and biologic markers. J Am Acad Dermatol. 2014; 70(2): 205.e1-16; quiz 221-2.
[11] Yumeen S, Mirza FN, Lewis JM, Carlson KR, King B, Cowper S, et al. CD8+ mycosis fungoides palmaris et plantaris with peripheral blood involvement. JAAD Case Rep. 2020; 6(5): 434-7.
[12] Bakels V, van Oostveen JW, Gordijn RL, Walboomers JM, Meijer CJ, Willemze R. Frequency and prognostic significance of clonal T-cell receptor beta-gene rearrangements in the peripheral blood of patients with mycosis fungoides. Arch Dermatol. 1992; 128(12): 1602-7.
[13] Horna P, Wang SA, Wolniak KL, Psarra K, Almeida J, Illingworth AJ, et al. Flow cytometric evaluation of peripheral blood for suspected Sézary syndrome or mycosis fungoides: International guidelines for assay characteristics. Cytometry B Clin Cytom. 2021; 100(2): 142-55.
[14] Wilkinson B, Chen JYF, Han P, Rufner KM, Goularte OD, Kaye J. TOX: an HMG box protein implicated in the regulation of thymocyte selection. Nat Immunol. 2002; 3(3): 272-80.
[15] Kioussis D. Thymocyte differentiation: it’s time to bend a little. Nat Immunol. 2002; 3(3): 214-5.
[16] Aliahmad P, Kaye J. Development of all CD4 T lineages requires nuclear factor TOX. Journal of Experimental Medicine. 2008; 205(1): 245-56.
[17] Skov AG, Gniadecki R. Delay in the histopathologic diagnosis of mycosis fungoides. Acta Derm Venereol. 2015; 95(4): 472-5.
[18] Ortonne N, Buyukbabani N, Delfau-Larue MH, Bagot M, Wechsler J. Value of the CD8-CD3 ratio for the diagnosis of mycosis fungoides. Mod Pathol. 2003; 16(9): 857-62.
[19] Amorim GM, Quintella DC, Niemeyer-Corbellini JP, Ferreira LC, Ramos-e-Silva M, Cuzzi T. Validation of an algorithm based on clinical, histopathological and immunohistochemical data for the diagnosis of early-stage mycosis fungoides. An BrasDermatol. 2020; 95(3): 326-31
[20] Zhang Y, Wang Y, Yu R, Huang Y, Su M, Xiao C, et al. Molecular markers of early-stage mycosis fungoides. J Invest Dermatol. 2012; 132(6): 1698-706.
Cite This Article
  • APA Style

    Pinilla-Pagnon, I., Rojo-López, R., Hompanera, T. S., Casasola, G. G. D., Chao-Crecente, M. (2024). Histopathological Characterization and Development of Objective Diagnostic Criteria in Mycosis Fungoides. International Journal of Clinical and Experimental Medical Sciences, 10(4), 48-59. https://doi.org/10.11648/j.ijcems.20241004.12

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    ACS Style

    Pinilla-Pagnon, I.; Rojo-López, R.; Hompanera, T. S.; Casasola, G. G. D.; Chao-Crecente, M. Histopathological Characterization and Development of Objective Diagnostic Criteria in Mycosis Fungoides. Int. J. Clin. Exp. Med. Sci. 2024, 10(4), 48-59. doi: 10.11648/j.ijcems.20241004.12

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    AMA Style

    Pinilla-Pagnon I, Rojo-López R, Hompanera TS, Casasola GGD, Chao-Crecente M. Histopathological Characterization and Development of Objective Diagnostic Criteria in Mycosis Fungoides. Int J Clin Exp Med Sci. 2024;10(4):48-59. doi: 10.11648/j.ijcems.20241004.12

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  • @article{10.11648/j.ijcems.20241004.12,
      author = {Ignacio Pinilla-Pagnon and Rosa Rojo-López and Tania Sierra Hompanera and Gonzalo Garcia de Casasola and Montserrat Chao-Crecente},
      title = {Histopathological Characterization and Development of Objective Diagnostic Criteria in Mycosis Fungoides
    },
      journal = {International Journal of Clinical and Experimental Medical Sciences},
      volume = {10},
      number = {4},
      pages = {48-59},
      doi = {10.11648/j.ijcems.20241004.12},
      url = {https://doi.org/10.11648/j.ijcems.20241004.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcems.20241004.12},
      abstract = {Background: Mycosis Fungoides is a subtype of Cutaneous T Cell Lymphomas, often difficult to diagnose in its early stages due to its histopathological resemblance to inflammatory dermatoses. Objectives: To refine and enhance the diagnostic criteria for Mycosis Fungoides by utilizing digital scanning and analysis systems for the quantitative evaluation of immunohistochemical markers. Methods: A retrospective longitudinal observational descriptive study based on the reevaluation and comparison of diagnostic criteria (histological and immunohistochemical) of patients with a clinical suspicion of MF, creating two groups: patients whose diagnosis, despite requiring numerous biopsies, was finally Mycosis Fungoides (MF Group), and patients who, despite clinical suspicion, always had a diagnosis of Inflammatory Dermatoses (Control Group). The study was conducted on 62 patients with clinical suspicion of MF who underwent punch biopsies between 2000 and 2022 at Severo Ochoa University Hospital. Histological and immunohistochemical markers (CD2, CD3, CD4, CD5, CD7, CD8, TOX) were assessed using APERIO AT2 LEICA BIOSYSTEMS scanner and CIVAGENIUS software, ensuring objective and reproducible results. Results: Basal epidermotropism, lymphocytic atypia, and peri-lymphocytic halo showed strong associations with MF diagnosis. Significant differences were observed in the CD3/CD8 and CD5/CD8 ratios between Mycosis Fungoides and Inflammatory Dermatoses groups. High TOX antibody expression correlated with early-stage MF diagnosis. These findings suggest the potential of combining marker ratios and TOX expression with digital analysis to improve diagnostic accuracy. Conclusions: Digital scanning and automated analysis systems significantly enhance the precision and efficiency of Mycosis Fungoides diagnosis. Implementing these methods in routine practice can reduce diagnostic delays and improve patient outcomes by differentiating Mycosis Fungoides from similar dermatological conditions more effectively.
    },
     year = {2024}
    }
    

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  • TY  - JOUR
    T1  - Histopathological Characterization and Development of Objective Diagnostic Criteria in Mycosis Fungoides
    
    AU  - Ignacio Pinilla-Pagnon
    AU  - Rosa Rojo-López
    AU  - Tania Sierra Hompanera
    AU  - Gonzalo Garcia de Casasola
    AU  - Montserrat Chao-Crecente
    Y1  - 2024/11/13
    PY  - 2024
    N1  - https://doi.org/10.11648/j.ijcems.20241004.12
    DO  - 10.11648/j.ijcems.20241004.12
    T2  - International Journal of Clinical and Experimental Medical Sciences
    JF  - International Journal of Clinical and Experimental Medical Sciences
    JO  - International Journal of Clinical and Experimental Medical Sciences
    SP  - 48
    EP  - 59
    PB  - Science Publishing Group
    SN  - 2469-8032
    UR  - https://doi.org/10.11648/j.ijcems.20241004.12
    AB  - Background: Mycosis Fungoides is a subtype of Cutaneous T Cell Lymphomas, often difficult to diagnose in its early stages due to its histopathological resemblance to inflammatory dermatoses. Objectives: To refine and enhance the diagnostic criteria for Mycosis Fungoides by utilizing digital scanning and analysis systems for the quantitative evaluation of immunohistochemical markers. Methods: A retrospective longitudinal observational descriptive study based on the reevaluation and comparison of diagnostic criteria (histological and immunohistochemical) of patients with a clinical suspicion of MF, creating two groups: patients whose diagnosis, despite requiring numerous biopsies, was finally Mycosis Fungoides (MF Group), and patients who, despite clinical suspicion, always had a diagnosis of Inflammatory Dermatoses (Control Group). The study was conducted on 62 patients with clinical suspicion of MF who underwent punch biopsies between 2000 and 2022 at Severo Ochoa University Hospital. Histological and immunohistochemical markers (CD2, CD3, CD4, CD5, CD7, CD8, TOX) were assessed using APERIO AT2 LEICA BIOSYSTEMS scanner and CIVAGENIUS software, ensuring objective and reproducible results. Results: Basal epidermotropism, lymphocytic atypia, and peri-lymphocytic halo showed strong associations with MF diagnosis. Significant differences were observed in the CD3/CD8 and CD5/CD8 ratios between Mycosis Fungoides and Inflammatory Dermatoses groups. High TOX antibody expression correlated with early-stage MF diagnosis. These findings suggest the potential of combining marker ratios and TOX expression with digital analysis to improve diagnostic accuracy. Conclusions: Digital scanning and automated analysis systems significantly enhance the precision and efficiency of Mycosis Fungoides diagnosis. Implementing these methods in routine practice can reduce diagnostic delays and improve patient outcomes by differentiating Mycosis Fungoides from similar dermatological conditions more effectively.
    
    VL  - 10
    IS  - 4
    ER  - 

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Author Information
  • Department of Pathology, University Hospital Severo Ochoa, Leganés (Madrid), Spain; Faculty of Health Sciences (Department of Medicine), University Alfonso X El Sabio, Villanueva de la Cañada (Madrid), Spain

  • Faculty of Health Sciences (Department of Medicine), University Alfonso X El Sabio, Villanueva de la Cañada (Madrid), Spain

  • Department of Pathology, University Hospital Severo Ochoa, Leganés (Madrid), Spain

  • Department of Pathology, University Hospital Severo Ochoa, Leganés (Madrid), Spain

  • Department of Pathology, University Hospital Severo Ochoa, Leganés (Madrid), Spain; Faculty of Health Sciences (Department of Medicine), University Alfonso X El Sabio, Villanueva de la Cañada (Madrid), Spain

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