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CC BY-NC-ND 4.0 · South Asian J Cancer
DOI: 10.1055/s-0045-1805056
Original Article

Diagnostic Utility of Molecular Analysis in Cutaneous T-Cell Lymphoma: Tunisian Series on Clonality of TCRG Gene Rearrangement

Sarra Klai
1   Department of Pathology, Habib Thameur Hospital, Tunis, Tunisia
,
Imen Helal
1   Department of Pathology, Habib Thameur Hospital, Tunis, Tunisia
,
Raja Jouini
1   Department of Pathology, Habib Thameur Hospital, Tunis, Tunisia
,
Houda Hammami
2   Department of Dermatology, Habib Thameur Hospital, Tunis, Tunisia
,
Maher Kharrat
3   LR99ES10 Human Genetics Laboratory, Faculty of Medicine of Tunis (FMT), University of Tunis El Manar, Tunis, Tunisia
,
Sami Fenniche
2   Department of Dermatology, Habib Thameur Hospital, Tunis, Tunisia
,
Fatma Khanchel
1   Department of Pathology, Habib Thameur Hospital, Tunis, Tunisia
,
Aschraf Chadli-Debbiche
1   Department of Pathology, Habib Thameur Hospital, Tunis, Tunisia
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Abstract

Introduction

The diagnosis of cutaneous T-cell lymphoma (CTCL) is sometimes difficult. Detection of monoclonal T-cell receptor gamma (TCRG) gene rearrangement by polymerase chain reaction (PCR) has become an important adjunct to the diagnosis of CTCL. This study was designed to explore the concordance in terms of the diagnostic value of BIOMED-2 TCRG PCR protocol with the histological diagnosis.

Methods

Confirmed and doubtful CTCLs were included in this descriptive cross-sectional study performed in the Habib Thameur Hospital in 2021. These cases were followed in the department of dermatology from 2012 to 2021. PCR tests were performed with TCRG BIOMED-2 clonality methods followed by capillary electrophoresis and GeneScan analysis. Clonality and statistical results were analyzed.

Results

Monoclonality was identified in 51% of confirmed CTCL cases (16/28 cases with confirmed mycosis fungoides and 2/7 other CTCL cases) and in 63% of doubtful cases, which were converted to malignant diagnosis. The results of TCRG clonality demonstrated a significant correlation with histopathology diagnoses of specimens. A moderate concordance was found between histology and molecular clonality.

Conclusion

Results from this molecular clonality emphasize the importance of interpreting data in association with histopathological features of the lesions.

Keywords

cutaneous T-cell lymphoma - mycosis fongoides - clonality - TCRG - BIOMED-2 protocol - histology

Declaration of Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.


Ethical Approval

This study was approved by the ethical committee of Habib Thameur Hospital.




Publication History

Received: 07 January 2025

Accepted: 29 January 2025

Article published online:
07 March 2025

© 2025. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Dummer R, Vermeer MH, Scarisbrick JJ. et al. Cutaneous T cell lymphoma. Nat Rev Dis Primers 2021; 7 (01) 61
    CrossrefPubMedSearch in Google Scholar
  • 2 Wong HK, Mishra A, Hake T, Porcu P. Evolving insights in the pathogenesis and therapy of cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome). Br J Haematol 2011; 155 (02) 150-166
    CrossrefPubMedSearch in Google Scholar
  • 3 Kirsch IR, Watanabe R, O'Malley JT. et al. TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL. Sci Transl Med 2015; 7 (308) 308ra158
    CrossrefPubMedSearch in Google Scholar
  • 4 Jonak C, Tittes J, Brunner PM, Guenova E. Mycosis fungoides and Sézary syndrome. J Dtsch Dermatol Ges 2021; 19 (09) 1307-1334
    PubMedSearch in Google Scholar
  • 5 Mahe E, Pugh T, Kamel-Reid S. T cell clonality assessment: past, present and future. J Clin Pathol 2018; 71 (03) 195-200
    CrossrefPubMedSearch in Google Scholar
  • 6 Zamò A, Bertolaso A, van Raaij AW. et al. Application of microfluidic technology to the BIOMED-2 protocol for detection of B-cell clonality. J Mol Diagn 2012; 14 (01) 30-37
    CrossrefPubMedSearch in Google Scholar
  • 7 Langerak AW, Groenen PJTA, Brüggemann M. et al. EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations. Leukemia 2012; 26 (10) 2159-2171
    CrossrefPubMedSearch in Google Scholar
  • 8 van Dongen JJM, Langerak AW, Brüggemann M. et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2003; 17 (12) 2257-2317
    CrossrefPubMedSearch in Google Scholar
  • 9 Zhang B, Beck AH, Taube JM. et al. Combined use of PCR-based TCRG and TCRB clonality tests on paraffin-embedded skin tissue in the differential diagnosis of mycosis fungoides and inflammatory dermatoses. J Mol Diagn 2010; 12 (03) 320-327
    CrossrefPubMedSearch in Google Scholar
  • 10 Walia R, Yeung CCS. An update on molecular biology of cutaneous T cell lymphoma. Front Oncol 2020; 9: 1558
    CrossrefPubMedSearch in Google Scholar
  • 11 Miyata-Takata T, Takata K, Yamanouchi S. et al. Detection of T-cell receptor γ gene rearrangement in paraffin-embedded T or natural killer/T-cell lymphoma samples using the BIOMED-2 protocol. Leuk Lymphoma 2014; 55 (09) 2161-2164
    CrossrefPubMedSearch in Google Scholar
  • 12 Massone C, Kodama K, Kerl H, Cerroni L. Histopathologic features of early (patch) lesions of mycosis fungoides: a morphologic study on 745 biopsy specimens from 427 patients. Am J Surg Pathol 2005; 29 (04) 550-560
    CrossrefPubMedSearch in Google Scholar
  • 13 Gibbs JD, Ma S, Kim A. et al. Utility of flow cytometry and gene rearrangement analysis in tissue and blood of patients with suspected cutaneous T–cell lymphoma. Oncol Rep 2021; 45 (01) 349-358
    CrossrefPubMedSearch in Google Scholar
  • 14 Xu C, Wan C, Wang L, Yang H-J, Tang Y, Liu W-P. Diagnostic significance of TCR gene clonal rearrangement analysis in early mycosis fungoides. Chin J Cancer 2011; 30 (04) 264-272
    CrossrefPubMedSearch in Google Scholar
  • 15 Ashton-Key M, Diss TC, Du MQ, Kirkham N, Wotherspoon A, Isaacson PG. The value of the polymerase chain reaction in the diagnosis of cutaneous T-cell infiltrates. Am J Surg Pathol 1997; 21 (07) 743-747
    CrossrefPubMedSearch in Google Scholar
  • 16 Hsiao P-F, Hsiao C-H, Lin Y-C, Tseng MP, Tsai TF, Jee SH. Histopathologic-molecular correlation in early mycosis fungoides using T-cell receptor gamma gene rearrangement by polymerase chain reaction with laser capture microdissection. J Formos Med Assoc 2007; 106 (04) 265-272
    CrossrefPubMedSearch in Google Scholar
  • 17 Kamarádová K, Hrochová K, Salavec M, Belada D. T-cell receptor antibodies expression in benign and malignant cutaneous lymphoid infiltrates in comparison with T-cell receptor gene rearrangement and its diagnostic utility in borderline cases. Pathol Res Pract 2020; 216 (12) 153279
    CrossrefPubMedSearch in Google Scholar
  • 18 Sandberg Y, van Gastel-Mol EJ, Verhaaf B, Lam KH, van Dongen JJM, Langerak AW. BIOMED-2 multiplex immunoglobulin/T-cell receptor polymerase chain reaction protocols can reliably replace Southern blot analysis in routine clonality diagnostics. J Mol Diagn 2005; 7 (04) 495-503
    CrossrefPubMedSearch in Google Scholar