Page 76 - The lraternational Journal of the Royal Society of Thailand.indd

The International Journal of the Royal Society of Thailand
Volume XV-2023

classification (1975) initiated such an immunological approach (Lukes & Collins, 1974;
Lennert et al, 1975). Unfortunately, in real world, simplicity won as the working
formulation (WF) for clinical usage in classifications of NHL had been well accepted
since its publication in 1982 (National Cancer Institute, 1982). In many countries,
especially those with limited resources, morphological approach alone in this WF had

been used for nearly 20 years until the well accepted 3rd edition of the WHO
classification of tumours of haematopoietic and lymphoid tissues published in 2001
(Jaffe et al, 2001). But in developed countries, the updated Kiel classification (Stansfeld

et al, 1988) had been used for nearly 20 years before the revised European-American
Classification for Lymphoid neoplasms (REAL classification) published in 1994
(Harris et al, 1994). Then, the REAL classification transformed into the WHO
classification, 3rdedition. Since then, the D&C of lymphoma requires 4 main findings

– clinical, morphological, immunophenotypic, and genetic (Harris et al, 1994; Jaffe

et al, 2001). Such a multiparameter approach has been carried out, mostly completely
in the developed countries but not in the developing or underdeveloped countries
where limited resources force the pathologic diagnosis of lymphoma based on

morphology and a limited panel of immunohistochemistry (immunostaining).
Cytogenetic study has been introduced to search for a specific genetic marker

in a particular type of lymphoma. Non-random karyotypic abnormality eventually
paid off when the t(8;14) translocation was identified in 1982 in Burkitt lymphoma
(Dalla-Favera et al, 1982; Taub et al, 1982). Later, molecular genetic technics allow us

to detect rearrangements of immunoglobulin (Ig) genes and T-cell receptor (TCR) genes
in B-cell and T-cell, respectively. Clonal rearrangement of Ig gene or TCR gene
detected by polymerase chain reaction (PCR) in any tissue suspected of B-cell or T-cell
lymphoma, respectively, supports the diagnosis of lymphoma as monoclonality
considered as indicative of neoplasm (Jaffe, 2019).

Fluorescence in situ hybridization (FISH) provides detection of any genes of
interest. In lymphoma, rearrangements of BCL2, BCL6, MYC, and IRF4/MUM1 genes
have been used to support the diagnosis of follicular lymphoma, diffuse large B-cell
lymphoma (DLBCL), Burkitt lymphoma, high grade B-cell lymphoma (HGBCL) with
MYC and BCL2 rearrangments/HGBCL with MYC and BCL6 rearrangements, and large

B-cell lymphoma with IRF4/MUM1 rearrangement (WHO Classification of Tumours
Editorial Board, 2022), respectively. Then came gene expression profiling using array
comparative genomic hybridization in order to compare patient’s genome against a

reference genome in term of gain or loss of chromosomes or subchromosomal regions.
The first application of this molecular genetic technic was the determination of the cell

68 Reflections on How to Diagnose and Classify Lymphoma