Browse > Article
http://dx.doi.org/10.7314/APJCP.2016.17.2.491

The Polymerase Chain Reaction in Diagnosis of Small B-Cell Non-Hodgkin Lymphomas  

Antoro, Ester Lianawati (Department of Anatomical Pathology, Faculty of Medicine, Universitas Gadjah Mada)
Dwianingsih, Ery Kus (Department of Anatomical Pathology, Faculty of Medicine, Universitas Gadjah Mada)
Indrawati, Indrawati (Department of Anatomical Pathology, Faculty of Medicine, Universitas Gadjah Mada)
Triningsih, FX Ediati (Department of Anatomical Pathology, Faculty of Medicine, Universitas Gadjah Mada)
Harijadi, Harijadi (Department of Anatomical Pathology, Faculty of Medicine, Universitas Gadjah Mada)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.17, no.2, 2016 , pp. 491-495 More about this Journal
Abstract
Background: Small B-cell non-Hodgkins lymphoma (NHL) is difficult to be distinguished from non-neoplastic reactive processes using conventional haematoxylin-eosin (HE) staining due to different interpretations among pathologists with diagnosis based on morphologic features. Ancillary examinations such as immunohistochemical (IHC) staining are essential. However, negative or doubtful results are still sometimes obtained due to unsatisfactory tissue processing or IHC technique. The polymerase chain reaction (PCR) as a molecular diagnostic technique is very sensitive and specific. Clonality detection of heavy chain immunoglobulin (IgH) gene rearrangement has been widely used to establish diagnosis of B-cell NHL. Aims: To elaborate interobserver variation in small B-cell NHL diagnosis based on morphologic features only and to confirm sensitivity and specificity of the PCR technique as an ancillary method. Materials and Methods: A toptal of 28 samples of small B cell NHL and suspicious lymphoma were interpreted by 3 pathologists in Sardjito General Hospital based on their morphology only. The reliability of assessment and the coefficient of interobserver agreement were calculated by Fleiss kappa statistics. Interpretation results were confirmed with IHC staining (CD20, CD3, Bcl2). PCR was performed to analyze the clonality of IgH gene rearrangement. Results: Interobserver agreement in morphologic evalution of small B cell NHL and chronic lymphadenitis revealed kappa coefficient 0.69 included in the substantial agreement category. The cases were divided into 3 groups based on morphology and IHC results; lymphoma, reactive process and undetermined group. PCR analysis showed 90% sensitivity and 60% specificity. Conclusions: The present study revealed a substantial agreement among pathologists in small B-cell NHL diagnosis. For difficult cases, PCR is useful as complementary method to morphologic and IHC examinations to establish definitive diagnosis.
Keywords
Small B-cell non-Hodgkins lymphoma; immunohistochemistry; heavy chain immunoglobulin; PCR;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Campo E, Jaffe ES, Harris NL (2011). Normal lymphoid organs and tissue, in haematopathology. Saunders Elsevier, Philadelphia. 97-117.
2 El-Zimaity HMT, Wotherspoon A, Jong D (2005). Interobserver variation in the histopathological assessment of malt/malt lymphoma: towards a consensus. Blood Cells Mol Dis, 34, 6-16.   DOI
3 Elenitoba-Johnson KS, Bohling SD, Mitchell RS, et al (2000). PCR Analysis of the Immunoglobulin Heavy Chain Gene in Polyclonal Proceses Can Yield Pseudoclonal Bands as an Artifact of Low B Cell Number. J Mol Diagn, 2, 92-6.   DOI
4 Farmer PL, Bailey DJ, Burns BF, et al (2007). The reliability of lymphoma diagnosis in small tissue samples is heavily influenced by lymphoma subtype. Am J Pathol, 128, 474-480.
5 Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al (2013). Cancer Incidence and Mortality Pattern in Europe: estimates for 40 countries in 2012. Eur J Cancer, 49,1374-403.   DOI
6 Hsi ED and Schnitzer B (2011). The Reactive Lymphadenopathies in Haematopathology.Saunders Elsevier, Philadelphia. pp118-139.
7 Ishtiaq S, Hassan U, Mushtaq S, et al (2013). Determination of frequency of Epstein-Barr virus in non-Hodgkin lymphomas using EBV latent membrane protein 1 (EBV-LMP1) immunohistochemical staining. Asian Pac J Cancer Prev, 14, 3963-67.   DOI
8 Iwamuro M, Okada H, Takata K, et al (2014). Diagnostic accuracy of endoscopic biopsies for the diagnosis of gastrointestinal follicular lymphoma: a clinicopathologic of 48 patiens. Ann Diagn Pathol, 18, 99-103.   DOI
9 Jaffe ES, Harris NL, Stein H, et al (2008). Pathology and genetics of tumours of hematopoietic and lymphoid tissues, in: WHO Classification of Tumours, France: IARC Press. Lyon, 166.
10 Kitamura Y, Nanba E, Inui S, et al (1996). Diagnosis of lymphoma in paraffin wax sections by nested PCR and immunohistochemistry. J Clin Pathol, 49, 333-37.   DOI
11 Langerak AW, Groenen PJTA,Bruggemann M, et al (2012). EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations. Leukemia, 26, 2159-71.   DOI
12 Pongpruttipan T, Sukpanichnant S, Assanasen T, et al (2014). Interobserver variation in classifying lymphomas among hematopathologist. Diagn Pathol, 9, 162.   DOI
13 Rizzo K, Nassiri M (2012). Diagnostic Workup of Small B Cell Lymphoma: A Laboratory Perspective. Lymphoma, 2012, 1-15.
14 Rosai J (2011). Lymph nodes, in surgical pathology. saunders elsevier, Philadelphia. 1778-86.
15 Sader-Ghorra C, Rassy M, Naderi S, et al (2014). Type distribution of lymphomas in lebanon: five-year single institution experience. Asian Pac J Cancer Prev, 15, 5825-28.   DOI
16 Taheri ZM, Ziazi LM, Dorudinia A, et al (2011). Clonality of the immunoglobulin heavy chain genes in B cell non-Hodgkin lymphoma using semi-nested PCR. Tanaffos, 10, 25-31.
17 Viera AJ and Garrett JM (2005). Understanding interobserver agreemnet: The happa statistic. Fam Med, 379, 360-3.
18 Werner M, Chott A, Fabiano A, et al (2000). Effect of formalin tissue fixation and processing on immunohistochemistry. Am J Surg Pathol, 24, 1016-19.   DOI
19 Xie R, Chung JY, Ylaya K, et al (2011). Factors influencing the degradation of archival formalin-fixed parrafin-embedded tissue sections. J Histochem Cytochem, 59, 356-65.   DOI
20 Zhou XG, Sandvej K, Gregersen N, et al (1999). Detection of clonal b cells in microdissected reactive lymphoproliferations:possible diagnostic pitfalls in pcr analysis of immunoglobulin heavy chain gene rearrangement. Mol Pathol, 52, 104-10.   DOI
21 Zekri ARN, Hassan ZK, Bahnassy AA, et al (2013). Gene expression profiling of non-Hodgkin lymphomas. Asian Pac J Cancer Prev, 14, 4393-98.   DOI
22 Braunschweig R, Baur AS, Delcretaz F, et al (2003). Contribution of IgH-PCR to the evaluation of b-cell lymphoma involvement in paraffin-embedded bone marrow biopsy specimens. Am J Clin Pathol, 119, 634-42.   DOI
23 Amara K, Trimeche M, Ziadi S, et al (2006). PCR-based clonality analysis of B-cell lymphomas in paraffin-embedded tissue:Diagnostic value of immunoglobulin ${\kappa}$ and ${\lambda}$ light chain gene rearrangement investigation. Pathol Res Pract, 202, 425-31.   DOI
24 Arber DA (2000) Molecular Diagnostic Approach to Non-Hodgkin's Lymphoma. J Mol Diagn, 2, 178-190.   DOI