immunohistochemistry

Comparative Pathomorphology of Lymph Node Changes in Kikuchi-Fujimoto and Autoimmune Diseases with Lymphadenopathy: Own Experience

AUTOIMMUNE THROMBOCYTOPENIA ,

AM Kovrigina

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Prof. Alla Mikhailovna Kovrigina, PhD in Biology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: kovrigina.alla@gmail.com

For citation: Kovrigina AM. Comparative Pathomorphology of Lymph Node Changes in Kikuchi-Fujimoto and Autoimmune Diseases with Lymphadenopathy: Own Experience. Clinical oncohematology. 2021;14(1):80–90. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-80-90

ABSTRACT

Background. Pathomorphological analysis of lymph node tissues in immune-mediated lymphadenopathies commonly presupposes differential diagnosis with tumors of lymphoid and myeloid tissues with partial lesions in lymph nodes. Besides, further study is required on pathogenetic relationship between autoimmune diseases with lymphadenopathy and Kikuchi-Fujimoto disease (KFD) with morphological substrate characterized by histiocytic necrotizing lymphadenitis.

Aim. To compare, based on biopsy material, morpho-immunohistochemical characteristics of changes in lymph node tissues in patients with pathomorphological diagnosis of KFD and in patients with autoimmune diseases with lymphadenopathy, i.e. systemic lupus erythematosus (SLE) and adult Still’s disease (ASD).

Materials & Methods. Morphological and immunohistochemical analyses were carried out on lymph node biopsies of 20 patients, 16 out of them with KFD (men/women 15:1, median age 26.5 years, range 18–47 years; in 44 % of cases lesions were only in cervical lymph nodes). In 2 female patients (aged 19 and 33 years) SLE was diagnosed based on clinical and laboratory data, and 2 patients (a woman aged 43 years and a man aged 25 years) were diagnosed with ASD.

Results. Morphological and immunohistochemical analyses detected three major cell populations similar in KFD and SLE and probably reflecting pathogenetic relationship of these diseases: histiocytes expressing myeloperoxidase (MPO+), CD123+ plasmacytoid dendritic cells, cytotoxic CD8+ T-cells, and granzyme B+. In 55 % of KFD cases and 2 SLE cases there were many activated CD30+ lymphoid cells clustered and scattered in the areas of cytotoxic T-cells.

Conclusion. To exclude SLE during subsequent additional examination of patients with morphological substrate characterized by histiocytic necrotizing lymphadenitis it is reasonable to use the term “Kikuchi-like changes” instead of KFD. When the data of immunohistochemical analysis in KFD, SLE, and ASD patients are compared, MPO+ histiocytes in lymph node tissue can serve as diagnostic immunohistochemical marker of immunoinflammatory process. If they are detected, differential diagnosis with myeloid sarcoma is required. CD30 expression by activated cytotoxic lymphoid cells was identified in SLE and in 55 % of KFD cases, which is another important common diagnostic characteristic of the substrate of two diseases (KFD and SLE) and requires differential diagnosis with anaplastic large-cell lymphoma and Hodgkin’s lymphoma. Within the analyzed group of 20 patients morphological substrate of lymph nodes in 2 ASD patients differed in its morphological and immunohistochemical parameters from that in KFD and SLE patients and was characterized by expanded paracortex and morpho-immunohistochemical characteristics of extrafollicular B-cell activation.

Keywords: morphology, immunohistochemistry, Kikuchi-Fujimoto disease, histiocytic necrotizing lymphadenitis, systemic lupus erythematosus, adult Still’s disease, CD30, myeloperoxidase.

Received: July 30, 2020

Accepted: December 2, 2020

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Pathomorphological Diagnosis of Splenic Diffuse Red Pulp Small B-Cell Lymphoma

LYMPHOID TUMORS , , ,

AM Kovrigina, SM Korzhova, LS Al’-Radi, UL Dzhulakyan, BV Biderman, IA Yakutik, AB Sudarikov

Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Alla Mikhailovna Kovrigina, DSci, Professor, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: 7(495)612-61-12; e-mail: kovrigina.alla@gmail.com

For citation: Kovrigina AM, Korzhova SM, Al’-Radi LS, et al. Pathomorphological Diagnosis of Splenic Diffuse Red Pulp Small B-Cell Lymphoma. Clinical oncohematology. 2016;9(3):287-95 (In Russ).

DOI: 10.21320/2500-2139-2016-9-3-287-295

ABSTRACT

Background. Unclassifiable splenic B-cell lymphoma/leukemia is a rare and poorly studied disorder introduced in the WHO classification of hematopoietic and lymphoid tissue malignancies for the first time in 2008. This type of lymphoma requires differential diagnosing between hairy cell leukemia-variant (HCL-V) and splenic diffuse red pulp small B-cell lymphoma (SDRPL).

Aim. To develop criteria for diagnosis of SDRPL by comparison of bone marrow biopsies (BMB) and surgical specimens of the spleen.

Methods. In the Department of Morbid Anatomy of the Hematology Research Center, preoperative BMBs and surgical specimens of the spleen (2013–2015) were compared in 71 patients (men/women ratio 1:2.6, age range 44–81, median age 58 years) using morphological and extended immunohistochemical studies. Sanger sequencing and PCR assay were carried out to analyze the mutational status of IgHV and to identify mutations in MAP2K1, NOTCH, BRAF.

Results. SDRPL was diagnosed in 5 (7 %) of 71 patients. In 2 groups of patients (with normal and high WBC count), the morphological features of spleen tissue were similar to those of a neoplastic substrate of HCL-V. The immunohistochemical assay demonstrates monomorphic expression of CD20 and DBA.44 and heterogeneous expression of CD11c, TRAP, CD103, CD123 in all cases. In none of the 5 cases, expression of CD25, CD27, Cyclin D1, Annexin-1 was found. In bone marrow (unlike HCL and HCL-V), predominantly interstitial and intravascular scant CD20+ lymphoid infiltration (4 of 5 cases) was found without detectable nucleoli in nuclei of small lymphoid cells. In 1 case, there was a combined lymphoid infiltration: CD20+ microfocal-interstitial infiltration with an intravascular component. No persistent molecular mutations in the spleen tissue specimens were found.

Conclusion. SDRPL is diagnosed in 7 % of splenic B-cell lymphomas. It is a rare disorder, whose verification requires an integrated approach taking into account clinical and laboratory data, results of flow cytometry, cytological, morphological, extended IHC and molecular biological studies.

Keywords: immunohistochemistry, splenic diffuse red pulp small B-cell lymphoma, splenectomy, bone marrow biopsy.

Received: April 28, 2016

Accepted: April 29, 2016

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ЛИТЕРАТУРА

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MYC and BCL2 Protein Expression in Patients with Diffuse Large B-cell Lymphoma

LYMPHOID TUMORS , , , ,

AE Misyurina1, AM Kovrigina1, EA Baryakh1, VA Misyurin2, SK Kravchenko1, AV Misyurin2, TN Obukhova1, SM Kulikov1, AN Kopylov2, AU Magomedova1, EG Gemdzhyan1, AI Vorob’ev1

1 Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Anna Evgen’evna Misyurina, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(909)637-32-46; e-mail: anna.lukina1@gmail.com

For citation: Misyurina AE, Kovrigina AM, Baryakh EA, et al. MYC and BCL2 Protein Expression in Patients with Diffuse Large B-cell Lymphoma. Clinical oncohematology. 2015;8(1):44–53 (In Russ).

ABSTRACT

Objective. The objective of this study is to analyze the incidence and the role of MYC and BCL2 protein expression in patients with diffuse large B-cell lymphoma (DLBCL) and to compare data of histological, immunohistochemical, genetic, and moleculobiological analyses with clinical characteristics.

Methods. 62 patients with confirmed diffuse large B-cell lymphoma (DLBCL) were enrolled in the study; they underwent treatment according to the original modified protocol NHL-BFM-90 ± R in the Hematology Research Center under the Ministry of Health of the Russian Federation. A reference group consisted of 13 DLBCL patients who underwent СНОР-like ± R therapy. In all observations, histological and immunohistochemical tests were performed in archived biopsy samples of a tumor tissue or a lymph node (paraffin blocks) using BCL2 (clone 124, Dako) and MYC antibodies (clone Y69, Epitomics). Based on C.P. Hans’s algorithm (2004), GCB and non-GCB immunohistochemical subtypes of DLBCL were determined. Standard cytogenetic tests (n = 22) and FISH analysis (n = 52) were performed in this study in order to determine locus translocation of с-MYC gene, IgH gene, t(8;14)(q24;q32), BCL2 gene, t(14;18)(q32;q21). Quantitative RT-PCR on paraffin tumor/node biopsy samples was also performed to evaluate the number of mRNAs of с-MYC and BCL2 genes.

Results. MYC expression was found in 24 (39 %) of 62 DLBCL patients and BCL2 in 36 (58 %) of 62 patients (threshold values were 40 % and 50 % of tumor cells, respectively). MYC/BCL2 coexpression was diagnosed in 15 (24 %) of 62 DLBCL patients. 4 (27 %) of 15 patients with MYC/BCL2 coexpression had a GCB-subtype of DLBCL, 73 % patients with MYC/BCL2 coexpression were diagnosed with non-GCB subtype of DLBCL (p < 0.02). c-MYC rearrangement was found in two cases (3 %), one of them had a MYC protein expression score more than 40 %. 10 (19 %) patients had one or more additional signal from 8q24 locus of c-MYC gene. We didn’t find any correlation between the presence of additional signals from c-MYC gene locus and the level of immunohistochemical expression of MYC protein ³ 40 % (p < 0.05). BCL2 gene rearrangement was detected in one case; it was accompanied by BCL2 protein immunohistochemical expression ³ 50 %. BCL2 amplification was observed in 17 (40 %) patients. There was a correlation between the amplification of BCL2 gene and immunohistochemical expression of BCL2 protein (threshold value was ³ 50 % of positive cells) (p = 0.0053). There was a direct correlation between the amount of mRNAs and MYC protein (correlation coefficient 0.86; p < 0.0001). There was no correlation between the level of BCL2 gene expression and the amount of protein (correlation coefficient 0.14; p = 0.57). Four-year overall survival for DLBCL patients treated with m-NHL-BFM-90 ± R was 71 % (in patients without MYC/BCL2 coexpression) vs 57 % (in patients with MYC/BCL2 coexpression) (p = 0.39). The probability of relapse or progression of DLBCL was significantly higher in patients with MYC/BCL2 coexpression, than in patients without MYC/BCL2 coexpression (65 % vs 15 %; p = 0.0029).

Conclusions. The MYC/BCL2 coexpression is observed mainly in DLBCL patients with non-GCB immunohistochemical subtype of the disease. The MYC/BCL2 coexpression is vital for prediction of the risk of relapses/progression of the disease in patients receiving an intensive chemotherapy according to the m-NHL-BFM-90 ± R protocol. Taking into account a relatively stable structure of the protein substrate, the obtained data may become a basis for development of a diagnostic immunohistochemical algorithm for stratification of DLBCL patients.

Keywords: DLBCL, intensive therapy, MYC/BCL2 coexpression, immunohistochemistry, unfavorable prognostic factor.

Received: November 8, 2014

Accepted: November 11, 2014

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