Abstract

Background:Angioimmunoblastic T‐cell lymphoma (AITL) is a rare T‐cell lymphoma characterized by a pronounced reactive microenvironment, represented by B and T lymphocytes, eosinophils and histiocytes. In most cases, infection of B‐immunoblasts with Epstein‐Barr virus (EBV) is noted. Anemia, leukopenia, thrombocytopenia and gammopathy could develop through the disease course. Futhermore tumor cells could appear in peripheral blood and bone marrow. Therefore examination of blood smears and bone marrow aspirates is an crucial step in the initial diagnosis and staging in AITL.Aims:To correlate cell composition of peripheral blood (PB) and bone marrow (BM) samples with the the presence of RHOA gene (G17 V) mutation in tumor cells, small non‐coding EBV RNA in the lymph node biopsy specimen and bone marrow involvement in primary patients with AITL.Methods:The study includes 53 primary patients with AITL, admitted to the National Research Center for Hematology between 2002 and 2018. The diagnosis of AITL was based on the morphological study of the lymph node biopsy according to the criteria of the WHO classification 2017. A morphological study of BM biopsy was performed in 52 patients. RHOA gene (G17 V) point mutation was tested in 51 patients using quantitative allele‐specific real‐time PCR. The expression of small non‐coding EBV (EBER) RNA in lymph node biopsy specimens was determined in 43 patients by in situ hybridization. A complete blood count was performed on a Sysmex‐XT 4000i automated analyzer, the leukocyte counts were calculated using a PB smear. For BM counts were used 2 smears of BM aspirate (Pappenheim stain).Results:Anemia (52.8%), an increase in relative counts of granulocytes and lymphocytes for more than 4 times (51.9%), thrombocytopenia (43.4 %) were most frequently observed in PB. Absolute and relative lymphopenia was detected in 44.2% and 51.9% of patients, respectively. Plasma cells in PB were found in 11.5% of cases. The prevalence of the relative number of granulocytes over lymphocytes more than 4 times (82.2%) and abnormal leuco‐erythroblastic ratio (66.7%) were most often detected in BM. A decrease of erythroid lineage was observed in 48.9% of patients, that was combined with anemia of varying severity in 26.7% of cases. In patients with morphological involvement of the BM, anemia and thrombocytopenia were significantly more frequent (p = 0.0001, p = 0.002, respectively). Plasma cells in PB were found only in cases with morphological involvement of the BM (p = 0.01). Also, in this group of patients, a decrease in granulocyte lineage in the BM was significantl(p = 0.04). In patients with RHOA gene (G17 V) mutation, the average hemoglobin level was significantly lower than in patients without mutation (p = 0.01). Anemia was significantly more frequent (p = 0.04) in PB of EBER‐positive patients. On the other hand in EBER‐negative group of patients leukopenia and neutropenia where more frequent (p = 0.01 and p = 0.02, respectively).Summary/Conclusion:Appearance of plasma cells in the PB is associated with the morphological involvement of the BM in AITL. This finding could be possibly used as a new non‐invasive marker of BM involvement in AITL. Furthermore differences in PB and BM counts were associated with small non‐coding EBV RNA, the G17 V mutation of the RHOA and BM morphology.

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