PMC6336602_01
Histopathological examination of liver tissue sections: multiple focal hepatocytes necrosis and apoptosis in hepatic lobule; ballooning degeneration and fatty degeneration of some hepatocytes; mildly expanded hepatic sinusoids with beaded arrangement of lymphocytes; and patches of severe piecemeal necrosis and severe lymphocytic infiltration in portal tracts, mixed with occasional atypical lymphocyte with dark cytoplasm, prominent nucleoli, and vacuolar nucleus. A) Hematoxylin-eosin staining (200x); B) Masson-trichrome staining (200x); C) Reticular fiber staining (200x); D) Periodic acid-Schiff staining (200x); E) Cytokeratin 19 staining (200x); F) CD38 staining (200x).
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F1
Liver biopsy was performed and then the diagnosis of DILI was considered based on liver pathology (Fig. 1). Repeat evaluation of the pathologic section of the liver (borrowed from the local hospital) showed mildly expanded hepatic sinusoids with beaded arrangement of LYs; severe lymphocytic infiltration in portal tracts, mixed with occasional atypical LY with dark cytoplasm, prominent nucleoli, and vacuolar nucleus (Fig. 1).
The proportion of NK cells was increased and the phenotype was abnormal based on immunophenotyping for hematological malignancy analysis (bone marrow) detected by flow cytometry with CD45/SSC gating and normal cells as internal reference. Cell population proportion in total 105 cells: lymphocyte (green) 31.8%, monocyte (purple) 2.3%, granulocyte (blue) 57.6%, blast cell (red) 2.0%, erythroblast (gray) 6.3%. Results: CD34+ cells accounted for 0.1% of nuclear cells, and lymphocytes accounted for about 31.8% of nucleated cells, of which CD3-CD56+ NK cells accounted for about 79.8% and the cells were CD2, CD38, CD56, CD94 positive, and CD7 negative. CD = clusters of differentiation, NK = natural killer, SSC = side scatter.
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F2
Bone marrow immunophenotyping for hematological malignancy by flow cytometry with CD45/side scatter (SSC) gating and normal cells as internal reference showed that: lymphocytes (LYs) accounted for about 31.8% of nucleated cells, of which CD3-CD56+ NK cells accounted for about 79.8% and the cells were CD2, CD38, CD56, CD94 positive, and CD7 negative (Fig. 2).
Bone marrow aspiration showed the presence of focal hemophagocytosis and atypical lymphoid cells. Cytomorphologic features (A, B, 1000x): 3 cell-lineage of erythrocyte, granulocyte, and thrombocyte in bone marrow showed active proliferation with toxic change in some granulocytes. The proportion of lymphocytes was within the normal range; occasionally, atypical lymphocytes characterized by dense chromatin and purple-red particles in cytoplasm. The mononuclear-macrophage showed active proliferation and phagocytic red blood cells, platelet fragments and coarse particles were scattered within the cytoplasm. Bone marrow pathology: clusters or cord-shaped cells distributed in hematopoietic tissues, with large cell volume and deep nuclear staining. Reticular fiber staining: myelofibrosis-1.
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F3
Reticular fiber staining: myelofibrosis-1 (Fig. 3).