PMC9464917_01
(A) Fluorescence in situ hybridization on bone marrow from case 1 showing a reciprocal BCR::ABL1 fusion (arrows, indicated in yellow); red signal, probe for ABL on the long arm of chromosome 9 (9q34); green signal, probe for BCR on the long arm of chromosome 22 (22q11). (B) Cytogenetic analysis on bone marrow from case 1 showing the translocation t(9;22)(q34;q11). (C) Agarose gel analysis from cDNA extracted from peripheral blood from case 1 showing a positive result for the rare e6a2 transcript. BPM, base pair ladder (lines 1, 6, 7, and 13); 19-1250 M (lines 2 and 8), cDNA from patient 1; BV 173, K562, e19a2 (lines 9, 10, and 11), cDNA from BCR::ABL1 positive cell-line controls; Mix (lines 5 and 12), negative controls; rare transcript controls (lines 3 and 4), e6a2 and e8a2.
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However, fluorescence in situ hybridization (FISH) analysis on bone marrow revealed a reciprocal BCR::ABL1 fusion in 99% of 500 cells counted ( Figure 1A ) and cytogenetic analysis was positive for translocation t(9;22)(q34;q11) in 14 metaphases as well ( Figure 1B ). Interestingly, in a second attempt, quantitative real-time PCR, targeting the rare transcript e6a2, revealed a BCR::ABL/ABL1 transcript ratio of 40.563% ( Figure 1C ). Of course, all analyses were performed according to good clinical and laboratory practice, e.g., all analyses were performed as double analyses, including negative and positive controls from peripheral blood of healthy persons ( Figure 1 ).
PMC9464917_02
Immunohistochemistry of the skin biopsy from the second patient. (A) Infiltration of small cellular lymphoid cell components in CD 8 staining; scale bar, 500 microm. (B) Antigen loss of CD2 of the lymphoid infiltrates detected in hematoxylin and eosin staining; scale bar, 500 microm.
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First, the skin effusions showed a CD5, CD7, and CD8 expression ( Figure 2A ), leading to a CD8+ T-cell lymphoma of the skin with aberrant expression of CD117 and loss of CD2 ( Figure 2B ).
Lymph node biopsy from case 2 with myeloperoxidase staining showing infiltration of myeloid precursors; scale bar, 1,000 microm.
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Second, multiple organs showed a severe infiltration with myeloid precursors ( Figure 3 ).
Renal biopsy from case 2 with myeloperoxidase staining showing infiltration of myeloid precursors; scale bar, 2,000 microm.
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Lung involvement (about 50% of the parenchyma), splenic involvement (90%), hepatic involvement (20%), and renal involvement (30%) ( Figure 4 ) possibly explain the relatively sudden worsening of the performance status and multi-organ failure.