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So, Park, Cho, Mun, and Huh: Anaplastic Large Cell Lymphoma with Massive Eosinophilia and Complex Karyotype Initially Misdiagnosed as Chronic Eosinophilic Leukemia


We report a patient with massive eosinophilia and a complex karyotype that was initially misdiagnosed as chronic eosinophilic leukemia (CEL), but later diagnosed as anaplastic large cell lymphoma (ALCL) masked by massive eosinophilia. The complex karyotype observed at initial diagnosis remained unchanged later, after the evidence of bone marrow involvement of ALCL was obtained. At diagnosis, genetic aberrations corresponding to metaphase cytogenetics were not identified by interphase fluorescence in situ hybridization, although abnormal results were noted at follow-up. Together, these observations indicate that the complex karyotype at initial work-up has been derived from a low proportion of lymphoma cells with high mitotic ability that were not identified by microscopy, rather than from massive eosinophils. These findings suggest that our patient had ALCL with secondary eosinophilia rather than CEL since initial diagnosis.


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Fig. 1.
Morphology, cytogenetic studies, and interphase fluorescence in situ hybridization (iFISH) at diagnosis (A) and follow-up (B). (A1) Peripheral blood smear showing eosinophilia without abnormal lymphoid cells. (A2) BM examination showing hypercellularity with marked eosinophil predominance. No abnormal lymphoid cells were observed. (A3) G-banded karyotype result showing a complex karyotype at diagnosis. (A4) iFISH using D13S319/13q34 probes and RUNX1/RUNX1T1 probes shows normal hybridization signals. (B1) Peripheral blood smear revealing abnormal lymphoid cells with eosinophilia. (B2) BM aspiration revealing large irregular lymphoid cells with some eosinophils. (B3) G-banded karyotype revealing the same complex karyotype at follow-up as at diagnosis. (B4) iFISH using D13S319/13q34 probes shows two green signals (LAMP1) and one orange (D13S319) signal, indicating deletion of the 13q14.3 locus. iFISH using RUNX1/RUNX1T1 probes shows three green (RUNX1) and two orange (RUNX1T1) signals, demonstrating RUNX1 amplification.
Table 1.
Laboratory characteristics at initial diagnosis and follow-up study
  At initial diagnosis One year after initial diagnosis
Peripheral blood    
 Hemoglobin (g/dL) 13.9 8.0
 Platelet (×109/L) 149 33
 WBC (×109/L) 49.7 45.3
 Differential count    
 Segmented neutrophils (%) 17 29
 Lymphocyte (%) 5 7
 Monocyte (%) 7 3
 Eosinophil (%) 70 28
 Basophil (%) 1 1
 Abnormal lymphocyte (%) 0 32
Absolute eosinophil count (×109/L) 34.8 12.7
Flow cytometry (% of lymphocyte cells)    
 Surface CD3+ 61.0% 1.1%
 Cytoplasmic CD3+ NT 59.0%
 CD3-/CD4+ NT 97.4%
 CD3-/CD8+ NT 0.6%
 CD3+/CD4+ 48.0% 0.3%
 CD3+/CD8+ 9.0% 0.8%
 CD19+ 19.0% 0.0%
 CD16+/CD56+ 7.0% 5.9%
Bone marrow study    
 Cellularity Hypercellular (80–90%) Normocellular (40–50%)
 Myeloblast (%) 0.2 1
 Eosinophil (%) 46.2 20.6
 Lymphocyte (%) 4.8 16.8
 Abnormal lymphocyte (%) not observed 11
  CD30 Negative Negative
  CD3 Negative Negative
  CD20 Negative NT
  CD4 Negative Positive in some aggregates
  CD8 Negative NT
  ALK Negative Negative
Cytogenetic/Molecular study    
  Karyotype 46,XY,add(1)( p31~32),del(1)(q31q32),del(6)(q13),add(7) 46,XY,add(1)( p31~32),del(1)(q31q32),del(6)(q13),add(7)
  (q22),add(9)(q22),add(10)(p11.2),?der(11)t(11;12)(q23;q13), (q22),add(9)(q22),add(10)(p11.2),?der(11)t(11;12)(q23;q13),
  -13,add(16)(p13.3),add(19)(q13.1),add(21) -13,add(16)(p13.3),add(19)(q13.1),add(21)
  (q22),+mar[13]/46,XY[7] (q22),+mar[7]/46,XY[13]
  BCR/ABL1 rearrangement Negative (0.0%) NT
  FIP1L1/PDGFRA rearrangement Negative (0.0%) NT
  PDGFRB rearrangement Negative (0.5%) NT
  KMT2A (MLL) rearrangement Negative (0.5%) Negative (0.0%)
  13q14.3deletion Negative (1.0%) Positive (53.5%)
  RUNX1 amplification Negative (0.0%) Positive (47.0%)
  6q21 deletion NT Positive (19.0%)
  7q31 amplification Negative (0.5%) Positive (30.0%)

cutoff: 1.5%; cutoff: 3.7%.

Abbreviations: ALK, anaplastic lymphoma kinase; FIP1L1/PDGFRA, FIP1-like-1–platelet-derived growth factor receptor-alpha; iFISH, interphase fluorescence in situ hybridization; MLL, myeloid lymphoid leukemia, NT, not tested; PDGFRB, platelet-derived growth factor receptor-beta; RUNX1, Runt-related transcription factor.

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