| Session: Chronic myelogenous leukemia |
| Case number: 160 |
Submitter(s): Nitin J. Karandikar, Franklin Fuda, Daniel Nussenzveig, Atousa Maleki, Kathleen Wilson, Huan-You Wang, Robert W. McKenna.
Clinical history
74-year old woman with a history of chronic myeloid leukemia, diagnosed in 2000, was treated with imatinib (Gleevec) achieving clinical, morphologic and cytogenetic remission. She recently presented with leukocytosis, composed of 45-50% blasts, consistent with a blast transformation (02/2007).
Details of gross/microscopic pathology:
Morphologic evaluation of blood and bone marrow specimens from 2000/2001 were consistent with chronic phase CML. The current blood and bone marrow specimens showed 40-50% small to medium-sized blasts with sightly irregular nuclear contours, moderately dispersed chromatin, occasional prominent nucleoli and scant basophilic cytoplasm. The blasts were negative for MPO and NSE (cytochemical stains).
Immunophenotype (flow cytometry/immunohistochemistry):
Flow cytometric evaluation of a bone marrow specimen from 08/2006 revealed a small population (1.6-1.8%) of blasts with aberrant immunophenotypic features, suggestive of an imminent blast transformation. Evaluation of the current blood and bone marrow specimen (02/2007) revealed an expansion of these blasts (45-50%) with the following immunopehnotypic features: CD34(bright +), CD45(predominatly - to partial dim +), CD38(moderately +), CD33(partial dim + to -), CD13(dim + to -), CD11b(partial dim + to -), CD22(predominantly -/few +), CD117(predominantly -), CD15(-), HLA-DR(+), CD4(dim +), CD1a(-), CD41(-), CD56(-), MPO(-), TdT(+), other T- and B-cell markers(-). These blasts are probably best characterized as "myeloid" but with very unusal features and minimal markers of differentiation along any lineage.
Cytogenetics:
The diagnostic bone marrow specimens (from 2000) showed a 46,XX,t(9;22)(q34;q11.2) karyotype. Interim blood and marrow specimens during the course of therapy (up to 11/2002) continued to show the t(9;22) translocation by conventional karyotyping studies or by FISH [nuc ish 9q34(ABLx2),22q11.2(BCRx2)(ABL con BCRx1)]. Since 04/2003, both blood and bone marrow specimens revealed a normal karyotype by conventional karyotyping (and were negative by FISH). The current blood and marrow specimens were also negative for the t(9;22) translocation by FISH and conventional karyotyping, but revealed an abnormal clone with trisomy 13 as the sole cytogenetic abnormality [47,XX,+13].
Molecular analysis:
Current specimen was negative for bcr/abl rearrangement by PCR.
Interesting feature(s) of submitted case:
1. Gleevec-resistant CML with "blast transformation".
3. t(9;22)-negative status in the face of blast transformation, with the emergence of a new clone.
3. Extremely unusual immunophenotype of blasts: myeloid? null ("stem cell")? some lymphoid features? Some of the most unusual blasts in our experience.
Proposed diagnosis:
Philadelphia chromosome-negative blast transformation of CML under Gleevec therapy.
Panel diagnosis:
agree with proposed diagnosis
Comments:
Images:
 |
Figure 1 |
 |
Figure 2 |
 |
Figure 3 |
 |
Figure 4 |
 |
Figure 5 |
 |
Figure 6 |
 |
Figure 7 |
 |
Figure 8 |
 |
Figure 9 |
 |
Figure 10 |
Back to Top
Back to Cases by Session
Back to Cases by Contact Submitter