| Session: Chronic myelogenous leukemia |
| Case number: 049 |
Submitter(s): Jonathan W. Said, Sheeja Pullarkat, Dinesh Rao.
Clinical history
60 year old man presented with back pain and workup at an outside institution suggested acute leukemia, at which time he was refererred to UCLA and a repeat bone marrow biopsy yielded a dry tap. Flow cytometry, cytogenetics, and FISH studies were performed on the core.
Details of gross/microscopic pathology:
The peripheral blood smear demonstrates normal or slightly elevated white cell count with 80% mature neutrophils and 5% immature myeloid cells (myelocytes). Platelets are reduced and red cells are unremarkable.
The bone marrow is replaced by an infiltrate of large malignant cells with prominent nucleoli including large anaplastic and Reed Sternberg-like cells. Many cells are multinucleated and include wreath-like forms. There are only a few residual hematopoietic elements.
Immunophenotype (flow cytometry/immunohistochemistry):
The cells are positive for CD45. There is weak variable expression of CD7, CD30, and CD117 by a fraction of the malignant cells and a few cells have cytoplasmic staining for granzyme B. Stains for ALK, CD20, CD99, CD10, CD34, hemaglobin A, myeloperoxidase, Factor VIII, CD2, and TdT are negative.
Flow cytometry perfomed on a blast gated population that accounted for about 3% of the cells, positive for CD3, CD13, CD33, and CD45 with less than 1% positive for CD34 and cD117.
Cytogenetics:
Cytogenetics revealed a near triploid karyotype with non-random gains on several chromosomes. The cells were all PH-positive with a 9;22 translocation, and 50% of cells there had an extra Ph-chromosome.
FISH detected BCR-ABL fusion signals in 80% of the cells including small cells and the large anaplastic cells. 36% of the abnormal cells had three fusion signals, suggesting an extra Ph-chromosome. Also an additional copy of the ABL specific signal was detected in 42% of cells suggesting evolution. FISH analysis with "breakapart" rearrangement probes specific for the 2p23 locus detected three chromosome 2 specific signals (trisomy 2) in 38% of cells. There was no evidence of ALK rearrangement. "Breakapart" rearrangement probe specific for the 11q13 locus detected 4 chromosome 11 specific signals in 17% of cells.
Molecular analysis:
None.
Interesting feature(s) of submitted case:
Morphologic features favor anaplastic large cell lymphoma but the presence of a philadelphia chromosome and about half the cells with two philadelphia chromosomes as well as additional cytogenetic abnormalities raises the question of the relationship to CML or evolution from CML. One possibility is that the Philadelphia chromosome occurred in a primitive stem cell followed by additional hits including a second philadelphia chromosme and trisomy 2 and 11 resulting in a unique histologic appearance resembling anaplastic large cell lymphoma. The authors are grateful for the insights of Dr. James Vardiman at the University of Chicago who kindly consulted on this case.
Proposed diagnosis:
Philadelphia chromosome positive anaplastic large cell lymphoma, possible evolved from CML.
Panel diagnosis:
CML, blast phase (AML)
Comments:
Stains performed by the panel: neoplastic cells, including large multinucleated forms, are positive for CD33, CD61, CD117(occasional), and negative for CD3.
Images:
 |
Figure 1 |
Back to Top
Back to Cases by Session
Back to Cases by Contact Submitter