Chronic Myelogenous

Leukemia

Sara Ohanessian M.D.

Pathology Resident
Penn State Milton S Hershey Medical Center
Hershey, PA

Clinical History
23 year old male diagnosed with juvenile CML at age 11.
Multiple admissions for blast crisis with white blood cell
count >400K
Transferred to Hershey Medical Center on December 13,
2013 with shortness of breath on exertion, productive
cough, and nasal symptoms.
Treated with the tyrosine kinase inhibitor Nilotinib and
allopurinol which decreased his white blood cell count.

1
 Laboratory Values

Peripheral Smear

FLORID LEUKOCYTOSIS WITH

LEFT SHIFT INCLUDING BLASTS
AND BASOPHILIA

2
BONE MARROW BIOPSY

Blasts within the normal range

High percentage of the immature
myeloid cells
High basophil and eosinophil
percentages
Erythroid precursors are low

Analyzer Results

XE-5000 XN-1000

3
Analyzer results

XE-5000
XN-1000

Molecular testing

He was known to have a p210

BCR/ABL molecular fusion
transcript
ABL Gene Mutation
Resistance to certain tyrosine
kinase inhibitor drugs

4
 .

Interesting CML Facts

Up to 5% will not have this 9;22 Philadelphia chromosome
translocation BCR/ABL negative CML
These patients have:
A poorer prognosis
Are generally older
Lower platelet and basophil counts
Lower rate of blast transformation, but shorter mean survial

Martiat P, Michaux J, et al. Philadelphia-negative chronic myeloid leukemia: comparison with Ph+ CML
and chronic myelomonocytic leukemia. 1991; 78: 205-211.

5
 Acute Undifferentiated
Leukemia

Sara Ohanessian M.D.

Pathology Resident
Penn State Milton S Hershey Medical Center
Hershey, PA

Clinical History

85 year old male

Complaining of swelling in his left wrist and
hand
The patient is currently receiving
Decitabine

1
Laboratory Values

Peripheral Smear

Peripheral smear shows 65% blast cells.

2
Flow Cytometry

Acute Unclassifiable Leukemia

Undifferentiated blasts expressing HLA DR,
CD7, CD13, and CD56

Flow Cytometry Report Comment: Blasts are very undifferentiated expressing

several T-associated but not T-specific markers including CD5, CD7 with small
subpopulation co-expressing cytoplasmic CD3 (1%) along with myeloid-associated
antigens such as CD33 and CD13, negative for cMPO. According to WHO 2008
classification, such cases are best considered acute unclassifiable leukemia.
Correlation with marrow morphology and clinical presentation is required.

Bone Marrow Biopsy

Hypercellular marrow
95% cellularity including undifferentiated blasts
Decrease in other cell lines

3
Molecular Studies

Molecular Studies

FTL3 Internal Tandem Dup Not Detected

FTL3 TKD Mutation Not Detected
NPM1 Mutation - Negative
CEPA Mutation Not Detected
(CEPA = CCAAT/enhancer binding protein alpha)

4
Analyzer Results
XE-5000 XN-1000

Analyzer Results
XE-5000
XN-1000
*

*WPC Channel is not available in the US

5
CEBPA Transcription Factor
What type of gene is CEBPA?
A transcription factor involved with granulocyte maturation and
controls proliferation and differentiation of myeloid progenitors.
They are seen in 13-18% of patients with cytogenetically normal
AML.
What is the prognostic significance?
This mutation is an independent and favorable prognostic factor
for outcome, similar to that of the t(8;21), inv(16), and t(15;17)
subgroups.

6
 Plasma Cell Leukemia

Keri Donaldson M.D.

Assistant Professor, Division of Clinical Pathology
Penn State Milton S Hershey Medical Center
Hershey, PA

Case Study - Clinical History

75 year old female diagnosed with

monoclonal gammopathy of uncertain
significance (MGUS) February 2001
Progressed to plasma cell myeloma
September 2005.
She showed relapse in 2012 (rapid
increase in IgG-lambda restricted).

1
Case Study - Clinical History

The patient was considered for an

autologous stem cell transplant
Her peripheral plasma cell count was 30%,
which indicated secondary plasma cell
leukemia.

Laboratory Values

2
Peripheral Smear
Numerous plasmacytoid
lymphocytes
Plasma cells, consistent with
plasma cell leukemia

Bone Marrow Biopsy

Bone marrow biopsy showed 48% plasma cells

FISH showed t(14;16)

3
Analyzer Results
XE-5000
XN-1000
*

*WPC Channel is not available in the US

Analyzer Results

XE-5000 XN-1000

4
Analyzer Results
XE-5000 XN-1000

Plasma Cell Leukemia

The peripheral blood shows clonal plasma

cells in excess of 2x109/L or 20%.
They can be present at diagnosis (primary
PCL 2-5% of cases) or evolve as a late
feature in the course of plasma cell
myeloma (secondary PCL).
This is an aggressive disease with short
survival.

5
 Heredity Spherocytosis

Keri Donaldson M.D.

Assistant Professor, Division of Clinical Pathology
Penn State Milton S Hershey Medical Center
Hershey, PA

Clinical History

6 year old girl with hereditary

spherocytosis who presented with
headaches, vomiting, poor PO intake, and
bone pain.
She has had previous similar episodes of
hemolytic and sequestration anemia.
She received fluid hydration, red blood cell
transfusion, and underwent a laparoscopic
splenectomy.

1
Laboratory Values

Peripheral Smear
Normocytic, normochromic anemia
Marked aniso-poikilocytosis
Polychromasia
Numerous spherocytes seen

2
Final Pathologic Diagnosis
Splenectomy
Spleen with features consistent with hereditary
spherocytosis
Microscopic Description
Sections show a spleen with quiescent white pulp and
markedly congested pulp cords with variably empty or
squeezed sinusoids

Analyzer Results
XE-5000
XN-1000
*

*WPC Channel is not available in the US

3
Analyzer Results
XE-5000 XN-1000

Hereditary Spherocytosis
Hereditary spherocytosis results in:
Congenital hemolytic anemia due to cytoskeletal
instability
Osmotic fragility with an increased spherical shape
and lack of plasticity
Most families show autosomal dominance:
25% recessive, varying from mild to severe
phenotypes
The variance is due to one of several defects in
cytoskeletal proteins including band 3, protein 4.2,
spectrin, and ankyrin
Splenectomy prolongs the survival of red blood
cells

4
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
(CLL / SLL)

Michael Creer M.D.

Professor and Chief of Clinical Pathology
Director Clinical Laboratory
Pathology Residency Program Director
Penn State Milton S Hershey Medical Center
Hershey, PA

Case 5

1
CASE 5

Clinical History
64 year old male with a history of Chronic Lymphocytic
Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
since May 2012
It had been diagnosed by flow cytometry as a B-cell lymphoid
population expressing HLADR, CD5, CD19, CD20, CD22, CD23
and negative for CD10.
Began experiencing abdominal pain, fever, and
worsening fatigue with shortness of breath since October
2013.
He was transferred from an outside hospital for a white
blood cell count of 217,000.

Laboratory Values

CellaVision
data

2
Analyzer Results
XE-5000 XN-1000
*
B
B
L G
L G E
E

*WPC Channel is not available in the US

Analyzer Results
XE-5000 XN-1000

3
Peripheral Smear (CellaVision Image)

*
*

Flow Cytometry Peripheral Blood Results

CD5+, CD23+ lambda light chain restricted monotypic B

cells, consisten with B cell lymphoma
Neoplastic cells are CD38 positive
Percentage of cells with abnormal phenotype: 87% -
Compared to 86% abnormal cells by smear
Comments: The phenotype is compatible with chronic
lymphocytic leukemia. If not previously done, FISH for
(11;14) should be considered to rule out blastic mantle
cell.

4
CLL / SCL Mantle Cell Lymphoma

Hydroxyurea and allopurinol with fluid

resuscitation were administered.
FISH confirmed t(11;14) which revealed
blastic mantle cell lymphoma (MCL)

CLL / SCL Mantle Cell Lymphoma

MCL is usually positive for CD5, CD20 and

CD38, but negative for CD10 and BCL6.
CD23 is usually only weakly positive.
Aberrant blast-like phenotypes have
been described and the t(11;14)(q13;q32)
between IGH and the cyclin D1 (CCND1)
genes is present in almost all cases.

5
 Acute Myeloid Leukemia

Michael Creer M.D.

Professor and Chief of Clinical Pathology
Director Clinical Laboratory
Pathology Residency Program Director
Penn State Milton S Hershey Medical Center
Hershey, PA

Clinical History
4 year old female presented to her pediatrician
with her mother for a non-resolving fever.
Noted to have hepatosplenomegaly, skin
bruises, and tachycardia.

1
Laboratory Values

Analyzer results
XE-5000 XN-1000
B B = Basophils
B E = Eosinophils
G = Granulocytes
M = Monocytes
L = Lymphoytes
M G L MG
L E E
few
reticulocytes
no
schistocytes

no
schistocytes few
reticulocytes

2
Analyzer Results
XE-5000 XN-1000

Reticulocyte production index (RPI) = 0.4

Peripheral Smear

monoblast

3
 Bone Marrow
Final Pathologic Diagnosis:
Acute Myeloid (monoblastic features) Leukemia
Phenotype:
Abnormal myeloid/monocytic blasts expressing: CD45, CD33, CD11c, CD64,
HLA-DR and CD34, CD34 is negative.
They are aberrantly positive for TdT (dim) and aberrantly negative for CD13 and
CD117. All other markers were negative

Promonocyte
Monoblast Promonocyte
Undifferentiated Blast Mature Lymphocyte

Acute Myeloid (monoblastic features)

Leukemia
Induction chemotherapy with a modified 7+3
regimen consisting of donorubicin, etoposide,
and cytarabine was completed.
Cytogenetics showed an unfavorable t(10,11)
translocation.
Based on these high risk features, she is being
HLA typed for a possible bone marrow
transplantion.