Estudio de Casos Xe vs Xn

8/18/2019 Estudio de Casos Xe vs Xn

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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.


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Laboratory Values

Peripheral Smear

FLORID LEUKOCYTOSIS WITH

LEFT SHIFT INCLUDING BLASTS

AND BASOPHILIA


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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


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Analyzer results

XE-5000XN-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


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Martiat P, Michaux J, et al. “Philadelphia-negative chronic myeloid leukemia: comparison with Ph+ CML

and chronic myelomonocytic leukemia”. 1991; 78: 205-211.

.

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 general ly older

– Lower platelet and basophil counts

– Lower rate of blast transformation , but shorter mean survial


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Laboratory Values

Peripheral Smear

Peripheral smear shows 65% blast cells.


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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


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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)


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Analyzer Results

XE-5000 XN-1000

Analyzer Results

XE-5000XN-1000

*WPC Channel is not available in the US

*


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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.


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Plasma Cell Leukemia

Keri Donaldson M.D.

Assistant Professor, Division of Clinical Pathology


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).


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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


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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)


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Analyzer Results

XE-5000XN-1000


*

Analyzer Results

XE-5000 XN-1000


16/29

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.


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Heredity Spherocytosis

Keri Donaldson M.D.

Assistant Professor, Division of Clinical Pathology


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.


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Laboratory Values

Peripheral Smear

• Normocytic, normochromic anemia

• Marked aniso-poikilocytosis

• Polychromasia

• Numerous spherocytes seen


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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 ResultsXE-5000

XN-1000*



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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 shapeand 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 bloodcells


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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


Hershey, PA

Case 5


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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


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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)

• 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.

CLL / SCL – Mantle Cell Lymphoma


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Acute Myeloid Leukemia

Michael Creer M.D.

Professor and Chief of Clinical Pathology

Director Clinical Laboratory

Pathology Residency Program Director


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.


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Laboratory Values

L G

EM

B

no

schistocytes

few

reticulocytes

L MEG

B

no

schistocytes

few

reticulocytes

B = Basophils

E = Eosinophils

G = Granulocytes

M = Monocytes

L = Lymphoytes

Analyzer results

XE-5000 XN-1000


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Reticulocyte production index (RPI) = 0.4

Analyzer Results

XE-5000 XN-1000

monoblast

Peripheral Smear


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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

Monoblast PromonocyteUndifferentiated Blast

Promonocyte

Mature Lymphocyte

Acute Myeloid (monoblast ic 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.

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Estudio de Casos Xe vs Xn