Lymphocytosis and Lymphoid Leukemias Flashcards
Similar to the myeloid counterparts (i.e. neutrophils, eosinophils), lymphocytes can be expanded in the blood in either reactive or neoplastic processes and this is referred to as:
lymphocytosis
A lymphocytosis is defined as an absolute lymphocyte count of
>4k/uL.
Clinical scenario, morphology, duration, and WBC count are important in differentiating benign (reactive) from neoplastic lymphocytoses.
In general, reactive increases in lymphocytes are_________, while neoplastic
proliferations are_______
transient
chronic (persisting for >6months)
Reactive expansions in general do not exceed
_______, while neoplastic lymphocytoses can cause extremely elevated WBC counts.
10k/uL
________expansions tend to have heterogeneous-appearing lymphocytes, which vary in size and cytoplasm
________proliferations tend to be composed of monotonous-appearing lymphocytes.
reactive
neoplastic
Most common causes of reactive leukocytosis are:
Infectious
transient stress lymphocytoses
List common infectious causes of lymphocytosis
Mononucleuosis (from EBV), cytomegalovirus (CMV), hepatitis, varicella,
adenovirus, toxoplasmosis, and pertussis
What are common causes of transient stress lymphocytoses?
trauma, myocardial infarctions, or seizures and rapidly reverse within
hours
Describe the morphology of lymphocytes seen in mononucleosis
heterogeneous, large, and have abundant, lightly basophilic cytoplasm, which
encroaches on neighboring red blood cells
In mononucleosis, lymphocytes represent ______, which are
responding to the EBV-infected B cells.
cytotoxic T cells
A presumptive diagnosis of infectiousmononucleosis can be made from peripheral blood smear examination by meeting the following 3 criteria:
1) >50% mononuclear cells in the differential (monocytes and lymphocytes)
2) marked lymphocytic heterogeneity
3) >10% reactive lymphocytes (>10/100 leukocytes).
(Confirmation of the diagnosis is made with identification of
heterophil antibodies in the “monospot” test.)
Neoplastic proliferations of mature lymphocytes include:
chronic lymphocytic leukemia (CLL), hairy cell leukemia, splenic marginal zone lymphoma, large granular lymphocytic leukemia, adult T-cell leukemia (ATLL), and Sezary syndrome
In neoplastic lymphocytosis, do we expect to see all disorders to present with elevated lymphocyte counts?
No, but abnormal lymphocyte morphology is certainly observed in the majority of these diseases.
In unexplained lymphocytosis, morphology may not be enough to identify the disease thus we should perform:
Flow cytometry
________will identify what
predominant cell type is present, as_______ does not allow definite distinction
between T cells, B cells, or NK cells.
Flow cytometry
morphology
By definition, the neoplastic proliferations will show
evidence of clonality how?
by monoclonal light chain expression
or immunophenotypic aberrancy
(abnormal antigen expression, such as CD5 on B cells).
(kappa or lambda-restricted populations of B cells)
would be polyclonal and demonstrate an admixture of kappa- and lambda-expressing B cells and CD4(+) and CD8(+) T cells.
Reactive expansions
Be able to recognize a histogram and what it is telling you
note the X and Y axsis. These will tell you if you have just kappa, just lambda or mixed
When neoplastic lymphoid cells involve the blood predominately, the process is termed a
leukemia
When neoplastic lymphocytes are predominately tissue-based (lymph nodes, spleen, liver), the process is termed
lymphoma.
How does WHO classify lymphoid neoplasms?
By cell of origin, cell size/morphology, genetics, and clinical features
Acute Lymphoblastic Leukemia/Lymphoma
(ALL) is predominately a ______ neoplasm defined by increased lymphoblasts
ALL is as immature lymphoid neoplasm***
pediatric
What is the precursor cell in ALL?
Precursor B cell in the bone marrow
Salient Clinical Features of ALL
Predominantly children; symptoms relating to marrow replacement and
pancytopenia; aggressive
What genetic abnormalities in ALL are associated with a good prognosis?
Hyperdiploidy
t(12;21)
What genetic abnormalities in ALL are associated with a BAD prognosis?
Hypodiploidy
t(9;22)
11q.23 abnormalities (MLL)
What is the immunophenotype for ALL?
CD34(+)
CD10(+)
TDT(+)
CD19(+)
CD20(-)
Cell of origin for T-cell acute lymphoblastic leukemia/lymphoma
(T-ALL)
Precursor T cell (often of thymic origin)
Predominantly a_dolescent male_s; thymic/mediastinal masses and variable bone marrow involvement;
aggressive
Classic T-ALL
*board question
what specific chromosomal abnormalities are associated with T-ALL?
None
What is the immunophenotyping for T-ALL
CD3(+)
CD4-8 dual (+)
TDT(+)
T-ALL and B-ALL are both examples of
immature lymphoid neoplasms
Lymphocytosis composed of small lymphs with round nuclei and “soccer
ball” or“gingersnap” chromatin
Chronic lymphocytic leukemia/small lymphocytic lymphoma
(CLL/SLL)
Clinical picture of individuals with Chronic Lmphocytic Leukemia
Older adults with bone marrow and lymph node disease; usually
asymptomatic; autoimmune hemolysis and thrombocytopenia in a minority; indolent
What two cytogenetic abnormalities are associated with a good prognosis in CLL?
Good prognosis:
Deletion 13q
Mutated IgHV
What two cytogenetic abnormalities are associated with INTERMEDIATE prognosis in CLL?
Trisomy 12
What two cytogenetic abnormalities are associated with BAD prognosis in CLL?
Bad prognosis:
Deletion 11q
Deletion 17p
Unmutated IgHV
Immunophenotype:
CD5(+)
CD19(+)
CD23(+)
CLL
Describe the morphology of hairy cell leukemia
Lymphocytes with “hairy” cytoplasmic projections and reniform nuclei
Classic clinical picure of pt with Hairy cell leukemia
40-60y/o males with pancytopenia and
splenomegaly; indolent
Chormosomal abnormality in hairy cell leukemia
No specific
chromosomal
abnormality
Immunophenotype of hairy cell leukemia
CD19, CD20(+), CD11c, CD22 bright (+)
What 2 mature B cell leukemias do we need to know
Chronic lymphocytic leukemia
Hairy Cell leukemia
What is the cell of origin for Adult T-cell leukemia/ Lymphoma (ATLL)
Helper T cell
CD4(+),
CD25(+)
HTLV-1 provirus
present in tumor cells
Adult T-cell
leukemia/Lymphoma (ATLL)
Adults with skin lesions, hepatosplenomegaly, lymphadenopathy, and
hypercalcemia; endemic in Japan, West Africa, and the Caribbean due to HTLV
prevalence; aggressive
ATLL
adult T cell leukemia/lymphoma
A pathologist points out the “Flower” cells on the HE smear, what is this indicitive of and what does it mean?
lymphocytes with lobulated nuclei; often lymphocytosis
Seen in ATLL
What is the cell of origin in Mycosis fungoides/ Sézary syndrome
(MF/SS)
Helper T cell CD4(+)
What genetic abnormality is present in Mycosis fungoides/
Sézary syndrome (MF/SS)?
No specific
chromosomal
abnormality
What is the clinical picture of patient with mycosis fungoides/Sezary syndrome?
Adult patients with cutaneous patches, plaques, nodules (MF),
Sezary generalize erythema adn lymphadenopathy and is more aggressive
A pathologist points out lymphocytes on a slide with “cerebriform” nuclei and powdery chormatin. The smear was taken from the blood.
Dx?
How would the Dx change if the sample was obtained from the skin?
Sezary Syndrome (blood)
Mycosis Fungoides from skin
What is the clinical picture in a patient with Sezary Syndrome?
or generalized erythema and lymphadenopathy (SS); SS has a more aggressive behavior than MF
What is the cell of origin in a patient with T-cell Large granular lymphocytic leukemia
(LGLL)
Cytotoxic T cell CD8(+)
What is the genetic abnomality in a patient with T-cell Large granular lymphocytic leukemia
(LGLL)
No specific
chromosomal
abnormality
What is the clinical picture in a patient with LGLL?
Adult patients with neutropenia, anemia, splenomegaly; may be
associated with autoimmune disease (i.e. rheumatoid arthritis); indolent
Lab findings in patient with T-cell Large granular lymphocytic leukemia
(LGLL)
Lymphocytes with eosinophilic granules
What are the three neoplasms of mature T cells?
Adult T cell leukemia/lymphoma (ATLL)
Mycosis fungoides/Sézary syndrome (MF/SS)
T-cell Large granular lymphocytic leukemia (LGLL)
