Transcript MLAB 1315- Hematology Fall 2007 Keri Brophy

MLAB 1415- Hematology
Keri Brophy-Martinez
Chapter 20:
Nonmalignant Lymphocyte
Disorders
Review


Lymphs originate primarily from bone
marrow and thymus
Secondary organs include spleen,
lymph nodes, tonsils, and Peyer’s
patches in GI tract
Review

3 general
populations



B- lymphs: 10-20 %
T-lymphs: 60-80%
NK: < 10%
Pluripotent Stem cell
Lymphocyte Stem cell
B-cell
T-cell
Characteristic Cell

Reactive lymphocyte - transformed or benign lymph


Similar terms are transformed lymph, atypical lymph,
virocyte, immunoblast, plasmacytoid, Downey cell
What causes them?


Once stimulated by infection or inflammatory condition,
lymphs enter various stages of activation
Morphologically heterogeneous population presents signs
of activation:

Large irregular shape

Cytoplasmic basophilia

Vacuoles

Azurophilic granules can be present and are thought
to contain pore-forming proteolytic enzymes and serine
proteases with pro-apoptotic activity.
Antigen-stimulated lymphocytes pg. 129





Reactive or Atypical: Atypical is widely used; however, connotes abnormal or
malignant
Downey Cell: obsolete term for reactive lymph and immunoblasts
Immunoblasts:

large cells with prominent nucleoli

fine clear chromatin

dark purple-blue cytoplasm

preparing for or engaged in mitosis in response to stimulus
Plasmacytoid lymphs:

daughters of B immunoblasts

Eccentric nucleus with moderate amount of deep blue cytoplasm
Plasma Cell

Fully differentiated B cell

Eccentric nucleus with “cartwheel appearance” with large amount of
basophilic cytoplasm

Perinuclear clearing (Golgi apparatus)

Releases Ig
Reactive Lymph Characterisitcs
Reactive Lymph
Normal Lymph
Size
9-30 µm
8-12 µm
N:C ratio
Decreased
High
Cytoplasm
Abundant
Colorless to dark blue
Azurophilic granules
Can scallop the RBCs
Scant
Colorless to light blue
Nucleus
Elongated, irregular
Round
Chromatin
Coarse to moderately
fine
Coarse
Nucleoli
Absent to distinct
Absent
Introduction

Majority of disorders affecting
lymphocytes are acquired



Hallmark: reactive lymphocytosis
Reactive process
Congenital disorders

Defect is found within lymphocytic system
Introduction

Important to differentiate benign conditions
associated with lymphocytosis from malignant
lymphoproliferative disorders
 How?
 Presence of heterogeneous reactive lymphs
 Positive serological test for antibodies against
infectious organisms
 Absence of anemia and thrombocytopenia
 All of above favor a benign diagnosis
Lymphocytosis







Excess of lymphocytes in the blood.
Absolute lymphocyte count (ALC) > 4.8 x 109 /L in adults
Relative count > 35-45%
Self-limited
Reactive process is due to infection or inflammatory conditions
B and T cells involved
Lymphocytes develop in response to antigenic stimulation.
They become “activated”
Causes of Reactive Lymphocytosis

Infectious mononucleosis (IM)




Caused by the Epstein-Barr Virus (EBV) which enters the body via
saliva (“kissing disease”)
EBV Pathophysiology

EBV attaches to B lymphs by receptor CD21 which causes it to
express the activation marker CD23 that stimulates Blymphocyte growth factor.

The virus is incorporated into the lymph genome making the cell
express viral proteins on the cell membrane and immortalizes
the line of EBV-lymphs.

Activated cytotoxic T-lymphs are released to inhibit the
activation and proliferation of EBV infected lymphs. These are
the characteristic Reactive Lymphs.
Clinical symptoms

Classic triad: fever, pharyngitis and lymphadenpathy

Dysphagia (difficulty swallowing)

General malaise

Fatigue

Spleen is enlarged and nodes are firm but not tender or warm
Generally seen in children and young adults (14-24 yrs old)
Lab features of IM



CBC

Relative lymphocytosis
 Peaks at 2-3 weeks of infection, remains elevated for
2-8 weeks

Leukocyte count 12-25 x 109/L
Peripheral smear

Reactive lymphocytes , historically referred to as a
Downey cell with irregular cytoplasmic border, increased
cytoplasm and dark blue edge around the periphery of the
cytoplasm.

>20% reactive lymphs
Serologic test

Heterophil antibody test (i.e Monospot)
Causes of Reactive Lymphocytosis

Toxoplasmosis
 Infection with intracellular protozoan
Toxoplasma gondii
 Acquired infections in children and adults
due to ingestion of oocysts from cat feces
or undercooked meat
 Can be transmitted via placenta
Causes of Reactive Lymphocytosis

Cytomegalovirus (CMV) Infection





Belongs to herpes family
Endemic worldwide
Acquired through transfusions, sexual
contact and close contact
Can be transmitted across placenta
Poor prognosis for immunocompromised
individuals who contract virus
Causes of Reactive Lymphocytosis

Infectious lymphocytosis



Affects children
Viruses include adenovirus, coxsackie A
and Bordetella pertussis
Leukocytosis and lymphocytosis occur in
first week of illness then return to normal
Lymphocytopenia


Absolute lymphocyte count< 1.0 x 109/L
Causes





Decreased production or increased destruction of
lymphocytes
Changes in lymphocyte circulation patterns
Corticosteroid therapy
Other unknown causes
Refer to page 411, table 20-4
Immune Deficiency Disorders



Impaired function of one or more of the
components of the immune system: T,
B, or NK lymphocytes
Body unable to mount an adaptive
immune response
Can be acquired or congenital
Acquired Deficiencies

Acquired immune deficiency syndrome
(AIDS)



Infection with a retrovirus, human
immunodeficiency virus type-1 (HIV-1)
Transmission through sexual contact or
contact with blood and/or blood products
Binds CD4 antigen on helper T
lymphocytes which results in cell lysis
Congenital Deficiencies


Decrease in lymphocytes and
impairment in either cell-mediated
immunity (Tcells), humoral
immunity(Bcells) or both
Lymphocytes appear normal on ps
Congenital Deficiencies

Severe Combined immunodeficiency Syndrome
 Major qualitative immune defects involving both
humoral and cellular immune functions
 Fatal by 2 years if untreated by bone marrow
transplant or gene therapy

Wiskott-Aldrich Syndrome
 Patients have recurrent infections due to
immunodeficiency (decreased CD8 T-lymphs),
thrombocytopenia and eczema