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 AbundantColorless to dark blueAzurophilic granulesCan scallop the RBCs

ScantColorless 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 B-lymphocyte 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