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47 Cards in this Set

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Primary (central) lymphoid tissues?
Contain B or T-lymphoid precursors and provide their maturation to fxnally mature, but naive B or T cells.

1. Bone Marrow
-- origin and differentiation of B-lymphocytes

2. Thymus
-- origin and differentiation of T-lymphocytes
Secondary (peripheral) lymphoid tissues?
Sites where Ag specific rxns of mature B and T lymphocytes occur

1. lymph nodes
2. spleen
-- naso and oropharynx --> Waldryer's ring: adenoid and tonsils
-- GI tract --> Peyer's patches
Two major phases of differentiation in T and B cell systems?
1. Early Ag INDEPENDENT phase
-- occurs in primary organs, BM and thymus
-- lymphoid precursors (blasts) give rise to mature cells capable of recognizing Ag but are "naive"

2. Later Ag-DEPENDENT phase
-- exposure to Ag
-- naive lymphocytes undergo "blast transformation" (change in appearance and growth characteristics)
-- become large, proliferating cells that give rise to Ag-specific memory B and T cells and Ab producing plasma cells
B and T cell systems have what two major types of cells?
1. precursor lymphoblasts (primary lymphoid tissue)

2. mature B and T cells
-- can be naive or memory cells
What is the third type of lymphoid cell (other than B and T)?
Natural killer (NK) cells
-- can kill targets w/o prior sensitization and w/o MHC restriction

Appear to derive from common progenitor w/ T cells

Cytoplasm contains azurophilic granules, called larage granular lymphocytes (LGL)
Quantitative lymphocytic disorders can be due to...?
1. congenital immunodeficiency
2. HIV
3. cytotoxic

1. Blood: lymphocytosis
-- reactive
-- neoplastic --> lymphocytic leukemia
2. Lymphoid tissues: lymphadenopathy
-- reactive
-- neoplastic --> malignant lymphoma
What is the most frequent lymphocytic disorder?
Lymphocytosis -- INCREASE in lymphocyte number
Define lymphocytosis.
An increase in the ABSOLUTE lymphocyte count in the peripheral blood (CBC).
-- should be distinguished from relative lymphocytosis due to increase in PMNs

Image of normal vs. absolute vs. relative (185)
Causes of lymphocytosis?
-- infectious mono
-- IM-like syndromes: CMV, acute HIV, Herpesvirus 6, Adenovirus
-- Viral hepatitis
-- Bordatella pertussis

-- Acute lymphocytic leukemia (ALL)
-- Chronic lymphocytic leukemia (CLL)
-- Hairy cell leukemia
-- lymphoma (some lymphomas have cells that circ in peripheral blood)
Compare reactive vs. neoplastic lymphocytosis.
-- Transient
-- WBC <30K/mm3
-- heterogeneous
-- polyclonal

-- sustained
-- WBC >30K/mm3
-- monotonous (monomorphic)
-- clonal
What is infectious mononucleosis?
A benign, self-limiting disorder caused by Epstein Barr virus (EBV)
Clinical presentation of infectious mono?
Typically btwn 10-25y.o.

Fever, malaise

Sore throat (pharyngitis)

Lymphadenopathy and splenomegaly

Pathogenesis of infectious mono?
1. Route of transmission: intimate contact w/ saliva (kissing) from previously infected person
2. EBV infects B lymphocytes -- binds mbrn CD21 -- in the oropharynx
3. Virus disseminates to lymphoid tissues
4. Provokes and intense immune response and symptoms
What are the two types of mono infections?
1. Lytic (productive) infection w/ release of virus, then reinfection

2. Latent infection (incorporated into genome) -- leads to polyclonal B cell prolif
How is mono infection controlled?
1. CTL (CD8+) and NK cells --> the reactive atypical lymphocytes in peripheral blood

2. EBV specific or non-EBV specific (heterophil) antibodies
Pathology of mono?
Peripheral blood smear:
-- atypical lymphocytosis

Lymph node histology:
-- predominant paracortical hyperplasia
How to confirm mono dx?
1. Monospot
-- heterophile Ab test

2. Specific Ab for EBV Ag
-- EA
-- VCA
Clinical course for mono?

resolves in 4-6wks
What is the differential for lymphocytosis?
1. Benign
-- viral infections - mono, CMV, hep
-- Bordatella pertussis

2. Malignant
-- Acute lymphoblastic leukemia
-- Chronic lymphocytic leukemia
-- lymphoma
What is chronic lymphocytic leukemia (CLL)?
a chronic neoplastic (clonal) lymphoproliferative disorder of small mature B-lymphocytes
Clinical presentation of CLL?
-- most common leukemia of adults, middle aged, and elderly
-- often asymptomatic
-- weakness, easy fatigue, weightloss
-- generalized lymphadenopathy (50-60%)
-- splenomegaly and/or hepatomegaly
Lab findings in CLL?
-- sustained peripheral blood lymphocytosis

2. Morphologically small, monotonous, mature lymphocytes w/ condensed (hyperchromatic) chromatin; smudged cells

3. May have anemia, thrombocytopenia (high clinical stages)

4. Hypogammaglobilinemia w/ increased susceptibility to infection
Differential diagnosis of lymphocytosis?
1. reactive lymphocytosis

1. Mature
-- Hairy cell leukemia
-- Lymphoma
2. Immature
-- ALL
BM aspirate and biopsy in CLL?
1. infiltrate of small lymphocytes

2. patterns: interstitial, nodular, and diffuse
Lab tests to confirm dx of CLL?
1. Immunophenotyping
-- clonal mature B lymphocytes
-- monoclonal B-cells (expression of monoclonal kappa or lambda light chain, CD20, CD19)
-- dim surface Ig
-- CD5+
-- CD23+

2. Cytogenetics
-- trisomy 12q
-- deletions of 13q12-14, 11q, and 17p
What will CLL lymph node biopsy look like?
1. diffuse effacement by an infiltrate of small lymphocytes

2. pseudonodule "growth centers" of prolymphocytes and paraimmunoblasts

3. CLL and/or SLL
Compare CLL with SLL (small lymphocytic lymphoma).
They are morphologically, genotypically, and phenotypically identical

Differ in clinical distribution:
-- CLL --> bone marrow and blood; circulate and infiltrate LN, liver, spleen
-- SLL --> predominantly involves LN but cells spread to BM and blood

Some pts may present later in disease and have involvement of all sites, prompting term CLL/SLL
Clinical course of CLL?
1. indolent but UNCURABLE

2. infections

3. Richter transformation to large cell lymphoma
-- ~10% manifest as rapidly enlarging mass in LN or spleen

4. Prolymphocytic transformation (15-30%)
-- worsening cytopenias
-- large cells w/ prominent nucleoli (prolymphocytes) in blood
-- increasing splenomegaly
What is Hairy cell leukemia (HCL)?
a clonal lymphoproliferative disorder of mature B cells
-- represents 2% of all leukemias
HCL clinical presentation?
Adults (mean of 50)

More common in men

Splenomegaly -- often massive

Often symptomatic:
-- fatigue
-- recurrent infection
-- abdominal discomfort
HCL peripheral blood smear findings?
1. pancytopenia
2. neutropenia
3. monocytopenia
4. circulating abnormal lymphocytes "hairy cells"
Lab tests to confirm dx of HCL?
1. Tartrate Resistant Acid Phosphatase (TRAP) Stain
-- TRAP +

2. Immunophenotyping
-- Clonal mature B-lymphocytes
-- Monoclonal B cells
-- strong surface Ig
-- CD11c+, CD25+, CD103+
HCL BM biopsy will show...?
-- usually leads to "dry tap" on attempted BM aspiration

Interstitial infiltration by hairy cells w/ pale to clear cytoplasm
- "fried egg" appearance
HCL splenectomy will show?
infiltration of red pulp forming "blood lakes"
Features distinguishing HCL from CLL?
1. splenomegaly but NO lymphadenopathy

2. pancytopenia NOT leukocytosis

3. hairy cells NOT small lymphocytes

4. Bone marrow NOT aspirable

5. TRAP(+)

6. Immunophenotype
Clinical course of HCL?
Long lasting remissions w/ newer chemo agents
-- 2CDA, deoxycoformycin, alpha-interferon
What is lymphadeopathy?
Enlarged LN due to benign or neoplastic disorders
What type of neoplastic disorders can cause lymphadenopathy?
metastatic malignancies
-- carcinoma

neoplasms primary to lymphoid system
-- lymphoma
Cellular composition of the normal lymph node?
1. mantle cells
-- naive B cells
2. follicle center cells
-- centroblasts - large noncleaved cells
-- centrocytes - small cleaved cells
3. marginal zone B cells (memory B)
-- normally only seen as a well-defined compartment in the spleen and mesenteric lymph nodes

-- paracortex

-- medulla

-- sinuses
Causes of reactive lymph node hyperplasia?
Infections: bacterial, protozoal, fungal
Autoimmune disease
Patterns of reactive lymph node hyperplasia?
1. follicular

2. paracortical

3. mixed (follicular and paracortical)

4. sinusoidal
Acute lymphadenitis?
1. bacterial infection
2. viral infection

1. follicular hyperplasia
-- germinal centers
-- tingible body macrophages
2. suppuration
Chronic lymphadenitis that causes follicular hyperplasia?
Autoimmune D/O's
Viral infection (early HIV)
Chronic lymphadenitis that causes paracortical hyperplasia?
Dermatopathic lymphadenopathy
Drug HSN rxn - Dilantin
Chronic lymphadenitis that causes sinus histiocytosis?
Rosai-Dorfman disease
-- sinus histiocytosis w/ massive lymphadenopathy
Causes of chronic granulomatous lymphadenitis?
caseating granulomas
-- mycobacterial
-- fungal

suppurative granulomas
-- cat scratch disease
Differential for lymphoid hyperplasia?
1. Distinguish from lymphoma
-- preservation of architecture
-- heterogeneous cell population
-- polyclonal
-- usually self-limited

2. Identify etiologic agent