Sloka WBC disorders

Normal Bone marrow

Non-neoplastic disorders
o Qualitative
Defects in structure and function
Diseases
Chediak-higashi syndrome
o Neutropenia
o AR
o Failure of lysosomes to fuse w/ phagosome to form
phagolysosomes
Selectins- Integrins
o Corticosteroids, catecholamines, lithium can decrease
activation of neutrophil adhesion molecules
Phagocytosis/Inflammation
Chronic granulomatous disease
Myeloperoxidase deficiency
Symptoms
Unusual pathogens
Frequent infections + growth failure
Severe gingivitis
Lack of inflammatory response
o Quantitative
Neutrophilia- >7000
Infections- appendicitis
Sterile inflammations- AMI
Drug induced- corticosteroids
Stress- labor
Leukocyte adhesion deficiency
o AR
o LAD1 defucuebct if CD11a:CD18 (integrin on neutrophils)
Neutropenia- <1500
o Aplastic anemia
o Immune destruction- SLE
o Chemo
o Septic shock
o B12/Folate deficiency- affects all dividing cells
Decreased production or increased destruction
Activation of adehesion molecules
Eosinophilia= >7000
T1HS- allergies
Parasitic infestation
o Pinworms, adult ascariasis, and single cell organisms DO
NOT
Polyarteritis nodosa
Hodgskins disease

 Addisons disease
Eosinopenia
Corticosteroids
Cushings
Basophils
Myeloid disorder
Leukemia
Lymphocytosis
Viral infection
Whooping cough
Phenytoin
Graves disease
Infectious mononucleosis
EBV
Kissing disease
CD21 receptor for C3d, infects epithelial cells via a5/b1
Worldwide 5-6 y/o common w/ mild flu-like symptoms
Clinical
o Extreme fatigue
o Fever
o Sore throat
o Exudative tonsillitis
o Tender hepatosplenomegaly
Spleen rapid enlargement; possible rupture
Liver only moderately enlarged
o Generalized tender lymphadenopathy
o Ampicillin rash
20-25%; commonly on legs
Does NOT= allergic
Atypical lymphocytosis
20% or more
Atypical benign T lymphocytes kill off B lymphocytes
No contact sports
Positive heterophile test
Positive VCA/EBNA
Increased serum transaminases
Lymphopenia
HIV
Primary immunodeficiency
Autoimmune destruction
Corticosteroids
Radiation- most sensitive
JOB syndrome
o Staph pyoderma
o Hyper IgE and decrease in T17 due to mutation in STAT3: IL-17
o Cold abscesses
o Decreased neutrophil chemotaxis

o Coarse skin
o Lion-like face; reddish hair, large nose
Unusual benign reactions
o Leukoerthroblastic reaction
Leukemoid reactions
o Neutrophils
Acute appendicitis
o Lymphocytes
Whooping cough
Phenytoid
Atypical lymphocyte appearance
o Eosinophils
Parasitic infection of the tissues
Strongyloides
Hookworms
Pinworms
NOT single cell
Leukoerythroblastic reaction
o Fibrosis
o Amyloidosis
Diffuse large B cell Non-hodgkin lymphoma
o MC NHL
o Often w/ autoimmune disease
o Usually elderly adults
o EBV association w/ aids
o Aggressive but potentially curable
Extranodal marginal zone lymphomas
o Derive from mucosa-associated lymphoid tissue (MALT)
o H. pylori= stomach; Sjorgens= salivary glands/intestines; Hashimoto=
thyroid
o May arise in setting of large inflammation
Follicular lymphoma
o Germinal center translocation t(14;18)= overexpression of BCL-2 (antiapoptotic gene)
o Generalized lymphadenopathy that's often asymptomatic
o Older adults
o Follows a indolent course
Hairy Cell leukemia
o Middle-aged men (40-60)
o B cell
o TRAP (tartrate resistant acid phosphatase) presence is used for ID; stains
brown
o BRAF- number one mutation (oncogene)
o Splenomegaly in 90%
o Lymphadenopathy is rare
o Pancytopenia- anemia, leukopenia, and thrombocytopenia
o Hairy cells- hairy projections from cytoplasm
o Monocytopenia- atypical mycobacterial infections

Mantle cell lymphoma

o Nave B cell (CLL small cell lymphoma also is from nave b cell)
o Older males w/ disseminated disease; moderately aggressive
Multiple myeloma/Solitary plasmacytoma
o Post-germinal-center bone marrow homing plasma cell
o Diverse rearrangements involving IgH; 13q deletions
o Older adults- lytic bone lesions, pathologic fractures, hypercalcemia,
renal failure
o Moderately aggressive; Monoclonal antibodies
o Isolated plasma cell masses in bone or soft tissue, indolent
o MC death is infections, 2nd MC is renal failure
Plasma Cell Dyscrasias
o Monoclonal B-cell disorders
Excessive monoclonal Ig and light chain production; detected as spike
on urine SPE
o M components
MC is increased IgG but can be others IgM
Other plasma cell clones (lymphoidpoeis) are suppressed
Bence Jones protein
Light chains in urine associated w/
o B-cell malignancy
o Waldenstorms macroglobulinemia Typically associated w/ a lymphoplasmoid cytoid
lymphoma
High IgM can cause high viscosity ; Thrombosis
common
Immunoelectrophoresis or immunofixation
Specifically identifies Ig and light chain in serum and urine
Classification of plasma cell dyscrasias
o Multiple myeloma
MC in blacks & ages 50-60; Rare under 40
Increased risk w/ radiation exposure
M-spike in 80-90 %
IgG followed by IgA and pure light chain myeloma
BJ protein in urine is positive in 60-80%= toxic to kidneys
Chromosome abnormalities via deletions, translocations
Normal plasma cells to MGUS to myltiple myeloma
Bone marrow w/ sheets of malignant plasma cells in biopsy; lytic
lesions
Aspirate shows greater than 30% of plasma cells
Bone pain
Lytic bone lesions via inhibion of osteoblast differentiation
o Release of IL-1 ( osteoclast activating factor)
Vertebra MC; pathologic fractures
Hypercalcemia
Renal failure in 30-50%
Proteinaceous tubular casts (BJ protein); packaged by
macrophages

o
o

Nephrocalcinosis
o MC acute renal failure
Metastatic disease to interstitial tissue
Primary amyloidosis
o Light chains-amyloid-nephrotic syndrome
Hematologic
Normocytic anemia w/ rouleaux
Thrombocytopenia
Increased sed rate
Prolonged bleeding time due to defect in platelet aggregation
Radiculopathy from bone compression and vertebral fractures
Recurrent infections is a common cause of death
Sepsis due to H. influenza, S. pneumonia
Diagnosis using BM, SPE and UPE, and XR
Lymphoplasmacytic lymphoma- MC gives rise to Waldenstorms
macrogloblnemia
Neoplastic lymphoplasmacytoid B cells
Elderly male-dominat disease
Main risk factor is MGUS
M spike with IgM
BJ protein is present
Generalized lymphadenopathy (not present in myeloma)
Anemia and bone marrow (no lytic lesions like myeloma), liver, and
spleen involved
Hyperviscosity syndrome due to increased IgM
Retinal hemorrhages, strokes, platelet aggregation defects
Heavy chain disease
M protein heavy chain without light chains
No BJ protein
Plasmacytoma- isolated lytic lesions in bone or soft tissue
Vertbra, ribs, pelvis
Slight increase in monoclonal protein
No plasmablasts in bone marrow
No BJ protein
75% develop multiple myeloma
URT (nasopharynx, sinuses, larynx)
Slight increase in monoclonal protein
Absence of malignant plasma cells in bone marrow
Absence of BJ protein
Small percentage may develop multiple myeloma
Amyloidosis
MGUS
MC monoclonal gammopathy
Small IgG M spike in elderly patients
Plasma cells <10% in bone marrow
No BJ protein

Increased risk for multiple myeloma, Waldenstroms

macroglobulinemia
Adult T-cell lymphoma
o HTLV-1 provirus
TAX- TP53, NF-kB- protranscription factor
o Tropical spastic paraparesis
Japan, West Africa, and Caribbean
3-5% develop lymphoma leukemia after 40-60 years
o Aggressive; cutaneous lesions, marrow involvement, and hypercalcemia
o Hepatosplenomegaly, generalized lymphadenopathy, skin infiltration, lytic
bone lesions
o WBC: 10-50k; CD4 lymphoblasts; TdT neg, NN anemia, thrombocytopenia
Mycosis fungoides/Sezary syndrome
o Helper T cell; no specific chromosomal abnormality
o Cutaneous patches, plaques, nodules, or generalized erythema; indolent
o Neoplastic peripheral CD4 Th cells
o Adults 40-60 years
o MF involves skin and other extracutaneous sites
o Skin involvement presents with a rash secondary to T cell infiltration of
epidermis and formation of Pautriers abscesses
Rash to plaque to nodular masses
o Spreads to other sites; lymph nodes MC
o Sezary syndrome refers to skin involvement plus presence of abnormal
Sezary cells which have a prominent fold in nucleus