1. Chronic infections 2. Malignancy

1. Viral infections 2. Bordetella pertusis infections (lymphocytosis promoting factor --> prevents lymphocytes from entering the lymph nodes)

White Cell Disorders Flashcards by Elizabeth Ludwig

Clinical features of neutropenia

Fever, chills, malaise with marked weakness and fatigue
Often infections are the cause, esp ulcerative or necrotizing lesions of the oropharynx that contains lots of microrganisms
Treatment may include GCSF

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DDx for Neutrophilic leukocytosis

Acute bacterial infection
Tissue necrosis
High cortisol (margination pool)

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DDx got Eosinophillic Leukocytosis

Allergy
Parasite
Hodgkins lymphoma –> IL5

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DDx Basophilic Leukocytosis

CML

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DDx Monocytosis

Chronic infections

2. Malignancy

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DDx Lymphocytosis

Viral infections
Bordetella pertusis infections (lymphocytosis promoting factor –> prevents lymphocytes from entering the lymph nodes)

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Infectious Mononucleosis

Cause: EBV (or CMV) infection of oropharynx that also infects liver and B cells
Clinical Picture: LAD (paracortex) and Spleenomegaly (PALS) due to T cell response, increased WBC with atypical lymphocytes
Test: Monospot (screen for heterophile antibodies, 1 week post infection) - if negative think CMV, if + test for EBV viral capsule antigen
Complications: Spleenic rupture; Rash if exposed to PCN, dormant virus in B cells (risk of reoccurance, risk development B cell lymphoma)

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X- linked lymphoproliferative syndrome

SH2D1A gene that encodes protein that activates T cells and NK cells is mutated
EBV either causes a fatal infection or die from lymphoma
Similar rxn in those lacking T cell immunity for other reasons like organ or bone marrow transplant recipients or HIV infected patients)

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Three types of chronic, nonspecific lymphadenitis

Follicular hyperplasia - B cells - RA, toxoplasmosis, early HIV
Paracortical Hyperplasia - T cells - viral (EBV), vaccines (smpx), drug (phenytoin)
Sinus Histiocytosis - macrophages in sinus endothelial lining - immune response to tumor (in lymph nodes draining cancer)

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Cat scratch disease

Self limited lymphadenitis usually in head and neck
Bartonella henselae bacteria
Cat scratch, thorn, or splinter
Children
Rarely encephalitis, osteomyelitis, or thrombocytopenia
Sarcoid like granules progress to stellate necrotizing granulomas

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HSC are CD____ +

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Complications of Infectious Mononucleosis

Splenic rupture
Rash if exposed to PCN
Dormancy of virus in B cells (increases risk of recurrence for mono, risk for development of lymphoma if immunodeficient)

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Causes of neutropenia

Drug toxicity (chemotherapy)
Severe infections (PMNs in tissue)
Treat with GM-CSF or G-CSF

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Causes of lymphopenia

Immunodeficiency (DeGeorge no thymus)
High cortisol state (induces apoptosis of lymphocytes, cushings)
Autoimmune (SLE)
Whole body radiation (most sensitive cell is lymphocyte)

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ALL: pre B

Acute Lymphoblastic Leukemia/Lymphoma precursor B cells ; lymphoblasts in bone marrow >20%
Children associated with Downs after 5 y/o
TdT+ (terminal deoxynucleotidyl transferase; DNA polymerase, in nucleus of lymphoblastic cells) –> Pre B (CD10, CD19, CD20) –> t(12:21) good prognosis; t(9:22) Philadelphia Abl Bcr (Ph+ ALL) poor prognosis, more common in adults
Treat with chemo, prophlaxis to scrotum and CSF (privileged)

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ALL: pre T

Acute lymphoblastic leukemia/lymphoma ; lymphoblasts in bone marrow greater than 20%
TdT positive (terminal deoxynucleotidyl transferase, DNA polymerase, found in nucleus) –> CD2-CD8
Thymic mass, Teenager “acute lymphoblastic lymphoma”

AML

acute myeloblastic leukemia
Myeloblasts in bone marrow > 20%
MPO+
auer rods 
adults 50+

Acute leukemias

Block of differentiation at the pro-blast stage (myeloblast or lymphoblasts)
Blasts differentiate and crowd out bone marrow resulting in penias that portray common acute systemic symptoms
Neutropenia –> infection
Anemia –> fatigue, hypoxia
Thrombocytopenia –> bleeding

Acute promyelocytic leukemia

Type of AML
t(15:17) 15= PML, 17= RAR
Complications: DIC and differentiation syndrome (pulm infiltrates, kidney disease, hypotension)
Can also see t(8: 21), myc and CBFa (needs to be w/CBFb to act as a differentiation TF)
Treat with ATRA, arsenic trioxide

Acute monocytic leukemia

Type of AML
increased number of monoblasts
characterized by gum infiltrates

Acute megokaryoblastic leukemia

no MPO (don't need it because not killing bacteria)
associated with Downs syndrome before the age of 5

Pathophysiology of pre-existing dysplasia causing AML

Alkylating agents (chemo) or radiation can cause Myeloblastic syndrome (hypercellular bone marrow with 20% blasts and become an acute leukemia (AML)

Follicular Lymphoma

t(14:18) [18: Bcl2, 14: IgH]
painless, generally LAD
Tumor cells proliferate in lymph nodes in a way that resembles normal germinal centers but no mitoses or necrotic cells unlike follicular hyperplasia
Not curable, often progresses to diffuse large B cell lymphoma

Mantle cell lymphoma

Area around germinal center in lymph node; cell resembling naive B cells found in mantle ones of normal lymphoid follicles
t(11:14) [14- IgH, 11: cyclin D]
Usually co CD5 and CD19 CD20+ but can be distinguished from CLL/SLL by the lack of proliferation centers and presence of cyclin D

Diffuse Large B cell lymphoma

most common type of lymphoma in adults (median age 50) BCL6 mutation (3q27 rearrangement or pt mutation) can also see a t(14:18) Large neoplastic B cells Present as rapidly enlarging mass often extranodal (GI, brain) Respond well to anti-CD20 immunotherapy and chemo

EBV associate diffuse large B cell lymphoma

subtype of acute large B cell lymphoma | Associated with EBV infection in AIDS patients or immunosuppressed (i.e. transplant)

Primary effusion lymphoma

Associated with Kaposi sacroma virus (HSV 8) Arise in pleural cavity, pericardium, peritoneum latently effected with KSV

Mediastinal large B cell lymphoma

occurs most often in young women, shows predilection for spread to abdominal viscera and CNS

Burkitt's lymphoma

MYC(8) translocation to IgH (14) or light chain K or lambda (2,22) that gives you constitutively active MYC High rate of proliferation and apoptosis brings in macrophages to clean the debris (starry sky appearance) Tumor cells latently infected with EBV Often arises as maxillary or mandibular masses

What types of infections are neutropenic persons at risk for?

bacterial and fungal (rises sharply after count falls below 500 cells / uL -normally 2,000-8,000)

CLL

Mature B cells, increase WBC, older adults CD20/CD5+ LAD (just in LN = SLL

Hairy Cell Leukemia

Mature B cell TRAP + (tartrate resistant acid phosphatase) Spleenomegaly (red pulp) Dry tap bone marrow no LAD Treat with 2CDA (adenosine deaminase inhibitor)

Adult T cell Leukemia Lymphoma

``` CD4+ Tell cells HTLV-1 Asian and Caribbean background Rash LAD with spleenomegaly Lytic bone lesions and hypercalcemia (ddx MM) ```

Mycosis Fungiodes

CD4+ T cells rash, plaque, nodule, Pautrier microabcesses : T inflitrative skin lesions Sezary syndrome : infected cells in the blood, cerebriform nuclei- look like brains)

Myeloproliferative disorders

all of precursors are increased, named by relative increase Older people, High WBC (granulocytes) and Hyperproliferative marrow Hyperuricemia, Gout (high turnover, nucleus of RBCs etc removed and degraded by purine degradation pathway the end product of which is uric acid) Marrow fibrosis Can progress to an acute leukemia

Chronic leukemia

Adults Increased WBC Mature cells

Acute leukemias

>20% blasts in marrow Blasts in blood increase WBC, large immature cells with punched out nucleus (nucleolus) Crowded out marrow leads to anemia, thrombocytopenia, and neutropenia (fatigue/hypoxia, bleeding, infection)

CML

Mutation in HSC Increase in granulocytes, relative greater increase in basophils t(9:22) Chronic, accelerating, and transforming phases Can transform to ALL or AML (mutation in HSC so can become either) No LAP (leukocyte alkaline phosphotase) (differentiates from leukomoid rxn)

Myeloblast markers

Cd34 cd117