Lecture 13: Leukocyte Disorders Part 2 Flashcards
Where are the extranodal lymph sites?
Skin
GI tract & liver
Bone marrow
Testicles
Which lymph nodes are largest in children? Smallest?
Largest are anterior cervical <= 2cm
Smallest are axillary <= 1cm
What lymph nodes should I palpate on children vs adults?
Anterior cervical, axillary, and inguinal are the best for children.
Adults can be palpated at any lymph node site. (<1cm)
When does lymph node atrophy begin?
Early adolescence, so adult lymph nodes are expected to be smaller than children.
What should you note regarding the physical characteristics of a lymph node?
Size
Location
Consistency
Tenderness
Fixation
What do hard lymph nodes suggest?
Fibrotic cancers
What do firm and rubbery nodes suggest?
Lymphomas
Chronic leukemia
What do softer lymph nodes suggest?
Acute leukemia
Inflammation
What does tenderness in a lymph node suggest?
Acute enlargement would suggest an inflammatory process.
What does lack of tenderness in a lymph node suggest?
Malignancy
Are lymph nodes normally fixed or mobile? What does it suggest if they aren’t?
Mobile is NORMAL.
Fixed suggests malignancy or inflammation.
How do we describe lymph nodes combining?
Matted
How do we manage isolated LAN in children?
Depending on area, we treat empirically for a short time.
High CA-MRSA prevalence = clindamycin.
Low CA-MRSA prevalence = keflex or augmentin
Cat/kittens (B. henselae) = add azithromycin.
f/u in 2-4 wks.
This is NOT recommended for adults.
CA-MRSA = community acquired MRSA.
How do we manage isolated LAN in adults?
Work up to r/o malignancy.
Possible biopsy.
DO NOT TREAT empirically.
What is non-hodgkin’s lymphoma?
The MC lymphoma.
A malignant overgrowth of the lymphocyte or its precursor within the lymphatic tissue.
MC site: lymph nodes
What is the pathophysiology of Non-hodgkin’s lymphoma?
Monoclonal proliferation of lymphocytic cells.
All 3 cells can be affected. Mainly B-cells (85%)
What are the etiologies of Non-hodgkin’s lymphoma?
Chromosomal translocations
Infections (EBV, Hep B/C, H. pylori, Kaposi sarcoma Herpes Virus)
Environmental factors
Immunodeficiency states
Chronic inflammation (autoimmune)
What is the MC demographic of Non-hodgkin’s lymphoma?
50-60yo
White males
What are the two ways non-hodgkin’s lymphoma presents clinically?
Indolent (slow-growing) but often disseminated by time of Dx.
Aggressive
How does indolent non-hodgkin’s lymphoma present?
PAINLESS and SLOW growing LAN. (can be local or generalized)
HSM
Cytopenias
Note:
Lymph nodes can swell and regress periodically.
How does aggressive non-hodgkin’s lymphoma present?
PAINLESS and FAST GROWING LAN.
Usually progresses fast enough to cause compression of nearby vessels.
B-symptoms in advanced stage.
HSM
Abd/testicular mass
Symptoms of disseminated disease (vertebra, GI, BM, CNS)
What are the B-symptoms of aggressive Non-hodgkin’s lymphoma?
Unexplained weight loss > 10% in past 6 months.
Unexplained fever > 38C
DRENCHING night sweats.
Also known as constitutional symptoms.
What are symptoms of a disseminated disease in the bones?
EX: vertebra would result in bone pain.
BM: deep aching bone pain
How does a CBC for non-hodgkin’s lymphoma present?
Normal until the BM is infiltrated, which results in pancytopenia.
How does a CBC for non-hodgkin’s lymphoma present?
NORMAL.
How does a CMP for non-hodgkin’s lymphoma present?
Elevated BUN/Cr in hydronephrosis if ureter compressed.
Elevated LFTs with hepatic involvement
Elevated ALP in liver/Bone involvement
When is LDH elevated in non-hodgkin’s lymphoma?
Advanced disease.
What viruses would we screen for in non-hodgkin’s lymphoma?
HIV
HCV
HBV
EBV is not tested since most pts have had it.
We can also treat the other viruses.
What are we looking for in a CXR or a CT for non-hodgkin’s lymphoma?
CXR: mediastinal nodes/mass
CT w/ contrast:
Neck/chest/abd/pelvis
Evaluate extent of lymph node involvement.
Mainly for staging.
What is the diagnostic test for non-hodgkin’s lymphoma?
LYMPH NODE BIOPSY.
What would we see in a positive lymph node biopsy in non-hodgkin’s lymphoma?
+ for monoclonal lymphocytes.
We do it if there is a suspicious lymph node. (>2.25cm2 or 2cm diameter)
What kind of lymph node do we prefer to biopsy? What is the alternative?
Preferred is a peripheral node.
Alternative is a CT-guided fine needle biopsy.
What are bilateral bone marrow biopsies used for in non-hodgkin’s lymphoma?
For staging.
You must have 2 biopsies in 2 different sites.
How does a PET scan work? Why can we use it to monitor lymphoma?
PET Scans show areas of HIGH metabolic activity.
Cancers are highly metabolic, so they appear very active via the radioactive tracers. (radioactive glucose)
Often used for metastatic cancers.
How do we stage Non-hodgkin’s lymphoma?
Ann Arbor staging system.
Stages 1-4
Subcategory of A or B
A = non-systemic
B = B-symptoms/systemic symptoms.
What is required to stage non-hodgkin’s lymphoma?
PET/CT of the neck, chest, abdomen, and pelvis + a bilateral BM biopsy/aspiration.
What is stage 1 of non-hodgkin’s lymphoma?
Single lymph node AREA or single extranodal site.
What is stage 2 of non-hodgkin’s lymphoma?
2+ lymph node AREAS on SAME SIDE of diaphragm.
What is stage 3 of non-hodgkin’s lymphoma?
Lymph node AREAS on both sides of diaphragm.
What is stage 4 of non-hodgkin’s lymphoma?
Disseminated or multi organ involvement.
What are the additional staging modifications (Cotswolds) avaiable for non-hodgkin’s lymphoma?
E = extralymphatic site
S = splenic
P = pulmonary
H = hepatic
M = marrow
How is indolent non-hodgkin’s lymphoma treated?
If it is disseminated by the time of diagnosis, it is incurable.
1-2 drug chemo only used for symptomatic treatment.
How is aggressive non-hodgkin’s lymphoma treated?
Chemo +/- radiation therapy.
Allogeneic stem cell transplant
What is the prognosis of an indolent NHL diagnosis?
10-15 yrs.
What are the poor prognosis factors for NHL?
Age > 60
Elevated LDH
Poor response to standard therapy
Stage 3-4
What is hodgkin’s lymphoma?
A malignancy of the B-LYMPHOCYTES within lymph tissue characterized by Reed-Sternberg cells.
What are Reed sternberg cells?
Large, abnormal lymphocytes with more than 1 nucleus.
What are the etiologies of Hodgkin’s lymphoma?
EBV and HIV
What is the MC demographic of Hodgkin’s lymphoma?
20s or 50s
Males (White and african american are equal, other races less likely)
How does hodgkin’s lymphoma present?
PAINLESS mass lymph node, MC in the neck.
Pain after ETOH consumption (specific but infrequent)
B symptoms in 40% of pts.
Generalized pruritis
HSM (rare)
Mediastinal mass (possible)
How does a CBC, LDH, ALP, and viral serology present for hodgkin’s lymphoma?
CBC: normal or non-specific
LDH: elevated in advanced disease
ALP: elevated if liver/bone involvement.
Viral serology: HIV, HBV, HCV
What is the confirmatory test for hodgkin’s lymphoma? What is the finding?
Lymph node excisional biopsy positive for reed-sternberg cells.
What scans do we use to stage hodgkin’s lymphoma?
CXR
CT
PET
How do we stage hodgkin’s lymphoma?
Identical to NHL.
Stage 1-4 via ann arbor staging.
What is the treatment for stage 1-2 (non-bulky) hodgkin’s lymphoma?
Multi drug chemo +/- field radiation therapy
What is the treatment for stage 3 or 4 or bulky stage 2 hodgkin’s lymphoma?
Multi drug chemo
What is the treatment for relapsing hodgkin’s lymphoma?
High dose chemo
Autologous stem cell transplant
What are the poor prognostic factors for hodgkin’s lymphoma?
Low serum albumin < 4
Low Hgb < 10.5
Male
> 45 yo
Stage 4
High WBC > 15k
Low ALC count < 600, less than 8% of total WBC count, or both.
What are the key differences between hodgkin’s and non-hodgkin’s?
Non-hodgkin’s is NON-contiguous lymph node spread.
Non-hodgkin’s has NO reed-sternberg cells.
Non-hodgkin’s is NOPE survival (lower survival rate compared to hodgkin’s)
What is polycythemia vera?
An ACQUIRED disorder resulting in overproduction of all 3 hematopoietic cell lines.
Mutation of Janus Kinase (JAK2 gene), causing excessive cell growth and division.
What is the etiology of polycythemia vera?
Unknown, mainly ionizing radiation and toxins suggested.
When is polycythemia vera MC age-wise?
50-70.
No other demographic factors.
How does polycythemia vera often present?
Increased blood viscosity (fatigue, HA, dizziness, vertigo, tinnitus, visual disturbances, chest pain, and intermittent claudication)
Generalized pruritis worsened after a hot shower.
Bleeding: epistaxis, bleeding gums, ecchymosis, GI bleeding.
What does increased blood viscosity cause?
Impaired O2 delivery to tissues.
Why does generalized pruritis occur in polycythemia vera?
Basophilic histamine release
Why does bleeding occur in polycythemia vera?
Engorged vessels and platelet dysfunction.
Why does abd pain/discomfort occur in polycythemia vera?
Ulcer formation from increased gastric acidity due to excessive histamine.
HSM
Why is thromboembolism more common in polycythemia vera?
Increased blood viscosity and platelet dysfunction.
Why does early satiety occur in polycythemia vera?
Splenomegaly
What are some visible vessels that may be engorged in polycythemia vera?
Retinal and conjuctival vessels.
Why does the face appear very red and uneven in polycythemia vera?
Excess blood.
What does a CBC look like in polycythemia vera?
Elevated RBC, PLT, WBC.
HCT: >54 in males and > 51 in females is the hallmark sign!
What does a peripheral smear look like in polycythemia vera?
Normal.
Why is EPO low or normal in polycythemia vera?
EPO is increased if we were low. Because we have an excess, our body thinks we don’t need EPO.
What are the confirmatory tests for polycythemia vera?
EPO level.
Genetic testing for JAK2
How is polycythemia vera managed?
Therapeutic phleb by heme.
1 unit of whole blood (500mL) weekly until Hct < 45%.
DO NOT TREAT IRON DEFICIENCY FROM THIS.
ONLY TAKE 1 UNIT A WEEK.
81mg asa unless active blood loss.
How much does 1 unit of phlebotomy lower Hct by?
3%
What lifestyle modifications are suggested for polycythemia vera?
Anything causing O2 impairment.
Smoking cessation
CV Risk factors
Hypoxic conditions (COPD, sleep apnea)
When is cytoreductive therapy indicated? What is it?
Used if the therapeutic phlebotomy is insufficient.
Hydroxyurea is used.
It suppresses BM production by interfering with DNA repair.
When is hydroxyurea CI?
Severe BM suppression, pregnancy, attempted conception, breast feeding.
What is the last line treatment option for polycythemia vera?
JAK1/JAK2 inhibitor (Jakafi)
Pemazyre (FGFR inhibitor)
Must have failed HU and phlebotomies.
AND 1 of the following:
Markedly symtomatic splenomegaly.
Severe, protracted pruritis
Post-PV myelofibrosis
What is a low-risk polycythemia vera?
< 60 yo
No hx of thromboembolism
How is a low-risk polycythemia vera treated?
Therapeutic phlebotomies, 81mg asa, and lifestyle modifications.
What would indicate us to add cytoreductive therapy in low-risk polycythemia vera?
Uncontrolled PV-associated symptoms.
Progressive increase of leukocytes or platelet counts
Symptomatic or progressive splenomegaly
Poor tolerance of phlebotomy.
How is high-risk PV treated?
Therapeutic phlebotomy
Low dose ASA
Life-style modifications
Hydroxyurea
What is the prognosis of PV?
15 year median survival.
MC of death is thrombosis
What can PV end up causing?
Myelofibrosis
CML
AML (Rare)
What is essential thrombocytosis?
Disorder of increased proliferation of the megakaryocytes (platelet precursor)
Caused by JAK2 mainly.
Others include calreticulin (CALR) or myeloproliferative leukemia virus oncogene (MPL)
What is the etiology of essential thrombocytosis (ET)?
Unknown
What is the MC demographic of ET?
50-60 yo.
How does ET typically present?
Microvascular occlusion (finger/toe pain relieved by asa)
Thrombosis
HA
Transient dizziness, unsteadiness, vertigo, syncope
Bleeding (rare)
What does a CBC for ET look like?
Plts > 2million
Mild leukocytosis
What does a peripheral smear for ET look like?
large plts
What does a BM biopsy/aspiration for ET look like?
Increased megakaryocytes
What genetic testing can be done for ET?
JAK2, CLR, MPL
What are the risk factors for thrombosis in ET?
60 YO
HX OF THROMBOSIS
JAK2 MUTATION
plt> 1.5mil
Obesity
CV risk factors
Hypercoagulable state
How do we stratify risk in ET?
High-risk = Hx of thrombosis and/or >60 + JAK2 mutation.
Intermediate-risk = >60, no JAK2, no hx of thrombosis
Low-risk = <60, JAK2 +, no hx of thrombosis
Very low-risk = <60, no JAK2, no hx of thrombosis
Having jak2 is lower risk than being old
How do we manage very low-risk or low-risk ET pts?
Observation and baby asa.
Avoid NSAIDs.
How do we manage intermediate-high risk ET pts?
HU with target plt count of 100k-400k
What is the MC of death in ET?
Thrombosis.
Keep plt < 500k
What is secondary erythrocytosis?
Elevated RBC/Hgb/Hct due to an acquired or congenital disorder.
What are the main etiologies of secondary erythrocytosis?
Tissue hypoxia
Decreased renal perfusion
Inappropriate EPO secretion
Testosterone administration
What is the key finding that differentiates secondary erythrocytosis from PV?
NO SPLENOMEGALY
What does clubbing of the fingers in secondary erythrocytosis suggest?
Long-term hypoxia
What is the main lab finding that suggests secondary erythrocytosis?
Elevated EPO.
How is secondary erythrocytosis managed and treated?
Treat the underlying condition.
What is reactive thrombocytosis?
Elevated PLT count that develops 2/2 to another disorder.
What is the pathophysiology of reactive thrombocytosis?
Depends on etiology.
Increased megakaryocyte proliferation/maturation.
Accelerated plt release
Reduced plt sequestration/turnover (asplenia)
What causes increased megakaryocyte proliferation maturation in reactive thrombocytosis?
Increased production of the inflammatory cytokines (Infection, chronic inflammatory processes, or malignancy)
Stimulation of the RBC progenitors leading to plt progenitor increase as well. Caused by anemias (hemorrhage, iron deficiency, and hemolysis)
How would we evaluate an inflammatory condition for reactive thrombocytosis?
ESR
CRP
ANA
RF
What would I expect in a CBC for reactive thrombocytosis?
Elevated PLTs
Variable RBCs
How would we evaluate an underlying hematologic disorder causing reactive thrombocytosis?
Iron studies
Peripheral Smears
Retic counts
How do we manage reactive thrombocytosis?
Treating the underlying condition.
