leukocyte disorders pt 2 Flashcards
what organs are part of the lymph system
- lymph nodes and lymph vessels
- thymus
- tonsils/adenoids
- spleen
what are the extranodal lymph tissue sites
- skin
- GI tract, liver
- bone marrow
- testicles
lymph node masses increase and become easier to palpate in what population?
between birth - 12y/o
what is the normal LN sizes in children
- anterior cervical ≤ 2 cm
- axillary ≤ 1 cm
- inguinal nodes ≤ 1.5 cm
normal LN sizes of adults
Normal Findings in Adults
< 1 cm at any location
what types of exposures to infectious etiology would lead to enlarged LNs
- cat scratch
- undercooked meat
- tick bite
- travel to endemic area
- high risk behavior
local adenopathy often indicates a
local etiologic pathology
hard nodes = ?
firm, rubbery nodes = ?
softer nodes = ?
- fibrotic cancers
- lymphomas, chronic leukemia
- acute leukemia, inflammation
tender lymphadenopathy is indicative of?
acute rapid enlargement = indicative of inflammatory process
nontender lymphadenopathy is indicative of ?
malignancy
normal LNs should have what type of fixation?
mobile, freely moveable
a fixed LN to the skin, underlying or adjacent tissues is indicative of ?
malignancy or inflammation of surrounding tissues
what does a “matted” LN mean?
nodes become fixed to each other
management/tx for lymphadenopathy alone in children
- short course of broad-spectrum antibiotic
- High CA-MRSA prevalence - clindamycin
- Low CA-MRSA prevalence - cephalexin or amoxicillin-clavulanate
- Exposure to cat/kittens (cover B. henselae) - add azithromycin - follow up 2-4 wks
management for lymphadenopathy in adults or those with constitutional symptoms
- work up to r/o malignancy
- referral for lymph node biopsy
A malignant overgrowth of the lymphocyte or its precursor within the lymphatic tissue
non-hodgkin lymphoma
MC site - lymph nodes
pathophys of non-hodgkin lymphoma
- a monoclonal proliferation of lymphocytic cells
- All 3 lymphocytic cells can be affected; MC = B cells
causes of non-hodgkin lymphoma
- Chromosomal translocations
-
Infections - chronic antigenic stimulation and cytokine dysregulation = lymphocyte stimulation & proliferation
- EBV (Mono)
- Hepatitis B/C
- H. pylori
- Kaposi sarcoma-associated herpesvirus -
Environmental factors
- chemicals, chemotherapy, radiation exposure -
Immunodeficiency
- AIDS
- iatrogenic immunosuppression
- congenital immunodeficiency disorders -
Chronic inflammation
- autoimmune disorders
what is the MC type of lymphoma?
non-hodgkin
epidemiology of non-hodgkin
50-60y/o
white
male
2 types of clinical presentation of non-hodgkin
- Indolent - painless, slow growing (worst one)
- Aggressive - painless, rapid growth, spread
what are the “B-symptoms” of aggressive non-hodgkins
- Unexplained weight loss
- Unexplained fever
- Drenching night sweats
seen in advanced stage
clinical presentation of indolent non-hodgkins
-
painless and slow growing lymphadenopathy
- isolated or generalized
- peripheral or central
- spontaneous regression may be noted in history - HSM
- cytopenias
clinical presentations of aggressive non-hodgkins
- Fast growing painless lymphadenopathy
- compresses on surrounding structures - lungs, SVC, bowel, ureters - B-symptoms
- HSM, abd/testicular mass
- disseminated disease
work up for non-hodgkins
- CBC - normal until BM infiltrated
- peripheral smear - normal
- CMP - depends on organ affected
- ↑ BUN/Cr with hydronephrosis
- ↑ LFT with hepatic involvement
- Alkaline phosphatase (ALP) - ↑ liver/bone involvement - LDH - increased if advanced
- viral serology
- imaging
- CXR - mediastinal nodes/mass
- CT w/ contrast - evaluate extent of lymph node involvement -
excisional LN bx - diagnostic
- (+) monoclonal lymphocytes
- peripheral > central site - BL bone marrow bx
- PET scan
what is the diagnostic work up for nonhodgkins
Excisional lymph node bx
(+) presence of monoclonal lymphocytes
when is Excisional lymph node bx indicated
suspicious lymph node > 2.25 cm² or 2 cm in a single diameter
what site to use for LN excision for nonhodgkins
peripheral preferred over central
if peripheral node is absent - CT-guided core needle biopsy or laparoscopic biopsy
what staging system is used for nonhodgkins and hodgkins? describe the stages
Ann arbor staging system
1. stage 1 = single LN area
2. stage 2 = 2+ LN in same side of diaphragm
3. stage 3 = LN on both sides of diaphragm
4. stage 4 = disseminated or multiple extranodal organs involved
Ann Arbor staging system requires what other work ups
PET/CT of the neck, chest, abdomen and pelvis in addition to bilateral bone marrow aspiration/biopsy
“A”/”B” symptomatology of the Ann Arbor staging system means?
A - no systemic symptoms
B - presence of “B-symptoms”
what are the additional Ann Arbor staging that indicate which system it involves?
E = Extralymphatic site
S = Splenic involvement
P = Pulmonary involvement
H = Hepatic involvement
M = Marrow involvement
tx for indolent nonhodgkins
- often disseminated at time of diagnosis - incurable
- treatment has not shown to increase overall survival
- treatment is only recommended if symptomatic
- single or multidrug chemotherapy
tx for aggressive nonhodgkins
- chemotherapy +/- local radiation therapy
- allogeneic stem cell transplant
what is the avg survival rate after indolent NHL diagnosis?
10-15 yrs
what is the prognosis for aggressive NHL
depends how many factors they have - decreases by 25%
- 0-1 factor - 75% 5 year survival rate
- 2-3 factors – 50% 5 year survival rate
- 4 -5 factors – 25% 5 year survival rate
a malignancy of the B-lymphocytes within lymph tissue characterized by the presence of Reed-Sternberg cells
Hodgkin Lymphoma
etiology of Hodgkin Lymphoma
- viral
- EBV
- HIV - genetic (slight)
epidemiology of HL
-
age - 2 peaks
- young adults - 20’s
- middle age - 50+ y/o
no race/ethnic correlation
if a pt presents with a painless “mass” on their neck and experiences pain after alcohol consumption, what is the probable diagnosis?
hodgkin
MC in neck
presentation of hodgkins
- painless “mass” lymph node
- B-symptoms
- generalized pruritus
- +/- hepatosplenomegaly
- abdominal fullness, early satiety - +/- mediastinal mass
- chest pain, cough, SOB
- SVC syndrome
work up for HL
- Labs
- CBC: normal or nonspecific findings
- LDH:↑ with advanced “bulk” disease
- Alkaline phosphatase (ALP): ↑ liver/bone disease
- Viral Serology: HIV, HCV, HBV - Lymph node excisional bx
- (+) Reed-Sternberg cells - Imaging for staging purposes
- CXR, CT, PET
what confirms the diagnosis of HL
Reed-Sternberg cells from LN excision biopsy
“bulk” with HL means?
lymph node >10 cm
or
mediastinal mass >⅓ thoracic diameter
tx for HL
- Stage I-II (with no bulky masses)
- multi-drug chemotherapy +/- field radiation therapy - Stage III-IV or bulky stage II
- multi-drug chemotherapy - Relapse after initial treatment
- high dose chemotherapy and autologous stem cell transplant
what are the poor prognostic risk factors for HL
- Low serum albumin < 4 g/dL
- Low hemoglobin < 10.5 g/dL
- Male sex
- > 45 y/o
- Stage IV disease
- High WBC > 15,000/mm3
- Low ALC count <600/mm 3, <8% of total WBC count, or both
an acquired disorder resulting in overproduction of all 3 hematopoietic cell lines
Polycythemia Vera
a mutation on the JAK2 gene leading to excessive cell growth and division causes what disorder?
Polycythemia Vera
etiology of Polycythemia Vera
ionizing radiation and toxins suggested as risk factors
unknown otherwise
epidemiology of polycythemia vera
peak incidence seen between 50-70 y/o
no sex or ethnic predilection
clinical presentation of polycythemia vera
- Fatigue, HA, dizziness, vertigo, tinnitus, visual disturbances, chest pain, intermittent claudication
- from increased blood viscosity - generalized pruritus (basophilia)
- worse after warm shower/bath - bleeding - epistaxis, bleeding gums, ecchymosis, GI
- engorged vessels and platelet dysfunction - Venous thrombosis/thromboembolism/stroke
- abd pain
- Early satiety (HSM)
- Engorged conjunctival and retinal vessels
- Plethora
labs for polycythemia vera
-
CBC
- elevated RBC (normocytic/normochromic), WBC, Plt
- HCT: > 54% male and 51% female (hallmark) - Peripheral smear (normal)
- CMP
- Erythropoietin lvl = low (occasionally normal)
- Genetic testing: (+) JAK2 mutation
what confirms polycythemia vera
low erythropoietin levels + presence of JAK2 mutation
tx for polycythemia vera
- therapeutic phlebotomy
- 1 unit of whole blood (500 ml) removed weekly until hct < 45 %
- Do not treat resulting iron deficiency - will reverse phlebotomy effects - ASA 81 mg daily - unless CI by active blood loss
- lifestyle modifcations
- Smoking
- CV risk factors
- hypoxic conditions - Cytoreductive therapy - hydroxyurea: suppresses bone marrow cellular production by interfering with DNA repair
- Ruxolitinib (Jakafi) - (JAK1/JAK2 inhibitor) or pemigatinib (Pemazyre) - (FGFR inhibitor¹)
indicated if failure to phlebotomy and HU and any of the following:
- Markedly symptomatic splenomegaly
- Severe, protracted pruritus
- Post-PV myelofibrosis
what is used if failure to phlebotomy and HU for PV?
Ruxolitinib (Jakafi)
also if any of the following happen:
1. Markedly symptomatic splenomegaly
2. Severe, protracted pruritus
3. Post-PV myelofibrosis
SE and CI of hydroxyurea
- SE: neutropenia, anemia, oral ulcers, mild GI upset, rash, nail changes hyperpigmentation
- CI: Severe bone marrow suppression, pregnancy, attempted conception, breast feeding
POC for low-risk pts with polycythemia vera
- Therapeutic phlebotomy
- 81 mg ASA
- life-style modifications
- Cytoreductive therapy only if:
- uncontrolled PV-associated symptoms
- progressive increase of leukocyte and/or platelet counts
- symptomatic or progressive splenomegaly
- poor tolerance of phlebotomy
POC for high-risk pts with polycythemia vera
Therapeutic phlebotomy, low dose ASA, life-style modifications and HU
what is the MC of death with polycythemia vera?
thrombosis
complications with polycythemia vera
- thrombosis
- conversion to myelofibrosis, CML or rarely AML
a disorder of increased proliferation of the megakaryocytes (precursor for platelet)
Essential Thrombocytosis (ET)
from genetic mutation - MC is JAK2
clinical presentation of essential thrombocytosis (ET)
- Microvascular occlusion - pain in fingers/toes
- relieved with ASA - Thrombosis - mesenteric, hepatic or portal vessels, peripheral DVT
- HA
- Transient dizziness, unsteadiness, vertigo, syncope - transient ischemic attacks (TIA - “mini-stroke”)
- Bleeding (less common)
labs for essential thrombocytosis (ET)
- CBC
- elevated platelet count may be >2,000,000 /mcL
- mild leukocytosis - Peripheral blood smear
- large platelets - CMP
- Bone marrow aspiration/biopsy
- increased megakaryocytes - Genetic testing
- (+) JAK2, CALR or MPL mutation
risk factors for thrombosis in essential thrombocytosis (ET)
- > 60 y/o
- hx of thrombosis
- Plt > 1,500,000/µL
- obesity
- CV risk factors : smoking, HTN, hyperlipidemia
- hypercoagulable state
- JAK2 mutation
Risk staging for Essential Thrombocytosis (ET)
- High-risk disease
- hx of thrombosis at any age and/or age >60 with a JAK2 mutation - Intermediate-risk disease
- Age >60, no JAK2 mutation detected, and no hx of thrombosis - Low-risk disease
- Age ≤60 with JAK2 mutation and no hx of thrombosis - Very-low-risk disease
- Age ≤60, no JAK2 mutation detected, and no hx of thrombosis
Management for very low - low risk ET
- observation, ASA 81 mg daily
- avoid NSAIDS - use increases risk of bleeding
management for Intermediate - High risk with ET
hydroxyurea with a target plt count of 100,000 to 400,000/µL
An elevated RBC/Hgb/Hct related to an acquired or congenital disorder
Secondary Erythrocytosis
etiology of Secondary Erythrocytosis
- Tissue hypoxia
- Decreased renal perfusion
- Inappropriate EPO stimulation
- Testosterone administration
presentation of Secondary Erythrocytosis
- arterial oxygen - low in hypoxemic conditions
- skin
- ruddy complexion - “plethora”
- hypoxic patients will present with acrocyanosis - neurologic - related to increased blood viscosity
- headaches, lethargy, and confusion - clubbing of fingers - long term hypoxia
- NO splenomegaly
what differentiates Secondary Erythrocytosis from PV?
NO splenomegaly in secondary
labs with secondary erythrocytosis
- CBC - increased RBC, Hgb, Hct, +/- slight increase in plt
- (-) JAK2 gene
- Increased EPO level
- Elevated carboxyhemoglobin levels in CO poisoning or heavy smokers
an elevated platelet count that develops secondary to another disorder
Reactive Thrombocytosis
pathophys of Reactive Thrombocytosis
-
increased megakaryocyte
- increased inflammatory cytokines
- stimulation of RBC progenitors stimulates- Anemia: hemorrhage, iron deficiency, hemolysis
- accelerated platelet release
-
reduced platelet sequestration/turnover
- asplenia
(depends on the etiology)
labs for Reactive Thrombocytosis
- CBC
- elevated plt, (+/-) low RBC, H&H - Inflammatory condition evaluation?
- Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Antinuclear antibody (ANA), rheumatoid factor (RF) - Malignancy?
- Cytogenetic analysis - Hematologic disorder?
- Iron studies
- Peripheral blood smear
- Reticulocyte count
(based upon your DDx)
