Transcript White Blood Cells (Leucocytes)

T. Kozák, lecture for the summer semester 2013
Introduction
Immune system is very complex system of cells and
tissues with complicated interactions in order to
recognize own and foreign structure.
It is composed mainly of blood leukocytes & tissue cells
derived from the leukocytes.
These cells work in 2 ways to prevent disease:
i) by actually destroying the invading bacteria or
viruses by phagocytosis and
ii) by forming antibodies & sensitized lymphocytes,
one or both of which may destroy or inactivate the
invader.
 Leukocytes: mobile units of body’s immune system.
 Leukocytes primarily function as defense agents
outside the blood, to carry out their function,
leukocytes use “seek out & attack” strategy. (i.e. they
go to sites of invasion or tissue damage.)
 Leukocytes are formed partially in the bone marrow &
in the lymphoid tissue.
 The main reason WBCs are present in blood is to
rapidly transported from their sites of production or
storage to wherever they are needed: areas of serious
infection & inflammation. Thus Providing rapid and
potent defense.
 Unlike erythrocytes, (which are of uniform structure,
identical function, & constant no.) leukocytes vary in
structure, function & no.
 According to staining properties of WBCs, WBCs are
divided into
Leukocytes in peripheral blood (WBC)
(4,0 – 10,0 x109/l)
Granulocytes
Agranulocytes
Polymorphnuclear
Unlobed nucleus
Neutrophil
40-70%
Eosinophil
2-7%
Basophil Lymphocyte
Monocyte
0-1%
20-40% 2-10%
B, T, NK cell
 Unlike erythrocytes, (which are of uniform structure,
identical function, & constant no.) leukocytes vary in
structure, function & no.
 According to staining properties of WBCs, WBCs are
divided into
Leukocytes in peripheral blood (WBC)
(4,0 – 10,0 x109/l)
Differential count
Granulocytes
Agranulocytes
Polymorphnuclear
Unlobed nucleus
Neutrophil
40-70%
Eosinophil
2-7%
Basophil Lymphocyte
Monocyte
0-1%
20-40% 2-10%
B, T, NK cell
-penias & -philias (-osis) I
 E.g neutropenia or neutrophoilia, lymphopenia or
lymphocytosis, monocytosis, etc.
refer to ABSOLUTE COUNTS (NUMBERS) from the
differantial lekocyte count:
Neutropenia: ANC < 1,6 x 109/l
Neutrophilia: ANC > 7,0 x 109/l
Lymphocytosis: Ly > 4,0 x 109/l,
Lymphopenia: Ly < 0,8 x 109/l
Relative -penias or –philias (-osis):
relative (%) decrease or increase in differential
leukogram in the absence of change in absolute
number.
(-penias) & -philias (-osis) II
1. Reactive. Refer to changes in blood counts as
reponse to various attacks, mostly inflammatory
reaction.
2. Malignant (clonal, primary) refer to changes
reflecting clonal (= malignant) haematology diseases
(leukemia, etc.)
3. Idiopathic: etiology and pathphysiology not known,
underlying reactive or malignant ciondition ruled
out
4. Congenital (inherited). Rare but exist.
 Normal count of WBC in PB: : 4,0 – 10,0 x109/l
1. Marrow pool: 90% neutrophils
2. Blood pool: 3%
3. Tissue pool: 7% Mucosas etc.

Leukopoiesis
 In bone marrow → PHSC (Pluripotential
hemopoietic stem cells) differentiates →
committed stem cells → CFU-GM



Granulocytes & monocytes are formed only in
bone marrow,
Lymphocytes are produced in MB + in various
lymphoid tissues (thymus, lymphnodes, splen,
etc)
WBCs formed in the bone marrow are stored in
the marrow & lymphocytes are stored in
lymphoid tissue & small no. circulate in the
blood.
Genesis of WBCs , distinguised by morphology
Row [a] represents the myelocytes showing neutrophilic, basophilic and eosinophilic from left to
right. Row [b] represents the metamyelocyte cells again starting with neutrophilic on the left.
Life span of WBCs
 Granulocytes:
 after released from bone marrow, 4-8 hours circulate in
blood
 & another 4-5 days in the tissues.
 Survive only for few hours in serious infection
 Monocytes:
 10-20 hrs in blood.
 Once in tissue they get much larger size to become
tissue macrophage → life span month(s)
 Lymphocytes:
 Life span for week or years depending on body’s need.
 They continually circulate in blood & move from blood
to tissues & from tissues to blood and again blood to
tissues.
Neutrophils:
 Size: 10-14 µm in diam.
 Nucleus:
1. Multilobed (1-6 lobes)
therefore called
polymorphnuclear leucocytes.
2. Young cell have single horse
shoe shaped nucleus.
3.
4.
As the cells grow older nucleus becomes multilobed.
Lobes are connected with one another by chromatin
threads.
Arneth count: More the no. of lobes, the more mature is
the neutrophil. More the no. of mature cells, Arneth
count shifts to right (Vit. B12 or folate deficiency).
More the younger cells → shift to left (infection).
Cytoplasm: contains neutrally
stained granules
2 types of granules are present
1.
Primary/ lysosomal granules: less in no.

2.
3.
containing acid hydrolases, which can digest bacteria. After
a bacterium is phagocytosed by the neutrophil, primary
granules release their enzymes which remain within the
neutrophil & kill the bacterium, thus no harm to innocent
cells. In addition, primary granules also contain powerful
broad spectrum antimicrobial polypeptide defensin
Secondary granules: more numerous. Contain
i.
Lactoferin,
ii. Vit B12 binding protein &
iii. Components of enzyme system that produce free
radicals like H2O2, which kills the microbes.
iv.
Substances that facilitates chemotaxis.
Toxic granules: During infection toxic coarse granules are
seen.
Neutrophil function
1. Phagocytosis: 1st line of defence, ingest & destroy a
bacteria.
2. Pyrogens & inflammatory cytokines: endogenous
pyrogen which is an important mediator of febrile
response to bacteria + other regulation and inflam.
defense reaction
Changes in neutrophil count I
REACTIVE
 Neutrophilia: ↑in neutrophil count.


A. Physiological 1)Exercise, 2)After injection of
epinephrine, 3)Pregnancy, menstruation & lactation,
4)Newborn, 5)After meals, 6)Mental or emotional stress.
B. Pathological 1)Acute pyogenic (pus forming)
infections, 2)Following tissue destruction, e.g. i) Burns
After hemorrhage, iii) myocardial infarction, iv) After
surgery v) poisoning by lead, mercury, insect
venom
 Neutropenia: ↓ in neutrophil count:
ii)
In children, 2) Typhoid, paratyphoid fever, 3) Viral
infection, 4) Malaria, 5) Bone marrow supprepression
(failure).
1)
Leukemoid reaction, etc.
Non malignant excesive increase in leukocytes (in most cases
neutrophils) in reaction to mostly inflammatory noxas.
WBC can increase up to 40-60 x 109/l , if neutrophilia
significant left shift in differential is apparent.
In most cases: sepsis (diffuse peritonitis, acute cholecystitis,
acute pyelonephritis, etc.)
WBC (ANC) 26 x 109/l: might be benign (leukemoid reaction)
WBC (ANC) 106 x 109/l: very rarely benign
Changes in neutrophil count II
Malignant neutrophilia
1. Myeloprolipherative diseases (MPD): in all cases
Chronic myelogenous leukemia (CML), in some
cases: Primary myelofibrosis (PMF), Polycythaemia
vera (PV), Essential thrombocythaemia (ET).
2. Acute myelogenous leukemia (AML): increased
number of immature precursors of neutrophils –
blasts and/or promyelocytes
Case I
 48 years old man, medium position manager of large
nuclear power station. Former marathon runner, still
runs 10-20km on sundays, drinks 0,7 l of french red
wine in the evening, smokes 20-30 cig/day, takes
sedatives every other night. Does not have any physical
complain.
 Because of sleeplesness he visited GP on monday, with
no significant physical finding but in laboratory WBC
15.4 x109 with clear neutrophilia revealed. No other
significant laboratory findings. Repeated BC 4 days
later: 14.2 x109 . Absolutely no signs of inflammation.
Case I cont.
 GP screened the patient for infection (ENT, dental,
respiratory, urology) & most common malignancies
incl. CT. Nothing found.
 The patient was seen by a haematologist, no MPD or
leukemia was found, no cytogenetic and molecular
finding.
 What will be following GP´s approach & advise?
Changes in neutrophil count
REACTIVE
 Neutrophilia: ↑ in neutrophils.


A. Physiological 1)Exercise, 2)After injection of
epinephrine, 3)Pregnancy, menstruation & lactation,
4)Newborn, 5)After meals, 6)Mental or emotional stress.
B. Pathological 1)Acute pyogenic (pus forming)
infections, 2)Following tissue destruction, e.g. i) Burns
After hemorrhage, iii) myocardial infarction, iv) After
surgery v) poisoning by lead, mercury, insect
venom
 Neutropenia: ↓ in neutrophils:
ii)
In children, 2) Typhoid, paratyphoid fever, 3) Viral
infection, 4) Malaria, 5) Bone marrow supprepression
(failure).
1)
Changes in neutrophil count
REACTIVE
 Neutrophilia: ↑ in neutrophils.

A. Physiological 1)Exercise, 2)After injection of
epinephrine, 3)Pregnancy, menstruation & lactation,
4)Newborn, 5)After meals, 6)Mental or emotional stress.
Tobacco SMOKING

B. Pathological 1)Acute pyogenic (pus forming)
infections, 2)Following tissue destruction, e.g. i) Burns
After hemorrhage, iii) myocardial infarction, iv) After
surgery v) poisoning by lead, mercury, insect
venom
 Neutropenia: ↓ in neutrophils:
ii)
In children, 2) Typhoid, paratyphoid fever, 3) Viral
infection, 4) Malaria, 5) Bone marrow supprepression
(failure).
1)
 Size:10-14
µm in diam. (2%)
 Nucleus:
1.
2.

Usually (85%) cells ‘bilobed’.
Remaining 15% cells have
trilobed nucleus.
Cytoplasm:
1.
Acidophilic, appears light pink in colour after staining
Granular

Granules
1.
Coarse, stain bright brick red with acidic (eosin) dye.
Granules do not cover the nucleus.
They contain very high peroxidase content (histaminase),
lysozymes & Major Basic Protein (MBP)
2.
3.
2.
 Functions:
Mild phagocytosis: because
less mo bile than neutrophils
2. Eosinophils collect at the sites
of allergic reactions & detoxify
Inflammation inducing substances by degrading the
mediators (e.g. histamine, bradikinin)
3. They enter the tissues & are specially abundant in
the mucosa of respiratory tracts, GIT, urinary
tract, where they provide mucosal immunity
4. Eosinophils attack parasites that are too large to
be engulfed by phagocytosis. Eosinophil granules
release chemicals (peroxidase) which are toxic to
larvae of parasites
1.
 Variation in count:
 Eosinophilia: ↑ in eosinophils
Causes are:- 1)Allergic conditions e.g.
bronchial asthma, hay fever, filariasis 2)
Parasitic infestation, trichinosis &
schistosomiasis e.g. worms (hookworm,
roundworm & tapeworm), 3) Skin disease
like utricaria.
4. Malignant diseases: Myeloprolipherative
diseases (esp: Eosinophilic leukemia,
Systemic mastocytoisis), Hypereosinophilic
syndrome, etc.
5. Connective tissue diseases: SLE, etc.

 Eosinopenia: ↓ in eosinophils
Causes are:- 1) ACTH & steroid therapy, 2)
Stressful conditions, & 3) Acute pyogenic
infections
basophils:
 Size:8-10 µm in diam.
 Nucleus:
1. irregular bilobed, often ‘S’
shaped & its boundary is not
clear because of overcrowding
with coarse granules.
 Cytoplasm:
1. Is slightly basophilic & appear blue, it is full of
granules.
Granules:
1. Contain heparin, histamine & 5HT.
 Functions:
1. Mild phagocytosis
2. Role in allergic reaction:
Basophils release histamine,
bradykinin, no. of lysosomal enzymes, slow
reacting substance of anaphylaxis (SRS-A) &
serotonin (5HT). These substances cause local
vascular & tissue reactions that cause many allergic
manifestations.
Liberates heparin which
3.
i.
ii.
Acts as anticoagulant & keeps blood in fluid state.
Activates the enzyme lipoprotein lipase: removes fat
particles from the blood after fatty meal.
 Variation in count:
 Basophilia: ↑ in basophil count
REACTIVE:- 1) Viral infections, e.g. influenza, small
pox & chicken pox 2) Allergic diseases
MALIGNANT: Chronic myeloid leukemia (CML),
Systemic mastocytosis (SM), other MPD
 Basopenia: ↓ in basophil count
Causes are:- 1) Corticosteroid therapy, 2) Drug
induced reactions & 3) Acute pyogenic infections
 Large tissue cells resembling basophils. Present in
bone marrow & immediately outside the capillaries
in the skin.
 These do not enter the blood circulation (normally).
 Functions: Mast cells play role in allergic reactions
similar to the basophis.
 Size: Largest WBC 18-20 µm.
 Nucleus:
1. Is large single unlobed,
eccentric in position (present on
one side of the cell).
2. It is notched/ indented (kidney
Shaped)
3. It has reticulated chromatin network.
 Cytoplasm:
1. Is abundant, pale blue & usually clear with no
granules.
Granules:
1. Sometimes contain fine purple dust like granules
called Azur granules
Functions:
Role in phagocytosis:
capable of phagocytosing as
many as 100 bacteria,
large particles such as RBCs
& malarial parasites.
2. Precursor of tissue macrophages:
The mature monocyte stay in blood only for few
hours & then they leave blood and enter
extravascular tissue, to become tissue
macrophages.
3. Role in tumor immunity: kill tumor cells after
sensitization by lymphocytes
1.
4. Synthesis of:
Complement & sis of biological substances:
PGE & clot promoting factors.
Also: Interleukin-1, Hemopoietic factors (GCSF, GM-CSF),TNF-α,
Binding proteins like transferrin, lysosomes,
Proteases, Acid hydrolases
5. Key role in the lymphocyte – mediated immunity
as ANTIGEN PRESENTING CELLS.
 Variation in count:
 Reactive monocytosis: ↑ in monocyte count


Causes are:- 1) Certain bacterial infections, e.g.
tuberculosis, syphilis & subacute bacterial
endocarditis 2) Viral infections 3) Protozoal &
rickettsial infections, e.g. malaria, kala azar
Malignant monocytosis: Monoblasts in Acute
leukemia (monocytic, myelomonocytic) Monocytes in
CMML (Chronic myelomonocytic leukemia)
 Monocytopenia: ↓ in monocyte count
Causes are:- It is rare, may be seen in hypoplastic bone
marrow.
Morphologically: small & large (LGL)
 Functionally: T & B lymphocytes,
(and NK cells)
 Small lymphocytes: 7-10 µm
Nucleus rounded, cytoplasm: just rim is seen. Older cells.
 Large lymphocytes: 10-14 µm Nucleus is big with
indentation, definite cytoplasm is seen.
B lymphocyte: originate from BM(primary lymphoid
organ), mature also in secondary lymfoid organs:
lymphnode, spleen, MALT etc.
1. Involved in the humoral immunity: Antibody
production, antigen presentation.
2. Flow cytometry: sIg, cytIg, CD19, CD20
T lymphocyte: processed in thymus, concerned with
the cellular immunity: defensive role against viral & bacterial
infections and tumor cells
Flow cytometry: CD3 (compl. TCR = T cell receptor)
CD4: T helpers, function: Th0, Th1, Th2
CD8: cytotoxic T cells
NK cells: direct cytotoxicity: CD56, CD57
Variation in lymphocyte count
 No. of Eosinophils and Lymphocytes are the most sensitive to
various external and internal changes
 Lymphocytosis: ↑ in absolute lymphocyte count

Physiological 1) In healthy & young children
during menstruation
2)
In female
Pathological: Reactive X Malignant
Lymphocytopenia: ↓ in absolute lymphocyte count

Causes are:- 1) Patients on corticosteroid &
immunosuppressive therapy 2) Hypoplastic bone marrow
Widespread irradiation 4) Acquired Immune Deficiency
syndrome (AIDS)
3)
Variation in lymphocyte count
 No. of Eosinophils and Lymphocytes are the most sensitive to
various external and internal changes
 Lymphocytosis: ↑ in absolute lymphocyte count

Physiological 1) In healthy & young children
during menstruation
2)
In female
Pathological: Reactive X Malignant
Lymphocytopenia: ↓ in absolute lymphocyte count

Causes are:- 1) Patients on corticosteroid &
immunosuppressive therapy 2) Hypoplastic bone marrow
Widespread irradiation 4) Acquired Immune Deficiency
syndrome (AIDS)
3)
Reactive lymphocytosis
 Lymphocytes > 4 (-5) x 109/l
 Morfology: usually heterogenous
 Flow cytometry: polyclonal
Cuases:
- infections: EBV, CMV, toxoplazmóza, HSV, measels
(rubeola), Hepatitis A?B?C, HIV. Bakt: TBC,
brucelosis, ricketsioss, Pertussis
- Hypothyreosis, thyreoditis, Addison´s, stress
- Allergy, Celiac d. Chronic inflam. Intestinal disease
- Hyposplenism, asplenism,
- Other: Chronic granular T lymphocytosis (LGL sy)
Malignant – clonal - lymphocytosis
 Chronic lymphocytic leukemia (CLL) and
Prolymhocytic leukemia (PLL)
 Leukemised („spillover“) non-Hodgin lymphoma,
usually indolent NHL:
Follicular lymphoma, Marginal zone lymphoma (SLVL:
splenic lymphoma with villous lymphocytes),
Immunocytoma (Waldenström´s diasese).
Rarely: Hairy cell leukemia (HCL)
Aggressive NHL: mantle cell lymphoma (MCL)
PTCL, Sézary´s
Rarely: DLBCL (dif. Large B cell lymphoma)
CD5
CD19
CD79b
CD20
SmIg
CD23
CD22
„spillover lymphomas“ dif. diagnosis
Differenciální dg.
Spleen
Morfology (chromatin)
CLL
MCL
FL
HCL
+
+
+/-
++
dense
Pleomorfic
chromatin
„cleaved“
‘Hairy’
Imunophenotype
CD5
++
++
-
-
CD23
++
-
-
-
-
+
+
-
weak
strong
strong
strong
CD79b
SIg
CD10
Molek. genetics
(cytogenetics)
-
-
++
+12; del 13q
bcl1
bcl2
11q-, 17p-
t(11;14)
t(14;18)
různé
Lymphopenia
Lymphocytes < 0,8 x 109/l
1. Combined immune defficiency, Wiskott-Aldrich´s,
Ataxia teleangiectatica, Severe aplastic anemai, end
stage of cancer, Hodgin´s lymphoma
2. Radiotherapy, chemotherapy, corticosteroid th +
other immunosuppressive th, antithymocyte gl. th,
Stress, Heart failure, Cushing´s
3. Intestinal lymphodrenage, drenage of Ductus
thoracicus, Wiple´s, right heart failure etc.
4. Sarcoidosis, mysthenia gravis, SLE, milliar TBC, renal
failure,
Disorders in quality of leukocyte
 Pelger Huët´s abnormal morphology:
autosomal dominant inher. disease:
hyposegmentation of the nucleus.
versus Pseudopelger: severe infection, leukemias,
metastatic carcinoma in bone marrow, sulfonamides
May-Hegglin´s abnormality: inherited together
leukopenia + Döhle´s inclusions in neutrophils +
thrombocytopenia with giant platelets. Acquired:
burns, infections, trauma, malignancies
Disorders in quality of leukocyte II
 Leukocyte adhesion defect (LAD): autos. Recessive
membrane defect due to lack of CD18 molecule. Defect
in chemotaxis, aggregability and phagocytosis.
Clinicaly: necrotic skin infections, pneumonits, otitis
etc. Therapy: aloSCT.
 Chediak-Higashi´s syndrome: autom. recessive
disease with impaired migration and degranulaction
of granulocytes. Comes with albinism, nystagmus,
photophobia, mental retardation, frequent bacterial
infections, peripheral neuropathy. Therapy: aloSCT

etc.
Döhle bodie and toxic granulations
Pelger-Huët anomaly
May-Hegglin anomaly
General consideration
• As many as 56% seemingly healthy adults have palpable
lymph nodes
• Further follow up is necessary:
• In individuals < 30 years: 80% benign etiology
• In individuals > 50: 60% malignant etiology
Adenopathy, general approach
Further investigation of respective adenopathy must be driven by
clinical judgement and by proper assesment of all circumstances
History
Possible cause
Physical exam.
Lab. exam.
Confirmed cause
histology
Assessing adenopathy: History
Age
Tumor or TBC in the history
Allergy
Drugs/medication
Duration of adenopathy
Associated complains (symptoms): fever, night swetting, malaise,
weight loss, artralgy, sore throat, fatigue etc.
Smoking
Travels
Assessing adenopathy: Physical
examination
Single lymphnode, region
Location
Advanced involvement
Generalized adenopathy
Symetry
Size
Lymphadenopathy vs. pseudolymphadenopathy
Sensitivity
Consistence (texture)
Reaction of the surrounding area
Causes of lyphadenopathy
Infections:
EBV (IM), CMV, IH, postvaccinal lymphadenitis, adenovirus, VZV, HIV,
HTLV-I
Staphylococcus, Streptococcus spec.,TB, atypical mycobacteria,
syphilis, cat scratch disease, Chlamydias (lymf. venereum)
Toxoplasmosis, histoplasmosis, coccidiomycosis,
Scrub typhus,
filariosis
Autoimmune disorders:
RA, SLE, dermatomyositis, MCTD, Sjögren´s
Causes of lyphadenopathy
Allergy & hypersensitivity:
Serum sickness, silicone reaction, vaccination, graft vs. host disease.
Drugs: diphenylhdantoin, carbamazepin, gold, allopurinol,
indomethacin, sulfonamides, hydralazines etc.
Miscellaneous Benign Disorders:
Hypothyreoidism, sarcoidosis, amyloidosis, dermathopathic
lymphedanopathy, hypertriglyceridemia, extramedullary
hematopoiesis
Unusual causes of Lymphadenopathy:
Kikuchi´s, Rosi-Dorfman´s, Inflammatory pseudotumor of
lymphnodes, Vascular transformation of sinuses, Gaucher´s,
Nieman-Pick, Letterer-Siwe´s, Wipple´s, etc.
Causes of lyphadenopathy
Potentially malignant causes:
Angiofollicular lymh node hyperplasia (Castleman´s disease)
Lymphomatoid granulomatosis
Wegener´s granulomatosis
Malignant causes:
Hematologic: Hodgkin´s, NHL, chronic lymphocytic leukemia
(CLL), Waldenström´s disease, some acute leucemias (ALL),
systemic mastocytosis. Rare: multilple myeloma
Metastic cancers: breast, lung, renal, stomach, melanoma etc.
Frequent causes of adenopathy according to the
location
Inguinal (or axillar) adenopathy  1cm: usually benign
Cervical adenopathy: infections, carcinomas (consistency),
lymphomas. Sialoadenitis (pseudolymphadenopathy)
Mediastinal adenopathy: lymphomas (mediastinum anterior),
sarcoidosis, metastatic cancer
Isolated axillar adenopathy: infection, breast Ca, lymphoma
Isolated inguinal adenopathy (significant): infection (also
veneral), lymphoma, metastatic Ca (consistency)
Generalized adenopathy: infection (EBV, HIV, etc.), malignant
lymphomas, CLL
lymph nodes that are tender are more likely to be due to
an infectious process,
whereas painless adenopathy raises the concern of
malignancy.
Lymph node consistency
lymph nodes containing metastatic carcinoma are rock
hard,
lymph nodes containing lymphoma are firm and
rubbery,
lymph nodes enlarged in response to an infectious
process are soft.
The larger the lymph node, the more likely a serious
underlying cause exists, and lymph nodes greater than 3
to 4 cm in diameter in an adult are very concerning
Initial evaluation of adenopathy
History, physical examiniation: done
Lab:
Full blood count (smear), ESR, serology, blood cultures,
Chemistry includes: LDH, beta2 microglobulin, TSH
If carcinoma suspected: tumor markers (CA 15-3, Ca 125,
CEA, NSE, etc.)
If sarcoidosis suspected: angiotensin-coverting enzyme
Imaging studies:
Chest X-ray, abdominal ultrasound
CT, MRI, PET
Lymph node biopsy: when
Must be done after a complex clinical judgement, but usual
indications are:
• Constitutional symptoms (weight loss, fever, night sweats) otherwise
unexplained
• Persistent adenopathy > 4 - 6 weeks, otherwise unexplained
• Increasing size of the lymph node for several weeks
• Appearence of additional lymph nodes
• Abnormal blood test results (anemia, elevetad ESR, LDH, liver
chemistries), otherwise unexplained
• Abnormal chest radiograph (e.g. mediastinal adenopathy)
Lymph node biopsy: how
• Excision of the whole lymh node strongly
preferred
• Reasonably experienced surgeon preferred
• Fine needle biopsy must be avoided
• In selected cases: „core cut biopsy“
• Second pathologist´s opinion