- Introductory Lecture
Objectives
This lecture is designed to provide general
histopathology of lymph node. By the end of the learning,
you should:
Know the normal histology of lymph node
Know how to assess the lymph node under microscope
Be able to distinguish malignancy from reactive or benign
disorders
Be able to make diagnosis or narrow down the diagnoses based
on morphology
Know what other tests needed to make a definite diagnosis
Know the markers for common pediatric lymphomas
Normal lymph node architectures
Normal lymph node histology
Capsule
Subcapsular sinus
Trabeculum
Follicles of cortex
Paracortex
Medullary sinus
Medullary cords
Lymphocyte homing
The site of T cell homing is the
After initial maturation in the primary
paracortex
immune organs, "virgin" B and T
The separation of B and T lymphocytes
lymphocytes --> peripheral blood -->
not absolute,
home to specific sites within the lymph
Both cell types present throughout
node (and the other secondary organs),
lymph node, necessary for coordinated
The sites of B cell homing include: lymphoid immune response.
The primary and secondary follicles
of cortex-the sites of
Antigen presentation
Consequent lymphocyte
proliferation and differentiation
The medullary cords -->plasma
cells aggregate--> release their
immunoglobulins into the efferent
lymph
Lymph node variation
Lymph node histology
is dynamic: follicles
In the absence of
immune stimulation,
primary follicles (no
germinal centers)
In the presence of
immune stimulation,
secondary follicles and
germinal centers
2nd
follicle
( GC)
Ki67
Normal IHC pattern
A: HE
B- CD20: B cells,
concentrated in folicles
D- CD23: Folicular
dendritic cells and B
cells
E- CD10: germinal
center cells
G-Bcl2: absent in
germinal center (GC)
B cells
H-CD3: T cells,
concentrated in
paracortical area,
I-CD57: Scattered
follicular regulatory T
cells
J-PD1: GC regulatory
T cells
K-Ki67: GC
proliferating cells
(polarity)
L-CD21: Follicular
dendritic cells
Where to begin?
LZ
DZ
Feature Reactive Neoplastic(FL)
Shape of follicles Variable, fused, dumbbell regular, similar sized
Location of follicles Predominantly cortex Throughout
Interfollicular areas Gen. preserved Scant, back-to-back fol.
GC cells heterogeneous monotonous
Tingible Body Macroph present absent
Mitoses frequent Very rare
Mantle zones Present, sharply Often obliterated
demarcated
polarity present absent
Fol. in perinodal tis. absent May present
BCL-2 in GC negative Positive (90%)
IG gene rearrangement poly mono
CD10/BCL-6 GC only Outside GC
Syphilitic lymphadenoapthy
Generalized lymphadenopathy----- feature of 2
syphilis
Follicular hyperplasia
Plasma cell expands medullary cords
Epithelial cell clusters in paracortex
Naked giant cells
Capsular fibrosis
Arteritis and phlebitis of capsular vessels
Perivascular lymphoplasmacytic cuffing
Silver stains ----Spirochetes
Vascular proliferation and plasmacytosis in the interfollicular
region
Generalized lymphadenopathy
Florid Follicular HyperplasiaFollicular.
Involution (PRGC) Lymcyte Depletion
HIV Lymphadenitis (acute stage)
Florid FH, large, irregular
May coalesce to form giant, geographic
structures
Thin mantle zones---naked GC
Follicle lysis (MZ invagination)
Paracortex monocytoid B-cell
hyperplasia
Warthin-Finkeldey giant cells
Follicular lysis
Young adults
Common location: mediastinum or neck
Microscopic:
Concentric layering of lymphocytes
Atrophic germinal center (GC), multiple GCs
Small hyaline vessels radially penetrating the
GC (lollipop)
Vascular interfollicular tissue
Reactive process, curable by surgical resection
Monoclonality shown in a recent study
Chang KC, et al. Modern Path (2014) 27, 823-
831
Castlemans disease of plasma cell type
Wide age range
Systemic symptoms
Anemia, hyperglobulinemia,
ESR
Increased plasma cells in
BM
Abdominal nodes
FH with narrow mantle
zones; dense interfollicular
plasma cells obscuring
sinus; 1/3 light chain
restriction!
Multicentric CD
Old age
Primary or associated with HIV/AIDS, KS
Histopathology similar to PCD
Assosiated with HHV-8, IL-6-----
systemic symptoms
60% POEMS syndrome
Poor prognosis
Sinus histocytosis
Common in nodes draining the limbs,
mesentery
Nodes draining carcinoma (breast ca, etc.)
Histocytes originate from the sinus lining
cells, which are derived from blood
monocytes
Rosai-Dorfman disease
Childhood and young adult
Fever, night sweats, weight loss, elevated ESR
Bilateral non-tender cervical lymphadenopathy
1/3 extranodal (skin, upper airways, bone)
Marked dilated sinus with histiocytes
Striking emperiopolesis
: S100+, CD1a-, CD207-
Whipples disease
Non-caseating
granulomas
Foamy macrophages
contain bacilli,
Tropheryma whippelli,
and characteristically
stain with PASD.
Increased levels of double negative T-cells (CD4 CD8) are found in the
blood and tissues
Examples:
Lymphoma: lambda restricted - Reactive, K/L: 0.9 ~ 3.7(?)
Common in children
M>F(3.7:1)
Birbeck granules on
Electron microscopy
Single site or single system
multisysyem
Langerhans histiocytosis
Solitary or multiple lesions (papules, nodules, plaques) containining
Langerhans cells
Grooved histiocytes in the sinus
Multinucleated giant cells
Increased eosinophils
+: S100, CD1a, langerin / CD207
Common lymphomas in pediatric population
Lymphoblastic lymphoma
Hodgkin lymphoma
Burkitt lymphoma
Diffuse large B cell lymphoma
Anaplastic large cell lymphoma
Lymphoblastic lymphoma
One of the most common lymphomas in children
lymphoblastic lymphoma and Acute Lymphoblastic Leukemia (ALL)
represent the same disease entity based on morphologic, genetic,
and immunophenotypic features, the WHO classification has unified
these entities as B or T lymphoblastic leukemia/lymphoma.
Most institutes use >=25% blasts in PB or BM as the diagnostic
criterion for ALL though the distinction is not clearcut
Immature T in 85-90% of cases and immature B in the remainder.
No difference on morphologies of T or B origin.
Immunophenotyping and cytogenetics studies for classification and
subclassification
Typical flow cytometric findings for B-lymphoblastic lymphoma:
CD19+ CD10 bright, CD20+/, CD22+/, TdT+, HLA-DR+, CD34+/, slg;
T-lymphoblastic lymphoma: sCD3, but cCD3+, CD4+ CD8+ or CD4-
CD8, CD1a+/-, CD2+/, CD5+/, CD7+/, TdT+, CD34+/, CD10+/.
Lymphoblastic lymphoma
3 CLINICAL VARIANTS
ENDEMIC
SPORADIC
IMMUNOSUPPRESSED
ENDEMIC BURKITT LYMPHOMA
Africa
Children 4-7 y/o
Male
Malaria
Jaw/facial bones
95% EBV
Immuno
-Positive for CD20, CD10 & bcl-6
-Ki-67 100% of cells
-Neg for bcl-2, or weakly+ in 20%
Molecular
-T(8;14) IgH/myc
-T(2;8) myc/kappa
-T(8;22) myc/lambda
Diffuse Large B cell lymphoma
Common morphologic variant Other lymphomas of large B cells
-Centroblastic -Primary mediastinal (thymic)
-Immunoblastic
large B cell lymphoma
-Anaplastic
-Intravascular large B cell
Molecular subgroups lymphoma
-Germinal centre B cell like -DLBCL associated w chronic
-Activated B cell like inflammation
-Lymphomatoid granulomatosis
IHC subgroups -ALK-positive LBCL
-CD5+ DLBCL
-Plasmablastic lymphoma
-Germinal centre B cell like
-LBCL arising in HHV8+
-Non germinal centre B cell
like multicentric Castlemans
-Primary effusion lymphoma
Subtypes
-T cell/histiocyte-rich large B
cell lymphoma Borderline cases
-Primary DLBCL of the CNS
-Primary cutaneous DLBCL, leg type
-EBV + DLBCL of the elderly
Score 10 if the arrow hits center Germinal center type: CD10+
Score 5 if it hits Para-center zone Burkitt
No scores if it hits marginal zone Follicular lymphoma
Some DLBCL
AITL (GC T cells)
B Lymphoblastic Lymphoma
CD5+:
Mantle cell lymphoma
CLL/SLL
10 Rare DLBCL
5
CD10- CD5-:
0 Marginal zone lymphoma
HCL
others
Immunoblastic variant
Centrablast variant
Anaplastic variant
Lung, brain, liver, kidney skin
Grading based on # of EBV+ cells
Grade 1 <5 EBER+ per hpf
Grade 2 5-20 EBER+ per hpf
Grade 3 >50 EBER+ per hp
WHO classification:
- Nodular lymphocyte predominant
- Classical
Nodular sclerosis
Mixed cellularity
Lymphocyte-rich
Lymphocyte-depleted
Nodular Lymphocyte Predominant Hodgkin
lymphoma
5% HL
Common in young middle age male (30-50yo)
Classic Hodgkin lymphoma
-- 95% of HL with bimodal age with
15-35 year peak and 2nd peak late life
-- Mediastinal
Nodular Sclerosis Hodgkin lymphoma
Nodular pattern with fibrous bands and scattered large multilobated cells: nodular
sclerosis type of classical Hodgkin lymphoma (HL).
CD30+, CD15+ (75-85%); CD45 neg, LMP-1 and EBER variable, BSAP(PAX5)+
Mixed cellularity Hodgkin lymphoma (MCHL)
5% of all HL
nodular growth pattern
Regressed germinal centers
RS cells in mantle zone
No eos + PMNs in background
Lymphocyte depleted Hodgkin lymphoma (LDHL)
clinically:
-First three decades of life, M:F =1.5:1
-maybe nodal or extranodal
-B symptom
-aggressive, but excellent response to
chemo
pathologically:
- broad morphologic spectrum
- typically sinusoidal/subcapsular
-hallmark cells: eccentric, embryo-like,
reniform, wreath-like nuclei, eosinophilic
Golgi zone in cytoplasm, multiple nucleoli
-numerous variants:
common; small cell; monomorphic;
lymphohistiocytic; giant; sarcomatoid
ALCL, ALK+ common type
Left: The neoplastic cells are difficult to identify: they are medium-sized to large, and possess distinct
nucleoli. The background is rich in small lymphocytes, histiocytes and plasma cells. Right:
Immunostaining for CD30 reveals a surprising number of neoplastic cells not appreciated on routine
microscopy.
ALCL, ALK+ Small cell type
5-10%.
Small to
medium-sized
neoplastic
cells with
irregular
nuclei.
Hallmark cells
are present
and often
around blood
vessels.
ALCL, ALK+
immunophenotypically:
-variable T-cell marker: CD3- (75%),
CD4+, CD2+, CD5+, CD8-, CD43+,
CD25+
-Cytotoxic associated antigens: TIA1,
granzyme B, perforin
- null-cell type: negative T- and B-
markers
- CD30+, EMA+
genetically:
- t(2;5)(p23;q35) by karyotype
-NPM (nucleophosmin):ALK fusion
- ALK on 2p23
Prognosis
- ~ 15% have partners other than
- Better than ALCLALK-
NPM: cytoplasmic and/or nuclear
ALCL, ALK-
Definition: CD30+ T-cell neoplasm, indistinguishable from
ALCL, ALK+ based on morphology. ALK-
Clinical:
Adults (40-65 yo), M:F =1.5:1
LN and extranodal involvement
Advanced stage, Lymphadenopathy, B symptoms
Morphology: similar to ALCL, ALK+
Immunophenotype:
CD30 strong positive, ALK-
Null T-cell type
CD43+; CD2+, CD3+; CD5+; CD4+
Cytotoxic associated markers: TIA1, granzyme B and/or perforin
Postulated normal counterpart:
Activated mature cytotoxic T-cell
Genetics: TCR rearrangement, chromosome abnormalities deffer from
ALCL, ALK+
Questions?
Email: pedhemepath@gmail.com