Week 10 Part 2 - FNA Lymph Node Cytopathology

Question 1

Low Grade, Scattered Large Cell and High Grade Lymphoma Examples

Answer 1

Low grade lymphoma
- monotonous small cell pattern
- mixed cell pattern
Scattered large cell pattern
- Hodgkin lymphoma
- some NHL
High grade lymphoma
- large malignant cell pattern
- blastic/Burkitt pattern

Question 2

What to Look for in Flow Cytometry for Lymphoma Classification

Answer 2

CD45+ Lymphocytes
CD19+ B cells + CD3+ T cells
(Check T cell populations- CD4, CD8, loss of other T markers)
Look for CD20-/weak, CD10+ and CD5+ B cells
Check Kappa + Lambda = B cells
Look for B cell clonality

Question 3

Abnormal Flow Findings in Lymphoma

Answer 3

Light chain restricted B cell population
Surface and cytoplasmic negative population (>20% of B cells)
Aberrant T cell population (e.g. loss of pan-T markers, abnormal ratios)

Question 4

Strengths of Flow Cytometry in Lymphoma Analysis

Answer 4

Separation of low grade lymphomas from benign nodes

Question 5

Limitations of Flow Cytometry in Lymphoma Analysis

Answer 5

Hodgkin Lymphoma
T cell lymphoma
Some B cell lymphoma- fragile large cells, light chain negative
False positives in solid organs (e.g. thyroid)
Thymic lymphoid populations

Question 6

Low Grade Lymphoma - Monotonous Small Cell Pattern Differential Diagnosis

Answer 6

Quiescent/benign lymph node
CLL/SLL
Mantle cell lymphoma
Lymphoplasmacytic lymphoma

Question 7

Chronic/Small Lymphocytic Leukaemia (CLL/SLL) - Clincal

Answer 7

Largely a disease of older adults (i.e. very rare before age 40)
Usually have nodal, peripheral blood, bone marrow and splenic involvement
Clinical course is relatively indolent in most cases
Often receive no or mild treatment
10-20% develop Richter’s Syndrome

Question 8

CLL/SLL Cytology

Answer 8

Small round lymphoid cells with clumped chromatin
Population of slightly larger cells with vesicular chromatin and nucleoli
Generally less nuclear irregularity than MCL

Question 9

CLL/SLL IHC

Answer 9

CD5+, CD19+, CD23+, weak CD20, CycD1-

Question 10

Mantle Cell Lymphoma Cytology

Answer 10

Monotonous population of small lymphocytes
Population of large cells with slight but distinctive nuclear irregularity

Question 11

Mantle Cell IHC

Answer 11

CD5+, CD20+ (bright) CycD1+, CD23-
Also has t(11:14) chromosomal abnormality

Question 12

Comparison of SLL and MCL

Answer 12

SLL
- round
- smooth
- prolymphocytes
- CD23+, CD20 dim
MCL
- irregular
- more monotonous
- histiocytes
- CD23-, CD20 bright

Question 13

Scattered Large Cell Pattern Lymphoma

Answer 13

Hodgkin lymphoma
T cell rich B cell lymphoma
Non-haematopoietic tumours
Need cell block
Flow not useful in HL
Need histological conformation

Question 14

Hodgkin Lymphoma

Answer 14

Usually arises in lymph nodes, preferentially cervical
Small numbers of neoplastic cells in a variable reactive background

Question 15

Hodgkin Lymphoma Cytology

Answer 15

Reed-Sternberg cells
Atypical mononuclear cells (‘Hodgkin cell)
BG eosinophils, plasma cells and histiocytes
Lymphocytes dispersed within the background

Question 16

Nodular Lymphocyte Predominant HL (NLPHL)

Answer 16

Relatively uncommon (5% of HL)
The histological description is of “popcorn cells” with a background of lymphocytes
Immunophenotype is that of B cells:
- CD45 and CD20 pos
- CD15 and CD30 neg
Small cells are a mixture of B cells and CD4+ Th cells

Question 17

Low Grade Lymphoma - Mixed Cell Pattern Lymphoma Differential Diagnosis

Answer 17

Reactive lymph node
Follicular lymphoma
CLL/SLL with prominent proliferation centres
Marginal zone lymphoma
Tricky large cell pattern cases
T cell lymphoma

Question 18

What does a Reactive Background Contain?

Answer 18

Lymphocytes
Eosinophils
Histiocytes

Question 19

Follicular Lymphoma

Answer 19

Common, usually indolent lymphoma of elderly
Grading based on number of centroblasts:
- Grade 1: 0-5 centroblasts/HPF
- Grade 2: 6-15 centroblasts/HPF
- Grade 3a: > 15 centroblasts but centrocytes are still present
- Grade 3b: centroblasts form solid sheets with no residual centrocytes
Tendency to progress in grade, develop diffuse growth
t(14:18) translocation
Shows follicular pattern on cytology

Question 20

Follicular Lymphoma IHC

Answer 20

Positive: CD10, CD20, >MUM1 expression (75%) and >Ki-67 proliferation rate
Negative CD5, Cyclin D1

Question 21

Examples of Large Cell Lymphomas

Answer 21

Diffuse large B cell lymphoma
Grade 3 follicular lymphoma
T cell lymphoma
Generally not a diagnostic challenge to recognise as malignant
Flow cytometry of limited value
Cell block critical

Question 22

Diffuse Large B Cell and High Grade Follicular Lymphoma

Answer 22

DLBCL and grade 3b FL are similar on FNA
There is overlap in immunophenotype and genetics
DLBCL
- may be centroblastic, immunoblastic or anaplastic in type
- is characterised by the immunophenotype CD5+ large B cell lymphoma
- T cell rich large B cell lymphoma is clinicopathologically a distinct type of DLBCL

Question 23

Diffuse Large B Cell and High Grade Follicular Lymphoma Cytology Comparison

Answer 23

FL - High grade monotonous population of large lymphocytes with nuclear abnormality and prominent nucleoli
DLBCL - with large cells showing plasmacytoid diff

Question 24

Blastoid Lymphomas

Answer 24

Medium size cells, 1-3 nucleoli
Vacuolated cytoplasm makes it easy to identify
Features of proliferation
- mitoses
- TBMs
- Ki67>90%
Need:
- flow
- cell block- Ki67, TdT, cyclin D1
- FISH

Question 25

Blastoid Lymphomas Differential Diagnosis

Answer 25

Burkitt lymphoma
“Burkitt-like” lymphoma
Lymphoblastic lymphoma
Blastoid mantle cell lymphoma
Acute leukaemia
Other aggressive lymphomas

Question 26

Burkitt’s Lymphoma - Sub-Types

Answer 26

3 clinical sub-types (endemic, sporadic, immunodeficiency related)
Sporadic cases occur mainly in children and young adults
Often abdominal, but many other extranodal sites
Typically advanced stage/high tumour burden at presentation

Question 27

Burkitt’s Lymphoma Cytology

Answer 27

Medium sized cells, 1-3 nucleoli
Moderate amount of cytoplasm with lipid vacuolation on DQ
Mitoses
TBMs

Question 28

T Cell Lymphomas

Answer 28

Less common than B cell
A heterogenous group of diseases:
- many are primarily extranodal
- distinct clinicopathological “syndromes”
Many cases are cytologically malignant
Flow of limited value

Question 29

How is Metastatic Malignancy Recognised?

Answer 29

Abnormal non-lymphoid cells amongst normal/reactive lymphoid cells
Cytological criteria of malignancy

Question 30

Pitfalls and Problems Associated with Metastatic Malignancy

Answer 30

Partial lymph node involvement resulting in a false negative
Benign epithelial, mesothelial or naevoid inclusions
Necrosis or cystic change
Lymphoma
Pseudoepithelial clustering of lymphoid cells or histiocytes in bloody smears