Lymph Nodes 1

Question 1

Bcl-6

Answer 1

Follicular centers - nuclear

Question 2

CD10

Answer 2

Follicular centers - cytopasmic

Question 3

CD21

Answer 3

Follicular dendritic cell network

Question 4

IgD

Answer 4

follicular mantle zone

Question 5

Patterns of benign lymphadopathy - Follicular

Answer 5

– Follicular Hyperplasia
– Giant lymph node hyperplasia-hyaline vascular (Castleman disease)
– Progressively transformed germinal centers
– HIV-related lymphadenopathy
– Rheumatoid lymphadenopathy
– Syphilitic lymphadenopathy

Question 6

Patterns of benign lymphadopathy - Paracortical

Answer 6

– Viral infections, NOS
– Post-vaccinial lymphadenitis
– Infectious mononucleosis (Epstein-Barr virus)
– Drug induced hypersensitivity
– Angioimmunoblastic lymphadenopathy
– Dermatopathic lymphadenitis
– Histiocytic necrotizing lymphadenitis (K-F disease)
– Systemic lupus erythematosus

Question 7

Patterns of benign lymphadopathy - Sinus Pattern

Answer 7

– Sinus histiocytosis
– Langerhans cell histiocytosis (EG, H-X)?
– Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)
– Monocytoid B cell hyperplasia
– Hemophagocytic syndromes
– Whipple disease
– Vascularization of sinuses
– Lymphangiogram effect

Question 8

Follicular hyperplasia VS Follicular lymphoma

Answer 8

Hyperplasia:

• -Polymorphic cells
• -↑ mitosis
• -Macrophages
• -Bcl-2 (-) and t(14;18)(-)
• -Architecture preserved
• -Variation in G.C.
• -No back to back follicles

Lymphoma:

• -Monotonous cells
• • ↓ mitosis
• • ↓ Macrophages absent
• -Bcl-2 (+) and t(14;18)(+)
• -Architecture effaced
• -Little variation in G.C.
• -Back to back follicles

Question 9

Castleman lymphadenopathy

Answer 9

– Mediastinal lesions
– Regressed germinal centers
– broad mantle zone, onion skin
– dendritic reticulum cells
– Interfollicular vascularity—lollipop
– HHV8
– Mulitcentric Castleman disease worse prognosis
– Multicentric Castleman disease assoc w POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin abnormalities)

Question 10

HIV related lymphadenopathy

Answer 10

Three stages are seen:

Follicular hyperplasia
Follicular involution
Lymphocyte depletion

Question 11

TOXOPLASMA LYMPHADENOPATHY

Answer 11

Follicular Pattern

• CLINICAL
– Asymptomatic or fever, cervical lymph nodes
– Organism: Toxoplasma gondii
ARCHITECTURE/CYTOLOGY
- Follicular hyperplasia
- Epithelioid histiocytes near GC
- Monocytoid B-cells in sinuses
- Serology confirms diagnosis

Question 12

INFECTIOUS MONONUCLEOSIS

Answer 12

Paracortical pattern

• CLINICAL FEATURES
– Usually self limited, usually cervical lymph nodes, teens presenting with infections
ARCHITECTURE /CYTOLOGY
- Paracortical proliferation of immunoblasts
- Sinuses distended by monocytoid B cells or immunoblasts
- Focal necrosis/apoptosis
- Hodgkin’s-like cells sometimes
- LMP(+) or EBER(+)
- Diff dx: DLBCL

Acute: IgM + IgG VCA
Heterophile Ab (monospot) react w sheep or horse RBC 

Remote: IgG EBNA, IgG VCA

CD8+ T cells stop EBV infected B cells from circulating

CD30+

Question 13

DERMATOPATHIC LYMPHADENOPATHY

Answer 13

Paracortical pattern:

CLINICAL
– Chronic dermatoses may be present but the most florid reactions are seen with exfoliative dermatitis
ARCHITECTURE/CYTOLOGY
- Paracortex expansion
- Many pale histiocytes, some with with melanin
- Langerhans cells and interdigitating reticular cells
- Atypical T cell should be absent
- Mycosis Fungoides must be considered if confluence is present

Question 14

HISTIOCYTIC NECROTIZING LYMPHADENITIS

Answer 14

• CLINICAL
– Kikuchi-Fujimoto disease—Asian, women, mean age 30 years
– Usually cervical lymph nodes
– Serologic tests for organisms negative (CMV, EBV, Toxo.)
– Self limiting disease
– Forme fruste of SLE
ARCHITECTURE/CYTOLOGY
- Necrosis with karyorrhectic dust
- Acute inflammation is absent (polys and eos)
- Plasmacytoid monocytes, cresentic histiocytes
- No plasma cells, unlike SLE

Question 15

CAT SCRATCH LYMPHADENITIS

Answer 15

• CLINICAL
– Contact with cat
– The offending organism is Bartonella henselae

ARCHITECTURE/CYTOLOGY
Suppurative granulomas (stellate abscesses)
Neutrophils & monocytoid B-cell hyperplasia
Granulomas can be seen outside the L.N.
Warthin-Starry and Brown-Hopps stains

Question 16

Rosai-Dorfman -

sinus histiocytosis with massive lymphadenopathy

Answer 16

• CLINICAL
– Bilateral cervical lymph nodes in a teen with fever

ARCHITECTURE/CYTOLOGY
Distended sinuses with foamy histiocytes
Emperipoiesis (inflam cells in histiocytes)
No erythroid phagocytosis (hemophagocytic
syndrome)

S-100(+), CD68(+), lysozyme (+)
Rosai-Dorfm

Question 17

Hemophagocytic syndrome

Answer 17

Viruses, T-cell lymphoma, X-linked syndrome,

Erythrophagocytosis, viral inclusions

Question 18

BACILLARY ANGIOMATOSIS

Answer 18

• CLINICAL
– Immunodeficient patients, lymph nodes draining skin lesion
– Organism Bartonella henselae

ARCHITECTURE/CYTOLOGY

• Vascular nodular parenchymal proliferation
• Amphophilic and eosinophilic material
• Vascular spaces are lined by plump endothelium
• Warthin-Starry stain shows organisms

Question 19

Bacilary angiomatosis VS Kaposi sarcoma

Answer 19

Bacilary angiomatosis -

• Plump endothelial cells
• Little atypia
• Pos for organisms
• HHV8 -

Kaposi sarcoma-

• Spindle shaped cells;
• Slit shaped vessels
• More atypic, mitosis (+)
• Neg for organism
• HHV8 +

Question 20

CLL/SLL DEFINITION

Answer 20

A neoplasm of monomorphic small, round
B-lymphocytes admixed with
prolymphocytes and paraimmunoblasts
forming pseudofollicles.

CLL/SLL makes up 6.7% of all lymphomas

Question 21

CLL/SLL - Pseudofollicles

Answer 21

• Low magnification

• Spherical structures
• Pale staining
• Poorly defined
• Never surrounded by mantle cell zone

• High magnification
--Cells loosely packed together with
clear spaces often separating cells
--Prolymphocytes (cells with one centrally
placed prominent nucleolus)

Question 22

CLL/SLL - Peripheral Blood

Answer 22

• absolute lymphocytosis
• prolymphocytes less than 10%
- smudge cells

Question 23

CLL/SLL Phenotyping

Answer 23

Positive:

CD20--weak
CD79a 
CD5 (85%) 
CD23 (85%)
CD43 (98%)
CD11c
IgM
IgM and IgD
cIg (5%)

Negative:
CD3
CD10
Cyclin D1 (90)%

Question 24

CLL is really two diseases

Answer 24

Favorable
CD38, Zap70 negative
Post germinal center cell

Adverse
CD38, Zap70 positive
Naïve B-cell

Question 25

CLL/SLL Immunoglobulin Gene Mutations

Answer 25

IgH variable chain mutations normally occur
during germinal center stage of B cell
maturation

CD38 and ZAP70 are surrogate markers for
IgH variable chain gene mutation status

Question 26

B- CLL GENETICS

Answer 26

Normal karyotype 50%

Del(13q) 25% good px

Tri 12 30% atyp histology/poor px

Del(11q) 2% poor prognosis

Del(17p) 10% poor prognosis

Question 27

Hairy Cell Leukemia

Answer 27

• Medium B cells w pale cytoplasm,
oval/reniform/beanshaped nuclei

• Pancytopenia, monocytopenia

• Spleen morphology
– Localized to red pulp w red pulp lakes
– Inconspicuous white pulp

• Bone marrow
– Often subtle infiltrate, dispersed B cells wi pale cytoplasm, “fried egg appearance”
– ↑ reticulin fibrosis with dry tap

• Lymph node
– Paracortical infiltrate with sparing of follicles.

Question 28

Hairy Cell Leukemia

Answer 28

• Phenotype
– Bright CD11c, CD25, CD103,
– Annexin A1, TRAP, DBA.44 positive

• Treatment
– High response rates to purine analogues, 2CDA
NO CHOP

Question 29

Hairy cell leukemia variant

Answer 29

• Leukocytosis,
• Presence of monocytes,
• Prominent nucleoli like PLL
• Missing CD25 or CD103
• Resistant to HCL therapy
• Poor prognosis
• WHO 2008, these cases are not thought to be biologically related to HCL

Question 30

Follicular lymphoma

Answer 30

•BCL-2+ ↓with grade with nearly
100% positive in grade 1 and 75%
grade 3

•BCL-2 often - in cutaneous follicular
lymphoma

•t (14;18)(q32;q21) present in 90% of
FL leads to overexpress BCL2 protein

•t (14;18) not sufficient to diagnose FCL detectable by PCR in some normal subjects
also found in 15-20% DLCBCL

• PCR is limited based on variation in the breakpoint involving BCL2.
• MBC and mcr breakpoints account for 70% of cases
• FISH detects nearly all breakpoints

Question 31

Mantle Cell lymphoma

Answer 31

• Clinical
–Lymphomatous polyposis is mantle cell which studs the GI tract
• Phenotype
– CD20+, CD5+ (90%), CD43+, BCL-2+,
and nuclear BCL-1+ (80% cases)
• Genotype
– t (11;14) with rearrangement and
over-expression of BCL-1 (cyclin D1, PRAD1)
– 13q14 deletion and trisomy 12 frequent (yes, similar to CLL)

Question 32

Marginal zone lymphoma

Answer 32

1. Malignant
– Monocytoid cells
– Plasmacytoid cells
– Dutcher bodies
– Expanded\confluent marginal zones
– Lymphoepithelial lesions
2. Reactive
– Reactive germinal centers may be
colonized by marginal zone cells

Question 33

Marginal zone lyphoma - genetics

Answer 33

– t (11;18) in 25-50% MALT
– t(11;18) not in primary nodal MZL
– t(11;18) not in MALT with DLBCL
– t (11;18) resistant to antibiotic therapy

Question 34

Marginal zone lymphoma - precursor legions

Answer 34

• In gastric MZL H. pylori infection is 90%
• Sjogren syndrome—44 fold increase
• Hashimoto thyroiditis
• Hepatitis C
• Borrelia burgdorferi (Lyme dz), skin
• Campylobacter jejuni, eye

Question 35

WHO 2008 Waldenstrom macroglobulinemia

Answer 35

• WM is defined as LPL with bone
marrow involvement + IgM monoclonal
gammopathy of any concentration
• IgM paraprotein without LPL is not WM
• Level of IgM paraprotein is irrelevant

Question 36

Lymphoplasmacytic lymphoma

Answer 36

• Morphology–small B lymphocytes, plasmacytoid lymphocytes and plasma cells, Dutcher bodies
• Clinical—Hyperviscosity (30%), Neuropathy (10%), Cryoglobulinemia
• Immuno–CD5-, CD10-, CD23-
• Molecular–No recurrent abnormality
PAX5 translocation (t(9;14)) not seen