Lymph node and spleen

Question 1

What is/are the differences between the primary and secondary follicle in a lymph node?

Answer 1

Primary follicle consists of aggregates of small, dark staining inactive (naive) B lymphocytes, usually near the capsule, within a network of follicular dendritic cell processes. No germinal center is present.

A secondary follicle arises from primary follicle that develops germinal centers due to antigenic stimulation of B cells and production of antibodies. Contains pale staining germinal center which may be polarized towards site of antigen entry. Surrounded by a mantle zone and marginal zone lymphocytes.

Question 2

Which cell population occupies the germinal centre of secondary follicles?

Answer 2

Contains predominantly B lymphocytes (including centroblasts and entrocytes) and scattered follicular T helper cells ans and T regs.
Also tingible body macrophages and follicular dendritic cells.

Question 3

What are centroblasts and centrocytes?

Answer 3

Centroblasts are large noncleaved follicular center cells (B cells) with moderate amounts of basophilic cytoplasm, large round nuclei, open chromatin, multiple peripheral nucleoli. Frequent mitotic figures.
Centrocytes are large and small cleaved follicular center cells (B cells) with scant cytoplasm and inconspicuous nucleoli.

Question 4

What is CD20+ used to stain for?

Answer 4

Maturing B cells (normally in follicles)

Question 5

What is CD3+ used to identify?

Answer 5

mature T cells.

Question 6

A normal germinal center is said to be ‘polarized’. What does this refer to?

Answer 6

Refers to large centroblasts clustered at one side ofhte follicle creating a lopsided appearance.

Question 7

What composes the mantle zone and where is this?

Answer 7

The mantle zone refers to teh dark outer rim of the follicle which consists of the displaced remains of the primary follicle. It consists of antigen-naive B cells

Question 8

What supporting elements reside in the germinal centres?

Answer 8

follicular dendritic cells and tingible body macrophages, which clean up the apoptotic debris.

Question 9

What is CD45 stain?

Answer 9

Stains for human leucocyte antigen, (used to dx metastatic lymphoma)

Question 10

Which stains, when positive, rule out lymphoma?

Answer 10

Melanoma stains and cytokeratins

Question 11

Describe the genetic profile of high-grade DLBCL

Answer 11

Genetic rearrangements of MYC, BCL2, and/or BCL6 genes.

Question 12

How would you characterise Burkitt’s lymphoma?

Answer 12

High grade B cell lymphoma that is identified by its high mitotic rate (Ki67 index of nearly 100%) and its population of medium-sized, densely packed lymmphocytes with intermixed macrophages and apoptotic bodies. “Starry Sky” analogy.
Densely packed tumour
A/W EBV and most cases involve a MYC translocation.

Question 13

What is the most common lymphoma?

Answer 13

DLBCL

Question 14

What is the prominent genetic profile of follicular lymphoma?

Answer 14

translocation of BCL2 (an antiapoptotic factor) such that it is abnormally upregulated. NB: BCL2 usually turns off in germinal centers, making the centroblasts and centrocytes susceptible to apoptosis. Abnormal retention of BCL2 leads to cells that do not die.

Question 15

Histologically, at low power, how does follicular lymphoma appear on a slide?

Answer 15

Nodular proliferation of back-to-back neoplastic follicles that fill the lymp node. Within these fllicles are a mixture of neoplastic centrocytes (smaller) and centroblasts (larger); the realtive proportion determines the grad eof lymphoma. The lymph node is replaced by malignant follicles which lack the mantle zones, polarization and cell heterogeneity of germinal centres. FL can grow and spread to the marrow and transform to DLBCL.

Question 16

What is the DDx for FL and how would you distinguish the two?

Answer 16

Benign reactive lymphoid hyperplasia can also present as a nodular collection of follicles in an enlarged node.

Features of benign follicular hyperplasia (not seen in follicular lymphoma).

• Germinal centers of variable sizes and cuffed by mantle zones (as opposed to back to back)
• Polarity of germinal centers in which the centroblasts and centrocytes tend to take up opposite positions in the follicle, creating an asymmetry.
• Tingible body macrophages
• “open sinuses” (which are not seen as open, really, but full of histiocytes)
• Abundant mitoses and apoptoses.

Question 17

What is MUM1?
Which cells normally express this?

Answer 17

MUM1 / IRF4 is the abbreviation of multiple myeloma 1 / interferon regulatory factor 4
Normally expressed in plasma cells, melanocytes, activated B cells and activated T cells.
nuclear stain

Question 18

Burkitts lymphoma

Frequent mutations?

Answer 18

translocations of the MYC gene on chromosome 8. Mostly commonly: MYC + IGH [t(8;14)] but may also be [t(2;8)] or [t(8;22).

Question 19

mantle zone lymphoma

Common mutation?
What does this mutation lead to

Answer 19

(11;14) translocation involving the IGH locus on chromosome 14 and the cyclin D1 locus on chromosome 11 that leads to overexpression of cyclin D1. The resulting upregulation of cyclin D1 promotes G1-S phase progression during the cell cycle.

Question 20

pathogenesis of Hairy cell leukemia

genetic pathogensis

Answer 20

Activating point mutations in the serine/threonine kinase BRAF (lies immediately downstream of RAS in the MAPK signaling cascade).

Question 21

Lymph node biopsy

Dx?
Key features
IHC

Answer 21

Rosai Dorfmann disease
Accumulation of histiocytes with enlarged, round to oval hypochromatic nuclei and abundant eosinophilic cytoplasm, often containing engulfed intact inflammatory cells known as emperipolesis. associated with fibrosis and prominent inflammatory infiltrate comprised of plasma cells and lymphocytes.
IHC: CD68(+), CD163(+), cyclin D1(+), S100 (+) for emperipolesis material. Negative for BRAF, CD1a, Langerin.

Question 22

What are the markers for T-follicular helper cell phenotype?

Answer 22

PDL1, CD10, BCL6, ICOS, CXCL13, CXCR5, SAP.
CXCL13 is more specific than CD10 (CD10 is specific not sensitive)

Question 23

What are your cytotoxic T cell markers?

Answer 23

TIA-1, granzyme B, perforin.

Question 24

Describe your panel to work-up a T-cell lymphoma:

Answer 24

CD3/CD20
CD2/5/7 (pan-T cell markers)
CD4 and CD8 (subsets)
TFC markers: PD1, ICOS, BCL6, SAP, CXCR5, CXCL13
Cytotoxic markers: TIA-1, granzyme B, perforin
CD30 and ALK
CD21/23 FDM expansion (in case of AITCL)
EBERish
Ki67
Mum1 etc if B-cell component present…

Question 25

Describe the Hans algorith for large B cell lymphoma

Answer 25

Question 26

mantle cell lymphoma

gene rearrangment

Answer 26

demonstration of CCND1 rearrangement or CCND1::IGH translocation

Question 27

Describe features of Kimura disease (histological; demographic, clin presentation)

Answer 27

Morphologic diagnosis characterized by hyperplastic reactive follicles surrounded by eosinophilic infiltrates in a background of polymorphous inflammatory cells

Clinical:
Young males; Slow growing nodules / masses, often painless and nontender

Sites: Nodal and extranodal
Extranodal commonly includes skin and subcutaneous tissue, head and neck sites, including major salivary glands