Lymphoid Proliferation

2 histological signs of a reactive lymph node

Paracortical (T-cell) nodule

Lymphoid follicle

Name some features/structures of Reactive lymph nodes

Paracortical (T-cell) nodule

Lymphoid follicle

Mantle zone

Germinal centre

Centrocytes

Centroblasts

Follicular dendritic cells

Tingible body macrophages

What does each immunohistochemical marker identify?

• CD20

• CD3

• CD10

• CD21

• BCL2

CD20: B cells.

CD3: T cells.

CD10: germinal-centre B cells.

CD21: follicular dendritic cell networks.

BCL2(: an anti-apoptotic protein; in a typical reactive follicle, germinal-centre B cells are BCL2-negative or show markedly reduced expression, while mantle-zone lymphocytes are positive)

What is the normal palpable size range of adult inguinal lymph nodes

0.5–2 cm

What proportion of enlarged lymph nodes seen in general practice are reactive

98-99%

8 causes of Lymph node enlargement

Local infection

Systemic infection

Autoimmune disease

Medications

Malignancy: Metastatic or Lymphoma

Sarcoidosis

Castleman’s disease

Foreign body

Infectious lymphadenitis can have viral/bacterial/mycobacterial/fungal/protozoan cause. Name 2 specific viral causes

HIV

Infectious mononucleosis

What type of hyperplasia is associated with infectious mononucleosis

Paracortical hyperplasia

What type of hyperplasia is associated with HIV Lymphadenitis

Follicular hyperplasia

Classic histology of sarcoidosis

Well-defined non-caseating granulomata

What’s this

Castleman’s Disease

Features of Lymphocytic/ lymphoblastic leukaemia (bone marrow involvement, where are tumour cells found)

Lymphoid neoplasms presenting with widespread involvement of the bone marrow, accompanied by large numbers of tumour cells in the peripheral blood

Lymphoma → Lymphoid proliferations where

Lymphoid proliferations resulting in discrete extranodal or nodal tissue masses

Name a Plasma cell dyscrasia

Multiple myeloma

Lymphoma involves what types of cells

A heterogeneous group of malignancies of B cells, T cells and rarely NK cells

Lymphomas usually originate where (but can also originate where)

usually originate in the lymph nodes

May originate in any organ of the body

True/False Lymphomas are genetically stable

True - Relatively genetically stable

Genetic changes that occur in lymphomas

Recurring molecular aberrations/ chromosomal translocations

How do lymphomas present macroscopically

“Fish-flesh” or “Firm rubber” (when they efface the architecture of lymph node)

True'/False lymphomas have polymorphous cell population

False - Relatively uniform/ monomorphous cell population

What is unique about lymphomas

They have a unique / Characteristic aberrant immunohistochemical expression

Hodgkin Lymphoma usually arises where (specific)

Lymph nodes, preferentially in the cervical region

Average age of diagnosis for Hodgkin Lymphoma

Young adults - 32 years

Describe the histology of Hodgkin Lymphoma

Small numbers of scattered large mononucleated and multinucleated tumour cells (Reed-Sternberg cells) in a heterogeneous mixture of non-neoplastic inflammatory and accessory cells

What does it mean if a Hodgkin Lymphoma is annotated with A, B, X or E

A – Asymptomatic

B – Fever, drenching sweats, weight loss

X – Bulky disease

E – Single extranodal site, or contiguous to known nodal site

Describe the 4 stages of Lymphoma

I – Single lymph node region or lymphoid structure

II – Two or more lymph node regions on same side of diaphragm

III – Lymph node involvement on both sides of the diaphragm

IV – Involvement of extranodal sites beyond those designated E

Describe the 4 stages of lymphoma on a PET-CT

What are the 4 subclassifications of Classical Hodgkin lymphoma 95%

Nodular sclerosis

Mixed cellularity

Lymphocyte rich

Lymphocyte depleted

What is a type of Lymphoma that doesn’t fall under the 4 classic subtypes (that makes up the other 5%)

Nodular lymphocyte predominant Hodgkin lymphoma

What does it mean that Classical Hodgkin lymphoma has a bimodal age curve

Prevalence peaks at 15-35 years and has a second peak in late life

There is a Higher incidence of Classical Hodgkin lymphoma in patients with a history of what

infectious mononucleosis

Most common lymph nodes involved in Classical Hodgkin lymphoma

Most commonly involves cervical lymph nodes (75%), then mediastinal, axillary & para-aortic

Does Classical Hodgkin lymphoma generally present early or late

55% stage I or II at presentation

Clinical features of Classical Hodgkin lymphoma

Peripheral lymphadenopathy

Systemic ‘B’ symptoms – fever, drenching night sweats and weight loss – in 40%

2 risk factors that can → Classical Hodgkin lymphoma

EBV infection

Immune deficiency

Classical Hodgkin lymphoma macroscopic features

Enlarged, encapsulated lymph nodes with a ‘fish flesh’ cut surface

Classical Hodgkin lymphoma microscopic features

Reed-Sternberg cells in a rich inflammatory background

Describe Reed-Sternberg (RS) cells

Large, abundant cytoplasm, binucleate.

Large nuclei, prominent nuclear membrane, pale chromatin, prominent eosinophilic nucleoli

Name 2 variants of RS cells

Mummified cells

Lacunar RS cells

Name 2 characteristic immunohistochemical markers of Reed–Sternberg cells (CD__ & CD__)

CD15

CD30

What type of normal cell do Reed–Sternberg (RS) cells develop from

B cells

What has gone wrong with the B cells to → Reed Sternberg cells

RS cells originate from B cells in the germinal centres of lymph nodes.

They have monoclonal immunoglobulin (Ig) gene rearrangements → crippled B cells

Normally, B cells express transcription factors such as PAX5, OCT2 and BOB.1, which help maintain B-cell identity and immunoglobulin production.

In RS cells:

- OCT2 and BOB.1 are often lost or reduced.

- PAX5 is usually retained, but weakly expressed.

- Immunoglobulin production is generally lost.

Which of these have a M>F preference

• Nodular sclerosis

• Mixed cellularity

• Lymphocyte rich

• Lymphocyte depleted

Mixed cellularity

Lymphocyte rich

Lymphocyte depleted

Each of these is generally present at what stage

• Nodular sclerosis

• Mixed cellularity

• Lymphocyte rich

• Lymphocyte depleted

• Nodular sclerosis - I/II

• Mixed cellularity - III/IV

• Lymphocyte rich - I/II

• Lymphocyte depleted - Advanced

Which of these is generally present has mediastinal involvement

• Nodular sclerosis

• Mixed cellularity

• Lymphocyte rich

• Lymphocyte depleted

Nodular sclerosis

Normal age for each of these:

• Nodular sclerosis

• Mixed cellularity

• Lymphocyte rich

• Lymphocyte depleted

Nodular sclerosis - Young adults

Mixed cellularity - young adults, then age > 55 years

Lymphocyte rich - Older patients

Lymphocyte depleted - Median age 37 years

Which of these has the best prognosis:

• Nodular sclerosis

• Mixed cellularity

• Lymphocyte rich

• Lymphocyte depleted

Lymphocyte rich

Do Lymphocyte rich & Lymphocyte depleted present with B symptoms

Just Lymphocyte depleted

Which type of Lymphoma is associated with HIV infection, seen in developing countries

Lymphocyte depleted

Most important prognostic predictors of lymphoma

Stage and presence of systemic symptoms

Generally the prognosis for HL is good/bad

Good - With modern combined modality therapy, HL is curable in the majority of cases

Hodgkins Lymphoma

• Complete remission rate

• 5-year event-free survival (EFS)

• Overall survival (OS) rates

Complete remission rate 97%

5-year event-free survival (EFS) 85%

Overall survival (OS) rates 90%

Is recurrence prevalent in HL

Yes

Describe the morphology of Nodular lymphocyte Predominant Hodgkin Lymphoma

Nodular infiltrate of small lymphocytes, histiocytes and L&H cells (Lymphocytic and/or histiocytic Reed Sternberg cell variants)

Which of these are positive & negative in Nodular lymphocyte Predominant Hodgkin Lymphoma

CD20

CD15

CD30

Oct2/BOB.1

CD20 +ve

CD15 –ve

CD30 –ve

Oct2/BOB.1 +ve

Is prognosis good/bad for Nodular lymphocyte Predominant Hodgkin Lymphoma

Prognosis good if early stage

The International Prognostic Index (IPI) estimates prognosis in non-Hodgkin lymphoma name 5 factors that score a point for bad prognosis

Age > 60 years

Serum LDH > twice normal

Performance status >/= 2

Ann Arbor Stage III/ IV

Extranodal involvement at >1 site

Name 4 types of low grade B cell Non-Hodgkin lymphoma

Follicular lymphoma

Marginal zone lymphoma

Lymphoplasmacytic lymphoma

CLL/SLL (Chronic/Small Lymphocytic Lymphoma)

Name an intermediate grade B cell Non-Hodgkin lymphoma

Mantle cell lymphoma

Name a high grade B cell Non-Hodgkin lymphoma

DLBCL

Mantle cell variants

Name 2 aggressive B cell Non-Hodgkin lymphomas

Burkitt’s lymphoma

Lymphoblastic lymphoma

What specific types of cells in what pattern are involved with Follicular Lymphoma

A neoplasm of follicle centre B cells (centrocytes and centroblasts) with at least a partially follicular pattern

Median age for Follicular Lymphoma

59

Is there an increased prevalence for M/F

Female

M:F = 1:1.7

List the sites where follicular lymphoma can be found

Lymph nodes

Spleen

Bone marrow

Peripheral blood

Waldeyer’s ring (lymphoid tissue around the throat)

Non-haematopoietic sites in setting of disseminated disease

Sx of follicular lymphoma

Lymph node enlargement

Otherwise asymptomatic

Most common stage at diagnosis for follicular lymphoma

Stage III/ IV

What % follicular lymphoma has bone marrow involvement at diagnosis

40%

Name & describe the specific clonal Immunoglobulin gene rearrangement associated with Follicular Lymphoma

t(14;18)

Rearrangement of the bcl-2 anti-apoptotic gene to the IgH locus

Describe the prognosis for Grade I/II vs III Follicular Lymphoma

Grades 1 & 2: Indolent; relapsing/ remitting

Grade 3: Aggressive; possibly curable

What % Follicular Lymphoma progress to DLBCL

25-35%

Where & with what tissue is malt lymphoma associated

Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue

General age & gender of MALT Lymphoma pts.

Slight female preference - median age 61

Name a condition that is a risk factor for MALT lymphoma

Chronic inflammatory conditions: Helicobacter associated chronic gastritis

Most common sites for MALT lymphoma

GIT 50%; also lung, head and neck, skin, thyroid, breast

MALT lymphoma in gastric lamina propria and muscularis mucosae leads to formation of what type of lesions

Lymphoepithelial lesions

What IHC marker & what Ig marker would be positive for Malt lymphoma

CD20 +ve

IgM +ve

(no aberrant/unique markers)

What 2 genetic mutations are associated with MALT lymphoma

Trisomy 3 (in 60%)

t(11;18) (in 25-50%)

MALT lymphoma is fast/slow to disseminate

Slow (Indolent natural course)

Risk of progression from MALT lymphoma → what

DLBLC

2 Tx options for MALT lymphoma

May respond to eradication of H. pylori with antibiotics

Radiation therapy

Mantle cell lymphoma is a B cell neoplasm composed of what type of cells

Monomorphous small lymphoid cells

Mantle cell lymphoma represents what % of NHL

3-10%

Median age & which gender preference for Mantle cell lymphoma

Median age 60 years

M>F 2:1

Where does Mantle cell lymphoma affect

Lymph nodes, spleen, bone marrow; GIT (30%), Waldeyer’s ring

Mantle cell lymphoma typically presents at what stage with what Sx

Stage III/ IV Lymphadenopathy, hepatosplenomegaly, marrow involvement (> 50%)

IHC markers of mantle cell lymphoma

CD20 +ve

CD5 +ve

Cyclin D1 +ve

Mutation associated with Mantle cell lymphoma

t(11;14)

What do 11 and 14 normally encode (& what does their fusion protein do)

Chromosome 11: Encodes Cyclin D1.

Chromosome 14: Contains the immunoglobulin heavy-chain (IGH) gene

(Fusion → Excess Cyclin D1)

What is the prognosis for Mantle cell lymphoma - good/bad? explain

Prognosis poor: Median survival of 3-5 years; cannot be cured

Describe Diffuse Large B Cell Lymphoma (DLBCL)

A heterogeneous group of disorders - diffuse proliferation of large neoplastic lymphoid cells

Median age of diagnosis & gender preference in DLBCL

Median age 70

M > F

Is DLBCL usually nodal/extranodal & say most common location when extranodal

Nodal (60%) or Extranodal (40%) (most commonly GIT)

Diffuse Large B Cell Lymphoma presentation

Rapidly enlarging mass

Diffuse Large B Cell Lymphoma morphology

Diffuse sheets of large B lymphocytes

Diffuse Large B Cell Lymphoma IHC markers

CD20 +ve

Diffuse Large B Cell Lymphoma genetic mutation

Rearrangement of BCL6 (Chromosome 3q27) in 30%

t(14;18) in 10-30%

Diffuse Large B Cell Lymphoma prognosis

Aggressive, but potentially curable

Does a high/low International Prognostic Index (IPI) indicate worse prognosis

High IPI predicts poorer survival