29. Indolent B-cell lymphomas (FL, CLL, MCL, MZL)

What can we divide the WBC into?

- Myeloid cells

- Lymphoid cells

Lymphoid cells?

- T-cells

- B-cells (plasma cells)

- NK-cells

- Dendritic cells

Myeloid cells?

- Erythrocytes

- Thrombocytes

- Neutrophils

- Eosinophils

- Basophils

- Monocytes -> Macrophages

What are the three major types of haematological malignancies?

- Lymphoid neoplasms

- Myeloid neoplasms

- Histiocytic/dendritic neoplasms

Lymphoid neoplasms originate from?

- T-cells

- B-cells

- NK-cells

Myeloid neoplasms originate from?

Myeloid progenitor cells

Histiocytic/dendritic neoplasms originate from?

- Macrophages

- Dendritic cells

Lymphoid neoplasms can manifest as?

- Leukaemias = tumor cells are present in the peripheral blood and bone marrow

- Lymphomas = tumor cells produce masses in lymph nodes or other tissues

After which properties are the lymphoid neoplasms classified?

- Whether they are Hodgkin lymphoma or non-Hodgkin lymphoma

- Whether they originate from T or NK-cells, or B-cells

- Whether they originate from precursor cells or mature cells

- Whether they are aggressive, indolent or in-between

Nodal vs. extra-nodal lymphomas?

- A lymphoma is nodal if it originates in a lymph node

- A lymphoma is primary extranodal if it starts in other lymphoid tissue

- A lymphoma is secondary extranodal if it spreads from a lymph node to other tissues

What are B symptoms?

Fever, night sweats, weight loss

- common symptoms in patients with lymphoid neoplasms

Which staging is used for lymphoid neoplasms?

Ann Arbor staging

How does Ann Arbor staging work?

- Stage I = cancer in a single region, usually one lymph node and the surrounding area

- Stage II = cancer in more lymph node regions, on one side of the diaphragm

- Stage III = cancer in more lymph node regions, on both sides of the diaphragm

- Stage IV = cancer in one or more extralymphatic organs

Other modifiers of Ann Arbor staging?

- E = extranodal involvement

- A = no B-symptoms

- B = B-symptoms

- X = larger than 10cm mass

Types of indolent lymphomas?

- Follicular lymphoma

- Chronic lymphocytic leukaemia

- Marginal zone lymphomas

Follicular lymphoma?

Indolent, mature, non-Hodgkin B-cell lymphoma

Follicular lymphomas manifests as? why is it called follicular lymphoma?

Slowly progressive, painless, generalized lymphadenopathy

- the neoplastic cells form "neoplastic follicles" in the lymph nodes

Follicular lymphoma translocation?

t(14;18)

- BCL2 on chromosome 18 is fused to the IgH gene on chromosome 14

= overexpression of the Bcl-2 protein

Bcl-2

Cellular protein that inhibits apoptosis

Chronic lymphocytic leukaemia? why is it called leukaemia?

Indolent, mature, non-Hodgkin B-cell lymphoma

- called leukaemia because tumor cells are found in the blood in 90-100% of the cases

Symptoms of CLL?

- Painless lymphadenomegaly and splenomegaly

- Symptomless leukocytosis

- B-symptoms

What are the two types of CLL?

- Pre-follicular type

- Post-follicular type

Pre-follicular CLL? originate from?

- Immunoglobulin heavy chain gene (IgH) has not been mutated

- Much worse prognosis

- Originate from CD5+ B-cells prior to somatic hypermutation

Post-follicular CLL? originate from?

- Immunoglobulin heavy chain gene (IgH) has been mutated

- Better prognosis

- Originate from CD5+ B-cells after somatic hypermutation

What is somatic hypermutation?

Rearrangement of Ig genes

- resulting in various antibodies, in which some have higher affinity

What is the Richter Transformation?

Transformation of CLL into Diffuse large B cell lymphoma (DLBCL)

Marginal zone lymphoma? develops from?

Indolent, mature, non-Hodgkin lymphoma

- develops from marginal zone B-cells

Subtypes of marginal zone lymphoma?

- Extranodal marginal zone lymphoma

- Nodal marginal zone lymphoma

- Splenic marginal zone lymphoma

Extranodal marginal zone lymphoma?

MALT

- arise most commonly from lymphoid tissue in organs such as the stomach, salivary glands, intestines, lungs or breasts

What is MALT lymphomas associated with?

- H.pylori gastritis

- Sjögren syndrome

Nodal marginal zone lymphoma?

Arise in lymph nodes

- most commonly cervical lymph nodes

Splenic marginal zone lymphoma?

Arise in the spleen or bone marrow

Mantle cell lymphoma? develops from?

Mature, non-Hodgkin B-cell lymphoma - belongs to "the other type"

- originates from mantle zone B-cells

Mantle cell lymphoma? translocation

t(11;14)

- Cyclin D1 gene is fused to the IgH locus = overexpression of Cyclin D1

- Cyclin D1 is involved in cell proliferation

Mantle cell lymphoma in the GI?

Manifest as multifocal submucosal nodules

- can resemble polyps