Leukemia and Lymphoma Simplified

To understand the different types of leukemia and lymphoma, we must first have a basic overview of how blood cells are made.

Terminology and Definitions

White blood cells generally refer to cells of the immune system
- White blood cells can originate from either myeloid or lymphoid lineage
- White blood cells is synonymous with leukocytes
- White blood cells is NOT the same as lymphocytes
Cells of the myeloid series include granulocytes (neutrophils, eosinophils, basophils and mast cells), red blood cells, platelets
- Myeloproliferative neoplasm therefore refers to uncontrolled proliferation of cells of the myeloid series
  - Uncontrolled proliferation of platelets = essential thrombocytosis
  - Uncontrolled proliferation of red blood cells = polycythemia vera
  - Uncontrolled proliferation of monocytes = chronic myelomonocytic leukemia (CMML)
  - Uncontrolled proliferation of granulocytes = chronic myeloid leukemia
Cells of the lymphoid series include B cells, T cells, and natural killer cells
- Uncontrolled proliferation of lymphocytes that involve bone marrow and peripheral blood on presentation is referred to as leukemia
- Uncontrolled proliferation of lymphocytes that involve lymph nodes or lymphoid organs, and present as masses is referred to as lymphoma
Blasts are early myeloid or lymphoid progenitor cells
- In blood cancer, we want to differentiate between blood cancer that involves blasts or blood cancer that involves mature cells
- Why? Because blasts are so immature that they do not have any actual function, and only serve to overcrowd the bone marrow and suppress production of mature normal red and white blood cells that are needed for daily function

Leukemia vs Lymphoma

Both leukemias and lymphomas involve uncontrolled proliferation of leukocytes, but whether we call one vs the other depends on how they present and whether the neoplasm presents as a mass (lymphoma) or whether it presents with peripheral blood and bone marrow involvement (leukemia). The line can get blurry between the two.

Neoplasm of immature lymphoid cells can be either
- Leukemia – Acute lymphoblastic leukemia
- Lymphoma – Lymphoblastic lymphoma
Neoplasm of mature lymphoid cells can be either
- Leukemia – Chronic lymphocytic leukemia
- Lymphoma – Small lymphocytic lymphoma

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are often considered different versions of the same disease because they are very similar.
Canadian Cancer Society. Article: “Chronic lymphocytic leukemia and small lymphocytic lymphoma”

Leukemia

Leukemias can be classified as either acute or chronic.

Acute leukemias can be described as

More aggressive
Originate from early myeloid or lymphoid progenitors (blasts)

There are two classes of hematological mutations: class 1 and class 2.

Class 1 mutations are seen in both acute leukemias as well as myeloproliferative disorders in which an activating mutation in tyrosine kinase results in growth factor-independent proliferation without affecting differentiation
Class 2 mutations which are seen in acute leukemias but not in myeloproliferative neoplasms cause an arrest in differentiation in hematopoietic progenitors

In acute leukemia, both class 1 and class 2 mutations are required. In other words, for acute leukemia to persist, there must be both an arrest in maturation as well as uncontrolled proliferation of the resultant blast cells which are unable to mature and differentiate.

Acute leukemias are defined by high blast count. Chronic leukemias do not have a high blast count.

>20 % blast cells in peripheral blood or bone marrow at presentation
WHO definition for acute leukemia

Leukemic blasts may not necessarily be seen in the peripheral blood smear. If suspecting leukemia, always confirm diagnosis with presence of blasts in the bone marrow!

Types of leukemia

Acute myeloid leukemia (AML) – Uncontrolled proliferation of myeloblasts. Rapidly progressive. 80 % of acute adult leukemias and 10 – 15 % of all childhood leukemias. Tumors may be composed of myeloblasts (granulocyte precursors), monoblasts, megakaryoblasts and erythroblasts. Auer rods are a specific finding for AML.

Pearl: Acute promyelocytic leukemia (also known as the M3 variant) is a type of AML in which there is a predominance of promyelocytes (developed from myeloblast and develops into myelocyte). It is the only leukemia that can be treated with vitamin A.

Acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL) – Uncontrolled proliferation of lymphoblasts. Most common pediatric cancer. Two types of ALL:

T cell ALL (T-ALL): present as lymphomas with mediastinal lymphomatous mass as T cells normally develop in the thymus
B cell ALL (B-ALL): present as leukemias with bone marrow involvement as B cells develop in the bone marrow

Chronic myeloid leukemia (CML) – Increased proliferation of the granulocyte cell line (neutrophils). Median age 65. Usually also categorized as a myeloproliferative disorder. Recall that chronic myeloproliferative disorders result in over-production of mature myeloid cells such as megakaryocytes, red blood cell or granulocytes. They have the class 1 mutation (so there is increased proliferation) but no class 2 mutation (differentiation is preserved so few blasts).

Pearl: If left untreated, CML patients will progress to acute leukemia marked by a blast crisis. Interestingly, it can progress either to an acute myeloid leukemia OR acute lymphoblastic leukemia.
Associated with Philadelphia chromosome (mnemonic: City of Motherly Love) which is a translocation between chromosomes 9 and 22.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) – Neoplasm of mature B-cells. Slowly progressing disease (“die with it not from it”), classically affecting older men (median age 70). Often picked up incidentally in asymptomatic patients.

Lymphoma

Hodgkin lymphoma: uncontrolled proliferation of lymphoid cells; distinguished from non-Hodgkin lymphoma by presence of Reed-Sternberg cells. Associated with Epstein-Barr virus in up to half of cases.

Non-Hodgkin lymphoma (NHL): uncontrolled proliferation of lymphoid cells without Reed-Sternberg cells. NHL can involve either B cells or T cells.