Introduction to Hematologic Malignancies

Question 1

List the main manners in which hematologic malignancies may manifest: Leukemia

Answer 1

A malignancy of hematopoietic cells, where the chief manifestation is involvement of the blood and marrow

Question 2

List the main manners in which hematologic malignancies may manifest: Lymphoma

Answer 2

A malignancy of hematopoietic cells, derived from lymphocytes or their precursors, which presents primarily as a solid mass

Question 3

List the main manners in which hematologic malignancies may manifest: Extramedullary myeloid tumor (aka granulocytic sarcoma)

Answer 3

A malignancy of hematopoietic cells, derived from myeloid cells or their precursors (granulocytes, monocytes, etc.), which presents primarily as a solid mass

Question 4

Explain how the main manners in which hematologic malignancies may overlap (with an example)

Answer 4

• While many hematologic malignancies almost always prefer one type of manifestation, note that these types of disease manifestations are not exclusive of each other, and in some hematologic malignancies often overlap.
• A prime example of such overlap is chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL). CLL and SLL are the same biologic disease, the difference between the terms being whether the disease is primarily involving the blood and marrow (CLL), or primarily present as enlarged lymph nodes due to solid growth (SLL). In many cases, both manifestations might be prominent, and the term “CLL/SLL” can be used.

Question 5

A high grade lymphoma (what is it and what else is it called?)

Answer 5

may present as a rapidly enlarging mass. A high grade, or acute, leukemia might present as a very high white blood cell count with near replacement of all normal cells in the marrow.

Question 6

A low grade lymphoma (what is it and what else is it called?)

Answer 6

may come to attention as a mildly enlarged neck lymph node that has been present for years, or as a mild degree of lymphadenopathy (enlarged lymph nodes) noticed incidentally on an imaging study. A low grade, or chronic, leukemia may have very subtle symptoms, but very often is noticed incidentally on the results of a CBC performed for some other reason

Question 7

Recall the biological reason that many lymphomas contain balanced translocations involving the immunoglobulin and T cell receptor genes

Answer 7

the natural susceptibility of the genome to translocations during normal periods of genomic instability, namely during the initial immunoglobulin / T-cell receptor rearrangement during the maturation of B cells / T cells, and during the class recombination and somatic hypermutation process during the activation of B cells.

Question 8

Relate the importance of specific recurrent translocations in certain hematologic malignancies in regard to the clinical care of patients

Answer 8

a) Their persistent presence allows them to be used as diagnostic markers for certain hematologic malignancies
b) Their persistent presence suggests they place a critical role in the development of the hematologic malignancy they are associated with

Question 9

List 3 viruses known to have oncogenic roles in some cases of lymphoma

Answer 9

1. Epstein-Barr virus (EBV): Some cases of classical Hodgkin lymphoma, some cases of Burkitt Lymphoma, some other B cell non-Hodgkin lymphomas
2. Human T cell leukemia virus-1 (HTLV-1): Causative factor in adult T cell leukemia/lymphoma (ATLL)
3. Kaposi sarcoma herpesvirus/Human herpesvirus-8 (KS`V/HHV-8): Primary effusion lymphoma

Question 10

Contrast the incidences of leukemia and lymphoma in adult populations versus childhood populations

Answer 10

• non-Hodgkin lymphoma and leukemia occur at rates that are about four to five times lower than the rates of the most common cancers, such as prostate cancer and breast cancer.
• Non-Hodgkin lymphoma is the 7th most deadly, but “leukemia” does not appear in the list of the 15 deadliest cancers, reflecting that many types of leukemia are either indolent or curable, to a much greater extent than lymphoma
• childhood cancers (age <20), leukemia is the most common type, representing 37% of childhood cancers. Lymphoma is the 3rd most common type

Question 11

BASIC SCHEMES OF CLASSIFICATION OF HEMATOLOGIC MALIGNANCIES

Answer 11

• Myeloid malignancies are those arising from mature or immature members of the granulocytic, monocytic, erythroid, megakaryocytic, and mast cell lineages.
• Lymphoid malignancies are those arising from mature or immature members of the B cell, T cell, and NK cells lineages.

Question 12

MULTIPARAMETER CLASSIFICATION

Answer 12

The WHO classification system draws from various different sources of information to diagnostically define entities. This information can include:

• microscopic appearance of the malignant cells
• histologic growth pattern of the malignant cells in the marrow, lymph node, or other tissue
• presence or absence of specific cytogenetic findings or molecular findings
• relative amount of malignant cells present in the blood or marrow
• presence or absence of certain cell surface markers / cytoplasmic markers / nuclear markers