How a Diagnosis of T Cell or NK Cell Leukemia/Lymphoma is Made: T-Cell Pathology Dictionary

By: Lorinda Soma, M.D.

Assistant Professor

Associate Director, Hematopathology Laboratory

University of Washington

The way cancers are diagnosed can be somewhat of a “black box” to those who are not familiar with pathology and the clinical laboratory.  In order to handle samples that are submitted for a cancer diagnosis, many specialized people and instruments will be involved.  This article will try to demystify what goes into handling, processing, and testing samples in order to make a diagnosis of lymphoma (cancer of lymphocytes).

What are T Cells and NK (natural killer) Cells?

NK cells (natural killer cells) and T cells are a normal part of our immune system.  They are lymphocytes, part of the white blood cell component, which circulate in the peripheral blood, and monitor for infections and abnormal cells.  These cells also move through tissues to look for any abnormal cells or infectious organisms. However, as with any cell type in our body, these cells can become cancerous/malignant.

Here are some terms that you may have come across on your pathology report, in your reading or discussions with your health care providers:

White Blood Cells (WBC)

WBC’s are cells that travel around your body in the blood that identify and fight infections, abnormal cells, foreign particles and cancer cells.  WBC’s will move out of the blood into tissues to be on surveillance for any infections/abnormal cells, and can be recruited in greater numbers to move to a site of infection. The most common WBC’s are lymphocytes, monocytes and neutrophils.  They are called “white” because they appeared white or pale/clear to the first scientists looking under the microscope at blood that was not specially stained.

Lymphocyte

Lymphocytes are one of the white blood cells (WBC) that travel around in your blood and help identify infections, abnormal cells, and cancerous cells and recruit other WBC’s to help destroy the offending cell/infection.  Lymphocytes will travel in the blood stream to populate various organs/tissues. They also accumulate in large numbers in lymph nodes and the spleen — the main immune organs.

T Cells

T cells are a type of lymphocyte which is specialized in identifying abnormal cells and cancer cells, and also in recruiting other WBC’s to mount a response to infections and destroy abnormal cells — much like a blood hound helps to look for an escaped convict, and will bay if the convict’s scent is identified to recruit more people/dogs to the right area.  Some T cells are also capable of destroying abnormal cells – much like the German shepherd, which can directly attack the convict.  T cells are called “T” cells, because they mature in the thymus (an organ in your chest, near your heart, that is largest when you are young, and gets much smaller as you age).

NK Cells

NK cells are a type of lymphocyte that specializes in identifying and destroying infectious cells and tumor cells. NK cells, or natural killer cells, are defined as such, because they can act on their own without help from other WBC’s (again, like the German shepherd, which can attack the convict).  NK cells can identify and destroy abnormal cells on their own.

T Cell Lymphoma

This is a type of lymphoma that originates from T-lymphocytes. This occurs when abnormal / cancerous T cells multiply unchecked in tissue (often times in lymph nodes, but can occur in any tissue).

T Cell Leukemia

This occurs when abnormal / cancerous T cells accumulate in the bone marrow and circulate in peripheral blood. On occasion, they can also populate other organs/tissues like lymph nodes.

Natural Killer (NK) Cell Lymphoma

This is a type of lymphoma that originates from NK-lymphocytes. This occurs when abnormal / cancerous NK cells multiply unchecked in tissue (often times in the sinonasal tract, but can occur in any tissue)

Natural Killer (NK) Cell Leukemia

This occurs when abnormal / cancerous NK cells accumulate in the bone marrow and circulate in peripheral blood

Antibody

An antibody is a protein that can recognize another protein.  The antibody protein can have a color attached to it, so it can be seen (thereby identifying the protein you are looking for).   As an analogy, if you are an antibody, and you’re looking in a crowd of people (various proteins) to identify a lost friend (the specific protein of interest), you would be able to identify that friend (protein), take that friend/protein by the hand, and raise a blue flag, so the rest of your friends would know where your lost friend (protein) is. That is what the antibody does to identify the protein you are looking for – allows you to see the “blue flag”.

Immunophenotype

Using antibodies (the “immune” component of immunophenotype) to determine what markers, or proteins, are expressed by the cells. The immunophenotype of a cell reflects what markers/proteins are made by the cell, and can be identified by antibodies directed against those markers/proteins, through various methods (flow cytometry and immunohistochemistry). These markers/proteins help us identify what type of cell is present.  Sometimes, there are specific patterns of marker/protein expression that help the hematopathologist make a diagnosis of lymphoma, and further help in classification of the lymphoma.

Hematopathologist

The M.D. or M.D., Ph.D. who has gone through medical school, with subsequent training in a clinical and/or anatomic pathology residency, with additional fellowship training in Hematopathology. The hematopathologist will evaluate the sample and testing that is performed, report the findings, as well as render the diagnosis.

Flow Cytometry

The process of identifying markers/proteins on cells (using antibodies), to tell what type of a cell it is.  This process can also identify abnormal markers/proteins that are not usually expressed by the cell. This evaluation uses a machine called the flow cytometer, and a computer to analyze the information (using the computer to see the blue flag/protein – see above under antibody for further description of the blue flag).

Immunohistochemistry

The process of identifying markers/proteins on cells (using antibodies), to tell what type of cells it is.  This process can also identify abnormal markers that are not usually expressed by the cells.  This evaluation uses the light microscope to visualize what markers the cells are expressing (using the microscope to see the blue flag/protein – see above under antibody for further description of the blue flag).

Cytogenetics

Cytogenetics is a process that consists of looking at the number and structure of chromosomes that make up the cancer cells. You can think of this process as a chromosomal census bureau survey, of sorts. This test can identify crude alterations in number and general structure of chromosomes. It can also identify large exchanges between different chromosomes called translocations, loss of part or whole chromosomes called deletions, and abnormal additions to chromosomes called duplications. These changes can be specific to certain types of lymphomas and facilitate the diagnosis. They can also predict how well patients will respond to treatment.

Fluorescence In Situ Hybridization

Fluorescence in situ hybridization (FISH) is a specific cytogenetic technique that researchers and physicians use to find and concentrate on specific DNA sequences of a chromosome; based on the results, this technique aid in diagnosis and/or in the course of treatment. In this analysis, the physicians look for specific known defects in genes. The results of this test are generally very specific for subtypes of lymphoma, but not all lymphomas have identified defects. Hence, FISH analysis will not be performed on all of the lymphoma subtypes — only those that harbor a known discovered genetic defect would be tested.

Molecular Studies

This is a very sophisticated test that allows us to prove that the abnormal cells identified in previous studies are “clonal,” meaning they originated from one cell — the main feature of the cancerous process. This test is frequently referred to as T cell receptor rearrangement study.