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Diagnosis

How Is Cutaneous Lymphoma Diagnosed?

A diagnostic work-up for cutaneous lymphoma may contain any number of the following exams or tests:

Personal and family medical history

Your doctor will likely ask you a series of questions relating to your personal medical history and your family's medical history.

Physical Exam

Your physician will ask you a series of questions and is likely to do a physical exam. The physical exam will including examining any specific areas of concern, especially as they relate to the reason for your visit to the office.

Punch Biopsy

The physician uses a sharp, hollow, round tool to remove a circle of tissue from the area of concern. The physician rotates the tool on the surface of the skin until it cuts through all of the different layers of skin and removes a tissue sample. This allows for better sampling of the depth of the lesion. The edges of the skin are typically stitched together following the biopsy.

Incisional Biopsy

A scalpel is used to remove part of the growth.

Excisional Biopsy

A scalpel is used to remove the growth in its entirety and some of the surrounding tissue. Excisional biopsies are generally performed on growths that appear to be melanomas.

Blood Tests

A common tool for disease screening, blood tests provide information about many substances in the body, such as blood cells, hormones, minerals, and proteins.

Imaging tests for cancer

Physicians use imaging tests primarily to detect the spread of disease. For this reason, they are usually not necessary for patients with early-stage cancer, as the disease is not likely to have spread. Imaging tests may also be used to look at the effectiveness of treatment or to detect signs of a recurrence (the cancer coming back) after treatment.

Following the biopsy, the skin samples are sent to a lab to be examined under a microscope by a physician called a pathologist.

 

Lymph Node Biopsies

Lymph node biopsies are generally performed to confirm a diagnosis of cutaneous lymphoma or determine the extent of the disease. A lymph node biopsy may also be performed if the physician noticed swelling in the lymph nodes during the physical exam.

Incisional Biopsy

A scalpel is used to remove part of the growth.

Surgical (excisional) lymph node biopsy

The physician removes an enlarged lymph node through a small cut in the skin. If the lymph node is close to the surface of the skin, a local anesthetic will be used to numb the area being biopsied. If it is located deep under the skin, you may be given drugs to make you drowsy or be put to sleep (using general anesthesia). Surgical lymph node biopsies are generally performed if the lymph node’s size indicates the melanoma has spread, but an FNA was not performed or did not yield conclusive results.

Fine Needle Aspiration (FNA) Biopsy

FNA uses a thin, hollow needle (thinner than the needles used to draw blood) to draw out fluid or tissue from a lump. Depending on the size and location of the lump, the needle is sometimes directed into the lump simply by feeling it. Other times it may be guided into the lump with the assistance of an ultrasound. FNAs are rarely painful and don’t tend to leave scars. Although FNA is the easiest type of biopsy to have, it doesn’t always provide a clear result.

Other Types of Biopsies

The following procedures may be done in special circumstances to confirm a diagnosis of lymphoma. Most often, these procedures are used to determine the extent of the disease (a process called staging).

Bone marrow aspiration and biopsy

For a bone marrow aspiration (also called a bone marrow biopsy), the doctor uses a thick, hollow needle to remove a sample of bone marrow and bone marrow fluid.

Lumbar Puncture

In a lumbar puncture, a physician uses a thin, hollow needle to remove a sample of cerebrospinal fluid (the fluid that washes the brain and spinal cord) from between the bones and the lower part of the spine.

 

Lab Tests of Biopsy and Blood Samples

In order to accurately diagnose and classify cutaneous lymphomas, biopsy and blood samples are sent to a lab to be thoroughly examined under a microscope by a physician called a pathologist. The pathologist may need to perform one or more special tests on the samples to confirm the diagnosis. These tests include:

Immunohistochemistry

Immunohistochemistry treats the skin or lymph node biopsy sample with special antibodies that bind to cells with a specific molecule present on or inside of them, causing the cells to change color. These color changes are visible under the microscope and help categorize cancer.

Flow Cytometry

Flow cytometry uses antibodies to identify cells by the molecules present on their surfaces (called immunophenotyping). The antibodies cause the cells to give off light when passed in front of a laser beam. Flow cytometry can identify several types of cells at once and determine if they are cancerous or not.

Cytogenetics

Cytogenetics testing looks for changes in the chromosomes in cells, such as translocations (when part of a chromosome breaks off one chromosome and attaches to a second) and other abnormalities. Pathologists use these abnormalities to help classify the type of cancer. Before the pathologist can view the chromosomes under a microscope, the cells must be given time to grow in lab dishes. For this reason, cytogenetics testing may take two to three weeks to yield results.

Flow Cytometry

Flow cytometry uses antibodies to identify cells by the molecules present on their surfaces (called immunophenotyping). The antibodies cause the cells to give off light when passed in front of a laser beam. Flow cytometry can identify several types of cells at once and determine if they are cancerous or not.

Molecular Genetic Tests

Molecular genetic tests look carefully at the genetic makeup (DNA) of cells and help pathologists confirm whether a lesion is the result of a cancerous or non-cancerous condition. One type of test is fluorescent in situ hybridization (FISH), which uses fluorescent dyes to identify chromosome abnormalities that are too small to be viewed under a microscope and specific gene changes in a cell. FISH is used on regular blood or bone marrow samples. Unlike standard cytogenetics testing, which may take two to three weeks to yield results, FISH provides accurate results in a matter of days. Another type is polymerase chain reaction (PCR), a highly sensitive DNA test that can detect changes too small to be visible under a microscope.

Skin samples may also need to be examined by a dermatopathologist (a dermatologist or pathologist with additional training in the diagnosis of skin samples).

 

Blood Tests

Blood tests are generally performed to determine the extent of the disease. They can also be used to indicate how well a patient’s bone marrow and organs are functioning while the patient is undergoing certain types of treatment. For patients with cutaneous lymphoma, the physician may order a complete blood count (CBC) or blood chemistry tests.

Blood Count

Doctors measure the levels of red blood cells, white blood cells and platelets using a test called a complete blood count (CBC). If there are too many or two few of any type of cell, it can be an indication of why certain symptoms are being experienced, or of disease.

Blood chemistry tests

Doctors use blood chemistry tests to check the levels of different chemicals and electrolytes, such as potassium and sodium, in the blood. Doctors also check the blood for high levels of calcium and creatinine (a compound passed from the body in the urine). The level of creatinine in the blood is directly correlated with kidney health. When the kidneys are damaged, the blood level of creatinine rises.

The results of one particular blood test can help physicians determine the extent of the disease. This test, called lactate dehydrogenase (LDH), measures levels of a certain enzyme found in the tissues and blood. Very high levels of LDH in the blood may mean the lymphoma has spread.

 

Imaging Tests

For cutaneous T-cell lymphoma patients who have only a few lesions, imaging tests may not be necessary. However, for patients with a lot of skin involvement or for whom lymphoma cells are present in the lymph nodes or the blood, physicians often order one or more of the following imaging tests:

Chest X-ray

Chest x-rays provide an image of the heart, lungs, airways, blood vessels and bones in the spine and chest area. They can be used to look for broken bones, diseases like pneumonia, abnormalities, or cancer.

Computed Tomography (CT) Scan

CT scans use x-ray equipment and computer processing to produce 2-dimensional images of the body. The patient lies on a table and passes through a machine that looks like a large, squared-off donut. Doctors order CT scans when they want to see a two-dimensional image of the body to look for tumors and examine lymph nodes and bone abnormalities. If contrast dye is used to improve the computer image, the patient may need to avoid eating or drinking for 4 to 6 hours before the test. Patients should tell their provider before the test if they have any allergies or kidney problems.

Magnetic Resonance Imaging (MRI)

This test uses a magnetic field, radiofrequency pulses, and a computer to produce detailed images of body structures in multiple places. You may be asked to drink a contrast solution for better imaging, and you will most likely lie on a moving table as pictures are taken. MRI is a more detailed tool than x-ray and ultrasound and for certain organs or areas of the body, it provides better images than CT. MRI may not be recommended if you have a pacemaker or other metal implant.

Ultrasound

Diagnostic ultrasound, also called sonography or diagnostic medical sonography, is an imaging method that uses high-frequency sound waves to produce images of structures within the body. The images can provide valuable information for diagnosing and treating a variety of diseases and conditions. Most ultrasound examinations are done using a sonar device outside the body, though some ultrasound examinations involve placing a device inside the body.

Positron Emission Tomography (PET) scan

A PET scan is used to detect cellular reactions to sugar. Abnormal cells tend to react and "light up" on the scan, thus helping physicians diagnose a variety of conditions. For the PET scan, a harmless chemical, called a radiotracer, is injected into your blood stream. Once it has had time to move through your body, you will lie on a table while a scanner follows the radiotracer and sends three-dimensional images to a computer screen. Patients are generally asked to wear comfortable clothing and refrain from eating for 4 hours before the scan. Tell your doctor if you are pregnant or breastfeeding. Patients with diabetes should discuss diet guidelines with their physician for the hours leading up to the scan.

Imaging tests are also done as part of the process of diagnosing cutaneous B-cell lymphoma patients to make sure they do not have internal involvement by a systemic lymphoma.

 

Staging

The stage of a disease refers to the extent of a disease (how widespread it is). Staging is most commonly done for mycosis fungoides and Sezary syndrome. Once a patient has been diagnosed with these conditions, the next step is to determine the stage of the disease.

Physicians use a number of tests and exams to determine the stage, including physical exams, biopsies, imaging tests, and blood tests.

Staging helps physicians determine the best course of treatment for patients. It is also helpful in predicting prognosis (outlook).

The staging system for cutaneous lymphomas was developed by the International Society for Cutaneous Lymphomas (ISCL) and the European Organization for Research and Treatment of Cancer (EORTC). There are two staging systems for cutaneous lymphomas, one for mycosis fungoides and Sezary syndrome and one for other cutaneous lymphomas.

 

Stage Grouping for Mycosis Fungoides and Sezary Syndrome

The stage of mycosis fungoides or Sezary syndrome is based on four factors: the level of skin involvement, if the disease is affecting the lymph nodes, if it has spread (metastasized) to other organs or tissues in the body, and if lymphoma cells are present in the blood. When these factors are combined to determine the overall stage of the disease, it is called stage grouping.

  • Stage IA and IB: The disease is limited to the skin and consists of patches and plaques, with Stage IA having less than 10% skin involvement and Stage IB having 10% or more skin involvement. The number of Sezary cells present in the blood is low.
  • Stage IIA: Skin lesions consisting of patches and plaques involve up to 80% of the skin, but no tumors are present. The lymph nodes are enlarged but are not involved with lymphoma. In other words, the enlargement is reactive and not due to disease spread. The disease has not spread to other organs or tissues in the body. The number of Sezary cells present in the blood is low.
  • Stage IIB: In addition to patches and plaques, at least one tumor is present that is one centimeter across or larger. The lymph nodes may or may not be enlarged and are not involved with lymphoma. In the latter case, they are reactive in nature. The disease has not spread to the lymph nodes or other organs or tissues in the body. The number of Sezary cells present in the blood is low.
  • Stage IIIA: At least 80% of the skin is involved. The lymph nodes may or may not be enlarged and are not involved with lymphoma. The disease has not spread to other organs or tissues in the body. Few or no Sezary cells are present in the blood.
  • Stage IIIB: At least 80% of the skin is involved. The lymph nodes may or may not be enlarged and are not involved with lymphoma. The disease has not spread to other organs or tissues in the body. The number of Sezary cells present in the blood is low.
  • Stage IVA1: Any amount of the skin may be involved. The lymph nodes may or may not be enlarged and are not involved with lymphoma. The disease has not spread to other organs or tissues in the body. The number of Sezary cells present in the blood is high.
  • Stage IVA2: Any amount of the skin may be involved. Lymph nodes are enlarged due to the spread of lymphoma here. The disease has not spread to other organs or tissues in the body. Sezary cells may or may not be present in the blood.
  • Stage IVB: Any amount of the skin may be involved. The lymph nodes may or may not be enlarged/involved by lymphoma. The disease has spread to other organs or tissues in the body. Sezary cells may or may not be present in the blood.
    (American Cancer Society 2014)

 

Staging for Other Cutaneous Lymphomas

The staging system for other cutaneous lymphomas is relatively new, and its effectiveness is still being determined. It is based on three factors: the level of skin involvement, if the disease is affecting the lymph nodes, and if the disease has spread to other organs or tissues in the body.

Unlike the system for mycosis fungoides and Sezary syndrome, this staging system does not assign an overall stage to the disease.

References

Cutaneous Lymphoma Foundation. 2012. A Patient’s Guide to Understanding Cutaneous Lymphoma. PDF.
Lymphoma Association. 2013. Cutaneous B-cell lymphoma. PDF.
Lymphoma Research Foundation. 2013. Getting the Facts: Cutaneous T-Cell Lymphoma (CTCL). PDF.

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