Grey Zone Lymphoma (GZL)

Grey Zone Lymphoma is a very rare and aggressive subtype of lymphoma with features of both Hodgkin Lymphoma (HL) and Primary Mediastinal B-cell Lymphoma (PMBCL) – a subtype of Non-Hodgkin Lymphoma. Because it has features of both Hodgkin and Non-Hodgkin Lymphoma it can be particularly difficult diagnose. Many people are only diagnosed with Grey Zone Lymphoma after receiving treatment for either HL or PMBCL that did not work effectively.

Grey Zone Lymphoma is officially recognised as a subtype of Non-Hodgkin Lymphoma.

On this page:

Grey Zone Lymphoma (GZL) Fact Sheet PDF

Grey Zone Lymphoma (GZL) – also sometimes called Mediastinal Grey Zone Lymphoma, is a very rare and aggressive subtype of B-cell Non-Hodgkin Lymphoma. Aggressive means that it grows very quickly, and has the potential to spread throughout your body. It happens when a specialised type of white blood cell called B-cell lymphocytes mutate and become cancerous.

B-cell lymphocytes (B-cells) are an important part of our immune system. They support other immune cells to work effectively, and make antibodies to help fight infection and disease.


Lymphatic system

However, unlike other blood cells, they do not usually live in our blood, but instead in our lymphatic system which includes our:

  • lymph nodes
  • lymphatic vessels and lymph fluid
  • thymus
  • spleen
  • lymphoid tissue (such as Peyer’s Patches that are groups of lymphocytes in our bowels and other areas of our body)
  • appendix
  • tonsils
B-cells are specialised immune cells, so they can travel to any part of our body to fight infection and disease. This means lymphoma can also be found in any area of your body.

Overview of Grey Zone Lymphoma

Grey Zone Lymphoma (GZL) is an aggressive disease that can be difficult to treat. However, it may be curable with standard treatment. 

GZL starts in the middle of your chest in an area called the mediastinum. It is thought that the B-cells living in your thymus (thymic B-cells), undergo changes that make them cancerous.  However, because B-cells can travel to any part of our bodies, GZL can also spread to other parts of your body. 

The reason it is called Grey Zone is because it has features of both Hodgkin and Non-Hodgkin Lymphoma, making it somewhat in the middle of these two major classes of lymphoma, and harder to diagnose accurately.

Who gets Grey Zone Lymphoma?

Grey Zone Lymphoma can affect anyone of any age or race. But it is more common in people aged between 20 and 40 years old, and is a little more common in men than in women.

We still don’t know what causes most subtypes of lymphoma, and this is true for GZL too. It is thought that people who have had an infection with Epstein-Barr virus – the virus that causes glandular fever, may be at increased risk of developing GZL, but people who haven’t had the infection can get GZL too. So, while the virus may increase your risk, it is not the cause of GZL. For more information on risk factors and causes, see the link below.

Symptoms of Grey Zone Lymphoma

The first side effects you may notice is often a lump that comes up in your chest (a tumour caused by a swollen thymus or lymph nodes as they fill with cancerous lymphoma cells). You may also:

  • have trouble breathing 
  • get short of breath easily
  • experience changes to your voice and sound hoarse
  • feel pain or pressure in your chest. 

This happens as the tumour gets bigger and starts to put pressure on your lungs or airways. 


General symptoms of lymphoma


Some symptoms are common in all types of lymphoma so you may also get any of the following symptoms:

  • Swollen lymph nodes that look or feel like a lump under your skin often in your neck, armpits or groin.

  • Fatigue – extreme tiredness not improved by rest or sleep.

  • Loss of appetite – not wanting to eat.

  • Itchy skin.

  • Bleeding or bruising more that usual.

  • B-symptoms.

Contact your doctor immediately if you are getting these symptoms.
For more info see
Symptoms of Lymphoma

Diagnosis and staging of Grey Zone Lymphoma (GZL)

When your doctor thinks you may have lymphoma, they will  organise a number of important tests. These tests will either confirm or rule out lymphoma as the cause for your symptoms. 

Blood tests

Blood tests are taken when trying to diagnose your lymphoma, but also throughout your treatment to make sure your organs are working properly, and can cope with treatment.


You will need a biopsy to get a definite diagnosis of lymphoma.  A biopsy is a procedure to remove part, or all of an affected lymph node and/or a bone marrow sample. The biopsy is then checked by scientists in a laboratory to see if there are changes that help the doctor diagnose GZL.

When you have a biopsy, you may have a local or general anaesthetic. This will depend on the type of biopsy and what part of your body it is taken from. There are different types of biopsies and you may need more than one to get the best sample.

Core or fine needle biopsy

Core or fine needle biopsies are taken to remove a sample of swollen lymph node or tumour to check for signs of GZL. 

Your doctor will usually use a local anaesthetic to numb the area so you don’t feel any pain during the procedure, but you will be awake during this biopsy. They will then put a needle into the swollen lymph node or lump and remove a sample of tissue. 

If your swollen lymph node or lump is deep inside your body the biopsy may be done with the help of ultrasound or specialised x-ray (imaging) guidance.

You might have a general anaesthetic for this (which puts you to sleep for a little while). You may also have a few stitches afterwards.

Core needle biopsies take a bigger sample than a fine needle biopsy, so are a better option when trying to diagnose lymphoma.

Some biopsies may be done with the help of ultrasound guidance
For more info see
Tests, Diagnosis and Staging

Staging of lymphoma

Once you know you have Grey Zone Lymphoma, your doctor will want to do more tests to see if the lymphoma is only in your mediastinum, or if it has spread to other parts of your body. These tests are called staging. 

Other tests will look at how different your lymphoma cells are from your normal B-cells and how quickly they are growing. This is called grading.

Click on the headings below to learn more.

Staging refers to how much of your body is affected by your lymphoma or, how far it has spread from where it first started.

B-cells can travel to any part of your body. This means that lymphoma cells (the cancerous B-cells), can also travel to any part of your body. You will need to have more tests done to find this information. These tests are called staging tests and when you get results, you will find out if you have stage one (I), stage two (II), stage three (III) or stage four (IV) GZL.

Your stage of GZL will depend on:
  • How many areas of your body have lymphoma
  • Where the lymphoma is including if it is above, below or on both sides of your diaphragm (a large, dome-shaped muscle under your rib cage that separates your chest from your abdomen)
  • Whether the lymphoma has spread to your bone marrow or other organs such as the liver, lungs, skin or bone.

Stages I and II are called ‘early or limited stage’ (involving a limited area of your body).

Stages III and IV are called ‘advanced stage’ (more widespread).

Staging of lymphoma
Stage 1 and 2 lymphoma are considered early stage, and stage 3 and 4 are considered advanced stage lymphoma.
Stage 1

one lymph node area is affected, either above or below the diaphragm

Stage 2

two or more lymph node areas are affected on the same side of the diaphragm

Stage 3

at least one lymph node area above and at least one lymph node area below the diaphragm are affected

Stage 4

lymphoma is in multiple lymph nodes and has spread to other parts of the body (e.g. bones, lungs, liver)

Your diaphragm is a dome shaped muscle that separates your chest and your abdomen.

Extra staging information

Your doctor may also talk about your stage using a letter, such as A,B, E, X or S. These letters give more information about the symptoms you have or how your body is being affected by the lymphoma. All this information helps your doctor find the best treatment plan for you. 


A or B

  • A = you have no B-symptoms
  • B  = you have B-symptoms
  • If you have B symptoms when you are diagnosed, you may have a more advanced-stage disease.
  • You may still be cured or go into remission, but you will need more intensive treatment

E & X

  • E = you have early stage (I or II) lymphoma with an organ outside of the lymph system – This might include your liver, lungs, skin, bladder or any other organ 
  • X = you have a large tumour that is larger than 10cm in size. This is also called “bulky disease”
  • If you have been diagnosed with limited stage lymphoma, but it is in one of your organs or is considered bulky, your doctor may change your stage to an advanced stage.
  • You may still be cured or go into remission, but you will need more intensive treatment


  • S = you have lymphoma in your spleen
  • You may need to have an operation to remove your spleen

(Your spleen is an organ in your lymphatic system that filters and cleans your blood, and is a place your B-cells rest and make antibodies)

Tests for staging

To find out what stage you have, you may be asked to have some of the following staging tests:

Computed tomography (CT) scan

These scans takes pictures of the inside of your chest, abdomen or pelvis. They provide detailed pictures that provide more information than a standard X-ray.

Positron emission tomography (PET) scan 

This is a scan that takes pictures of the inside of your whole body. You will be given and needle with some medicine that cancerous cells – such as lymphoma cells absorb. The medicine that helps the PET scan identify where the lymphoma is and the size and shape by highlighting areas with lymphoma cells. These areas are sometimes called “hot”.

Lumbar puncture

A lumbar puncture is a procedure done to check if the lymphoma has spread to your central nervous system (CNS), which includes your brain, spinal cord and an area around your eyes. You will need to stay very still during the procedure, so babies and children may have a general anaesthetic to put them to sleep while the procedure is done. Most adults will only need a local anaesthetic for the procedure to numb the area.

Your doctor will put a needle into your back, and take out a little bit of fluid called “cerebral spinal fluid” (CSF) from around your spinal cord. CSF is a fluid that acts a bit like a shock absorber to your CNS. It also carries different proteins and infection fighting immune cells such as lymphocytes to protect your brain and spinal cord. CSF can also help drain any extra fluid you may have in your brain or around your spinal cord to prevent swelling in those areas.

The CSF sample will then be sent to pathology and checked for any signs of lymphoma.

Bone marrow biopsy
A bone marrow biopsy is done to check if there is any lymphoma in your blood or bone marrow. Your bone marrow is the spongey, middle part of your bones where your blood cells are made. There are two samples the doctor will take from this space including:
  • Bone marrow aspirate (BMA): this test takes a small amount of the liquid found in the bone marrow space.
  • Bone marrow aspirate trephine (BMAT): this test takes a small sample of the bone marrow tissue.
bone marrow biopsy to diagnose or stage lymphoma
A bone marrow biopsy can be done to help diagnose or stage lymphoma

The samples are then sent to pathology where they are checked for signs of lymphoma.

The process for bone marrow biopsies can differ depending on where you are having your treatment, but will usually include a local anaesthetic to numb the area.

In some hospitals, you may be given light sedation which helps you to relax and can stop you from remembering the procedure. However many people do not need this and may instead have a “green whistle” to suck on. This green whistle has a pain killing medication in it (called Penthrox or methoxyflurane), that you use as needed throughout the procedure.

Make sure you ask your doctor what is available to make you more comfortable during the procedure, and talk to them about what you think will be the best option for you.

More information on bone marrow biopsies can be found at our webpage here

Your lymphoma cells have a different growth pattern, and look different to normal cells.  The grade of your lymphoma is how quickly your lymphoma cells are growing, which affects the way look under a microscope. The grades are Grades 1-4 (low, intermediate, high).  If you have a higher grade lymphoma, your lymphoma cells will look the most different from normal cells, because they are growing too quickly to develop properly. An overview of the grades is below.

  • G1 – low grade – your cells look close to normal, and they grow and spread slowly.  
  • G2 – intermediate grade – your cells are starting to look different but some normal cells exist, and they grow and spread at a moderate rate.
  • G3 – high grade – your cells look fairly different with  a few normal cells, and they grow and spread faster. 
  • G4 – high grade – your cells look most different to normal, and they grow and spread the fastest.

All this information adds to the whole picture your doctor builds to help decide the best type of the treatment for you. 

It is important that you talk to your doctor about your own risk factors so you can have clear idea of what to expect from your treatments.

For more info see
Staging Scans & Tests

Waiting for results

Waiting for your results can be a stressful and worrying time. It is important to talk about how you are feeling. If you have a trusted friend or family member it can be good to talk to them. But, if you don’t feel you can talk to anyone in your personal life, talk to your local doctor, they can help organise counselling or other support so you are not alone as you go through the waiting times and treatment for GZL.

You can also contact our Lymphoma Care Nurses by clicking on the Contact Us button at the bottom of the screen. Or if you are on Facebook and would like to connect other patients living with lymphoma you can join our Lymphoma Down Under page.

Before you start treatment

Grey Zone Lymphoma is aggressive and can spread quickly, so you will need to start treatment soon after you are diagnosed. However there are some things to consider before you start treatment.


Some treatments for lymphoma can affect your fertility, making it harder to get pregnant, or get someone else pregnant. This can happen with several different types of anticancer treatments including:

  • chemotherapy
  • radiotherapy (when it is too your pelvis) 
  • antibody therapies (monoclonal antibodies and immune checkpoint inhibitors)
  • stem cell transplants (because of the high-dose chemotherapy you will need before the transplant).
If your doctor hasn’t already spoken to you about your (or your child’s fertility), ask them how likely it is your fertility will be affected and if needed, how to preserve your fertility so you can have children later on. 

Questions to ask your Doctor

It can be a whirlwind finding out you have cancer and need to start treatment. Even asking the right questions can be a challenge when you don’t know what you don’t know yet. To help get you started, we have put together some questions you may like to ask your doctor. Click on the link below to download a copy of Questions to ask your doctor.

Download Questions to ask your Doctor

Treatment for Grey Zone Lymphoma (GZL)

Your doctor will consider all the information they have when deciding on the best treatment options to offer you. These will include:

  • the subtype and stage of your lymphoma
  • any symptoms you are getting
  • your age and overall wellbeing
  • any other medical problems you have, and treatments you may be having for them
  • your preferences once you have all the information you need, and have had time to ask questions.

Common treatment options you may be offered

  • DA-EPOCH-R (dose adjusted chemotherapy including etoposide, vincristine, cyclophosphamide and doxorubicin, a monoclonal antibody called rituximab, and a steroid called prednisolone).
  • Radiotherapy (usually after chemotherapy).
  • Autologous stem cell transplant (a stem cell transplant using your own stem cells). This may be planned for after your chemotherapy keep you in remission longer and possibly stop the lymphoma coming back (relapsing).
  • Clinical trial

Patient education before you start treatment

Once you and your doctor decide on the best treatment option you will be given information about that specific treatment, including the risks and benefits of the treatment, the side-effects you should look out for and report to your medical team, and what to expect from the treatment.

The medical team, doctor, cancer nurse or pharmacist, should provide information about:

  • What treatment you will be given.
  • Common and serious side effects you may get.
  • When to contact your doctor or nurse to report side-effects or concerns. 
  • Contact numbers, and where to attend in case of emergency 7 days a week and 24 hours per day.
For more info see
Treatments for Lymphoma
For more info see
Autologous stem cell transplants

Common side effects of treatment

There are many different side-effects of anti-cancer treatment and these are dependent on the type of treatment you have.  Your treating doctor and/or cancer nurse can explain the side effects of your specific treatment.  Some of the more common side effects of treatments are listed below. You can learn more about them by clicking on them.

Second-line treatment for Relapsed or Refractory GZL

After treatment you will likely go into remission. Remission is a period of time where you have no signs of GZL left in your body, or when the GZL is under control and doesn’t require treatment. Remission can last for many years, but sometimes, GZL can relapse (come back). If this happens you will need more treatment. The next treatment you have will be a second-line treatment. 

In rarer cases you may not achieve remission with your first-line treatment. When this happens, the lymphoma is called “refractory”. If your have refractory GZL, your doctor will want to try a different type of treatment. This too is called second-line treatment, and many people will still respond well to second-line treatment. 

The goal of second-line treatment is to put you into remission (again) and can include different types of chemotherapy, immunotherapy, targeted therapy or stem cell transplant.

How your second-line treatment is decided

At the time of relapse, the choice of treatment will depend on several factors including:

  • How long you were in remission for
  • Your general health and age
  • What GZL treatment/s you have received in the past
  • Your preferences.
For more info see
Relapsed and Refractory Lymphoma

Clinical Trials

It is recommended that anytime you need to start new treatments, you ask your doctor about clinical trials you may be eligible for. Clinical trials are important to find new medicines, or combinations of medicines to improve treatment of GZL in the future. 

They can also offer you a chance to try a new medicine, combination of medicines or other treatments that you would not be able to get outside of the trial. 

There are many treatments and new treatment combinations that are currently being tested in clinical trials around the world for patients with both newly diagnosed and relapsed GZL.

For more info see
Understanding Clinical Trials

What to expect when treatment finishes

When you finish your treatment your haematologist will still want to see you regularly. You will have regular check-ups including blood tests and scans. How often you have these tests will depend on your individual circumstance, and your haematologist will be able to tell you how often they want to see you.

It can be an exciting time or a stressful time when you finish treatment – sometimes both. There is no right or wrong way to feel. But it is important to talk about your feelings and what you need with your loved ones. 

Support is available if you are having a difficult time coping with the end of treatment. Talk to your treating team – your haematologist or specialist cancer nurse as they may be able to refer you for counselling services within the hospital. Your local doctor (general practitioner – GP) can also help with this.

Lymphoma Care Nurses

You can also give one of our Lymphoma Care Nurses or email. Just click on the “Contact Us” button at the bottom of the screen for contact details.

Late Effects  

Sometimes a side-effect from treatment may continue, or develop months or years after you finish treatment.  This is called a late-effect. It is important to report any late effects to your medical team so they can review you and advise you how best to manage these effects. Some late effects can include:

  • Changes to your heart rhythm or structure
  • Effects to your lungs
  • Peripheral neuropathy
  • Hormonal changes
  • Mood changes.

If you experience any of these late effects, your haematologist or general practitioner may recommend you see another specialist to manage these effects and improve your quality life. It is important though to report all new, or lasting effects as early as possible for the best outcomes.

For more info see
Finishing Treatment
For more info see
Health & Wellbeing

Survivorship - Living with and after cancer

A healthy lifestyle, or some positive lifestyle changes after treatment can be a great help to your recovery.  There are many things you can do to help you live well with GZL. 

Many people find that after a cancer diagnosis or treatment, that their goals and priorities in life change. Getting to know what your ‘new normal’ is can take time and be frustrating. Expectations of your family and friends may be different to yours. You may feel isolated, fatigued or any number of different emotions that can change each day.

Main goals after treatment for your GZL

  • be as active as possible in your work, family, and other life roles
  • lessen the side effects and symptoms of the cancer and its treatment      
  • identify and manage any late side effects      
  • help keep you as independent as possible
  • improve your quality of life and maintain good mental health.

Different types of cancer rehabilitation may be recommended to you. This could mean any of a wide range of services such as:     

  • physical therapy, pain management      
  • nutritional and exercise planning      
  • emotional, career and financial counselling. 

It can also help to talk to your local doctor about what local wellness programs are available for people recovering from a cancer diagnosis. Many local areas run exercise or social groups or other wellness programs to help you get back to your pre treatment self.


  • Grey Zone Lymphoma (GZL) is subtype of Non-Hodgkin Lymphoma with features of both Hodgkin, and Non-Hodgkin Lymphoma.
  • GZL begins in your mediastinum (middle of your chest) but can spread to any part of your body.
  • Symptoms can be due to abnormal growth of B-cells expanding in your thymus or lymph nodes of your chest, and putting pressure on your lungs or airways.
  • Some symptoms are common in most types of lymphoma – B-symptoms should always be reported to your medical team
  • There are different types of treatment for GZL and you doctor will talk you through the best options for your situation.
  • Side-effects can begin soon after you start treatment, but you can also get late-effects. Both early and late-effects should be reported to your medical team for review.
  • Even stage 4 GZL can be often be cured, though you may need more than one type of treatment to achieve this.
  • Ask your doctor what your chances of being cured are.
  • You are not alone, specialist or local doctor (GP) can help connect you with different services and support. You can also contact our Lymphoma Care Nurses by clicking on the Contact Us button at the bottom of this page.

Support and information

Learn more about your blood tests here – Lab tests online

Learn more about your treatments here – eviQ anticancer treatments – Lymphoma

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