10 Commonly Confused Retinoblastoma Terms, What They Mean and Why Getting Them Right Matters.


Do you know the difference between a biopsy and pathology, or an RB1 gene deletion and Chromosome 13q deletion?  Do you know how a retinoma becomes retinoblastoma or when remission becomes cure?  WE C Hope CEO Abby White explains these and other terms, and why using them correctly is important.


Navigating life with retinoblastoma treatment and genetics can be a very confusing experience. Even before diagnosis, families rapidly amass information from medical professionals, support organizations, other parents and survivors, general awareness, and Doctor Google.  The process reveals a bewildering slew of terms whose meanings or connection with other terms may be unclear.

In part 2 of this mini-series, we define ten commonly confused sets of terms, and discuss why confusion can be harmful and understanding is important.

This is Part 2 in a mini-series. Read Part 1: 8 Commonly Confused Terms.

Pathology slide showing advanced retinoblastoma

A pathology slide shows advanced retinoblastoma invading the optic nerve and choroid.

1. Biopsy and Pathology

Biopsy: Surgery to remove a sample of tumour for pathology analysis.

Pathology: Microscopic examination of surgically removed tissue (such as an eye) to confirm diagnosis, determine type and extent of the cancer, risk of relapse and need for further treatment.

Why This Matters

Due to the risk of spreading tumour outside the eye, surgical biopsy is never done to confirm a diagnosis of retinoblastoma.  Pathology can be done safely only after surgical removal of the whole eye.  Research is currently developing liquid biopsy (taken from fluid at the front of the eye) as a method of confirming retinoblastoma diagnosis without risking cancer spread, and gaining genetic information about the cancer to improve individualised care.

2. Focal, Whole Eye and Systemic Chemotherapy

Focal Chemotherapy: Injected directly into a specific location in or around the eye during EUA to target individual medium and large tumours or seeds that are not at risk to escape from the eye.  Intravitreal chemotherapy (injected into the vitreous behind the lens, through the sclera) and periocular chemotherapy (injected into the space behind the eye or under the mucus membrane that coats the eye and lines the eyelids) are examples.

Whole Eye Chemotherapy: Chemotherapy is administered during EUA directly into the eye, without targeting a specific site.  Currently, Intra-Arterial Chemotherapy is the only form of whole-eye chemotherapy – anticancer drugs are delivered through the ophthalmic artery, via a catheter inserted in the child’s femoral artery (in the leg).

Systemic Chemotherapy: Chemotherapy that travels around the entire body. For retinoblastoma, this is usually administered through a vein, but may be given orally. The most common systemic chemotherapy for retinoblastoma is a 3-drug regimen involving carboplatin, etoposide and vincristine.

Why This Matters

Focal and systemic chemotherapy are used in combination with laser, cryotherapy and other treatments in eye salvage therapy.  Focal chemotherapy can be effective alone in treating small tumours, but neither approach is effective alone in curing medium or large retinoblastoma.  Combination therapy can very effectively target larger individual tumours and seeds.  Focal therapy is only used when there is no evident risk for the targeted tumours to escape the eye.

Intra-Arterial Chemotherapy (IAC) cannot target specific areas of the eye. Instead it infuses anticancer drugs through the blood supply feeding the eye, increasing potential to reach cancer cells anywhere within the eye.  However, it may not treat cancer on the outer layers of the eye, and does not treat cancer that has already spread beyond the eye.  Clinical studies have shown high success in saving children’s eyes when there is no risk for cancer spread beyond the eye.  It is not yet clear what value IAC has as a stand-alone therapy, or the most effective combination of therapies.

Focal and systemic chemotherapy continue to have high value in treating children with retinoblastoma. Especially for babies under 6 months who are too small for IAC treatment, and children who require intensive treatment for both eyes.  Some leading retinoblastoma specialists advise against bilateral simultaneous IAC treatment due to the very small but potentially devastating risk of vision loss from complications.

IAC has recently replaced combination systemic chemotherapy and focal therapy as the most common primary treatment for retinoblastoma at many specialist hospitals.  If cancer cells invade outer layers of the eye or beyond at diagnosis, or at any time during treatment, the child will be under-treated and have high risk of metastatic cancer.  Identifying which children can safely benefit from IAC, and the clinical features that indicate high risk to life, will ensure best care for every child when considering treatment options.

3. Remission and Cure

Remission: Can be partial or complete.  In partial remission, signs and symptoms of cancer are reduced, and the cancer is detectible on examination, imaging scans or other tests, but it is not growing.  In a complete remission, all signs and symptoms of cancer have gone and there is “no evidence of disease” (NED) – no detectable living cancer on exams, scans or other tests.  Some people refer to complete remission as being “cancer free”.

Cure: When a child has been in complete remission from retinoblastoma for 5 years or more, they are considered to be cured of the eye cancer.

Why This Matters

Media reports often describe a child as being “cancer free” or “cured” barely months after therapy.  Readers of such articles rarely learn in follow up stories of any relapse experienced by the child.  It is best to read such articles with caution, understanding that the child is in remission, and is not yet considered cured.

There is one important exception in retinoblastoma to the accepted definition of remission and evaluation of signs and symptoms.  Leukocoria – white pupil – is the most common sign of retinoblastoma leading to diagnosis.  However, once treatment begins, presence or absence of leukocoria does not define remission.  This is because when retinoblastoma tumours die, they frequently calcify but don’t disappear completely.  A white pupil reflection may continue to appear in flash photographs or dim light, even years after treatment.  This is simply the light bouncing off the chalky surface of the dead tumour scar.

Cure of retinoblastoma does not reduce the risk of second primary cancers for individuals with a heritable RB1 mutation or those treated with radiotherapy.  This risk remains present throughout life. However, by five years after active treatment, the risk of chemotherapy-related second primary cancer has significantly reduced.

A smiling African child - the pupil in one eye glows white while the other appears normal.
An older child wears a Christmas cracker hat. The left eye glows white while the other has normal red reflex.

Leukocoria – white pupil – is the most common reported early sign of retinoblastoma, and can also be caused by dead tumour scars. The photo on the left led to the child’s diagnosis. The photo on the right was taken years after treatment that saved the child’s eyes.

4. Experience and Opinion

Experience: The process of acquiring knowledge or skill from doing, seeing or feeling things. Experience is neither good nor bad; it is interpreted by the individual according to their personal mind-set.  An experience may not have been right for the situation, but it is always factual and can only be described by the people who have undergone it.

Opinion: An individual’s perspective about something or someone – a personal belief, view, idea, feeling or judgement.  An opinion may be shaped by fact, logic, misinformation, assumption, bias, loyalty, surrounding influences, other related opinions, personal experience, personality, fears, emotions and mind-set or a combination these.  Anyone can hold an opinion, whether or not they have relevant experience.  That opinion may or may not be correct or appropriate.

Why This Matters

There is a fine line between experience and opinion, but it’s an important one to understand to ensure parents and survivors provide safe peer support in our retinoblastoma community.

Our opinions are limited by our individual experience, knowledge and understanding.  We can’t turn back time to relive an experience differently, and we can’t all have first-hand experience of something.  But our opinion about something can change over time through ongoing experiences, by broadly educating ourselves, listening to and learning from others – especially about subjects we know little about or hold a strong opinion on.  By sharing our diverse first-hand human experiences and clear facts of a particular topic, we can help educate one another, broaden our collective understanding, and balance our opinions.

This is especially important when responding to parents and survivors who ask questions in our retinoblastoma community.  Here is an example of how this can play out:

Opinion: “Do / Go to X.  This worked great for us.  You don’t need to do Y. Avoid Z if you can.”

Experience: “Our child was diagnosed with X stage of Rb and we did Y treatment at Z hospital.  We had XX experience and we had YY outcome. Our child is doing ZZ today.”

The responder’s Opinion assumes X treatment or hospital is appropriate for the individual child and is accessible to the family.  But this is impossible to know without full knowledge and understanding of the child’s medical record and the family’s personal circumstances, so a potentially very dangerous assumption.  There is no supportive experiential information to help the parent make an informed decision or give real hope.

In contrast, the Experience shares the same factual information, but wrapped in a personal story of real value.  The responding parent includes the stage of diagnosis so the enquiring parent can put the story in context and compare it to their own child’s situation.  They describe the treatment experience and outcome, and end with an encouraging update of how their child is now.  There’s no overt opinion here, and the enquiring parent has much more information from which to develop an informed opinion of the options, in combination with information given by the child’s doctors.

5. RB1 Gene and RB1 Gene Mutation

RB1 Gene: RB1 also has a role in genome integrity – keeping DNA healthy.

RB1 Gene Mutation: A change in DNA sequence that damages RB1 gene function and may cause cancer to develop, or contribute to its growth.  Retinoblastoma occurs when both copies of the gene become mutated in a retinal cell.

Why This Matters

Everyone has two copies of the RB1 gene. When RB1 is working correctly, it helps to prevent cancer from developing.  It is thus incorrect to describe the presence of an RB1 mutation in a retinoblastoma patient as “I/my child has the gene”.   This fails to recognise the key role of RB1 in preventing cancer in people who do not have an RB1 mutation.  This is particularly significant as RB1 was the first tumour suppressor gene ever identified.

“I have a heritable RB1 gene mutation” or “he has a mosaic RB1 mutation” is correct.  This also helps clarify the genetic situation to the child as they grow up, and to primary care providers who are responsible for lifelong medical care.

A small group works together.

In small groums, parents, survivors, researchers and medical professionals discussed different genetic scenarios and the implications for patient and family care at the 2017 One Retinoblastoma World meeting in Washington D.C., USA.

6. Retinoma and Retinoblastoma

Retinoma: A benign retinal tumour that forms when both copies of the RB1 gene become mutated in a single retinal cell. The genetic make-up of the cell usually becomes unstable, leading to a cascade of mutations in other genes in the cell.

Retinoblastoma: Malignant cancer that develops when a chain of genetic mutations follow mutation of both RB1 genes in a single retinal cell. 

Why This Matters

The combination of gene mutations, and the nature of each genetic mutation, defines how aggressive the individual tumour will be.  This is why two children with familial retinoblastoma can have very different experiences – one with few tumours that are easy to treat, and the other with many aggressive tumours.  This is also why one eye can have some very easy-to-treat tumours while others regrow after every treatment.

Rarely, some mechanism slows or stops the domino effect of genetic mutations happening after initial mutation of the RB1 genes.  So the retinoma remains a benign tumour. It may never be diagnosed if it remains stable and causes no issues.

When a child is diagnosed with retinoblastoma, doctors examine the eyes of the parents and siblings. If they find a retinoma, it is more likely that parent or sibling, and the diagnosed child, has a previously unknown hereditary RB1 mutation.

Individuals with a known retinoma should be followed by an ocular oncologist who is familiar with retinoblastoma and its treatment at the very earliest stages.

7. Genetic Counselling and Genetic Testing

Genetic counselling: An educational process for individuals and families affected by or at risk for heritable disease. Provides information on the lifelong implications of a genetic mutation, risk for other family members, screening protocols and reproductive options. A Genetic Counsellor can organise genetic testing.

Genetic testing: The process of analyzing the gene or genes of an individual to confirm, eliminate or reduce the risk that a heritable mutation is present.

Why This Matters

Genetic counselling can greatly enhance the care of children with retinoblastoma and survivors, even when genetic testing is unavailable or inaccessible.  The process can identify at risk children for early screening, and help parents understand why screening from birth is necessary.  Whenever it is available, genetic counselling should be offered and welcomed, even if genetic testing is not available or if the family does not wish to pursue testing.

8. Heritable, Hereditary and Familial

Heritable: A genetic mutation that can be passed on to the next generation, but is not necessarily inherited from a parent.

Hereditary: A genetic mutation that has been passed from parent to child.  The parent may or may not have had retinoblastoma.

Familial: Retinoblastoma affecting more than one member of the same family, caused by the same RB1 mutation.

Why This Matters

50% of retinoblastoma is caused by a heritable RB1 mutation that can be passed to the next generation, but only 5-10% of retinoblastoma is actually inherited from a parent.   Both heritable and hereditary mutations may also be called a “constitutional mutation”.

Without genetic testing, young siblings and first cousins of a diagnosed child are routinely examined regularly under general anaesthetic for signs of cancer.  Genetic testing of blood relatives, especially young siblings, can identify those truly at risk of retinoblastoma, and eliminate regular screening eye exams for the majority.

Playing with an anaesthetic mask, this child practices taking deep breaths in and out.  Genetic counselling can identify all children at risk of retinoblastoma who need regular eye exams under general anaesthetic to find cancer early.  Genetic testing can eliminate risk and the stressful anaesthetic process for 90-95% of these children.

9. Somatic and Sporadic Cell MutationsHello

Somatic Cell Mutation: A mutation that has occurred in any cell other than the germ cells (egg or sperm) and is therefore neither inherited nor passed on to children – it is non-heritable.

Sporadic Cell Mutation: A mutation that has occurred at or after conception and is therefore not inherited from a parent. This can refer to a somatic (non-heritable) mutation or a heritable mutation that can be passed to the next generation.

Why This Matters

Parents sometimes describe their child as having “sporadic retinoblastoma” before genetic testing, when there is no known family history of childhood eye cancer.  This may be incorrect as it is possible for a parent to be an unknown carrier of an RB1 mutation who never developed retinoblastoma.  Only genetic testing can identify if retinoblastoma is caused by a sporadic or somatic cell mutation, and any risk that other family members carry a previously unknown RB1 mutation.

10. RB1 Gene Deletion and Chromosome 13q Deletion

RB1 Gene Deletion: a mutation in which all or a portion of DNA in the RB1 gene is lost, but the rest of chromosome 13, on which it is located, is otherwise unaffected.

Chromosome 13q Deletion: The loss of DNA on chromosome 13, where the RB1 gene is located. This may involve all or part of the chromosome, including the RB1 gene and adjacent genes.

Why This Matters

Deletion of part of the RB1 gene can initiate retinoblastoma and predispose to later second cancers, but does not have any additional effects.  In contrast, the loss of additional parts of chromosome 13 causes a range of symptoms.  The combination and severity depend on location and extent of the deletion, but may include symptoms such as failure to thrive, global development delay, small stature, low muscle tone, seizures, skeletal and organ malformations.

Understanding a genetic testing report is vital to clarify the child’s true medical situation and appropriate ongoing medical care.  It can also manage levels of worry for parents and survivors as they grow up and begin to take control of their own care.

About the Author

Abby’s father was diagnosed with bilateral retinoblastoma in Kenya in 1946. Abby was also born with cancer in both eyes. She has an artificial eye and limited vision in her left eye that is now failing due to late effects of radiotherapy in infancy.

Abby studied geography at university, with emphasis on development in sub-Saharan Africa. She co-founded WE C Hope with Brenda Gallie, responding to the needs of one child and the desire to help many in developing countries.  After receiving many requests for help from American families and adult survivors, she co-founded the US chapter to bring hope and encourage action across the country.

Abby enjoys listening to audio books, creative writing, open water swimming and long country walks.