Pathology and diagnosis of nephroblastoma

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Published: 27 Nov 2013
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Dr Gordan Vujanic – University of Cardiff, UK

Dr Gordan Vujanic talks to ecancer at the 2013 AORTIC meeting in South Africa about the pathology and treatment of nephroblastoma and how this is based on their histological diagnosis and stage.

A pathologist deals with a nephrectomy specimen that is altered with pre- operative chemotherapy and has to be familiar with chemotherapy-induced changes, to assess their amount (first on gross and then on histological examination) and to follow the protocol for examining and sampling the tumour, as it is critical for accurate sub-typing and staging.

Since nephroblastoma is a relatively rare tumour, pathologist’s experience is rather limited resulting in inaccuracies in diagnosis/sub-typing and staging. However, rapid central pathology review makes sure that children with renal tumours are treated appropriately.

I’ll be talking about the role of pathologists in the diagnosis of renal tumours of childhood, nephroblastoma in particular which is a common tumour. I’ll be trying to explain why pathology is important in diagnosis and treatment of these tumours.

Why is pathology important in those tumours?

Because treatment of tumours is really based on pathology so without accurate pathology treatment is meaningless and very often wrong. So before clinicians will treat children with tumours they need to know what exactly they’re going to treat and that’s what a pathologist does. So it’s a critical step in treatment of any tumour, in children or adults; without pathology basically treatment is a guess.

With this tumour is it of particular importance because the patients are so young?

Renal tumours of childhood are the most common solid tumours in children; more common are leukaemias which are on the top of the list, leukaemias and lymphomas and the brain tumours, but then when we are talking about solid tumours renal tumours are on the top of that list. In Africa it’s even more important because there are more children in African than, for example, in Europe and these tumours are very treatable as long as the correct diagnosis and stage are established, which is what the pathologists do. Then treatment is actually very efficient and in Europe about 90% of these children are completely cured from that disease. The results unfortunately in Africa are not so brilliant for a number of reasons, many of which are well-known – that they don’t have access to treatment and they don’t follow treatment fully for a number of reasons; for some of these tumours there is no radiotherapy available which is part of the treatment and so on. So the results are not as good as they could be. That’s what the organisation in which I work is trying to address and maybe improve the outcome of these children because these tumours are really the most treatable tumour in humans actually; there is no other malignant tumour with a 90% rate of survival which is remarkable.

Is your institute looking for alternative ways to bring treatment to children in Africa?

These tumours, despite the fact that they are most common in children, solid tumours, they are still very rare and there is a big problem because people don’t see enough of these tumours and their histology and staging are not so simple. So, for example, in the UK where I work I diagnose about one hundred tumours a year of these tumours but there are 21 different departments where these tumours are diagnosed and each department has two to four pathologists so on average each department will see five tumours a year and there are four people working in that department, or three, which means that every person will see one or two tumours a year. So if you see something like that very rarely it’s not surprising that you won’t remember exactly what the criteria for diagnosis are, how to stage them and so on. So even in the UK these tumours are in about 25% of cases misdiagnosed and mis-staged which, in theory, could lead to the wrong treatment, either over-treatment or under-treatment of these children. Luckily in the UK some ten or twelve years ago we introduced a system which enables that these tumours are accurately diagnosed, the system of so-called Rapid Central Pathology Review. So all tumours, wherever they are diagnosed, are automatically sent to me as the person with most experience in this field in the country so post-operative treatment will not start without my diagnosis and stage. But when I compare the diagnosis which these tumours came to me with with my own diagnosis it’s about a 25% discrepancy and in Africa it’s probably even worse because people here have even less experience although they see a lot of tumours. But, as I said, these tumours are not so simple and actually I’ve just finished one small study with cases from Malawi where the results were remarkably similar to the UK which is actually a compliment to the Malawi pathologists, I think, because in the UK these tumours are diagnosed by paediatric oncologists which means people who really sub-specialise in the field of children’s pathology whereas in Malawi there are, I believe, two pathologists for the whole country and still the results are almost identical, about 25% of cases which are, as I say, either mis-diagnosed or mis-staged. But, unlike in the UK, in Malawi there was no Rapid Central Pathology Review and that’s something actually that we are trying to address and try to… we are starting a new project, I think, from January 2014 where six or eight African countries will be joining into this trial where we will try to address a number of issues, protocols for treatment which in Europe include, as I said earlier, radiotherapy; we are trying to adapt them to the African setting where radiotherapy literally doesn’t exist. And also we’ll try to address these issues in pathology by educating people in the first place and I’ll be offering also a central pathology review but it might be a problem sending material from Ghana, for example, to Britain, it might take longer than in Britain where I get these cases within a day or two, it may take much longer to get them from Africa. But also we will have a series of educational meetings once or twice a year; I will be going to these countries, talking to people who will be responsible for looking through these cases and trying to basically educate them to make sure that they reduce their diagnostic errors to a minimum.

What are some of the characteristics that pathologists should be looking for?

There are two things the pathologist needs to do: first to establish diagnosis and then to establish the stage, both things are equally important for treatment; treatment is based on histology and stage. So these tumours are usually very complex tumours so they have a lot of different histological components. All other tumours of childhood, at least, you can have a small piece of tissue, maybe 5x5mm, and that’s enough to establish diagnosis and further treatment is then decided on the basis of that. For renal tumours you need a lot of slides, a lot of samples from the tumours, so you need anything between thirty and seventy samples from the tumour and then as you’ll go through these sections of the tumour you need to analyse different components of the tumour because on the basis of their percentage you finally decide how to sub-classify the tumour and that’s where the problem is because it’s not so easy if you do it once or twice a year to go through, say, fifty slides and build in your brain a puzzle and say, ‘OK, in this tumour I have 50% of blastemal component and 30% of stromal component and 20% of epithelial component and this much is necrotic and the tumour is infiltrating renal sinus and so on.’ So it’s a very complicated sort of way of analysing these tumours and that’s why people find them difficult and, as I say, on the basis of this assessment you end up sub-classifying the tumour as a certain subtype and then that subtype means different treatment in comparison to another subtype so that’s why it’s so important. Then on top of that you also have to look for tumour growth, whether it’s growing into surrounding structures such as the adrenal gland, perirenal fat, liver, renal sinus and so on because all these also will determine the final stage of the tumour. Then in your conclusion you basically have to say very clearly what the tumour is, what sub-type it is and what stage it is and why and only on the basis of that the clinician will know how to treat the tumour. So clinicians 100% rely on pathology and depend on pathology because they cannot make a diagnosis, they know it’s a renal tumour but they don’t know which one, so it’s the pathologist who needs to tell them, ‘This is this tumour, this sub-type, this stage,’ and then then they know very easily, OK, this tumour is treated according to protocol A, this tumour is treated according to protocol B, this according to protocol C but they cannot start the treatment without very accurate diagnosis and stage.