A Matter of Life and Death. Sue Armstrong

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СКАЧАТЬ abnormal piece because it looks deceptively normal. But then we began to understand that, and the biology of this disease has been unpicked over the last 15 years. I have been more active in determining how to diagnose this disorder than in trying to understand the genetic basis, because for paediatric pathologists this is a serious daily problem. Frequently a biopsy comes to your table that says, ‘Please rule out Hirschsprung’s disease,’ and it is very difficult to make the diagnosis, because it is based on the absence of neurons, and absence of proof doesn’t mean proof of absence.

       And is this a common condition?

      It occurs in about one in 5,000. But the thing that I am more interested in is a little more uncommon. It’s called neurocutaneous melanocytosis. This is a disorder of neural crest cells that produce melanin – so-called melanocytes. All the pigment in our skin, melanin, is produced by these cells, which all come from the neural crest – with the exception of those that are in the eye. Every other melanocyte in our bodies – including those in the brain – comes from the neural crest. There are babies born with abnormalities in the population of melanocytes, and they develop this condition, neurocutaneous melanocytosis, where they have extensive areas of their bodies covered by moles, or ‘naevi’. These darkly pigmented areas can cover portions so extensive that they are sometimes called ‘bathing trunk naevi’. Or they look like Dalmatians – hundreds, thousands, of little satellite lesions here and there. And the problem with those situations is that not only is the skin abnormal, but the deeper tissues are also abnormal and can develop malignant tumours, melanomas, inside those naevi. Frequently they develop a naevus inside the brain, and that can interfere with the development of other structures. They have seizures, they have hydrocephalus – dilatation of the ventricles of the brain – and frequently they die. The condition is relatively rare, though I can’t give you an exact figure. One in 20,000 newborns will have a giant naevus, and some of those will be neurocutaneous melanocytosis.

      But just over 10 years ago, I came in contact with a newly developing support group of parents. They had each had a child born with a giant naevus, and the doctors had freaked out and said, ‘I’ve never seen this. I don’t know what it is.’ Or, ‘It’s a melanoma; let’s treat it like this …’ There was very little knowledge. So parents created this family support group. All of the members are either parents of children with these lesions, or they are patients themselves, because many people have survived 20, 50, 60 years suffering with this situation, and they are ‘freaks’. Sometimes people can hide it. But other times, half your face may be black with a tremendously disfiguring lesion.

      So that is where I concentrate most of my research efforts. I was doing that with my late wife – she passed away five years ago.

       What are you discovering?

      First of all that this is much more frequent than we used to think. People are now aware of this group and are coming forward and saying, ‘I have one of those. I was born with this naevus.’ We are also discovering that it’s a very complex disorder in terms of genetics. We know of no twins, for example, that have this problem, so there is not an inherited basis. It does not repeat in families. There is nothing the mother did during the pregnancy that would represent a particular risk.

      So we are first eliminating a number of things. We are sure that these are real clonal lesions – by which I mean lesions that arise from a single cell that starts to reproduce and forms a clone. But we need to gather a lot more samples and make a very organised effort in our research. And when you don’t have such a massive number of patients, it’s very difficult to gather data and get researchers interested.

       What made you particularly interested in this condition?

      Well, when I was a pathologist in Mexico there was a baby that came to the department of oncology, and it immediately became the ‘patient of the month’ – everybody was talking about it. The baby was born with something in the genital area that was very striking – they couldn’t even tell if the baby was a boy or a girl. They thought it might be a tumour that would kill the baby rapidly, so they took a biopsy. What I saw was something very strange: it reminded me of what is described in congenital naevi, and at the same time it had features of nervous tissue.

       Nervous tissue? From where?

      From the neural crest. Melanocytes, in my opinion, are really modified neurons. They are cells that become specialists in synthesising pigment, but they have these dendrites, these prolongations – they are like an octopus, literally. They have cytoplasm that is the body of the octopus and they have all these ‘tentacles’ that carry the melanin and transfer it to surrounding cells.

      I never stopped thinking about that case. When I moved to Chicago I told Dr González-Crussí about it and he said, in his classic reflective way, ‘Very interesting … I have never seen a case like that.’ Then a couple of months later he called me up for a frozen section analysis. They were operating on a patient with a melon-sized tumour in the perineal area that was surrounded by a patch of hyper-pigmentation, like a naevus, and I remember his voice on the phone: ‘Miguel, you remember the case you told me about from Mexico a few years ago? I think we have something very similar.’ Sure enough, it was identical under the microscope. So we decided to publish those two patient cases together, in the oldest pathology journal, Virchow’s Archive. From that point on I was hooked into the biology of melanocytic development.

      Dr González-Crussí was telling me that paediatric pathology, as a specialism, is relatively new. Were you aware of that when you came into this field?

      Yes, I was aware. I remember that when I went to Yale, some of my colleagues were wondering, ‘Why do we need this guy? We can do the paediatric cases.’ It was a fantastic department at the time, and people were very well trained and experienced in many fields – but paediatric pathology is completely different from adult pathology. Under a microscope, tissue from a child that is one day old is different from the tissue of a child that is one month old, and that’s different from tissue of a one-year-old, and that’s different from the tissue of an 18-year-old. In paediatrics the key is development. When you take a case to an adult pathologist, the questions he or she will ask when looking at a slide, of a tumour, for example, are essentially, ‘Where is the lesion? How fast did it grow? How big is it?’ The first question a paediatric pathologist will ask is, ‘How old is the patient?’

      So yes, when I came to paediatric pathology, I think people had started to recognise the need. There had been paediatric pathologists, pioneers, but as a speciality it became more recognised around 25 years ago.

      Tell me, how important is your profession to you on a personal level?

      Well, pathology is a very important part of my life, but it’s not the only one – and it’s probably not the most important one. A friend of mine, another doctor who was with me in Chicago, said something that has remained with me. He said, ‘You know, before I see you as a doctor, as a pathologist, I see you as a parent.’ And I think that is what defines me: I am a father. Three of my four children live close by, my youngest lives with me, and we all get together every other week. We drink a bottle of wine; we cook and have fun. We speak about matters, we travel together.

      That brings me to one final question: you didn’t go back to Mexico?

      I couldn’t. The rupture with my ex-wife was so difficult that when my children were kept against the law for a few days in Mexico, I realised I had to keep a distance, for their health and for their education. So even though my original plan was to be a pathologist in Mexico after some speciality training here, I couldn’t. I remained here and tried to make the best of it, but I have tried to give something back to Mexico, and to Latin America.

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