Elective Report - Alistair Heath

Elective in Neuropathology undertaken at UCL Institute of Neurology, Queen Square, London.

by Alistair Heath

During my medical school training at the University of Liverpool my interest has become increasingly focussed on the following areas - Pathology, Medical Education and the Neurosciences. My career intention is to become a histopathologist or a neuropathologist. So for my medical school elective I chose to visit The National Hospital for Neurology and Neurosurgery at Queen Square in London, which is world renowned for specialising in neurological diseases. I specifically elected to be attached to the academic Division of Neuropathology in the UCL Institute of Neurology and the Queen Square Brain Bank, which perfectly matched my interests.

I spent five weeks shadowing Professor Janice Holton, a neuropathologist with a particular specialist expertise in muscle disease, observing her and her team in their day to day practice in a busy specialised Neuropathology department. I also gained some experience of the general work of a histopathologist, clinical neurological and neurosurgical practice by attending clinics and theatres, and finally also the use of teaching materials – going on to apply these by personally giving several departmental case presentations during my stay.

The aims of my elective were:

1. To shadow neuropathologists in their day to day work to help me understand what working as a neuropathologist entails
2. To gain an understanding of specialist neuropathological techniques, including histological diagnosis of muscle disease and the use of specialist staining to classify brain tumours and
3. To identify the ways by which specialist neurological teaching materials are disseminated to health professions.

As well as shadowing neuropathologists in their day to day work I did experience some general histopathology, including several post mortem examinations. I was able to explore the multidisciplinary role of a pathologist, attending a muscle biopsy meeting which led on to attending the neurology clinic with the same clinicians. This gave insight into how the human genome project was providing a chance to those in the future with genetically predisposed neurological diseases. I came across many types of muscle disease such as fascioscapulohumeral muscular dystrophy. Other specialist clinics included one for patients affected with mitochondrial diseases. Although far too specialist for the likes of a medical student to be familiar with, I did find attending the clinic interesting as well as insightful in terms of the implications of genetically linked diseases, so much so that I reflected upon the experience for a document for the university. I was also able to shadow a neurosurgeon for two days that went remarkably better than my previous experiences. The neurosurgeon went through the imaging, how the procedure was planned, what anatomical landmarks one would see as they proceeded with the brain surgery and then was able to show us, within a few feet, what he was doing. The two operations I observed were a trigeminal nerve decompression and evacuation of a chronic subdural haematoma.

The main experience I obtained was in specialised neuropathology. Mornings consisted of reviewing the previous day’s surgical biopsies. I became able to identify the characteristics of normal brain tissue and by the second week I was able to identify gliomas and the characteristics of high grade astroglial tumours. I was also able to differentiate between cell types such as oligodendrocytes, neurones, astrocytes, and ependymal cells. By the end of my attachment I felt reasonably confident at identifying the characteristics of common brain tumours, differentiating gliomas from extrinsic tumours as well as identifying the different classifications of gliomas and determining their staging. In particular I was lucky enough to observe a subependymal giant cell astrocytoma, which is so rare I was told I was only likely to see it three or four times in my career if I were to become a neuropathologist. I became familiar with the immunostaining methods now used in modern histopathology. No longer are tumours diagnosed by a pathologist based solely on their tissue cytoarchitecture. Immunohistochemistry adds a further dimension to diagnostic work, allowing doctors to better identify the likely cell of origin, predict prognosis and suggest possible treatment. Of note KI67 is a marker for proliferative activity, prevalent in cancerous cells, and glial fibrillary acidic protein is primarily used for detection of gliosis and neoplastic astrocytes. The use of molecular techniques is re-shaping our approach to brain tumour diagnosis and ultimately our treatment of many brain neoplasms. I learned how molecular characteristics of brain tumours are now being included in the latest tumour classification of the WHO. I also gained some experience of the neuropathological interpretation of muscle biopsy specimens to help neurologists to accurately diagnose muscle disease and provide patients with a clear diagnosis, prognosis and likely genetic implications.

I was able to observe how a slide was prepared from the sample that was delivered to the laboratory to produce the slide that was eventually presented to the pathologist. This process involves a series of different fixation techniques depending on what sort of slide is needed. For example, if a specimen is needed for immediate interpretation in a patient that is still on the operating theatre table then a smear in required. This involves spreading the cells on the slide easy viewing; this is then placed in a staining solution called toluidine blue, and then a fixing solution, ethanol. Much of the tissue architecture is lost, however one can still observe the vessels, cell types and findings such as Rosenthal fibres. These would regularly arrive into the microscope room, at which point the team would stop their work and come to a consensus as to the most likely diagnosis. This was important as the surgical team were always awaiting the diagnosis as the patient was still on the operating table. Prompt yet accurate diagnosis helped inform the neurosurgeons’ appropriate course of action.

During my elective I attended many educational activities and also become personally involved in undertaking several case presentations and talks. I attended numerous case presentations that involved analysing the patient’s neurological complaints, deciding which investigations should be performed, analysing the results and then putting forward the top differentials as the case evolved eventually into a firm diagnosis. Together with a registrar I personally presented a case of familial Alzheimer’s disease. This involved data collection from the patient’s online notes and converting this into a presentable format. I presented the macroscopic findings of the case which included blanching of the substantia nigra and overall atrophy of the cerebral hemispheres. The histological aspect of the case presentation involved examination of stained brain tissue sections from the deceased patient for signs of gliosis and deposition of characteristic proteins such as tau, amyloid beta and alpha-synuclein. Images were then taken of the slides to illustrate my argument for the diagnosis of familial Alzheimer’s disease. In addition, I gave a short presentation on the current knowledge of the Zika virus focussing on what scientific papers add to the current knowledgebase and what consequences this has for neuropathology. This was especially relevant to my education in view of Liverpool’s recognised expertise in tropical diseases.

The positive experience from my elective has confirmed my wish to become a histopathologist. I did find from shadowing a neuropathologist that the majority of work, especially in neuropathology, is microscope work and review of specimens. Certain individuals had taken up niche positions in the department, for example the ‘cut-up’ for brains in the brain bank was mostly conducted by a single neuropathologist, and another neuropathologist did most of the autopsy work. Talking with the neuropathologists I found that autopsy work is much rarer in neuropathology than general histopathology which I found unfortunate as that is one of my major interests.

So with regard to my own future learning needs my experience from this elective has helped inform me:

1. To try to pursue an academic foundation pathway in preference to a clinically orientated one
2. Given my encouraging experience in London to consider training potentially widely within the UK and
3. Probably to pursue a career eventually as a general histopathologist but retaining neuropathology as a possible option.

What was clear to me was that the demand for histopathologists, and particularly the subcategory of neuropathologists is extremely high. This is important for me as I was initially apprehensive about applying to neuropathology due to the competitive nature of neurology. The NHS quite clearly is under substantial financial pressure and even in an auxiliary support department such as pathology one can see the stresses. Something of note was that the services that I had experience of in London are much more focused towards the academic side of medicine than I have been used to. Because of this, the departments were more multinational and work closely with scientists that are non-medics.

There is a national shortage of histopathologists generally and neuropathologists in particular in the UK. By undertaking this elective it has confirmed my wish to become a work in one of these fields. I very much enjoyed my attachment at Queen Square, where I was made to feel very welcome and the staff were very supportive.

To any medical students thinking of a career in pathology and more specifically those considering neuropathology, I would greatly encourage you to consider an elective at Queen Square, it is a great opportunity to sample all the benefits in such a flourishing field of medicine and address the national recruitment problem.

I am most grateful to the British Neuropathological Society and Neuropathology and Applied Neurobiology for kindly funding the Medical Student Bursary that I was awarded to help me undertake this elective.