“Dans les champs de L’observation le hasard ne favorise que les esprits préparés”.

Louis Pasteur 1854

“Change requires one to start now here or nowhere. Both places require one to pass through the same starting point – today, right now”

H. L. Balcomb’s blog

Life is a complex series of decisions. Little does one appreciate their importance as an adolescent or young adult.  Turning left or right has such huge consequences. Change in one variable has the consequence of an exponential change in the system. (1)

It was never my intention to study medicine let alone pathology but parental influence determined that I would continue in the family tradition. Like other teenagers, I was thinking more along the lines of becoming a rock star, or a pilot or doing nothing very much at all.  Having said that, the older generation knew best.  And so, at the age of 17 years and 3 months, I embarked on training in the Medical School at Queen’s University Belfast. Since then, life has been a roller coaster of a ride.

Fast forwarding to 1972, a game changing year for me. I had completed my internship at the Royal Victoria Hospital Belfast, Northern Ireland and began training in pathology under the guidance of Professor D. L. Gardner.  I clearly remember my first experience in the autopsy room on day 1 of the program. A middle-aged male had somehow become caught up in the inner workings of a very large industrial canning machine. His body was almost disembowelled and partially dismembered. Such an introduction to the specialty! Needless to say, some of the residents fainted. I was very close to a career-change from that experience

Although I found surgical pathology more to my liking, challenging wouldn’t even begin to describe the Herculean task of grasping even the fundamentals. In those days, the subject was much more of an art than a science (to me, it stil is!). To quote the late Bernie Ackerman, diagnosis was all about pattern recognition. A melanoma is a melanoma because that’s what a melanoma looks like! (Fig 1). One of our Professors had the unshakable belief that “it is what it is because I say that it is”. Difficult to argue with that but hardly a great educational experience. To us, as very junior residents, pathology was an unfathomable mystery. How on earth would one ever master this difficult subject? For example, how did one recognize a Spitz nevus when one didn’t even know that such an entity existed? Obviously with the passage of time, we gained experience and came to think that we had a much better understanding of the subject than we really had. Little did we know. I am still learning. There is always someone who knows more than oneself.

Diagnosis in those days was based solely on hematoxylin and eosin-stained slides and very limited special stains. If one didn’t recognize an entity with H/E then one was lost! Having said this, life was a great deal easier. So much had yet to be discovered. Immunofluorescence was in its infancy and generally not available. Immunohistochemistry and molecular studies hadn’t yet been dreamed of. Inflammatory subepidermal blisters were either neutrophil-rich representing dermatitis herpetiformis or eosinophil-rich and diagnostic of bullous pemphigoid Nothing to it really! Our special stain armamentarium included Masson Fontana for melanin, DPAS, Alcan blue and mucicarmine for mucin and reticulin to outline tumor nodules. The Warthin Starry for spirochetes never worked! With hindsight, it is a wonder we ever got anything right. The patients must have survived despite us.

On a weekly basis we were interrogated in front of the entire departmental staff for about an hour on 12 unknown and very difficult cases- the so-called “Red Box” meeting. Confidence was of utmost importance but bluffing never succeeded. Useful life lessons for the future. Dermatopathology slides figured prominently largely because none of the senior staff like the subject and they always wanted a consensus diagnosis! The meeting was beyond stressful. A wrong diagnosis resulted in total humiliation lasting until the following meeting and beyond. We took these meetings very seriously indeed. They were an invaluable tool in preparing us for the day when we would have to take the responsibility of giving a definitive diagnosis. Training in those days was a lot more flexible than in today’s litigation-driven environment. We were given increasing responsibility for signing out cases on our own with periodic spot checks my members of the faculty. Our excitement knew no bounds when we were permitted to report appendices, gall bladders and the like unsupervised. In this way, our transition to a consultant position or member of the faculty was not so abrupt as it is now with 

Sometime around midway through my second year I experienced an epiphany. It was probably in part serendipitous but never the less, it set the scene for the rest of my working life. I was walking along the corridor of the Pathology Department when I saw the Deputy Head of Department and a senior consultant in Dermatology having a heated discussion. My professor called me over and announced, “here he is, our expert in Dermatopathology, he will make sure that all of your cases are reported perfectly!”.  I was in no position to argue and so armed with an early edition of Lever’s “Histopathology of the Skin” and “Dermal Pathology “by Graham, Johnson and Helwig, I set about the daunting task of teaching myself Dermatopathology.

One of my lasting memories from those early informative years was the case of an elderly farmer who presented with a tumor behind the ear surrounded by a large purple plaque (Fig 1). Biopsy revealed primary cutaneous angiosarcoma. The patient died soon after admission and at autopsy had metastases in the liver, vertebrae and femur (Figs 2 and 3). Skin tumors were a lot more serious than I had believed.

During my training, I was obliged to undertake an M.D. thesis research project. I had recently encountered a patient with Di George syndrome and decided that I wanted to develop an animal model with absent parathyroid glands and thymus. Using a magnifying glass and very basic electrocautery equipment, I set about my task with great enthusiasm. A very large number of Wistar rats died at my hands before the Head of Department decided that “enough was enough” and my license was revoked.

During my training, I started attending Dermatology clinics, ward rounds and the weekly conference. I presented the pathology at the last and slowly over the years gained experience in dermatopathology. Northern Ireland is a very small country and it wasn’t difficult for me to become quite a large fish in the pond. In 1978 I decided that I had better get some proper training in dermatopathology and Professor Edward Wilson-Jones at St. John’s Hospital for Diseases of the Skin very kindly accepted me as a Fellow in Dermatopathology. I had an appointment to meet with the Professor before I took up my appointment. Young and care free, I thought that I had better dress for the occasion. At that time denim was very much the fashion and so I arrived in a blue denim suite with a black string tie and highly polished pointed leather shoes! Eduard and the late Neil Smith were waiting at the top of the stairs in the entrance hall. Neil took one look at me and suggested that I had come to the wrong address. Perhaps I had meant to visit next door- one of Leicester Square’s many brothels. St John’s was sandwiched between two such premises. This was extremely handy for customers of the latter as they could visit the Venereal Clinic immediately after their assignation! Both Eduard and Neil had a wicked sense of humor and I was at their mercy for quite some time.

I remember my first day with vivid clarity. I had just entered the reporting room and Professor Wilson-Jones, and Drs. Neil Smith and George Wells were looking at cases. Professor Wilson-Jones greeted me warmly and asked if I would like to give an opinion on a fascinating case. My heart sank as I realized this was the moment when I sank or swam! I looked down the microscope and saw a large and very edematous vascular lesion. Without hesitation, I said “this is Orf”. It was just a shot in the dark which happened to be correct. The day and my reputation were saved. I was never tested like this again!

Late in 1978 I was appointed consultant pathologist at St Thomas’ Hospital and subsequently in 1992 at St John’s Hospital for diseases of the Skin (at that time incorporated into St Thomas’ Hospital). During those years, I developed a love for electron microscopy and immune-electron microscopy of bullous dermatoses for both diagnostic and research activities. Deciding whether the split lay above or below the lamina densa and where the immunoreactants localized to was regular source of excitement (Figs 4, 5). Partly as a consequence of my interest in blister formation, I became involved with the late Dr. Robin Eady and Professor John McGrath’s work with epidermolysis bullosa patients. I served as the pathologists for all of their squamous cell carcinomas (Figs 5 & 6). However, the onset of the molecular era in pathology with various immunoblotting techniques soon supplanted morphology. The diagnosis and classification of epidermolysis bullosa became on much firmer grounds and defined by mutations in basement membrane genes rather than the constellation of clinical features with innumerable eponyms.

Histopathology and dermatopathology was transformed by the evolution of the era of immunohistochemistry. What powerful tools we acquired. Needless to say, there were disadvantages! Specificity was short-lived. Nevertheless, our simplistic disease and particularly tumor classifications were rapidly rendered obsolete. Diagnoses made with supreme confidence based on the hematoxylin and eosin-stained sections could be and were challenged by the new generation. As a consequence, the patients benefited enormously and therapies can now be tailored to diagnostic information gleaned from the new tumor classifications and diagnoses. Cutaneous T-cell lymphoma was no longer just mycosis fungoides and Sézary syndrome. There were a host of other T-cell proliferations that could be characterized accurately with antibodies.

“Pathology of the Skin with Clinical Correlations” was to dominate my life.  It was in the mid 1980’s that through a great friend of mine, Antony Du Vivier, I had the pleasure of meeting up with Timothy Hailstone and Vitek Tracz, joint owners of Gower medical publishing. He wanted me to write a book on Dermatopathology. My excitement knew no bounds. Success! I was going to be an author. At that time Professor John Tighe was Head of Department and when I told him my exciting news he responded “writing a book is about as much value to your curriculum vitae as doing a 6-week locum in an under developed country”! Well, my ego was damaged almost beyond repair. Never the less I set out to write the book despite his scathing comment. It is amazing how one brims with self-confidence and arrogance at such a young age, Without the use of any references what so ever, I proceeded to write and illustrate “Pathology of the Skin with Clinical Correlations”.  To my surprise and great relief, it was a great success and as a 2^nd edition was sought. I realized with each succeeding edition that the book would need to acquire respectability in the form of ever-increasing numbers of references.

In 1998, through the efforts of Professors Ramzi Cotran and Christopher Fletcher, I was given the privilege of an academic post at Brigham and Women’s Hospital and Harvard Medical school, Boston. This was a very different world from that I had been used to. 24-hour reporting was the norm. Dermatologists very frequently called to get the result of an “urgent” report. Life was very demanding. My day started at about 6.00 am and frequently I couldn’t leave until 7.00 or 8.00 pm. At the same time, I was frantically working on the 4^th edition.

Melanocytic pathology is fraught with hidden and not so hidden dangers. While in Brigham and Women’s Hospital, dysplastic nevi dominated my life. I cannot imagine that Clarke and Lynch could ever have anticipated that the term would have resulted in a firestorm of controversy that reverberates even to this day. It seems that a cat with only three legs might not be a cat after all! The Barnhill grading system proved to be even more contentious. In the Boston environment, dysplastic nevi were considered very real and grading was of the utmost importance. In fact, if I forgot to give the lesion a grade, I sometimes received a call from an irate dermatologist complaining that without a grade he/she didn’t’ know whether to re-excise the nevus or not.

This brings me to the present. People often quote the aphorism “you only get out of life what you put in”. I think that this is only half of the truth. To my mind, the rewards are far greater than the sacrifices. Dermatopathology has certainly been my life over the past decades, but I have gained much more than I put in. There are so many rewards that have no monetary value. I think trust from the patients and the clinicians is the greatest gift. As physicians, we owe it to our patients to give 100% of ourselves. I used to teach residents that even a boring epidermoid cyst is of importance to the patient. My rule of thumb when looking at cases was to pretend that the specimen came from a family member or close friend.

Teaching

In 2017, aided and abetted by Professor Jerad Gardner, I decided to re-invent myself. I wanted to create an environment where dermatologist and dermatopathologists could come together in a safe environment and share interesting or problematical cases. It would be a way that I could give back to the community that had been so kind to me. Teaching residents and fellow was my first intention but the Group developed a life of its own and like Topsy, it grew and grew. Currently there are 13,000 members. Each month we have 300-400 cases posted. With the interest generated by the many comments, although it is not intended to amount to a real consultation, often the diagnosis becomes obvious obviating the need for a proper consultation.

For the younger folk reading this article, Horace could not have said it better:

“While we’re talking, time will have meanly run on: pick today’s fruits, not relying on the future in the slightest” Odes (23 BC).

References

1. Oestreicher C. A history of chaos theory. Dialogues Clin Neurosci. 2007; 93:279-289.