Distinguished Pathologist Award: Tony Leong. Presented by Bob Eckstein, President of the Australian Division

During his two-year term of office, the President of the Australasian division of the International Academy of Pathology has the opportunity of recognising an outstanding pathologist of our division by the bestowing of the Distinguished Pathologist Award.

Prof. Anthony Leong has made a unique contribution to the practice of pathology in the Australasian region. Tony was born in Singapore and gained his MBBS at the University of Malaya. His pathology residency was undertaken at the University of Washington, in the early 70’s. He moved to Adelaide in 1976, gaining an FRCPA, and an MD. His thesis was entitled “The spalling and migration of silicone from blood pump tubings”. I think that it was through this work, published also in the New England Journal of Medicine in 1982, that I first became aware of Tony’s work. “Spall” means to “splinter”, “chip”, according to the concise Oxford dictionary, and his thesis dealt with the migration of debris from tubes used in haemodialysis. This work led to changes in the composition of the tubing used in haemodialysis.
Tony spent most of the next 20 years in Adelaide, working predominantly at the Institute of Medical and Veterinary Science (the IMVS) and becoming Director of Surgical Pathology and Clinical Professor of Pathology. During this time he also spent a period of two years in Queensland. This was followed by a period from 1996 to 1998 as visiting Professor of Anatomical Pathology at the Chinese University of Hong Kong. In 1999, he took up the role of Medical Director at the Hunter Area Pathology Service in Newcastle, and Professor of Anatomical Pathology at the University of Newcastle.

On the way he has collected Fellowships of Colleges of Pathology in the United Kingdom, the United States, Hong Kong and Thailand.
Whilst practising general diagnostic pathology, Tony has had a prodigious output in terms of publications and reviews, with over 310 papers and reviews published. Tony has been on the editorial boards of many journals, and has contributed to the activities of many colleges and societies. He was President of the Australasian Division of the International Academy of Pathology between 1995 and 1997.
He has had particular interests in lymphoma, breast cancer and liver cancer, and especially in the use of new technologies applied to the practice of histopathology. He has made major contributions to developments in immunohistochemistry techniques, and is responsible for the now almost universal use of microwave fixation for antigen retrieval. He has published a number of books, written many book chapters, and given innumerable lectures and workshops. Tony’s contributions to the practice and progress of the science of pathology are immense by any standards, but earlier I used the word unique in describing his contribution to our Division, and I want to expand on this.

Our division is the Australasian Division. The name puts Australia together with Asia. The vast majority of the membership practice in Australia or New Zealand, but our membership includes significant numbers of pathologists in Asia or who are of Asian origin. Tony’s career is an example of a career that is exquisitely Australasian. He grew up and trained in South Asia, and has practiced in three States of Australia, as well as in East Asia. As a pathologist he is equally well known, respected and sought after as a consultant and lecturer in Australia and Asia. Wherever he has practised, he has trained and nurtured pathologists from all areas of Australia and Asia. He has gone to great lengths to appoint trainees from Asia to his pathology programmes in Australia, and maintain professional links with them after their return to their home countries.
I therefore now ask Tony to accept, from the Australasian Division of the International Academy of Pathology, the Distinguished Pathologist Award.
Bob Eckstein

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Warick Delprado, President 2003 to 2005

In May 2003, the Australasian Division of the International Academy of Pathology came together in Sydney for its Annual Scientific Meeting. It was the last of two meetings organised by Robert Eckstein, who completed his term as President at the end of the meeting. As the incoming President, it firstly falls to me to acknowledge Bob’s contribution to the Division, and to thank him for his organization, his effort, and his commitment during his term of office. On behalf of everyone, well done.

2003 was a great meeting. Robert Kurman led an outstanding series on gynaecological pathology, followed by Sylvia Asa’s presentations of endocrine pathology. Both presentations, but particularly Sylvia’s, changed the way we approach pathology in that field.

In August 2003, the world’s attention turned to Athens and the 2004 Olympics, and that it was only twelve months to the Olympic Games. Would Athens be ready in time? When were the venues going to be finished? What was the program? Was it all going to work? But all this fades into insignificance compared to what follows.

In October 2003, the world’s attention (well, the pathology world’s attention) turned to Brisbane and the 2004 International Academy of Pathology Meeting. Would Brisbane be ready in time? When were the venues going to be finished? What was the program? Was it all going to work? Well, the answer (with apologies to Optus) is “yes”. The venues are finished, the hotels ready, the program finalised and it is all going to work.
In October 2004, where will you be? The only answer is Brisbane!

Thanks to the remarkable efforts of an organising committee headed by Robin Cooke, it is all happening. The scientific program has been organised by Robert Eckstein and is complete. A large team of session convenors are bringing the speakers together. The social and companion programs will be amazing and exciting. It promises to be one of the best International Meetings.
See you there.

Warick Delprado
President, Australasian Division IAP

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Commentaries are available at the seminar on the night. If you are from outside the metropolitan Sydney region, another State or overseas, a commentary will be posted to you with the slide set.

For more details and/or an order form for the slide sets, please phone or email me as below.
Don’t miss out on this great opportunity to acquire a collection of wonderful cases. Or even better, come and join us for an enjoyable social and educational evening!

Best Wishes
Jenny Ma Wyatt, Convenor,
Ph: 02 4734 2176 or 0412119322
Email: mawyatjm@wahs.nsw.gov.au

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Above: Some senior members of the Pathology Society of Papua New Guinea. L-R. Robin Cooke, Jacob Morewaya, O.B. Orgunbanjo, Evelyn Lavu, Emenike Anyiwo, , Philip Golpak, Joe Igo (President of the Society).

About the time of World War 2, a small Pathology Laboratory was established in the rather primitive Port Moresby Hospital which was built on stilts over the sea, in a similar fashion to that of the houses occupied by the local villagers. In 1958 the hospital and the Pathology Department moved to new buildings in the suburb of Boroko. From 1962 the pathology service in Port Moresby was extended and strengthened and began to contribute to teaching of undergraduate medical students in what was called the Papuan Medical College. As modern hospitals were built in the provincial towns, the Port Moresby department was responsible for establishing Pathology Services in these hospitals.

The Papuan Medical School became a Faculty of the University of Papua New Guinea in 1969, and since then it has taken an active role in the teaching of pathology.
Master of Medicine postgraduate training programs were instituted in the various disciplines of medicine within the Medical Faculty from the 1970’s. A number of postgraduate students have now graduated from the M.Med program in Pathology. Some of them have received further postgraduate education in overseas institutions, and have obtained internationally recognised degrees. Initially, all of the senior staff were expatriates, but progressively the senior positions have been filled by nationals.
In 1993 a Papua New Guinea Society of Pathology was formed. The Society has conducted a number of scientific meetings since then. These meetings are held in conjunction with the annual Meetings of the Papua New Guinea Medical Society. In early May 2003, the Society met to celebrate the awarding of an Order of the British Empire to Robin Cooke, a Foundation Honorary Member of the Society. The award was presented by the Governor General of Papua New Guinea in a colourful ceremony at Government House which overlooks the beautiful harbour of Port Moresby, the capital city of Papua New Guinea. The OBE was given in recognition of Robin’s contribution to the initial development, and continuing enhancement of pathology services in Papua New Guinea.

Seven of the ten Pathology trainees studying for their M.Med postgraduate qualifications.

The present younger generation of Pathologists is building on the efforts of previous staff members, and they are providing effective leadership within the medical fraternity. The Master of Medicine program is attracting good quality medical graduates and their educational courses are being attended by M.Med trainees from other disciplines.

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Companies:
Gastroenterological Society of Australia
Mayne Health
Sonic Health Care
Queensland Medical Laboratory
PaLMS: Pacific Laboratory Medicine Services
Queensland Cancer Fund
Ventana
RCPA and RCPA - QAP Pty. Ltd.
The Australian Council for Safety and Quality in Health Care
Dako
QML Pathology
S&N Pathology
Mater Laboratory Services
Cytyc Thin Prep
PKF Accountants

Individuals:
Ann Warrell
Prasantha Murthy

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HER2 testing by immunohistochemistry has problems both in the technique used and in the assessment of the stained slides and ensuring the accuracy of results can be difficult. With this in mind, a staining and reporting educational slide circulation exercise was planned to specifically address HER2 testing in breast cancer. The HER2 staining exercise was voluntary, free and administered by the RCPA Quality Assurance Program in Brisbane.

A preliminary questionnaire was sent to 200 Australian anatomical pathology laboratories and 146 replies were received. Sixty-seven of the laboratories requested the staining exercise and of those, 58 laboratories returned the test cases.
Unstained paraffin sections of breast cancers were circulated to participants and the laboratories were asked to stain and assess the HER2 status of the tumours. The HER2 status of each cancer had already been assessed by FISH and immunohistochemistry at a central laboratory. The returned slides were then assessed by a panel of 4 drawn from the HER2 Testing Advisory Board who had extensive experience in HER2 testing by immunohistochemistry.

Summary of HER2 immunohistochemical scoring:
3+ staining is when there is strong, complete membrane staining in more than 10% of cells; 2+ staining is when there is weak or moderate complete membrane staining in more than 10% of cells; 1+ staining is when there is staining in more than 10% of cells, but this is incomplete, while 0 staining means there is staining in fewer than 10% of cells.

Summary of results:
Three cases were selected, Case A which was scored by the panel as 1+, Case B as 3+ and Case C also as 1+. Each de-identified laboratory submitted their results and also their three stained slides. A panel of 4 pathologists from the HER2 advisory board then reviewed each of these stained slides around a multiheader microscope. The results for how the laboratories scored each case, compared with how the panel scored each case, are given in Tables 1-3.
Case B which showed strong complete membrane staining and thus 3+, was scored by all of the laboratories as 3+ (Figure 1). The panel thought 3 of the cases should only have been scored as 2+. In usual clinical practice, these 2+ cases would have been sent for FISH testing. FISH testing would have been positive and so there would have been no instances where the hypothetical patients would have missed out on Herceptin therapy.

Figure 1

Both the staining and interpretation were less straightforward for the two 1+ cases, Cases A and C. As can be seen in Table 1, in only 9 of the 58 cases, did the panel and laboratories agree that the staining for Case A was 1+. The panel tended to downgrade the scoring intensity reported by the laboratories. While in 21 cases, FISH would have been performed with a negative result, more reassuring is that only one of 58 cases would have been given Herceptin inappropriately. An example of the weak and incomplete membrane staining of Case A is shown in Figure 2.
With HER2 staining, the normal ducts and lobules in the breast do not usually stain, and if this normal breast tissue is staining, the results of the staining of the carcinoma cannot be considered reliable. HER2 staining is a membrane stain. If there is significant cytoplasmic staining, any membrane staining also cannot be considered reliable and also becomes very difficult.

Figure 2

to interpret. In some examples of Case A, there was an artefact, seen as large cytoplasmic deposits in cells. While also making interpretation difficult, no membrane staining was ever identified when this artefact was present.
Case C (Figure 3) also showed 1+ staining. In addition, this case had some DCIS present in the slide. Some of the cells in the DCIS showed strong membrane staining and this was therefore a useful in built positive control. In examples where the laboratories scored Case C as negative, this internal DCIS staining was usually also Figure 3

Figure 3

negative or very weak. One laboratory scored Case C as 3+, as they were unaware that only the invasive component should be assessed with regard to scoring and the potential use of Herceptin therapy.

In the study, most (37) laboratories used the Dako AO485 antibody. Thirteen used the CB11 antibody and 4 used HercepTest. As the numbers are so small, it is difficult to draw accurate conclusions about staining using the different antibodies. Staining with HercepTest performed well. With CB11 there was a slight trend towards underscoring the staining, while with AO485, there appeared to be a slight trend towards overcalling the staining.

As a summary of the scoring, the 58 examples of Case B (3+) were performed well. Combining Cases A and C, there were 116 examples of 1+ staining. The laboratories results overall, compared with how the panel scored these cases overall is given in Tables 4 and 5.
As well as some staining deficiencies, there also appeared to be deficiencies of interpretation. The laboratories called 37 cases 1+, whereas the panel scored 55 of them as 1+. The laboratories also overcalled some of the staining, reporting 45 as 2+, compared with 19 by the panel. While only two (hypothetical patients) would have been given Herceptin inappropriately for their 1+ cases, sending 45 cases for FISH (with a negative result) becomes somewhat expensive. More of a concern would be the 32 cases reported by the laboratories as negative. While calling a case zero, when it is really 1+ does not matter in terms of Herceptin therapy, it is a concern that such laboratories may also undercall 2+ cases as 1+. As 1+ cases are not sent for FISH analysis, some potentially positive cases may be missed.

Overall, when the results of the 58 laboratories were compared with the “true results” (ie Case A = 1+, Case B = 3+ and Case C = 1+), the kappa level was 0.39 (fair). Showing that part of the discrepancy relates to interpretation and not just staining technique, all 58 panel results for the three cases was k=0.46 or moderate.

Ongoing quality assurance testing for HER2 is clearly important and until results are more standardised it may be worth considering centralising testing of HER2 immunohistochemistry. Laboratories staining and reporting fewer than 250 cases per year may find it difficult to achieve accurate scoring, unless there is substantial and ongoing FISH validation of their results.

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