The Making of a WHO Book on Tumour Classificaton

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Gold Medal Awards of the IAP

History of Pathology at Charite Hospital

The Making of a WHO Book on Tumour Classification

From Saturday January 12th, to Wednesday January 16th, 2002, an Editorial and Consensus Conference was held in Lyon, France, in the headquarters building of the International Agency for Research on Cancer (IARC), a research institute of the World Health Organization (WHO). The meeting was chaired by Drs Paul Kleihues, IARC Director and Leslie Sobin, Chief of the Division of Gastrointestinal Pathology at the A.F.I.P., Washington, in their capacity as Series Editors for the third Blue Book edition - the World Health Organization Classification of Tumours. This new book series is primarily for pathology and oncology communities world-wide. Therefore, each book needs to be based on a broad consensus of experts from many countries and regions. It is not the function of these books to present new and untested hypotheses. They are designed to be as concise as possible, to have relevant up to date references, and a generous number of high quality colour images that illustrate typical histopathological features of all tumour entities and their variants.

THE WORKING GROUP

At the heart of each book is a Working Group which is responsible for making recommendations for the WHO classification of human tumours. This time it consisted of 22 internationally recognised pathologists, geneticists and epidemiologists from 8 different countries.

Objectives of the Conference
The aim of the meeting was to review manuscripts, to select colour photographs, charts and tables and, most importantly, to come to a consensus agreement on terminology and classification of breast tumours, so that everything would be ready for layout not later than Wednesday morning. A similar meeting on neoplasms of female genital organs took place in March. Both parts will be combined in the volume Pathology and Genetics of Tumours of the Breast and Female Genital Organs, to be launched at the International Congress of the I.A.P. in Amsterdam, October 5 - 11, 2002.

A Plenary session.

Juan Rosai and Tanya Tavassoli chairing the Working Group discussing Precursor Lesions of Invasive Breast Carcinoma

Working Group discussing Precursor Lesions of Invasive Breast Carcinoma.

ANATOMY OF THE BOOKS

Series Editors
The Series Editors for the third Blue Book edition are Drs. Paul Kleihues and Leslie Sobin. Paul Kleihues was Professor of Neuropathology in Zurich, Switzerland. He was invited to be the Editor of the WHO Classification of Tumors of the Central Nervous System, together with Bernd W. Scheithauer (Mayo Clinic) and Peter C. Burger (Johns Hopkins). He gained additional editorial expertise as founding editor of Brain Pathology. After his appointment as IARC Director in 1994, he developed plans for the 3rd edition of the WHO Classification of Tumors, commonly referred to as WHO Blue Books from the colour of their covers. He decided that it should combine the histopathological and genetic typing of human tumours in a new format that would appeal not only to pathologists, but also to oncologists, geneticists and basic researchers. Leslie Sobin worked for WHO in Geneva from 1970 - 1981. When he moved to his present position at the A.F.I.P., he continued supervising the WHO classification. As a result, he was Series Editor for twenty of the twenty three books in the first edition, and all twenty three books in the second edition. The Series Editors have chosen the ten topics to be covered in the third edition. They have recruited Professor Nikolai Napalkov, Director Emeritus of the N.N. Petrov Institute of Oncology, St Petersburg, Russia, in a part time advisory capacity to prepare a template for each of the books. He checks that despite new developments and tumour entities, the continuity with the previous edition is maintained. He is well qualified to do this, because he was Assistant Director General of WHO in Geneva when the first series of WHO Tumor Classifications was begun. The first two books in the new WHO series, on tumours of the Nervous System and the Digestive System were published in 2000. Tumours of Haematopoietic and Lymphoid Tissues was published in 2001. The Series editors hope that the entire range of human neoplasms will be covered in 10 volumes and published by the end of 2003. Close to 10,000 copies of Tumors of Haematopoietic and Lymphoid Tissues were sold within 6 months of publication.

Scientific Editors
The Series Editors choose Main Editors who are responsible for each book. Paul likes to visit prospective editors, preferably in their place of work, to ensure that they share his approach, that they are not overcommitted, and that they agree to keep to the very rigid time schedule necessary for these publications. The Main Editors for the Breast Pathology book are Tanya (Fattaneh) Tavassoli, Chief of the Gynaecologic and Breast Pathology Section at the A.F.I.P., Washington, U.S.A. and Peter Devilee, Ph.D., geneticist in the Department of Pathology, Leiden University Medical Centre, The Netherlands.

Authors
For each disease entity, a responsible author is chosen, often together with one or more contributing authors, particularly if the topic is contentious. However, authorship is not stringently defined, since the entire book is the product of a Working Group; authorship rather indicates which colleagues took care of this respective entity.

Co-ordinating Editors
One of the most important persons in this whole process is the full time Co-Ordinating Editor. For Tumors of the Breast, this is Dr Rosemary Millis who retired a few years ago from her position at GuyÕs Hospital, London where she was in charge of breast pathology, and had established a considerable national and international reputation in this field. Her husband, John Pettit, a retired lawyer, also helped editing. One or two Co-Ordinating Editors are appointed for each book; they have a short term contract with IARC and live and work for 3-6 months in Lyon. They correspond (mostly by e-mail) with the editors and authors, receive the manuscripts, edit (i.e., shorten) them, check references, ensure that correct and consistent terminology is used throughout the book, and prepare manuscripts for the Editorial and Consensus Conference in Lyon. Dear Reader: if you are interested in spending some months on an exciting topic in the South of France, please send an e-mail to Paul Kleihues - email: kleihues@iarc.fr

Working Group discussing Precursor Lesions of Invasive Breast Carcinoma.

Working Group on Invasive Breast Carcinoma.

Working Group on Benign and other Tumours of the Breast, selecting images to be presented at the Plenary Session for selecting images for the book.

PRE-INVASIVE BREAST CANCER

Since the publication of the second WHO edition on Breast Tumors in 1981, the biggest challenge in this field has resulted from imaging techniques which have allowed clinicians to identify and aspirate or biopsy small, non palpable lesions. This has led in some countries that can afford such tests, to the introduction of population screening with the objective of reducing mortality from breast cancer. As a result, pathologists are being presented with increased numbers of pre- invasive lesions which need to be histopathologically classified in a reproducible way, and assessed for their biological behaviour, in particular the risk of progression to invasive breast cancer.

DCIS vs. DIN
Not surprisingly, the section labelled Precursor Lesions of Invasive Breast Carcinoma, caused the greatest problems for the Working Group. Everyone had an opinion which they wanted to voice. To accommodate this, the whole of the first half day was devoted to a plenary session to discuss this topic. The core of the controversy was the classification system. The majority of participants was strongly in favour of maintaining the terminology Ductal Carcinoma in situ (DCIS), divided into three grades, low grade (DCIS 1), intermediate (DCIS 2) and high grade (DCIS 3). Although used by pathology labs world-wide, the DCIS system suffers from high inter-observer variability, in particular, in delineating DCIS 1 from atypical ductal hyperplasia (ADH). Several recent consensus meetings in the US and Europe made an attempt to define more clearly the decisive morphological criteria which are most significant with respect to clinical outcome. Since ADH is now generally considered a precursor lesion of invasive breast cancer, its separation from DCIS was considered by some participants to be anachronistic. Some members of the working group, including the Series Editors, proposed that the 'carcinoma in situ' terminology be replaced by 'intraepithelial neoplasia', reserving the term carcinoma, for invasive tumours. This would avoid the possibility of overtreatment, particularly in countries with population-based mammography screening programmes.

In several other organ sites, the shift in terminology has already occurred, e.g. cervix (CIN), prostate (PIN) and in the WHO classification of tumours of the G.I. tract, published in 2000. On the other hand, the current ductal intraepithelial neoplasia (DIN) classification was considered unacceptable by the participants, mainly because DIN 1 comprises lesions of vastly different biological behaviour. In particular, the designation of Ususal Ductal Hyperplasia (UDH) as DIN 1A was contested, on the basis that there is currently neither epidemiological nor genetic evidence indicating that UDH is a precursor of invasive breast cancer in a significant number of cases. There was general agreement that DCIS 2 and DCIS 3 largely correspond to DIN 2 and DIN 3, respectively. Because the pre-meeting e-mail correspondence on this topic was very lively, and sometimes heated, Juan Rosai from the National Cancer Institute in Milan, Italy, was asked to be Chairman and Facilitator - a task he performed very well. By the end of the second day, a basic consensus had been reached: (1) the DCIS classification remains the recommended terminology and will be used throughout the book; (2) in the histopathology section of pre-invasive breast cancer, a DIN classification that does not include UDH, will be presented as an alternative terminology. Despite this agreement, there was still quite a lot of controversy right up to the end of the meeting. The international community of pathologists, and all those involved in the management of cancer patients, will ultimately decide which classification is best suited to making evidence-based treatment decisions.

Working Groups
On the second day, the experts divided into three Subcommittees or Working Groups: Invasive Breast Carcinoma, chaired by Dr Ian Ellis (Nottingham, UK), Precursor Lesions of Invasive Breast Carcinoma, chaired by Dr Juan Rosai (Milano, Italy) and Tanya (Fattaneh) Tavassoli (AFIP, Washington), and Benign and Other Tumors of the Breast, chaired by Rosemary Millis (ICRF, London, UK, currently at IARC, Lyon). At midday there was a plenary session to report on progress and problems. Then, after a quick lunch, it was back to the committee rooms. Image Selection The last hour of each day was usually devoted to the selection, of images for possible publication, by the entire Working Group.

This was a very serious, but very lighthearted, boisterous, amusing and enjoyable session in which this group of experts who have been lecturing pathologists all around the world for many years, showed their best (and most prized) pictures. The session was conducted in the manner of an auction; another analogy would be the Roman Emperor adjudicating the result of gladiatorial combat in the Colosseum in Rome. "Do we accept or reject this photograph?" "Yes? No?", "Thumbs Up?, Thumbs Down?". Does the image illustrate the lesion it is supposed to? Is it in focus? Are the colours O.K.., if not, can they be corrected in Photoshop? "But Mr Chairman, colleagues, this is my most loved picture". "Objection over-ruled". "REJECT".

After each image selection session, the owners of the photographs joined Sibylle Soring and her colleagues of the Technical Support Team in the computer room, to dictate captions for the images. At the end of the conference, more than 700 images had been collected. They will now be reviewed by the technical editors to choose format and magnification, and examined by design experts to ensure they are technically acceptable.

METRO, FOOD, Ð AND CHAMPAGNE

Lyon is the second largest city in France and considered (particularly by les Lyonnais) the world capital of gourmets. The Metro connecting IARC and the town centre is driver-less and trains run every 3-5 minutes. It was amusing to see a group of highly intelligent people trying to work out how to buy a ticket. This was complicated by the fact that the new currency unit - the Euro - was less than two weeks old. Some of the machines would only take French francs, some only Euros, and one machine had "given up". Professional "conference facilitators" could never have dreamed up such a wonderful game to relax delegates and to get them talking and joking with each other. The slightly more structured social events were: drinks and finger food in PaulÕs apartment overlooking the River Saone on the first evening; a dinner at the Brasserie Carnot the next evening; and, to celebrate the consensus, a champagne reception in the IARC cafeteria on the third evening.

IARC support staff for the meeting of authors for the WHO Tumour Pathology Series 3 Tumours of the Breast: Sybille Soring, Christine Yorian, Vojtek Bieurnat, Anike Revoire.

Sunil Lakhani (England), Maria Drijkoningen (Belgium) and Xavier Sastre-Garau (France). John Pettit in the background.

An uninvited "guest" to the conference was a virulent upper respiratory tract virus which caused great discomfort to a number of participants. On Wednesday the delegates returned to their normal places of work after a very busy and tiring four days of intense effort. They left the equally exhausted Support Staff at IARC to recover, and then to make the final preparations for publication of the fourth volume in the new series of WHO Tumor Classifications, to be published in September 2002.

The author is grateful to Dr Paul Kleihues for the invitation to report on this meeting for the information and interest of readers of the News Bulletin. Paul provided assistance with the information included in the article. His IARC staff were all extremely helpful in assisting the author to compile the information in the shortest possible time. Drs. Leslie Sobin and Rosemary Millis generously provided information and editorial guidance.

Robin Cooke

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The Chairman of the Nominating Committee of the IAP (Dr. Anna Kadar) invites nominations from individual members and from Divisions for the following offices which will be filled by election at the meeting of the International Council during the XXIV International Congress in Amsterdam, The Netherlands. President-Elect (2 year term, incumbent at the conclusion of his/her term becomes President) Vice Presidents (2 year term; however, a vice-president may succeed himself/herself in office without limitation). Africa - 2, Asia - 3, Australasia - 1, Europe - 3, N. America - 3, S. America - 2. In accordance with the Constitution, the duly elected persons will assume office one month after the end of the Amsterdam Congress.

All members of the IAP are entitled to submit names for consideration either directly or through Divisional Secretaries. Nominations need to be sent via the International Secretary:

Dr. Florabel G. Mullick,
AFIP, Bldg 54, Rm 1097
14th Street and Alaska Ave. NW,
Washington DC 20306-6000 USA.

Nominations need to arrive not later than September 5th, 2002.

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MEETINGS

BRITISH DIVISION

Joint Meeting with the Pathological Society of Great Britain and Ireland.

Bristol, 1-4 July 2003.

Symposium on Lymphoreticular Disease

London, 28-29 November, 2003.
Contact: Mrs C Harris, PO Box 73, Westbury on Trym, Bristol BS9 1RY. Ph: 0117 907 7940. Fax: 0117 907 7941. Email: bdiap@cableinet.co.uk

Intraeuropean-Mediterranean Conference

8 to 10 May, 2003.
Meeting Venue: Astir Palace Resort, Vouliagmeni, Athens - Greece.
Topics:
Breast Cancer: Sunhil Lakhani, London, UK
Endometrial and Ovarian Cancer: Jaime Prat, Barcelona, Spain
Pigmented Lesions of the Skin: Martin C. Mihm, Jr, Boston, MA, USA
Prostate Pathology: Rodolfo Montironi, Ancona, Italy

Organized by the Hellenic Division: www.mednet.gr/hsap
Scientific information: George Kontogeorgos M.D. gkonto@cc.uoa.gr
Meeting Secretariat: Alex Soutsou 8, 106 71 Athens, Greece.
Phone: +301 363-4944, Fax: +301 363-1690,
E-mail: infor@era.gr

Postgraduate Course

Current Concepts in Surgical Pathology
November 11 - 15, 2002
The Four Seasons Hotel, Boston, Massachusetts
Course Directors: Eugen J. Mark, Robert H. Young, Nancy Lee Harris.
This course has Category 1 accreditation for 36 hours CME credit by the American Medical Association. The fee for the course is $995 (residents and fellows $695).
For further information contact: Department of Continuing Education, Harvard Medical School, P.O. Box 825, Boston, MA 02155. Ph: 617 432 1525 (0195) ; Fax: 617 432 1562 ;
Email: hms-cme@warren.med.harvard.edu

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