JOURNEY THROUGH HALF A CENTURY OF HEMATOPATHOLOGY

When I became a Pathologist 50 years ago, the Chairman of Internal Medicine in Bologna told me: “Pileri, you belong to the category of those who know everything, but always arrive late”. Since then, for me it has been an exciting journey in which the finish line has forever moved forward. From pure microscopic observation, I saw the birth of immunophenotypic characterization1 and biomolecular techniques2 up to single cell genomics3. Indeed, the boundaries between diagnostics, innovation and research are growing increasingly blurred. Every result is the result of teamwork, just as multidisciplinarity is the winning paradigm. This is the way to Precision Medicine and targeted therapy4,5, which take account of bio-pathological diversity among patients. The fallout is economic and social. In fact, the goal is to cure as many patients as possible, using personalized, possibly chemo-free and low or no-toxic schemes. On the other hand, given the costs of biologic drugs, the goal must also be to use them wisely in order to keep health care spending within sustainable limits. Pathologists play a pivotal role in this process, becoming more and more actors in therapeutic decisions (Figure 1). This position involves constant growth and the ability to take on new challenges, combining clinical-morphological interpretation with a mastery of new technologies, as first stated by the REAL Classification6 and later on validated by the WHO Classification7-9 and International Consensus Classification10. This landscape prospectively sees the use of telepathology and artificial intelligence becoming more and more widespread, thus enabling the collection of large case histories and the development of algorithms, which will never alone replace humans, but should be governed by humans who compare the individual case with robust predictive models. Haematopathology, however hyper-technological it may be, cannot disregard the human relationship with the patients, who must receive information about the disease, they are suffering from, in an empathetic way, providing the elements that will support them in the therapeutic pathway. The Pathologist must remain a Physician, who now knows everything (or a great deal, at any rate) and who with the information he is able to produce arrives not too late. Communication is the most difficult but also the most rewarding part of the work, always making it clear that the properly informed and motivated patient is the one who is most easily cured. Figure 1. Operational network for haematological cancer Patients. What about pathology? References 1. Pileri S, Serra L, Martinelli G. The use of pronase enhances sensitivity of the PAP method in the detection of intracytoplasmic immunoglobulins. Basic Appl Histochem. 1980;24(3):203-7. 2. Marafioti T, Hummel M, Anagnostopoulos I, Foss HD, Falini B, Delsol G, Isaacson PG, Pileri S, Stein H. Origin of nodular lymphocyte-predominant Hodgkin's disease from a clonal expansion of highly mutated germinal-center B cells. N Engl J Med. 1997 Aug 14;337(7):453-8. 3. Pileri S. Karl Lennert Lecture. 22nd Meeting of the European Association for Haematopathology. Dubrovnik, September 23, 2024. 4. Falini B, Flenghi L, Aversa F, Barbabietola G, Martelli MF, Comeli P, Tazzari PL, Broe MK, Stein H, Dürkop H, Pizzolo G, Bolognesi A, Sabattini E, Pileri S. Response of refractory Hodkin’s disease to monoclonal anti-CD30 immunotoxin. Lancet 12992;339(8803):1195-6. 5. Zinzani PL, Bendandi M, Martelli M, Falini B, Sabattini E, Amadori S, Gherlinzoni F, Martelli MF, Mandelli F, Tura S, Pileri SA. Anaplastic large-cell lymphoma: clinical and prognostic evaluation of 90 adult patients. J Clin Oncol. 1996 Mar;14(3):955-62. 6. Harris N, Jaffe E, Stein H, Banks P, Chan J, Cleary M, Delsol G, De Wolf-Peeters C, Falini B, Gatter K, Grogan T, Isaacson P, Knowles D, Mason D, Müller-Hermelink HK, Pileri S, Piris M, Ralfkiaer E, Warnke R. A Revised European-American Classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994, 84(5):1361-92. 7. Jaffe ES, Harris NL, Stein H, Vardiman JW eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 3rd edition. IARC Press, Lyon, 2001. 8. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th Edition. IARC Press, Lyon, 2008. 9. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J eds. WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues, Revised 4th Edition. IARC Press, Lyon, 2017. 10. Campo E, Jaffe ES, Cook JR, et al. The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee. Blood. 2022;140(11):1229-53.