The Microscope as a Tool for Disease Discovery-A Personal Voyage

Abstract

This review reflects the trajectory of my career in hematopathology, and my personal reflections on scientific advances in the field. During the course of more than 40 years, the approach to classification of hematological malignancies has evolved from descriptive approaches, based on either cytological or clinical features, to a modern approach, which incorporates cutting-edge technologies. My philosophy has focused on defining individual diseases, an approach that can best lead to an understanding of molecular pathogenesis. To quote Carolus Linnaeus ( 1 , p. 19), the father of taxonomy, "The first step in wisdom is to know the things themselves; this notion consists in having a true idea of the objects; objects are distinguished and known by classifying them methodically and giving them appropriate names. Therefore, classification and name-giving will be the foundation of our science."

Keywords: B cells; T cells; autobiography; cell of origin; malignant lymphoma; molecular diagnosis; molecular oncology.

Figure 1.

Laboratory of Pathology resident class of 1970–71. Shown left to right. Front Row: Gerhard Krueger, Elaine Jaffe (author), Hugh Bonner. Second Row: Joel Roth, L. Maximilian Buja, Ronald DeLellis.

Figure 2.

Hanging drop technique. This method was used to visualize sheep erythrocyte rosettes (E rosettes) and EAC rosettes on frozen sections mounted on glass slides, respectively identifying T-cells or B-cells in situ.

Figure 3.

Follicular lymphoma showing binding of EAC rosettes to a frozen section. Neoplastic follicles bind the complement coated red blood cells, visualized by dark field microscopy.

Figure 4.

Meeting of the International Lymphoma Study Group held in Berlin, Germany, in 1993. At this meeting the group developed the consensus classification that came to be known as the REAL (Revised European American Lymphoma) classification.

Figure 5.

Clinical Advisory Committee meeting, Airlie, Virginia, November 3–5, 1997. A joint meeting was held for discussion of lymphoid and myeloid neoplasms, including lymphomas and leukemia, in preparation for the publication of the WHO monograph, published in 2001.

Figure 6.

Clinical Advisory Committee meeting, Chicago, Illinois, held in preparation for the revised 4^th Edition of the WHO classification. Concurrent meetings were held to discuss mature lymphoid neoplasms (A) and myeloid neoplasms and acute leukemias (B).

Figure 6.

Clinical Advisory Committee meeting, Chicago, Illinois, held in preparation for the revised 4^th Edition of the WHO classification. Concurrent meetings were held to discuss mature lymphoid neoplasms (A) and myeloid neoplasms and acute leukemias (B).