Description:
It turns out the old adage from our medical school days, “If you hear hoofbeats, think of horses, not zebras,” was not completely correct!  Indeed, the diagnosis of a “rare disease” turns out to be not as rare as we previously thought.  The faculty speaking in this important session have focused their entire careers to patient care and cutting-edge research in areas of rare and even ultra-rare hematologic malignancies. The coupling of increasing pathologic technology and diagnostic methods along with augmented education and awareness have shed light on some of the more rare blood cancers in our field, especially over the past decade.  In particular, in the field of myeloid neoplasms, the emerging importance of dividing these entities into specific subgroups distinguished by unique clinicopathologic characteristics has had a tremendous impact not only on diagnosis, but also on prognosis and development of novel treatment decision approaches.  

In this first talk, Dr Robert P Hasserjian focuses his remarks on understanding the growing field of chronic neutrophilic leukemia (CNL) and CSF3R-related disorders. In the decade since the elucidation by, Maxson et al (Maxson, NEJM 2013), of frequent oncogenic CSF3R mutations in patients with CNL and atypical CML, this field has rapidly expanded as we are beginning to understand that these Philadelphia negative hematologic myeloid malignancies  are more commonly present than we previously thought.

In the second talk, Dr Naveen Pemmaraju highlights the encouraging developments in a rapidly emerging field in hematologic malignancies, that of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN).  BPDCN is a singularly unique malignancy that is known for involving cutaneous sites, followed by bone marrow/blood lymph nodes, and of interest, a high rate of CNS involvement. Despite many nomenclature and disease category changes over the past three decades, BPDCN is now recognized as its own unique entity which expresses, via flow cytometry and immunohistochemistry: CD123+, along with CD4+, CD56+, TCL-1+ and TCF-4+. The clinical pioneering of the first approved CD123-targeted agent in the field (tagraxofusp, led by Pemmaraju et al NEJM April 2019) has led to the development of a  worldwide clinical/translational interest in BPDCN, targeting CD123 by various therapeutic approaches, and for interest in developing combination approaches and CNS-directed therapies for this rare blood cancer.

In the final talk of this session, Dr Olga Weinberg very nicely draws attention to acute leukemias of ambiguous lineage, a field that is rapidly growing as it benefits from deeper, faster, and more directed targeted sequencing efforts and improved patho-biologic understanding of the various subsets that make up this unique entity. Among the keys to this topic will be understanding several of the newer tests, at the level of the blood, bone marrow, flow cytometry, cytogenetics and molecular next generation sequencing that are available in the pathologists’ and clinicians’ tool kits in searching for identification and diagnosis of particular subtypes of this historically elusive diagnosis that is becoming more and more common to encounter.