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White Cell Neoplasms

  • Neoplasias of leukocytes represent a diverse set of disease entities that range from indolent, chronic pathologies to those that can be rapidly fatal. In general, these diseases represent clonal proliferation of a cell that resembles a cell type found in the natural sequence of hematopoiesis. The resemblance includes not only histopathological similarities seen under microscopy, but also "immunophenotypic" similarities, meaning the neoplastic cells carry the same protein surface markers as the normal cells from which they are likely derived. In some cases, the neoplastic cells display some preserved functionality, continuing to synthesize and secreting the same products as their normal counterparts. Taken together then, it is unsurprising that diagnosis and categorization of white cell neoplasms often rests on their histopathology, assessment of surface markers by flow cytometry, and evaluation of synthesized products.
  • The pathogenesis of white cell neoplasms is still being understood; however, in many cases the key etiologic event can be traced back to a large chromosomal event such as a translocation or an enormous deletion that can be appreciated by karyotype analysis. In the case of chromosomal translocations, a frequent finding is that the novel chromosomal fusion point places a proliferation-inducing proto-oncogene normally on, say, Chromosome A, under a very strong promoter for a highly-synthesized gene on say, Chromosome B. Consequently, a normally very tightly-regulated proto-oncogene suddenly becomes highly synthesized, thus promoting uncontrolled cell growth.
  • A large amount of data now exists on the clinical significance of particular chromosomal translocations. Indeed, treatment regimens and prognosis can change depending on what type of chromosomal translocation the patient's tumor carries. Consequently, a knowledge of the most classic translocations is usually expected for beginning medical students.
  • However, it should be pointed out that with the advent of whole genome tumor sequencing, we are now appreciating that more minute genetic lesions, such as small deletions affecting single tumor suppressor genes, amplifications of oncogenes, or even single nucleotide mutations can also be responsible for white cell neoplasms.
Morphology: Leukemia vs Lymphoma
  • Unique histomorphological characteristics of particular pathologies will be discussed on their own page. Here we solely discuss the difference between a "leukemia" and a "lymphoma". In general, when tumor cells are mostly found in the blood or bone, the disease is termed a "leukemia". However, when tumor cells are mostly found in solid lymphatic tissue, such as lymph nodes or the spleen, then the disease is termed a "lymphoma".
  • These terms, however, may give a false sense of mutually exclusive anatomic involvement and tumors can often involve all three locations: blood, bone, and solid lymphatic tissue. Additionally, some tumors may change their sites of primary involvement from the usual leukemic locations to the usual lymphoma locations over the course of disease