Fig. 12.25 Cancerhallmarksexemplifiedbyparticularlymphoidneoplasms.Someofthebestcharacterizedpathogenicmechanismsinlymphoidmalignanciesaresummarizedhere,includingdysregulationofMYCinBurkittlymphoma(leadingtoWarburgmetabolismsandrapidcellgrowth);dysregulationofBCL2infollicularlymphoma(leadingtoresistancetoapoptosis);PD-1ligandgeneamplificationinHodgkinlymphoma(leadingtoevasionofhostimmunity);eventsleadingtolossofcellcyclecontrol(cyclinD1rearrangementsinmantlecelllymphomaandlossoftheCDKN2A geneinacutelymphoblasticleukemia[ALL]);mutationsinvarioustranscriptionfactors,particularlyinALL,thatblockdifferentiationandenhance“leukemiastemcell”self-renewal;andchronicimmunestimulation,inmarginalzonelymphoma.Bycontrast,becauselymphoidcellsnormallycirculatethroughoutthebody,thereisrelativelylittleselectivepressureinlymphoidmalignanciesforaberrationsthatincreaseangiogenesisoractivateinvasionandmetastasis.
MatureBcelltumorthatusuallymanifestswithadvanceddiseaseinvolvinglymphnodes,bonemarrow,andextranodalsitessuchasthegut
Associatedwithan(11;14)translocationthatresultsinover-expressionofcyclinD1,aregulatorofcellcycleprogression
MatureBcelltumorarisingatextranodalsitesinvolvedbychronicinflammationresultingfromautoimmunityorinfection(e.g.,H. pylori)
UnusualBcelltumorconsistingmostlyofreactivelymphocytes,macrophages,andstromalcells
MalignantRScellsmakeupaminorpartofthetumormass.
Myeloid neoplasms arise from hematopoietic progenitors and typically give rise to proliferations that involve the bone marrow and replace normal marrow elements. There are three broad categories of myeloid neoplasia: • In acute myeloid leukemia (AML), the neoplastic cells are blocked at an early stage of myeloid cell development. Immature myeloid cells (blasts) accumulate in the marrow and replace normal elements, and frequently circulate in the peripheral blood.
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In myeloproliferative neoplasms, the neoplastic clone continues to undergo terminal differentiation but exhibits increased or dysregulated growth. Commonly, these are associated with an increase in one or more of the formed elements (red cells, platelets, and/or granulocytes) in the peripheral blood.
In myelodysplastic syndromes (MDS), terminal differentiation occurs but in a disordered and ineffective fashion, leading to the appearance of dysplastic marrow precursors and peripheral blood cytopenias.
Although these three categories provide a useful starting point, the divisions between the myeloid neoplasms sometimes blur. Both MDS and myeloproliferative neoplasms often transform to AML, and some neoplasms have features of both myelodysplasia and myeloproliferative neoplasms. Because all myeloid neoplasms arise from early multipotent progenitors, the close relationship among these disorders is not surprising.
It also is now recognized that AML and MDS often arise from an asymptomatic precursor referred to as clonal hematopoieis of indeterminant prognosis (CHIP) CHIP is characterized by normal blood counts despite the presence of one of more clonal acquired “driver” mutations in myeloid cells in the blood and the marrow. CHIP progresses to an overt white cell neoplasm at a frequency of about 1% per year and appears to be an important risk factor for cardiovascular disease (Chapter 10).