MORPHOLOGYInleukemicpresentations,the marrow is hypercellular and packed with lymphoblasts, whichreplacenormalmarrowelements.Mediastinal masses occurin50%to70%ofT-ALLs,whicharealsomorelikelytobeassociatedwithlymphadenopathyandsplenomegaly.InbothB-andT-ALL,thetumorcellshavescantbasophiliccytoplasmandnucleiwithdelicate,finelystippledchromatinandsmallnucleoli(
Fig.12.14A ).Inkeepingwiththeaggressiveclinicalbehavior,themitoticrateishigh.Theappearanceoftheblastsisidenticalinpre-Bandpre-TALLsandisnotsufficientlycharacteristictoexcludetheothermajorsubtypeofacuteleukemia,acutemyeloidleukemia(AML,discussedlater).Forthisreason,definitivediagnosisreliesonstainsperformedwithantibodiesspecificforBandTcellantigens(
Fig.
12.14B–C ).Histochemicalstainsarealsohelpful,inthat(incontrasttomyeloblasts)lymphoblastsaremyeloperoxidase-negativeandoftencontainperiodicacid-Schiff–positiveglycogengranules.
http://ebooksmedicine.net
Table 12.8 Characteristics of the More Common Lymphoid Leukemias, Non-Hodgkin Lymphomas, and Plasma Cell Tumors
Clinical Entity Frequency Salient Morphology Cell of Origin Comments
Theperipheralbloodfindingsarehighlyvariable.Thewhitecellcountmaybegreaterthan100,000cells/µLbutinabouthalfofthepatientsislessthan10,000cells/µL.Afewpatientshavenocirculatingblasts(aleukemicleukemia).Anemiaalmostalwaysispresent,andtheplateletcountusuallyisbelow100,000/µL.Neutropeniaisanothercommonfinding.
Genetics. Approximately 90% of ALLs have nonrandom karyotypic abnormalities. Most common in childhood pre–B cell tumors are hyperdiploidy (more than 50 chromosomes/cell) and a (12;21) translocation involving the ETV6 and RUNX1 genes, creating a fusion gene encoding an aberrant transcription factor, whereas about 25% of adult pre–B cell tumors have a (9;22) translocation involving the ABL and BCR genes. Pre–T cell tumors are associated with diverse chromosomal aberrations, including frequent translocations involving the T cell receptor loci and certain transcription factor genes, as well as mutations that inactivate tumors suppressor genes such as PTEN (leading to increased pro-growth signaling) and CDKN2A, which encodes a negative regulator of the cell cycle and a positive regulator of p53.
Immunophenotype. As mentioned, immunophenotyping is very useful in subtyping ALLs and distinguishing them from AML. Terminal deoxynucleotidyl transferase (TdT), an enzyme specifically expressed in pre–B and pre–T cells, is present in more than 95% of cases. Further subtyping of ALL into pre–B and pre–T cell types relies on stains for lineage-specific markers, such as the B cell marker CD19 and the T cell marker CD3.
Clinical Features. ALL is an aggressive disease, and most patients present within a few weeks of the onset of symptoms. Among the most important signs and symptoms are the following:
Symptoms related to depression of marrow function, including fatigue resulting from anemia; fever, reflecting infections secondary to neutropenia; and bleeding due to thrombocytopenia