Transcription
Okay, good day! Continuing with our hematology review, we are now going to discuss the different leukocyte disorders. I have classified these leukocyte disorders into four categories for better understanding and correlation later with the different characteristics or laboratory findings of these leukocyte disorders.
First, we have the non-malignant granulocytic disorders. These are classified into two groups: quantitative abnormalities and qualitative abnormalities. The first four here are quantitative abnormalities, while we have functional disorders, nuclear abnormalities, and cytoplasmic abnormalities as qualitative in nature.
Now, I will point out the important things to note regarding these non-malignant granulocytic disorders. Our focus for this discussion will be the malignant ones.
First, we have physiologic pseudo-neutrophilia. As the name suggests, "physiologic" means it is normal in nature. Because it is normal, we do not expect toxic changes in our white blood cells in this case. Toxic changes refer to toxic granulation, vacuolation, and the presence of Döhle bodies. These changes are not found in physiologic pseudo-neutrophilia. In this case, there is an increase in the number of WBCs. When we say neutrophilia, it is defined as an increase of greater than 7,500 per microliter.
Again, for physiologic pseudo-neutrophilia, it is a normal finding; therefore, toxic changes are not found. Unlike in the case of pathologic neutrophilia, this is where we could find toxic changes. So, when we say toxic changes, we expect the presence of granulations, vacuolations, and Döhle bodies.
Next, we have the neutrophilic leukemoid reaction. We will later differentiate this from chronic myelogenous leukemia because they show similarities, especially in what we call the left shift. This is characterized by a left shift, meaning there is an increased presence of immature WBCs in the peripheral blood smear, including bands, metamyelocytes, and myelocytes.
Other than the left shift, one differentiating feature of the leukemoid reaction from chronic myelogenous leukemia is that it will have an increased LAP score.
Now, let us proceed to the different functional disorders. For the functional disorders, we have two to discuss: chronic granulomatous disease and Chédiak-Higashi syndrome.
First, let's discuss chronic granulomatous disease. This is a group of conditions where our white blood cells can ingest but cannot digest the pathogens they have engulfed. This group of disorders is characterized by ineffective intracellular destruction of ingested organisms due to a defect in the respiratory burst. The WBCs cannot mount the respiratory burst, which is necessary for producing reactive oxygen species to kill the ingested organisms.
In the case of chronic granulomatous disease, if we check the WBC morphologically, it appears morphologically normal. However, functionally, it is abnormal. The particular enzyme we need to note in chronic granulomatous disease is the deficiency of the NADPH oxidase. This enzyme is essential for the phagocyte to mount the respiratory burst. Because of this, chronic granulomatous disease is characterized by severe recurrent infections.
Now, let's go to the other functional disorder, Chédiak-Higashi syndrome. This syndrome is characterized by an abnormal fusion of primary and secondary granules due to a mutation in the lysosomal trafficking regulatory gene, specifically the CHS1 and LYST genes. Morphologically, we expect the presence of gigantic granules that, when stained using peroxidase, give a positive result.
Both chronic granulomatous disease and Chédiak-Higashi syndrome are functionally abnormal. However, in chronic granulomatous disease, the WBCs are morphologically normal, while in Chédiak-Higashi syndrome, there is a morphological anomaly present, which is the presence of gigantic granules that are peroxidase positive.
Next, we move on to nuclear abnormalities. We will talk about hypersegmentation, which is often a manifestation of nuclear-cytoplasmic synchrony. This is often associated with megaloblastic anemia. Hyposegmentation occurs when the lobulations of our WBCs are less than two. We have Pelger-Huët and pseudopelger-Huët anomalies for hyposegmentation.
For inherited cytoplasmic anomalies, we have May-Hegglin anomaly and Alder-Reilly anomaly.
First, May-Hegglin anomaly is characterized by large crystalline Döhle-like bodies present in the cytoplasm. This anomaly is also characterized by having giant platelets. Because the platelets are larger than normal, they are not counted as platelets, especially if the principal use is electrical impedance. In electrical impedance, we differentiate cells based on their size, so because the platelets here are giant, they are no longer counted as platelets. We expect the platelet count to be decreased, and these platelets also do not function well, leading to bleeding as a characteristic of May-Hegglin anomaly. This condition is due to the MYH9 gene mutation.
The other cytoplasmic anomaly is Alder-Reilly anomaly, which is characterized by large azurophilic granules containing degraded mucopolysaccharides. This type of anomaly is associated with mucopolysaccharidoses, namely Hunter, Hurler, and Sanfilippo syndromes.
Now, let us proceed to the monocytic disorders. For the monocytic disorders, we have Gaucher's disease and Niemann-Pick disease. In Gaucher's disease, the deficiency is in glucocerebrosidase. Because of this deficiency, glucocerebroside accumulates in the macrophages, particularly in the spleen, liver, and bone marrow. This leads to a crumpled tissue paper appearance of the macrophages due to the accumulation of glucocerebroside.
On the other hand, Niemann-Pick disease is due to sphingomyelinase deficiency. Similarly, sphingomyelin accumulates in macrophages, giving them a foamy appearance.
Next, we go to non-malignant lymphocytosis associated with viral infections. We have three here: infectious mononucleosis, cytomegalovirus, and infectious lymphocytosis agents.
Infectious mononucleosis is caused by the Epstein-Barr virus, which targets B cells. In this condition, we see reactive T lymphocytes attacking the B cells. Note that in the case of infectious mononucleosis caused by EBV, the heterophile antibody test is positive.
Cytomegalovirus infection can also cause an infectious mononucleosis-like condition. However, it is the most common transplacentally transmitted infection. In this case, there are no reactive lymphocytes, and the heterophile antibody test is negative.
Lastly, we have infectious lymphocytosis, commonly caused by adenovirus and Coxsackie A infection. In this case, there is also an absence of reactive lymphocytes.
Now, let’s highlight the malignant leukocyte disorders. We have five groups: acute lymphoproliferative disorders, acute myeloproliferative disorders, chronic leukemias, other lymphoid malignancies, and myelodysplastic syndrome.
I will discuss selected classifications. We have the FAB (French-American-British) classification and the WHO classification. The FAB classification is the older classification often discussed in schools but not really utilized in diagnosis. The WHO classification is the most commonly used and is considered the standard for diagnosis.
The WHO classification defines leukemia as the presence of greater than 20% blasts in both the bone marrow and peripheral blood smear.
Now, let us proceed to acute myeloid leukemia (AML). The WHO has classified this into four categories: AML with recurrent genetic abnormalities, AML with myelodysplasia-related changes, therapy-related myeloid neoplasms, and AML not otherwise specified.
Acute myeloid leukemia is typically the common type of leukemia affecting both adults and infants. The WBC count is usually increased due to the increased circulating blasts. However, this can vary depending on the type of acute myeloid leukemia.
Genetic abnormalities associated with AML include translocation from chromosome 8 to 21, inversion in chromosome 16, translocation from chromosome 15 to 17, and translocation from chromosome 6 to 9.
For AML not otherwise specified, we have M0, which is AML with minimal differentiation, M1, which is AML without maturation, M2, which is AML with maturation, M4, which is acute myelomonocytic leukemia, M5, which is acute monoblastic and monocytic leukemia, M6, which is acute erythroid leukemia, and M7, which is acute megakaryoblastic leukemia.
Now, we have myelodysplastic syndromes, which are myeloid neoplasms characterized by ineffective hematopoiesis, leading to cytopenia and dysplasia in at least one of the major myeloid lineages. These are usually seen in older adults, but if seen in younger adults, it is often secondary to chemotherapy, radiation exposure, or inherited bone marrow failure.
Lastly, we have myeloproliferative neoplasms, which are characterized by abnormal proliferation of all myeloid lineages, usually affecting one cell line prominently.
That concludes our lecture on the different leukocyte disorders. If there are disorders I failed to mention, I have included the names of those that are high yield for this session. That would be all for this session.