EDUCATIONAL COMMENTARY – BLOOD CELL IDENTIFICATION Educational commentary is provided through our affiliation with the American Society for Clinical Pathology (ASCP). To obtain FREE CME/CMLE credits click on Continuing Education on the left side of the screen. Learning Outcomes Upon completion of this exercise, the participant will be able to: • Identify morphologic characteristics of mature and immature leukocytes. • Describe morphologic features associated with the May-Hegglin anomaly. The photographs presented in this testing event represent normal peripheral blood findings associated with pregnancy as well as abnormal findings seen in the May-Hegglin anomaly, as diagnosed in this patient. Picture BCI-01 is a normal lymphocyte. Lymphocytes are variable in size, although the one depicted here represents a smaller lymphocyte. In lymphocytes, the cytoplasm is blue and often scanty. Nuclei may be oval, round, or slightly indented. The chromatin is condensed and clumped. BCI-02 illustrates a normal monocyte. The cytoplasm is abundant, blue-gray, and has numerous vacuoles. Notice the faint lilac or purple “azurophilic” granules. The cytoplasm in monocytes also often appears bumpy and rough. Many times the cellular margins are not even, and sometimes, as is seen in this example, cytoplasmic extensions are present. The nuclei in monocytes may be oval, lobulated, kidney-shaped, or round. The chromatin in monocytes stains lighter shades of purple and contains no visible nucleolus. The cell in this picture does have a lighter staining area within the nucleus, but it is not defined enough to be considered a nucleolus. American Proficiency Institute – 2006 1st Test Event EDUCATIONAL COMMENTARY – BLOOD CELL IDENTIFICATION (cont.) The cell in photograph BCI-03 is a band or stab neutrophil. These cells are about the same size as segmented neutrophils. In fact, bands are the earliest precursors of neutrophil maturation that can normally be seen in the peripheral blood. The nucleus in a band cell is characteristically shaped like a band, a sausage, or the letters “C” or “U.” The cells are maturing as evidenced by a fairly clumped and condensed chromatin. The cytoplasm contains numerous specific granules that stain pink, tan, or violet. The band shown in this picture is a classic example of this cell. However, sometimes it can be difficult to distinguish bands from segmented neutrophils, especially when the nucleus is twisted or folded. Generally, segmented neutrophils have at least 2 nuclear lobes separated by a thin filament. The lobes in bands are characteristically connected by a bridge, with clear areas of chromatin and parachromatin visible. When in doubt regarding the classification of a cell, the commonly accepted rule of thumb is to identify the cell as the most mature stage. The platelet in picture BCI-04 can be described as “large.” Normally, platelets are only 1-4 µ in diameter. This enlarged platelet reflects the underlying inherited anomaly associated with this patient. Platelets may be irregularly shaped or round. Sometimes the cellular margins appear frayed and the cytoplasm grainy. Platelets generally stain a light purple color, although distinct reddish-purple granules may also be visible. BCI-05 is a normal segmented neutrophil. Notice the nuclear lobes connected by only thin strands of chromatin. Compare this segmented neutrophil with its filaments to the band cell with its thick, bridging chromatin, shown in BCI-03. Neutrophils usually have 2-5 lobes with clumped, dense nuclear chromatin. These cells also have numerous pink, tan, or violet cytoplasmic granules. American Proficiency Institute – 2006 1st Test Event EDUCATIONAL COMMENTARY – BLOOD CELL IDENTIFICATION (cont.) BCI-06 depicts a metamyelocyte. These cells are not normally seen in the peripheral blood. However, it is not surprising to see a metamyelocyte in this case since the stress associated with labor and delivery could cause these cells to be released into circulation. The prefix “meta” denotes change, and the metamyelocyte is the first cell in the granulocyte maturation sequence that is no longer capable of mitosis. Metamyelocytes characteristically have a nucleus that is barely indented or shaped like a kidney-bean. The nuclear chromatin is dense and clumped. However, some loose chromatin reflects the immaturity of this cell. Generally, the cytoplasm contains pink, tan, or violet specific granules, though the cell in this picture has also retained some bluish cytoplasm. The pink granules, uniform cytoplasmic margins, and slightly indented nucleus distinguish this cell as a metamyelocyte. The cell shown in picture BCI-07 has a May-Hegglin inclusion, characteristic of the condition diagnosed in this patient. These inclusions are light blue or blue-gray and oval, crescent, or round masses within the cytoplasm and consist of RNA. They are similar in appearance to Döhle bodies. In contrast to true Döhle bodies, however, which are usually located peripherally in the cell, May- Hegglin inclusions are often more randomly distributed within the cytoplasm. Likewise, May-Hegglin inclusions are larger than Döhle bodies. All mature granulocytes, and sometimes monocytes, can have the May-Hegglin inclusions, whereas only neutrophils can have Döhle bodies. Döhle bodies are commonly associated with infections. Other toxic changes that may also be present in infectious conditions include cytoplasmic vacuolation and/or toxic granulation. Neutrophils in a patient with the May-Hegglin anomaly will not show these other toxic changes unless there is a concomitant infection. Neither true Döhle bodies nor May-Hegglin inclusions affect the function of the cells. While Döhle bodies are a transient finding associated with a general activation of neutrophils, the inclusions seen in the May-Hegglin patient are always present. The May-Hegglin anomaly is an inherited, autosomal dominant condition. In addition to the prominent blue masses seen in granulocytes, variable thrombocytopenia and enlarged platelets are characteristic. Although the neutrophils function normally, some patients experience mild bleeding problems related to the thrombocytopenia. The abnormally large platelets and bleeding conditions probably result from premature fragmentation of megakaryocytes. Note the very low platelet count of 22.0 x10 9/L in the patient presented for this testing event. Also notice that photographs BCI-03 through BCI-06 all contain American Proficiency Institute – 2006 1st Test Event an enlarged platelet (and very few, if any, normal platelets) and the granulocytes in pictures BCI-03, BCI- 04, BCI-05, and BCI-06 each have a May-Hegglin inclusion. It is not possible to know if this patient’s baby also has the May-Hegglin anomaly without viewing a peripheral blood smear, but the newborn’s platelet count of 38.0x10 9/L would be cause for concern. © ASCP 2006 American Proficiency Institute – 2006 1st Test Event .