How to tell apart blood and marrow smears

Why do I have to find out myself at the exam if it is blood or marrow?

We mentioned at the description of the pathophysiology exam that you get an unlabeled or coded smear you will have to find out if it is a blood or a bone marrow specimen. This problem rarely arises in real life, because the physician usually knows where he got the specimen from. However, we decided to organize the exam this way, for the following reasons: Here are a few ways to tell the difference between blood and bone marrow specimens (you should probably use more than one method):

Macroscopical examination (look at the smear)

You can tell if a smear is made of peripheral blood or bone marrow many times just by looking at it. Peripheral blood forms a homogenous layer on the glass plate, without any apparent structure. On the other hand, bone marrow smears are not homogenous, the inner portions look different from those at the sides.

Microscopical examination, using low magnification

The situation is similar to the macroscopic examination: the peripheral blood preparations are homogenous, while the bone marrow ones are not. You can often see empty areas in the bone marrow, corresponding to dissolved fat, the inner areas look different from those at the sides.
Normal peripheral blood smear, homogenous picture. the WBC count is normal.
Normal bone marrow. The fat dissolved during the staining procedure leaves apparently empty areas.
The side portion of a normal peripheral blood smear. You may see some inhomogeneity here. Don't mix this up with a bone marrow preparation! This shows that you really need to examine a preparation at many places, not just one.
CML peripheral blood. The high WBC count is charateristic.
AL in peripheral blood. The WBC count is variable, here it is high.
Hypercellular bone marrow in CML. The megakaryocyte count is often increased in the first phase of the disease.

Identification of the cells in the smear

There are cells that never get out to the peripheral blood, even under pathological conditions. (To be precise: any cell can get out, but some cells appear in the peripheral blood very rarely, and they have rather unusual morphological characteristics when they do so.) So, if we see a cell like like this (e.g. plasmocyte or megakaryocyte) we know that the specimen we are looking at is probably a bone marrow one. A few normoblasts often appear in peripheral blood films of leukemic patients, because they usually have anemia. That is why normoblasts are not very good to tell the difference between blood and bone marrow. (If you see really large number of normoblasts, then it is likely to be bone marrow, of course.)

Plasmacytes rarely get out to the peripheral blood. The so called plasmocytic leukemia is such a rare condition. So if you see plasmacytes, in a smear it is likely to be bone marrow.

Megakaryocytes very do not get out to the peripheral blood. There is a condition called megakaryoblastic leukamia (FAB M7), where the tumor cells appear in the peripheral blood, but these cells are small, and don't look like the normal megakaryocytes in the normal bone marrow. So megakaryocytes are very useful in differentiating blood from bone marrow: if you see one, you know it is a bone marrow specimen. The only problem is, that there are very few of them in the bone marrow, so you must be lucky to find one with the usual high magnification. You can easily find them, however, using a low magnification, because of their enormous size.
Megakaryocyte in a bone marrow, using low magnification. This field looks like peripheral blood, but the presence of the megakaryocyte rules this out. In situations like this, it is a good idea to put the megakaryocyte precisely into the middle of the field, and to change over to high magnification, so that you can see if it is really a megakaryocyte or not. This is the following picture.
The same megakaryocyte using high magnification.

László L. Tornóci
Copyright © Inst. Pathophysiology, Semmelweis Medical University