What’s the connection between dysplasia and neoplasia?

dysplastic vs. normal epithelium

Q. What is the connection between dysplasia and neoplasia? I understand that dysplasia is a precancerous condition. Grades I and II are not neoplastic. But grade III dysplasia, also called carcinoma in situ, is neoplastic, right? But is it a true carcinoma, or is it not at that point malignant?

A. Dysplasia is not a neoplastic process. While it is often a precursor to neoplasia, not all cases will evolve into malignancy (e.g., mild cervical dysplasia usually does not progress to carcinoma. We watch patients who have it carefully, though, to catch those patients that do go down that path.).

Carcinoma in situ is neoplastic. The cells in carcinoma in situ have the potential to invade (and definitely will, if left alone and untreated). They have acquired enough genetic mutations to have the characteristics of malignant cells (they are able to invade, able to grow on their own without growth signals, insensitive to growth-inhibiting signals, able to metastasize, etc).

Some classification schemes equate grade III dysplasia with carcinoma in situ, while others leave carcinoma in situ in its own category at the far end of the nastiness spectrum. Personally, I prefer the latter way of looking at things, because keeps the separation between dysplasia and neoplasia intact.

The important thing to remember, no matter what semantics you choose, is that the chances of evolution into overt carcinoma rise with the degree of dysplasia. Mild dysplasia usually does not evolve into carcinoma, whereas severe dysplasia usually does.

The image above shows a portion of cervical epithelium that has undergone dysplastic change. The right hand side of the image shows normal squamous epithelium, and the left hand side of the image shows moderately dysplastic epithelium. The dysplastic epithelial cells are pleomorphic (varying in size and shape) and hyperchromatic (darkly-staining) nuclei. Their architecture is also disrupted. Instead of the nice basal layer and orderly maturation and flattening-out of cells that you see in normal epithelium, much of the epithelial thickness resembles the basal layer.

Leukocyte alkaline phosphatase

 

lap +4

lap +1

What if you had a blood smear in which you thought the diagnosis was chronic myeloid leukemia (CML), but you didn’t have access to a cytogenetic or molecular lab (to look for the Philadelphia chromosome or the bcr-abl translocation)? (more…)

Name that anemia!

See if you can identify these types of anemia. Answers are in the first comment associated with this post. (more…)

Anemia quiz

Megaloblastic anemia with hypersegmented neutrophil

People seem to love the quizzes! Here’s another one, in a more traditional format, this time on anemia. (more…)

Cytogenetics quiz

chromosomes

Many hematopoietic malignancies have characteristic cytogenetic changes, such as translocations or inversions. It’s important to know about these because they can be used for diagnosis in tough cases, and they often carry a prognostic significance. (more…)

Food poisoning quiz

fried-rice

I thought we’d do something a little different today. Take out your pencils and paper, please, we’re going to have a quiz. (more…)

Why is the hemoglobin normal right after a big blood loss?

blood-drop

Q. Immediately after an acute episode of blood loss – following a motor vehicle accident, for example – the hemoglobin level is normal. Why is that?

A. It’s true: immediately after acute blood loss, the hemoglobin is indeed normal!

This might seem counterintuitive at first. Shouldn’t the hemoglobin be decreased since there’s less blood in the patient?

But if you think about this a bit more, during acute blood loss, you’re losing not just red cells but also every other blood component (including plasma). So the blood remaining in the patient at that point is totally normal – it’s just that there isn’t enough of it.

This means that if you take a sample of the patient’s blood right after a big blood loss, it will look normal. It has a normal number of red cells per unit volume, and the red cells themselves are perfectly normal (assuming the patient’s blood was normal to begin with).

After a few hours (sooner, if you give the patient fluids), the blood will start to become more dilute as the patient pulls fluid from tissues into vessels. If you measure the hemoglobin (and the RBC) at this point, both will now appear decreased – and rightly so, because the total blood volume has now increased.

The RDW, MCH, and MCHC, by the way, will be normal even at this point – because these tests measure the variation in size of the red cells (in the case of the RDW) and the amount of hemoglobin in each red cell (in the case of the MCH and MCHC). The patient’s problem is that there are not enough red cells around. The ones that are there, though, are completely normal.

How to read a bone marrow biopsy

normal marrow

There are several things you should look for when evaluating a bone marrow biopsy specimen – see if you can see them in the image above.

First, take a look at the cellularity. The white spaces are fat cells that have washed out during processing; the cells in between the fat cells are hematopoietic precursors. The ratio of cells to fat is called the “cellularity.” The marrow above is approximately 30-40% cellular. You need to know the age of the patient to estimate whether the cellularity is normal. Here is a rough guide to cellularity by age:

0-3 months: 100%
3 months – 10 years: 80%
20 years: 65%
30 years: 50%
40 years: 45%
50 years: 40%
60 years: 35%
70 years and over: about 30%

Next, take a look at the composition of the marrow. Myeloid cells make up the largest percentage of the normal marrow cellularity; erythroid cells are second most common. The ratio of myeloid to erythroid cells should be about 2:1 to 4:1. It’s easier to see these cells on an aspirate smear, but you can get a pretty good idea on the marrow section too. Neutrophils and precursors often have eosinophilic, granular cytoplasm; if you look closely, you can see the indented nuclei of metamyelocytes and segmented nuclei of mature neutrophils. Erythroblasts generally have very round, dark nuclei; earlier forms are large, and later forms are small. A few megakaryocytes (large cells with abundant eosinophilic cytoplasm and multiple nuclei) should be sprinkled throughout the marrow too. Lymphocytes normally represent about 10-15% of the marrow cellularity. The above marrow appears to have a myeloid:erythroid ratio of 2:1, and megakaryocytes are normal in number.

Finally, take a look through all the sections to see if you see anything weird, like fibrosis, metastatic carcinoma, lymphoid aggregates, or amyloid deposition. As you scan the sections, you should see evenly-distributed cellularity, with evenly-spread hematopoietic precursors. Anything that deviates from this pattern should be investigated on higher power.