Pathology Student

Anaplasia

We talked recently about differentiation. Here’s another new word to learn: anaplasia.

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Tumor differentiation

Well-differentiated squamous cell carcinoma

Moderately-differentiated squamous cell carcinoma

Poorly-differentiated squamous cell carcinoma

“Differentiation” is a term used to describe the microscopic appearance of tumors. (more…)

What’s the connection between dysplasia and neoplasia?

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

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

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

Cytogenetics quiz

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

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…)

Thyroid nodules, mutlinodular goiters, and toxic multinodular goiters

Q. What is the difference between a thyroid nodule, a multinodular goiter and a toxic multinodular goiter?

A. Great question! Let’s look at each separately.

Thyroid nodule

A thyroid nodule is simply what it sounds like: a lump in the thyroid, usually one that’s felt by the patient or the clinician. The term “thyroid nodule” doesn’t indicate anything about the underlying pathology, it is simply a clinical, descriptive term.

Lumps or nodules in the thyroid can be caused by many different things, including both non-neoplastic disorders (multinodular goiter, thyroiditis, Graves disease), and neoplasms (adenoma and carcinoma). Non-neoplastic disorders are the most common cause, followed by adenoma, and then carcinoma.

So nodules should always be investigated because of the possibility (though small) of carcinoma.

Multinodular goiter

A multinodular goiter is simply a goiter that’s been around for a while and has had a chance to grow and become lumpy. “Goiter” simply means “enlarged thyroid” – so technically, you can use the term goiter to refer to any big thyroid.

But when you put the term multinodular in front of goiter, it usually means that the goiter is caused by an inability to produce thyroid hormone at a normal rate. There are lots of reasons a patient may be unable to make thyroid hormone.

In underdeveloped countries multinodular goiters most commonly are a result of iodine deficiency. This really bugs me, because how hard would it be to just give people in these areas iodinized salt? Not hard at all. So why don’t we do this?

In this country, iodine deficiency is rare (check out the photo above of iodinized salt), and the reasons for decreased thyroid hormone production are often unclear.

Either way, a low T4 level causes the pituitary to secrete more TSH, which makes the thyroid grow bigger (hence, the goiter). As this process evolves, some areas of the thyroid are growing and trying to produce thyroid hormone and others are not growing, but involuting. Repeated cycles of growth and involution can damage the thyroid, and as it repairs itself, fibrosis occurs, leading to a lumpy-bumpy, multinodular goiter.

Toxic multinodular goiter

“Toxic” means that the thyroid is producing thyroid hormone at a greatly increased rate. The term “toxic multinodular goiter” is loosely used to describe any lumpy thyroid that is producing excess thyroid hormone.

This could occur in a thyroid adenoma that’s producing thyroid hormone (and which appears clinically as a lump) or it could occur within the context of a true multinodular goiter (caused by the inability to make thyroid hormone).

Sometimes, for reasons that are not clear, a nodule within a multinodular goiter can sort of break away and start producing thyroid hormone autonomously (without the input of TSH). In these instances, the patient may actually become hyperthyroid!

Note: the cool vintage Morton Salt ad belongs to jbcurio, and can be found at: http://w.com/photos/jbcurio/2173554959/.

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

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.