definitions | Pathology Student

What exactly does “storiform” mean?

Do you know what a “storiform” pattern is? Yeah, neither did I when I was a medical student. However, that term did get thrown around in pathology lectures a lot, without any description or definition. There are lots of terms like this – so I’m gonna just go ahead and create a new category called:

Words Pathologists Use In Lecture As If You Know What They Mean.

I think it’s important to pause and define these terms, because otherwise this is what happens: given the sheer volume of stuff you’re supposed to learn, and the minimal amount of time you have to accomplish this task, you’re not going to look up every word you have a nagging doubt about. You’re going to infer the meaning from whatever was said in lecture, and wind up with a fuzzy and probably incorrect definition. And then someone will ask you about it on rounds, and it will be frustrating.

SO. We’ll start with “storiform” today – and I’ll keep adding posts about terms in this category as I run across them. Please email me if you find a word like this! Then we’ll wind up with a nice glossary of these formerly-unexplained terms, and you’ll look like the star you are when one of these terms comes up on rounds.

First, a little Latin

Storiform comes from the Latin storea (woven mat) and formis (form, or pattern) – so technically, storiform means “having the pattern of a woven mat.” When we use “storiform” in pathology, though, it has a more specific meaning. It refers to a tumor pattern consisting of spindle cells in a pinwheel-shaped arrangement (radiating out from a central core).

Ready to see the labeled image? Okay, scroll down….

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Keep going…

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Here’s the same image, faded out a bit so you can see the pinwheel-shaped areas outlined in black:

Okay, they’re not perfectly symmetrical pinwheels, but they do look pinwheel-ish, with tumor cells radiating out from a central core region.

One last thing, now that we’ve got the pinwheels down…if you go back and look at the unmarked image again, you might be able to imagine that the cells are arranged like a woven mat, like the Latin term suggests.

I hope you feel comfortable with “storiform” now. That’s one less undefined term!

What does megaloblastic mean?

Here are a few great questions about megaloblastic anemia I received by email.

Megaloblastic vs. macrocytic

Q. Do I have to say “megaloblastic macrocytic” anemia? Aren’t megaloblastic and macrocytic the same thing?

A. Macrocytic refers to the size of the mature red cells in the blood. It means that the red cells are big. Normal is 80-100 femtoliters. If the red cells are over 100, they’re macrocytic; if they’re under 80, they’re microcytic.

Megaloblastic refers to the weird morphologic changes (immature nucleus, mature cytoplasm, large overall size) you see in red cell precursors (and, to some extent in neutrophil precursors), in patients who are B12 deficient. So the term is really referring to the cells in the bone marrow, not mature, circulating red cells. However, you can also see changes in the blood that indicate megaloblastic anemia, the most common of which is hypersegmented neutrophils (like the one above).

So the terms are not equivalent.

That being said, you don’t need to say both terms if you have a megaloblastic anemia, because all megaloblastic anemias are also macrocytic. You just say “megaloblastic anemia.”

Conversely, if you just say “macrocytic anemia,” that doesn’t say anything about whether there are megloblastic changes present or not! It just says: there’s an anemia, and the red cells are big.

Non-megaloblastic anemia

Q. What really is non-megaloblastic anemia? Because my lectures have mentioned it but I’m not sure what it really is.

A. Non-megaloblastic anemia just means an anemia without megaloblastic changes – and technically, that encompasses every single anemia except megaloblastic anemia! But really, when people say non-megaloblastic anemia, they’re usually referring to a macrocytic anemia (one in which the red cells are large, over 100 femtoliters) without megaloblastic changes (funny looking red cells). This type of anemia can be seen in liver failure and in myelodysplasia.

Pernicious anemia and megaloblastic anemia

Q. I don’t understand the difference between pernicious anemia and megaloblastic anemia. Pernicious anemia is just a deficiency in intrinsic factor that helps with absorption of B12…so patients have low B12 levels. But how is that different from megaloblastic anemia?

A. The best way to think about these two terms is: pernicious anemia is one cause of megaloblastic anemia.

Megaloblastic anemia is a type of anemia in which you get weird morphologic changes (megaloblasts, hypersegmented neutrophils, oval macrocytes) due to a lack of B12 and/or folate. There are lots of things that can cause a lack of B12 and/or folate…so when you see a case of megaloblastic anemia, you have to investigate to find out what the cause is.

Pernicious anemia (in which patients can’t absorb B12 due to a lack of intrinsic factor) is one cause. Another cause is folate-depleting drugs (like chemotherapy drugs); another is dietary deficiency.

It’s kind of confusing because they put the term “anemia” in pernicious anemia – so it makes it sound like pernicious anemia is a category in and of itself. It’s not – it just falls under the heading of megaloblastic anemia.

What does “differentiation” mean?

Q. I have Googled and YouTubed this thing to death, and I still can’t grasp the meaning of “differentiation.” It seems the opposite of its definition. To “differentiate” means to recognize what makes something different. But according to your post on tumor differentiation, well-differentiated tumors resemble (don’t look different from) their tissue of origin. I would think if something is well-differentiated, it would look very different from the thing it’s being compared to. Why is the use here opposite of its meaning?

A. I totally get where you’re coming from. It’s REALLY frustrating in pathology when things are described in terms that don’t seem to make sense. You are not alone in questioning the use of this term!

The problem is that the word in question – differentiation – has a specific meaning in the real world. You’re exactly right in your definition: to differentiate between two things means to recognize what’s different or unique.

So you’d think that “differentiation” in the pathology world would mean the same thing: the recognition of things that are unique, different, or not the same. By logical reasoning, then, a “differentiated” tumor would be one that looked different from its cell of origin. And you’d think a “well-differentiated” tumor would be one that looked very different from its cell of origin.

Unfortunately, “differentiation” doesn’t have the same definition in the pathology world. So we have to put aside our logic and knowledge of vocabulary for a moment, irritating as that may be, and learn a new definition for this word.

The definition of “differentiation” in pathology-speak.

When we’re talking about tumors, the definition of “differentiation” is simply this: the degree to which tumor cells resemble their cell of origin. A well-differentiated tumor is one in which the tumor cells look very much like their cell of origin. A poorly-differentiated tumor (like the poorly-differentiated squamous cell carcinoma shown above) is one in which the tumor cells barely resemble their cell of origin.

That’s it. Yes, it’s an annoying word choice, because it is used here in a way that seems counterintuitive. But maybe it’s not as far off as it seems.

Maybe this will help.

I think about it (okay, rationalize it) this way. When cells are really immature, they don’t have a lot of features that make them look different from other cells. Myeloblasts don’t look very different than lymphoblasts, for example. So we could say that these immature cells are undifferentiated; it’s hard to tell what kind of cell they really are, and hard to tell them apart from other cells.

The same thing is true of the cells in poorly-differentiated tumors! The cells show practically no features that give away their identity; it’s hard to even tell what kind of cells they are. They are, in effect, undifferentiated.

If you think about “differentiation” this way (undifferentiated cells lack identifying features; it’s hard to tell what kind of cell they are), then the concept of tumor differentiation is a little easier to swallow. A little.

Tumor invasion and metastasis: are they the same thing?

Here are a couple great questions from one of my lovely students regarding invasiveness and metastasis.

Q. I have a quick question on today’s lecture. There is a slide near the end that has a picture of non-invasive carcinoma. For a tumor to be malignant, should it not be invasive?

A. Great question! I think you may be referring to the image above, which shows a gland with either severe dysplasia or carcinoma in situ.

Cancers are usually invasive, as opposed to benign tumors, which grow with pushing borders and are typically encapsulated.

However, very early cancers are called “carcinoma in situ”, which means they have not broken through the basement membrane yet (and thus are non-invasive). Every cancer has to start somewhere!

The only really definitive quality of malignancy is metastasis. If a tumor has metastasized, that is definite evidence of malignancy.

Q. But is invasiveness different from metastasis? That is, can a cancer metastasize without first invading tissue? Or are we talking about a tumor that has the ability to metastasize, but has not yet metastasized?

A. I’ll answer your questions separately.

1. Yes – invasiveness is different than metastasis.

Invasiveness is the ability of a tumor to extend into the surrounding tissue, and it is almost always a sign of malignancy. Benign tumors (with very few exceptions), are encapsulated and grow simply by expanding and pushing the surrounding tissue aside. Malignant tumors (with very few exceptions), are unencapsulated and grow by reaching into the surrounding tissue.
Metastasis is the ability of the tumor to move to a different location in the body and set up shop (start growing) there. Benign tumors NEVER metastasize. Malignant tumors usually do, although if detected early, they may be removed before they have the chance.

2. No: a cancer cannot metastasize without first invading tissue. In order to metastasize, tumor cells must first invade tissue, then make their way into vessels (either blood vessels or lymphatics), and then make their way out of those vessels and into new tissue.

3. Yes, the image above shows a non-invasive malignancy (carcinoma in situ), which is a malignant tumor that has not yet metastasized (or even invaded) yet. Left to its own devices, carcinoma in situ almost always becomes invasive carcinoma. As the tumor grows, some cells will most certainly develop the ability to become metastatic. So it’s way better to detect a carcinoma when it is in the carcinoma in situ stage rather than the invasive stage.

Intracorpuscular vs. extracorpuscular anemias

Q. I am wondering if you could differentiate between what extracorpuscular and intracorpuscular anemia are in terms of where they occur and why there is a difference in the two types. (more…)

How to tell apart promyelocytes and myelocytes

Here’s a quandry you may find yourself in soon, if you have a habit of sitting at the multiheaded scope down in hematopathology.

You’re looking at a bone marrow smear, and you can differentiate between some of the myeloid cells (blasts have a high nuclear-cytoplasmic ratio; segmented neutrophils are all mature with their multilobed nuceli; metamyelocytes look kinda like mature neutrophils only with a more horseshoe-shaped nucelus.)

But two cells will give you gout or a migraine if you don’t learn a couple simple facts: promyelocytes and myelocytes. How are you supposed to tell them apart, when they can look quite similar? They’re both kinda big, they both kinda have granules…so what gives?

Let’s do a little pre-test here to see what you think about these cells, before we discuss the “official” way of distinguishing between the two. We can leave the lymphoycte and the red cell precursors out of the discussion (top of the slide). But what’s your diagnosis on cells 1, 2, and 3? Are they promyelocytes, myelocytes, or a mixture of the two?

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Here’s the morphologic criteria from my path residency (and my histology course as a medical student) that we used to differentiate between promyelocytes and myelocytes:

The promyelocyte is the biggest cell in the neutrophil series.
It also has huge, dark purple, primary (azurophilic) granules both in the cytoplasm and overlying the nucleus.
However, it does NOT have the beginnings of secondary (specific, pink, salmon-colored) granulation! If you see any of that (even just a little blush of it in the cytoplasm), you HAVE to call a myelocyte.

So for our cells above:

Cell #2 is a pretty spectacular promyelocyte. It’s huge, it’s got tons of dark granules, and no specific granulation. It does have the beginnings of a little “hof” (a clear zone next to the nucleus) but that should not be confused with specific granulation.
Cell #3 is pretty clearly a myelocyte. It’s a smaller cell, and there are very few azurophilic granules left; the cytoplasmic granules are mostly just pale, specific granules.
Cell #1 could be a bit of a challenge because it’s a rather large cell, with abundant dark purple granulation…but it also has the clear beginnings of specific granulation in the cytoplasm. So this cell should rightly be classified as a myelocyte. It’s a pretty early one, for sure – but the presence of the specific granulation pushes it into the myelocyte category.

What’s the difference between serum and plasma?

$fractionation$ Q. Quick question for you about serum vs. plasma: I wrote in my notes during class that serum is plasma without the clotting factors. (more…)

Microcytosis and hypochromasia

Q. What is the pathophysiology of microcytes in iron-deficiency anemia (IDA)? I mean I understand that hypochromasia is due to low hemoglobin content, but what makes the cells smaller? Is it something like first there is hypochromasia and then the cells shrink? Aren’t hypochromatic cells normocytic? Why don’t red cells keep shrinking as they become hypochromatic? Please help. The question is bothering me a lot. 🙂

A. First of all, you’re right: in IDA, the red cells do get smaller. Since the bulk of the red cell is composed of hemoglobin, the less hemoglobin there is in the cell, the smaller the cell volume, and the smaller the cell overall. So in iron-deficiency anemia, there is less iron around, and therefore less hemoglobin – which results in the cells being smaller than normal. Same thing happens in thalassemia: less hemoglobin around (though not because of iron, but because of a genetic defect in a hemoglobin chain), so the red cells are smaller.

Just to clarify: chromasia just refers to the amount of hemoglobin in the cell. Cells can be normochromic (as they are in normal blood), or hypochromic (as they are in IDA). The size of the red cell is measured separately from the chromasia. Normally-sized red cells are called normocytic, small ones are called microcytic, and large ones are called macrocytic.

You asked if hypochromic cells are normocytic – and for the reason stated above, the answer is no, they usually aren’t. They are usually microcytic, because there’s less hemoglobin in the cell, so the cell gets smaller.

Finally, to answer your last question, in iron-deficiency anemia, the red cells do keep shrinking as they become more and more hypochromic! Assuming the iron deficiency is a continuing problem, as each new wave of red cells is produced, there will be less and less iron around – and therefore cells will get smaller and smaller.

So when you look at a blood smear from a patient with IDA (like the one above), you’ll see some cells that are a little bigger (these are older red cells that were made when there was still a fair amount of iron around), and some that are a little smaller (these are newer red cells, made when the iron level had dropped). Check out the two cells in the center of the image: both are hypochromic, but the one in the center is about twice as big as the one to its left.

This is why you can use the RDW to help differentiate between IDA and mild-moderate thalassemia!

MHC genes demystified

Q. I have a question on MHC receptors being polymorphic. Does this mean your MHC receptors are all the same, but just different from all of mine, which are the same as each other? Or are all MHC receptors polymorphic?

(more…)