The four main myeloproliferative disorders share several similarities such as a hypercellular marrow, a high white count with a left shift, and splenomegaly. (more…)
Q. My professor asked this on an exam: What’s the difference in molecular mechanism between metaplasia and neoplasia?
A. Metaplasia is the changing of one cell type to another. The term is used most often in reference to epithelial cells, for example, when the normal glandular epithelium of the cervix is replaced with squamous epithelium, it is called “squamous metaplasia”. It simply means that the basal cells (the stem cells of the epithelial layer) switch from making one type of epithelial cell to another.
Though it is not malignant or even premalignant, in and of itself, metaplasia sometimes indicates that there has been damage to the area, and if the insult continues, dysplasia or even frank malignancy can occur. This is fairly common in the lung: metaplasia of the bronchial epithelium is followed by dysplasia, which is followed by carcinoma. The molecular mechanisms of this whole process of metaplasia are not well understood.
“Neoplasia” literally means “new growth.” Neoplastic cells have several characteristics that make them nasty: they grow autonomously without any need for growth signals, they are insensitive to normal growth-inhibitory signals, they don’t die off like they should, they are capable of limitless replication, and – if they are malignant neoplastic cells – they invade vessels and travel to different parts of the body and set up shop.
There are lots of molecular mechanisms (and corresponding genetic mutations) that underlie these neoplastic qualities; most neoplasms have several such mutations. A cancer cell can have mutations in many different genes – for example, the genes encoding growth factor receptors, signal-transducing proteins, nuclear transcription factors, or cyclins.
Sometimes these mutations turn on a gene that promotes growth. The normal variants of these growth-promoting genes are called “proto-oncogenes” and the mutated variants are called “oncogenes.” An example of just such a gene is the RAS proto-oncogene, which makes a signal transduction protein involved in cell growth. Many neoplasms have a mutated RAS gene (called the RAS oncogene) that has been altered in such a way that it is always turned on. Which means that the cells containing the mutation are always transducing growth signals, and always growing and dividing.
Another type of mutation can occur in genes (called “tumor suppressor genes”) that normally put brakes on cell growth. An example of this type of gene is the retinoblastoma tumor-suppressor gene, which normally stops cells at the G1 checkpoint in the cell cycle. In certain tumors, the retinoblastoma gene is mutated in such a way that it doesn’t work. Cells that have this mutated gene proceed without pause through the G1 checkpoint, heading full-tilt on to mitosis.
So, to summarize: the molecular mechanisms of metaplasia are not well understood. The molecular mechanisms underlying neoplasia are numerous and complex.
There are four major types of myeloproliferative disorders: chronic myeloid leukemia, chronic myelofibrosis, polycythemia vera, and essential thrombocythemia. (more…)
We’ve talked already about how you’d differentiate chronic lymphocytic leukemia from a benign lymphocytosis. So how about the same thing for the myeloid series, namely, how do you tell apart chronic myeloid leukemia from a benign neutrophilia? (more…)
Q. If you have a blood smear that shows a lymphocytosis, and all the lymphocytes look pretty mature, how do you know whether it’s chronic lymphocytic leukemia (CLL) or just a plain old benign lymphocytosis? (more…)
Here’s a very good question about the diagnostic use of the bleeding time.
Q. I’m currently studying heme for boards and came across a practice questions that used platelet count, bleeding time, PT and PTT values to differentiate between certain diseases/problems. I was just wondering how in both Vitamin K deficiency and liver disease you can get an increase in PT and PTT but the bleeding time doesn’t change…I guess I figured that bleeding time would have to increase. Can you explain this to me?
A. Yeah, that does sound weird, you’d think the bleeding time would change – but actually, the bleeding time is only a measure of platelet function. It really has nothing to do with coagulation!
I kind of think of it like this: the platelet plug is the first thing to form, and that is enough to stop the bleeding from the incision made at the beginning of the test. The coagulation cascade happens next, and the status of that won’t be apparent in the bleeding time results. The patient might have some more bleeding later if their coagulation system is really screwed up…but the bleeding time assay will be done by then. In reality, it probably happens a little more concurrently than that (platelet plug is followed very closely by fibrin formation – the two probably even overlap a bit), but I think it’s a good way to remember the concept.
The same reasoning fits with the way that people with coagulation factor disorders bleed (as opposed to patients with platelet disorders). People with platelet abnormalities tend to bleed spontaneously into mucous membranes without much provocation (probably because they’re having a hard time forming that initial platelet plug) whereas patients with coagulation factor abnormalities, like hemophilia, tend to have deep, severe bleeds that happen after some time has elapsed (because they form the initial platelet plug okay, but they can’t seal it up with fibrin very well, so they end up bleeding later on).
Before you can really appreciate pathologic changes in red cells, you need to know what normal red cells look like. Â Here is a normal blood smear image, taken at high power. (more…)
Who names this stuff, anyway?!
Coagulation factors, for the most part, have two names: a Roman numeral name and an English wordy name. (more…)
Mapo doufu is an ancient Chinese dish that made me feel dizzy the first time I ate it. (more…)
Rudolf Virchow, a German pathologist in the 1800s, is considered by many to be “the father of pathology.” His famous Omnis cellula e cellula (“every cell originates from another existing cell like it”) theory, published in1858, rejected the then-prevalent belief that organisms could spontaneously arise from non-living matter (e.g., that maggots could spontaneously appear in decaying meat). (more…)
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