neoplasia | Pathology Student

Tumor cell differentiation

Here’s a good question that gets at a concept you should understand: tumor cell differentiation. (more…)

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.

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…)

Metaplasia vs. neoplasia

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.