Happy New Year!

new year

Pathology Student is back after a nice long holiday hiatus. We will begin 2010 with a new series of real live questions from real live students. It is important to hear other students’ questions (and answers) because 1) you will probably learn or clarify something, and 2) it will hopefully encourage you to ask your own questions. So, without further ado, here are some questions and answers about female reproductive system pathology.

Q. In endometriosis, is the glandular tissue found outside of the uterus and not associated with it at all other than being of similar cellular makeup? In other words, is it essentially extra-uterine menses?
A. Endometriosis is extra-uterine endometrial tissue, not associated with the stuff inside the uterus at all – other than it is under the same hormonal control, so when the endometrial tissue inside the uterus undergoes cyclic changes, so will the endometrial tissue (endometriosis) outside the uterus.

Q. Is nulliparity a risk factor in endometrial hyperplasia?
A. Yes, actually, it is, although our textbook [Robbins Basic Pathology] doesn’t mention it. It falls into the category of things-that-increase-estrogen-exposure, so it’s a risk factor for any of the tumors related to estrogen excess.

Q. The risk factors for endometrial hyperplasia include exogenous hormone use. Is this the same thing as estrogen replacement therapy?
A. In this setting, yes, they are the same thing.  If you want to be complete about it, there are other kinds of exogenous hormones – like birth control pills – but when we’re talking about endometrial hyperplasia, the exogenous hormomes referred to are estrogen replacement therapy (birth control pills don’t have that effect on the endometrium).

Q. It seems like too much estrogen causes a bunch of issues. Do many of these pathologies arise simultaneously in the presence of excess estrogen?
A. No, not usually. The chances of any one tumor or lesion arising are relatively small (even though the risk is increased compared to the setting of normal estrogen), so the chances of two developing at the same time are very small.

Q. Can you give an example of what metrorrhagia is and when it might take place?
A. Metrorrhagia means there is bleeding outside the normal period time, for example: abnormally-timed bleeding during menopause, or bleeding from an intra-uterine tumor (which would not follow normal hormonal stimuli).

Q. Could a teratoma be an ectopic pregnancy?
A. No – a teratoma is a neoplasm; it is monoclonal. It arises from a germ cell that has gone bad and decided to develop into all three germ cell layers. The cells may grow to look like normal tissues, but they’re not under any embryologic organization or control (they just grow haphazardly). A pregnancy, whether it is intrauterine or extrauterine, is not monoclonal; the tissues are growing in response to embryologic signals, and if left alone, will organize into a human.

Q. What is peau d’orange?
A. Peau d’orange (French for “skin of the orange”) happens when you have a breast cancer that has infiltrated the lymphatics of the breast skin, making the skin edematous and orange-peel-looking. This change often happens in inflammatory breast cancer (so-named because the skin can look inflamed), in which the tumor preferentially involves lymphatics.

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.