Breast Apocrine Metaplasia
Apocrine Metaplasia is a particular kind of cellular change associated with a variety of breast cystic disorders. It is a completely benign condition which in itself does not increase risk for subsequent breast cancer. Apocrine metaplasia is sometimes described as a 'benign epithelial alteration' of breast tissue, which means that epithelial cells are undergoing an unexpected change. These changes which may show on a mammogram as a potential mass or lesion, or possibly even develop into a palpable mass. Because similar changes to breast tissue may be associated with apocrine breast carcimona, it is quite important to investigate the situation thoroughly to confirm the benign differential diagnosis of apocrine metaplasia. There are no clear mammographic distinctions for apocrine metaplasia, so it will most likely have to be followed up with confirming ultrasound, or small biopsy.
What exactly is breast apocrine metaplasia?
Apocrine metaplasia is a 'non-proliferative' breast lesion, and is usually associated with breast fibrocystic disease. The term "proliferative" would mean that cells are growing and growing, and in a somewhat unpredictable way. Proliferative cells growth is therfore usually associated with carcinoma. But apocrine metaplasia is 'non-proliferative', which means there will be new cell growth and change, but only in a limited and predictable way. In fact "metaplasia", ( derived from the Greek word 'meta', meaning 'change in form') implies a reversible replacement of once type of cell with another type of cell. Usually this is the result of some kind of irritation. Once the cause of the irritation is discovered and treated, the cells should return to normal. In most cases the source of 'stress' which is causing the apocrine metaplasia is the development of a breast cyst, and these may be caused by any number of normal biological processes and obstructions in the breast. It is believed that apocrine-like cells form in a lining of developing microcysts due to the increased intraluminal pressure caused by secretions.
Why is it called "apocrine" metaplasia?
The name can be a bit misleading. Apocrine metaplasia does not in fact have anything to do with 'apocrine glands', which are associated with sexual function, odour, and sweat secretion. By extension, apocrine metaplasia is also unrelated to apocrine breast carcinoma, which can develop within the apocrine glands of the breast. Instead, Apocrine metaplasia is named accoding to the shape of the new cells, which have a visual resemblance to apocrine glandular cells. Specifically, they tend to show an accumulation of 'secretory granules'(small proteins) in the apical cytoplasm (the top layer of the 'filler fluids' of the overall tissue formation.)
Apocrine metaplasia arises in the TDLUs
Apocrine metaplasia is believed to arise from the lobular cells located in the terminal ductal-lobular units (TDLU) of the breast (the final junction where milk produced in the lobules enters the breast ducts ). Usually, these metaplasic cells will show up in the epithelial lining ( the wall ) of breast cysts which are developing or have already developed.
How would apocrine metaplasia of the breast be detected?
Apocrine metaplasia is a cellular transformation which begins very early on in the development of a cyst. For this reason, it presents with a certain amount of ambiguity and may cause anxiety for the patient. Usually a breast cysts will primarily contain fluids (unlike breast cancer), and perhaps scattered mineral deposits and calcifications. A fully developed breast cyst will tend have rather obvious and clinically apparent symptoms. Ultrasounds are also very useful in distinguishing a benign breast cysts from a more 'solid' breast carcinoma. But, in the very early stages of cyst development these mature features will not be apparent.
It is difficult to rule out breast cancer from X-rays of apocrine metaplasia
So, what usually happens is a women goes in for a routine screening mammogram and a strange psuedo-mass or lesion is discovered on the X-ray. From the X-ray, the radiologist will note the development of unexpected features and cellular change, but will be unable to distinguish the benign nature of apocrine metaplasia from the more worrisome features of breast carcinoma. The main issue regarding apocrine metaplasia is that, due to the immature nature of a breast cyst which is developing, follow-up evaluations are called for as a differential diagnosis from breast cancer, and this can cause anxiety.
Apocrine metaplasia of the breast diagnosed on a mammogram is usually followed up with a small biopsy
A mammogram of apocrine metaplasia will typically reveal an equal density mass, in a lobular shape and possibly with microlobulated margins. There may also be groups or clusters of heterogenous calcifications. Depending on the age of the lesion, ultrasound may not be able to detect any other relevant characteristics. The consensus opinion among screening physicians is therefore that features commonly associated with apocrine metaplasia, unless clearly related to corresponding ultrasound finding or clincially palpable symptoms , should be followed up with a needle biopsy just to be sure.
in the ultrasound image above, the darker area would be called a "hypoechoic nodule with margins that aren't smooth enough to call benign", so it would need to be biospied. And in this case, the biopsy result is benign apocrine metaplasia
The HER-2 protein is normally not present in apocrine metaplasia
A topic of current breast cancer research resolves around other ways of distinguishing apocrine metaplasia from breast carcinoma, without the inconvenience and expense of a core biopsy. Among the ideas being tested is the notion that the HER-2 protein, which is associated with cell membranes and adhesion, is commonly overexpressed in breast carcinoma, but would not be present in apocrine metaplasia.
Apocrine Metaplasia is most commonly associated with older, post menopausal women
Microscopic apocrine metaplasia is not uncommon with women in their 30s, but generally speaking the condition is associated with older, post-menopausal women, and is most common with women in their 50s. By the time women reach their 80s and 90s, about 50% will have developed apocrine metaplasia.
Conclusions regarding apocrine metaplasia and breast cancer
Apocrine metaplasia in itself is a benign condition usually associated with breast fibrocystic disease. It can also be associated with other benign breast irritations like papilloma, hamartoma, and fibroadenoma. But, it is also a condition which may develop alongside 'solid lesions' such as breast cancer. This is why it has to be taken seriously and investigated fully. As to the quesion of increased risk or suggestions of breast cancer, only in so-called 'atypical' or 'complex' apocrine metaplasia, where the apocrine metaplasia (non-proliferative) is accompanied by proliferative cellular growth (hyperplasia) would it be considered an elevated risk factor. (And this is due to the hyperplasia, not the metaplasia) Otherwise, any increased risk would only be the same very low risk elevation common for all women who show a genetic predisposition for fibrocystic breast disease.
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Copyright Steven B. Halls, MD Last edited 22-August-2011