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.

Dr. Halls Dr. Halls
The word apocrine means something to do with sweat, but only a resemblance. It’s not actually sweat gland related.


Talking Moose
Talking Moose
So not really Skin-related? Internal breast cells that start to resemble skin cells?


Hector Hector
Metaplasia means change, like cheese getting hard when it’s left out.



 
 
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 carcinoma, 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.

Betty Betty
But if my biopsy already showed apocrine metaplasia, I can relax, right?



 
 

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 therefore usually associated with carcinoma. apocrine metaplasia of the breastBut 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, odor, and sweat secretion. By extension, apocrine metaplasia is also unrelated to apocrine breast carcinoma, which can develop within the apocrine glands of the breast.

Megan Megan
Good to know, that it doesn’t turn into cancer.



 
 
Instead, Apocrine metaplasia is named according 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 pseudo-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.

Dr. Halls Dr. Halls
If I saw the picture below on a ultrasound, I would not know exactly what it was. I would biopsy it.


Dr. Halls Dr. Halls
And when the biopsy result shows it is benign, then everyone can relax.



 
 

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 heterogeneous calcifications. Depending on the age of the lesion, ultrasound may not be able to detect any other relevant characteristics.breast apocrine metaplasia The consensus opinion among screening physicians is therefore that features commonly associated with apocrine metaplasia, unless clearly related to corresponding ultrasound finding or clinically 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 biopsied. 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 over-expressed 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 question 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.

 

Q and A time.

  • What is apocrine metaplasia? It’s like a sweaty dandruffy guy surrounded by normal handsome men.
  • What does it mean? What are its cells? It’s cells are feeling unwanted, awkward, like a certain relative you know.
  • What if there is duct ectasia or adenosis or columnar cell change or atypia? Pathologists can outline lots of descriptive words onto their reports, like saying the girl has red hair short and curly, freckles and dimples and long eyelashes. All these words still mean it’s not cancer. It does not increase breast cancer risk.
  • What is papillary apocrine metaplasia? and what are apocrine metaplastic cells? Papillary is a word meaning that under the microscope, the cells are forming together into finger-like shapes. Whether papillary or not, it doesn’t change things. The word metaplastic means the cells are weird-looking in some way, but not in a cancer way.

 

References

  1. Hiatt KM, Pillow JL, Smoller BR., Her-2 expression in cutaneous eccrine and apocrine neoplasms. Mod Pathol. 2004 Jan;17(1):28-32
  2. Paties C, Taccagni GL, Papotti M, Valente G, Zangrandi A, Aloi F. Apocrine carcinoma of the skin. A clinicopathologic, immunocytochemical, and ultrastructural study. Cancer 1993 Jan 15;71(2):375-81
  3. Warner JK, Kumar D, Berg WA. Apocrine metaplasia: mammographic and sonographic appearances. AJR 1998;170:1375 -1379
  4. Kushwaha, AC., O’Tolle, M., Sneige, Nour. Stelling, CB., Dryden, M., Mammographic—Pathologic Correlation of Apocrine Metaplasia Diagnosed Using Vacuum-Assisted Stereotactic Core-Needle Biopsy: Our 4-year Experience. American Journal of Roentgenology (2003) 180:795-8.
  5. Rosen PP. Invasive mammary carcinoma. In: Harris JR, Lippman ME, Morrow M, Hellman S, eds. Diseases of the breast. Philadelphia: Lippincott-Raven, 1996:83 -88
  6. Consensus Meeting. Is "fibrocystic disease" of the breast pre-cancerous? Arch Pathol Lab Med 1986;110:171 -173
  7. Wellings SR, Alpers CE. Apocrine cystic metaplasia: subgross pathology and prevalence in cancer-associated versus random autopsy breasts. Hum Pathol 1987;18:381 -386
  8. Bussolati G, Cattani M, Gugliotta P. Patriarca E, Eusebi V. Morphologic and functional aspects of apocrine metaplasia in dysplastic and neoplastic breast tissue. Ann N YAcad Sci 1986;464:262-274
  9. Wells CA, McGregor IL, Makunura CN,YeOmans P.Davies ID. Apocrine adenosis: a precursor of aggressive breast cancer?J Clin Pat/ia! 1995;48:737-742
  10. Haagensen D Jr. Is cystic disease related to cancer? Am J Surg Pathol 1991; 15:687-694
  11. Elayat G; Selim AG; Wells CA. Cell turnover in apocrine metaplasia and apocrine adenosis of the breast. Annals of Diagnostic Pathology (Feb. 2010) 14(1):1-7.

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