Collagenous Spherulosis of the Breast
Collagenous spherulosis of the breast is a curious finding in a breast lesion which results from an accumulation of basement membrane material in the form of eosinophilic or rarely basophilic spherules. These spherules (which are ‘circular‘ formations) will tend to demonstrate a concentric and radiating fibrillar patterns.
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Breast collagenous spherulosis is really an incidental microscopic finding, which may occur in isolation or multifocally, and it sometimes develops adjacent to benign proliferative breast lesions. However, collagenous spherulosis of the breast can also develop alongside malignant breast processes, though rarely.
The main concern surrounding this condition is that it might be misinterpreted as adenoid cystic carcinoma of the breast. Collagenous spherulosis of the breast most often occurs in association with benign lesions such as breast papilloma and florid ductal hyperplasia. But it is a very rare finding, occuring in only 1% to 2% of biopsies for hyperplastic breast lesions.
Breast collagenous spherulosis has also been referred to historically as mucinous spherulosis, or simply spherulosis. It has also been referred to as ‘adenoid cystic hyperplasia‘. It is basically an intraluminal process which partially fills breast terminal ducts or acini.
Collagenous spherulosis of the breast is generally a very small development, less than 3 mm in diameter, which is almost always an incidental microscopic finding, (in other words, something you might find accidentally while looking for something else, like breast carcinoma) and is usually confined to one medium or high power field on the microscope. It almost never presents as a ‘mass‘ on its own.
Microcalcifications in the breast tissue will prompt a biopsy
Sometimes this breast condition is analyzed by a biopsy, but usually only if microcalcifications are present. Evidence of microcalcifications would be more suspicious of a malignant process such as breast cancer in adjacent breast tissue.
Mammographically, one might encounter collagenous spherulosis of the breast as a suspicious mass or density, possibly associated with microcalcifications. (I.e. one would suspect breast carcinoma given a suspicious mass or asymmetric density, and while investigating one might then find collagenous spherulosis ‘by accident‘).
However, due to increased frequency and improvements in breast cancer screening, one might expect a perceived increase in the incidence of breast collagenous spherulosis. The screening physicians must be cautious not to overinterpret collagenous spherulosis as atypical or ductal carcinoma in situ.
Cytological and Histological features of breast collagenous spherulosis
Breast collagenous spherulosis will usually appear as an aggregate of acellular eosinophilic spherules, which gives a somewhat ‘cribriform‘ appearance. These spherules are very very small, only 20-100 microns in diameter, and usually one will find only up to 50 spherules in a given section of a breast lesion.
Usually these spherules will appear discrete and in isolation, but they may also coalesce. Spherules in breast collagenous spherulosis will quite often show fibrillar structure, which will usually appear concentric or possibly with radial spikes.
Mitosis is usually not evident
The cellular component of collagenous spherulosis of the breast will typically be a mixture of epithelial and myoepithelial elements. The myoepithelial cells will usually surround both the spherules and the lesion as a whole.
The myoepithelial cells commonly associated with breast collagenous spherulosis will usually appear as intermediate to large round hyaline spherules, cytologically bland, and virtually identical in appearance to normal duct lining cells. Usually, there is no evidence of mitosis with breast collagenous spherulosis.
Often appears in a ‘radiating‘ appearance, unlike breast cancers.
Collagenous spherulosis of the breast will normally involve the ductules and lobular acini, and usually consists of intraluminal clusters of eosinophilic spherules. These spherules are quite often found in (and appear to originate in) the spaces of fenestrated epitheliosis (also called papillomatosis).
Also, the often ‘radiating‘ appearance of collagenous spherulosis cells differ in appearance from the disorganized appearance, cellular debris, and flocculent mucin found in many in situ breast cancers.
Stains can help determine the collagen content of a breast lesion
The use of various histological stains can determine that the spherules are rich in collagen, and will usually also show that the spherules contain varying amounts of acidic mucin, elastin, membrane-like materials, and PAS-positive proteins.
The cells immediately surrounding the collagenous spherules will tend to stain positive for actin, and for keratin 8/18, which suggests a myoepithelial cell differentiation. Conventional ‘in situ‘ breast carcinomas do not typically contain the same kind of myoepithelial cells found in collagenous spherulosis.
Mucinous spherulosis of the breast is a related variant of collagenous spherulosis. It is characterized by cribiform structures which contain lightly basophilic material, embedded in a loosely mucinous a cellular background, rather than a collagenous background. Like collagenous spherulosis, it is a benign incidental finding, the only concern being that it might be misdiagnosed as certain forms of breast carcinoma.
Causes of collagenous spherulosis of the breast
There are two basic theories about the possible causes of breast collagenous spherulosis. One theory is based on ‘stromal invagination‘ based on ultrastructural observation of stromal invagination into cellular lobules. A second theory suggests that breast spherulosis is the result of extra-cellular material deposition secreted by the proliferative myoepithelium.
This latter theory seems have a greater degree of acceptance among the breast cancer experts. No matter which theory is applied to explain their appearance, there is no doubt, based on immunohistochemical and ultrastructural studies, that breast collagenous spherulosis derives from a progressive accumulation of extra-cellular material, which includes mucopolysaccharides and basement membrane materials.
Overall outlook about breast collagenous spherulosis
Collagenous spherulosis of the breast is essentially a very rare and localized pattern of deposits of basement membrane material, which could conceivably be mistaken for an atypical neoplastic proliferation of certain rare forms of breast cancer. It is clinically benign, but has to be distinguished from potentially malignant lesions such as adenoid cystic breast carcinoma and also intraductal signet-ring breast carcinoma.
Collagenous spherulosis of the breast is typically either situated within or adjacent to other benign proliferative breast changes which would include papilloma, sclerosing adenosis, and radial scars (infiltrating epitheliosis). In some cases, collagenous breast spherulosis may actually be caused by a confluence of lobular neoplasia and spherulosis.
Collagenous spherulosis of the breast is associated with benign causes about 75% of the time
Breast collagenous spherulosis will typically develop in women between the ages of about 40 to 55. According to recent studies, collagenous spherulosis of the breast is associated with benign breast lesions about 70%-80%% of time time.
In the remaining cases, collagenous spherulosis might be associated with lobular breast carcinoma around 20%-25% of the time, and with atypical ductal hyperplasia in less than 1% of cases. Interestingly, microcalcifications are found in legions involved with collagenous spherulosis approximately 25% of the time.
The presence of microcalcification can raise suspicious for potentially malignant breast cancer, so these situations tend to be investigated with biopsy.
The main point to remember is that collagenous breast spherulosis is a completely benign finding, unrelated to breast cancer and presenting no increased risk for breast cancer whatsoever.
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