Mucinous Spherulosis of the breast
Mucinous spherulosis of the breast is a rare variant of breast collagenous spherulosis. A spherulosis is basically a breast lesion composed of intraluminal clusters of spherules. And in some cases these intraluminal spaces contain only clusters of mucoid material, in which case this feature of the lesion is more appropriately termed ‘mucinous‘ spherulosis.
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The cells immediately surrounding these spherules tend to be myoepithelial in nature. Mucinous spherulosis of the breast is extremely rare, occuring is less than 0.5% of biopsy samples screening for potential breast cancer. The average age in which women will develop either mucinous or collagenous spherulosis is about 50 years.
Cytological features of mucinous spherulosis of the breast
Cytologically, breast mucinous spherulosis is characterized by cribriform structures containing lightly basophilic material, and embedded in a loosely mucinous a cellular background. One will typically see large to intermediate-size round spherules, which are either ‘naked‘ or surrounded by myoepithelial cells.
Mucinous spherulosis of the breast will usually present as an aggregate of a cellular eosinophilic spherules which are very small, less than 100 microns in diameter. These are small, round, and cytologically bland cells which are in many respects identical in size and appearance to normal duct lining cells, so they usually require a ‘second look‘ just to be sure.
Immunohistological features common to mucinous breast spherulosis
In terms of immunohistochemistry, mucinous spherulosis of the breast will typically show reactivity with smooth muscle actin and focally with cytokeratin. A minority of cases of spherulosis seem to be composed of a predominately ‘basophilic‘ material, and these situations are often termed ‘mucinous breast spherulosis‘.
(Note, a ‘basophilic‘ material is one in which certain elements of the tissue are ‘stained‘ readily by a ‘basic‘ dye, the most commonly used being haematoxylin. Collagenous spherulosis tends to stain more readily with an ‘eosinophilic‘ dye, while the mucinous variant of breast collagenous spherulosis gives a prominent positive reaction to basophilic dyes.)
Breast mucinous spherulosis often shows distinct septa
The appearance of the basophilic materials in breast lesions involving spherulosis is not consistent, but seems to present variably in both character and distribution. But the most common pattern for the basophilic/mucinous variant of breast spherulosis is one in which there is a central floccular aggregate with radiating spokes that merges with scalloped projections at the periphery.
The periphery of the sphere-shape common to mucinous and collagenous spherulosis is often marked by an eosinophilic cuticle of variable thickness and staining intensity, which can be associated with a myoepithelial cell nucleus. Mucinous spherulosis of the breast often additionally displays distinct septa, composed of thin strands of eosinophilic material with myoepithelial and occasional epithelial cell nuclei, presented in a radial pattern.
Differences between mucinous and collagenous forms of breast spherulosis
In about 80-85% of cases, mucinous spherulosis appears admixed with collagenous spherulosis. In fact, the coexistence of collagenous and mucinous types of breast spherulosis would tend to suggest that the mucinous form is simply an earlier stage of the same disease process.
Myoid breast spherulosis contains mucinous and collagenous elements
In some respects, one could use the term ‘myxoid‘ to describe a breast spherulosis pattern containing both collagenous and mucinous elements, which is a more all-encompassing term more accurately describing the accumulation of connective tissue mucopolysaccharides. However, the term ‘mucinous‘ spherulosis of the breast best describes the localized accumulation of basophilic material in an intraductal location.
Longitudinal orientation confirms a myoepithelial cell phenotype
In a mucinous spherulosis of the breast, myoepithelial cells are more easily appreciated by the recognition of a ‘change of orientation‘ of the cells adjacent the spherule. They form a more ‘longitudinal‘ orientation which confirms a myoepithelial cell phenotype, and this of course may be confirmed with staining for actin.
Myoepithelial cells are more easily identified in collagenous breast spherulosis
Identification of myoepithelial cells is easier in collagenous breast spherulosis than mucinous spherulosis of the breast, as the accumulation of basement membrane material and collagen in the former makes their nuclei more apparent.
Mucinous and collagenous breast spherulosis tend to occur in conjunction with other common breast neoplasms
Mucinous spherulosis will often occur in connection to a complex hyperplasia, perhaps containing foci of sclerosing adenosis, or elements of atypical ductal hyperplasia. Mucinous spherulosis of the breast can sometimes also occur in conjunction with intraductal papilloma, fibroadenoma, lobular neoplasia of the breast, and other fibrocystic changes.
Mucinous and collagenous breast spherulosis can often be misdiagnosed as breast carcinoma
Collagenous spherulosis and mucinous spherulosis of the breast are frequently incorrectly diagnosed, and of more concern, are mistakenly identified as atypical or malignant in up to 28% of cases.
Breast collagenous and mucinous spherulosis are incorrectly diagnosed as invasive breast carcinoma in up to 11% of cases. Failure to correctly identify mucinous and collagenous breast spherulosis can naturally lead to over-estimations of breast cancer risk and inappropriate treatments.
Basophilic mucin may be present in a variety of intraductal breast, so some of the ways in which collagenous and mucinous spherulosis may be differentiated are by close attention to the pattern and distribution of the basophilic material and also the shape and margin of the space in which this is present.
But the most important differentiating feature of mucinous and collagenous breast spherulosis is the nature of the adjacent cells. Unfortunately, the potential for mistaking mucinous spherulosis of the breast as a cribiform pattern of breast carcinoma is increased when nearby ductal cells have even slightly atypical features.
But this misdiagnosis is quite easily avoided if the pathologist searches for the thin cuticle that is variably present in cases of spherulosis.
Causes of breast mucinous spherulosis
It is not clear what brings about a mucinous breast spherulosis, but for a variety of reasons it does seem that it is brought about as a result of an intraductal proliferation. The actual stimulus for the formation of spherules in a breast lesion is unclear, but the apparent association of these features with radial scars suggests that a localized pattern of breast fibrosis might create an environment which promotes their development.
There may be an association with radial scars
Collagenous and mucinous spherulosis of the breast appear to be related lesions derived from a progressive accumulation of extra-cellular materials, which may include mucopolysaccharides, collagen IV, and laminin.
It is believed that the mucinous form of spherulosis is an ‘early stage‘, which transforms into collagenous spherulosis of the breast at the ‘end-stage‘ of the lesion. (The mucinous form is not a ‘degeneration‘ of the collagenous form, which was believed to be the case at one time).
The stimulus for spherule formation is unclear, but the association with radial scars suggests that localized patterns of fibrosis may serve as a promoting environment.
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