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Breast-nonmalignant
Fibrocystic disease
Collagenous spherulosis of breast
Reviewer: Hind Nassar, M.D. in January 2009 (see Authors page)
Revised: 6 October 2012, last major update May 2010
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.
Definition
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● Rare benign change occurring in proliferative lesions (papilloma, florid ductal hyperplasia) and characterized by intraluminal spherules (Am J Surg Pathol 1987;11:411)
Terminology
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● Also described as “adenoid cystic hyperplasia”
Epidemiology
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● In 1-2% of biopsies with hyperplastic lesions (Rosen’s Breast Pathology, page 130)
Etiology
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● The spherules consist of basement membrane material
Clinical features
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● Almost always an incidental finding, only rarely presents as a mass
● Associated with intraductal papilloma, sclerosing adenosis, radial sclerosing lesions; also LCIS (Am J Surg Pathol 1995;19:1366)
Case reports
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● 48 year old woman with adenomyoepithelioma (J Clin Pathol 2004;57:83)
● 54 year old woman with DCIS (Pathologica 2002;94:317)
Treatment
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● Requires no treatment by itself, but may be associated with malignancy
Gross description (Macroscopy)
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● Usually multifocal, 1 to 3 mm (not visible grossly)
Micro description (Histopathology)
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● Intraluminal clusters of eosinophilic or rarely basophilic (“mucinous spherulosis”, Arch Pathol Lab Med 1999;123:626), collagen-rich spherules within spaces, surrounded by flattened myoepithelial cells; spherules can calcify
● Associated with LCIS (25%) and microcalcifications (25%, Am J Surg Pathol 2006;30:20)
Micro images
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Tubular adenosis with features Within adenomyoepithelioma
of collagenous spherulosis
Adenoid cystic carcinoma (first column) vs. collagenous spherulosis (second column)
p63 c-kit p63 and c-kit
Cytology description
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● Hyaline pink globules surrounded by benign myoepithelial cells in Giemsa stained smears (Cytopathology 2002;13:116)
● Note: cytological evidence of spherulosis also suggests intraductal papilloma (Cytopathology 2009 Mar 7 [Epub ahead of print])
Mucinous spherulosis:
● Cribriform structures with lightly basophilic material embedded in loosely mucinous acellular background
● Intermediate to large, round hyaline spherules are naked or surrounded by myoepithelial cells
● Diff-Quik stain shows fibrillary radial appearance (Diagn Cytopathol 2006;34:626)
Positive stains
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Myoepithelial cells:
● Smooth muscle actin, smooth muscle myosin heavy chain, calponin
● p63 (nuclear staining, examine at high power, Mod Path 2006;19:1351)
Negative stains
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Myoepithelial cells:
● c-kit/CD117
Electron microscopy descriptions
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● Epithelial cells and myoepithelial cells plus associated basement membrane-like material (Breast J 2000;6:199)
Differential Diagnosis
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● Adenoid cystic carcinoma: denser and tightly nodular material is rarely degenerated, stromal invasion, CD117+ luminal cells, calponin and smooth muscle actin negative, may have collagenous spherulosis-like structures (Pathol Int 2004;54:332)
● Cribriform DCIS: multiple secondary lumens with round, regular spaces having sharp borders that appear to be made from “cookie-cutters”; no amorphous pink material within lumens
● Signet ring variant of lobular carcinoma
Additional references
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End of Breast-nonmalignant > Fibrocystic disease > Collagenous spherulosis of breast
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