Collagenous Spherulosis

Collagenous Spherulosis

Collagenous spherulosis of the breast is shown. This lesion is characterized by aggregates of eosinophilic fibrillar or hyaline spherules surrounded by an inner layer of myoepithelial cells and luminal cells.

A higher power view shows dense spherules of eosinophilic basement membrane-like material surrounded by cells. This arrangement gives the proliferation a fenestrated or cribriform appearance.



  • Collagenous spherulosis (CS)


  • Mucinous spherulosis


  • Incidental microscopic finding in 1-2% of biopsies that contain hyperplastic ductal lesions

    • Important to recognize CS because lesion may superficially resemble cribriform DCIS

    • CS may also superficially resemble low-grade adenoid cystic carcinoma



  • Incidental finding

    • Typically seen in breast tissue containing other sclerosing benign proliferative lesions

      • Includes sclerosing adenosis, papillomas, ductal hyperplasia, and atypical ductal hyperplasia

    • Calcification of CS can lead to mammographic detection and diagnosis by needle core biopsy


  • CS may be seen associated with atypical ductal hyperplasia, LCIS, or DCIS

  • Appropriate treatment is related to other lesions present


  • Benign process

  • No evidence that CS is directly associated with precancerous lesions or predisposes to future development of breast cancer


Mammographic Findings

  • CS may be detected mammographically for those lesions with calcifications


Histologic Features

  • CS characterized by lobulocentric aggregates of eosinophilic fibrillar &/or hyaline spherules of extracellular material

  • Spherules composed of varying amounts of basement membrane-like material, including polysaccharides, laminin, and type IV collagen

    • Positive staining for PAS and Alcian blue by histochemistry

    • In some cases, spherules contain mucoid-like material (“mucinous spherulosis”)

  • Spherules surrounded by inner myoepithelial layer and outer luminal layer of cells

    • Myoepithelial cells may become attenuated and difficult to appreciate in H&E sections

    • Immunohistochemical stains for myoepithelial cells (calponin, p63, myosin heavy chain) to highlight myoepithelial cells may be helpful

  • Spherules and cellular arrangement give rise to appearance of cribriform or fenestrated proliferation when viewed at low power


Low-Grade Cribriform DCIS

  • Microlumens formed and surrounded by single monotonous population of neoplastic epithelial cells

  • Nuclei of cells tend to stand apart and appear polarized around microlumens

  • Gives rise to a rigid or “punched-out” appearance due to microlumens with round or smooth internal contours

    • Microluminal spaces may be empty, contain secretions, necrotic cells, or calcifications

  • Stains to highlight myoepithelial component of CS may be helpful in difficult cases

Low-Grade Adenoid Cystic Carcinoma

  • Typically demonstrates invasive growth pattern at periphery with tumor infiltrating beyond central gross nodule

  • Tumor is composed of 2 different components

    • True glandular component (formed by luminal-type cells)

    • “Pseudoglandular” component consisting of basement membrane deposition surrounded by myoepithelial-like cells

    • Different components typically show heterogeneity in distribution throughout tumor

  • Higher grade lesions typically show areas with solid growth pattern

  • Adenoid cystic carcinomas may have luminal cells positive for C-Kit (CD117) whereas cells of CS are negative for this marker


Clinically Relevant Pathologic Features

  • Tissue distribution

    • Ductal or lobular process only

    • May involve intraductal papillomas

    • Most often seen in association with sclerosing adenosis, ductal hyperplasia, and papillomas

  • Usually incidental finding

    • Important to recognize because it can mimic other more serious processes

  • Rarely CS can be involved by lobular neoplasia

    • Neoplastic lobular cells displace indigenous luminal cells, leaving myoepithelium and spherules in place

    • May be difficult to distinguish from cribriform DCIS

    • Presence of basement membrane material and dyshesive quality of lobular cells may be helpful

    • Immunostains for E-cadherin and myoepithelial cells can identify 2 cell types

Pathologic Interpretation Pearls

  • Cribriform or fenestrated proliferation

    • Luminal spaces tend to have irregular or angulated shapes

    • Look for acellular spherules of basement membrane-like material within luminal spaces

    • Look for attenuated myoepithelial cells surrounding luminal spaces admixed with luminal cells

      • Immunostains can help to highlight different cell types

  • CS typically associated with other sclerosing and benign proliferative lesions


1. Hill P et al: Collagenous spherulosis with lobular carcinoma in situ: a potential diagnostic pitfall. Pathology. 39(3):361-3, 2007

2. Rabban JT et al: Immunophenotypic overlap between adenoid cystic carcinoma and collagenous spherulosis of the breast: potential diagnostic pitfalls using myoepithelial markers. Mod Pathol. 19(10):1351-7, 2006

3. Resetkova E et al: Collagenous spherulosis of breast: morphologic study of 59 cases and review of the literature. Am J Surg Pathol. 30(1):20-7, 2006

4. Mooney EE et al: Spherulosis of the breast. A spectrum of municous and collagenous lesions. Arch Pathol Lab Med. 123(7):626-30, 1999

5. Sgroi D et al: Involvement of collagenous spherulosis by lobular carcinoma in situ. Potential confusion with cribriform ductal carcinoma in situ. Am J Surg Pathol. 19(12):1366-70, 1995

6. Stephenson TJ et al: Nodular basement membrane deposits in breast carcinoma and atypical ductal hyperplasia: mimics of collagenous spherulosis. Pathologica. 86(3):234-9, 1994

7. Clement PB et al: Collagenous spherulosis of the breast. Am J Surg Pathol. 11(6):411-7, 1987

Image Gallery

Microscopic Features

(Left) Collagenous spherulosis image is a benign sclerosing process, typically seen with other benign sclerosing lesions. This example is associated with florid sclerosing adenosis image. The lesion gives the appearance of an intraductal proliferation; however, studies of the earliest phases suggest that the process usually affects lobules. (Right) A higher power view shows the typical fenestrated or cribriform appearance of the epithelium surrounding eosinophilic hyaline material image.

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Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Collagenous Spherulosis

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