Collagenous Spherulosis

Definition

• Breast lesion composed of intralumenal clusters of spherules

Alternate/Historical Names

• Mucinous spherulosis
• Spherulosis

Diagnostic Criteria

• Intralumenal process
  • Partially fills terminal ducts or acini
• Aggregate of acellular eosinophilic spherules imparts a cribriform appearance
  • 20-100 microns diameter
  • Few to 50 spherules per section of lesion
  • Usually discrete but may coalesce
  • Basophilic, mucinous variant has been reported
• Spherules show fibrillar structure, usually concentric or with radial spikes
  • Other patterns
    • Hollow with eosinophilic cuticle
    • Hyaline eosinophlic granules, 1-2 microns
  • May have associated microcalcification
• Cellular component is mixed epithelial and myoepithelial
  • Myoepithelial cells surround spherules and whole lesion
  • Small round cytologically bland cells
    • Identical in size and appearance to normal duct lining cells
  • No mitotic figures
• Nearly always an incidental microscopic finding
  • Usually confined to one medium or high power field
    • Two cases reported 2-3 mm diameter
    • May be multifocal
  • One case reported to be palpable
  • May be biopsied because of associated microcalcifications

Richard L Kempson MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting:: December 23, 2006

Supplemental studies

Immunohistology

• Myoepithelial cells present around periphery and surrounding spherules
  • Keratin positive
  • S100, actin, calponin, p63 positive, smooth muscle myosin
• Remainder of lesional cells are epithelial cells
  • Keratin positive
  • S100, actin, calponin, p63, CD117 negative
• Spherules are positive for type IV collagen

Histochemical stains

• Spherules:
  • PAS and Alcian Blue variable
    • May stain with both or either
  • Trichrome: stain blue
  • Mucicarmine positive (reported in cases with basophilic spherules)

Differential Diagnosis

Adenoid Cystic Carcinoma	Collagenous Spherulosis
Grossly visible or palpable lesion	Nearly always an incidental microscopic finding
Invasive architecture	Circumscribed, intraductal or intralobular
Uniform cores of basement membrane material	Variable, frequently fibrillar spherules
Nuclei slightly enlarged compared to normal	Nuclei identical in size and appearance to normal
CD117 positive lumenal cells	CD117 negative
Calponin, smooth muscle myosin negative (even myoepithelial component)	Calponin, smooth muscle myosin positive

Both contain myoepithelial and epithelial components

Clinical

• Three large series with age range 36-90, mean about 50 years
• Nearly always an incidental histologic finding
  • One reported palpable case
  • May be associated with microcalcifications
• Benign finding with no known significance
  • May be associated with other lesions of significance

Grading / Staging / Report

• Grading and staging are not applicable

Bibliography

• Clement PB, Young RH, Azzopardi JG. Collagenous spherulosis of the breast. Am J Surg Pathol. 1987 Jun;11(6):411-7.
• Mooney EE, Kayani N, Tavassoli FA. Spherulosis of the breast. A spectrum of municous and collagenous lesions. Arch Pathol Lab Med. 1999 Jul;123(7):626-30.
• Grignon DJ, Ro JY, Mackay BN, Ordonez NG, Ayala AG. Collagenous spherulosis of the breast. Immunohistochemical and ultrastructural studies. Am J Clin Pathol. 1989 Apr;91(4):386-92.
• Divaris DX, Smith S, Leask D, Troster M, O'Malley FP. Complex Collagenous Spherulosis of the Breast Presenting as a Palpable Mass: A Case Report with Immunohistochemical and Ultrastructural Studies. Breast J. 2000 May;6(3):199-203.
• Resetkova E, Albarracin C, Sneige N. Collagenous spherulosis of breast: morphologic study of 59 cases and review of the literature. Am J Surg Pathol. 2006 Jan;30(1):20-7.
• Rabban JT, Swain RS, Zaloudek CJ, Chase DR, Chen YY. Immunophenotypic overlap between adenoid cystic carcinoma and collagenou spherulosis of the breast: potential diagnostic pitfalls using myoepithelial markers. Mod Pathol. 2006 Oct;19(10):1351-7.