Breast
Other nonneoplastic
Collagenous spherulosis
Editorial Board Member: Julie M. Jorns, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Minor changes: 17 November 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Collagenous spherulosis [title] breast
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Genco IS, Hajiyeva S. Collagenous spherulosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastcollageneousspherulosis.html. Accessed January 23rd, 2021.
Definition / general
- Nonneoplastic alteration characterized by spherules of basement membrane material surrounded by myoepithelial cells (Hoda: Rosen's Diagnosis of Breast Pathology by Needle Core Biopsy, 4th Edition, 2017)
- Almost always an incidental finding in association with proliferative lesions (papilloma, sclerosing adenosis and rarely carcinoma in situ) (Pathology 2017;49:181)
Essential features
- Benign proliferation with intraluminal pink basement membrane material (spherule) surrounded by myoepithelial cells
Terminology
- Collagenous spherulosis
- Simple spherulosis
- Mucinous spherulosis
- Adenoid cystic hyperplasia (not recommended due to confusion with adenoid cystic carcinoma)
ICD coding
Epidemiology
- Adult women
- Frequency < 1% of excision specimens (Hoda: Rosen's Diagnosis of Breast Pathology by Needle Core Biopsy, 4th Edition, 2017); likely underreported
Sites
- No specific site in the breast
Pathophysiology
- Unclear
- Accumulation of basement membrane material in spaces
Etiology
- Unknown
Clinical features
- Usually incidental
- Very rarely presents as mass (Pathology 2017;49:181)
Diagnosis
- Based on histologic examination of removed tissue
Radiology description
- May present as radiologic or rarely as architectural distortion, density or mass (Pathology 2017;49:181)
Prognostic factors
- No evidence of association with precancerous state (Hoda: Rosen's Diagnosis of Breast Pathology by Needle Core Biopsy, 4th Edition, 2017)
- May be seen in association with neoplastic proliferations, particularly lobular carcinoma in situ (LCIS) (Am J Surg Pathol 2006;30:20)
Case reports
- 48 year old woman with collagenous spherulosis in an adenomyoepithelioma (J Clin Pathol 2004;57:83)
- 50 year old woman with cystic mass with solid component (Breast J 2008;14:301)
- 51 year old woman with slow growing mass (Acta Cytol 2010;54:314)
- 47 year old and 51 year old women with cases of collagenous spherulosis associated with lobular carcinoma in situ (J Pathol Transl Med 2018;52:420)
- 53 year old woman with a 3.5 cm breast mass (Breast J 2000;6:199)
Treatment
- No treatment required
Gross description
- No specific gross features (usually not discernable from background breast tissue)
Microscopic (histologic) description
- Round spaces filled with acellular pink basement membrane material (spherules) (Pathology 2017;49:181)
- Spherules measure 20 - 100 μm in diameter (Hoda: Rosen's Diagnosis of Breast Pathology by Needle Core Biopsy, 4th Edition, 2017)
- Center of the spherules may be transparent but thin rim of basement membrane material always present
- Radiating stellate fibrils or microcalcifications may be seen in the spherules
- Spherules surrounded by small oval / spindle myoepithelial cells with interspersed cuboidal luminal cells
- Myoepithelial cells are uniformly present at the periphery of involved glands
- Majority associated with benign proliferative lesions, mostly intraductal papilloma
Microscopic (histologic) images
Contributed by Iskender Sinan Genco, M.D. and Sabina Hajiyeva, M.D.
Cribriform architecture
Multiple ducts
2 different sized ducts
Cribriform architecture
Partial involvement
Adjacent apocrine metaplasia
Columnar cell changes
Smooth muscle myosin heavy chain
CD10
KIT / CD117
In situ carcinoma
ER
CK5/6
Adjacent invasive carcinoma
Smooth muscle actin
Smooth muscle myosin heavy chain
Calponin
p63
PAS
Cytology description
- Hyalinized green (Papanicolaou stain) or dark purple (Giemsa stain) spherules (Cytopathology 2010;21:157)
- 20 - 60 μm in diameter
- Present in the center of epithelial clusters (Cytopathology 2002;13:116)
- Surrounded by 1 - 2 layers of small uniform oval / spindle cells (Cytopathology 2002;13:116, Acta Cytol 2010;54:314)
Cytology images
Contributed by Mark R. Wick, M.D.
FNA
Positive stains
- Myoepithelial cells:
- Cytoplasmic: alpha smooth muscle actin, smooth muscle myosin heavy chain, calponin, CK5/6 (Mod Pathol 2006;19:1351)
- Membranous: CD10 (Pathol Res Pract 2012;208:405)
- Nuclear: p63, S100 (Mod Pathol 2006;19:1351)
- Basement membrane material:
Negative stains
- Myoepithelial cells: KIT / CD117, ER and CK7 (Mod Pathol 2006;19:1351)
Electron microscopy description
- Myoepithelial cells with intracytoplasmic myofilaments (Breast J 2000;6:199)
- Spherules composed of collagen fibers and external laminar material (Ultrastruct Pathol 1998;22:239)
Videos
Breast calcifications
Sample pathology report
- Breast, left, 3 o'clock, stereotactic core biopsy:
- Lobular carcinoma in situ (LCIS) involving collagenous spherulosis, with microcalcifications (see comment)
- Comment: Immunohistochemical stain for E-cadherin is negative in LCIS, supporting the diagnosis. Controls are appropriate.
Differential diagnosis
- Adenoid cystic carcinoma:
- Invasive pattern
- Intraluminal material is denser
- Myoepithelial cells are negative for CD10
- Luminal cells are positive for KIT / CD117, negative for ER and PR
- Ductal carcinoma in situ, cribriform type:
- Cribriform spaces are rounder and more regular (cookie cutter appearance)
- No pink material present in cribriform spaces
- Cribriform spaces surrounded by luminal cells, not myoepithelial cells
- Negative for CK5/6
- Lobular carcinoma in situ, signet ring cell type:
- Intracytoplasmic vacuoles
- Negative for E-cadherin
- Some, but not all, features of low grade ductal carcinoma in situ (see above)
- Negative for CK5/6
Additional references
Board review style question #1
H&E
A premenopausal woman had a stereotactic breast core biopsy for calcifications. Microscopic examination revealed fibrocystic changes with microcalcifications as well as the microscopic finding shown above (H&E). Regarding this entity, which of the following statements is true?
- Comprised of a clonal (neoplastic) proliferation
- Epithelial cells interspersed between spaces are negative for ER
- Flattened (myoepithelial) cells around spaces are positive for CD10
- Luminal epithelial cells are positive for KIT / CD117
- Surgical excision should be performed
Board review style answer #1
C. The flattened (myoepithelial) cells around spaces are positive for CD10. The picture shows slightly expanded ducts with spaces filled with eosinophilic material. The spaces are surrounded by small oval / spindle myoepithelial cells with interspersed cuboidal luminal cells, features consistent with collagenous spherulosis. Collagenous spherulosis is a benign finding and does not require treatment. Adenoid cystic carcinoma is the main differential diagnosis which shows MYB-NFIB fusion gene, is negative for ER and PR, positive for KIT / CD117 and should be surgically excised.
Comment Here
Reference: Collagenous spherulosis
Comment Here
Reference: Collagenous spherulosis
