Breast
Other nonneoplastic
Collagenous spherulosis

Editorial Board Member: Julie M. Jorns, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Iskender Sinan Genco, M.D.
Sabina Hajiyeva, M.D.

Minor changes: 14 May 2021

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PubMed Search: Collagenous spherulosis [title] breast

Iskender Sinan Genco, M.D.
Sabina Hajiyeva, M.D.
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Cite this page: Genco IS, Hajiyeva S. Collagenous spherulosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastcollageneousspherulosis.html. Accessed May 17th, 2021.
Definition / general
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
    ICD-10:
  • N60.8 - other benign mammary dysplasias
  • N60.9 - unspecified benign mammary dysplasia

    ICD11:
  • GB20.Y - other specified benign breast disease
  • GB20.Z - benign breast disease, unspecified
Epidemiology
Sites
  • No specific site in the breast
Pathophysiology
  • Unclear
  • Accumulation of basement membrane material in spaces
Etiology
  • Unknown
Clinical features
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
Case reports
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

Cribriform architecture

Multiple ducts

Multiple ducts

2 different sized ducts

2 different sized ducts

Cribriform architecture

Cribriform architecture

Partial involvement Partial involvement

Partial involvement


Adjacent apocrine metaplasia

Adjacent apocrine metaplasia

Columnar cell changes

Columnar cell changes

Smooth muscle myosin heavy chain

Smooth muscle myosin heavy chain

CD10

CD10

KIT / CD117

KIT / CD117

In situ carcinoma

In situ carcinoma


ER

ER

CK5/6

CK5/6

Adjacent invasive carcinoma

Adjacent invasive carcinoma

Smooth muscle actin (SMA)

Smooth muscle actin

Smooth muscle myosin heavy chain (SMMHC)

Smooth muscle myosin heavy chain

Calponin

Calponin


p63

p63

PAS PAS

PAS

Cytology description
Cytology images

Contributed by Mark R. Wick, M.D.
FNA

FNA

Negative stains
Electron microscopy description
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
  • Atypical ductal hyperplasia:
    • Some, but not all, features of low grade ductal carcinoma in situ (see above)
    • Negative for CK5/6
  • 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?

    1. Comprised of a clonal (neoplastic) proliferation
    2. Epithelial cells interspersed between spaces are negative for ER
    3. Flattened (myoepithelial) cells around spaces are positive for CD10
    4. Luminal epithelial cells are positive for KIT / CD117
    5. 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
    Board review style question #2
    Collagenous spherulosis Collagenous spherulosis Collagenous spherulosis


    A 34 year old woman was diagnosed with invasive ductal carcinoma on core biopsy and subsequently underwent surgical excision. One of the surgical specimen sections showed the microscopic lesion with cribriform architecture (middle) adjacent to invasive carcinoma. Based on the provided H&N, SMMH, and PAS stains, what is the correct diagnosis?

    1. Atypical ductal hyperplasia
    2. Collagenous spherulosis
    3. Ductal carcinoma in situ
    4. Lobular carcinoma in situ involving ductal carcinoma in situ
    5. Usual ductal hyperplasia
    Board review style answer #2
    B. Collagenous spherulosis

    The H&E slide shows invasive carcinoma (upper), benign breast tissue (right lower), and a duct with cribriform architecture (middle). SMMH highlights the myoepithelial cells around the cribriform spaces and the periphery of the involved duct, whereas invasive carcinoma is negative for SMMH. This lesion with cribriform architecture represents collagenous spherulosis. PAS stain highlights the basement membrane material within the cribriform spaces produced by the surrounding myoepithelial cells. The other options may also show cribriform architecture but do not have myoepithelial cells surrounding the cribriform spaces. PAS stain helps confirm the diagnosis of collagenous spherulosis, but does not entirely rule out the other options.

    Comment Here

    Reference: Collagenous spherulosis
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