Fibrocystic changes

Apocrine adenosis / atypical apocrine adenosis

Editorial Board Member: Gary Tozbikian, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Julie M. Jorns, M.D.

Last author update: 12 January 2021
Last staff update: 29 April 2021

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PubMed Search: Apocrine adenosis "free full text" [sb]

Julie M. Jorns, M.D.
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Cite this page: Jorns JM. Apocrine adenosis / atypical apocrine adenosis. website. Accessed February 22nd, 2024.
Definition / general
  • Defined as the presence of apocrine cytology in a recognizable terminal duct lobular unit (TDLU) associated with sclerosing adenosis (J Clin Pathol 2007;60:1313)
  • Preserved 2 cell layer (inner epithelial and outer myoepithelial cells) in which the epithelial layer has prominent apocrine features
Essential features
  • Lobulocentric proliferation with distortion by stromal fibrosis / sclerosis and apocrine cytology
  • Recommended by WHO:
    • Apocrine adenosis
  • Not recommended by WHO:
    • Sclerosing adenosis with apocrine metaplasia
    • Nodular adenosis with apocrine metaplasia
  • Terminology apocrine adenosis has also been used to refer to adenomyoepithelial adenosis, a different lesion
  • Atypical apocrine adenosis (AAA): rare, defined as ≥ threefold variation in nuclear size
  • Previous (historical) names for AAA:
    • Atypical apocrine hyperplasia
    • Atypical apocrine metaplasia
ICD coding
  • ICD-10:
    • N60.3 - fibrosclerosis of breast
    • N60.8 - other benign mammary dysplasias
  • ICD-11:
    • GB20.Y - other specified benign breast disease
    • GB20.Z - benign breast disease, unspecified
  • Terminal duct lobular unit; otherwise, no specific location within the breast
  • Loss of heterozygosity in several loci (1p, 3, 11q, 16 and 17q)
  • Accumulation of losses and gains if progression through apocrine DCIS and apocrine carcinoma
Clinical features
  • Considered a part of the spectrum of fibrocystic changes
  • Often an incidental finding or detected by screening
  • Can present as a palpable mass if nodular adenosis / adenosis tumor
  • Histologic examination of tissue with or without immunohistochemistry
Radiology description
  • Variable depending on the size / extent of breast involvement
  • If focal, may not be visualized (i.e. incidental finding on histologic examination)
  • Amorphous or pleomorphic clustered microcalcifications; architectural distortion or circumscribed to spiculated mass on mammogram
  • Irregular, noncircumscribed mass on ultrasound is associated with upgrade to malignancy on resection (J Ultrasound Med 2020;39:1517, Breast J 2017;23:569)
Prognostic factors
  • Increased risk of cancer of 1.5 - 2 times, as seen with proliferative fibrocystic changes
  • Atypical apocrine adenosis (AAA): conflicting evidence of increased cancer risk
    • Study of 37 patients showed no increased risk for carcinoma (Arch Pathol Lab Med 2012;136:179)
    • Study of 37 patients showed the relative risk of developing carcinoma was 5.5 (95% CI 1.9 - 16), with age association - all patients developing cancer were > 60 years at diagnosis of AAA (Cancer 1996;77:2529)
    • Upgrade risk: surgical resection showed carcinoma only in patients with coexisting carcinoma present on core biopsy (N = 10) in a study of 41 patients with apocrine adenosis (N = 29) and atypical apocrine adenosis (N = 12) (Ann Diagn Pathol 2016;24:4)
Case reports
  • 37 year old woman with atypical apocrine adenosis diagnosed via fine needle aspiration (Acta Cytol 2002;46:369)
  • 54 year old woman with atypical apocrine adenosis diagnosed via incidental discovery on coronary angiogram CT (Cureus 2020;15:e8624)
  • 66 year old woman with nodular atypical apocrine adenosis with monoclonality via restriction fragment length polymorphism (RFLP) (Histopathology 2001;38:221)
  • Presence of apocrine adenosis alone in a core biopsy does not require surgical excision
  • Coexisting atypia typically prompts surgical consultation, although excision is controversial based on limited prognostic data
Gross description
  • Variable depending on extent of involvement and calcifications
  • May be indistinguishable from surrounding breast tissue
  • Multinodular, ill defined cuts with increased resistance due to fibrosis
  • Gritty due to frequent calcifications but no chalky yellow white foci or streaks as seen in fat necrosis
  • Circumscribed to ill defined white, fibrotic mass if nodular adenosis / adenosis tumor
Microscopic (histologic) description
  • Cells with apocrine metaplasia have abundant eosinophilic cytoplasm with bright eosinophilic granules that are PAS positive
  • Apocrine cells have round nuclei and may show nuclear pleomorphism (≥ threefold in atypical apocrine adenosis); a central, round, eosinophilic nucleolus is generally seen
  • Rare multinucleation may be observed and is not considered atypical
  • Rare to no mitosis
  • No necrosis
Microscopic (histologic) images

Contributed by Julie M. Jorns, M.D.
Distortion, apocrine features

Distortion, apocrine features

Apocrine features

Apocrine features

Distortion, cytologic atypia

Distortion, cytologic atypia

Cytologic atypia

Cytologic atypia

Virtual slides

Images hosted on other servers:

Atypical apocrine adenosis

Cytology description
  • Often highly cellular
  • Cells have apocrine metaplasia with prominent nucleoli and pleomorphism, possibly resembling carcinoma but minimal hyperchromasia
  • Naked nuclei are present (Diagn Cytopathol 2007;35:296)
Cytology images

Contributed by Volodymyr Shponka, M.D.
Fine needle aspiration

Fine needle aspiration

Negative stains
Electron microscopy description
  • Distinct basal lamina present
Sample pathology report
  • Left breast, core biopsy:
    • Fibrocystic changes, including apocrine adenosis with microcalcifications
Differential diagnosis
  • Apocrine carcinoma:
    • Infiltrative growth
    • Associated desmoplasia
    • Lack of myoepithelium
  • Cancerization of lobule by apocrine DCIS:
    • Architectural atypia: expansile glandular involvement by atypical, monotonous cells
    • Other architectural patterns of DCIS are typically also present (e.g. comedo, cribriform, etc.)
    • Mitosis and necrosis frequently identified
  • Microglandular adenosis:
    • Glands are smaller, more regular
    • Lacks myoepithelial cells
  • Tubular adenosis:
    • Haphazard proliferation of elongated tubules
Board review style question #1

The above pictured lesion was from a breast biopsy for mammographically detected calcifications. The area of concern was successfully biopsied. What are the next steps in patient care?

  1. Excision
  2. Magnetic resonance imaging (MRI)
  3. Neoadjuvant chemotherapy
  4. Observation
  5. Rebiopsy
Board review style answer #1
D. Observation. The pictured lesion is apocrine adenosis with microcalcifications. There is no significant atypia present; thus, this biopsy is benign and concordant with imaging findings and the patient can be observed with routine screening. There is no need to rebiopsy, excise, do additional imaging or initiate any therapies.

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Reference: Apocrine adenosis
Board review style question #2
What feature is present in apocrine ductal carcinoma in situ (DCIS) but is lacking in atypical apocrine adenosis (AAA)?

  1. Calcifications
  2. Cytologic atypia
  3. Epithelial expansion
  4. Myoepithelium
  5. Prominent nucleoli
Board review style answer #2
C. Epithelial expansion. Atypical apocrine adenosis (AAA) and apocrine ductal carcinoma in situ (DCIS) share features of apocrine cytology, including enlarged nuclei with prominent nucleoli and eosinophilic cytoplasm, as well as significant cytologic atypia and an intact myoepithelial cell layer. Both may also have calcifications; however, apocrine DCIS is differentiated from AAA by architectural atypia or epithelial expansion by clonal, monotonous cells.

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Reference: Apocrine adenosis
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