This document summarizes several benign proliferative breast diseases: fibroadenomas, which are the most common breast tumor in young women; adenomas including tubular, lactating, and apocrine types; intraductal papillomas which involve the terminal duct lobular unit; adenosis such as blunt duct, sclerosing, and nodular types; microglandular adenosis; and fibrocystic breast disease. Many of these conditions are associated with a mildly increased 1.5-2 fold risk of developing breast carcinoma later in life. The document provides microscopic features and differences between variants to help distinguish between types.
3. 1. FIBROADENOMA
Introduction:
● Most common breast tumor especially in young women
● Biphasic tumor composed of proliferation of both epithelial and stromal
components
● Variants:
Juvenile fibroadenoma
Myxoid fibroadenoma
Complex fibroadenoma
5. 1. FIBROADENOMA
Microscopic appearance:
Two recognized growth pattern in the glandular component
Intracanalicular Pericanalicular
Glands are compressed into
linear branching structures
Glands retain open
lumens
Both patterns can co-exist in the same lesion
6. 1. FIBROADENOMA
Variants of fibroadenoma with unknown significance
Morphologic variations such as hyalinization, calcification, metaplastic change are
common. Some of the rare morphologic variations are squamous metaplastic
change and apocrine metaplasia.
Variants of fibroadenoma with clinical significance
Myxoid fibroadenoma
Cellular fibroadenoma
7. 1. FIBROADENOMA
Differences between important variants of fibroadenoma
Variants Juvenile Myxoid Cellular Complex
Age Usually young but not
always
Young women
Associated with
carney complex
Can occur at any age Usually older age
Microscopic
appearance
Increased epithelial and
stromal cellularity
Epithelial >Stromal
hyperplasia
(Pericanalicular pattern)
Abundant pale,
blue-gray extracellular
matrix material
(myxoid) in the stroma
Diffuse stromal
hypercellularity
Cysts > 3 mm,
sclerosing adenosis,
microcalcifications or
papillary apocrine
metaplasia
Risk of breast
carcinoma
No increased risk Same as classic
fibroadenoma
Same as classic
fibroadenoma
Increased relative
risk (1.5 - 2.0)
Molecular MED12 exon 2 mutation Lack MED 12 (usually
seen in classic
fibroadenoma)
Higher rates of
mutation in PIK3CA
and MAP3KI
MED12 exon 2
mutation
9. 2. ADENOMA
Tubular adenoma:
● A type of ductal adenoma with tubular features has been found to be associated with the
above-mentioned Carney syndrome.
● Needs to be differentiated from carcinoma.
Lactating adenoma:
● Microscopically, proliferated glands are seen lined by actively secreting cuboidal cells.
● This lesion should be distinguished from the proliferative and secretory changes brought on
by pregnancy in a preexisting fibroadenoma.
10. 2. ADENOMA
Apocrine adenoma:
● This exceptionally rare lesion should be distinguished from fibrocystic disease with focally
prominent apocrine changes and from well-differentiated apocrine carcinoma.
Nipple adenoma:
● Occurs in the fifth decade, almost always unilateral.
● Retained myoepithelial layer
● Florid ductal hyperplasia, papilloma like pattern
11. 3. INTRADUCTAL PAPILLOMA
● Central intraductal papilloma: arises from large lactiferous ducts, usually solitary
● Peripheral intraductal papilloma: involves terminal duct lobular unit, usually multiple
(papillomatosis)
● Frequently associated with usual type ductal hyperplasia and apocrine metaplasia, less
frequently squamous, osseous or chondroid metaplasia may be seen
● Myoepithelial cell markers are positive in fibrovascular cores and at the periphery of the
involved duct
12. 4. ADENOSIS
Types
Blunt duct adenosis
Sclerosing adenosis
Nodular adenosis and related lesions
Microglandular and adenomyoepithelial adenosis
13. 4. ADENOSIS
Blunt duct adenosis
● Very common, shows blunting of both epithelial and myoepithelial cells.
Sclerosing duct adenosis
● Very common, shows blunting of both epithelial and myoepithelial cells.
● Increased risk of cancer of 1.5 - 2x.
● Myoepithelial cells may vary from being prominent to
indistinct on routine H&E staining
● Myoepithelial cells are readily apparent via
immunohistochemistry
14. 4. ADENOSIS
Nodular adenosis
● Nodular adenosis combines features of blunt duct adenosis and sclerosing adenosis.
Microglandular adenosis
Typical microglandular adenosis Atypical microglandular adenosis
● Glands lined by single layer of cuboidal / flat
cells with vacuolated / granular cytoplasm and
bland nuclei
● Increased complexity including multilayered
epithelium, fused glandular units, luminal
bridging, cribriform architecture
● Mild cytologic atypia, hyperchromatic
nuclei, prominent nucleoli, occasional mitotic
figures
15. 4. ADENOSIS
Microglandular adenosis
● Lumen consists of PAS-positive diastase resistant secretions
● Myoepithelial cells are absent, but immunohistochemistry with collagen IV can highlight basement
membrane.
● Cells of microglandular adenosis express cytokeratins, S 100, cathepsin D and EGFR (Her 1)
● Associated carcinomas include adenoid cystic, secretory and squamous, matrix producing and triple
negative, basal-like carcinomas.
16. 4. ADENOSIS
Complex sclerosing lesion (Radial scar)
● Low power stellate configuration
● Myoepithelial cells are intact
● Imaging features include irregular spiculated mass with dense center frequently mimicking
invasive carcinoma
