Invasive breast carcinoma of no special type and variants

NST (ductal)

Last author update: 1 September 2009
Last staff update: 10 March 2022

Copyright: 2002-2022,, Inc.

PubMed Search: Ductal carcinoma [title] breast (Review[ptyp] "loattrfree full text"[sb])

Monika Roychowdhury, M.D.
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Cite this page: Roychowdhury M. NST (ductal). website. Accessed May 18th, 2022.
Definition / general
  • Most common type of invasive breast carcinoma (75 - 80%)
  • Lacks features of any other subtypes (i.e. is a diagnosis of exclusion)
  • Arises from terminal duct lobular unit (as does lobular carcinoma), not ductal epithelium, so nomenclature is not actually accurate
  • Also called invasive ductal carcinoma, no special / specific type (NST)
Clinical features
Risk factors

Genetic risk factors
  • First degree relatives with breast cancer; having one first degree relative (mother, sister, daughter) creates a relative risk of 2 - 3x, higher if relative is affected before age 50 or had bilateral disease (Int J Cancer 1997;71:800); relative risk with two first degree relatives is 4 - 6x
  • Li-Fraumeni syndrome (germline p53 mutations) - 25% of patients develop breast cancer
  • Mutations of BRCA1 and BRCA2 genes are associated with familial breast cancer at an early age, account for 20 - 60% of familial breast cancer, but only 5% of all cases
  • Cowden's disease (multiple hamartoma syndrome) - autosomal dominant, due to 10q mutation: 30 - 50% risk of breast cancer (DCIS or invasive ductal carcinoma) by age 50; also benign skin tumors (Hum Pathol 1998;29:47)
  • Heterozygous carriers for ataxia-telangiectasia have an 11% risk of breast cancer by age 50
  • Blacks (compared to whites) have more frequent breast cancers in women < age 40; present with higher stage tumors with higher nuclear grade that are more likely ER / PR negative, have higher mortality rate
  • Women have 100x risk of breast cancer compared to men

Hormone related risk factors
  • Early menarche
  • Late menopause
  • Nulliparity
  • Having first child after age 30
  • Postmenopausal women with obesity (BJOG 2006;113:1160) or estrogen producing ovarian tumors
  • Women using combined hormone replacement therapy with progestins, or estrogens alone (Int J Cancer 2007;121:645)
  • Risk with oral contraceptives is controversial, but see Mayo Clin Proc 2006;81:1290
  • Proposed mechanism of hormonal related risk factors is strong or prolonged estrogen stimulation, which may allow secretion of growth promoters

Factors associated with reduced risk of breast cancer:
  • Oophorectomy before age 35 or first child before age 18
  • Obesity prior to age 40 - due to anovulatory cycles and lower progesterone levels in late cycle

Environmental risk factors
Other risk factors
Case reports
  • 50 year old woman with diffuse neuroendocrine differentiation in a morphologically composite mammary infiltrating ductal carcinoma (Arch Pathol Lab Med 2003;127:e131)
  • 71 year old woman with poorly differentiated tumor containing central necrosis, and resembling comedo DCIS (Case of the Week #236)
Clinical images

Contributed by Mark R. Wick, M.D.



Fungating, breast skin

Spot film

Gross description
  • Firm, poorly circumscribed, contracts from surrounding tissue, hard cartilaginous consistency, grating sound when scraped, streaks of chalky white elastotic stroma penetrating surrounding stroma ("crab like"), calcification
  • Large tumors have hemorrhage, necrosis and cystic degeneration
  • May be fixed to chest wall and cause skin dimpling or nipple retraction
Gross images

Contributed by Mark R. Wick, M.D.

Various images


Ductal carcinoma

Microscopic (histologic) description
  • Sheets, nests, cords or individual cells
  • Tubular formations are prominent in well differentiated tumors but absent in poorly differentiated tumors
  • Tumor cells are more pleomorphic than lobular carcinoma
  • Stroma usually desmoplastic and may obscure tumor cells
  • Calcification in 60% of cases, variable necrosis
  • Elastosis involves wall of vessels and ducts and causes grossly noted chalky streaks
  • Often DCIS (up to 80%), perineural invasion (28%)
  • Mitotic figures are often prominent
  • Mast cells are associated with low grade tumors
  • Uncommon features: eosinophils (BMC Cancer 2007;7:165), intraluminal crystalloids (Arch Pathol Lab Med 1997;121:593)
  • No myoepithelial cell lining (as seen in DCIS or benign lesions)
  • Melanotic: combination of ductal carcinoma and melanoma
  • Angiolymphatic invasion:
    • In 35% - differs from tissue retraction because:
      • Occurs outside margin of carcinoma
      • Does not conform precisely to space it is in
      • Endothelial lining is present and is CD31+, Factor VIII+
      • Blood vessels are in vicinity
Microscopic (histologic) images

Scroll to see all images:

Contributed by Mark R. Wick, M.D.

Cancerization of lobules

Ductal NOS

Involving skin

Pseduo DCIS



Estrogen receptor





Progesteron receptor

Angiolymphatic invasion

Various images



Grade I

Low grade, mixed

Grade II

Grade III

High grade

Contributed by Semir Vranic, M.D.

HER2 (3+)


AFIP images

Common histologic features

Occult invasive carcinoma and DCIS (arrows)

Perineural invasion


Primary tumor, lymphocytic
infiltration and fibrous stromal
reaction, contains invasive
carcinoma around duct with DCIS

Angiolymphatic invasion

Arrow: possible blood vessel invaded by carcinoma

Elastic stain accentuates
venous elastica involved
by carcinoma and artery


Not angiolymphatic invasion, shrinkage artifact
with partly necrotic tumor in space created by
shrinkage, no endothelial cells are present,
elastic stain highlights elastic tissue in walls
of vessels; marked lymphoplasmacytic infiltrate

Images hosted on other servers:

Common histologic features

Resembling comedo DCIS but negative for myoepithelial markers (cocktail)

Multinucleated giant cells (fig 3c, arrows)


Mast cells (stained with tryptase)


Calponin negative (normal ducts are positive)

Common histologic features

Perineural invasion

Cytology description
  • Can use cellular pleomorphism, nuclear size, nuclear margin, nucleoli, naked tumor nuclei and mitoses to assess cytologic tumor grade, which correlates with histologic grade (Diagn Cytopathol 2003;29:185)
Cytology images

Contributed by Mark R. Wick, M.D.

Needle biopsy


Diff quik

Contributed by Dr. Abdulaziz Mohamed

47 year old woman with 3 x 2 cm painless retroareolar mass and ipsilateral axillary lymphadenopathy

Positive stains
Negative stains
Molecular / cytogenetics images

Contributed by Mark R. Wick, M.D. and Semir Vranic, M.D.


TOP2A CEP17 FISH - no gene amplification

Electron microscopy description
  • Glandular differentiation (microvilli and terminal bars on luminal side)

Differential diagnosis
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