Breast

Invasive breast carcinoma of no special type and variants

NST (ductal)

Topic Completed: 1 September 2009

Minor changes: 12 October 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

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

Page views in 2020: 39,557

Page views in 2021 to date: 39,495

Table of Contents

Cite this page: Roychowdhury M. NST (ductal). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantductalNOS.html. Accessed October 24th, 2021.

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

Terminology

Also called invasive ductal carcinoma, no special / specific type (NST)

Clinical features

In patients > 65 years, 87% of patients have "no special type" (Crit Rev Oncol Hematol 2008;67:263)
Presence of focal neuroendocrine features has no prognostic significance (Hum Pathol 2003;34:1001)

Risk factors

Primarily genetic, hormonal or environmental
After menopause, about 40% of risk is modifiable (Am J Epidemiol 2008;168:404)

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

Rates in US > Japan / Taiwan (5:1), also high in Northern Europe, low in Asia / Africa; may be due to known risks of obesity / high fat diet (Nutr Cancer 2008;60:492) and heavy alcohol use (Am J Epidemiol 2000;152:950)
Differences diminish with immigration
Breast cancer is not associated with smoking
In Nigeria, breast cancers are high-grade, high-stage and high-proliferating, and occur at a younger age than in Western countries (Mod Pathol 2002;15:783)
Physical activity has a protective effect (J Natl Cancer Inst 2008;100:728, Breast Cancer Res Treat 2010;120:235)
Adult dietary soy foods (Am J Clin Nutr 2009;89:1920) and carotenoids (Int J Cancer 2009;124:2929) have protective effect

Other risk factors

Older age
Proliferative breast disease (see individual topics in Breast-nonmalignant chapter), particularly in situ carcinoma, and possibly concurrent multiple nonproliferative or proliferative benign breast lesions at biopsy (Clin Cancer Res 2007;13:5474)
Carcinoma of opposite breast or endometrium
Radiation exposure in young women, including women < age 30 with supradiaphragmatic radiation for Hodgkin's lymphoma (Int J Radiat Oncol Biol Phys 2009;73:69); reduced risk if also have irradiation of ovaries > 5 Gy (J Clin Oncol 2009;27:3901)
Mammographic density (J Br Menopause Soc 2006;12:186) is a highly heritable risk (Breast Cancer Res 2011;13:R132)
Birth weight > 3000 g (for cancers arising at age 50 years or less, Cancer Epidemiol Biomarkers Prev 2009;18:2447)
Previous breast biopsy (Rev Med Inst Mex Seguro Soc 2011;49:655)

American Cancer Society

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.

Invasive

Mammogram

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

AFIP

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

Cadherin

Desmin

Estrogen receptor

HER2

Ki67

p53

Popoplanin

Progesteron receptor

Angiolymphatic invasion

Various images

Podoplanin

Grading

Grade I

Low grade, mixed

Grade II

Grade III

High grade

Contributed by Semir Vranic, M.D.

HER2 (3+)

Topo II IHC

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
below

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)

Stains

Mast cells (stained with tryptase)

PR+

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

FNAB

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

CK8 / 18, CK19, CK7, EMA, e-cadherin (Am J Clin Pathol 2006;125:377), ER (70%)
Also milk fat globule, lactalbumin, CEA, B72.3, BCA225
Glycogen (60%), mucin (moderate / marked in 20%), cytokeratin 5 / 6 (30%)
S100 (10 - 45%), HER2 (15 - 30%), RCC Ma (renal cell carcinoma marker)
CD5 clone 4C7 (Arch Pathol Lab Med 2001;125:781)
Note: laminin, collagen IV and myoepithelial markers often show no or discontinuous staining