Table of Contents
Definition / general | Terminology | Clinical features | Risk factors | Case reports | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Virtual slides | Positive stains | Negative stains | Molecular / cytogenetics images | Electron microscopy description | Videos | Differential diagnosis | Additional referencesCite this page: Roychowdhury M. NST (ductal). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantductalNOS.html. Accessed January 22nd, 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)
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
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
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)
- 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
- In 35% - differs from tissue retraction because:
Microscopic (histologic) images
Scroll to see all images:
Contributed by Mark R. Wick, M.D.
Angiolymphatic invasion
Grading
AFIP
Common histologic features

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

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
Angiolymphatic invasion
Grading
Stains
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
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
Negative stains
- CK20
- Myoepithelial markers: p63 (positive in benign lesions, Am J Surg Pathol 2001;25:1054), CD10 (Mod Pathol 2002;15:397), calponin
Molecular / cytogenetics images
Electron microscopy description
- Glandular differentiation (microvilli and terminal bars on luminal side)
Videos
Differential diagnosis
- Cases with necrosis may resemble DCIS (J Med Case Reports 2007;8:83)
Additional references