Breast tumor

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Classification & Types of Breast Tumors

Breast tumors are broadly divided into epithelial tumors (the majority) and stromal/mesenchymal tumors. Carcinomas are further classified by two overlapping systems: morphological/histological type and molecular/biomarker type.

I. Carcinoma (Epithelial Malignancies)

A. In Situ Carcinoma (Non-Invasive)

These are confined within the ductal-lobular system with the basement membrane intact.

Type	Key Features
Ductal Carcinoma In Situ (DCIS)	Most common in situ lesion; precursor to invasive ductal carcinoma; detected on mammography as microcalcifications; when untreated, ~30-50% progress to invasive carcinoma in the same breast
Lobular Carcinoma In Situ (LCIS)	Marker of increased risk rather than a direct precursor; when invasive cancer later develops, ~2/3 arise in the same breast, ~1/3 in the contralateral breast; cells are small, rounded, and dyscohesive (E-cadherin negative)

LCIS histology - small rounded loosely cohesive cells filling acini; E-cadherin negative on IHC

Fig: LCIS. (A) H&E: dyscohesive cells filling lobular acini. (B) IHC: E-cadherin-negative LCIS vs E-cadherin-positive normal cells (bottom left). - Robbins & Cotran Pathologic Basis of Disease

B. Invasive (Infiltrating) Carcinoma

1. No Special Type (NST) - "Invasive Ductal Carcinoma"

Most common, ~75% of all invasive carcinomas
Heterogeneous group; does not fit criteria for any special subtype
Presents as a hard, irregular mass with desmoplastic stroma; grating sound on sectioning
Graded by Nottingham Histologic Score (tubule formation + nuclear pleomorphism + mitotic rate):
- Grade 1 (well differentiated): tubular/cribriform pattern, small uniform nuclei, low mitotic rate
- Grade 2 (moderately differentiated): mixed solid/glandular growth, moderate pleomorphism
- Grade 3 (poorly differentiated): ragged nests/sheets, marked pleomorphism, high mitotic rate, necrosis
"Medullary pattern" = high-grade NST with prominent tumor-infiltrating lymphocytes (TILs); previously considered a separate entity

2. Special Histologic Subtypes

Special histologic types of invasive breast carcinoma: (A) Lobular, (B) Mucinous, (C) Tubular, (D) Papillary, (E) Apocrine, (F) Micropapillary, (G) Metaplastic, (H) Secretory

Fig: Special histologic types of invasive carcinoma - Robbins & Cotran Pathologic Basis of Disease

Predominantly ER-positive / Luminal subtype:

Subtype	Morphology	Notes
Invasive Lobular Carcinoma	Dyscohesive single-file "Indian file" cords; signet ring cells with intracytoplasmic mucin; minimal desmoplasia	Most common special subtype; insidious spread, hard to detect on imaging; E-cadherin loss
Mucinous (Colloid) Carcinoma	Clusters of cells floating in large lakes of extracellular mucin; well-circumscribed	Soft, gelatinous gross appearance; better prognosis
Tubular Carcinoma	Exclusively well-formed tubules; may mimic benign sclerosing lesion	Excellent prognosis
Cribriform Carcinoma	Invasive nests with cribriform (sieve-like) morphology	Favorable prognosis
Papillary Carcinoma	True papillary fronds lined by tumor cells	Often intracystic; generally good prognosis

Predominantly HER2-positive:

Subtype	Morphology
Apocrine Carcinoma	Cells resemble apocrine sweat gland cells; enlarged round nuclei, prominent nucleoli, abundant eosinophilic granular cytoplasm
Invasive Micropapillary Carcinoma	Hollow "balls" of cells floating in intercellular fluid; mimics papillae but lacks fibrovascular cores; associated with lymphovascular invasion

Predominantly Triple-Negative (TNBC):

Subtype	Notes
Metaplastic Carcinoma	Squamous or mesenchymal (spindle, chondroid, osseous) differentiation; myoepithelial-like gene expression; poor prognosis overall
Salivary Gland-Like Carcinomas	Adenoid cystic, mucoepidermoid, secretory carcinoma; histologically identical to salivary gland counterparts; relatively favorable prognosis despite TNBC status

Clinical Presentation Subtype:

Inflammatory Breast Carcinoma - not a histologic subtype; caused by extensive dermal lymphovascular plugging by carcinoma cells; presents with erythema, skin thickening, and "peau d'orange" (skin dimpling due to tethering by Cooper's ligaments); no discrete palpable mass; usually high-grade; commonly mistaken for infection

II. Molecular (Biomarker-Based) Classification

This is the most clinically relevant classification for treatment decisions:

Molecular Group	Receptor Status	Intrinsic Subtypes	Key Features
Luminal A	ER+/PR+, HER2-, low Ki-67	Luminal A	Best prognosis; low proliferation; respond well to endocrine therapy
Luminal B	ER+/PR±, HER2-, high Ki-67 OR HER2+	Luminal B	Higher proliferation than A; less favorable prognosis
HER2-enriched	ER-, PR-, HER2+	HER2	HER2 gene amplification; responds to HER2-targeted therapy (trastuzumab)
Triple Negative (TNBC)	ER-, PR-, HER2-	Basal-like	Often BRCA1-mutated; high grade; poor prognosis; no targeted therapy historically
Normal-like	ER+, HER2-	Normal-like	Gene profile resembles normal breast; intermediate prognosis
Claudin-low	Often TNBC	Claudin-low	Low expression of cell-cell junction proteins; stem-cell-like features

The three major clinical groups used in practice are:

Luminal (ER-positive/HER2-negative) - most common; treated with endocrine therapy
HER2 - overexpression usually due to gene amplification; treated with HER2 inhibitors
TNBC - no targeted therapy; chemotherapy backbone; DNA repair defects common (BRCA1/TP53)

III. Stromal / Non-Epithelial Tumors

These arise from the two types of breast stroma:

From Intralobular Stroma (breast-specific "biphasic" tumors - contain both stromal and epithelial components):

Tumor	Notes
Fibroadenoma	Most common benign breast tumor overall; driven by MED12 mutations (same gene mutated in uterine leiomyomas); responds to estrogen; common in women aged 20-35
Phyllodes Tumor	Closely related to fibroadenoma; stromal overgrowth with leaf-like projections; ranges from benign to borderline to malignant; malignant phyllodes can metastasize hematogenously

From Interlobular Stroma:

Same mesenchymal tumors as in other tissues: lipoma, angiosarcoma (especially post-radiation), myofibroblastoma

IV. Summary Diagram

BREAST TUMORS
├── EPITHELIAL (Carcinoma) ─ ~95% of malignant breast tumors
│   ├── In Situ
│   │   ├── DCIS (ductal) → precursor to invasive
│   │   └── LCIS (lobular) → risk marker + precursor
│   └── Invasive
│       ├── No Special Type (NST) ~75% ← most common
│       └── Special Types
│           ├── Lobular (most common special type)
│           ├── Mucinous / Tubular / Cribriform / Papillary (luminal, good prognosis)
│           ├── Apocrine / Micropapillary (HER2-enriched)
│           ├── Metaplastic / Salivary gland-like (TNBC)
│           └── Inflammatory (clinical subtype, not histologic)
│
└── STROMAL / MESENCHYMAL
    ├── Intralobular: Fibroadenoma, Phyllodes tumor
    └── Interlobular: Lipoma, Angiosarcoma, Myofibroblastoma

Key points to remember:

Lifetime risk in US women: ~1 in 8 (by age 90)
~12% of breast cancers involve germline mutations; BRCA1/BRCA2 account for half of hereditary cases
High-risk genes: BRCA1, BRCA2, PALB2, TP53
NST (no special type) = ~75% of invasive carcinomas; invasive lobular = most common "special" subtype
Prognosis depends on biologic type (molecular group), grade, and anatomic stage (AJCC 8th edition combines molecular + anatomic stage into "prognostic stage")

Sources: Robbins & Cotran Pathologic Basis of Disease (9780443264528); Robbins & Kumar Basic Pathology (9780323790185)

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