Category Archives: Breast

Organ Systems, Breast

Breast – Complex Sclerosing Lesion (Radial Scar)

As the name indicates a complex sclerosing lesion is “complex” in that it has multiple parts, which contribute to is “scar-like” appearance.  These lesions can be detected frequently by mammography mimicking invasive carcinoma, and subsequently leads to biopsy.
 
These lesions contain a combination of different patterns discussed elsewhere, including sclerosing adenosis, papilloma, usual type hyperplasia (UTH), and fibrosis.  The architecture of this lesion is around a central area of compressed entrapped ducts within fibrosis, which radiate outward with varying dilation of duct structures and present of epithelial hyperplasia.
 
Complex scoring lesions are not neoplastic but are associated with a 1.5-2x increased relative risk for breast carcinoma.
Breast lesions and risk of developing an invasive carcinoma
Breast Cancer Risk Chart
Breast Cancer Risk Chart
References

Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015.

Organ Systems, Breast

Breast – Sclerosing Adenosis

Sclerosing Adenosis (SA) is an increased density of duct-lobular acini, which characteristically are compressed in the central portion of the lesion with dense stroma/fibrosis.  Sometimes these lesions can closely mimic an invasive ducatal carcinoma, immunohistochemistry is necessary to separate lesions.
 
SA is not a neoplastic process, but is associated with a 1.5-2X increased relative risk for breast carcinoma.
Breast lesions and risk of developing an invasive carcinoma
Breast Cancer Risk Chart
Breast Cancer Risk Chart
References
Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015.

 

Organ Systems, Breast

Breast – Usual Type Epithelial Hyperplasia (UTH)

Non-neoplastic luminal proliferation of ductal epithelial and myoepithelial cells, which can fill and expand ductal strucutures.  The morphology shows a mixed cellularity pattern with overlapping nuclei, which often have a “streaming” appearance.  In challenging cases immunohistochemistry can help differentiated these lesions from ADH or DCIS.
 
If present only focally, there is not an increased risk of breast carcinoma.  However, moderate to florid usual type hyperplasia is associated with a 1.5-2X increased relative risk of breast carcinoma.
 
 
Breast - Usual Type Hyperplasia
Usual type hyperplasia of the breast showing an intraductal proliferation of epithelial and myoepithelial cells with overlapping nuclei and streaming.
Breast lesions and risk of developing an invasive carcinoma
Breast Cancer Risk Chart
Breast Cancer Risk Chart
References

Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015. 

Organ Systems, Breast

Breast – Fibrocystic Change

This is a non-proliferative lesion characterized clinically as small lumps, which do not carry an increased risk of breast carcinoma.  Fibrocystic changes have three characteristic features, which may be present in part or whole, and include:  
  • Adenosis – Increased ductal acini density.  Calcification may be present as well as other epithelial changes such as flat epithelial atypia (see separate discussion).
  • Cystic change – Cysts (typically of varying sizes) lines by flat atrophic epithelium or apocrine metasplasia are characteristic.  Calcification are also common.
  • FIbrosis – Areas of fibrosis are characteristically present, and are thought to originate from chronic inflammation secondary to ruptured cysts.
Breast - Fibrocystic Change
Dilated duct structures with apocrine changes (low power).
Breast - Fibrocystic Change
Fibrocystic change with apocrine metaplasia and micropapillary formation.
Breast - Fibrocystic Change
Duct dilation in fibrocystic change (low power).
References

Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015.

Breast, Organ Systems

Micropapillary Breast Carcinoma

Key features
  •  Aggressive course
  •  High rate of axillary lymph node metastasis (66–100%)
  •  Morphology– tubulealveolar, morular clusters (spongelike), micropapillary
  •  Frequent calcifications, including psammoma bodies (42–67%)
  •  EMA (epithelial membrane antigen) has reverse membrane staining (outer border of cells)
  •  Receptor status
    • ER: 62–91% +
    • PR: 46–72% +
    • HER-2: 36-81% +
      • HER-2 FISH amplified tumors may have 1+ (negative) or 2+ (equivocal) staining by IHC, and it is recommended that IHC and FISH be used in cases with micropapillary pattern.

Continue reading Micropapillary Breast Carcinoma →

Organ Systems, Breast

Breast – Flat Epithelial Atypia (FEA)

Flat epithelial atypia (FEA) probably represents one of the earliest morphologically detectible findings towards the development of low-grade in situ and invasive carcinomas and lobular neoplasia.  Molecular studies have shown recurrent loss of 16q, which is characteristic of low grade lesions, and gene expression profiles similar to low-grade in situ and invasive carcinomas.  In the past there have been many other terms used to characterize a heterogeneous spectrum of lesions that fall under the umbrella of FEA:  “small ecstatic ducts lined by atypical ductal cells with apocrine snouts,” “clinging in situ duct carcinoma flat type,” atypical cystic duct,” “DIN 1-flat type,” and “columnar alteration with prominent apical snouts and secretions with atypia.”  The important take home point is that there must be low-grade atypia present to fall within this category.  No atypia, then it will be described in another way (e.g. columnar cell change).  If the atypic is “high-grade,” then the diagnosis of DCIS (clinging carcinoma) is warranted.

Continue reading Breast – Flat Epithelial Atypia (FEA) →

Organ Systems, Breast

Lobular Carcinoma In Situ (LCIS)

Lobular Carcinoma In Situ (LCIS)
  • Neoplastic proliferation within ducts/lobules (fill and expand lobules)
  • Associated with loss of expression of E-Cadherin
  • Incidental finding (not associated with calcifications or stromal reactions found by mammography)
  • LCIS is bilateral 20-40% of cases
  • Morphology
    • Mucin-positive signet ring cells often present
    • E-Cadherin negative cells
    • Uniform cells with oval/round nuclei
    • Pagetoid spread (cells present between the myoepithelial layer and over lying luminal epithelium 
    • Typically ER/PR positive
    • Her-2 is not overexpressed
  • 1%/year risk of developing an invasive tumor (similar to low-grade DCIS) – Lifetime risk is ~25-35% (20-30 year time period)
  • Cancer risk is equal in contralateral breast (unlike DCIS)
  • Pleomorphic variant of LCIS
    • High grade nuclei
    • May be ER negative
    • Some may overexpress Her-2
    • May be separate entity from typical LCIS
Photomicrographs
Breast - Lobular Carcinoma In Situ (LCIS)

LCIS characterized by filling and expansion of the lobular unit.

Breast - Lobular Carcinoma In Situ (LCIS)
LCIS characterized by filling and expansion of the lobular unit.
Breast - Lobular Carcinoma In Situ (LCIS)
LCIS characterized by filling and expansion of the lobular unit.
References

Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015.  p. 1045.

Breast, Organ Systems

Breast – General

Most patients with breast symptoms present with pain, nipple discharge, palpable mass, or “lumpiness”.  However, presentation of breast cancers most commonly present with an abnormal mammogram followed by a palpable mass, and as pain or nipple discharge and a small percentage of patients.  For a mass to be palpable, it has to be approximately 2–3 cm in size.  Mammography  can detect smaller non palpable lesions at about one half of the size of  palpable masses (1 cm).  Mammography identifies abnormalities is either densities or calcifications.  (Robbins, page 1045–1 046).
  Breast symptoms
  •   Pain
    • Common symptom which is often cyclic with menses
    • Localized pain more commonly associated with trauma, ruptured cyst, infection or idiopathic
    • Pain is the presenting symptom in 10% of breast cancers 
  •  Nipple discharge
    • Large duct papilloma-bloody/serous discharge
    • Milky discharge–elevated prolactin, hypothyroidism, drug effect
    • Malignancy risk
      • 7%, women < 60 y/o
      • 30%, women >60 y/o
  •  Palpable mass
    • Lesions must be 2–3 cm to be clinically palpable
    • Most palpable lesions are benign, but finding is not specific
    • Malignancy risk
      • 10%, women < 40 y/o
      • 60%, women > 50 y/o
  •  Location distribution of breast carcinomas
    • Upper outer quadrant – 50%
    • Central / subareolar region – 20%
    • Remaining quadrants – 10%
Breast lesions and risk of developing an invasive carcinoma
Relative
Risk
Absolute
Risk
(lifetime)
Breast
Lesion
1
3%
1.5 – 2
5-7%
4 – 5
13-17%
8 – 10
25-30%
References

Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015.

Organ Systems, Breast, WHO Classification

Breast – Normal IHC Expression

Normal breast ducts and lobules are lined by a 2-cell layer composed of luminal and myoepithelial cells.  There are also interspersed “basal” cells, which probably represent the epithelial progenitor cells.
 
IHC Marker
Luminal Cells
Myoepithelial Cells
LMWCKs
(CK7/8/18)
Positive
Negative
Variable Expression
Negative
HMWCKs
(CK5/14/17)
Negative
Positive
SMA
Negative
Positive
Negative
Positive
Negative
Positive
SMA=Smooth Muscle Actin, SMM-HC=Smooth Muscle Myosin Heavy Chain
 
An understanding of the normal IHC expression pattern in breast ductal tissue is important when considering IHC use in the differential diagnosis of breast pathology.
References
Hicks DG. Immunohistochemistry in the diagnostic evaluation of breast lesions. Appl Immunohistochem Mol Morphol. 2011;19(6):501–505. doi:10.1097/PAI.0b013e31822c8a48.
 
Liu H. Application of immunohistochemistry in breast pathology: a review and update. Arch Pathol Lab Med. 2014;138(12):1629–1642. doi:10.5858/arpa.2014-0094-RA.