Breast
Ductal carcinoma in situ
DCIS

Editor-in-Chief: Debra Zynger, M.D.
Gary Tozbikian, M.D.

Topic Completed: 20 May 2020

Minor changes: 21 June 2020

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PubMed Search: DCIS [title] pathology review [PT]

Gary Tozbikian, M.D.
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Cite this page: Tozbikian G. DCIS. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantdcis.html. Accessed July 13th, 2020.
Definition / general
  • Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of mammary ductal epithelial cells confined to the ductal-lobular system without evidence of invasion through the basement membrane into the surrounding stroma (Arch Pathol Lab Med 2009;133:15)
  • Is a nonobligate precursor lesion of invasive breast cancer (Breast Cancer Res Treat 2010;123:757, Cancer 2005;103:2481)
  • Encompasses a heterogeneous group of lesions in terms of histomorphology, underlying genetic alterations, biomarker expression profile and biologic potential for progression to invasive carcinoma
Essential features
  • Neoplastic proliferation of mammary ductal epithelial cells that is confined within ducts and lobules
  • Nonobligate precursor of invasive breast disease
  • Heterogenous entity with wide range of histologic appearances, growth patterns, genetic abnormalities and clinical behavior
Terminology
  • Ductal carcinoma in situ (DCIS)
  • Intraductal carcinoma
  • Ductal intraepithelial neoplasia: terminology never widely adopted and removed from the 4th Edition WHO classification of mammary neoplasms (International Agency for Research on Cancer: WHO Classification of Tumours of the Breast, 4th Edition, 2012)
  • Mammary intraepithelial neoplasia: a general term to include both ductal and lobular intraepithelial neoplasia but never adopted, terminology should not be used (Am J Surg Pathol 1991;15:209, Hum Pathol 2002;33:620, Am J Surg Pathol 1980;4:241)
  • Extensive DCIS / extensive intraductal component: terminology should only be used to describe DCIS that is associated with invasive carcinoma in which the DCIS component constitutes > 25% of the entire area of invasive carcinoma and DCIS extends beyond the invasive carcinoma into the surrounding breast tissue (Pathol Annu 1988;23:1)
  • Multicentric DCIS: no uniform definition, generally refers to DCIS that involves multiple breast quadrants and different distinct regions of the breast
ICD coding
  • ICD-10: D05.1 - intraductal carcinoma in situ of breast
  • ICD-0: 8500/2 - intraductal carcinoma, noninfiltrating, NOS
Epidemiology
Sites
  • Breast
  • Can occur in axillary breast tissue
Clinical features
Diagnosis
  • Calcifications or distortion on imaging raises concern and need for obtaining tissue
  • Diagnosis is made by histologic examination of tissue obtained via needle core biopsy, lumpectomy or mastectomy
Radiology description
Radiology images

Images hosted on other servers:

Microcalcifications detected by mammography and tomosynthesis

Microcalcifications detected by mammography

Irregular mass via ultrasound

MRI of an irregular mass


MRI of a linear enhancement

Prognostic factors
Case reports
Treatment
Gross description
  • Usually no gross lesion, but high grade DCIS may present as firm gritty mass with multiple yellow punctate flecks on the cut surface representing comedonecrosis
  • Serial sequential sampling with mammographic correlation is useful to estimate DCIS size (Arch Pathol Lab Med 2009;133:31, Arch Pathol Lab Med 2009;133:26)
Microscopic (histologic) description
  • DCIS traditionally classified based on architectural growth pattern (no clinical relevance other than comedo pattern):
    • Cribriform:
      • Fenestrated proliferation with multiple, round, rigid extracellular lumens with punched out appearance
      • Neoplastic cells are frequently evenly distributed equidistant and polarized with long axis of cell perpendicular to the central lumen
      • Trabecular bars comprised of rigid rows of cells with long axes perpendicular or at least not parallel to the long axis of the bar
      • Roman bridges comprised of curvilinear trabecular bars connecting two portions of the epithelial lining
    • Micropapillary:
      • Papillary fronds and tufts lacking fibrovascular cores projecting into duct lumen
      • Papillae often have club shaped cells comprising the micropapillae are uniform in appearance
      • Tips of fronds may fuse, forming bridges and arcades
    • Papillary:
      • Papillary fronds containing prominent fibrovascular septa projecting into duct lumen, papillary cores generally lack myoepithelial cell layer
    • Solid:
      • Lumen of ducts or lobules filled with sheets of cohesive cells
      • Cells are evenly spaced especially in low or intermediate grade DCIS
    • Flat or clinging:
      • 1 - 2 layers of generally high grade malignant cells lining a gland with a large empty lumen
    • Comedo:
      • Central expansile necrosis containing cellular debris, generally associated with high grade DCIS, frequently associated with course microcalcifications
  • No universally accepted grading system for DCIS but more recently endorsed classification systems stratify DCIS by nuclear grade (low, intermediate, high) and presence or absence of necrosis (Lancet 1995;345:1154, Hum Pathol 1998;29:1056, Cancer 1997;80:1798, Surg Clin North Am 1990;70:853)
  • Nuclear grade:
    • Low grade:
      • Monotonous, round nuclei with smooth contours, small size nuclei (size of normal ductal epithelial cell or 1 - 1.5 diameter of normal red blood cell)
      • Diffuse fine chromatin, absent or indistinct nucleoli, no or rare mitotic figures, necrosis is uncommon but does not preclude the diagnosis of low grade DCIS
    • Intermediate grade:
      • Moderate pleomorphism, mild to moderate variability in nuclear size
      • Variably course chromatin, occasional nucleoli, infrequent mitoses, features in between low and high grade DCIS
      • Loss of monotony can mimic usual ductal hyperplasia
    • High grade:
      • Prominent pleomorphism, large size nuclei (> 2.5 size of normal ductal epithelial cell)
      • Vesicular chromatin with irregular distribution, prominent nucleoli, frequent mitoses, comedo necrosis frequent but not required
  • Necrosis:
  • Myoepithelial cell layer surrounding ducts spaces containing DCIS is intact, but may be attenuated especially in high grade DCIS
  • Associated stromal reaction (chronic inflammatory infiltrate, fibrosis/sclerosis) may be prominent in areas surrounding DCIS, especially in high grade DCIS and does not indicate invasion
  • Cancerization of lobules, extension of DCIS into acini of terminal duct lobular unit
  • Variants include apocrine, cystic hypersecretory, squamous, spindle cell, clear cell, signet ring cell, mucinous, small cell, others
Microscopic (histologic) images

Contributed by Gary Tozbikian, M.D.

Low grade, cribriform

Intermediate grade, cribriform


Intermediate grade, papillary and cribriform

Intermediate grade, papillary

Intermediate grade, solid

Intermediate grade, micropapillary


High grade, flat

High grade, solid


High grade, solid and cribriform

Virtual slides

Images hosted on other servers:

Intermediate grade, solid, comedo necrosis

Intermediate grade,
solid and cribriform,
comedo necrosis and
microcalcifications

Intermediate grade, cribriform, microcalcifications

Cytology description
Cytology images

Images hosted on other servers:

Low grade

High grade

Positive stains
Negative stains
Molecular / cytogenetics description
  • Low grade DCIS and high grade DCIS are genetically distinct
  • Low grade has frequent chromosomal losses at 16q and 17p and gains at 1q
  • High grade has frequent losses at 8p, 11q, 13q and 14q, and gains at 5p, 8q and 17q (J Pathol 2005;205:248)
  • High grade DCIS has similar molecular profile as invasive breast cancer (Cancer Res 2015;75:3980)
Sample pathology report
  • Right breast, 10:00 calcifications with ribbon clip, stereotactic core needle biopsy:
    • Ductal carcinoma in situ (DCIS), intermediate nuclear grade, solid and cribriform patterns with comedo necrosis and microcalcifications
      • Immunohistochemical biomarker results: Estrogen receptor positive (90%, strong intensity), Progesterone receptor positive (40%, moderate intensity)
Differential diagnosis
  • Usual type ductal hyperplasia:
    • Heterogenous proliferation of cells with variable size/shape, that are irregularly distributed with cohesive or syncytial growth, haphazard orientation of nuclei, nuclear overlap, nonrigid peripheral slit-like fenestrations with nuclei parallel to the lumina
    • Heterogeneity can mimic intermediate grade DCIS
    • Variable or mosaic pattern of expression of CK5/6 and CK5 and estrogen receptor
  • Atypical ductal hyperplasia:
    • Architectural and cytologic features suggestive of but not diagnostic for a diagnosis of low grade DCIS, partial involvement of ducts, limited quantitative extent
  • Lobular carcinoma in situ:
    • Low grade discohesive cells, often feathery clear space between cells, with solid growth pattern, intracytoplasmic vacuoles, lack of polarization around luminal spaces
    • Reduced or absent membranous expression of E-cadherin, cytoplasmic reactivity for p120
  • Invasive cribriform carcinoma:
  • Adenoid cystic carcinoma:
  • Collagenous spherulosis:
    • Pseudolumens containing nodules of flocculent blue-grey basement membrane enclosed by cuticle of basement membrane and surrounded by stellate myoepithelial cells
    • Lacks true cribriform spaces with ductal epithelial cells polarized around true lumens
    • Can be involved by atypical lobular hyperplasia or lobular carcinoma in situ
    • Myoepithelial markers (p40 / p63 / SMMS / calponin / CK5/6 and CK5) highlight myoepithelial cell component
  • Lymphovascular invasion:
    • Surrounding space is lined by endothelial cells, lymphatic spaces often adjacent to blood vessels
    • Lack circumscription by most myoepithelial markers (p40 / p63 / CK5/6 and CK5), circumscribed by endothelial markers (CD31, ERG) and also circumscribed by SMMS
  • Gynecomastia:
    • Micropapillae have tapered (nonclubbed) configuration, features of usual type ductal hyperplasia (cellular heterogeneity, haphazard, nonuniform distribution)
  • Solid papillary carcinoma:
    • Solid growth pattern punctuated by delicate fibrovascular cores, perivascular pseudorosettes, neuroendocrine features, extracellular mucin
    • Lack circumscription by myoepithelial markers (p40 / p63 / SMMS / calponin / CK5/6 and CK5) at periphery of nodules
Board review style question #1
    Which of the following statements regarding DCIS is correct?

  1. Adjuvant anti endocrine therapy reduces the risk of local recurrence in patients with DCIS who have undergone breast conserving surgery with radiation therapy
  2. DCIS is generally a clinically and mammographically occult lesion
  3. Low grade DCIS is a nonobligate precursor lesion to high grade DCIS
  4. Recommended standard biomarkers to evaluate and report in patients with DCIS include estrogen receptor, progesterone receptor, and HER2
  5. Sentinel lymph node sampling is not indicated in patients with DCIS only, as the disease is noninvasive and there is no risk of metastatic involvement of axillary lymph nodes
Board review answer #1
A. DCIS is a nonobligate precursor lesion to invasive breast cancer. Molecular studies have demonstrated that low and high grade DCIS are genetically distinct biologic entities. DCIS most often presents mammographically as microcalcifications. Per ASCO/CAP guidelines, currently the only recommended biomarker for DCIS is estrogen receptor, while testing for progesterone receptor is optional. Unlike for invasive breast carcinoma, HER2 is not assessed in patients with DCIS only as anti HER2 therapy is not indicated. Sentinel lymph node sampling has a role in subset of DCIS only patients, the reported positive rate is 0.4 - 13.7% (mostly isolated tumor cell deposits and micrometastases) presumably due to missed or undersampled invasive disease. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 trial, tamoxifen reduced the likelihood of ipsilateral recurrence at five years from 9 - 6%, and also reduced the risk of a tumor in the contralateral breast. (J Clin Oncol 2014;32:1365, Lancet 1999;353:1993)

Reference: DCIS - general

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Board review style question #2

    A 55 year old woman undergoes a stereotactic core needle biopsy for mammographically detected microcalcifications. Which statement is true regarding the grade and expected immunohistochemical staining pattern of this lesion?

  1. Negative for circumferential calponin and p63
  2. Positive (Score 3+) for HER2 by immunohistochemistry
  3. Reduced or absent membranous reactivity for E-cadherin
  4. Strongly, diffusely positive for estrogen receptor
  5. The lesion is high grade
Board review answer #2
D. The biopsy shows low grade DCIS with a cribriform pattern and associated microcalcifications. Loss of E-cadherin expression is seen lobular neoplasia. Myoepithelial markers such as calponin and p63 will show retained myoepithelial cell layer surrounding foci of DCIS. Assessment of HER2 status in DCIS is not indicated per current guidelines, however HER2 overexpression is more often observed in high grade DCIS. Low grade DCIS typically shows strong estrogen receptor expression.

Reference: DCIS - general

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