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Breast malignant, males, children
In situ carcinoma
DCIS – general

Author: Cansu Karakas, M.D. (see Authors page)

Revised: 10 August 2016, last major update August 2016

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: DCIS [title]

Table of Contents
Definition / general | Epidemiology | Clinical features | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Additional references
Cite this page: DCIS - general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantDCIS.html. Accessed July 14th, 2017.
Definition / general
  • Defined as “noninvasive or intraductal cancer”
  • Neoplastic proliferation of 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)
  • May extend into lobules (cancerization of lobules)
  • Represents 20 - 25% of newly diagnosed breast cancers (American Cancer Society: Cancer Facts & Figures 2016)
  • DCIS is not a single disease, but encompasses a heterogeneous group of lesions in terms of morphology, underlying genetic alterations and biomarker expression
  • Several clinical studies have corroborated the hypothesis that DCIS is a precursor lesion of invasive breast cancer (Breast Cancer Res Treat 2010;123:757, Cancer 2005;103:2481)
Epidemiology
Clinical features
  • Mostly detected by mammography as microcalcifications (76% of cases), soft tissue densities (11%) or both (13%)
  • Can be detected incidentally during breast evaluation for an unrelated problem (Schnidt: Biopsy Interpretation of the Breast, 2012, 51–95)
  • Between 14 and 50% of DCIS lesions are estimated to progress to invasive lesions if left untreated (Breast Cancer Res Treat 2006;97:135)
  • Relative risk for invasive carcinoma of 8 - 10x compared to general population
  • Women diagnosed with DCIS have 10x higher risk of developing ipsilateral invasive breast if the lesion is left untreated (N Engl J Med 2004;350:1430, Cancer 1982;49:751)
  • Histologic parameters of clinical significance in DCIS include: architectural subtype, nuclear grade, presence or absence of microcalcifications and necrosis, estimate of size/extent of lesion, status of margins
Radiology description
  • Mammogram shows calcifications in 90%+ of cases,
  • In 75%, microcalcifications are the only radiologic finding; in 15%, calcifications coexist with a soft tissue abnormality
  • In 10%, DCIS manifests as a mass or architectural distortion on mammography (Eur J Radiol 2005;54:55)
  • Fine linear and fine linear branching morphologic features are usually associated with high grade DCIS, while amorphous calcifications are more common in low grade DCIS (Acta Radiol 2011;52:481)
  • Despite these findings, there are significant overlaps between the mammographic appearance of these lesions, and it has been shown that fine pleomorphic calcifications are the most common appearance for both high grade and non high grade lesions (Radiographics 2013;33:1569, Acta Radiol 2011;52:481)
  • MRI may be a useful adjunct to detect non calcified DCIS (Breast J 2005;11:382)
  • 30% of patients with non calcified DCIS have false negative imaging (J Ultrasound Med 2009;28:903)
Prognostic factors
    Risk factors for local recurrence:
Case reports
Treatment
  • Clinical treatment of DCIS is surgical excision with clear margins
  • Currently, treatment options for DCIS include breast conserving surgery (BCS) alone, BCS plus radiotherapy, and mastectomy
  • Careful assessment of clinical and pathologic factors related to the risk of recurrence is important to identify patients eligible for ablative treatment compared to BCS, and subgroups that may be treated by BCS without mastectomy
  • Radiation reduces the risk of recurrence by 50% in patients undergoing breast conserving therapy (J Clin Oncol 2008;26:1247)
  • Tamoxifen further decreases the risk of ipsilateral and contralateral recurrence in patients with ER+ DCIS (Breast Cancer Res Treat 2002;75:S7, Semin Oncol 2006;33:647)
  • Possibly sentinel lymph node dissection if patients are planned for mastectomy or who have DCIS size > 5 cm (Am J Surg 2008;196:81), or at high risk of microinvasive carcinoma (Breast J 2008;14:135)
  • Approximately half of recurrences are DCIS and half are invasive carcinoma
  • Omission of radiotherapy may be considered if DCIS is small, low grade and has wide, clear margins (J Clin Oncol 2009;27:3211)
  • In selected patients with close (< 2 mm) or focally / minimally involved margins, reexcision may be avoided and satisfactory local control may be achieved by increasing the radiation dose to the tumor bed (Int J Radiat Oncol Biol Phys 2009;75:1021)
  • Mastectomy may be recommended for multicentric DCIS, inability to attain clear surgical margins, large tumor size or diffuse microcalcifications on imaging studies
  • See US National Cancer Institute-PDQ
Gross description
  • Usually no gross lesion, but high grade DCIS may present as firm gritty mass with multiple areas of round, pale comedonecrosis
  • Must carefully examine specimens to exclude small foci of invasive carcinoma
  • For helpful guidelines on specimen handling and reporting, including methods to estimate DCIS size, see Arch Pathol Lab Med 2009;133:31, Arch Pathol Lab Med 2009;133:26

  • Measuring methods include:
    • Serial sequential sampling - map each block on sliced specimen radiograph and do 3D reconstruction; accurate but difficult
    • Calculate size based on areas of calcification
    • Record number of blocks involved by DCIS and multiply by 0.3 cm to 0.4 cm
    • Measure largest extent of DCIS on single slide - accurate if DCIS is present on only 1 slide
    • Mapping method - average thickness of each slice x number of consecutive slices with DCIS
Microscopic (histologic) description
  • DCIS has been classified based on architectural pattern, including comedo, cribriform, micropapillary, solid or mixed subtypes
  • Furthermore, DCIS is classified qualitatively by nuclear grade and presence / absence of necrosis (Arch Pathol Lab Med 2009;133:15)
  • Low grade (grade I): monotonous round cell population with subtle increase in N / C ratio, small (diameter of 1.5 - 2.0 red blood cells) monotonous round nuclei with smooth contours, diffuse fine chromatin, no / indistinct nucleoli; no / rare mitotic figures; polarized toward luminal spaces
  • High grade (grade III): nuclei are large (diameter > 2.5 red blood cells), markedly pleomorphic and angular with irregular contours, coarse chromatin, prominent nucleoli, frequent mitoses, usually not polarized toward luminal spaces
  • Intermediate grade (grade II): between high grade and low grade
  • Grade heterogeneity is common; place cases into higher category if 30% or more ducts are involved by higher grade cells
  • Van Nuys Prognostic Index: quantifies and gives a combined score of five known risk factors including margin status, histologic subtype, necrosis, tumor size and patient age, which help predict local recurrence (J Natl Cancer Inst Monogr 2010;2010:193)
  • A 2010 pathological classification system showed that women with high grade DCIS and a pure (> 50%) solid architecture with extensive necrosis (> 50%) had significantly worse outcome than those with high nuclear grade alone (Mod Pathol 2010;23:S8)

  • Molecular biomarkers in DCIS:
Microscopic (histologic) images

Images hosted on PathOut servers:

       

Courtesy of Cansu Karakas, M.D.



 

Cancerization of lobules: extension of DCIS into intralobular ducts

 

Strong E-cadherin staining for DCIS (in background of invasive ductal carcinoma)



Images hosted on other servers:

Grades 1 - 3 (Van Nuys scoring), p53 staining

High nuclear grade

 

Cancerization of lobules: extension of DCIS into intralobular ducts



No invasion identified

 

Not DCIS: Infiltrative carcinoma with central necrosis

With axillary nodal metastasis

Negative staining for myoepithelial markers

Cytology images

Images hosted on other servers:

Many carcinoma cells

Monomorphism of the tumor cells

High grade

Positive stains
Molecular / cytogenetics description
  • Low grade DCIS and high grade DCIS appear to be genetically distinct disorders
  • Low grade DCIS has chromosomal losses at 16q and 17p and gains at 1q
  • High grade DCIS has losses at 8p, 11q, 13q and 14q, and gains at 5p, 8q and 17q (J Pathol 2005;205:248)
  • Most high grade DCIS lesions have similar molecular profiles as invasive breast cancer (Cancer Res 2015;75:3980)
Differential diagnosis
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