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Breast malignant, males, children
In situ carcinoma
DCIS - general
Reviewer: Dina Kandil, M.D. (see Reviewers
page)
Revised: 19 January 2012, last major update January 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Neoplastic proliferation with malignant features and ductal phenotype, but confined within spaces bordered by myoepithelium and basement membrane
● May extend into lobules (cancerization of lobules)
● Variable tendency to progress to invasive carcinoma, based on nuclear grade
● Accounts for 15-30% of all breast carcinoma
Epidemiology
=========================================================================
● Mean age 50-59 years
● Five percent of women with DCIS carry a mutation in the BRCA1 or BRCA2 hereditary cancer gene
(N Engl J Med 2004;350:1430)
Clinical features
=========================================================================
● 90% diagnosed while clinically occult because of mammographic detection of microcalcifications (75% of cases), soft-tissue densities (10%), or both (15%)
● 2/3 with low to intermediate grade DCIS have multifocal disease (Hum Pathol 2007;38:1736)
● High grade DCIS tends to be more continuous
● Relative risk for invasive carcinoma of 8-10x compared to general population
● Invasive carcinoma has been reported in 14-60% of untreated women with low grade DCIS after 10 years follow-up
(N Engl J Med 2004;350:1430)
● Natural history of untreated high grade DCIS is not well characterized, since most patients have resections
● Ten fold increase in incidence in 1990’s is due to mass screening
(Breast Cancer Res Treat 2009;115:181)
● May arise in adenosis, radial scar, fibroadenoma or papilloma; rarely perineural invasion occurs
(Hum Pathol 2001;32:785)
Imaging
=========================================================================
● Mammogram shows calcifications in 70%+ of cases
● Linear calcifications are more common in comedo DCIS, while granular calcifications are more common in non-comedo types (AJR Am J Roentgenol 1992;159:483)
● 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)
Radiologic images
=========================================================================
Clusters of microcalcifications
Case reports
=========================================================================
● With osteoclast-like giant cells
(Hum Pathol 2006;37:369)
● DCIS skip lesion in nipple
(Int J Surg Pathol 2009 Jul 3 [Epub ahead of print])
Treatment and prognosis
=========================================================================
● Surgery: breast conservation therapy with negative margins; mastectomy is reserved for extensive disease
● Radiation therapy after local excision reduces ipsilateral recurrence by 50% (J Clin Oncol 2006;24:3381)
● Tamoxifen further decreases recurrence in patients with ER+ DCIS (Semin Oncol 2006;33:647)
● Possibly sentinel lymph node dissection if patients are planned for mastectomy
(Ann Surg Oncol 2008;15:268) or 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 carcinomas
● Omission of radiotherapy may be considered if DCIS is small size, 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 achieved by increasing the radiation dose to the tumor bed (Int J Radiat Oncol Biol Phys 2009;75:1021)
● See US National Cancer Institute
Risk factors for local recurrence
=========================================================================
● Positive surgical margins, high nuclear grade and presence of comedo necrosis are the most important predictors of local recurrence after lumpectomy
● Concurrent lobular neoplasia is associated with a higher risk of ipsilateral recurrence in women who receive breast conserving surgery
(Cancer 2009;115:1203)
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
● Difficult to accurately measure size
(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
Micro description / nuclear grading
=========================================================================
● Nuclear grade is determined using 6 morphologic features: nuclear pleomorphism, nuclear size, chromatin, nucleoli, mitosis and polarization
● Low grade (grade I): monotonous round cell population with subtle increase in N/C ratio, small (1.5-2.0x normal size) 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 (2.5x normal size), 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
Specific grading systems
(Am J Surg Pathol 2000;24:651):
● Van Nuys:
1: Non-high grade without necrosis
2: Non-high grade with necrosis
3: High grade with or without necrosis
(Lancet 1995;345:1154,
table)
● May guide treatment
(Cancer 1996;77:2267,
World J Surg Oncol 2008 Jun 18;6:61),
but validity has been questioned
(Cancer 2007;110:2648,
Br J Surg 2003;90:426)
● Scott (Modified Lagios system): low, intermediate, high grade; based on nuclear grade and necrosis (absent, focal, extensive,
Hum Pathol 1997;28:967)
● European Pathologists Working Group: well, intermediate or poorly differentiated; based on nuclear grade and cell polarization (absent, present/not prominent, prominent,
Semin Diagn Pathol 1994;11:167)
● Cancerization of lobules: DCIS growth pattern in which cells fill a lobule, with preservation of normal acinar pattern
Micro images
=========================================================================
Grades 1-3 (Van Nuys scoring), p53 staining
DCIS grade 1
Low grade
DCIS extending along a duct
Cancerization of lobules: extension of DCIS into intralobular ducts
No invasion identified based on myoepithelial markers present
Strong E-cadherin staining for DCIS (in background of invasive ductal carcinoma)
Not DCIS:
Infiltrative carcinoma with central necrosis
With axillary nodal metastasis
Negative staining for myoepithelial markers
Cytology images
=========================================================================
Other images:
#1;
#2;
high grade
Virtual slides
=========================================================================
DCIS
DCIS and LCIS
Positive stains
=========================================================================
● E-cadherin
(Am J Surg Pathol 2001;25:229)
● ER/PR (strong and diffuse positivity in low grade cases / variable in high grade cases
(Mod Pathol 2005;18:615)
● p53 is positive in some high grade DCIS myoepithelial cells
● Positive stains are less positive in DCIS myoepithelial cells than in those surrounding normal mammary ductal-lobular structures (Am J Surg Pathol 2009;33:227)
Negative stains
=========================================================================
● High molecular weight cytokeratin / 34betaE12
(Hum Pathol 2002;33:620,
Am J Surg Pathol 1999;23:1048)
Molecular/cytogenetics description
=========================================================================
● Allelic imbalance in region of BRCA1 gene in 74% of DCIS cases (Br J Cancer 1996;73:636)
● Low grade DCIS and high grade DCIS appear to be genetically distinct disorders
● Low grade DCIS show chromosomal losses at 16q and 17p and gains at 1 q
● High grade DCIS shows losses at 8p, 11q, 13q and 14q, and gains at 5p, 8q and 17q (J Pathol 2005;205:248)
Differential diagnosis
=========================================================================
● Lobular carcinoma in situ: E cadherin negative
● Atypical ductal hyperplasia: immunohistochemistry has no value in differentiating from low grade DCIS
● Invasive cribriform carcinoma or infiltrative ductal carcinoma with comedonecrosis: immunostains for myoepithelial cells are negative
(J Pathol 2005;205:248)
Additional references
=========================================================================
End of Breast malignant, males, children > In situ carcinoma > DCIS - general
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