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Breast-malignant, males, children

In situ carcinoma - DCIS (intraductal carcinoma) - general

Author: Nat Pernick, M.D, PathologyOutlines.com, Inc.

Reviewer: Daniel Visscher, M.D., University of Michigan Hospitals, February 2009 (see Reviewers page)

Revised: 15 August 2009

Last major update: July 2009

Definition

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● Neoplastic proliferation with malignant features and ductal phenotype, but confined to epithelial compartment (i.e. within spaces bordered by myoepithelium and basal lamina)

● May involve ducts or lobules

● Variable tendency to progress to invasive carcinoma, based on nuclear grade

● Accounts for 15-30% of all breast carcinoma

Epidemiology

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● Mean age 50-59 years

● Similar clinical factors in blacks versus whites (Cancer 2009;115:3181)

Features

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● Most cases are clinically occult / detected by mammography, but some present with nipple discharge or palpable lesion

● Rare lesions have nodal metastases for unclear reasons

● Often multifocal, particularly low grade DCIS (Hum Path 2007;38:1736); 10-20% develop contralateral in situ or invasive carcinoma, either synchronous [at same time] or metachronous [at a different time]

● May have regressive changes (Appl Immunohistochem Mol Morphol 2009 Apr 29 [Epub ahead of print])

● Relative risk for invasive carcinoma of 8-10x compared to general population

● Evolution to invasive disease may take decades (particularly for low grade lesions, Cancer 2005;103:2481), or be very short

● Increased 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 Path 2001;32:785)

X-ray

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● MRI may be a useful adjunct to mammography and ultrasound (Hong Kong Med J 2008;14:229)

● 30% of patients with non-calcified MRI have false negative imaging (J Ultrasound Med 2009;28:903)

X-ray images

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Clusters of microcalcifications

Case reports

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● With osteoclast-like giant cells (Hum Path 2006;37:369)

● DCIS skip lesion in nipple (Int J Surg Pathol 2009 Jul 3 [Epub ahead of print])

Treatment and prognosis

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● Surgery (including breast conserving) and radiation therapy; low risk of local recurrence (J Surg Oncol 2009;100:25)

● Some studies have deferred radiation for small (<1 cm) or low grade lesions (Pathol Oncol Res 2008;14:179)

● Radiation reduces ipsilateral recurrence (Cochrane Database Syst Rev 2009 Jul 8;(3):CD000563), but see Surgeon 2009;7:146

● Radiation may eradicate precursor lesions in addition to residual disease (AJSP 2003;27:828, AJCP 2007;128:1023)

● Concurrent lobular neoplasia is associated with a higher risk of ipsilateral recurrence in women who receive breast conserving surgery (Cancer 2009;115:1203)

● 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)

● Possibly tamoxifen if ER+ (Semin Oncol 2006;33:647)

● 30-50% of disease recurrences represent invasive disease at or near tumor site

● Must be vigilant about getting annual surveillance mammography post-diagnosis (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 Apr 20 [Epub ahead of print])

● See US National Cancer Institute

Risk factors for recurrence

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● Ipsilateral - comedonecrosis, micropapillary histology, multifocality

● Contralateral - micropapillary histology, gross size of 1 cm or more (AJCP 2007;128:86)

Gross description

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● 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), methods include

(a) serial sequential sampling - map each block on sliced specimen radiograph and do 3D reconstruction; accurate but difficult

(b) calculate size based on areas of calcification

(d) measure largest extent of DCIS on single slide - accurate if DCIS is present on only 1 slide

(e) mapping method - average thickness of each slice x number of consecutive slices with DCIS

Microscopic description / grading

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● Based on cytologic features of neoplastic cells

● Interobserver agreement is poor if no standardized criteria are used

● Low grade: 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; cells resemble LCIS; usually no/rare comedo-type necrosis, no/rare mitotic figures; usually cribriform, micropapillary, papillary or solid subtypes

● High grade: nuclei are large (2.5x normal size), markedly pleomorphic and angular with irregular contours, coarse chromatin, prominent nucleoli; frequent mitoses; comedo-type necrosis (central zone of necrosis within a duct) nearly always present and often extensive; often amorphous microcalcifications

● Intermediate grade: between high grade and low grade; either (a) cells resemble low grade, but some ducts contain intraluminal necrosis, or (b) nuclei have coarse chromatin and occasional nucleoli and variable necrosis

● Grade heterogeneity is common; place cases into higher category if 30% or more ducts are involved by higher grade cells

● Specific grading systems (AJSP 2000;24:651):

● Van Nuys: 1, 2 or 3: based on nuclear grade (low, intermediate, high grade) and necrosis (not applicable, absent, present) (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)

● Modified Lagios: low, intermediate, high grade: based on nuclear grade and necrosis (absent, focal, extensive) (Hum Path 1997;28:967)

● Holland: well, intermediate or poorly differentiated; based on nuclear grade and cell polarization (absent, present/not prominent, prominent) (Semin Diagn Pathol 1994;11:167)

● Lobular cancerization: a DCIS growth pattern in which cells fill a lobule, with preservation of normal acinar pattern

Micro images

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Grades 1-3 (Van Nuys scoring), p53 staining Low, intermediate, and high grade

DCIS grade 1 Low grade

DCIS extending along a duct

Cancerization of lobules

Solid expansion of acini Extension of DCIS into Marked pleomorphism is more

and ductules intralobular ducts (AFIP) typical of DCIS than LCIS

Lobular cancerization

Perineural invasion Tumor in dermal lymphatics, attributed

to benign mechanical transport

CD10 and smooth muscle actin No invasion identified based on

myoepithelial markers present

Preservation of myoepithelial

layer (smooth muscle actin)

ER and HER2 staining

NOT DCIS

Infiltrative carcinoma with central necrosis With axillary nodal Negative staining for

metastasis myoepithelial markers

Cytology images

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Other images: #1; #2; high grade

Virtual slides

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DCIS

DCIS and LCIS

Positive stains

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● E-cadherin (AJSP 2001;25:229)

● ER+ in low grade cases / ER is variable in high grade cases (Mod Path 2005;18:615)

● HER2 often positive in high grade DCIS but there is no clinical indication for HER2 testing in DCIS

● May have distinct features from the in situ component of invasive ductal carcinoma (Appl Immunohistochem Mol Morphol 2009 Jun 29 [Epub ahead of print])

● Note: myoepithelial cells associated with DCIS are less often positive than those surrounding normal mammary ductal-lobular structures (Am J Surg Pathol 2009;33:227)

Negative stains

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● High molecular weight cytokeratin / 34betaE12 (Hum Path 2002;33:620, AJSP 1999;23:1048)

Molecular / cytogenetics

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● Low grade DCIS and high grade DCIS appear to be genetically distinct disorders

● High grade DCIS has increase in chromosome gains by FISH compared to low grade (Hum Path 2000;31:201)

● Multicentric low grade tumors are more likely to represent different clones than multicentric high grade tumors (Hum Path 2003;34:1163)

● DCIS shares genomic alterations with invasive ductal carcinoma (Clin Cancer Res 2008;14:1956), particularly DCIS associated with invasive disease (Clin Cancer Res 2008;14:4446)

● Molecular profiling indicates a binary grading scheme (Clin Cancer Res 2008;14:8244)

Differential diagnosis

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● Lobular neoplasia - may resemble low grade DCIS but is E cadherin negative

● Atypical ductal hyperplasia

● Microinvasion

● Infiltrative ductal carcinoma with comedonecrosis (J Med Case Reports 2007;1:83)

Additional references

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● Mod Path 2002;15:95, Wikipedia

End of Breast – Malignant, Males, Children > DCIS (intraductal carcinoma) - general

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