Breast malignant, males, children - Lobular carcinoma in situ (LCIS)

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Breast malignant, males, children

In situ carcinoma

Lobular carcinoma in situ (LCIS)

Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update January 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

General
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● Lobulocentric proliferation of small, monotonous, loosely cohesive cells
● Must fill or distend lobular unit, in contrast to atypical lobular hyperplasia (ALH)

Terminology
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● “Lobular neoplasia” terminology is used by some authors to denote the histologic overlap / frequent co-existence of ALH and LCIS (Cancer 1978;42:737)

Epidemiology
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● Estimated incidence of 2.8 per 100K
● Present in 0.5 to 8% of benign breast biopsies
● Mean age 53 years
● Diagnosed as an incidental microscopic finding since no distinguishing features on gross examination and usually not associated with microcalcifications

Features
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● 30-70% are bilateral (vs. 20% for invasive lobular carcinoma and 10% for DCIS)
● 75% are multicentric; 5% have coexisting invasive carcinoma in another quadrant or opposite breast
● 20-30% risk of subsequent breast cancer, which may occur in either breast (8-10x relative risk) but is slightly more likely in ipsilateral breast, often develops after long follow up (up to 10 years, J Clin Oncol 2005;23:5534)
● Risk of invasive lobular carcinoma after LCIS is 5x risk after DCIS (Cancer 2006;106:2104)
● LCIS is considered to be a precursor of some invasive lobular carcinomas (Verh Dtsch Ges Pathol 2007;91:208, Breast Cancer Res Treat 2008;107:331)
● May be present in fibroadenomas or sclerosing adenosis (Am J Surg Pathol 1981;5:233)
● Not in nipple and only rarely in large lactiferous ducts
● Minimal risk of dying from breast cancer since most subsequent tumors are treatable and low stage

Treatment and prognosis
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● Watchful waiting (Cancer 2004;100:238), possibly with tamoxifen
● An alternative treatment to waiting is ipsilateral or bilateral mastectomy (if strong family history of carcinoma)
● Presence of LCIS at excision margin is not a risk factor for recurrence of DCIS or invasive carcinoma (Ann Surg Oncol 2008;15:2263, Cancer 2006;106:28) but see Int J Radiat Oncol Biol Phys 2006;66:365
● If LCIS in core biopsy, excision recommended due to subsequent invasive ductal or lobular carcinoma in 10-31% (Arch Pathol Lab Med 2008;132:979, Am J Surg Pathol 2005;29:534) but see Am J Clin Pathol 2006;126:310 - low risk of DCIS or invasive disease at excision
● Higher risk of invasive disease if neoplastic epithelial microcalcifications present (Am J Surg Pathol 2007;31:717) or if associated with a mass lesion (Mod Pathol 2003;16:120)
● If radiologic: pathologic discordance, pleomorphic features or necrosis (Mod Pathol 2008;21:1208)
● Note: residual LCIS is usually present at excisional biopsy

Case reports
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● Occurring within a fibroadenoma (Postgrad Med J 1999;75:293)

Gross images
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No distinct gross features

Micro description / grading
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● LCIS affects terminal duct lobular unit (TDLU) with expansion / effacement of acini
● Proliferation of monomorphic, evenly spaced cells that are loosely cohesive and slightly larger than normal with uniform nuclei, evenly distributed chromatin and small / no nucleoli
● Resembles “marbles in a bag”
● Intracytoplasmic lumina are common, but are not specific for LCIS
● Signet ring cells with mucin are common
● Classic type of LCIS lacks pleomorphism / necrosis
● “Pagetoid growth” refers to continuous row of tumor cells beneath adjacent terminal duct epithelium, causing cloverleaf or necklace patterns
● Myoepithelial cells may be replaced or unchanged
● Minimal mitotic figures
● May involve / arise in sclerosing adenosis, radial scar, fibroadenoma, collagenous spherulosis, papillary lesions
● Type A pattern: small, round, bland cells; diploid
● Type B pattern: larger cells with more cytoplasm, less uniform nuclei and distinct nucleoli
● By definition, E-cadherin negative (DCIS is positive)
● Page criteria for LCIS: cells must fill ALL acini, expand or distort 50%+ acini in lobule, otherwise call atypical lobular hyperplasia

Micro images
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“Subgross” image


Lobules are distended by monomorphic cells

Intracytoplasmic lumina

Core biopsy


Involving adenosis, with microcalcifications in biopsy

Involving sclerosing adenosis (Fig 4A/B)

With adjacent infiltrating lobular carcinoma

Comparison with low grade DCIS

Various images

Lobular neoplasia:

Monotonous cells obliterate lumina

Involving a micropapilloma


Involving foci of florid hyperplasia

AFIP Fascicle images (3rd Series):

Normal epithelium is replaced by uniform cells that fill acini,
individual glands are round and discrete

Discrete acini have haphazardly arranged monomorphic cells
with scant cytoplasm and dark nuclei

Monomorphic cells have no specific orientation to basement membrane

Pagetoid spread of LCIS cells into normal acini (arrow)

Type A (central) and type B (peripheral) cells

Involvement of duct and lobule, with pagetoid extension beneath duct epithelium in lower left

Layer of LCIS cells beneath attenuated ductal epithelium


Cytoplasmic vacuoles (arrows)

Signet ring cells

Serrated (sawtooth) pattern with LCIS involvement of ducts and ductules only

Cloverleaf pattern in atrophic TDLU in post-menopausal woman

Resembles invasive carcinoma but has alveolar pattern of LCIS

Merging with DCIS

With microinvasion (linear strands or single cells)

Stains:

Mucicarmine+

ER+

Fig 3a: Factor VIII staining shows reduced vascular proliferation; Fig 3b: low MIB1 staining


LCIS is E-cadherin negative

E-cadherin staining of mixed LCIS and DCIS

E-cadherin negative (Fig. G) and p-120 catenin positive (Fig. J)

Lobules are distended by monomorphic cells

With comedonecrosis

High power shows prominent intracytoplasmic vacuoles

Various images

Cytology description
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● Commonly either (a) benign appearing / nondiagnostic or (b) cell groups diagnostic or consistent with LCIS due to loosely cohesive cell groups of uniform cells with occasional intracytoplasmic lumina and slightly irregular and eccentric nuclei
● May have hypercellular, dissociated, pleomorphic tumor cells (Diagn Cytopathol 2002;27:22)
● Thin-Prep: tight or loosely cohesive clusters of crowded mildly enlarged nuclei with at least moderate cellularity; occasional single epithelial cells, small but prominent nucleoli, intracytoplasmic lumina (Diagn Cytopathol 2005;32:276)

Virtual slides
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LCIS

DCIS and LCIS

Videos
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LCIS #1; #2

Positive stains
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● ER (60-90%, both alpha and beta forms, Histopathology 2007;50:875)
● Usually PR
● 75% mucin positive (Alcian blue, mucicarmine)
● High molecular weight cytokeratin (34betaE12 / CK903-perinuclear)
● S100 (60%)
● p120 catenin (Am J Surg Pathol 2007;31:427)
● EMA
● Milk fat globule membrane antigen (Am J Surg Pathol 2007;31:427)

Negative stains
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● E-cadherin (Hum Pathol 2002;33:620, Am J Surg Pathol 2001;25:229)
● CK 5/6, p53, HER2

Molecular / cytogenetics description
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● 16q- (88%, Hum Pathol 2001;32:292, Breast Cancer Res Treat 2009;113:59)
● 17p- (18%), 8p- (12%), 12q24- (12%)

Differential diagnosis
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● Cancerization of lobules by DCIS: has high grade cytology, necrosis, different architecture
● Atypical lobular hyperplasia: normal sized lobules, central lumina still present
● Pregnancy-like or pseudolactational hyperplasia: premenopausal women who aren’t pregnant
● Myoepithelial hyperplasia: normal glandular cells remain with clear cytoplasm, small, round, hyperchromatic nuclei, image
● Clear cell change
● Poor tissue preservation: loosely cohesive cells but no lobular distension

End of Breast malignant, males, children > In situ carcinoma > Lobular carcinoma in situ (LCIS)

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