Lobular carcinoma in situ (LCIS)

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

Author: Monika Roychowdhury, M.D. (see Authors page)

Revised: 18 October 2016, last major update January 2012

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

PubMed Search: Lobular carcinoma in situ [title] breast

Table of Contents

Cite this page: Lobular carcinoma in situ (LCIS). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantlcis.html. Accessed July 14th, 2017.

Definition / general

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

Terminology

"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

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

Clinical features

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

Case reports

45 year old woman with lobular carcinoma-in-situ within a fibroadenoma of the breast (Postgrad Med J 1999;75:293)

Prognosis and treatment

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

Clinical images

Images hosted on PathOut server:

MRI, courtesy of Mark R. Wick, M.D.

Microscopic (histologic) description

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

Microscopic (histologic) images

Scroll to see all images:

Images hosted on PathOut server:

Courtesy of Mark R. Wick, M.D.

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)

Images hosted on Flickr:

Fibroadenoma with LCIS and invasive lobular carcinoma; courtesy of Semir Vranic, M.D.

Images hosted on other servers:

Various images

Lobules are distended by monomorphic cells

Intracytoplasmic lumina

Core biopsy

Involving adenosis

Involving sclerosing adenosis (Fig 4A/B)

With adjacent infiltrating lobular carcinoma

Comparison with low grade DCIS

Various images

Lobules are distended by monomorphic cells

With comedonecrosis

Prominent intracytoplasmic vacuoles

Various images

Stains:

Mucicarmine+

Fig 3a: Factor VIII, Fig 3b: low MIB1 staining

LCIS is E-cadherin negative

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

Cytology description

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)

Videos

Positive stains

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

Molecular / cytogenetics description

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

Differential diagnosis

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