Classic infiltrating lobular carcinoma

Breast malignant, males, children
Carcinoma subtypes
Classic infiltrating lobular carcinoma

Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)

Revised: 10 November 2015, last major update August 2012

Copyright: (c) 2002-2015, PathologyOutlines.com, Inc.

PubMed Search: lobular carcinoma [title] classic

Table of Contents

Cite this page: Classic infiltrating lobular carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantlobularclassic.html. Accessed July 14th, 2017.

Definition / general

Invasive tumor associated with LCIS, composed of noncohesive cells that are individually dispersed or arranged in a single file pattern (Infiltrating Lobular Carcinoma of the Breast - Stanford University)
Minimal desmoplastic response

Clinical features

10% of all breast carcinomas
Incidence decreasing in US (Cancer Epidemiol Biomarkers Prev 2009;18:1763)
10-20% are bilateral; multicentricity within same breast is more common than invasive ductal carcinoma
Often not well seen on mammograms, and may be more extensive than clinically suspected
Metastasizes to bone marrow, cerebrospinal fluid and leptomeninges (Arch Pathol Lab Med 1991;115:507), GI tract, ovary, serosal surfaces, uterus (resembles low grade stromal sarcoma) more than other subtypes
Pan-keratin staining of negative bone marrow biopsies is recommended to detect metastases (Am J Surg Pathol 2000;24:1593, Hum Pathol 1994;25:781), but has minimal value for nodal metastases (Hum Pathol 2008;39:1011)
Lack of cohesion due to alterations in E-cadherin, an adhesion molecule that is deleted or mutated
Variants usually coexist with classic pattern

Case reports

Array-based comparative genomic hybridization of ductal carcinoma in situ and synchronous invasive lobular cancer (Hum Pathol 2004;35:759)
56 year old woman with metastasis of lobular breast carcinoma to the uterus (Onkologie 2009;32:424)
56 year old woman with breast mass (Case of the Week #369)
58 year old man with synchronous bilateral invasive lobular breast cancer presenting as carcinomatosis (Am J Surg Pathol 2009;33:470)
60 year old woman with lobular carcinoma of the breast with extracellular mucin (Pathol Int 2009;59:405)
61 year old woman with C-kit-positive gastric metastasis of lobular carcinoma of the breast masquerading as gastrointestinal stromal tumor (Breast Cancer 2010;17:303)
62 and 92 year old women with metastatic breast lobular carcinoma involving tamoxifen-associated endometrial polyps (Mod Pathol 2003;16:395)
70 year old woman with orbital metastasis as the initial presentation of invasive lobular carcinoma of breast (Intern Med 2012;51:1635)
88 year old woman with anal metastasis from recurrent breast lobular carcinoma (World J Gastroenterol 2009;15:1388)

Treatment

Classic variant has better prognosis than non-classic variants overall (Cancer 2008;113:1511, Am J Surg Pathol 1990;14:12)
May have similar long term prognosis as infiltrating ductal carcinoma (Breast Cancer Res Treat 2009;117:211), but see J Clin Oncol 2008;26:3006 (lobular has better survival at 6 years but worse survival at 10 years)
In one study, 12 year local relapse free survival was 89%; predictors of relapse were positive margins, age >50 years and contralateral breast cancer (Eur J Surg Oncol 2010;36:176)

Clinical images

Mammogram, courtesy of Dr. Mark R. Wick

Gross description

Mass with ill-defined margins; often no mass because of diffuse growth pattern

Gross images

Solid firm mass

Infiltration into adipose tissue

Anal metastasis

Multiple foci with irregular margins

Microscopic (histologic) description

Cells grow in single file (linear, Indian file) or targetoid pattern of noncohesive cells encircling ducts, loosely dispersed throughout fibrous matrix
Tumor cells are usually small, uniform, round with minimal pleomorphism, evenly disbursed chromatin and no nucleoli (i.e. nuclear grade 1, like LCIS cells)
Commonly signet ring cells, intracellular lumina, intracellular mucin, LCIS (90%)
Variable dense fibrous stroma with periductal and perivenous elastosis
May have dense lymphoid infiltrate
No glandular formation in classic cases, but may have preservation of normal glandular structures and ìskip areasî uninvolved by tumor
< 10 mitoses/10 HPF, no necrosis
Histologic grading is recommended (Mod Pathol 2005;18:621)
Most tumors are histologic grade 2 (Breast Cancer Res Treat 2008;111:121)
2 tiered nuclear grading system may reduce interobserver variability (Ann Diagn Pathol 2009;13:223), as may nuclear and proliferation grading system (Ann Clin Lab Sci 2009;39:25)
Bone marrow biopsies:
- Highly suspicious features for metastatic disease are fibrosis, signet ring cells, cells with intracytoplasmic lumina, cells resembling histiocytes
- Architecture is often NOT disrupted

Microscopic (histologic) images

Single dyscohesive cells

Classic features

Targetoid pattern

Foci of tumor cells may be inconspicuous

Mimicking fat necrosis

Minute focus (arrow) of tumor around a small duct (AFIP)

Prominent intracytoplasmic mucin

Tumor of male breast

With LCIS

Grade I of III-minimal nuclear pleomorphism

Grade II of III-moderate nuclear pleomorphism

Grade III of III-severe nuclear pleomorphism

Case of the Week #369:

H&E images

pan-Cytokeratin (positive)

E-Cadherin (negative)

ER (positive: 25-75% tumor cells)

PR (positive: 25-75% tumor cells)

HER2 (negative)

Chromogranin (negative)

Synaptophysin (negative)

Images courtesy of Dr. Mark R. Wick:

Sheet like

Alcian blue stain

Estrogen receptor

Type 3

Invasive lobular carcinoma within fibroadenoma:

Left to right: H&E (2), ER, CK5/6, E-cadherin

Metastases:

Endometrial polyp: H&E and AE1/AE3

Soft tissue

Stomach

Cytology description

Moderate / highly cellular, pattern is predominantly or partly dissociated
Usually small / intermediate cells with intracytoplasmic lumina in 57%, light cytoplasm
Small, eccentric nuclei with finely granular chromatin (Acta Cytol 2000;44:169, Med Mol Morphol 2008;41:121, Cancer 2008;114:111)

Cytology images

FNAB, courtesy of Dr. Mark R. Wick

Small cells arranged in linear pattern (figure B)

Various images

Positive stains

ER, PR
HMW keratin (helpful in bone marrow biopsy)
Mucicarmine (intracellular mucin)
GCDFP-15 (30%)
PLEKHA7 (Hum Pathol 2012;43:1902)

Negative stains

E-cadherin (complete absence suggests lobular carcinoma, but rarely is positive and may vary by antibody, Am J Surg Pathol 2008;32:773, Mod Pathol 2008;21:1224)
p53, HER2, Ki-67

Molecular / cytogenetics description

Usually diploid
Truncation mutations in E-cadherin gene (16q) or inactivation of wild-type allele

Electron microscopy images

Line of tumor cells surrounded by collagen, with cytokeratin bundles (arrows), but no basement membrane

Intracytoplasmic lumina lined by microvilli, elastic tissue (arrows) and collagen in stroma

Intracytoplasmic lumen with numerous microvilli and perinuclear mucin granules

Videos

Differential diagnosis

Lymphoma: resembles lobular metastases to axillary nodes or eyelid
Invasive ductal adenocarcinoma: may have focal lobular features, immunostains may be helpful (Appl Immunohistochem Mol Morphol 2013;21:1)
Invasive ductal carcinoma with neuroendocrine features