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,, Inc.

PubMed Search: lobular carcinoma [title] classic

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)
Clinical Images
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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

Micro 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
Micro Images
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Single dyscohesive cells

Classic features

Targetoid pattern

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Foci of tumor cells may be inconspicuous

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Mimicking fat necrosis

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

Prominent intracytoplasmic mucin

Tumor of male breast


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:

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Sheet like

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Alcian blue stain

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Estrogen receptor

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Type 3

Invasive lobular carcinoma within fibroadenoma:

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


Endometrial polyp: H&E and AE1/AE3

Soft tissue


Cytology Description
Cytology Images
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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
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


Differential Diagnosis