Lobular carcinoma

Topic Completed: 1 August 2017

Minor changes: 8 March 2021

Copyright: 2002-2019,, Inc.

PubMed Search: Invasive lobular carcinoma[TI] free full text[sb]

Mirna B. Podoll, M.D.
Emily S. Reisenbichler, M.D.
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Cite this page: Podoll MB, Reisenbichler ES. Classic. website. Accessed March 9th, 2021.
Definition / general
  • Invasive mammary carcinoma lacking cellular adhesion proteins
Essential features
  • Tumor is composed of noncohesive cells that are individually dispersed or arranged in a single file pattern with a minimal desmoplastic response
  • Often associated with lobular carcinoma in situ (LCIS)
  • Displays a loss of adhesion proteins, resulting in a discohesive morphologic pattern (~85% lack E-cadherin)
  • May form spiculated masses or asymmetry on mammography; sometimes are not well seen
  • Invasive lobular carcinoma comprises between 5 - 15% of all breast carcinomas
  • More commonly multifocal than invasive ductal carcinoma, no special type
  • E-cadherin (CDH1) germline mutation is seen in many tumors, resulting in the loss of E-cadherin gene expression
Clinical features
  • Most tumors form mass-like lesions or result in architectural distortion
  • May be difficult to identify clinically due to the lack of strong desmoplastic response
  • Multicentricity within same breast is more common than invasive ductal carcinoma
  • More likely to be multifocal and confer a 0.5 - 1% yearly risk of contralateral breast involvement (10 - 20% are bilateral)
  • Metastasizes to bone marrow, cerebrospinal fluid and leptomeninges (Arch Pathol Lab Med 1991;115:507), GI tract, ovary, serosal surfaces, uterus and retroperitoneum (resembles low grade stromal sarcoma) more than other subtypes
  • Variants usually coexist with classic pattern
Radiology description
  • Tumors are most commonly detected as spiculated mass lesions on mammography, followed by findings of asymmetric densities and opacities
  • Approximately 15% of cases may be difficult to identify on imaging or may present with benign findings
  • Since these tumors are more commonly multicentric and bilateral, evaluation of both breasts is critical
  • Use of magnetic resonance imaging can aid in the detection of multicentric and contralateral lesions
Radiology images

Contributed by Dr. Mark R. Wick


Prognostic factors
Case reports
Gross description
  • Mass with ill defined margins; often no mass because of diffuse growth pattern
Gross images

Images hosted on other servers:

Anal metastasis

Multiple foci with irregular margins

Microscopic (histologic) description
  • Cells grow in single file, linear pattern and are loosely dispersed throughout fibrous matrix
  • Cells can often be seen encircling normal ducts (onion skin pattern)
  • Variable dense fibrous stroma with periductal and perivenous elastosis
  • Dense lymphoid infiltrate may accompany tumor at periphery
  • Classic invasive lobular carcinomas will not show tubule formation and will commonly be given a tubule score of 3 ( < 10% tubule formation)
  • Tumor cells are usually small, uniform, round with minimal pleomorphism, evenly dispersed chromatin and no nucleoli (nuclear grade 1 or 2, like LCIS cells)
  • Commonly signet ring cells, intracellular lumina and targetoid cytoplasmic mucin can be seen
  • Typically not very mitotically active with < 10 mitoses/10 HPF without necrosis and usually given a mitotic score of 1
  • Most commonly tumors are of intermediate histologic grade (Nottingham grade 2)
  • Lymph node metastasis:
    • Metastatic tumor cells may resemble histiocytes or lymphocytes; the use of cytokeratins may help highlight the malignant cells
  • 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
  • Metastasis to other sites:
    • Leptomeningies and cerebrospinal fluid
    • Gastrointestinal tract: the differentiation from primary gastric tumors can be difficult histologically; immunohistochemistry may be necessary
    • Ovary, uterus and retroperitoneum
Microscopic (histologic) images

Contributed by Mirna B. Podoll, M.D.

Adjacent to LCIS

Pleomorphic cells with cytoplasmic mucin

Single cells around normal duct

Lymph node macrometastasis

Macrometastatic focus

Cytoplasmic p120 staining

Surrounding normal duct (p120)

Loss of E-cadherin

Case #369

Classical type and solid / alveolar variant

H&E images

Pancytokeratin (positive)

E-cadherin (negative)

ER (positive: 25 - 75% tumor cells)

PR (positive: 25 - 75% tumor cells)

HER2 (negative)

Chromogranin (negative)

Synaptophysin (negative)

Cytology description
Cytology images

Contributed by Dr. Mark R. Wick


Images hosted on other servers:

Small cells arranged in linear pattern (figure B)

Various images

Positive stains
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)
  • Ki67 shows low proliferation rate (typically putting these tumors in mitotic score of 1)
  • HER2 is typically negative although 25 - 50% grade 3 invasive lobular carcinomas can be HER2+
Electron microscopy images

AFIP 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

Molecular / cytogenetics description
  • Usually diploid
  • Truncation mutations in E-cadherin gene (16q) or inactivation of wild type allele
  • Loss of adhesion proteins are seen in the invasive lobular carcinoma as well as its precursor lesions, atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS)
  • E-cadherin binds actin cytoskeleton through interaction with p120 and alpha, beta and gamma catenins; loss of chromosome 16q22.1, the E-cadherin locus, confers loss of protein
  • Typically are luminal A category (Gene Expr 2011;15:105)

Histopathology breast - lobular carcinoma
Differential diagnosis
  • Gastric carcinoma: may also display loss of E-cadherin proteins, immunohistochemical stains such as mammaglobin and GATA3 may be of use
  • Histiocytes of a lymph node: will display positivity for histocytic markers such as CD68 and will be negative for cytokeratins
  • Invasive ductal carcinoma: may have focal lobular features but will show more cohesion between tumor cells, a retained membranous E-cadherin staining and will membranous p120 staining
  • Lymphoma: less cytoplasm without cytoplasmic mucin, positive for CD45 and other lymphoma markers
  • Melanoma: will display positivity for melanocytic markers such as MelanA and HMB45
    • Note that SOX10 positivity can be seen in both breast carcinoma and melanoma
    • Cytokeratins should be negative
  • Myofibroblastoma: epithelioid variant may mimic malignancy but will be well circumscribed often and will not show a spiculated mass-like lesion seen with invasive carcinoma
Board review style question #1
Which of the following is true of invasive lobular carcinoma?

  1. Is most commonly associated with cytoplasmic E-cadherin immunostaining
  2. Is most commonly associated with cytoplasmic p120 immunostaining
  3. Is most commonly associated with membranous E-cadherin immunostaining
  4. Is most commonly associated with membranous p120 immunostaining
Board review style answer #1
B. Is most commonly associated with cytoplasmic p120 immunostaining; invasive lobular carcinomas commonly have a CDH1 germline mutation, causing the cells to lose membranous E-cadherin staining and resulting in cytoplasmic p120 expression
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