Lobular carcinoma

Pleomorphic lobular carcinoma

Last author update: 1 May 2018
Last staff update: 3 April 2023

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PubMed Search: Lobular carcinoma pleomorphic variant

Mirna B. Podoll, M.D.
Emily S. Reisenbichler, M.D.
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Cite this page: Podoll MB, Reisenbichler ES. Pleomorphic lobular carcinoma. website. Accessed October 4th, 2023.
Definition / general
  • Cytologic variant of invasive lobular carcinoma (ILC)
Essential features
  • Aggressive variant which accounts for approximately 10% of ILC
  • May show focal areas of classical ILC
  • Predominant cytologic features determine the histologic type of ILC
  • ILC are more common in older women (mean age 57, range 24 - 92) and very rare in men
  • When they do occur in men, it is often in BRCA2 carriers
  • CDH1 germline mutation is seen in many ILC tumors, resulting in the loss of E-cadherin gene expression in approximately 85% of ILC
Clinical features
Radiology description
  • Tumors are most commonly detected as spiculated mass lesions on mammography
  • Use of magnetic resonance imaging can aid in the detection of multicentric and contralateral lesions
Prognostic factors
  • Factors which result in worse prognosis include high histologic grade (particularly high mitotic scores) and negative hormone receptor status
  • Although the prognosis is typically worse for this variant versus the classic type ILC, it is thought to be more related to tumor grade versus variant type
Case reports
  • Similar to that of invasive ductal carcinoma and depends on the tumor pathologic stage and hormone receptor status
Gross description
  • Spiculated mass with ill defined margins; often no mass because of diffuse growth pattern
Gross images

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Circumscribed tumor

Microscopic (histologic) description
  • Moderately to poorly differentiated carcinomas
  • Multifocal nodular aggregates of pleomorphic, high grade tumor cells with grade 2 - 3 nuclei which may contain prominent nucleoli
  • Typical single file pattern or targetoid growth in a background of dense fibrotic breast parenchyma
  • Distinctive cytologic cellular features with abundant eosinophilic cytoplasm (may look apocrine), signet ring and plasmacytoid cells
  • Commonly positive for apocrine marker GCDFP-15
  • Prognosis is related to the high tumor grade
Microscopic (histologic) images

Contributed by Mirna B. Podoll, M.D.
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Desmoplastic stroma

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Pleomorphic invasive lobular carcinoma

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Contributed by Mark R. Wick, M.D.

Pagetoid spread

Cadherin neg

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Pleomorphic tumor cells

E-cadherin negative


Cytology description
  • More cellular than classic lobular, large tumor cells with single filing, tumor cells have cytoplasmic vacuoles and pleomorphic nuclei (Cancer 1997;81:29)
  • May have apocrine features and resemble atypical mesothelial cells (Diagn Cytopathol 2008;36:657)
  • Ductal lavage: similar features, although less striking, including epithelial cells in small clusters, single-file or isolated; also nuclear atypia, cytoplasmic vacuoles and signet ring features (Acta Cytol 2008;52:207)
Cytology images

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Various images

Positive stains
  • GCDFP-15: 71%, due to apocrine nature
  • HER2: overexpression in approximately 20%
  • p53: 20 - 60%
  • Variable ER and PR (approximately 5 - 10% are hormone receptor negative)
Negative stains
Molecular / cytogenetics description
Molecular / cytogenetics images

Contributed by Mark R. Wick, M.D.

HER2 amp

Differential diagnosis
  • Invasive ductal carcinoma single cell pattern of infiltration in ILC; can be difficult to recognize particularly at metastatic sites
  • Lymphoma: may involve breast as primary site but is not seen associated with LCIS Immunohistochemical studies for cytokeratin and lymphoid markers can aid in the diagnosis
  • Metastatic melanoma: one of the most common metastasis to the breast; immunohistochemical studies for cytokeratin and melanoma markers can aid in the diagnosis
  • Chemotherapy or radiation treatment effect
Board review style question #1
    Which of the following is true of pleomorphic variant of invasive lobular carcinoma?

  1. Are usually hormone receptor negative
  2. Do not show HER2 overexpression
  3. Frequency of p53 expression is similar to that of classic ILC
  4. The aggressive nature of these tumors is reflected by the pleomorphic variant designation
  5. The high histologic grade contributes to the poor patient outcomes
Board review style answer #1
E. The aggressive nature of the pleomorphic variant of invasive lobular carcinoma (ILC) and poorer outcomes are related to the high histologic grade of this variant, rather than the pleomorphic designation itself. While these tumors may be ER and PR negative in approximately 5 - 10% of cases, the majority are hormone receptor positive. HER2 expression can be seen in approximately 20% of cases. In addition, the pleomorphic variant of ILC more commonly shows p53 expression when compared to the classic type ILC.

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