Breast

Lobular carcinoma

Classic


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Minor changes: 26 August 2021

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PubMed Search: Invasive lobular carcinoma [TI] free full text [SB] "last 5 years"[DP]

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Cite this page: Li JJX, Tse GM. Classic. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantlobularclassic.html. Accessed October 21st, 2021.
Definition / general
  • Invasive breast carcinoma with loss of cellular adhesion, characteristically arranged in discohesive or single file patterns
Essential features
  • Special subtype of invasive breast carcinoma characterized by discohesive tumor cells arranged in single files or as individual single cells
  • Shows 16q loss (CDH1 gene located at 16q22.1 encodes E-cadherin, integral in formation of adherens junction responsible for cell adhesion)
  • Loss of E-cadherin expression on immunohistochemistry helpful but not required for diagnosis
Terminology
  • Invasive lobular carcinoma, classic type
ICD coding
  • ICD-O: 8520/3 - lobular carcinoma, NOS
  • ICD-11: 2C61.1&XH2XR3 - invasive lobular carcinoma of breast & lobular carcinoma, NOS
Epidemiology
Sites
  • Breast
  • Can occur in axilla accessory breast tissue
Etiology
  • Invasiveness and loss of cellular cohesion due to abnormalities of the adherens complex, formed by cadherins and catenins (Biochim Biophys Acta 2008;1778:660)
  • Lobular carcinoma in situ is a risk factor and nonobligate precursor of invasive lobular carcinoma
Clinical features
Diagnosis
  • Mainly histological or radiological
Radiology description
  • Ultrasound (Radiographics 2009;29:165)
    • Hypoechoic mass with spiculated or ill defined margins and posterior acoustic shadowing
  • Mammography (Radiographics 2009;29:165)
    • Does not consistently present as a mass (44% - 65%)
    • Less commonly manifests as architectural distortion
    • Microcalcification infrequent
  • Magnetic resonance imaging findings similar (Radiographics 2009;29:165)
    • Can aid in identifying multifocal or residual disease
    • Preoperative breast MRI may improve surgical planning (Breast J 2016;22:143)
Radiology images

Contributed by Dr. Mark R. Wick

Mammogram



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Irregular mass (mammography), hypoechoic area (ultrasound)

Prognostic factors
  • Older age, larger tumor size and metastatic axillary lymph node involvement are independent risk factors for survival and recurrence (Cancer 2008;113:1511)
  • Higher histological grade is associated with poorer outcome (Breast Cancer Res Treat 2008;111:121, Histopathology 2015;66:409)
    • Independently predicts shorter disease specific survival and disease free interval
    • Associated with higher stage and hormone receptor negativity
  • Classic type more favorable than solid, pleomorphic and other types (Cancer 2008;113:1511)
    • Lower number of lymph node metastases and risk of recurrence
  • E-cadherin negative lobular carcinomas have a higher disease specific mortality than E-cadherin positive counterparts (Histopathology 2015;66:409)
  • High Ki67 index associated with risk of distant metastasis (Cancer 2008;113:1511)
  • Better initial outcome but worse long term (> 10 years after diagnosis) survival compared with invasive ductal carcinoma (Eur J Cancer 2008;44:73)
Case reports
Treatment
Clinical images

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Carcinoma en cuirasse

Gross description
  • Can form a discrete irregular mass (BMJ Case Rep 2016;2016:bcr2016215665)
  • Frequently ill defined borders, due to lack of sclerotic stromal response
  • Not uncommonly grossly unidentifiable or is grossly underestimated, only slightly firm on palpation
Gross images

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Anal metastasis

Multiple foci with irregular margins

Frozen section description
  • Discohesive tumor cells may be difficult to identify on frozen sections, particularly when cellularity is low
  • Single tumor cells can be mistaken as inflammatory cells (histiocytes and lymphocytes) and vice versa
  • Ill defined nature of lesion increases chance of margins sent for frozen section being involved by tumor microscopically
Frozen section images

Contributed by Emily S. Reisenbichler, M.D.
Invasive lobular carcinoma

Invasive lobular carcinoma

Microscopic (histologic) description
  • Tumor cells arranged in single files, cords and single cells (Breast Cancer Res 2015;17:12)
    • Can be arranged concentrically around normal ducts, giving a targetoid appearance
  • Tumor cells discohesive, small, monomorphic and lacking marked atypia
    • Round or notched ovoid nuclei, usually grade 1 or 2 nuclear score
    • Scant cytoplasm, occasional with intracytoplasmic lumen
    • Mitosis infrequent
  • Desmoplastic reaction and necrosis uncommon
  • Requires high index of suspicion for metastasis
  • Other (nonclassic) patterns of lobular carcinoma
    • Solid:
      • Sheets or large nests of tumor cells
    • Alveolar:
      • Clusters and aggregates of ≥ 20 cells
    • Tubulolobular carcinoma:
      • Tumor cells arranged in small round tubules mixed with classical lobular carcinoma
    • Pleomorphic:
      • Markedly pleomorphic (nuclear size > 4 times lymphocyte or nuclear pleomorphism equivalent to high grade ductal carcinoma in situ)
      • Higher rate of hormone receptor negativity, HER2 and p53 immunohistochemistry positivity
    • Histiocytoid:
      • Foamy cytoplasm resembling histiocytes
    • Apocrine:
      • Abundant eosinophilic granular cytoplasm
    • Signet ring
Microscopic (histologic) images

Contributed by Joshua J.X. Li, M.B.Ch.B., Gary M. Tse, M.B.B.S and Kristen E. Muller, D.O.
Tumor cells in single file

Tumor cells in single file

Low grade nuclei

Low grade nuclei

Adjacent in situ component

Adjacent in situ component

E-cadherin loss E-cadherin loss

E-cadherin loss


Intracytoplasmic vacuoles

Intracytoplasmic vacuoles

Luminal A subtype Luminal A subtype Luminal A subtype Luminal A subtype

Luminal A subtype


Alveolar pattern

Alveolar pattern

Signet ring pattern

Signet ring pattern

Solid pattern

Solid pattern

Virtual slides

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Core biopsy

In situ and invasive tumor

Gastrointestinal metastasis

Cytology description
  • Cellularity can be low
  • Tumor cells arranged in chains, single files or as single cells
    • Tumor cells arranged in small chains are helpful clues
  • Nuclear atypia mostly mild
    • Nuclei round to oval and eccentric
  • Cytoplasm scanty with a high nuclear / cytoplasmic ratio
    • Occasional intracytoplasmic vacuolations may be seen
  • Cytologic features can resemble mesothelial cells in effusion fluid (Diagn Cytopathol 2012;40:311)
Cytology images

Contributed by Joshua J.X. Li, M.B.Ch.B. and Gary M. Tse, M.B.B.S
Discohesive tumor cells

Discohesive tumor cells

Mild atypia

Mild atypia

Loose chains of cells

Loose chains of cells

Intracytoplasmic vacuolation

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Left breast, mastectomy:
    • Invasive lobular carcinoma (see comment)
    • Comment: Sections show breast tissue with malignant cells in a diffuse and discohesive pattern, with some forming single files and small clusters. Targetoid pattern is noted. The tumor cells show mild nuclear pleomorphism with rare mitoses, corresponding to a Nottingham histological grade of I. No lymphovascular permeation is seen. The tumor measures ___cm in maximal dimension. The remaining breast tissue and nipple are unremarkable. All the resection margins are clear, with a minimal clearance of ___cm at the ___ margin. Immunohistochemical staining shows tumor cells are E-cadherin negative. The features are those of an infiltrating lobular carcinoma, classic type.
Differential diagnosis
  • Primary disease
    • Mixed invasive breast carcinoma and invasive lobular carcinoma:
    • Lobular carcinoma in situ involving sclerosing adenosis:
      • Retained lobular architecture
      • Myoepithelial cells present and can be demonstrated by immunohistochemistry
    • Inflammatory infiltrates and lymphoma:
      • Lacks background lobular carcinoma in situ
      • Lymphoid cells may be more hyperchromatic and have less cytoplasm
      • No intracellular cytoplasmic vacuolation
      • Cytokeratin negative and lymphocyte markers positive
    • Melanoma:
      • Lacks background lobular carcinoma in situ
      • Can display marked nuclear atypia
      • Cytokeratin negative and melanocytic markers positive
    • Myofibroblastoma, epithelioid variant:
      • Well circumscribed borders
      • Lacks background lobular carcinoma in situ
      • Presence of spindle cell component
      • Cytokeratin negative
  • Metastatic disease
Board review style question #1
Which of the following germline mutations is associated with an increased risk of developing lobular carcinoma of the breast?

  1. APC
  2. BRCA1
  3. BRCA2
  4. CDH1
  5. TP53
Board review style answer #1
D. CDH1. CDH1 encodes E-cadherin and germline mutation results in hereditary diffuse gastric cancer syndrome. No increased risk of developing lobular carcinoma of the breast is reported for germline BRCA1 and BRCA2 mutations. Germline TP53 and APC mutations result in Li-Fraumeni syndrome and familial adenomatous polyposis, which are not associated with lobular carcinoma of the breast. (Cancer Epidemiol Biomarkers Prev 2012;21:134, Breast J 2019;25:16)

Comment Here

Reference: Classic lobular carcinoma
Board review style question #2
Which of the following features is more commonly seen in classic lobular carcinoma compared with pleomorphic lobular carcinoma?

  1. Formation of invasive tubular structures
  2. Grade 3 (markedly pleomorphic) nuclear features
  3. HER2 positivity
  4. Hormone receptor positivity
  5. TP53 mutation
Board review style answer #2
D. Hormone receptor positivity. Compared with classic lobular carcinoma, pleomorphic lobular carcinoma is more likely to be HER2 positive, hormone negative and TP53 mutated. Marked nuclear pleomorphism is a required feature of pleomorphic lobular carcinoma. Neither classic nor pleomorphic lobular carcinoma feature glandular formation. (Cell Oncol (Dordr) 2012;35:111)

Comment Here

Reference: Classic lobular carcinoma
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