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lobular carcinoma in situ

LCIS

Wednesday 4 July 2012

Breast lobular carcinoma in situ; mammary lobular carcinoma in situ; LCIS

Definition: Breast carcinoma in situ (CIS) is classified into ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). Lobular carcinomas in situ (LCIS) represent 1-2% of all breast cancers. Both significance and treatment remain widely debated, as well as the possible similarities with DCIS.

LCIS has uniform, loosely cohesive cells. It is E-Cadherin negative, and commonly in the breasts bilaterally. Radiography frequently shows no changes, but can show non-specific calcifications.

Lobular carcinoma-in-situ (LCIS) is usually an incidental finding most commonly seen in upper outer and upper inner quadrants. It is multicentric in about 70% of cases and bilateral in 30% to 40% of cases.

DCIS is treated with surgical excision while LCIS can be clinically followed with or without hormonal treatment. Thus, it is critical to distinguish DCIS from LCIS.

Images

- LCIS at breastpathology.info

- Invasive and non-invasive lobular carcinoma of the breast

- LCIS

- LCIS with comedonecrosis

- vacuolar cells in LCIS

- pleomorphic LCIS

- DCIS vs LCIS differential diagnosis by p120

- Cytology of LCIS

- bone marrow metastasis of LCIS

- LCIS focally involving a radial scar

- LCIS involving collagenous spherulosis. p63 - and E-cadherin -

- ADH and LCIS association. E-cadherin stain.

- LCIS and CK34beta12

Digital case

- JRC:5418 : Breast lobular carcinoma in situ

Microscopy

Images: http://www.webpathology.com/case.asp?case=291

cohesive, mosaic pattern of cell growth (distinct cell borders), E-cadherin negative

The lobules are expanded and completely filled by a uniform population of round, small to medium-sized tumor cells. However, lobular enlargement and the complete absence of lumens are not absolute diagnostic requirements.

Atypia, nuclear pleomorphism, mitotic activity and necrosis are usually absent – except in a small subset of cases called Pleomorphic LCIS. The tumor cells show loss of cohesion. Scattered signet ring cells are frequently present. The tumor cells may show pagetoid spread into the neighboring terminal ducts; however, Paget disease is almost never seen.

- Central tumor necrosis can be seen.

- Possible pagetoid spread into the neighboring terminal ducts.

Associations

- LCIS may be present in benign proliferative lesions such as fibroadenomas, papillomas, radial sclerosing lesions and sclerosing adenosis.

When present in sclerosing lesions, LCIS distorts the lobular configuration and it is difficult to rule out invasion in such foci. However, in sclerosing lesions, the glandular units are surrounded by a basement membrane, myoepithelial cells and stroma.

These components can be highlighted by reticulin stain, immunostains for laminin and type IV collagen, and myoepithelial markers.

The presence of intracytoplasmic mucin supports LCIS. In addition, LCIS will show loss of E-Cadherin - a feature not seen with benign proliferative lesions mentioned previously.

Immunochemistry

Stains for mucin are positive in about 75% of LCIS cases. Immunohistochemically, the lack of E-Cadherin and beta-catenin and positivity for high molecular weight cytokeratin (perinuclear pattern) in LCIS help distinguish it from DCIS.

- E-cadherin (CDH1)

- p120 catenin (24966968)
— * Recent studies have shown that DCIS has membranous staining of p120 catenin and LCIS has diffuse cytoplasmic staining of P120 catenin.

  • This antibody cocktai CDH1-p120l can be applied in daily practice on paraffin-embedded tissue and is especially useful in small biopsies with small foci of CIS lesions.
  • mmunohistochemical staining with the antibody cocktail showed 100% concordance with the traditional single antibody immunostaining using either E-cadherin or P120 catenin antibody.
  • This antibody cocktail includes E-cadherin as a positive membranous stain for DCIS and P120 catenin as a positive cytoplasmic stain for LCIS, which may enhance accuracy and confidence in the differential diagnoses. (24966968)

Prognosis

LCIS is not always an indolent disease. The long-term outcome is quite similar to most ductal carcinomas in situ (DCIS).

LCIS is a risk Factor: About 20% to 30% of LCIS patients will develop invasive breast cancer which may be either lobular or ductal type. The risk is greater in cases with well-developed LCIS lesions. The risk is not dependent upon the quantity of LCIS. The increased risk applies to both breasts.

The patients with LCIS may be safely followed. Therapeutic intervention (such as simple mastectomy) may be considered in patients with strong family history of breast cancer, apprehensive patients, or in patients with extensive fibrocystic disease.

The main problems are the accuracy of pathological definition and a clear identification of more aggressive subtypes, in order to avoid further invasive LR.

BCS + WBRT should be discussed in some selected cases, and the long-term results seem comparable to DCIS.

Differential diagnosis

- atypical lobular hyperplasia ( ALH )

  • In atypical lobular hyperplasia (ALH), the lobules are normal sized and still contain identifiable lumina.
  • The term LCIS is used when the proliferative changes result in marked expansion of the lobular units by solid nests.
  • However, lobular enlargement is not an absolute diagnostic criterion for LCIS.
  • Likewise, complete absence of lumens is not necessary for the diagnosis of LCIS.
  • Image: http://www.webpathology.com/image.asp?n=10&Case=291

CGH

- gains

  • 20q13.13 gain

- losses

  • 19q13.2-q13.31 loss
  • 16q21-q23.1 loss

See also

- mammary lobular carcinomas

  • mammary invasive lobular carcinoma

- carcinoma in situ

Open references

- Current Concepts in Diagnosis, Molecular Features, and Management of Lobular Carcinoma In Situ of the Breast With a Discussion of Morphologic Variants. 2017. http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2016-0421-RA

- Lobular carcinoma in situ (LCIS) of the breast: is long-term outcome similar to ductal carcinoma in situ (DCIS)? Analysis of 200 cases. Cutuli B, De Lafontan B, Kirova Y, Auvray H, Tallet A, Avigdor S, Brunaud C, Delva C. Radiat Oncol. 2015 May 6;10(1):110. doi : 10.1186/s13014-015-0379-7 PMID: 25944033 (Free)

- Diagnostic utility of E-cadherin and P120 catenin cocktail immunostain in distinguishing DCIS from LCIS. Li X, Schwartz MR, Ro J, Hamilton CR, Ayala AG, Truong LD, Zhai QJ. Int J Clin Exp Pathol. 2014 Apr 15;7(5):2551-7. eCollection 2014. PMID: 24966968 (Free)

References

- Mastracci TL, Shadeo A, Colby SM, Tuck AB, O’Malley FP, Bull SB, Lam WL, Andrulis IL. Genomic alterations in lobular neoplasia: a microarray comparative genomic hybridization signature for early neoplastic proliferationin the breast. Genes Chromosomes Cancer. 2006 Nov;45(11):1007-17. PMID: 16897748