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ductal carcinoma in situ

DCIS

Monday 20 June 2005

Ductal carcinoma in situ of the breast; DCIS; mammary ductal carcinoma in situ

Microinvasion

@<@ 1 mm of invasion beyond the basement membrane is considered microinvasion in the breast. See : tumoral microinvasion

Links

 http://www.webpathology.com/case.asp?case=289
 http://www.breastpathology.info/Carcinoma%20in%20situ.html
 http://www.breastdiseases.com/slides/dcisslid.htm (TransMed)

Images

 DCIS

 roman bridges in situ ductal carcinoma (DCIS)

 micropapillary DCIS

 solid DCIS

 LCIS arising within collagenous spherulosis

 DCIS with pagetoid spread. E-cadherin and p120 catenin

 DCIS vs LCIS differential diagnosis by p120

 Chemotherapy-induced nuclear changes seen in an intraductal carcinoma of the breast

 DCIS with spindle cell morphology. Negative CK 5/6 helps to distinguish from florid (usual) ductal hyperplasia.

Microscopy

 DCIS involving multiple dilated ducts.
 Periductal fibrosis and chronic inflammation occur in the stroma.
 Extension of DCIS into lobules, so called cancerization of lobules, results in solid expansion of the acini and ductules. Notice the preservation of lobular architecture.

Types

 micropapillary DCIS
 cribriform DCIS
 solid-type DCIS / solid DCIS
 apocrine-type DCIS
 comedonecrosis / comedo type DCIS
 cystic hypersecretory DCIS
 lobular cancerization

 micropapillary DCIS

  • Image : http://www.webpathology.com/image.asp?case=289&n;=1
  • The dilated ducts are lined by multiple finger-like projections.
  • Dilated ducts are lined by multiple isolated papillae, some of which are fused to form Roman arches.
  • Roman arches derived from fusion of individual papillae.
  • Lack of fibrovascular cores within the papillae.
  • Multiple sieve-like glandular spaces can occur within ducts.
  • The lumens contain necrotic and secretory material.
  • Slender elongated epithelial fronds projecting into the glandular lumen.
  • These projections are solid and lack true fibrovascular cores.
  • They are composed of a uniform population of tumor cells with intermediate nuclear grade.
  • The papillae in micropapillary DCIS range from small bumps or mounds of tumor cells to slender papillary structures. The nuclear grade is high.
  • Some of the papillary fronds projecting into the lumen may be cut transversely resulting in appearance of small detached irregular clusters of tumor cells in the lumen (as seen here).
  • Cellular debris, usually a feature of cases with high nuclear grade, is also present in the lumen.
  • The papillary structures in some micropapillary DCISs show bulbous expansion of their tips.
  • Some of the adjacent papillary fronds have coalesced creating Roman bridge arches.
  • When fusion between adjacent fronds is extensive, it results in formation of cribriform structures.
  • Micropapillary and cribriform patterns of DCIS often coexist.

 cribriform DCIS

  • Image : http://www.webpathology.com/image.asp?n=4&Case;=289
  • multiple dilated ducts.
  • Cribriform spaces made up of a homogeneous population of cells which have uniformly round to oval nuclei.
  • These nuclei have low grade atypia.
  • Periductal fibrosis and chronic inflammation occur in the stroma.
  • In the cribriform DCIS, round fenestrations are found within the glands.
  • The more regular these spaces are in size, shape and distribution, the more likely the lesion to be malignant.
  • Cribriform DCIS shows superficial resemblance to adenoid cystic carcinoma and collagenous spherulosis and should not be mistaken for those entities.
  • cribriform DCIS can associate fenestrations, Roman bridges, and trabecular bars.
  • cribriform DCIS can show microcalcifications.

 solid-type

  • Solid filling of the ducts by malignant cells without necrosis.
  • Higher magnification can reveal the nuclei to be enlarged, hyperchromatic, irregular in size and shape. Nucleoli are small and few in number. The nuclear grade falls into the intermediate category.

 apocrine-type DCIS

 comedonecrosis / comedo type

  • Image : http://www.webpathology.com/image.asp?n=10&Case;=289
  • Macroscopy: multiple tiny spaces containing necrotic material, evident when compressing the specimen.
  • Solid sheets of malignant cells fill the dilated ducts.
  • The center of the involved ducts undergoes necrosis and calcification.
  • In DCIS with comedonecrosis, the involved duct shows a solid growth with high nuclear grade along the perimeter of the duct.
  • The lining cells can have large, round to oval hyperchromatic nuclei and prominent nucleoli characteristic of high grade appearance.
  • Mitotic activity is brisk and necrosis is always present in the lumen.
  • Coarse calcifications may be present in the necrosis.
  • The periductal tissue shows fibrosis and evidence of angiogenesis.

 lobular cancerization

  • Carcinoma cells are present within structures clearly identifiable as a lobule.
  • The lobule is greatly expanded by its involvement with DCIS.
  • The tumor cells have high nuclear grade.
  • The phenomenon of lobular cancerization further supports the notion of terminal duct-lobular unit (TDLU) as the site of origin of many of the intraductal carcinomas.

 DCIS with spindle cell morphology. Negative CK 5/6 helps to distinguish from florid (usual) ductal hyperplasia.

Grade

 mammary low-grade ductal carcinoma in situ

  • In low nuclear grade, small to medium sized nuclei which are uniformly round to oval in shape. There is little variation in nuclear size. The chromatin particles are finely granular and evenly distributed. Nucleoli are absent or indistinct.

 Intermediate nuclear grade.

  • The nuclei are medium to large in size and moderately irregular in shape.
  • The chromatin particles vary from finely to coarsely granular.
  • Small nucleoli are evident.

 mammary high-grade ductal carcinoma in situ

  • The nuclei are large, hyperchromatic, and highly variable in size and shape.
  • The chromatin particles are coarsely granular and unevenly distributed.
  • The nucleoli are large and easily seen.
  • The nuclei are pleomorphic and gigantic.
  • The vesicular appearance results from uneven distribution of coarse chromatin.
  • The nucleoli are prominent and multiple.

Differential diagnosis

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.

Breast carcinoma in situ (CIS) is classified into ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS).

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.

Immunochemistry

 E-cadherin (CDH1)

  • Immunohistochemical (IHC) staining for E-cadherin is routinely used to differentiate DCIS from LCIS in diagnostically challenging cases.
  • Circumferential diffuse membranous staining of E-cadherin is the typical pattern in DCIS, whereas LCIS lacks or shows decreased E-cadherin expression.

 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.
  • Immunohistochemical 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)

Management

 Consensus Guideline on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Ductal Carcinoma In Situ : 2 mm margins minimum

 Breast conservation in ductal carcinoma in situ (DCIS); what defines optimal margins?

Prognosis

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

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.

Molecular biology

 Breast ductal carcinoma in situ carry mutational driver events representative of invasive breast cancer. doi : 10.1038/modpathol.2017.21
http://www.nature.com/modpathol/journal/vaop/ncurrent/full/modpathol201721a.html

Links

 http://www.breastdiseases.com/slides/dcisslid.htm

See also

 invasive mammary carcinoma

  • invasive mammary ductal carcinoma
  • invasive mammary lobular carcinoma

 mammary carcinoma in situ (MCIS): DCIS and LCIS

Open references

 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

 Relationship between clinical and pathologic features of ductal carcinoma in situ and patient age: an analysis of 657 patients. Collins LC, Achacoso N, Nekhlyudov L, Fletcher SW, Haque R, Quesenberry CP Jr, Puligandla B, Alshak NS, Goldstein LC, Gown AM, Schnitt SJ, Habel LA. Am J Surg Pathol. 2009 Dec;33(12):1802-8. PMID: 19950406