Carcinoma in situ

• By definition, pre-invasive carcinoma
• Confined within ducts and/or lobules
• If genuinely in situ then no risk of metastatic behaviour
• Subclassified into "ductal" (DCIS) & "lobular" (LCIS)
• Immunostains very helpful in diagnosis e.g CK 5/6 or P63 to confirm single cell population or lack of invasion - see also Immunohistochemistry and examples on this page of intermediate and high grades below
• DCIS usually managed by excision
• LCIS usually observed

• Confined within ducts
• May occur in isolation - often screen-detected in this situation
• Luminal and periductal calcs common - visible on mammograms
• Nuclear grading most robust and reproducible in terms of predicting prognosis
• Usually admixed with invasive cancer
• When invasive & in situ together nuclear grade of each element often the same
• When present in large ducts beneath the nipple may present as Paget's Disease
• DCIS may extend from the adjacent duct ito lobules - Cancerisation
• Compare the cytology of these cancerisation cells with that of ALH and LCIS

 See also additional examples prepared for the Sloane Project website.

College of American Pathologists Guidelines for grading DCIS:

• Grade 1:
• Monotonous nuclei, 1.5 to 2.0 RBC diameters
• finely dispersed chromatin & only occasional nucleoli
• Grade 2:
• Neither nuclear grade 1 nor nuclear grade 3
• Grade 3:
• Markedly pleomorphic nuclei, usually greater than 2.5 RBC diameters
• coarse chromatin & prominent or multiple nucleoli

Low grade DCIS (Example 1)

Low grade DCIS (Example 2)- Low Power Left; High Power Right

Low grade cribriform DCIS (Example 3) - 'Mouse over' for high power view

Low grade micropapillary DCIS (Example 4) - 'Mouse over' for high power view
Note how the tufts of DCIS sit on a peripheral rim of intact myoepithelial cells (recognized by their clear cytoplasm in this example)

Intermediate grade DCIS (Example 1) - Core biopsy showing luminal calcs

Intermediate grade DCIS (Example 2)- Core biopsy - medium and high power

Intermediate grade DCIS - Medium power Left; high power Right

Intermediate grade DCIS (Example 3)- Excision biopsy - medium power

Intermediate grade DCIS - Excision biopsy - high power

Intermediate grade DCIS - CK 5/6 (Left) - arrows point to small numbers of peripheral basal cells. There is no basal/myoepithelial population admixed with the cells expanding this duct; P63 staining highlights the peripheral myoepithelial population (Right)

Intermediate grade DCIS - Intracystic papillary DCIS with focus of invasion (Lower right of each image)
E cadherin immunostaining (right) helps emphasise the invasive focus

Medium power view of intracystic papillary carcinoma (upper)
and invasive focus (lower)

High grade comedo DCIS

High grade comedo DCIS - medium power

High grade comedo DCIS - high power

High grade DCIS
Strongly positive ER - Left; Almost uniformly negative CK 5/6 - Right

High grade DCIS with central comedo necrosis
Low Power Left; High Power Right

High grade DCIS with cancerisation of lobules (Example 1) - 'Mouse over' for high power view
The duct is shown upper left with its lobules lower right

Cancerisation of lobules (Example 2)

Paget's Disease of the nipple


• Presents as nipple redness/excoriation
• Usually unilateral
• May be confused with eczema
• An indication of high grade DCIS in large ducts beneath
• Paget's cells highlighted with CK7 or CerbB2 immunostains





Paget's Disease of the nipple: CK7 stain on lower right highlights Paget's cells in epidermis




Toker's Cells


• Cytologically similar to Paget's cells
• Positive staining with CK7 and EMA
• Do not stain with CerbB2 (Her-2)
• Correlate carefully with clinical and mammographic findings before making diagnosis




Biopsy of nipple - Toker's cells in epidermis





Lobular carcinoma in situ (LCIS)





"Classical" LCIS

Contrast the uniformity of appearance of LCIS with cancerisation of lobules. LCIS is E cadherin negative.

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Lobular Carcinoma in Situ - Acini expanded by uniform population of lobular epithelial cells




LCIS in ducts



When LCIS extends into ducts it does so in a 'Pagetoid' manner undermining the native ductal luminal epithelial layer. This is illustrated very clearly in the pair of images below with E Cadherin staining of the luminal epithelial layer and negative staining of the LCIS population in the immuno preparation:



Duct showing Pagetoid infiltration by LCIS - 'Mouse-over' to view E Cadherin immunostain









"Florid" LCIS:

'Florid' or pleomorphic LCIS can easily be mistaken for high grade DCIS with comedo necrosis and calcification. Note:



• Ducts and lobules expanded by uniform population of lobular pattern cells with focal comedo necrosis.
• Looks more like DCIS and probably behaves similarly also
• E Cadherin negative
• Strong association with co-existent invasive lobular carcinoma





Further example of florid LCIS







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