Week 5 Part 2 - Malignant Breast Pathology Flashcards
Breast Carcinomas are Divided into what Categories?
In Situ carcinomas - those contained to ducts and lobules surrounded by basement membrane
Invasive carcinomas - synonymous with ‘infiltrating’ carcinoma, with invasion beyond the basement membrane into surrounding stroma, vasculature, regional nodes and eventually distant sites
Ductal Cell Carcinoma (DCIS)
Ductal cell carcinoma (DCIS) is proliferating epithelial cells confined to ducts and/or lobules, by the BM
When DCIS involves lobules, the expanded acini take on the appearance that resemble ducts
DCIS can spread through the ductal system to produce lesions that may involve entire sections of a breast
Identified by calcifications associated with necrosis or secretory material
Lobular DCIS
Is a clonal cell proliferation of cells within ducts and lobules that grow in a discohesive pattern due to the loss of tumour suppressive adhesion protein E-cadherin
Lobular is an incidental finding that is not associated with calcification or stromal reactions
Shows a uniform population of small oval to round cells with uniform nuclei
Small mucin like vacuoles can be present called ‘neolumina’
LCIS is positive for ER and PR however, overexpression of HER2 is not usually observed
Lobular DCIS - Microscopy
Proliferation of epithelial cells of TDLU with no invasion of BM
LCIS cells and lobules themselves are larger, distended and monomorphic compared to normal cells that line the lobules/acini
Lobules are filled by uniform, round, small to medium sized cells with round mildly hyperchromatic nuclei.
Classic cases, atypia, pleomorphism, mitotic activity and necrosis are minimal or absent, with discohesion among tumour cells
Invasive Carcinoma
Invasive carcinomas include all lesions with evidence of stromal invasion
Can be divided based on molecular and morphologic characteristics in several clinical subgroups:
- ER-Positive HER2 negative
- HER2-Positive
- ER-negative HER2 negative
Morphology - similar to in situ lesions, invasive lesions are divided into two major categories:
- ductal type
- lobular type
Invasive Ductal Carcinoma
Classic (NOS) invasive ductal ca:
- the most common expression of breast cancer without further qualification
- the size, shape, consistency and type of margins are highly variable and dependant on the relative amounts of tumour cells and stroma
Gross appearance:
- firm and poorly circumscribed, cuts with a gritty sensation and a yellow/grey cut surface with trabeculae radiating into surrounding tissue
- areas of necrosis, haemorrhage and cystic degeneration
Invasive Ductal Carcinoma Variants
Tubular carcinoma
Cribriform carcinoma
Mucinous carcinoma
Medullary carcinoma
Invasive Ductal Carcinoma - Microscopy
Tumours can grow in diffuse sheets, well-defined nests, cords or as individual cells
The amount of stroma may range from none to abundant, from densely fibrotic to cellular and desmoplastic
The amount of elastic fibres in the wall of the ducts and vessels is responsible for the chalky streak seen on gross examination
Calcification can be identified on imaging in ~60% of cases
Multiple patterns of ER, PR and HER2 markers
Invasive Tubular Carcinoma
Poorly circumscribed margins with a hard consistency
Usually multifocal in nature and can occur bilaterally, because of the well differentiated nature and younger age onset
Most are ER positive and HER2 negative
Invasive Tubular Carcinoma - Histology
Scant pleomorphism
Glands display a haphazard arrangement
Frequent invasion of adipose tissue is usually seen at the periphery of the lesion
Formation of trabecular bars with a lack of a myoepithelial component and a lack of a BM
Cribriform Carcinoma
Rare form of breast carcinoma closely related to tubular carcinoma, and usually has a good prognosis
Microscopy:
- tumour has a cribriform appearance
- sharp punched out round spaces
- exhibits stromal invasion, again seen in tubular carcinoma
- no BM
ER +ve
Mucinous Carcinoma
Grossly appears as a gelatinous carcinoma, usually well circumscribed, crepitant on palpation and formed by a jelly-like mass held together by septa
Microscopy:
- small clusters of tumour cells usually appear in a ‘floating’ sea of mucin.
- clusters may be solid or exhibit acinar formations
- mucin is almost entirely extracellular and may be of acid or neutral type
- MUC2 is strongly cytoplasmic positive
- ER positive with HER2 negative
Medullary Carcinoma
Usually appear in patients >50yrs age and common in Japanese women
Common in women with BRCA1 mutation
Gross appearance:
- soft, well circumscribed, smooth periphery
- cut surface is solid, homogenous and grey in appearance
Prognosis is better than infiltrating ductal or lobular carcinoma
Oestrogen and HER2 negative
Medullary Carcinoma - Histology
Borders can be ill defined and the pattern of growth is diffuse, with minimal or no glandular differentiation
No mucin secretion
Tumour cells are usually large and pleomorphic, with large nuclei and prominent nucleoli
Prominent lymphoplasmacystic infiltrate at the periphery of the tumour is often present
Invasive Lobular Carcinoma
Invasive lobular ca (ILC) often presents as a palpable mass or on mammography, a lesion showing density with irregular borders
In the classic form, ILC is characterised by the presence of small, relatively uniform tumour cells, grow singly in ‘stack of coin’ arrangement
Usually ER positive, with HER2 overexpression rare
Invasive Lobular Carcinoma - Histology
Tumour cells arranged in columns or single file structures, signet ring appearance
No evidence of gland architecture, stroma is abundant, of dense fibrous type
Lymphocytic infiltrate may be evident
HMW keratins, lack of P53, and most importantly decrease or absence of E-cadherin
