MALIGNANT EPITHELIAL BREAST LESIONS

Breast cancer - General notes.

Risk factors: family Hx (genes BRAC1 & BRAC2 are major factors), age, proliferative breast disease, personal Hx, radiation, oestrogen exposure (early menarche/late menopause), nulliparity, obesity, HRT (exogenous oestrogen therapy).

Incidence in breast quadrants: Left breast affected more (110:100), upper outer quadrant accounts for 50% of tumours.

Classification: In situ or Invasive. In situ (15-30%): ductal, lobular. Invasive (70-85%): ductal (no special type), lobular, tubular, colloid, medullary, papillary.

All breast Ca arise from the terminal duct lobular unit (TDLU).

1. IN SITU CARCINOMA

a) Duct carcinoma in situ: In this cancer, the epithelial cells lining the ducts show malignant characteristics: loss of polarity, pleomorphism, hyperchromasia, high nuclear/cytoplasmic ratio, increased mitotic activity, prominent nucleoli. The cancer is in situ, meaning there is NO invasion through basement membrane. The epithelium is more than 2 cell layers thick.
Morphology:

• Microscopy:
  
• Architecture:
  
• solid (lumen filled with malignant cells),
  
• cribiform/tubular (round regular spaces within glands --> indicates malignancy),
  
• papillary (epithelial projections into lumen without fibrovascular stroma).
  
• Cytological grade: a) low, b) intermediate, c) high. Low grade --> High grade just means cell atypia worsens (refer to above).
  
• Comedo (central) necrosis: present / absent. If present --> then its more likely to be high cytological grade --> worse.

Lobular carcinoma in situ is not discussed in the notes. You can read about it on Pg 1109, Robbins, Fig 25-19.

2. INVASIVE CARCINOMA
a) Invasive duct carcinoma of no special type (70-80%): In this cancer, the epithelial cells are malignant and invade into the stroma. Clinically, you will feel a mass of stony hard consistency.
Morphology: Microscopy: 1) tumours cells grow in sheets, cords, nests, individually, invade into stroma + fat 2) tumour cells vary from small - large, but are generally larger + prominent nuclei/nucleoli than their lobular counterparts, 3) absence of myoepithelial cells (special staining).

b) Tubular carcinoma: This cancer has lots of tubules lined with ductal epithelium.
Morphology: Microscopy: 1) tumour cells are arranged tubular fashion, absence of myoepithelial cells (special staining), 2) apocrine snouts.
Prognosis: excellent

c) Mucinous (colloid) carcinoma: This cancer usually occurs in post-menopausal women. Neuroendocrine differentiation occur in 25-50% of cases.
Morphology: Microscopy: 1) Small clusters of cells (solid/acinar formation) floating in a sea of mucin
Prognosis: excellent (no nodal mets)

d) Medullary carcinoma: This cancer is always 'pushing' the border type --> i.e: non infiltrative border.
Microscopy: 1) solid syncytium like sheets of large cells with pleomorphic nuclei, prominent nucleoli, high mitoses, 2) marked lymphoplasmacytic infiltrate at peripheral of tumour
Prognosis: mets to lower axillary lymph nodes + prognosis is better than invasive duct carcinoma

e) Invasive lobular carcinoma: This cancer has high proportion of bilaterality.
Morphology: 1) tumour cells growing in single file + invade into stroma, 2) tumour cells are not arranged in gland form, 3) signet ring configuration: if mucin abundant. Sometimes tumour cells do not grow in single file --> called variants (alveolar, trabecular, solid).
Prognosis: Although chances of bilaterality is high --> prognosis is same as invasive duct carcinoma. Particular mets to: abdominal cavity (GI tract, ovaries, serosal surfaces).

f) Paget's disease: This disease is characterised by eczema of the nipple. Paget's disease is like ductal carcinoma in situ where the cancer extends via the ducts into the nipple. Usually is accompanied by underlying duct carcinoma in situ
Morphology: Microscopy: 1) skin of the nipple ulcerated, ozzing, 2) large clear cells with atypical nuclei

SPREAD AND METASTASES

Routes of invasion: direct, lymphatics (axillary nodes, supraclavicular, internal mammary), haemotogenous
Distal metastases: skeletal system, lung, liver, ovary, adrenal, CNS.

PROGNOSIS
Stage: The higher stage --> worse prognosis
Size: Bigger --> badder, more chance of spreading --> even badder
Cytoarchitecture: Metaplastic = bad, Duct vs Lobular = same prognosis, Medullary / tubular / colloid: good prognosis.
Microscopic grade: The higher grade --> worse prognosis. Bloom-Richardson system is used for grading --> no need to know.
Skin/Nipple invasion: worse prognosis
Axillary lymph node mets: most important prognostic factors --> involvement = worse prognosis (factors: how many, extent of invidual node involvement etc)
Local recurrence: bad prognosis.

NON-EPITHELIAL BREAST MALIGNANCIES

Phylloides tumourL Basically this tumour is a cancer arising from intralobular stroma
Read Robbins pp 1103

Category: Pathology Notes