L29 - Pathology of breast cancer Flashcards
Commoner affected site of breast carcinoma
Ductal carcinoma are more common than lobular carcinoma
Histological classification of breast carcinoma
A) non-invasive - ductal carcinoma in situ (DCIS) - lobular carcinoma in situ (LCIS) B) invasive - invasive ductal carcinoma - invasive lobular carcinoma
DCIS features
- The tumour is still confined within the ductal basement membranes
- may be detectable by mammography at an early stage due to the presence of micro-calcification.
- About 50% are centrally situated and may form a palpable mass.
Histology of DCIS
- rounded lumen
- arch-like formation (roman arches)
- nuclei perpendicular to lumen
- cribiform formation (sieve-like)
- large pleomorphic cells
- central comedo necrosis (pus like granular content; microcalcification; common in high grade DCIS)
（High grade comedo DCIS has large pleomorphic cells and central comedo necrosis）
DCIS prognosis
- High grade comedo DCIS about 50%
evolve into invasive carcinoma within 5 years. - For non-comedo low grade DCIS, only 30% will
develop invasive carcinoma within the next 10-15 years - (Subsequent invasive carcinoma is usually in the same area as the initial DCIS)
LCIS general features
- Tend to occur in perimenopausal women, less common with advancing age.
- no distinguishing clinical features and radiologically undetecable (may be missed by mammography)
- often multicentric (70%) and bilateral (20-35%), usually concentrated within 5 cm of the nipple in the outer and the upper inner quadrants.
LCIS prognosis
- The likelihood of developing invasive carcinoma is about 10 times greater than that of the general population, with an absolute risk of 20-25% in 15 years.
- The site of later invasive carcinoma is equally divided between either breast. The subsequently developed carcinoma can be ductal or lobular.
LCIS histology
- rounded/oval nuclei
- small nucleoli
- rounded dyscohesive (not attached to adjacent cells) cells due to loss of E-cadherin
Invasive ductal carcinoma characteristics
- most common type of breast cancer (70% of invasive breast cancers)
- lack special features, termed NOS (not otherwise specified) or NST (no special type)
- characterized by a poorly defined hard, yellow-grey mass with radiating fibrous trabeculae. The tumor cuts with a gritty sensation and chalky streaks. The term cancer (crab-like) came from here.
Invasive lobular carcinoma characteristics
- accounts for approximately 5% of all breast tumours.
- Frequently multifocal and bilateral, presenting as a poorly circumscribed mass.
- very diffused (therefore difficult to palpate or visualize radiologically)
Invasive lobular carcinoma histology
- single cell infiltration, often in single file (Indian filing) or arranged as concentric rings around a duct (target-like lesion) of small to medium-sized tumour cells.
Special types of invasive ductal carcinoma
1) Tubular carcinoma
2) Mucinous carcinoma
3) Medullary carcinoma
Tubular carcinoma features
- Special type of low-grade invasive ductal carcinoma
- excellent prognosis in the pure form (Distant metatastasis are unlikely to occur and they rarely kill)
Mucinous carcinoma features
- special type of low-grade invasive ductal carcinoma
- excellent prognosis in the pure form.
- Tends to occur in older women
- presents as a slowly growing circumscribed mass that produces bulky, soft, gelatinous material. Islands of tumour cells are seen floating in large lakes of mucin.
Medullary carcinoma features
- Special type of invasive ductal carcinoma
- better prognosis than the usual infiltrative ductal carcinoma.
- characterized by syncytial-like sheets of large pleomorphic cells surrounded by heavy lympho plasmacytic infiltrate and well-circumscribed margins.
Spread of breast cancer
- Lymphatic spread is influenced by the location of the carcinoma (Lateral tumours will tend to spread to axillary and supraclavicular nodes. Medial and deep carcinomas will go to the internal mammary chain)
- Invasion to the pectoralis major muscle
- Haematogenous spread of carcinoma will result in metastases to skeleton, lung, liver, ovaries, adrenal glands, brains
Sentinel lymph node
Definition: The first lymph node(s) to which cancer cells are most likely to spread from a primary tumor.
Sentinel lymph node biopsy
Sentinel lymph node biopsy can be performed to determine whether cancer cells are present.
Positive: presence of metastatic cancer; more lymph nodes and sites might be affected
Negative: the cancer has not developed the ability to spread to nearby lymph nodes or other organs. further lymph node surgery unnecessary, which reduces the chances of potential adverse effects of lymph node surgery such as lymphedema.
Options of breast cancer treatment
- local excision
- partial mastectomy and combinations of radiotherapy and chemotherapy.
- includes the use of selective oestrogen receptor modulators (SERMS) such as tamoxifen and targeted
chemotherapeutic drugs such as Herceptin.
prognostic and predictive marker of breast carcinoma
1) size
2) histological type and grade
3) lympho-vascular permeation
4) lymph node metastasis
5) proliferative rate
6) clearance from resection margins
7) Steroid hormone receptor status
8) HER2 oncogene overexpression
histologic type and grade of breast cancer
Grade I to III, based on:
1) tubular formation
2) nucleus status
3) mitotic rate
lymph node metastases evaluation
Sentinel lymph node biopsy
- overall number of nodes involved
- level of nodal involvement
Steroid hormone receptor status indications
70% ER positive tumour show responce to hormonal manipulation (e.g. SERMs such as tamoxifen)
HER2 oncogene overexpression indications
1) marker of poor prognosis in lymph nodes
2) positive predictor for chemotherapy (reactive to herceptin doxorubicin-based chemotherapy)
FISH
Flourescent in-situ hybridization
An immunohistochemical assay to identify HER2 (very expensive with questionable reliability)
Breast cancer staging
Definition: The process to determine whether the cancer has spread within the breast or to other parts of the body; important in order to plan treatment
Procedures:
- Pathology (Sentinel lymph node/lymph node biopsy)
- Imaging (Chest X-ray, Bone scan, CT scan, PET scan)
TNM staging
- pTis: DCIS (including Paget’s disease)
- pT1 (pT1a <5mm; pT1b 5-10mm; pT1c 10-20mm)
- pT2: tumour (20-50mm)
- pT3: tumour (>50mm)
- pT4: tumour with direct extension to skin or chest wall
Molecular Classification of Breast Cancer
The major breast cancer subtypes can be classified as lumina, HER2 and Basal-like, each with characteristically different clinical features, treatment response and outcome.
major molecular subtypes can be approximated by the use of the traditional immunomarkers ER, PR and HER2.
Luminal carcinoma
ER positive, highly responsive to hormonal manipulation (use of selective oestrogen receptor modulators (SERMS) such as tamoxifen)
HER2 carcinoma
HER2 +
responsive to herceptin doxorubicin-based chemotherapy
Basal-like carcinoma
Triple negative (ER-, PR-, HER2 -)
- poor prognosis
- require combination therapy (surgery with adjuvant chemotherapy and radiotherapy)
