L29 - Pathology of breast cancer

Question 1

Commoner affected site of breast carcinoma

Answer 1

Ductal carcinoma are more common than lobular carcinoma

Question 2

Histological classification of breast carcinoma

Answer 2

A) non-invasive - ductal carcinoma in situ (DCIS) - lobular carcinoma in situ (LCIS) B) invasive - invasive ductal carcinoma - invasive lobular carcinoma

Question 3

DCIS features

Answer 3

• 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.

Question 4

Histology of DCIS

Answer 4

• 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）

Question 5

DCIS prognosis

Answer 5

• 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)

Question 6

LCIS general features

Answer 6

• 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.

Question 7

LCIS prognosis

Answer 7

• 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.

Question 8

LCIS histology

Answer 8

• rounded/oval nuclei
• small nucleoli
• rounded dyscohesive (not attached to adjacent cells) cells due to loss of E-cadherin

Question 9

Invasive ductal carcinoma characteristics

Answer 9

• 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.

Question 10

Invasive lobular carcinoma characteristics

Answer 10

• 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)

Question 11

Invasive lobular carcinoma histology

Answer 11

• 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.

Question 12

Special types of invasive ductal carcinoma

Answer 12

1) Tubular carcinoma
2) Mucinous carcinoma
3) Medullary carcinoma

Question 13

Tubular carcinoma features

Answer 13

• Special type of low-grade invasive ductal carcinoma
• excellent prognosis in the pure form (Distant metatastasis are unlikely to occur and they rarely kill)

Question 14

Mucinous carcinoma features

Answer 14

• 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.

Question 15

Medullary carcinoma features

Answer 15

• 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.

Question 16

Spread of breast cancer

Answer 16

• 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

Question 17

Sentinel lymph node

Answer 17

Definition: The first lymph node(s) to which cancer cells are most likely to spread from a primary tumor.

Question 18

Sentinel lymph node biopsy

Answer 18

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.

Question 19

Options of breast cancer treatment

Answer 19

• 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.

Question 20

prognostic and predictive marker of breast carcinoma

Answer 20

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

Question 21

histologic type and grade of breast cancer

Answer 21

Grade I to III, based on:

1) tubular formation
2) nucleus status
3) mitotic rate

Question 22

lymph node metastases evaluation

Answer 22

Sentinel lymph node biopsy

• overall number of nodes involved
• level of nodal involvement

Question 23

Steroid hormone receptor status indications

Answer 23

70% ER positive tumour show responce to hormonal manipulation (e.g. SERMs such as tamoxifen)

Question 24

HER2 oncogene overexpression indications

Answer 24

1) marker of poor prognosis in lymph nodes
2) positive predictor for chemotherapy (reactive to herceptin doxorubicin-based chemotherapy)

Question 25

FISH

Answer 25

Flourescent in-situ hybridization

An immunohistochemical assay to identify HER2 (very expensive with questionable reliability)

Question 26

Breast cancer staging

Answer 26

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:

1. Pathology (Sentinel lymph node/lymph node biopsy)
2. 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

Question 27

Molecular Classification of Breast Cancer

Answer 27

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.

Question 28

Luminal carcinoma

Answer 28

ER positive, highly responsive to hormonal manipulation (use of selective oestrogen receptor modulators (SERMS) such as tamoxifen)

Question 29

HER2 carcinoma

Answer 29

HER2 +

responsive to herceptin doxorubicin-based chemotherapy

Question 30

Basal-like carcinoma

Answer 30

Triple negative (ER-, PR-, HER2 -)

• poor prognosis
• require combination therapy (surgery with adjuvant chemotherapy and radiotherapy)