CLASSIFICATION OF
TUMOURS
Dr Mohamed Elkablawy
ناقص مالحظةالصور اضافة
Neoplasia 2
CLASSIFICATION OF TUMOURS
Intended Learning outcomes
By the end of this talk you should
•Be aware of the calssification of tumours
•Know how tumours are named
•Be familiar with the differences between
benign and malignant tumours
•Know how malignant tumours spread
CLASSIFICATION OF TUMOURS
Calssification Of Tumours
Usually on basis of presumed cell/tissue of origin
OR
On predicted behaviour
CLASSIFICATION OF TUMOURS
Calssification Of Malignant Tumours
Usually on basis of cell/tissue of origin
Main groups are:
•Epithelial
•Connective tissue (mesenchymal)
•Lymphoid/haematological
•Mixture of all (teratomas)
CLASSIFICATION OF TUMOURS
Nomenclature
Tissue of origin
Epithelial:
• cell of origin benign malignant
•Squamous cell Papilloma Sq C carcinoma
•Glandular Adenoma Adenocarcinoma
•Transitional TC Papilloma T C carcinoma
•Basal BC Papilloma B C carcinoma
CLASSIFICATION OF TUMOURS
Nomenclature
Tissue of origin
Mesenchymal:• cell of origin benign malignant
•Smooth Muscle Leiomyoma Leiomyosarcoma
•Striated Muscle Rhabdomyoma Rhabdomyosarcoma
•Blood Vs Heam(angioma) Angiosarcoma
•Nerves Neurofibroma Neurofibrosarcoma
•Adepose tissue Lipoma Liposarcoma
•Cartilage Chondroma Chondrosarcoma
•Bone Osteoma Osteosarcoma
CLASSIFICATION OF TUMOURSNomenclature
Tissue of origin
Mesenchymal:
• cell of origin benign malignant
•Lymphoid Lymphoma
•Hemopoietic Leukemia
•Melanocytes Neavus Melanoma
•Embryonic tisue
•Totipotential cells Teratoma Malignant teratoma
•Unipotential cells Retinoblastoma
Nephroblastoma
CLASSIFICATION OF TUMOURS
Benign Tumours
• Generally slow growing
•Remain localised
•Do not invade surrounding tissues
•Do not spread to distant sites
•Resemble tissue of origin i.e. Well
differentiated
CLASSIFICATION OF TUMOURSBenign Tumours (Microscopic)
• Mitotic activity is low
•Mitotic figures appear normal
•Nuclei appear normal
•No necrosis
CLASSIFICATION OF TUMOURS Benign Tumours (Effects)
• May be unsightly, removed for cosmotic
purposes
•Damage tissue by pressure effects
•Block ducts such as a pancreas or
bronchus
•Block flow of fluid in brain
•May secrete hormones
•May become malignant
CLASSIFICATION OF TUMOURS
Malignant Tumours
• Generally rapid growing
•Irregular edges poorly defined margins
•Invade surrounding tissues
•Spread to distant sites
•May not resemble tissue of origin i.e.
poorly differentiated or anaplastic
CLASSIFICATION OF TUMOURSMalignant Tumours (Microscopic)
• Mitotic activity is high
•Abnormal Mitotic figures
•Nuclei are hyperchromatic and
pleomorphic
•Necrosis usually occur
CLASSIFICATION OF TUMOURS
Malignant Tumours (Spread)
• Invade surrounding tissues
•Spread via lymphatic channels to lymph
nodes
•Spread via blood stream to other organs
i.e. metastasis
•Spread across body cavities
CLASSIFICATION OF TUMOURS
Malignant Tumours - Effects
• Destruction of adjacent tissues causing
pain and loss of function
•Pressure on structures leading to
necrosis and infection
•Haemorrhage from surface ulceration
•Obstruction of flow through vital
structures
CLASSIFICATION OF TUMOURS
Malignant Tumours - Effects
• Secondary deposits (metastasis) causing
damage at distant sites
•Cachexia (wasting) due to tumour
necrosis factor-α
•Production of hormones either
appropriate or inappropriate (ectopic)
•Paraneoplastic syndromes
carcinoma of breast. This is not a specific histologic type of breast cancer, but rather
it implies dermal lymphatic invasion by some type of underlying breast carcinoma.
Such involvement of dermal lymphatics gives the grossly thickened,
erythematous, and rough skin surface with the appearance of an orange peel
("peau d'orange"). BACK
CLASSIFICATION OF TUMOURS
Malignant Tumours - Metastasis
• Process by which neoplastic cells from
primary tumour spread to distant sites.
•Involves primary tumour invation into
surrounding tissues, specially vessels
(lymphatic or blood)
•Then detachment within vessels and
transport as emboli
CLASSIFICATION OF TUMOURS
Malignant Tumours - Metastasis
• Extravasation (move from vessel to
tissue) and growth at distant sites
•Lymphatic spread leads to lymph node
involvement
CLASSIFICATION OF TUMOURS
Malignant Tumours - Metastasis
• Blood vessel spread leads to
haematogenous metastasis (liver, lung,
bone and brain)
•Less commonly, transcoelomic spread
occurs (across body cavities)
CLASSIFICATION OF TUMOURS
Malignant Tumours
Stage/Grade of tumours
• GRADE refers to how closely tumours
resemble their tissue of origin
•STAGE refers to how far a tumour has
spread at the time of presentation
CLASSIFICATION OF TUMOURS
Malignant Tumours
Stage/Grade of tumours• Different systems exist for different tumours
•Dukes’ stage predicts prognosis for colorectal
tumours
•Duke’s A: 90% 5yrs, continued to bowel wall
•Duke’s B: 66% 5yrs, outside bowel wall, LN -ve
•Duke’s C: 33% 5yrs, LN +ve
CLASSIFICATION OF TUMOURS
Malignant Tumours
Stage/Grade of tumours
TNM system• T : Primary tumour size
•N : Lymph Node involvement
•M : Distant metastasis
•Different TNM for each different organ and
tumour
Breast Blood + Lymphatic Supply
• Arterial:
• Anterior perforating branches of internal
mammary artery (internal thoracic)
• Branches of external mammary artery (lateral
thoracic)
• Venous:
• Axillary vein
• Internal thoracic vein
Breast Blood + Lymphatic Supply
• Lymphatic:
• 75% To ipsilateral axillary lymph nodes
• Central
• Pectoral
• Subscapular
• Remainder to infra/supraclavicular and
parasternal lymph nodes, and to contralateral
breast
Breast Histology
Breast Histology
Breast Histology (lobules)
carcinoma of breast. This is not a specific histologic type of breast cancer, but rather
it implies dermal lymphatic invasion by some type of underlying breast carcinoma.
Such involvement of dermal lymphatics gives the grossly thickened,
erythematous, and rough skin surface with the appearance of an orange peel
("peau d'orange"). BACK
Duct Carcinoma In Situ (DCIS)
• Aka intaduct carcinoma
• Tumour cells confined to ducts and acini – no
evidence of any invation of surrounding stromal
tissue
• Tumour cells therefore have no access to
lymphatics or blood vessels
• Approximately 3 – 5% cancers in symptomatic
series and Up to 25% in screening series
• Clinical presentations: mass, nipple discharge,
paget’s disease.
• Mammographic presentation: microcalcification
Duct Carcinoma In Situ (DCIS)
Breast Cancer
• Second most common cancer after lung
• 10.4% of all cancer incidence
• Commonly arises in lobules or ducts
• Can present with symptoms e.g. lump,
lymphadenopathy, nipple discharge
• Can be identified on screening e.g. mammogram
• Requires triple assessment
• 1. Clinical examination
• 2. Radiology (mammogram, Ultrasound)
• 3. Tissue diagnosis (FANC, core biopsy, excisional
biopsy)
Br Ca Macroscopic Appearance
Br Ca Lymph Nodes
• Historically, large groups were removed
Side effects: lymphoedema
• Sentinel lymph node mapping
- Examines first node(s) to drain tumour
for evidence of malignancy
- Identify with dye & radiation
- Can prevent 65 – 70% of patients having
unnecessary axillary node clearance
صورة
Invasive Carcinomas
• Invasive duct carcinoma (carcinoma of no special
type [NST]
• Invasive lobular carcinoma
• Tubular carcinoma
• Mucinous carcinoma
• Medullary (like) carcinoma
• Metaplastic carcinoma
• Rarities
Ductal, NST
• Commonest up to 75%
• Contains <50% of special type characteristics
• Wide variety of histological appearances
Vertebral metastasis
Vertebral metastasis
Liver metastasis
Tumour staging
• Based on degree of tumour spread
• TNM classification
• T – local spread – size, involvement of local
structures e.g. skin, chest wall
• N – Nodes – axillary (IPSL – and contralateral),
internal mammary, supraclavicular. Number and
size (very complicated)
• M – distant metastasis
Stage grouping
• Grouped into stage 0 – stage IV according to TNM
classification
• Eg. Stage 1 – T1,N0,M0
• Stage IV – M1, any T and N
• Useful for clinical trials
Prognostic indicators
• Lymph node stage
• Tumour size
• Tumour grade
• Tumour type
• Lymphovascular invasion
• (extensive DCIS at margins)
• (Margin clearance)
Surgery
• Treatment depends on stage
• Surgery is the mainstay
• Clear margins important
• 1. Wide local excision (lumpectomy/ breast
conservative therapy)
• 2. Mastectomy if
• Multi-focal tumours
• Previous radiotherapy to breast
• Tumour large relative to breast
• Patient preference
Other treatments• Radiotherapy
• - Reduces risk of local recurrence
• Chemotherapy
• - Systemic treatment, more advanced disease
• Hormone Therapy
- Depending on ER/PR expression
- Tamoxifen (ER antagonist)
- Aromatase inhibitors (block oestrogen production)
• Monoclonal antibodies
• -Herceptin (HER2/neu receptor antagonist)
CLASSIFICATION OF TUMOURS
Intended Learning outcomes
By now you should
•Be aware of the calssification of tumours
•Know how tumours are named
•Be familiar with the differences between
benign and malignant tumours
•Know how malignant tumours spread
Breast Carcinoma
The most common malignancy in women
In UK 1 in 10-12 chances 1 in 8 women in US Less incidence in Asia Majority of cancers arise
in the ducts. Very rare before age 25
Normal Breast
Large ductLobules
Normal Breast
A normal breast acinus. Note the epithelial cells lining the lumen demonstrate apocrine secretion with
snouting, or cytoplasmic extrusions, into the lumen.
Comparison of the gross characteristics of a classic infiltrating ductal carcinoma on the left and a benign fibroadenoma on the right
Crab like shapedue to lines of infiltration
Infiltrating Duct Carcinoma
Prominent bands of collagen
Tendcy to form ductal strucures
Invasive Lobular CarcinomIndian File Strands
Infiltrating Duct CarcinomaLocal Spread
Retraction of nipple
Fixation to underlying muscle
Here is a surgical excision of a small mass from the breast. The mass is well-
circumscribed. Grossly it felt firm and rubbery. This is a fibroadenoma. The blue dye
around the fibroadenoma was used to mark the lesion during needle localization in
radiology so that the surgeon could find this small mass.
BACK
Here is the microscopic appearance of a fibroadenoma. To the right is compressed breast connective tissue
forming a "capsule" to this mass. The neoplasm itself is composed of a fibroblastic stroma in which are located elongated compressed ducts lined by benign appearing
epithelium
BACK
This is the gross appearance of fibrocystic changes in the breast. A 1.5 cm cyst is noted here. This can lead to palpation of an ill-defined "lump" in the
breast. Sometimes, fibrocystic changes produce a more diffusely lumpy breast.
BACK
Another example of microscopic fibrocystic changes of the breast are shown here. Fibrocystic changes
account for the majority of "breast lumps" that are found in women of reproductive years, particularly
between age 30 and menopause.
BACK
This is the histologic appearance of fibrocystic changes in breast. There are cystically dilated ducts, areas of
lobules that are laced with abundant fibrous connective tissue (sclerosing adenosis), and stromal fibrosis. There is even a small area of microcalcification seen just to
the upper right of center. No atypical changes are seen here
BACK
Prominent sclerosing adenosis, one of the features of fibrocystic changes, is demonstrated by the appearance
of a proliferation of small ducts in a fibrous stroma. Although it is benign, the gross and mammographic
appearance may mimic carcinoma, and it can be difficult to distinguish from carcinoma on frozen section.
BACK
There is prominent Apocrine Metaplasia change of the cells lining the cysts in this example of fibrocystic changes of breast. Note the tall, pink, columnar nature of the epithelial cells. This appearance is
benign.
BACK
A small benign intraductal papilloma appears here in a breast duct, typically in one of the main lactiferous
ducts beneath the areola. Note that the epithelial cells show no atypia and that there is a fine pink collagenous stroma within the papilloma. An intraductal papilloma
may be associated with a serous or bloody nipple discharge, or it may cause some nipple retraction.
BACK
Infiltrating ductal carcinoma, the pleomorphism of the carcinoma cells
within the duct in the center (in a cribriform pattern), as well as the
neoplastic cells infiltrating through the stroma and fat, can be seen
BACK
“Scirrhous carcinoma of the breast” , small nests and infiltrating strands of neoplastic cells with prominent
bands of collagen between them. It is this marked increase in the dense fibrous tissue stroma that produces the characteristic hard "scirrhous"
appearance of the typical infiltrating ductal carcinoma. Note the nerve surrounded by the neoplasm at the
lower left. BACK
Lobular carcinoma in situ is seen here. Lobular CIS consists of a neoplastic proliferation of cells in the terminal breast ducts and acini. The cells are small and round. Though these lesions are low grade, there is a 30% risk for development of invasive carcinoma in the same or the opposite breast.
BACK
The cells of this breast carcinoma are highly positive for estrogen receptor with this immunoperoxidase stain. Estrogen receptor positivity correlates with a better prognosis because such positive neoplastic cells are better differentiated and more sensitive to hormonal
manipulation. BACK
Paget's cells of Paget's disease of breast have abundant clear cytoplasm and appear in the epidermis either singly or in clusters. The nuclei of the Paget's cells are atypical
and, though not seen here, often have prominent nucleoli
BACK
This variant of breast cancer is known as colloid, or mucinous, carcinoma. Note the abundant bluish
mucin. The carcinoma cells appear to be floating in the mucin. This variant tends to occur in older women and
is slower growing, and if it is the predominant histologic pattern present, then the prognosis is better than for
non-mucinous, invasive carcinomas.
BACK
carcinoma of breast. This is not a specific histologic type of breast cancer, but rather
it implies dermal lymphatic invasion by some type of underlying breast carcinoma.
Such involvement of dermal lymphatics gives the grossly thickened,
erythematous, and rough skin surface with the appearance of an orange peel
("peau d'orange"). BACK