Pathology of Neoplasia
Tumor
– tissue mass
Neoplasm – “new growth”, clonal expansion of
cells with somatic mutations and
variable autologous growth regulatio
Cancer
–
neoplasm with invasive or metastat
properties
Morphology of Neoplasia
Malignant neoplasms invade
normal tissues and cause
mechanical disruption of
normal function
gastric cancer
mesothelioma
Superior vena cava
syndrome
Invasion and metastasis
of colon cancer
primary invasive
colon cancer
colon cancer
metastases
to liver
tubular adenoma with in situ and early invasive cance
tubular adenoma with in situ and early invasive cance
“Benign tumors” are not invasive
(leiomyoma of uterus)
Lymph node metastasis
Determinants of Cancer Metastatic Growth Sites
Breast Cancer
Colorectal Cancer
1. Pathways of lymphatic and
vascular drainage
2. Molecular determinants
for cell survival and growth
Summary: Growth of Metastatic
Cancer
• Spread of cancer cells to distant sites generally
follows pathways of lymphatic and vascular
drainage.
• Growth of cancer cells in metastatic site
depends on ability of neoplastic cells to
accommodate to new tissue (e.g., altered
molecular composition of cell surface).
Features of Benign and Malignant
Tumors
Benign
• Well circumscribed,
sometimes
encapsulated
• Non-invasive
• No associated
metastases
• Organized tissue
structures
Malignant
• Poorly circumscribed
• Penetrates capsule if
present
• Invasive into adjacent
tissues, lymphatics
and vasculature
• Metastases
• Poorly organized
aggregates of cells
Features of Benign and Malignant Cells
Benign
• Low N/C ratio
• Round nucleus, even
distribution of
chromatin
• Maintenance of
differentiation
• Uncommon mitoses
Malignant
• High N/C ratio
• Irregular nuclear
shape
• Clumped chromatin
• Prominent nucleoli
• Loss of differentiation
• Common mitoses,
often atypical
Cellular Features of Benign and
Malignant Cells
Benign
Malignant
Leiomyoma of Uterus
Leiomyosarcoma of Uterus
Follicular adenoma
(left) with intact
capsule
Follicular carcinoma
(right) invading
through capsule
Nomenclature of tumors
Pathological features of benign
and malignant tumors
Grading and staging cancer
Ancillary techniques to diagnose
and classify neoplasms
Nomenclature of Tumors
bile duct adenoma
tissue/ organ of origin
Nomenclature of Tumors
bile duct adenoma
pattern of differentiation
Nomenclature of Tumors
bile duct adenoma
benign
Nomenclature of Tumors
adenocarcinoma
malignant,
epithelial
Nomenclature of Tumors
squamous cell carcinoma
malignant,
epithelial
Nomenclature of Tumors
leiomyosarcoma
malignant,
mesenchymal
-oma as a suffix for malignant tumors
•
•
•
•
Lymphoma
Melanoma
Hepatoma (hepatocellular carcinoma)
Astrocytoma
Common terms for epithelial tumors
• Epidermoid – a synonym for squamous cell
• Adeno – glandular or ductal
• Transitional cell – urothelial cells lining
bladder, renal pelvis, ureters
Common terms for mesenchymal
tumors
•
•
•
•
•
Leiomyo – smooth muscle
Rhabdomyo – skeletal muscle
Chondro – cartilage
Osteo – bone (osteoid)
Fibro - fibrous
Features of Benign and Malignant
Tumors
Benign
• Well circumscribed,
sometimes
encapsulated
• Non-invasive
• No associated
metastases
• Organized tissue
structures
Malignant
• Poorly circumscribed
• Penetrates capsule if
present
• Invasive into adjacent
tissues, lymphatics
and vasculature
• Metastases
• Poorly organized
aggregates of cells
Features of Benign and Malignant Cells
Benign
• Low N/C ratio
• Round nucleus, even
distribution of
chromatin
• Maintenance of
differentiation
• Uncommon mitoses
Malignant
• High N/C ratio
• Irregular nuclear
shape
• Clumped chromatin
• Prominent nucleoli
• Loss of differentiation
• Common mitoses,
often atypical
Cellular Features of Benign and
Malignant Cells
Benign
Malignant
Leiomyoma of Uterus
Leiomyosarcoma of Uterus
Follicular adenoma
(left) with intact
capsule
Follicular carcinoma
(right) invading
through capsule
Tubular Adenoma of Colon
Invasive Colon Cancer
Descriptive terms used in cancer
nomenclature
•
•
•
•
•
•
Cystic
Papillary
Polypoid
Mucinous
Scirrhous
Annular
Neoplasms with intermediate levels
of malignancy
• Borderline / Low malignant potential
tumors (e.g., ovary)
• Carcinoid tumors (e.g., lung and
gastrointestinal system)
Pulmonary Carcinoid
Pulmonary
Carcinoid
Clinical situation as a determinant of
cancer diagnosis
• Site – smooth muscle tumor in uterus or in
retroperitoneum/ mesentery.
• Gender – teratoma in woman (ovary) or in
man (testis).
• Age – teratoma in testis of child or in testis
of adult man
Preinvasive neoplasia defies traditional
definitions of benign and malignant tumors
Tubular adenoma of colon
Carcinoma in situ (or severe
dysplasia) of squamous mucosa
In situ neoplasia
• Atypical cells
• Loss of maturation
• Mitotic activity
Examples of early (pre-invasive) neoplasia
neoplasm
“tumor”
risk for
malignancy
adenoma of colon
yes
variable
dysplasia of cervix
no
variable
dysplasia of bronchial
epithelium
atypical junctional
nevus
no
unknown
yes
moderate
Examples of “benign tumors”
neoplasm
“tumor”
risk for
malignancy
leiomyoma
yes
minimal
lipoma
yes
minimal
fibroadenoma
of breast
yes
minimal
intradermal nevus
of skin
yes
minimal
adenoma of colon
yes
variable
Grading and Staging Cancer
Grade: Loss of differentiation
and atypical nuclear features
Grade 1 – low grade
Grade 2 – intermediate grade
Grade 3 – high grade
Grade 1
Grade 2
Grade 3
Stage: size of tumor and extent
of spread
Stage 0 – non-invasive
Stage I –
Stage II – Variable extent of invasion
Stage III - and lymph node metastases
Stage IV – metastatic
TNM staging of cancer
• T – size and extent of local invasion
• N – lymph node metastases
• M – metastases to other organs
T Staging for Lung Cancer
T0
No evidence of primary tumor
T1
Primary tumor < 3 cm, does not affect pleura or
main bronchus
Tumor > 3 cm or involves pleura or involves
main bronchus
Tumor involves chest wall or bronchus within 2
cm of trachea
Tumor involves mediastinum, trachea, or
esophagus, or has pleural effusion
T2
T3
T4
T Staging for Breast Cancer
T0
No evidence of primary tumor
T1
Primary tumor < 2cm
T2
Tumor > 2 cm, < 5 cm
T3
Tumor > 5 cm
T4
Tumor invades chest wall, or inflammatory
carcinoma
N Staging for Lung Cancer
N0
No lymph node metastases
N1
Involves ipsilaterial hilar or peribronchial nodes
N2
Involves ipsilateral mediastinal nodes
N3
Contralateral spread
N Staging for Breast Cancer
N0
No lymph node metastases
N1
Metastases to same-side movable nodes
N2
Metastases to same-side fixed nodes
N3
Metastases to internal mammary nodes
Group Staging for Lung Cancer
Overall Stage
T Stage
N Stage
M Stage
Stage 0
Tis (In situ)
N0
M0
Stage IA
Stage IB
T1
T2
N0
N0
M0
M0
Stage IIA
Stage IIB
T1
T2
T3
T1
T2
T3
T3
Any T
T4
Any T
N1
N1
N0
N2
N2
N1
N2
N3
Any N
Any N
M0
M0
M0
M0
M0
M0
M0
M0
M0
M1
Stage IIIA
Stage IIIB
Stage IV
1.0
Stage-specific survival for lung cancer
Stage I
Stage II
Stage IIIa
Stage IIIb
Stage IV
Survival
0.8
0.6
0.4
0.2
1
2
3
Years after diagnosis
4
5
Ancillary techniques to diagnose
and classify neoplasms
Immunohistochemistry in diagnosis
and classification of cancer
• Markers can help to recognize normal
structures (e.g., basal cell layer)
• Some markers are differentially expressed
in normal and benign tissues
• Markers can identify pattern of
differentiation
Basal cell marker p63
(malignant glands lack staining)
Cancer marker α-methylacyl-CoA racemase
(malignant glands stain positive)
Cytokeratin 20
Colon
Urinary tract
Gastric
Pancreas/ biliary
Cytokeratin 7
Breast
Lung
Pancreas/ biliary
Ovary/ uterus
Salivary gland
Metastatic cancer in brain
CK 20
CK 7
Prognostic and Predictive Markers
for Cancer
• Pathological stage – most types of cancer
• Pathological grade
– Gleason score (prostate cancer)
• Biochemical and molecular markers
– Estrogen receptor (breast cancer)
– Proliferation markers (many types of cancers)
– Large numbers of other markers tested
Estrogen Receptor in Breast Cancer
•Favorable prognosis
•Responds to anti-estrogen therapy
Markers for early detection and
monitoring cancer
• Proteins – PSA is prototype
• RNA – usually inadequate stability
• DNA – stable and potentially fingerprint of
neoplasia
– Cancer specific mutations
– Cancer specific methylation patterns
Prostate-Specific Antigen (PSA)
• A protease that is made by prostate epithelial
cells
• Has the best positive predictive value of any
biochemical assay for cancer
0 – 2 ng/ml
2 – 4 ng/ml
4 – 10 ng/ml
> 10 ng/ml
1%
15%
25%
50%
PSA screening for Prostate Cancer
• Mortality rate has declined in post-PSA era.
• Comparison of incidence to mortality in
post-PSA era suggests over-diagnosis and
over-treatment