Pathology of Neoplasia

Tumor – tissue mass

Neoplasm – “new growth”, clonal expansion of cells with somatic mutations and

variable autologous growth regulation

Cancer – neoplasm with invasive or metastatic properties

Morphology of Neoplasia

Malignant neoplasms invade normal tissues and cause mechanical disruption of normal function

gastric cancer

mesothelioma

Superior vena cava syndrome

primary invasive colon cancer

colon cancer metastases to liver

Invasion and metastasis of colon cancer

tubular adenoma with in situ and early invasive cancer

tubular adenoma with in situ and early invasive cancer

“Benign tumors” are not invasive (leiomyoma of uterus)

Lymph node metastasis

Determinants of Cancer Metastatic Growth Sites

1. Pathways of lymphatic and vascular drainage

2. Molecular determinants for cell survival and

growth

Breast Cancer Colorectal Cancer

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

• Well circumscribed, sometimes encapsulated

• Non-invasive• No associated

metastases• Organized tissue

structures

• Poorly circumscribed• Penetrates capsule if

present• Invasive into adjacent

tissues, lymphatics and vasculature

• Metastases• Poorly organized

aggregates of cells

Benign Malignant

Features of Benign and Malignant Cells

• Low N/C ratio• Round nucleus, even

distribution of chromatin

• Maintenance of differentiation

• Uncommon mitoses

• High N/C ratio• Irregular nuclear

shape• Clumped chromatin• Prominent nucleoli• Loss of differentiation• Common mitoses,

often atypical

Benign Malignant

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

• Well circumscribed, sometimes encapsulated

• Non-invasive• No associated

metastases• Organized tissue

structures

• Poorly circumscribed• Penetrates capsule if

present• Invasive into adjacent

tissues, lymphatics and vasculature

• Metastases• Poorly organized

aggregates of cells

Benign Malignant

Features of Benign and Malignant Cells

• Low N/C ratio• Round nucleus, even

distribution of chromatin

• Maintenance of differentiation

• Uncommon mitoses

• High N/C ratio• Irregular nuclear

shape• Clumped chromatin• Prominent nucleoli• Loss of differentiation• Common mitoses,

often atypical

Benign Malignant

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 colonCarcinoma in situ (or severe dysplasia) of squamous mucosa

In situ neoplasia • Atypical cells• Loss of maturation• Mitotic activity

Examples of early (pre-invasive) neoplasia

moderate

unknown

variable

variable

risk for malignancy

yes

no

no

yes

“tumor”

atypical junctional

nevus

dysplasia of bronchial epithelium

dysplasia of cervix

adenoma of colon

neoplasm

Examples of “benign tumors”

minimalyesintradermal nevus

of skin

minimalyesfibroadenoma

of breast

minimalyeslipoma

minimalyesleiomyoma

risk for malignancy“tumor”neoplasm

adenoma of colon yes variable

Grading and Staging Cancer

Grade: Loss of differentiation and atypical nuclear features Grade 1 – low grade

Grade 2 – intermediate gradeGrade 3 – high grade

Grade 2 Grade 3

Grade 1

Stage: size of tumor and extent of spread

Stage 0 – non-invasiveStage I – Stage II – Stage III - Stage IV – metastatic

Variable extent of invasion and lymph node metastases

TNM staging of cancer

• T – size and extent of local invasion• N – lymph node metastases• M – metastases to other organs

No evidence of primary tumor T0

Primary tumor < 3 cm, does not affect pleura or main bronchus

T1

Tumor > 3 cm or involves pleura or involves main bronchus

T2

Tumor involves chest wall or bronchus within 2 cm of trachea

T3

Tumor involves mediastinum, trachea, or esophagus, or has pleural effusion

T4

T Staging for Lung Cancer

No evidence of primary tumor T0

Primary tumor < 2cmT1

Tumor > 2 cm, < 5 cmT2

Tumor > 5 cm T3

Tumor invades chest wall, or inflammatory carcinoma

T4

T Staging for Breast Cancer

No lymph node metastasesN0

Involves ipsilaterial hilar or peribronchial nodes N1

Involves ipsilateral mediastinal nodes N2

Contralateral spread N3

N Staging for Lung Cancer

No lymph node metastasesN0

Metastases to same-side movable nodes N1

Metastases to same-side fixed nodes N2

Metastases to internal mammary nodes N3

N Staging for Breast Cancer

Overall Stage T Stage N Stage M Stage

Stage 0 Tis (In situ) N0 M0

Stage IA T1 N0 M0Stage IB T2 N0 M0

Stage IIA T1 N1 M0Stage IIB T2 N1 M0  T3 N0 M0Stage IIIA T1 N2 M0  T2 N2 M0  T3 N1 M0  T3 N2 M0Stage IIIB Any T N3 M0  T4 Any N M0Stage IV Any T Any N M1

Group Staging for Lung Cancer

Years after diagnosis

Sur

viva

l

Stage IStage IIStage IIIaStage IIIbStage IV

Stage-specific survival for lung cancer1.0

0.8

0.6

0.4

0.2

1 2 3 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 Cytokeratin 7

Colon Urinary tract Gastric Pancreas/ biliary

BreastLungPancreas/ biliary Ovary/ uterusSalivary 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 1%2 – 4 ng/ml 15%4 – 10 ng/ml 25%> 10 ng/ml 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