pathology of neoplasia
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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. - PowerPoint PPT PresentationTRANSCRIPT
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