Dept of Pathology 1

Staging, Grading and Spread

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Dept of Pathology 2

Specific learning objectives

• Understand the invasion-metastasis cascade • Concept of tumor grade • Concept of tumor stage

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Dept of Pathology 3

Spread

Metastasis Invasion

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Dept of Pathology 4

Cascade • invasion of ECM• vascular dissemination

and homing of tumor cells

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Dept of Pathology 5

Invasion of ECM

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Dept of Pathology 6

1. loosening of tumor cells

Cadherin

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Dept of Pathology 7

2. Degradation of the basement membrane and interstitial connective tissue

Metalloproteinase

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Dept of Pathology 8

3. Changes in attachmentof tumor cells to ECM proteins

Receptor

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Dept of Pathology 9

4. Locomotion

Chemotaxis

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Dept of Pathology 10

Vascular dissemination and homing of tumor cells

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Dept of Pathology 11

Organ predilection ?

• location of the primary tumor and its vascular or lymphatic drainage

• organ that presents the first capillary bed they encounter after entering the circulation

• Natural pathways of drainage do not readily explain the distribution of metastases !

• Adhesion molecules – ligands

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Dept of Pathology 12

Molecular signature

• EMT - epithelial-to-mesenchymal transition

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Dept of Pathology 13

Grading / Staging

• quantify the probable clinical aggressivenessof a given neoplasm (grading) and

• its apparent extent and spread (stage) in the individual patient

• Why is it needed ? • Make an accurate prognosis and for comparing

end results of various treatment protocols

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Dept of Pathology 14

Grading

• estimate aggressiveness based on– cytologic differentiation of tumor

cells – Number of mitoses within the

tumor.

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Dept of Pathology 15

Staging • based on – the size of primary tumor– spread to regional lymph nodes – presence or absence of metastases

• TNM stage

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Dept of Pathology 16

Take home points

• Invasion – hallmark of malignancy • 4 steps of invasion • Metastatic site depends on location /

chemokines • Grading – cytologic appearance • Staging – TNM – more value than grading

clincially

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Dept of Pathology 17

Thank you

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