PATHOLOGY OF TUMOURSPATHOLOGY OF TUMOURS PART 3 PART 3

1.1. GRADING AND STAGINGGRADING AND STAGING2.2. PROGNOSISPROGNOSIS

PROGNOSIS

THE PREDICTION OF

FUTURE PROGRESS

OF A DISEASE

OR TUMOUR

PROGNOSIS1.BENIGN TUMOURS – GENERALLY GOOD…..

BUT DEPENDS ON SITE, TYPE ETC

2.MALIGNANT TUMOURS1. SITE e.g. visceral versus superficial

2. INHERENT NATURE OF THE TUMOUR PROGNOSIS ACCORDING TO THESE TWO FACTORS DEPENDS ON:-

PAST EXPERIENCE OF EACH TYPE OF TUMOUR

MENINGIOMA – A FAIRLY BENIGN TUMOUR ARISING FROM THE DURA. PRODUCES SYMPTOMS ACCORDING TO THE REGION OF THE BRAIN IN WHICH IT ARISES. CAN BE FATAL AS IT IS A “SOL”

BENIGN MENINGIOMA – DIAGRAM TO ILLUSTRATE HOW THE TUMOUR ERODES BONE BY PRESSURE ATROPHY AND COMPRESSESTHE UNDRELYING BRAIN RAISED INTRA-CRANIAL PRESSURE

BENIGN HAEMANGIOMA OF THE LIVER – THE COMMONEST BENIGNTUMOUR OF THE LIVER – CAN BLEED SEVERELY DUE TO MINOR TRAUMA TO THE ABDOMEN

BENIGN LEIOMYOMA OF THE SMALL BOWEL – CAN CAUSE INTESTINALOBSTRUCTION AND OFTEN BECOMES MALIGNANT ( c.f. UTERINE FIBROID)

BENIGN ADENOMA OF THE PARATHYROID GLAND.

CAUSES SEVERE METABOLIC DERANGEMENTS WHICH CAN BE FATAL

NORMAL PARATHYROID GLAND

PARATHYOID ADENOMA

NEPHROCALCINOSIS

CALCIUM DEPOSITED IN THE INTERSTITIUM OF THE KIDNEY

PROGNOSISOVERALL PROGNOSIS DEPENDS ON 3 FACTORS:-1.GROWTH - RAPID GROWTH = BAD PROGNOSIS2. EXTENT – THIS FORMS THE BASIS OF – THE “TNM” CLINICAL STAGING OF TUMOURS

a. SIZE OF PRIMARY TUMOUR T0-4 WHERE T0 = IN SITU MALIGNANCYb. LYMPH NODE SPREAD N0-3

c. DISTANT METASTASES – M0-4

3. DIFFERENTIATION – HISTOLOGICAL GRADE

PROGNOSIS

THE CLINICAL STAGING OF TUMOURS

a. SIZE OF PRIMARY TUMOUR - T0-4 WHERE T0 = IN SITU MALIGNANCY

b. PRESENCE/ABSENCE OF LYMPH NODE INVOLVEMENT – N0-3

c. PRESENCE/ABSENCE OF METASTASES –M0-4

HISTOLOGICAL GRADE

OF THE TUMOUR REFERS TO THE TISSUE AND CELLULAR DIFFERENTIATION

1.WELL DIFERENTIATED

2. MODERATELY DIFFERENTIATED

3. POORLY DIFFERENTIATED

3) Tumour Grading3) Tumour Grading

Measure of Measure of prognosisprognosisExample of breast cancer:Example of breast cancer:A) Glandular differentiationA) Glandular differentiationB) Cellular pleomorphismB) Cellular pleomorphismC) Mitotic activity (per 10 HPF)C) Mitotic activity (per 10 HPF)Scored as 3 – 9Scored as 3 – 9= (modified) Bloom & Richardson grading= (modified) Bloom & Richardson grading

DIFFERENTIATION IN A SQUAMOUS CARCINOMA LIES INTHE TUMOUR’S ABILITY OR FAILURE TO

FORM KERATIN

SQUAMOUS METAPLASIA IN BRONCHIAL MUCOSASQUAMOUS METAPLASIA IN BRONCHIAL MUCOSA

Mild dysplasiaMild dysplasia

Moderate dysplasiaModerate dysplasia

Severe dysplasia / carcinoma in Severe dysplasia / carcinoma in situsitu

CIN III/SEVERE DYSPLASIA CA-IN-SITU

SQUAMOUS CARCINOMA IN SITU – i.e. CONFINED BY THE BASEMENT MEMBRANE

WHEN THE TUMOUR CELLS BREAK THROUGH THE BASEMENTMEMBRANE THEY FORM CORDS OF CELLS

INFILTRATING THE UNDERLYING STROMA

TextIN WELL-DIFFERENTIATED TUMOURS THE CELLS ARE ABLE TO PRODUCE KERATIN SEEN HERE AS PINK MATERIAL WITHIN

A SPIRAL ARRANGEMENT CALLED A “KERATIN PEARL”

CONCENTRIC LAYERS OF KERATIN-CINTAINING CELLS IN A WELL-DIFFERENTIATED SQUAMOUS CARCINOMA

AS THE TUMOUR BECOMES LESS WELL DIFFERENTIATED ONLY SOME OF THE CELLS SHOW KERATIN FORMATION AND-INTER-CELLULAR BRIDGE FORMATION

POORLY OR UNDIFFERENTIATED TUMOURS, WHETHER SQUAMOUS OR GLANDULAR IN ORIGIN CONSIST OF SHEETS OF UNDIFFERENTIATED CELLS WITH NUMEROUS AND OFTEN ABNORMAL MITOTIC FIGURES

IN ADENO-CARCINOMAS THE DEGREE OF GLANDULAR STRUCTUREFORMATION WILL DETERMINE THE DEGREE OF DIFFERENTIATION

ADENOCARCINOMA – THE GLANDULAR ACINI ARE WELL- FORMED IN THIS WELL DIFFERENTIATED

TUMOUR

ANAPLASTIC CARCINOMA – i.e. POORLY OR UNDIFFERENTIATED TUMOUR WITH NUMEROUS MITOTIC

FIGURES ()

BREAST MASS EXCISED AT SURGERY. THE CUT SURFACE SHOWS THE TYPICAL YELLOWISH-WHITE TUMOUR TISSUE INFILTRATING THE

SURROUNDING FIBRO-FATTY BREAST TISSUE

NORMAL BREAST TISSUE INFILTRATING CARCINOMA

FAIRLY SOLID SHEET OF TUMOUR CELLS WITH SOME DUCTAL DIFFERENTIATION

Tumour Grading

Grade Score 5-year survival (%) 7-year survival (%)

1 3 – 5 95 90

2 6 – 7 75 65

3 8 - 9 50 45

Staging

• A uniform TNM system for staging cancer according to its anatomic extent at the time of diagnosis is extremely useful for many reasons, chiefly for comparing treatment results from different centres

4) Tumour Staging• Measure of prognosis• TNM classfication

T(umour size)N(ode numbers)

M(etastasis)• [Dukes and Astler-Coller

Large intestine – see later]

STAGE Definition 5-year % survival

7-year % survival

I < 2cm without nodal or regional mets

96 92

II > 2 < 5 cm with +ve nodes OR > 5 cm without nodes

81 71

III Any size but with fixation to skin, chest wall, etc

52 39

IV Tumour any size but distant metastases 18 11

5) Prognosis• Depends on grade and stage• Also tumour type – NB breast, lung,

melanoma (very unpredictable)• Site VIP (superficial vs. deep visceral)• Immune status, nutrition, pain threshold,

etc • (No evidence that “positive thinking,”

homeopathy and miracles can cure cancer!!)• General principle, earlier/smaller tumours

have better prognosis – therefore:• Importance of surveillance programs – PAP

smears, mammography, PSA, colonoscopy

Spread of Tumours• Local invasion

• Lymphatic spread

• Haematogenous

• Transcoelomic

• Implantation

• Fascial planes, ducts,

• Carcinoma. Permeation and embolisation. Retrograde spread

• Sarcomas. Early to lung

• Pleura, peritoneum, meninges. Example is Krukenberg tumour

• Rare due to good surgical practice

CARCINOMA• Majority (90%) of malignant tumours• Prevalence increases with age (cf

sarcoma)• Variable geographic differences (cf

sarcoma)• “ENVIRONMENTAL” (cf sarcoma)• NB. All epithelia have a basement

membrane therefore• Always a defined “pre-malignant”

phase• = DYSPLASIA (mild, moderate, severe)

PROGNOSIS OF A MALIGNANT TUMOUR

Text

ADENO-CARCINOMA SHOWING GLAND FORMATION

CIN III/SEVERE DYSPLASIA CA-IN-SITU