CORRELATION OF CLINICAL AND PATHOLOGICAL DIAGNOSIS OF NEOPLASM

1. Clinical Degree of Malignancy

Doubling time The shorter the D.T. the higher degree of malignancy

Low Degree ( > 4 Months ) Moderate ( 2 4 Months ) High ( < 2 Month )

Table 1. Mean volume doubling time in weeks. In Tannock IF and Hill R. The Basic Science of Oncology. 2nd ed. Mac Grow Hill Inc. Health Professionals Division. New York 1992, p. 155 NO TUMOR TYPE MEAN DOUBLING TIME

( in weeks )
1 Primary Lung Cancer - Adenocarcinoma 21

- Squamous cell carc.

- Anaplastic carc. 2 Breast Cancer

12
11

- Primary
- Lung metastasis - Soft tissue metastasis

14
11 3

3 Colon Rectum - Primary 90

- Lung metastasis
4 Lymphoma - Lymph node lesion 5 Lung Metastasis of - Testis carcinoma - Childhood tumours - Adult sarcoma

14

4 4 7

2. Pathological Degree of Malignancy

Grade of cell differentiation ( Pleomorphism, Mitotic Index, Necrotic Cell ) The higher grade of differentiation, the lower degrees of malignancy, and the better prognosis Lymphoid infiltration ( Medullary Ca, Invasive Ductal Ca. )

I. Clinical Manifestation
A. As Primary Tumor

Plaque Nodule tumor Erosion ulcer Nodular ulcerativa No Special form

B. As Metastasis

Lungs Lymph Node Liver Brain Bone

C. As Complication(s) of the Disease

Bleeding from the ulcer or abnormal bleeding or discharged from the body orifice. Obstruction of the body canal Malfunction or disfunction of the organ ( Organ Failure ) Infection

Fracture Cachexia Hormonal Disturbance

Serotonin Syndrome Cushing Syndrome Hyperparathyroidisme

II. Diagnostical Procedures

A. Clinical Procedure in Diagnosis

Taking History ( anamnesis )

Chief complain The rate of growth of the tumor Aetiology and risk factor Causes of delay Treatment carried out elsewhere and result

Performing physical examination Endoscopy Radiological examination Laboratory examination

B. Pathological

Procedures in

Diagnosis

Taking
Biopsi Cytology material Operative specimen

Process for microscopic slide Evaluating Histological slide is only small sample of tissue

in sampling / processing error interprestation The pathologist have be informed the clinical presentation and corelate to microscopic finding.
Error

Inconsistency Clinical Picture Reevaluate Rebiopsi Pathologic Report

Microscopic

Morphology Behaviour Grade of Differentiation Angioinvasion

Report of Operative
Form Size Angioinvasi Radically of Operation Involvement of Lymph Node

III. Diagnosis of Cancer

The Base of Diagnosis 1. Clinical Diagnosis

A lesion ( plaque, tumor, ulcer which grows progressively Sign of infiltration The presence of sign of metastasis to regional lymph nodes or to remote organs

Pathological diagnosis 3. Validity of diagnosis 4. Certainly of diagnosis

2.

IV. Correlation of Clinical and Pathological Diagnosis

Clinical Presentation and Histologic Type 2. Clinical Diagnosis and Pathological Diagnosis
1.
Benign tumor Tumor of uncertain behaviour In situ cancer Invasive cancer

3. Degree of Malignancy
Clinical Degree of

Malignancy Pathological Degree of Malignancy

Table 2 : Clinical characteristics of benign and malignant neoplasm

NO CHARACTE -RISTICS
1 Form 2 Border 3 Capsule 4 Vascular 5 Temperature

BENIGN TUMOR
Regular

MALIGNANT TUMOR
Irregular

Sharply demarcated No or demarcated Present Normal Normal No or pseudo-capsule Hyper & neo-vascular Hyperaemia

6 Necrotic
7 Ulceration 8 Recurrent

Seldom
Seldom Seldom

Often
Often Often

9 Growth

Progressive, slow,expansive, local and limited

No

Progressive,vast, expansive & invasive and unlimited

Yes and Often Often disturb Often Nearly always

10 Metastasis

11 Organs Function Seldom disturb 12 Systemic effect 13 Fatal Outcome Seldom Seldom

2 In situ neoplasma

D00 to D09

C00/2 to C80/2

3 Benign neoplasma 4 Ulcertain or unknown behaviour

2 Non - neoplasm

D10 to D36 D37 to D48

-

C00/0 to C80/0 C00/1 to C00/1

-

It is important to keep in mind when to think about early cancer. We have to think about cancer when discover : 1. One or more of the 7-danger signal of cancer CAUTION :

C = Change in bowel or bladder habit A = A sore that does not heal U = Unusual bleeding or discharge T = Thickening or lump in the breast or else where I = Indigestion or difficulty in swallowing N = Nagging cough or hoarseness

Table 3 . Clinical Diagnosis of Tumor

NO TYPE OF TUMOR
1 Malignant 1 Primary 2 III defined 3 Secondary 4 Unspecified /unknown primary 5 Lymphoid 6 Hemopoitic 7 Multiple primary

ICD X
C00 to D48
C00 to C97 C00 to C75 C76 C77 to C79 C80 C81 to C90 C91 to C96 C97

ICD - 0
C00 to C80
C00/. to C80/. C00/3 to C77/3 C76/3 C00/6 to C80/6 C80/9 C77/3 C42/3 -

1 Neoplasm

2.

3.

Tumor in a high risk group : old age, family history, post radiation, immune compromised. The present of small lesion ( plaque, tumor, erossion ) fit no to the clinical criteria of benign lession.

Table 4. Pathologic characteristic of neoplastic cells

BENIGN NO 1 2 3 CHARACTERISTICS Cell structure Vascular Necrotic / Ulceration TUMOR Typical Normal Rare MALIGNANT TUMOR Atypical Increased Often

4 Cancer cells
-

Nuclear / Cytoplasm ratio Normal Nuclear structure Normal

Approaches 1 Pleomorphic and polychromatic

Mitosis

Rare No

Often and atypical Present with grade of differentiation

- Anaplastic

5 Intercvellular space 6 Polarisation

Normal Regular

Loss Irregular

7 Cell infiltration 8 Capsule 9 Ultra structure

-

No

Present

Present No or present of pseudocapsule Normal Often irregular Normal Sometime aberrant Normal Present of free RNA particles

Nuclear membrane Mitochondria Endoplasmic reticulum

Golgy apparatus

Normal Often consist of microvesicles

No Present and often

10 Metastasis

Table 5. Grade of differentiation of squamous cell carcinoma according to Broder. The present of pearl formation indicate well differentiated
Grade I II III IV

Differentiation

Well

Moderately

Poorly

Undifferentiated

Mature Cell ( % )

> 75

50- 75

25 - 50

< 25

Table 6. Grade of differentiation of adeno carcinoma of the breast according to Bloom and Richardson. Mitotic index per 10 HPF = High Power Field
Grade Differentiation Tubular Formation ( % ) Nuclear pleomorphism Mitotic index ( % ) I Well > 75 min < 10 II Moderately 50 - 75 moderate 10 - 20 III Poorly 25 - 50 high 20 - 25 IV Undifferentiated <25 High >25

Table 7. Nottingham modification for grading of breast cancer

Grade Total score Score I 3-5 1 II 6-7 2 III 8-9 3

Pleomorphism
Mitotic index Tubular formation ( % )

> min
0-5 > 75

moderate
6 - 10 10 - 75

High
> 10 PPF < 10

Table 8. Grade of differentiation of soft tissue sarcoma

Grade Total score Score Cell differentiation I 3-4 1 Similar to mature cells II 5-6 2 Moderately diff. III 7-9 3 Undifferentiated

Necrotic cells (%)

Mitotic index

no
0-9

< 50
10 - 19

> 50
> 20

Table 9. Degree of Validity Diagnosis

NON MICROSCOPIC EXAMINATION MICROSCOPIC EXAMINATION

NO

1 Clinical Only 2 Clinical Investigation 3 Surgical Exploration 4 Biochemical / Imunological Test

Cytology or Hematology Histology of Metastases Histology of Primary Tumor Autopsy

The higher the degree diagnostic methods employed, the more valid is the diagnosis C Factor The higher the degree of C-Factor the more certain is the diagnosis

Table 10. Degree of Certainty of Diagnosis No Methods of Diagnostic

Evidence from standard diagnostic means (e.g. physical C1 examination, standard radiography, endoscopy for tumours of certain organs ) Evidence obtained by special diagnostics means (e.g. radiographic imaging in special projections, C2 tomography, CT-scan, USG, lymphography, angiography, scintigraphy, MRI, endoscopy with biopsy or cytology )

Evidence from surgical exploration, including biopsy C3 and cytology Evidence of the extent of disease following definitive C4 surgery and pathological examination of rescted specimen

C5 Evidence from autopsy

Table 11. Correlation of clinical presentations and pathological findings

No

Clinical Presentation

Pathological Findings
Infiltration of cancer cells to the ligament of Cooper

1 Skin retraction

2 Skin fixation
3 Peau d orange 4 Ulceration

Infiltration of cancer cells to the skin

Infiltration to the subcutaneous or cutaneous lymphatic vessels causing obstruction of lymphatic flow Necrotic tissues and infiltration of cancer cells to the skin

5 Satellite nodule of the skin

Metastasis to the skin

6 Mastitis carcinomatosa Widespread of skin and subcutaneous infiltration Restriction the of 7 tumor mobility to the pectoral muscle Infiltration of cancer cells to the pectoral fascia

Restriction of the
shoulder joint mobility

Infiltration of cancer cells to the pectoral

muscles Extensive obstruction of lymphatic flow due to metastasis into the lymph nodes and lymph vessels of the axilla

9 Lymphoedema of the arm

Clinical Diagnosis and Pathological Diagnosis 1. Benign Tumor :

Well defined Smooth surface Without sign of infiltration Located superficial in an organs

Small tumor Look like benign tumor Does not located in well known organs for benign tumor Does not necessary benign tumor

Clinical manifestation of malignant tumor in early stage practically the same of benign tumor The probability of the malignant always keep in mind Consider : Epidemiologic data, the age, risk, site of tumor

2. Tumor of uncertainty behaviour

Clinical and pathological examination benign Treated as benign Recurrent Malignant Granulosa, Leydig, Sertoli, Thymoma. Of boderline malignancy

3. Insitu Cancer

Only a few cancer :

Bowen disease Paget disease NIS of the cervix

No in soft tissue sarcoma Clinically : Plaque or erosion Final diagnoses based on pathological examination < 5% of the clinically diagnosis is right

4. Invasive Cancer A. Early Cancer

Difficult to diagnose clinically
No sign of infiltration Presentation nearly similar to benign tumor Clinically diagnosis

Tumour of the Path exam Discover diagnosis < 10% clinical diagnosis is right Correlation clinical diagnosis and early cancer is poor

B. Advanced Cancer
Sign of infiltration and metastaes Clinical diagnosis is not difficult > 70% clinical diagnosis is right Correlation between clinical diagnosis and

pathological diagnosis is good Recurrent tumor where the former diagnosis was benign, the current diagnosis is a big problem Epidemiological data for certain degree may help to solve the problem

Some problems (no correlation between the clinical and the pathological diagnosis) :

Clinically manifestation as benign neoplasm, but pathological as malignant, such as : Juvenile Melanoma Clinically manifest as malignant tumor, but pathologically as benign : Papillary Adenoma of Thyroid

Tumor of the first or second presentation clinically and pathologically look like as benign but if treated as benign usually after a periode of TME will recur : Deep seated fibroma and lipoma Clinical and pathological presentation as benign tumor, but demonstrate metastases to regional node or even remote organ : Thyroid Adenoma

No primary tumor can be discovered, but presents with pathologically proven metastases to one or more organs MUO (Metastases of Unknown Origin)

Terima Kasih