pathological, imagingand laboratorydiagnosticsin oncology ... · anamnesis •the generalstatus...

Pathological, imaging and

laboratory diagnostics in

oncology; tumor staging

The basis of treatment strategy

• Tumor type, „natural history”

• Histological type and other pathological

features

• Stage (TNM?)

• The general status of the patient,

comorbidities

• The wish of the patient

• Available treatment options

Tumor type,

„natural history”

• All experiences and knowledge about the development,

course, and treatment options of a specific malignant

disease that reflects outcome and prognosis

• The ways of progression– Local invasiveness,

– The mode of metastasis (lymphatic, hematogeneous, systemic spread)

• Therapeutic sensitivity

• The course of the disease is determined by the extent

and stage of the disease: premalignant lesion-local

/locoregional/systemic (tumor load!?)

• Exception: hematological malignancies, glioblastoma

multiforme, PNET/Ewing sarcoma, anal cancer

Diversity:

Etiologically

Diagnostically

Biologically

Therapeutically

Metastasis

Malignant melanoma

The significance of anamnesis

• Indicates the course of the disease and

the speed of progression : „natural history”

• Stage: distant metastasis?

• The general status of the patient and

comorbidities

• The wish of the patient

• Therapeutic options to count on

• Determines future examinations

The significance of inspection

• Indicates the course of the disease and the

speed of progression : „natural history”

• Stage: lokoregional vs. distant spread

• The general status of the patient,

comorbidities, performance status (PFS)

• The patient’s psychological status, and his

attitude to disease and treatment

• Determines the need of further examinations

The significance of physical

examination• Indicates the course of the disease and

the speed of progression : „natural history”

• Signs and symptoms that complete

anamnesis

• The general status of the patient and

comorbidities

• Determines further examinations

Patological diagnostics

• The basis of oncological care/therapy,

Histological/cytological sampling is

mandatory

• Close cooperation

• Biopsy versus surgical material

Patological diagnostics: biopsy

• Place of origin/Histological type

• Differentiation (grade and proliferative

markers)

• Molecular characterization (molecular

targets, tumor markers)

– IHC

– Molecular pathology methods

cerb-B2 3+

Dr. István Pálka, Dept. Pathol., SZTE

cerb-B2 1+


Estrogen receptor


CK5/6


Invasive ductal cancer lymph vessel invasion, H-E, 10x

(Dr. András Vörös, Dept. Pathol., SZTE, 2010)

Invasive ductal cancer lymph vessel invasion, H-E, 10x

(Dr. András Vörös András, Dept. Pathol., SZTE, 2010)

59 year old woman: anaemia, pancytopenia

– malignant state?

• 10 month ago negative breast screening, with physical examination:

faint, pale

• Abdominal UH, gastroscopy, chest rtg: negative

• Bone marrow biopsy: desmoplastic carcinoma with bone marrow

metastasis, ER positive

• Serum tumor marker levels: CA 15-3: 2355, CA-125: 116.09, CEA:

4.4, CA 19-9: 2.73

• Complex breast screening: palpable 1.5 cm lump in the outer-lower

quadrant of the left breast, and casting calcification

Bone marrow biopsy; Dr. András Vörös Inst. of Pathology, USZ

CK7 positive tumour cells, 200X

ER positive tumour cells, 400X

Cancer cells in bone marrow, H-E

Complex breast screening: palpable 1.5 cm lump

in the outer-lower quadrant of the left breast,

and casting calcification

Patological diagnostics: surgical

specimen• Histological type*

• Grade*

• pT

• pN: ?/? (sentinel biopsy?)

• Vessel (blood or lymph) and/or perineural invasion

• Molecular characteristics*: IHC and molecular geneticmarkers and their change

• Resection margin

• Tumor heterogeneity

*To be compared with the same parameters

in the biopsy specimen, may be indicative

of tumor response

• Was the surgical intervention radicalenough?

• Primary tumor?

• Regional lymph nodes?

Patological diagnostics: surgical

specimen

Tumor characteristics may be…

• Prognostic factor: indicates outcome (prognosis) without

the application of any treatment intervention, such as

– Stage

– Vessel invasion

– Molecular markers etc.

• Predictive factor: gives the likeliness of response to

(effectiveness of) a certain therapy

– ER, PR, HER2, TOP2A, K-Ras status etc.

Stage

• Different systems are available, the final

goal is a tool to regulate management

• TNM system: UICC/AJC vs. 7.0 – all

systems have deficiencies

• FIGO

• Dukes

Imaging diagnostics

• Extent of disease (stage)?

• General health status?

• Extra information on the metabolical status

and biological behaviour of the disease

• Direct use in radiotherapy treatment

planning

• Response to oncological therapy?

Routine imaging diagnostics in

oncology• Chest: X-ray, CT

• Abdomen, small pelvis: US/CT, liver or

small pelvis MR

• Brain: CT, MR

• Skeleton: bone scan, 18FDG-PET

• Breast: mammography, US, MR

• Organs with cavity: US

CTTumor localization,

Staging, follow-up,

treatment

planning,

CT-intervention

MR• Tumourlocalization

• Staging, extent

• Follow-up

• MR angiography

• MR spectroscopy

• Open MR- Guided intervention

The role of 18FDG-PET/CT

• Increased glycolitic activity of tumors makes PET a

sensitive and specific method for the investigation of

tumor extent (primary tumor, lymph node or distant

metastases)

• Prompt evaluation of tumor response to therapy

• Metabolic heterogeneity and geography of the tumor

may be evaluated,. And this information may be used in

radiotherapy planning (dosing)

GTVCT

Organs at

risk

XIO/FOCA

L

GTVPET

OTP

The utilisation of information provided by

imaging in radiotherapy

• CT-based radiotherapy planning

• CT-MR image-fusion

• CT-PET image-fusion

The significance of staging

• Determines the algorithm of patient

management

• Methods

– Clinical staging

• Physical examination

• Imaging

– Pathological staging

• Biopsy

• Surgical specimen

• Gives prognosis, and enables classification

Staging systems

• UICC/AJCC TNM system

– cT cN cM (clinical methods)

– pT pN pM (pathological methods)

– rT rN

– ypT ypN

• FIGO: gynecological malignancies

• Duke’s: colorectal cancer

• No staging: cerebral tumors

Tumor markers• Substances related to the presence of

cancer

– Blood, urine

– Tumor tissues

• Utilisation:

– Confirmation of diagnosis (biopsy specimen,

blood, urine)

– Serial determination for the monitoring of

therapeutic response, efficiency

– Screening method: ?? At present: PSA maybe

Tumor markers mostly used

Tumor marker Tumor type

alfa-foetoprotein (AFP)

CA 15-3

CA 19-9

CA-125

carcinoembrionális antigen (CEA)

CD34

Chromogranin

HMB-45

human choriogonadotropin (HCG)

inhibin

neuron specifikus enolase (NSE)

prosztata-specifikus antigen (PSA)

S100 protein

vimentin

germinal tumor, hepatocellular cancer

breast cancer

pancreatic, gut, gastrointestinal tumors

ovarial, endometrium cancer, lung cancer, breast cancer,

gastrointestinal cancer

colorectal, breast, pulmonary, cervical, genitourinary

cancer

mesenchymal tumors, GIST

neuroendocrine tumors, melanoma, adrenal carcinoma

germinal tumors, choriocarcinoma

sex cord stromal tumor, adrenal carcinoma

neuroendocrine tumor, small cell lung cancer

prostate cancer

melanoma, sarcoma, astrocytoma, GIST,

sarcoma, kidney cancer, melanoma, endometrial cancer,

lung cancer

Tumor response

• Evaluation of the change of tumor size/extent after

oncological treatment

– 1. complete regression: all cancerous lesions disappear (using

the same method as prior to therapy);

– 2. partial regression: the tumor is reduced in size but does not

diminish completely;

– 3. no change („stable disease”): the extent of the tumor does not

change significantly

– 4. progression: the size of the tumor increases

• Different systems: WHO, RECIST

• Evaluation of tumor response using pathological

determination: tumor regression grading systems

• pCR= no presence of cancer cells in the sample, but

fibrotic changes instead of normal parenchyma

Paraneoplastic symptoms

• The symptom is not a consequence of the

local presence of the malignant cells

• The symptom is a biological effect of, and

the consequence of the presence of

circulating substances produced by the

malignant tumor/cells, such as antibodies,

hormones, citokines etc.)

• Most effective therapy is antitumor

intervention

Paraneoplastic syndromes

• Endocrine

• Central nervous system

• Muscle

• Skin, mucosa

• Hematological

• Other

Paraneoplastic endocrine

syndromesSyndrome Tumor type Etiological factor

Cushing Small cell lung cancer

Pancreatic

Central nervous system tumor

Thymoma

ACTH/ACTH-likesubstance

SIADH SCLC

Central nervous system

ADH

Hypercalcemia Non small-cell lung cancer

Breast cancer

Kidney cancer

Melanoma

T-cell lymphoma, leukemia

Ovarian cancer

PTHrP

TGF-alfa

TNF

IL-1

Hypoglycaemia Fibrosarcoma

Hepatocellular liver cancer

Insulin

Insulin-like substance

IGF-II

Carcinoid Serotonin

Bradykinin

Paraneoplastic central nervous

system syndromes

Syndrome Tumor type Etiological factor

Eaton-Lamberthmyasthenia sy.

Small cell lung cancer Antibodies

Cerebellardegeneration

Lung cancer

Breast cancer

Ovarian cancer

Polymyositis

Paraneoplastic syndrome: skin and

mucosaSyndrome Tumor type Etiological factor

Acanthosis nigricans Gatsric cancer

Lung cancer

Uterine cancer

Immune mechanism

EGF-production

Dermatomyositis Lung cancer

Breast cancer

Immune mechanism

Necrolytic erythemamigrans

Glucagonoma

Sweet syndrome

Pyodermagangrenosum

Myeloma multiplex,

leukemiák

Neutrophil granulocytefunction problem, immunedeficiency

Pemphigus Immune mechanism

Pemphigoid Breast and othercancers

Immune mechanism

Seborrhoic hyperkeratosis Dermatomyositis

Bullous pemphigoid

Pneumonitis

accompanied with soft

tissue calcification

Haematological syndromes

Syndrome Tumor type Etiological factor

Polycythaemia Kidney cancer

Hepatocellular

Cerebellaris haemangioma

Erythropoietin

Thrombotikusendocarditis

Advanced cancers Coagulopathy

Anaemia Thymus tumors ?

Migratingthrombophlebitis

Several tumors Coagulopathy

Thrombosis of the

descendent aorta combined

with spleen infarct

Thrombosis of the

descendent aorta

Aorta thrombosis with multiple

splenic infarction

pathological, imagingand laboratorydiagnosticsin oncology ... · anamnesis •the generalstatus...

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