pathological, imagingand laboratorydiagnosticsin oncology ... · anamnesis •the generalstatus...
TRANSCRIPT
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+
Dr. István Pálka, Dept. Pathol., SZTE
Estrogen receptor
Dr. István Pálka, Dept. Pathol., SZTE
Dr. István Pálka, Dept. Pathol., SZTE
Dr. István Pálka, Dept. Pathol., SZTE
Dr. István Pálka, Dept. Pathol., SZTE
Dr. István Pálka, Dept. Pathol., SZTE
Dr. István Pálka, Dept. Pathol., SZTE
Dr. István Pálka, Dept. Pathol., SZTE
Dr. István Pálka, Dept. Pathol., SZTE
Dr. István Pálka, Dept. Pathol., SZTE
Dr. István Pálka, Dept. Pathol., SZTE
CK5/6
Dr. István Pálka, Dept. Pathol., SZTE
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
Pneumonitis
accompanied with soft
tissue calcification
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