Pathological, imaging and laboratory diagnostics in oncology; tumor staging
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1 Pathological, imaging and laboratory diagnostics in oncology; tumor staging
2 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
3 Tumor type, natural history Diversity: Etiologically Diagnostically Biologically Therapeutically 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
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11 Metastasis
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14 Malignant melanoma
15 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
16 The significance of inspection Indicates the course of the disease and the speed of progression : natural history Stage: lokoregionalvs. 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
17 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
18 Patological diagnostics The basis of oncological care/therapy, Histological/cytological sampling is mandatory Close cooperation Biopsy versus surgical material
19 Patological diagnostics: biopsy Place of origin/histological type Differentiation (grade and proliferative markers) Molecular characterization (molecular targets, tumor markers) IHC Molecular pathology methods
20 Dr. István Pálka, Dept. Pathol., SZTE cerb-b2 3+
21 Dr. István Pálka, Dept. Pathol., SZTE cerb-b2 1+
22 Estrogen receptor Dr. István Pálka, Dept. Pathol., SZTE
23 Dr. István Pálka, Dept. Pathol., SZTE
24 Dr. István Pálka, Dept. Pathol., SZTE
25 Dr. István Pálka, Dept. Pathol., SZTE
26 Dr. István Pálka, Dept. Pathol., SZTE
27 Dr. István Pálka, Dept. Pathol., SZTE
28 Dr. István Pálka, Dept. Pathol., SZTE
29 Dr. István Pálka, Dept. Pathol., SZTE
30 Dr. István Pálka, Dept. Pathol., SZTE
31 Dr. István Pálka, Dept. Pathol., SZTE
32 Dr. István Pálka, Dept. Pathol., SZTE CK5/6
33 Invasive ductal cancer lymph vessel invasion, H-E, 10x (Dr. András Vörös, Dept. Pathol., SZTE, 2010)
34 Invasive ductal cancer lymph vessel invasion, H-E, 10x (Dr. András Vörös András, Dept. Pathol., SZTE, 2010)
35 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: , 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
36 CK7 positive tumour cells, 200X ER positive tumour cells, 400X Cancer cells in bone marrow, H-E Bone marrow biopsy; Dr. András Vörös Inst. of Pathology, USZ
37 Complex breast screening: palpable 1.5 cm lump in the outer-lower quadrant of the left breast, and casting calcification
38 Patological diagnostics: surgical specimen Histological type* Grade* pt pn:?/? (sentinel biopsy?) Vessel (blood or lymph) and/or perineural invasion Molecular characteristics*: IHC and molecular genetic markers and their change Resection margin Tumor heterogeneity *To be compared with the same parameters in the biopsy specimen, may be indicative of tumor response
39 Patological diagnostics: surgical specimen Was the surgical intervention radical enough? Primary tumor? Regional lymph nodes?
40 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.
41 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
42 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?
43 Routine imaging diagnostics in Chest: X-ray, CT oncology 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
44 CT Tumor localization, Staging, follow-up, treatment planning, CT-intervention
45 MR Tumour localization Staging, extent Follow-up MR angiography MR spectroscopy Open MR- Guided intervention
46 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)
47 XIO/FOCA L GTV CT Organs at risk
48 OTP GTV PET
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50 The utilisation of information provided by imaging in radiotherapy CT-based radiotherapy planning CT-MR image-fusion CT-PET image-fusion
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60 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
61 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
62 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
63 Tumor markers mostly used Tumor marker 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 Tumor type 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
64 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
65 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
66 Paraneoplastic syndromes Endocrine Central nervous system Muscle Skin, mucosa Hematological Other
67 Paraneoplastic endocrine syndromes Syndrome Tumor type Etiological factor Cushing SIADH Hypercalcemia Hypoglycaemia Carcinoid Small cell lung cancer Pancreatic Central nervous system tumor Thymoma SCLC Central nervous system Non small-cell lung cancer Breast cancer Kidney cancer Melanoma T-cell lymphoma, leukemia Ovarian cancer Fibrosarcoma Hepatocellular liver cancer ACTH/ACTH-like substance ADH PTHrP TGF-alfa TNF IL-1 Insulin Insulin-like substance IGF-II Serotonin Bradykinin
68 Paraneoplastic central nervous system syndromes Syndrome Tumor type Etiological factor Eaton-Lamberth myasthenia sy. Small cell lung cancer Antibodies Cerebellar degeneration Polymyositis Lung cancer Breast cancer Ovarian cancer
69 Paraneoplastic syndrome: skin and mucosa Syndrome Tumor type Etiological factor Acanthosis nigricans Gatsric cancer Lung cancer Immune mechanism EGF-production Uterine cancer Dermatomyositis Lung cancer Immune mechanism Breast cancer Necrolytic erythema migrans Glucagonoma Sweet syndrome Pyoderma gangrenosum Pemphigus Myeloma multiplex, leukemiák Neutrophil granulocyte function problem, immune deficiency Immune mechanism Pemphigoid Breast and other cancers Immune mechanism
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71 Seborrhoic hyperkeratosis Dermatomyositis
72 Bullous pemphigoid
73 Pneumonitis accompanied with soft tissue calcification
74 Pneumonitis accompanied with soft tissue calcification
75 Pneumonitis accompanied with soft tissue calcification
76 Haematological syndromes Syndrome Tumor type Etiological factor Polycythaemia Kidney cancer Erythropoietin Hepatocellular Cerebellaris haemangioma Thrombotikus endocarditis Advanced cancers Coagulopathy Anaemia Thymus tumors? Migrating thrombophlebitis Several tumors Coagulopathy
77 Thrombosisofthe descendentaorta combined with spleen infarct Thrombosis of the descendent aorta
78 Aorta thrombosis with multiple splenic infarction
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