Metastasis. brain metastasis from bronchial carcinoma

Transcription

1 metastasis

2 Metastasis brain metastasis from bronchial carcinoma

3 How many genetic changes are needed for neoplastic transformation?... if you have some of these changes, but not all, you will never become malignant

4 Breast Carcinoma intraductal = in situ component (ductal carcinoma in situ (dcis) with comedo necrosis), 2 invasive component, 3 sclerosis of central parts. If we look to the primary tumor, we can up to now not judge about its ability for metastasis

5 Metastasis 1. heterogenous population of tumor cells: some break the basement membrane 2. migration in the mesenchymal tissue, survival without local growth factors Kollagen IV Laminin Cadherine Basement membrane 3. blood vessel invasion 4. survival of the attack by fibrin, NK cells, complement, antibodies, thrombocytes, macrophages, neutrophils, cytotoxic T cells Laminin/Fibronektin Rezeptor Typ IV Kollagenase 5. extravasation 6. proliferation 7. angioneogenesis if you fail in any one of these hurdles, you will never become a metastasis Fibronektin autocrine motility factor

6 Routes of Metastasis lymphogenous single tumor cells (or tumor cell groups?) enter the lymph vessels are transported with the lymph stream enter a lymph node grow out to form a metasis lymph node metastasis follow the lymphatic drainage => concept of sentinel node biopsy injection of a radioactive tracer or a dye immediately beneath a tumor detection of the draining lymph node resection of that lymph node careful histologic investigation

7 2 3 4 lymph node metastasis 1 and sinuscarcinosis 2 in breast cancer. 3 normal germinal center. 4 slight paracortical expansion (dermatopathic?) 1

8 stomach signet ring carcinoma, pt3pn2g3 diffuse type of Lauren L1 V1 R1 1 stomach mucosa, 2 serosal surface, 3 linitis plastica = the hyperplastic/hypertrophic M propria is well seen, 4 lymph node metastases

9 lung pleuritis carcinomatosa in breast cancer

10 lung lymphangiosis carcinomatosa in bowel cancer

11 Routes of Metastasis transcoelomic tumor cells break through the serosal surface distribute in the body cavity (mostly abdominal or thoracic) seed down grow out to form a metastasis

12 hematogenous Routes of Metastasis 1. portal type primary tumor in the abdominal cavity (colon, pancreas, stomach, gall bladder) venous transport by the portal vein into the liver second step: metastasis to the lung third step: metastasis to other organs (brain, bone,...) 2. vena cava superior type primary tumor in the upper body (breast cancer, head&neck cancer) venous transport to the lung second step: other organs 3. vena cava inferior type primary tumor in the lower body (kidney,...) metastasis to the lung second step: other organs

13 2 1 Liver metastasis in bronchial carcinoma 1 central tumor necrosis (Krebsnabel), 2 chronic liver congestion

14 liver 6,3 kg: metastases of bowel cancer

15 liver metastases in squamous cell carcinoma of the larynx

16 Routes of Metastasis peritumorous satellites in "older" tumors migration of tumor cells for several cm after stopping migration, start of growth

17 breast carcinoma with peritumorous satellites

18 malignant melanoma of skin with peritumorous sattelites

19 Bone Metastasis what's a bone? spine: multiple metastases of bronchial carcinoma

20 Bone Metastases should correctly be named Bone Marrow Metastases

21 Seed and Soil in Bone Marrow Metastasis red marrow spine rips hip scull yellow (fatty) marrow long bones

22 Osteoblastic and Osteolytic Bone Metastases

23 Osteolytic Bone Metastases multiple myeloma

24 multiple myeloma 2228/05

25 metastasis of follicular thyroid cancer with pathologic fracture in the humerus

26 Inactivity Osteoporosis 1 RAEB/M6, CR 6 months after therapy E 877/05. 1 osteoclasts actively dissect a bony trabecule

27 osteoblastic bone marrow metastasis in urothelial cancer, 24830/05 PAS x 20

28 osteoblastic bone marrow metastasis in urothelial cancer, 24830/05 PAS x 20

29 osteoblastic bone marrow metastasis in urothelial cancer, 24830/05 PAS x 20

30 1 osteolysis of lammelar bone (black) 2 build up of woven bone (yellow) 3 lack of maturation from woven to lammelar bone => osteoblastic is misleading because of danger of fracture => better: osteolytic with metaplastic ossification of tumor stroma osteoblastic bone marrow metastasis in urothelial cancer, 24830/05 PAS x 20

31 Why is there woven bone formation (like in a fracture), but no maturation to mature (firm) lamellar bone?

32 RANKL OPG Stephan Paget, 1889 Seed and Soil CFU-GM Osteoclast-Precursor PTHrP IL-6 PgE2 TNF M-CSF Stromal Cell (Osteoblast) RANKL RANK tumorgrowth Osteoclast BMP s IGF s TGFβ FGF s PDGF bone marrow carcinosis in breast cancer 9627/05

33 Why is there woven bone formation (like in a fracture), but no maturation to mature (firm) lamellar bone? growth factors from destructed bone enhance tumor growth and further metaplasia of desmoplastic stroma fibroblast to osteoblasts

34 idc, G1