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ELGP 22-23_Neoplastic growth.pdf
- 1. MODULE 5. Neoplastic growth Departmentof General and Clinical Pathology Medical University - Varna Peter Ghenev MD, PhD
- 2. 2 ETIOLOGY OF TUMORGROWTH Theories Chemical (irritative) R.Virchow Viral (genetic) Dysonthogenetic (Conheim) Polietiological
- 3. 3 Sir PercivalPott, London surgeon - more than 200 years ago correctly attributed scrotal skin cancer in chimney sweeps to chronic exposure to soot Chemical Carcinogenesis
- 4. 4 Carcinogenic agents fromthe environment Chemicals: insecticides, herbicides ... Drugs: anticancer, immunosuppressors Tobaco smoke Ethanol Heavy metals Microbial: Helicobacter pylori... VIRAL incl. Sexually transmitted: HIV, Herpes simplex, HCV, Human papilloma virus Radiation: UVL - formation of pyrimidine dimers in DNA
- 5. 5 4 phases naturalhistory of most malignant tumors: transformation - malignant change of target cell growth of the transformed cells; local invasion distant metastases
- 6. 6 Steps in Chemical Carcinogenesis INITIATION exposure of cells to sufficient dose of a carcinogen causes permanent DNA damage (mutations) rapid and irreversible and has “memory” PROMOTION - induction of tumors in initiated cells TRANSFORMATION
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- 8. 8 The net effectof HPV proteins - block of apoptosis and cell proliferation EVENTS IN VIRAL CARCINOGENESIS
- 9. 9 Dissemination of cancersmay occur through one of three pathways: (1) direct seeding of body cavities or surfaces, (2) lymphatic spread, and (3) hematogenous spread +Implantation during surgery Pathways of Spread
- 10. 10 DEFINITION: Tumor implantsdiscontinuous with the primary tumor Metastasis unequivocally marks a tumor as malignant because benign neoplasms do not metastasize The invasiveness of cancers permits them to penetrate into blood vessels, lymphatics, and body cavities, providing the opportunity for spread With few exceptions, all cancers can metastasize Metastases
- 11. 11 Millions of cellsare released into the circulation each day from a primary tumor, but only a few metastases are produced A clear understanding of the origin of metastasis is of major importance for the management of cancer patients and the development of effective therapies to prevent tumor spread METASTASIS
- 12. 12 involves two phases: (1)invasion of the extracellular matrix and (2) vascular dissemination and homing of tumor cells The metastatic cascade
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- 15. 15 Detachment ("loosening up") of thetumor cells from each other Degradation of ECM Invasion of the ECM is an active process that can be resolved into several steps
- 16. 16 Attachment to matrix components Migrationof tumor cells Invasion of the ECM is an active process that can be resolved into several steps
- 17. 17 Certain subclones possessthe right combination of gene products to complete all the steps for metastasis Mechanisms of metastasis development within a primary tumor
- 18. 18 Metastases are dueto gene expression pattern called a "metastasis signature” Mechanisms of metastasis development within a primary tumor
- 19. 19 Mechanisms of metastasisdevelopment within a primary tumor A combination of A and B, in which metastatic variants appear in a tumor with a metastatic gene signature
- 20. 20 Metastasis development isinfluenced by the tumor stroma, which regulates angiogenesis, local invasiveness and resistance to immune elimination
- 21. 21 Metastasis signature representsa general predisposition for metastasis, due to multiple abnormalities that occur in many, perhaps in most, cells of a primary tumor. This signature may involve not only properties intrinsic to the cancer cells, but also the characteristics of the stroma, the presence of infiltrating immune cells, and angiogenesis. Nat Rev Cancer. 2005; 5 (5): 338.
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- 27. 27 Axillary lymph nodewith metastatic breast carcinoma
- 28. 28 GRADING AND STAGINGOF CANCER GRADING - based on the degree of differentiation of the tumor cells and the number of mitoses within the tumor as presumed correlates of aggressiveness STAGING - based on the size of the primary lesion, its extent of spread to surrounding tissues, regional lymph nodes, and the presence or absence of blood-borne metastases TNM
- 29. 29 STAGING AND GRADINGOF TUMORS TNM DIFFERENTIATION •well •moderate •low (poor) G
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- 32. 32 Cancer Mortality byAge for Males All Ages Under 15 15-34 1) Lung 2) Prostate 3) Colorectum 4) Pancreas 5) Leukemia 1) Leukemia 2) CNS 3) Endocrine 4) Lymphoma 5) Connective Tissue 1) Leukemia 2) Lymphoma 3) CNS 4) Skin 5) Hodgkin’s Disease 35-54 55-74 75+ 1) Lung 2) Colorectum 3) CNS 4) Lymphoma 5) Pancreas 1) Lung 2) Colorectum 3) Prostate 4) Pancreas 5) Esophagus 1) Lung 2) Prostate 3) Colorectum 4) Pancreas 5) Leukemia
- 33. 33 Cancer Mortality byAge for Females All Ages Under 15 15-34 1) Lung 2) Breast 3) Colorectum 4) Ovary 5) Pancreas 1) Leukemia 2) CNS 3) Endocrine 4) Connective Tissue 5) Kidney 1) Breast 2) Leukemia 3) Uterus 4) CNS 5) Lymphoma 35-54 55-74 75+ 1) Breast 2) Lung 3) Colorectum 4) Uterus 5) Ovary 1) Lung 2) Breast 3) Colorectum 4) Ovary 5) Pancreas 1) Colorectum 2) Lung 3) Breast 4) Pancreas 5) Ovary
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- 35. 35 BIOCHEMICAL MARKERS tumormarkers – diagnostic and prognostic Follow up - therapeutic effect and recurrent disease
- 36. 36 LIST OF SOMEMARKERS hCG choriocarcinoma AFP hepatocellular ca calcitonin thyroid medullary ca prolactin pituitary adenomas CA 125 ovarian carcinoma PSA prostate carcinoma chromogranin A endocrine neoplasias
- 37. 37 Senile kerratosis Radiation dermatitis Leukoplakia Erythroplasia Queyrat Cryptorchism Villous adenoma Morbus Bowen Adenomatous hyperplasia of endometrium Familial polyposis Ulcerous colitis Atrophic gastritis Precancerous lesions
- 38. 38 Cancer patients usuallydie because of: Metastases Rupture of large vessels and hemorrhage Compression of vital organs Organ failure Infections Intoxication - cacchexia Paraneoplastic syndrome - tromboses
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- 56. 56 Squamous cell cancer- coli uteri
- 57. 57 Squamous cell cancer- coli uteri
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- 61. 61 Serous cystadenoma ofovarium
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- 71. 71 LIPOMA - anyage, any place Skin, in the wall of GIT organs, retroperitoneum
- 72. 72 CHONDROMA – longbones, hands, feet, ribs, vertebral column and pelvis
- 73. 73 atrium, 1-10 cm,pedunculated MYXOMA
- 74. 74 OSTEOMA - bonesof the skull - compact and spongious part - osteoma eburneum (durum)
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- 76. 76 rare myocardium– small white gray nodules up to several centimeters Myoblastic myoma of Abrikosov – tongue, esophagus – large cells with granulated cytoplasm RABDOMYOMA
- 77. 77 rare tumor malignant elongated cells in bundles – nuclei “hering bone" giant cells not common differentiated – more collagen undifferentiated – scant collagen FIBROSARCOMA
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- 79. 79 • about 20%of all primary mesenchymal tumors • 75% - until 25 years • Painful mass, fast growing in the methaphysis of long bones • 50% knee, flat bones • Sudden fracture •20% with metastases at time of diagnosis Osteogenic Sarcoma
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- 82. 82 most common in adults40-60 years deep in soft tissue of extremities, retroperitoneum Liposarcoma
- 83. 83 LIPOSARCOMA LIPOBLASTS – resemble fetal adipocytes,round cells with many lipid vacuoles
- 84. 84 Chondrosarcoma atypical chondrocytesin basophillic chondroid matrix formation of osteoid substance and primitive bone trabeculae, surrounded by neoplastic bizarre giant cells osteolytic osteosclerotic variants
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- 89. 89 Haemangioma cavernosum Skin, liver,brain, muscles ... red bluish spongy mass (1-2 cm) – may be extremely large
- 90. 90 Glomus angioma TumorBare-Masson Painful tumor, derived from modified SMC of glomus - specialized in arteriovenous anastomoses function in thermoregulation most common under nails >1 cm, elevated, firm, roundish, red blue nodule two component׃ Branched vascular channels Glomus cells arround vessels
- 91. 91 HEMANGIOPERICYTOMA venules, capillaries rare lower extremities, retroperitoneum 4-5cm branched, splitted, dilated vascular spaces, surrounded by pericytes
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- 97. 97 Ewing sarcoma Първичнималигнени дребноклетъчни тумори на костта /сарком на Юинг и PNET/ Неврална диференциация PNET – примитивни невроектодермални тумори Различават се по диференциация Туморите с неврална диференциация на светлинна микроскопия, имунохистохимично и ЕМ - PNET, а тези, които не се позитивират - Юинг сарком Двата тумора – 6-10% от първичните малигнени костни тумори При деца на 2-ро място след остеосаркома 10-15 г- възраст
- 98. 98 Сарком на Юинги PNET Произлизат от медуларния канал, инвазират кортекса и периоста и образува болезнена мекотъканна маса – жълтеникавобелезникава често с кръвоизливи и некрози В диафизата на дългите тръбести кости, плоските кости на таза Сарком на Юинг - малки сини кръгли клетки - ПАС + цитоплазма - гликоген. PNET - розетки на Homer-Wright розетки /туморни клетки подредени около централно фибриларно пространство/ е индикатор за невронална диференциация
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- 118. 118 Епендимом /Ependymoma/ итумори от плексус хориоидеус - 5%-10% от туморите до 20 г. - в съседство на епендима на вентрикулите /най-често IV/ - При възрастни – гръбначния мозък - Солиден или папиларни маси - Трудно се екстирпират – близо до понса и продълговатия мозък - образува розетки /наподобява ембрионален епендимален канал/ и периваскуларни розетки /около съдове/ - добре диференциран епендимом /II степен/ - Анапластичен/ епендимом /III степен/
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- 120. 120 Епендимни тумори итумори от плексус хориоидеус Папилом на Plexus chorioideus при деца латералните вентрикули; при възрастни - IV вентрикул папили /съединителнотъканна сърцевина покрита с кубичен или цилиндричен епител Хориоиден карцином !!!
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