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- 1. MODULE 5. Neoplastic growth Department of General and Clinical Pathology Medical University - Varna Peter Ghenev MD, PhD
- 2. 2 ETIOLOGY OF TUMOR GROWTH Theories Chemical (irritative) R.Virchow Viral (genetic) Dysonthogenetic (Conheim) Polietiological
- 3. 3 Sir Percival Pott, 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 from the 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 natural history 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
- 8. 8 The net effect of HPV proteins - block of apoptosis and cell proliferation EVENTS IN VIRAL CARCINOGENESIS
- 9. 9 Dissemination of cancers may 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 implants discontinuous 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 cells are 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
- 15. 15 Detachment ("loosening up") of the tumor 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 Migration of tumor cells Invasion of the ECM is an active process that can be resolved into several steps
- 17. 17 Certain subclones possess the right combination of gene products to complete all the steps for metastasis Mechanisms of metastasis development within a primary tumor
- 18. 18 Metastases are due to gene expression pattern called a "metastasis signature” Mechanisms of metastasis development within a primary tumor
- 19. 19 Mechanisms of metastasis development 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 is influenced by the tumor stroma, which regulates angiogenesis, local invasiveness and resistance to immune elimination
- 21. 21 Metastasis signature represents a 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.
- 22. 22
- 27. 27 Axillary lymph node with metastatic breast carcinoma
- 28. 28 GRADING AND STAGING OF 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 GRADING OF TUMORS TNM DIFFERENTIATION •well •moderate •low (poor) G
- 32. 32 Cancer Mortality by Age 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 by Age 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
- 35. 35 BIOCHEMICAL MARKERS tumor markers – diagnostic and prognostic Follow up - therapeutic effect and recurrent disease
- 36. 36 LIST OF SOME MARKERS 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 usually die because of: Metastases Rupture of large vessels and hemorrhage Compression of vital organs Organ failure Infections Intoxication - cacchexia Paraneoplastic syndrome - tromboses
- 40. 40
- 41. 41 Papilloma
- 42. 42 Adenoma of adrenal gland
- 44. 44
- 46. 46 ПОЛИПОЗНО-ПАПИЛАРНА ТИП “ЦВЕТНО ЗЕЛЕ” ФОРМА
- 47. 47
- 49. 49
- 53. 53 Lung cancer
- 54. 54 Liver cancer
- 55. 55 Carcinoma portionis vaginalis coli uteri
- 56. 56 Squamous cell cancer - coli uteri
- 57. 57 Squamous cell cancer - coli uteri
- 60. 60 LEIOMYOMA
- 61. 61 Serous cystadenoma of ovarium
- 63. 63
- 67. 67 Breast cancer
- 68. 68
- 69. 69 Seminoma
- 70. 70 FIBROMA
- 71. 71 LIPOMA - any age, any place Skin, in the wall of GIT organs, retroperitoneum
- 72. 72 CHONDROMA – long bones, hands, feet, ribs, vertebral column and pelvis
- 73. 73 atrium, 1-10 cm, pedunculated MYXOMA
- 74. 74 OSTEOMA - bones of the skull - compact and spongious part - osteoma eburneum (durum)
- 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
- 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
- 82. 82 most common in adults 40-60 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 chondrocytes in basophillic chondroid matrix formation of osteoid substance and primitive bone trabeculae, surrounded by neoplastic bizarre giant cells osteolytic osteosclerotic variants
- 88. 88 Hemangioma
- 89. 89 Haemangioma cavernosum Skin, liver, brain, muscles ... red bluish spongy mass (1-2 cm) – may be extremely large
- 90. 90 Glomus angioma Tumor Bare-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
- 94. 94 Angiosarcoma
- 95. 95 Angiosarcoma
- 96. 96 Synovioma
- 97. 97 Ewing sarcoma Първични малигнени 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 Юинг и 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
- 99. 99 Ewing sarcoma
- 100. 100 NEVUS
- 101. 101
- 102. 102
- 103. 103
- 104. 104
- 107. 107
- 108. 108
- 109. 109 Teratoma
- 110. 110 Gangliocytoma
- 111. 111 GANGLIOGLIOMA
- 112. 112 NEUROBLASTOMA
- 113. 113 Pheochromocytoma
- 114. 114 Astrocytoma
- 115. 115 Glioblastoma
- 116. 116 Glioblastoma
- 118. 118 Епендимом /Ependymoma/ и тумори 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/
- 119. 119 Ependymoma
- 120. 120 Епендимни тумори и тумори 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 !!!
- 122. 122 Meduloblastoma
- 123. 123 Meningioma
- 124. 124 Meningioma
- 126. 126 Meningioma
- 127. 127 Neurinoma
- 130. 130 Paraganglioma
- 131. 131 Paraganglioma
- 132. 132 PLASMOCYTOMA
- 133. 133 APUD
- 134. 134 CARCINOID
- 135. 135 SCC