Neoplasia Diskusi 5.pptx PDF

NEOPLASIA PEMBIMBING : dr. Hartono TJahjadi, Sp.PA, Susp. O.G.P (K) Arief Prasetiyo Aulia Fitri Firdausya Dessy Hayu P Erika Pratami Fitri Kurniawati Nadia Carolina N....

NEOPLASIA PEMBIMBING : dr. Hartono TJahjadi, Sp.PA, Susp. O.G.P (K) Arief Prasetiyo Aulia Fitri Firdausya Dessy Hayu P Erika Pratami Fitri Kurniawati Nadia Carolina N. Indah Widyastuty F. Nova Elisa Risya A. Rahmawanti Patobiologi TA 2024/2025 Gasal  NOMENKLATUR Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.277-279​  DEFINISI Neoplasia = Pertumbuhan baru Neoplasma = Kumpulan sel dan stroma yang menyusun pertumbuhan baru Istilah tumor pada awalnya digunakan untuk pembengkakan yang disebabkan oleh peradangan Saat ini → Tumor = Neoplasma NEOPLASMA: “Massa jaringan abnormal yang pertumbuhannya berlebihan dan tidak terkoordinasi dengan jaringan normal, serta tetap berlangsung meskipun rangsangan yang memicu perubahan tersebut telah berhenti” Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia: Komponen Dasar Tumor 1. Parenkim, terdiri atas sel yang mengalami transformasi atau sel neoplastik 2. Stroma, jaringan dan sel penunjang yang berasal dari inang dan tidak bersifat neoplastik tetapi sangat penting untuk mendukung pertumbuhan dan perkembangan tumor. Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia:  Pembagian Tumor Tumor Jinak Tumor tersebut tetap terlokalisasi di tempat asalnya dan dapat diangkat dengan tindakan bedah Tumor Ganas (Kanker) Lesi dapat menginvasi dan merusak struktur di sekitarnya dan menyebar ke tempat yang jauh (metastasis) Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia:  Tumor Jinak Nama berakhiran “– oma” pada jenis sel asal tumor tersebut Contoh: Berasal dari jaringan fibrosa = fibroma Berasal dari tulang rawan = kondroma Polip kolon.(kiri) polip melekat pada mukosa;(kanan) polip terlihat secara makroskopis (gastrointestinalatlas.com) Berasal dari osteoblast = osteoma Adenoma = kelompok neoplasma yang berasal dari jaringan epitel kelenjar Papiloma = tumbuh pada permukaan epitel dan secara makroskopis & mikroskopis terlihat seperti jari Polip = ketika neoplasma jinak atau ganas membentuk struktur yang terlihat secara makroskopis di atas permukaan mukosa dan menonjol. Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia: Tumor Ganas (Kanker) Berasal dari bahasa Latin cancers (kepiting) – sifatnya yang melekat erat di permukaan tempat tumor berada, seperti kepiting Tumor ganas yang berasal dari jaringan mesenkim padat disebut SARKOMA (fibrosarkoma, kondrosarkoma–mengikuti sel asal tumor); berasal dari sel mesenkim darah disebut LEUKIMIA/LIMFOMA Tumor ganas yang berasal dari sel epitel, yang berasal dari salah satu dari tiga lapisan germinal disebut KARSINOMA (Adenokarsinoma, karsinoma sel skuamosa) Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia:  Tumor Campur (Mixed Tumor) Jenis neoplasma yang terdiri dari beberapa jenis sel atau jaringan yang berbeda, Tumor ini berkembang dari satu jenis sel (stem cell atau sel pluripoten) yang kemudian berdiferensiasi menjadi beberapa jenis jaringan yang berbeda (contoh: jaringan epitel dan mesenkim) Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia:  Tumor Campur (Mixed Tumor) Contoh: adenoma pleomorfik (sering ditemukan di kelenjar liur) Tumor ini terdiri dari campuran elemen epitelial (seperti kelenjar atau duktus) dan stroma mesenkimal (seperti jaringan ikat, kartilago, atau tulang). ilovepathology.com/pathology-of-pleomorphic-adenoma/ Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia: Tumor Campur (Mixed Tumor) Terato Cystic teratoma ma pada ovarium Jenis neoplasma yang berasal dari sel germinal yang bersifat pluripoten – mengandung sel/jaringan yang imatur atau matur Teratoma dapat mengandung berbagai jenis jaringan dari ketiga lapisan embrional, seperti rambut, kulit, otot, tulang, dan bahkan jaringan saraf. Banyak ditemukan di daerah ovarium, https://medicine.nus.edu.sg/pathweb/virtual-pathology-museum/04276-2/ testis, atau area garis tengah tubuh (sakrum dan mediastinum) Contoh: ovarian cystic teratoma Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia: Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia: Pathways of Spread Dissemination of cancers occurs through three pathways: (1) direct seeding of body cavities or surfaces (2) lymphatic spread (3) hematogenous spread Seeding of Body Cavities and Surfaces Seeding of body cavities and surfaces occurs when a malignant neoplasm penetrates into a natural “open field” lacking physical barriers. Most often involved is the peritoneal cavity, but any body cavity pleural, pericardial, subarachnoid and joint spaces may be affected. Such seeding is particularly characteristic of carcinomas arising in the ovaries, which Lymphatic Spread The pattern of spread follows the natural Lymphatic Spread routes of lymphatic drainage. for example, because carcinomas of the breast usually arise in the upper outer quadrants, they generally disseminate first to the axillary lymph nodes and then to infraclavicular and supraclavicular lymph nodes. Carcinomas of the lung arising in the major respiratory passages metastasize first to perihilar tracheo bronchial and mediastinal lymph nodes. Hematogenous Spread Comparison between Benign and Malignant Tumors  EPIDEMIOLOGY OF CANCER Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.277-279​  https://gco.iarc.fr/en WHY IT’S IMPORTANT ? Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.277-279​  The Global Impact of Cancer In 2018 it was estimated that there were over 9.5 million deaths caused by cancer worldwide. Moreover, due to increasing population size and age, cancer cases and cancer-related deaths worldwide are projected to increase to 21.4 million and 13.2 million, respectively by the year 2030 https://gco.iarc.who.int/media/globocan/factsheets/ populations/900-world-fact-sheet.pdf Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.277-279​  In the last 50 years of the 20th century, the age-adjusted cancer death rate increased significantly in both men and women Since 1990 the cancer death rate has decreased by approximately 20% The cancer death rate has fallen by approximately 10% since 1991 The last half-century → sharp decline in deaths caused by cervical cancer in the United States. This decrease is largely attributable to the Papanicolaou (Pap) smear test, which enables detection of “precursor lesions” (discussed later) and early, curable cancers Between 1990–1991 and 2004, lung cancer death rates in women and liver and intrahepatic bile duct cancer death rates in men increased substantially Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.277-279​ https://gco.iarc.who.int/overtime/en/dataviz/trends?populations=752&sexes=1_2&types=1&multiple_populations=1&cancers=0  Although both genetic and environmental factors contribute, environmental influences are the Environmental Factors dominant risk factors for most cancers. 1998 20th century recently Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.277-279​  Environmental Factors 1. Infectious agents → 15% of all cancer, human papillomavirus (HPV) 2. Smoking → 90% of lung cancers 3. Alcohol consumption → increased synergistically when combined with tobacco use 4. Diet → colorectal carcinoma, prostate carcinoma, and breast carcinoma 5. Obesity → 14% of cancer deaths in men and 20% in women are associated with obesity 6. Reproduction history → cumulative exposure to estrogen stimulation 7. Environmental carcinogen → carcinogenic factors Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.277-279​  Age Most carcinomas occur in adults older than 55 years of age Cancer is the leading cause of death among women aged 40 to 79 and among men aged 60 to 79 The decline in cancer deaths after age 80 is due to the lower number of individuals who reach this age Cancer accounts for approximately 10% of all deaths in children younger than age 15 in the United States The types of cancers that predominate in children are different from those seen in adults Acute Leukemia, distinctive neoplasms of the central nervous system, neuroblastoma, Wilms tumor, retinoblastoma, acute lymphoblastic leukemia, and rhabdomyosarcoma Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.277-279​ https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf INDONESIA ACQUIRED PREDISPOSING CONDITIONS Acquired conditions that predispose to cancer divided into : 1. Chronic inflammatory disorders. 2. Precursor lessions. 3. Immunodeficiency states. Chronic inflammation. Individuals affected by a wide variety of chronic inflammatory disease (infectious or non infectious)🡪 cancer risk. Tumors arising from condition chronic inflammation🡪 Carcinoma. Example: Treatment and diagnosis of H.pylori gastritis with AB🡪 quell a chronic inflammatory condition🡪 may lead a gastric cancer Precursor lessions. Defined by localized morphologic changes🡪 identify a field of ephitelium that is at risk for malignant transformation. These changes : Hyperplasia, metaplasia, dysplasia. Precursor lesions consisting of hyperplasia 🡪 chronic exposure endometrium hyperplasia🡨 sustained estrogenic stimulation of the endometrium. Immunodeficiency and cancer. Patient who are immunno deficient🡪 deficits in T-cell immunity🡪 risk for cancer especially types caused by oncogenic viruse. These virus-associated tumors include lymphomas, certain carcinomas, and some sarcomas and sarcoma-like proliferations. Genetic Predisposition and Interactions Between Environmental and Inherited Factors In some families, cancer is an inherited trait. For instance, breast cancer risk in females who inherit mutated copies of the BRCA1 or BRCA2 tumor suppressor genes. CARCINOGENIC AGENTS AND THEIR CELLULAR INTERACTIONS Chemical Carcinogenesis Classic experiment of chemical carcinogenesis: Initiation results from exposure of cells to a sufficient dose of a carcinogenic agent. It causes permanent DNA damage (mutations). Promoters can induce tumors to arise from initiated cells, but they are not tumorigenic by themselves. Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia: Elsevier;2021. p.324-327 Initiating chemical carcinogens, highly reactive electrophiles. React with nucleophilic (electron- rich) atoms in the cell. Their targets are DNA, RNA, and proteins Mutations / cell death. Mutated cell passes on Cancer the DNA lesions to its daughter cells. Direct Acting vs Indirect-Acting Carcinogens Direct Acting Carcinogens Indirect-Acting Carcinogens Require metabolic conversion to become Do not require metabolic active carcinogens 🡪 called ultimate conversion to become carcinogenic. carcinogens. Some of the most potent 🡪 polycyclic Most are weak carcinogens hydrocarbons, benzo[a]pyrene. Some are important: cancer In the workplace and at home 🡪 vinyl chloride, chemotherapeutic drugs (e.g., alkylating arsenic, nickel, chromium, insecticides, fungicides, and polychlorinated biphenyls. agents). Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia:  Radiation Carcinogenesis Sinar Ultraviolet Paparan sinar UV dari matahari 🡪 pada individu yang rentan (umumnya yang berkulit putih) 🡪 berasosiasi dengan insidens KSS, karsinoma sel basal, dan melanoma pada kulit. Sinar UVB 🡪 menyebabkan dimer pirimidin (lesi molekular) 🡪 merusak double-strand DNA. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier;2021. P.324-327 Gambar: Pyrimidine dimer. In: Wikipedia [Internet]. 2024 [cited 2024 Aug 21]. Available from: Radiation Carcinogenesis Radiasi Pengion Radiasi elektromagnetik (x-ray, γ ray) dan partikulat (α particles, β particles, protons, neutrons) → karsinogenik. Contoh: Hiroshima dan Nagasaki → leukemia (setelah 7 tahun). Selanjutnya: karsinoma payudara, kolon, tiroid, dan paru. Anak-anak dengan paparan CT scan: ○ 2-3 kali paparan → risiko leukemia meningkat 3 kali lipat, ○ 5-10 kali paparan → risiko tumor otak meningkat 3 kali lipat. Secara teori dan praktis, sel apapun dapat bertransformasi menjadi kanker pada paparan radiasi yang cukup. Microbial Carcinogenesis Virus Bakteri Virus RNA Virus DNA Human T- Human Papillomavirus Helicobacter pylori → Cell (HPV) kanker lambung Leukemia Epstein-Barr Virus (EBV) Virus Type 1 Hepatitis B dan C Virus (HTLV-1) (HBV dan HBC)  Microbial Carcinogenesis Virus RNA Human T-Cell Leukimia Virus Type 1 HTLV-1 → CD4+ T-cells HTLV-1 memiliki gene TAX dan HBz Transmisi penyebaran ke manusia → hubungan seks, darah, atau menyusui. Source pict: Akram, N., Imran, M., Noreen, M., Ahmed, F., Atif, M., Fatima, Z., & Bilal Waqar, A. (2017). Oncogenic role of tumor viruses in humans. Viral immunology, 30(1), 20-27.  Microbial Carcinogenesis Virus DNA Human Papillomaviru s HPV tipe 1, 2, 4, 7 penyebab papiloma skuamosa jinak (kutil), HPV tipe 16 dan 18 merupakan penyebab karsinoma sel skuamosa leher rahim dan daerah anogenital. Genom HPV dapat berintegrasi dengan genom inang. HPV dapat mensekresikan protein E6 dan E7 penyebab onkogen. Apabila ditambahkan dengan gen RAS yang bermutasi akan meningkatkan keganasan sel kanker. Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia: Elsevier;2021. p.324-327  Microbial Carcinogenesis Virus DNA Epstein-Barr Virus EBV dapat berinteraksi terhadap tumor pada manusia, seperti limfoma, karsinoma, dan sarkoma. Umumnya EBV berinteraksi dengan sel B dan karsinoma nasofaring. Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia: Elsevier;2021. p.324-327  Microbial Carcinogenesis Virus DNA Hepatitis B dan C HBV berasosiasi dengan sel karsinoma hepatocellular Hepatocellular injury → aktivasi sel-sel imun → produksi mediator, ROS → mengaktivasi NF-kB → mencegah apoptosis → hepatosit divading → genotoxic stress → mutasi gen HBV memiliki gen HBx → aktivasi faktor transkripsi dan jalur transduksi sinyal Integrasi genom virus - genom sel inang → structural changes in Source pict: Shen, C., Jiang, X., Li, M., & Luo, Y. (2023). Hepatitis virus and hepatocellular carcinoma: recent advances. Cancers, chromosome → disregulasi onkogen 15(2), 533. dan gen tumor supresi  Microbial Carcinogenesis Bakteri Helicobacter pylori Infeksi H. pylori terlibat dalam pembentukan adenokarsinoma dan limfoma lambung H. pylori memiliki gen cytotoxin- associated A (CagA). Infeksi H. pylori → penetrasi CagA sel epitel lambung → stimulasi unregulated growth factor → infeksi kronik → atrophy sel-sel lambung → metaplasia → displasia → kanker Source pict: González, M. F., Díaz, P., Sandoval-Bórquez, A., Herrera, D., & Quest, A. F. (2021). Helicobacter pylori outer membrane vesicles and extracellular vesicles from Helicobacter pylori-infected cells in gastric disease development. International Journal of Molecular Sciences, 22(9), 4823. Kelenjar Hipofisis/pituitari Pancreatic ductal adenocarcinoma  Laboratory Diagnosis of Cancer Histologic and Cytologic Methods Immunohistochemistry Flow Cytometry Circulating Tumor Cells Molecular Diagnostics and Cytogenetics Molecular Profiles of Tumors: The Future of Cancer Diagnostics. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.331-335  Histologic and Cytologic Methods Most instances, not difficult. The laboratory evaluation of a lesion is only as good as the specimen made available for examination. It must be adequate, representative, and properly preserved. Several sampling approaches: 1. Excision or biopsy. 2. Fine needle aspiration (with small bore needle, minimal invasive, palpable lesions such as the breast, thyroid, and lymph nodes). 3. Cytologic smears (screening for carcinoma of the cervix and its precursor lesions or malignancy in which tumor cells are shed into fluids or are easily accessible, types of specimens include urine, cerebrospinal fluid, pleural effusions, and bronchial washes). Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.331-335 p.277-279​ https://www.surgipathcylab.com/fine-needle Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.331-335 p.277-279​  Immunohistochemistry Powerful technique that exploits the specific binding between an antibody and antigen to detect and localize specific antigens in cells and tissue. Most commonly performed on formalin fixed paraffin embedded (FFPE) tissue which has the advantage of being amenable to easy storage, Categorization of undifferentiated malignant tumors. Determination of site of origin of metastatic tumors. Detection of molecules that have prognostic or therapeutic significance. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.331-335 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749998/ Steps in IHC Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.331-335  Flow Cytometry Flow cytometry rapidly and quantitatively measures several cell characteristics but requires viable cells in suspension. It is mainly used to identify cellular antigens expressed by “liquid” tumors, those that arise from bloodforming tissues. An advantage of flow cytometry over immunohistochemistry is that multiple antigens are assessed simultaneously on individual cells using combinations of specific antibodies linked to different fluorescent dyes. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.331-335  https://www.youtube.com/watch? v=5IdYFgYb9ls https://www.youtube.com/watch? v=7bCZx5xPwt0 https://www.streck.com/wp-content/uploads/2020/11/flow-cytometry-light-scatter-illustration.jpg https://www.researchgate.net/profile/Joaquin-Marco-Brualla/publication/359649728/figure/fig2/AS:1139966172241922@1648800523951/Representative-flow- cytometry-results-Results-are-shown-for-MSCs-at-28-days-and.png  Circulating Tumor Cells Tumor cells that shed from the primary tumor and intravasate into the peripheral blood circulation system responsible for metastasis. Instrumentation that permits detection, quantification, and characterization of rare solid tumor cells (carcinoma, melanoma) circulating in the blood is being developed as a diagnostic modality. Some of the devices rely on three-dimensional flow cells coated with antibodies specific for tumor cells of interest (carcinoma cells) that efficiently capture rare tumor cells present in the blood. Such methods have the potential to permit earlier diagnosis, to gauge the risk of metastasis, and to provide a minimally invasive means of assessing the response of tumor cells to therapy, but are mainly being used currently in the realm of clinical research. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.277-279​ https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00419-4/fulltext  Molecular Diagnostics and Cytogenetics Molecular genetic diagnostics —> DNA, cytogenetic —> chromosomal abnormalities. Diagnosis of malignant neoplasms. Prognosis of malignant neoplasms. Detection of minimal residual disease. Diagnosis of hereditary predisposition to cancer. Guiding therapy with oncoprotein-directed drugs. Identifying mechanisms of drug resistance: liquid biopsies. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.331-335 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290954/  Molecular Profiles of Tumors: The Future of Cancer Diagnostics https://link.springer.com/chapter/10.1007/978-981-16-1197-1_16 Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.331-335 Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.331-335  Tumor Markers - Contribute to the detection of cancer - useful in following a tumor’s response to therapy and in detecting tumor recurrence Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.331-335 Screenshot 2024-08-10 234124 Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.331-335 TERIMA KASIH