j0305257 General pathology III. Inflammation II. (proliferative, granulomatous). Progressive changes. General oncology. j0305257 Inflammation II. j0305257 Proliferative inflammation ûHealing (reparation) of defects (wound, regressive changes, postinflammatory etc.) → granulation tissue → scar ð ûoften pronounced in chronic inflammation û ûprimary proliferative inflammation uncommon (fibromatosis) ûreactive fibro/myofibroblastic lesions ðproliferation of myofibroblasts, occasionally forming tumour-like masses •nodular fasciitis, myositisossificans – may be posttraumatic, often idiopathic • j0305257 Fibromatosis of the abdominal wall SoftTissue_Fibromatosis_Abdominal1 j0305257 Chronic inflammation û prolonged duration û tissue injury + inflammatory reaction + repair û Causes: persistent infection, immune mediated inflammatory reaction, prolonged exposure to harmful agents (toxin) j0305257 Granulation tissue ûMajor repair instrument û û In: ð wound, fracture, ulcer, necrosis healing; thrombus, haematoma organisation û û Gross: ð soft red tissue, granular surface (capillary loops) û ûMicro: ð fibrin fibers ð inflammatory reaction ð fibroblasts, myofibroblasts ð starting collagen fibers production ð proliferating capillaries – angiogenesis ð later intercellular matrix + tissue remodeling, retraction – scar formation ð û û û j0305257 Granulation tissue – inflammatory cells HE40x 1 surface 2 proliferation of capillaries 3 tissue with inflammatory cells 2 1 1 1 2 2 3 3 j0305257 Granulomatous inflammation ûdistinctive pattern of chronic inflammation ûhistorical classification: ð„non-specific“ infl. • common general microscopic picture, i.e. purulent infl. ð specific“ • micro typical for a specific cause ð ûaggregated macrophages unable to destroy cause → transformation into epithelioid and multinuclear cells → granuloma ûdelayed type hypersensitivity (T-cells, macrophages, sometimes eosinophils) ûforeign body granuloma x immune granuloma û j0305257 Granulomatous inflammation ûcauses of granulomatous disease: ðspecific infections •mycobacteria (e.g. Tuberculosis, leprosy, atypical mycobacteria), many types of fungi, parasites…) ð foreign bodies (undigestible) •endogenous (keratin, necrotic bone, cholesterol crystals, urate …) •exogenous (e.g. suture material, silica, talc, asbestos,…) ð chemicals and drugs •beryllium, sulphonamides ðunknown ? - pathologic hypersensitive reaction to some common antigenes (combination of inborn and external factors) •Crohn´s disease, sarcoidosis, Wegener‘s granulomatosis ð stromal and lymph node reaction in some tumors (Hodgkin‘s malignant lymphoma) • • • ð • • • • • j0305257 Tuberculosis ûetiology ðMycobacterium tuberculosis •Ziehl-Neelsen staining, acid-resistant bacteria , culture or PCR detection • û tuberculous granuloma - basic morphology: ðcentral caseous necrosis (basophilic nuclear fragments) ð epithelioid macrophages ð multinucleated Langhans‘ giant cells (fusion of macrophages) ð rim of T-cells • j0305257 Tuberculous granuloma 1caseous necrosis 2epiteloid cells 3Langhans´ giant cells 4lymphocytes 1 2 2 3 4 3 j0305257 caseous necrosis poprašková nekróza, 400x.jpg HE staining shows amorphous eosinophilic area stoppled by haematoxyphilic nuclear debris j0305257 Langhans´ giant cell j0305257 Ziehl-Neelsen staining, acid-resistant bacteria BK2, 400x.jpg j0305257 TB - morphology ûTB exudate – serofibrinous exudate + macrophages with M.tbc – Orth cells ûTB granuloma (tubercle) - proliferative form û caseification û colliquation û calcification j0305257 Tuberculosis ûPrimary tuberculosis ðlungs usually first site of contact (GIT, skin) ðGhon complex – focus of primary infection , similar granulomas in lymph nodes draining the affected portion of lung ð primary lession usually organise -> fibrocalcific nodule (tubercle bacilli may be still present) x complications ð ûSecondary tuberculosis: in previously sensitized host ðmostly caused by reactivation of old primary infection (event. reinfection) ð in lung - apical foci + cavitation, porogennous spread ðisolated organ tb (renal, adrenal, meningeal, osteomyelitis, salpingitis ð progression -> organism virulence x host sensitivity ð j0305257 Tuberculosis û miliary (disseminated) tuberculosis ð may be consequence of either primary or secondary tb ð hematogenous dissemination -> numerous small granulomas in many organs (lungs, meninges, kidneys, bone marrow, liver, … ð serious condition (untreated nearly 100% fatal) ð ðComplications: ð vessel arosion + rupture – hemoptysis / hemoptoe ð spine deformities (heart + lung function problems) ð secondary amyloidosis ð infertility ð … j0305257 j0305257 Image056 j0305257 Image057 j0305257 Sarcoidosis ûsystemic chronic granulomatous inflammatory disease, direct etiology unknown (disordered immune regulation in genetically predisposed hosts exposed to certain environmental agents), ↑ CD4+ T-cells û ûmostly in mediastinal LN, lung, skin, eye; any localisation possible û ûregular small „tuberculoid“ granulomas without caseous necrosis (asteroid inclusions, Schaumann‘s inclusions in Langerhans‘ cells) → x TBC (→ biopsy, dg. per exclusionem) û j0305257 Sarcoidosis ûclinically: ðmay be asymptomatic ðchest X-ray – bilateral lymphadenopathy ð ↑ IgG, Ca2+, angiotensin converting enzyme (ACE) in serum ðslow progression or variable remission + healing ð10% mortality (lung fibrosis, cor pulmonale) ð20% lung or ocular dysfunction ðtreatment: corticosteroids ð ð ð û j0305257 lung sarcoidosis sarkoidóza-plíce1, 100x.jpg j0305257 lymph node sarcoidosis sarkoidóza LU1, přehled40x.jpg j0305257 lymph node sarcoidosis sarkoidóza2-detail j0305257 lymph node sarcoidosis sarkoidóza LU2, 200x.jpg j0305257 syphilis (lues) ûTreponema pallidum – spirochaete û ûforms: ðacquired (mostly STD) – 3 stages ðcongenital (transplacental transmission) •late abortion or stillbirth •infantile liver and lung fibrosis, osteochondritis •childhood – keratitis, deafness, teeth anomalies û j0305257 syphilis (lues) - acquired ðprimary chancre •typically acquired by direct sexual contact •primary chancre (skin lession) appears in the entry site 3 wks after contact •Primary chancre - single, firm, painless, non-itchy skin ulceration with a clean base and sharp borders between 0.3 and 3.0 cm in size, serous exudate + treponemata • associated with unilateral or bilateral inguinal lymphadenitis • without treatment heals in a few weeks (3-6) -> atrophic scars ð ðsecondary •early generalisation – transient skin and mucosal rash, generalised lymphadenitis in many cases, non-specific + gen. signs (fever, sore throat, weight loss, …), numerous plasma cells in infiltrate in condylomata lata on moist skin, erosion on mucosa ð ðtertiary •specific changes, 8 – 25 years after primary infection, •symptoms according to localisation of gummata (cerebral cortical atrophy, progressive paralysis, aortic aneurysm) •gumma: mm-cm, tuberculoid granuloma without complete caseous necrosis (rubbery consistency) • ð û j0305257 Syphilis – primary 20-03 j0305257 Syphilis - secondary SecSyphilisRash Condylomata lata Syphilitic rash j0305257 Treponema pallidum (spirochetes visualized by silver staining) treponema j0305257 Leprosy ûMycobacterium leprae ðin developed countries very rare, usually imported û ûformy: ðtuberculoid form •vigorous imunological TH1 reaction -> granulomas without caseous necrosis in the skin, perineural – ulcers, paralysis, atrophy ðlepromatous form •multiple and diffuse infiltrates in the skin (facies leontina), eyes (blindness), lymph nodes, spleen •foamy macrophages + mycobacteria • often progresive (anergic host) • û j0305257 Leprosy – facies leontina j0305257 PROGRESSIVE CHANGES j0305257 ûhealing of tissue defects ðregeneration ðrepair •regeneration and repair often in combination û ûtissue adaptation to the changed conditions ðhypertrophy ðhyperplasia ðmetaplasia Progressive changes j0305257 REGENERATION ûreplacement by identical tissue (morphology, function) û û û ûaccording to regenerative ability: ðlabile cells •epithelial cells of skin, gut,…, bone marrow,…, •permanent regeneration from stem cells (rapid „turn-over time“) ðstable •liver, kidney (proximal tubule epithelial cells), smooth muscle •regeneration on demand in tissue loss ðpermanent (postmitotic) •neurons, cardiac muscle cells •mostly no complete functional regeneration j0305257 REPAIR ûreplacement of lost tissue usually by granulation tissue → fibrotic scar û û ûmay affect the function of the organ ðscar after myocardial infarction ðlung fibrosis, cirhosis,… j0305257 Chronic hepatitis û > 6 months û causes: ðviral hepatitis HBV , HCV, HDV, (HEV, HGV) ðnon-alcoholic fatty liver disease ð toxic (alcohol, drugs) ð autoimmune (antibodies antinuclear, x smooth muscle, x microsomal) ðinborn metabolic defects (Wilson disease, haemochromatosis, alfa-1-antitrypsin deficiency, etc.) ûgross: enlargement, tougher consistency, rougher surface û combination of damage, fibrosis, irregular hyperplasia of hepatocytes û progression to nodular transformation - cirrhosis j0305257 Chronic hepatitis ûDisease activity (grade): û û interface activity (periportal necrosis) û û portal inflammatory infiltrate û û intralobular necroinflammatory activity ûExtent of fibrosis (stage): û û fibrotic septa û bridging û nodule formation û cirrhosis j0305257 Chronic hepatitis j0305257 Cirrhosis û Etiology: ðmassive acute necrosis ðchronic hepatitis ðbiliary diseases • inborn (atresia), • acquired: autoimmune (primary biliary cirrhosis, prim. sclerosing cholangitis), sec. biliary cirrhosis (chronic obstruction) ðcryptogenic cirrhosis ð û Gross: tough, usually diminished size ðmicronodular ðmacronodular û j0305257 Cirrhosis û diffuse parenchymal injury + consequent fibrosis (bridging septa) û û nodular transformation (hepatocyte regeneration x failure of architectectural reconstruction), persisting regressive changes û û reorganisation of vascular architecture û û changes of intrahepatic biliary tract, incl. ductular hyperplasia û j0305257 Complications of cirrhosis ûliver failure: inadequate synthesis, inadequate detoxication, insufficient Kupffer cell function û ûportal hypertesion: splenomegaly, intestinal venous congestion (! infarsation, inflammation) û ascites (! peritonitis), portocaval anastomoses û ûcarcinoma (usually hepatocellular) û j0305257 Cirrhosis – nodular transformation 1jaterní cirhóza MAKRO.png j0305257 Cirrhosis – nodular transformation, chronic hepatitis, cholestasis 1jaterní cirhóza MIKRO.png j0305257 Cirrhosis j0305257 Cirrhosis 1jaterní cirhóza Go.png j0305257 Stomach erosions û NSAIDs + other drugs, alcohol, vomiting, stress, burns, infection, raised intracranial pressure û antrum and body, multiple û microcirculation disorder, capillary rupture, acid hypersecretion û < 3 mm û limited by m. mucosae !!! û healing by regeneration û j0305257 Image014 Erosion / stress ulcer j0305257 Chronic peptic ulcer ûchronic, usually solitary lesion in GIT parts exposed to acid and peptic juices, commonly at mucosal junction û extends through m. mucosae into submucosa or deeper û bulbus duodeni, stomach antrum, GE junction, stomic junction, Meckel diverticulum û imbalance between mucosal defence and damage by gastric juices/bile, drugs, ischaemia (stress) û H. pylori (100% in duodenal ulcers, cca 70% in gastric ulcers), but only 10-20% of infected develop ulcer û Image015 j0305257 Image015 j0305257 Chronic peptic ulcer û gross: starts as sharply demarcated defect, 4 – 40 mm, straight walls, haemorrhagic base û ûlater overhanging mucosa, sometimes slightly elevated borders, smooth base, scarring û ûhistology: in active ulcer 4 layers ð cell debris and fibrinoid necrosis ð mixed inflammatory infiltrate ðgranulation tissue ð fibrotic scar û j0305257 complications û haemorrhage (overt, occult, anaemia) û perforation, shock, peritonitis û penetration into adjacent organs û scarring, stenosis û malignant transformation (stomach) û j0305257 Chronic peptic ulcer Image018 j0305257 Image019 Perforated duodenal ulcer Image020 j0305257 1vřed1 1 surface of ulceration - cellular detritus) 2 granulation tissue 3 chronic inflammation in lamina propria mucosae 1 3 2 Chronic peptic ulcer - duodenum j0305257 1vřed2.jpg 1 surface of ulceration - cellular detritus) 2 Fibrinoid necrosis 3 granulation tissue with mixed inflammatory infiltrate 1 3 2 Chronic peptic ulcer - duodenum j0305257 MYOFIBROSIS DISPERSA CORDIS ûRepeated multiple microinfarcts/myomalatia of cardiomyocytes („angina pectoris“) û ûRepair by granulation tissue, scarring û ûDisperse scars – small whitish foci in myocardium û j0305257 obr14 1 cardiomyocytes 2 myofibrosis 3 vessels 1 MYOFIBROSIS DISPERSA CORDIS 2 3 j0305257 Hyperplasia ûincrease in cell number by cell division → tissue/organ enlargement û ûphysiological: hormonal, compensatory ðHyperplasia of breast tissue (in puberty, pregnancy, lactation) ð ûpathological: excess of hormones / growth factors, still under control (autonomous exceptions rare) ðBenign prostatic hyperplasia ðEndometrial hyperplasia ðThyroid hyperplasia (goiter) j0305257 BENIGN PROSTATIC HYPERPLASIA û common in older men, high incidence > 60 yrs û ûadenomyomatous hyperplasia ðstromal (smooth muscle, fibrotic tissue) ð+ glandular, alternating with atrophy, cystic and regressive changes ð!!! two cellular layers – outer myoepithelial, inner secretory !!! ð û gross: enlarged, nodular, tougher û û main changes in central (periurethral) region j0305257 BENIGN PROSTATIC HYPERPLASIA û Outcome: ð partial → complete urethra obstruction -> urinary residuum, risk of infection (+ ascending – pyelonephritis) ð bladder trabecular hypertrophy ð hydronephrosis û û Benign, but setting for possible preneoplastic changes û û Th: surgery, drugs û j0305257 j0305257 BENIGN PROSTATIC HYPERPLASIA hyperplazie prostaty 40x.jpg j0305257 hyperplazie prostaty 200x hyperplazie prostaty 40x BENIGN PROSTATIC HYPERPLASIA j0305257 Endometrium, menstrual cycle 25 1 2 3 4 1 early proliferative 2 late proliferative 3 early secretory 4 mid/late secretory j0305257 Hyperplastic endometrium 43 1 endometrial hyperplasia 2 Polypous endometrial hyperplasia 1 1 2 j0305257 ENDOMETRIAL HYPERPLASIA ûGross: thicker mucosa (USG) û ûMicro: ðboth glandular and stromal proliferation ð glands more numerous (norm 1:1) ðarchitectonics simple (cystic dilatation) or complex ð proliferative epithelium (basal nuclei, possible stratification) ð ATYPIA: nuclear enlargement, hyperchromasia, distinctive nucleoli, mitotic activity, anisokaryosis. û j0305257 Classification of endometrial hyperplasia ûSimple ðcystic glandular dilatation ðincreased glandular + stromal cellularity ðno atypias ð ûComplex ðmajor architectural change – infoldings ðlower amount of stroma – crowding ð ûAtypical (simple or complex) ðspecify architecture: simple or complex + cellular atypia ðendometrial intraepithelial neoplasia û j0305257 Simple hyperplasia Image058 j0305257 Complex hyperplasia Image059 j0305257 KH2, 200x complex hyperplasia without atypia 1 back to back glands with reduced stroma 2 myometrium 1 1 1 2 j0305257 Complex hyperplasia with atypia 1 AKH3, 200x j0305257 Thyroid hyperplasia ûGoiter ð diffuse • simple – nontoxic • Graves disease – autoimmune, • diff. hyperplasia • ûNodular goiter ðactivation of hypothalamic-pituitary-thyroidal axis (iodine defficiency) ð hyperplastic phase, colloid transformation – involution ðmixture of dilated follicles, regressive fibrosis, bleeding, calcification j0305257 thyr-multinod-ma thyr-hyperpl-ma j0305257 Thyroid hyperplasia nodular goiter struma 20x 01 j0305257 Graves‘ disease û Hyperplastic thyroid → hyperthyroidism û û Graves‘ (Basedow) disease ð organ-specific AI, ð autoantibodies bind on TSH receptor – long-acting thyroid stimulator (LATS) ð û Gross – enlarged, firm, red û û Micro – follicular hyperplasia, papillary, colloid reduction, stromal hyperaemia û j0305257 Hypertrophy ûincrease in cell size without cell division - ↑ production of cellular proteins û ûphysiogical: ðmuscle hypertrophy (response to increased workload) ðhormone-induced (pregnant uterus) ð ûpathological conditions: ð myocardial hypertrophy – essential hypertension, valvular disease (aortal, mitral stenosis, etc) ðarterial wall hypertrophy in hypertension ð ð j0305257 Metaplasia ûreversible replacement of one mature diffrerentiated cell type by another via stem cells (adaptive substitution under stress conditions) ûexxagerated differentiation (non-keratinizing squamous epithelium into keratinizing, cartilage ossification, …) û(rarely direct transformation of a cell by de-differentiation followed by different differentiation) ûepithelial or mesenchymal cells û may undergo further indirect transformation to neoplasia via dysplasia û ûchronic cell injury – smoking, reflux of gastric acid to oesophagus, etc. û ð squamous metaplasia (columnar → squamous) •bronchial epithelium – smokers •endocervical mucosa ð interstinal metaplasia •Barret´s oesophagus in reflux, gastric mucosa in chronic gastritis j0305257 Incipient squamous metaplasia of endocervical colummar epithelium 05 1 2 1 exocervical squamous epithelium 2 endocervical colummar epithelium 3 incipient squamous metaplasia 4 endocervical glands 3 4 j0305257 Incipient squamous metaplasia of endocervical colummar epithelium 06 j0305257 Immature sq. metaplasia Image062 j0305257 Barrett´s oesophagus Barrett 100x 01 Barrett 100x 02 1 intestinal metaplasia (goblet cells) 2 PAS staining – acid mucin substances detection in metaplastic cells 1 1 2 2 j0305257 Barrett´s oesophagus Barrettův jícen 100x 002 1 intestinal metaplasia 2 metaplastic epithelium with dysplasia 3 superficial squamous epithelium 1 2 2 3 j0305257 Tumour-like lesion ûa nonneoplastic demarcated growing focal lesion that resembles a true neoplasm (by naked eye or microscopy) û ðprogresive changes ðcysts, pseudocysts ðchronic inflammation (inflammatory pseudotumor) ðembryonal development changes (hamartoma, choristoma) û û j0305257 Tumour-like lesion Progressive changes ûSometimes a preneoplastic change ûhyperplasia, hypertrophy, hyperregeneration ðe.g. nodular hyperplasia •nodular goiter, •benign prostatic hyperplasia, etc. • ðpseudoepiteliomatous hyperplasia epithelial hyperplasia associated with chronic irritation and inflammatory response •e.g. squamous epithelium in the border of varicose ulcer j0305257 Tumour-like lesion Cysts, pseudocysts û ûcyst – pathological cavity lined by epithelium, usually fluid-filled û ûpseudocysts lack epithelial / endothelial / mesothelial lining cells ðe.g. pancreatic pseudocyst, postmalatic pseudocyst ð j0305257 Tumour-like lesion Cysts, pseudocysts û ûcommon types of cysts: ðcongenital – due to embryonal deffect •branchial, thyroglossal, familial polycystic disease ð retention – epidermoid, pilar cysts of the skin ð implantation – as a result of surgical or accidental implantation of epidermis ð parasitic – hydatid cysts due to Echinococcus ð ð neoplastic - true tumors– e.g. cystadenoma, cystadenocarcinoma • j0305257 Tumour-like lesion Cysts, pseudocysts û ûsolitary x multiple / polycystosis û ûaccording to content (serous, mucinous, sebaceous, colloid, hemorrhagic, …) • j0305257 Tumour-like lesion Chronic inflammation ûpart of a repair process (suture granuloma) ûrelapsing/chronic purulent inflammation (pelvic inflammatory disease, actinomycosis) ûxanthoma (accentuated macrophagic reaction, yellow color) ûinflammatory polyp/hyperplasia j0305257 ûchoristoma ðmass of histologically normal tissue that is present in an abnormal location – heterotopic tissue rest ðadrenal choristoma in kidney, etc. ð ûhamartoma ðbenign malformation consisting of an disorganized abnormal mixture of mature indigenous cells and tissues ðchondrohamartoma of lung (possibly a true tumor) , etc. û Tumour-like lesion Embryonal maldevelopment j0305257 chondrohamartom - přehled_upravený.jpg chondrohamartoma of lung 1.cartilage 2.adipose tissue 3.tubular structures lined by respiratory epithelium 1 2 3 j0305257 chondrohamartom - detail_upravený.jpg chondrohamartoma of lung 1 2 3 4 1.cartilage 2.adipose tissue 3.tubular structures lined by respiratory epithelium 4.fibrous tissue j0305257 General oncology j0305257 General oncology ûtumour ðlesion with persistent autonomous abnormal growth / unregulated cell division ð ûtumour structure: ðparenchyma (neoplastic cells) ðstroma (connective tissue - support and nutrition) – inadequate stroma → possible regressive changes û ð ð ð j0305257 General oncology ûepithelial dysplasia = premalignant condition ðmicro: •loss of normal maturation/differentiation •cellular atypia –cellular pleomorphism, ↑ N/C ratio, hyperchromatism •changes in the structural arrangement of cells in the epithelium • ðclassification: •Low-grade (mild) x high-grade (moderate/severe) dysplasia • ðmay be caused by chronic inflammation, irritation (physical or chemical injury), carcinogenic agents (HPV) ðmay be reversible in early stages (low-grade dysplasia), high-grade dysplasia has a higher risk of progression to carcinoma in situ or invasive carcinoma ð ð j0305257 Cervical dysplasia High-grade CIN (CIN II) j0305257 10 Cervical dysplasia High-grade CIN (CIN II) 1 mucosal stroma 2 basement membrane 3 koilocytes 4 dysplasia in 2/3 of the epithelium 1 2 3 4 j0305257 General oncology ûanaplasia ðloss of cell differentiation ðmorphology of anaplastic tumors may mimic immature/embryonal tissue ð ûcarcinoma in situ ðlocalized epithelial neoplasm with all the cellular features of malignancy, but without invasion through epithelial basement membrane ðoften together with dysplasia in the group (concept) of intraepithelial neoplasia (named after localisation – CIN, PIN, VIN, PanIN, etc.) ð û j0305257 General oncology ð ûinvasive carcinoma ðthe final step in the process of carcinogenesis ðinvasion of tumor cells through the basement membrane ðmetastatic potential ð ûdesmoplasia / desmoplastic stromal reaction ðproliferation of connective tissue, stromal response to neoplastic process. j0305257 General oncology Carcinogenesis ûMultifactorial, complex ð external factors •ionising, non-ionising radiation •carcinogens (tobacco smoke, aflatoxins, nitrosamines) •oncogennic viruses (HPV, EBV, HTLV-1, HSV-8), bacteria (Helicobacter) ð ðendogennous factors - hereditary •approx. 15% of malignancies due to genetic factors •inherited tumor risk – breast/ovary carcinoma by mutation BRCA1 či BRCA2; familial polyposis coli, neurofibromatosis, retinoblastoma, Li-Fraumeni syndrome j0305257 General oncology signs of malignancy ûCYTOLOGIC CHANGES (ATYPIA) : ðcytologic and/or nuclear pleomorphism, anisokaryosis, anisocytosis ðnuclear enlargement ðincreased nucleocytoplasmatic index (N/C) ðnuclear hyperchromasia ðirregular chromatin texture ðirregular shape of the nuclear membrane (grooves) ðincreased mitotic activity ðatypical mitoses (tripolar, multi-center, asymmetrical) ðsometimes multinucleated cells ð ð û j0305257 Atypical mitosis (tripolar) j0305257 benign malignant Histological resemblance to normal tissue Good Variable, often poor Mitotic activity Low High + atypical Grow rate Slow Relatively rapid Nuclear morphology Often normal Usually hyperchromatic Border Often circumscribed or encapsulated Often poorly defined or irregular Necrosis Rare Common Invasion No Yes (often) Metastases Never Frequent Principal characteristics of benign and malignant tumors j0305257 Nomenclature of tumours ûAll have the suffix „-oma“ û ûBenign epithelial tumor: papilloma, adenoma ûBenign connective tissue have a prefix denoting the cell of origin (fibr- , leiomyo-, hemangio -, lipo - ,…) û ûMalignant epithelial tumors are carcinomas ûMalignant connective tissue tumors are sarcomas û û j0305257 Examples of tumour nomenclature Type Benign Malignant Epithelial Squamous cell Glandular Squamous cell papilloma Adenoma Squamous cell carcinoma Adenocarcinoma Mesenchymal Smooth muscle Addipose tissue Blood vessels Leiomyoma Lipoma Angioma Leiomyosarcoma Liposarcoma Angiosarcoma j0305257 TUMOUR DIAGNOSIS 1.MICROSCOPIC ð+ event. IHC, electron microscopy, molecular biology, genetics ð 2.TUMOUR TYPE (histogenetic) •epithelial, •mesenchymal •neuroectodermal •germinal •mixed •(choriocarcinoma) •(mesothelial) • j0305257 3.GRADING ðhistologic grade of malignancy » possible biologic behaviour ð ðG1 – G4 well differentiated - undifferentiated ð 4.STAGING ðstage according TNM classification ð ðT N M ð TUMOUR DIAGNOSIS metastasis node tumor diagnostic algorithm clinical signs clinical examination yes no diagnostic imaging techniques (x-ray, CT, MRI,…USG,…) suspected cancer yes no exploratory biopsy malignant tumor benign tumor, pseudotumor typing, grading, staging Cancer staging → therapy cancer suspicion j0305257 Tumor code û WHO International Classification of Diseases for Oncology (ICD-O): ðnumerical classification and coding system by topography and morphology ð ûTNM Classification of Malignant Tumors (UICC), AJCC Cancer Staging Manual: ð coding system of tumor stage ð ûWHO Classification of Tumours, Pathology and Genetics: ð histologic classification by organ system j0305257 Tumor code û Topography (localization) C00.0 – C80.9 (lip – unknown primary localization) û Subdivision: C34 lung û C34.0 main bronchus û C34.1 upper lobe û … j0305257 Tumor code û Morphology (histology): digital û 4 digits – basic histogenetic structure û 8070 – tumor of squamous cell û 8140 – tumor of glandular cell û j0305257 Tumor code ûMorphology (histology): digital û5. digit – biologic behaviour û /0 benign (incl. low grade dysplasia) û /1 uncertain, intermediate biologic behaviour, low malignant potential û /2 high grade dysplasia, carcinoma/melanoma in situ û /3 malignant, primary localization û /6 malignant, metastasis û /9 malignant, unknown if primary or metastatic û û j0305257 Tumor code ûMorphology (histology): digital û 6. digit : grading/differentiation of malignant tumors û1 – 4 well – moderate – low – undifferentiated û8140/0 adenoma û8140/31: well differentiated adenocarcinoma in primary localization j0305257 Tumor code ûStaging ûT size or contiguous extension of the primary tumor ûN absence or presence/extent of cancer in the regional draining lymph nodes ûM absence or presence of distant spread or metastasis j0305257 Tumor code ûT0 no evidence of primary tumor ûTis tumor in situ ûT1,T2,T3,T4 increasing size/local extension ûTX primary tumor cannot be assessed û similarly N0, N1-4, NX ûM0,M1 j0305257 Tumor code ûExample: ðC16.1 ðM-8140/33 ðpT3,pN3,pM1 ð ðPoorly differentiated adenocarcinoma of stomach fundus with extension into subserosal connective tissue, metastases in 7 or more LN, with distant metastases j0305257 Treatment of tumors ûcancer treatment is striving to reduce (ideally eliminate) all tumor cells ûproblems: inoperable tumors, resistance to therapy, toxicity of therapy, late side effects of treatment û û palliative care ðsupportive care provided to patients with incurable diseases in order to improve the quality (often not the quantity) of life ð ûprevention is the most effective !!! j0305257 Treatment of tumors ûsurgery ðcancer location !!! Mostly solid tumors x leukemia ðthe goal of treatment is usually to remove the tumor with surgery ð ûchemotherapy ðare most often used for treating leukemia, lymphoma ðneoadjuvant therapy •aims to reduce the size or extent of the cancer before using radical treatment intervention) ûradiation ð ûhormone therapy ðbreat carcinoma, prostatic carcinoma,… ðthe histological examination determined the presence of hormone receptors on tumor cells j0305257 Treatment of tumors ûbiological therapy ðtype of treatment that works with your immune system •X chemotherapy attacks the cancer cells directly ð cytokines (IFNα, IFNγ, IL-2), monoclonal antibodies û û gene therapy in the future ???