j0305257 General pathology practice General oncology I Tumors: epithelial mesenchymal neuroectodermal germ-cell tumors j0305257 1. Epithelial tumors ûoriginate in superficial (covering) or glandular epithelium û ûtumor cells maintain epithelial features: ðcohesivity (they adhere to each other) ð ðsurface covering (tigmotaxis) ð ðimmunohistochemical positivity of epithelial markers û û j0305257 Epithelial tumors ûCLASSIFICATION BENIGN MALIGNANT SUPERFICIAL EPITHELIUM TUMORS PAPILLOMAS CARCINOMAS GLANDULAR EPITHELIUM TUMORS ADENOMAS ADENOCARCINOMAS j0305257 û û û û ûBenign epithelial tumors j0305257 Benign epithelial tumors ûoriginate in squamous-cell or transitional epithelium ûmainly exophytic growth ûpapillary or wart-like appearance ûa special form - inverted papilloma (endophytic growth) û2 types according to the amount of fibrous stroma: ðsoft papilloma (lower amount of fibrous stroma) •e.g. squamous cell papilloma of the oral cavity •transitional papilloma of the urinary bladder (rare) ð ðfibroepithelial papilloma (more fibrous stroma) •e.g. verruca vulgaris (skin wart) û û û û j0305257 Verruca vulgaris (common wart) ûetiology: HPV infection ûgross: ðpapules with a rough surface ûmicro: ðacanthosis ðhyperkeratosis, parakeratosis ðpapillomatosis ðkoilocytosis •viral alteration of keratinocytes: enlarged cells with cytoplasmic vacuolization, nuclear hyperchromasia and perinuclear halos û û û û û j0305257 Verruca vulgaris (wart) veruky-vulg-ruka j0305257 verruca-vulg-6708-01-he-1,25x Verruca vulgaris (wart) 1.Hyperkeratosis 2. Parakeratosis 3. Papillomatosis 1 2 3 j0305257 Verruca vulgaris (wart) verruca-vulg-6155-01-he-10x Parakeratosis j0305257 Seborrheic keratosis ûcommon epidermal tumor (benign) ûGross: ðflat or exophytic wart-like outgrowths ðsometimes with brown coloration ð ûMicro: ðproliferation of basaloid cells (small, round cells that resemble basal cells) ðkeratin pearls (horn pseudocysts) û û û j0305257 Seborrheic keratosis seboroicke-veruky-dyskeratozy-zada seboroicka-veruka-spanek j0305257 Seborrheic keratosis seboroicka-veruka-detail j0305257 Seborrheic keratosis ver-seb-8194-00-he-2,5x 1.Nests of tumor cells 2.Keratinisation 1 2 j0305257 Cervical dysplasia ûsquamous cell precancerosis associated with HR (high risk) HPV infection: ðHR HPV: •mainly 16, 18, 31, 33, 35 • ûLR (low risk) HPV (6,11) →→ koilocytic changes in the squamous cell epithelium ðcytopathic effect of HPV • û û j0305257 Cervical dysplasia ûmost used classification (now obsolete!) ûCERVICAL INTRAEPITHELIAL NEOPLASIA (CIN): ðCIN I: •changes in the basal third of the epithelium: –anisokaryosis –nuclear hyperchromasia –disorder of the cells` orientation –nuclear superposition ð ðCIN II: •changes in the lower 2/3 of the epithelium ð ðCIN III: •changes even in the superficial layer of the epithelium û û j0305257 Cervical dysplasia ûnow mostly 2 categories used: ðLG SIL (low grade squamous intraepithelial lesions) ð ðHG SIL (high grade squamous intraepithelial lesions) û j0305257 Cervical dysplasia ûdysplastic changes (particularly LG SIL) may regress with time ðdue to clearence of the virus û ûHG SIL (i.e. CIN II and CIN III) has high probability of progression into the squamous cell carcinoma û j0305257 Cervical dysplasia – mild epithelial dysplasia CIN I 09 mild cytonuclear atypia in the basal epithelial layer koilocytes j0305257 Cervical dysplasia – moderate epithelial dysplsia CIN II 11 Cytonuclear atypia in the lower 2/3 of the epithelium j0305257 Cervical dysplasia – severe epithelial dysplasia CIN III 14 Cytonuclear atypia in the superficial third of the epithelium Regular mitotic figures j0305257 û û û û ûMalignant epithelial tumors j0305257 Squamous cell carcinoma ûmalignant tumor of the squamous cell epithelium û ûsynonyms: ðspinocellular, epidermoid carcinoma, spinalioma û ûgrowth: ðexophytic ðendophytic (inwards) û ûoften necrotic +/- ulcerative disintegration ûroughly granular and dry on the cut section û û j0305257 Squamous cell carcinoma ûMicro: ðnests of tumor cells ð ðkeratinisation: •extracellular keratinisation –cancroid pearls •monocellular keratinisation ð ðintercellular bridges j0305257 Squamous cell carcinoma ûprognosis depends on the location: ðvery good prognosis in the skin (curative surgical excision) ð ðgenerally unfavorable prognosis in the internal organs (depends also on the stage of the disease) j0305257 Squamous cell carcinoma ca-spino-ucho j0305257 Squamous cell carcinoma well differentiated, keratinised spinaliom02 1.Solid nests of tumorous keratinocytes 2.Cancroid pearls 3.Stroma of the tumor 1 1 1 2 2 3 j0305257 Squamous cell carcinoma well differentiated, keratinised 02444-1 1.Nests of tumor cells 2.Monocellular keratinisation 1 1 2 j0305257 Squamous cell carcinoma well differentiated, keratinised spinaliom04 1.Intercellular bridges – tonofilaments 2.Nucleus with distinct nucleolus 1 2 j0305257 Basal cell carcinoma ûvery frequent skin tumor in higher age û ûtypically in areas with chronic sun exposure û ûrare metastases! û û j0305257 Basal cell carcinoma ûGross: ðpearly papules ðlater ulceration ðunhealing, progressive tendency û ûMicro: ðsmall basaloid cells in nodules or small nests ðperipheral palisading ðcommonly high mitotic activity û j0305257 Basal cell carcinoma basaliom-terebrans-spanek j0305257 Basal cell carcinoma ca-baso-ulc-detail j0305257 Basal cell carcinoma basal-solid-cyst-pigm-5211-99-he-1,25x 1.Nests of basophilic tumorous epithelium 2.Melanin pigmentation 1 2 j0305257 Basal cell carcinoma basal-solid-cyst-pigm-5211-99-he-10x 1.Nests of tumor cells 2.Peripheral palisading 3.Melanin pigmentation 1 2 3 j0305257 Basal cell carcinoma basal-pigm-1988-01-he-10x 1.Nests of tumor cells 2.Peripheral palisading 3.Melanin pigmentation 1 1 2 3 j0305257 Urothelial (transitional) cell tumors of the urinary bladder ûWHO classification: ðpapilloma ð ðpapillary urothelial neoplasms of low malignant potential (PUNLMP) ð ðpapillary urothelial carcinoma •low grade •high grade •Invasive •noninvasive j0305257 Papillary urothelial neoplasms of low malignant potential (PUNLMP) ûMicro: ðnormal width or slightly more layers of the transitional epithelium ð ðslightly enlarged nuclei ð ðlow mitotic activity ð ðtypically delicate papillary formations with hyperplastic urothelium and preserved stratification û û j0305257 Papillary urothelial neoplasms of low malignant potential (PUNLMP) papilom02 Delicate fibrovascular stroma Increased number of urothelial layers j0305257 Papillary urothelial neoplasms of low malignant potential (PUNLMP) papilom03 Delicate fibrovascular stroma Hyperplastic urothelium with minimal cytonuclear atypia j0305257 Papillary urothelial carcinoma, low grade ûMicro: ðarchitecture: •disordered papillary architecture with fused papillae • ðincreased number of cell layers ð ðcytological features: •low grade anisokaryosis •enlarged nuclei –rarely noticeable nucleoli ðlow mitotic activity ðpossible stromal invasion • ð û j0305257 Papillary urothelial carcinoma j0305257 Papillary urothelial carcinoma, low grade TCC 20x 1.Fused tumorous papillae 2.Delicate fibrovascular stroma 3.Subepithelial fibrous tissue 1 2 3 1 j0305257 Papillary urothelial carcinoma, low grade TCC 100x 1.Fused tumorous papillas 2.Delicate fibrovascular stroma 1 2 j0305257 Papillary urothelial carcinoma, high grade ûMicro: ðarchitecture: •focal residual papillary architecture •solid areas common • ðloss of urothelial stratification ð ðcytological features: •high degree of anisocytosis and anisokaryosis •frequent mitoses, including atypical ð û û û j0305257 Papillary urothelial carcinoma, high grade HG UCa 1.Solid areas with residual papillary architecture 2.Fibrovascular stroma 1 1 2 j0305257 Papillary urothelial carcinoma, high grade HG UCa 100x 1.Solid areas with residual papillary architecture 2.Fibrovascular stroma 1 2 j0305257 Papillary urothelial carcinoma, high grade tripolar_mit_HE_600x 1.Tripolar mitosis 2.Cytonuclear atypia 1 2 j0305257 û û û û ûGlandular epithelium tumors j0305257 Glandular epithelium tumors û imitate various glandular structures û û certain types with mucus production ð proof by histochemical staining methods: • PAS (neutral mucopolysaccharides) • ALCIAN (acid mucopolysaccharides) û û classification: ð adenoma • benign tumors – tubular or villous adenoma, cystic adenoma (cystadenoma), folicular adenoma, solid adenoma, … ð adenocarcinoma • malignant tumors – tubular, acinar, trabecular adenocarcinoma, cystic adenocarcinoma (cystadenocarcinoma), mixed adenocarcinoma, undifferentiated carcinoma ð ð ð j0305257 û û û ûBenign glandular epithelium tumors j0305257 Follicular adenoma û Mostly solitary û û Encapsulated û û pressure atrophy of adjacent parenchyma û û diff. dg. x follicular carcinoma ð similar histologic structure, transcapsular invasion into surrounding thyroid tissue and/or angioinvasion necessary for ca diagnosis ð ð û Diagnosis possible only with complete biopsy j0305257 Follicular thyroid adenoma FolikAd-20HE 1thyroid parenchyma with follicles 2structure of adenoma 3 Fibrotic capsule (adenoma demarcation) 1 2 3 j0305257 Follicular thyroid adenoma FolikAd-100HE Æ microfollicular adenoma j0305257 Polyps ûgross descriptive term ûpedunculated or sessile ûclassification: ðnon-neoplastic ðneoplastic ûthey can be: ðsolitary ðmultiple ðnumerous (> 100 = polyposis) û j0305257 Non-neoplastic polyps of the GIT (see PSP3) ûwithout malignant potential û3 basic types: ðhyperplastic polyps ðjuvenile polyps •mostly in children •also juvenile polyposis syndrome ðPeutz-Jeghers polyps •uncommon hamartomatous polyps •or Peutz-Jeghers syndrome (AD) –multiple polyps in the GIT j0305257 Neoplastic polyps – adenomas (GIT) ûadenomas arise as the result of epithelial proliferation and dysplasia û ûadenocarcinomas mostly arise in preexisting adenomatous lesions û û j0305257 Neoplastic polyps - adenomas ûMicro: ð epithelial dysplasia ð ðtall cells with darker cytoplasm (lack of mucus) ð ðdarker, elongated nuclei, hyperchromasia, distinct nucleoli ð ðmitoses û j0305257 Neoplastic polyps - adenomas ûsubtypes of GIT adenomas according to the epithelial architecture: ðtubular •mostly pedunculated, > 75% tubular glandular architecture ð ðvillous •often sessile, finger-like projections, > 50% villous structure ð ðtubulovillous •25 – 50% villous component û j0305257 Neoplastic polyps - adenomas ûrisk of malignant transformation depends on: ð polyp size ð ðhistologic type ð ðseverity of epithelial dysplasia •worse in large villous polyps û j0305257 Neoplastic polyps - adenomas _colon-polyps-1-387n j0305257 Tubular adenoma of the colon _s5-12-tub-adenom-2x-he 1.Colonic mucosa 2.Pedunculated tubular adenoma 3.Stalk 4.Lamina muscularis mucosae 5. 1 2 3 4 j0305257 Tubular adenoma of the colon _s5-12-tub-adenom-20x-he 1.Low and high grade dysplastic changes 2.Goblet cells 3.Mucosal stroma with inflammatory infiltrate 1 2 3 j0305257 û û û ûMalignant glandular epithelium tumors j0305257 Adenocarcinomas ûGeneral adenocarcinoma structure/consistency: ðmedullary •more tumor cells, less stroma ð ðscirrhous •more desmoplastic stroma ð ðsimple •balanced ratio of stroma and tumor cells ð • ð j0305257 Adenocarcinomas ûExamples of adenocarcinoma structure in the GIT: ðintestinal (tubular) ð ðdiffuse (scirrhous) ð ðgelatinous (mucinous) û j0305257 Adenocarcinoma - intestinal type ûtubular/glandular structure û ûinvasive growth (+/- destruction) into the wall û ûincreased mitotic activity û ûtumor glands of irregular in shape and size û ûvariable mucus production ðextracellular ðintracellular û j0305257 Adenocarcinoma, moderately differentiated, tubular _s4-5-carc-10x-he Invasive, moderately differentiated tubular adenocarcinoma Peripheral non-neoplastic epithelium j0305257 Adenocarcinoma infiltrating the muscularis propria _s4-5-carc-infi-10x-he 1.Adenocarcinoma 2.Muscularis propria infiltrated by adenocarcinoma 1 2 j0305257 Tubular adenocarcinoma in detail adenoca03 1.Mitotic figures 2.Atypia of the tumorous epithelium 1 2 j0305257 Diffuse adenocarcinoma ûdiscohesive tumor cells in small groups or isolated û ûsignet-ring cells û ûincreased amount of interstitial fibrous tissue û ûdesmoplastic stromal reaction û ûscirrhous adenocarcinoma with prevalent stroma ðtough consistence û j0305257 Diffuse adenocarcinoma _s4-6-zaludek-dif-ca-40x-he _s4-6-ca-diff-zaludek-40x-pas j0305257 Gelatinous adenocarcinoma ûjelly-like consistence û ûextensive extracellular production of epithelial mucus, mucin lake formation û ûintracellular mucus production with signet ring cells: ðlarge cytoplasmic mucin vacuole displaces nucleus to the periphery of the cell û ûpossible disperse tumor cells in mucin lakes û û û j0305257 Signet-ring cells infiltrating the muscularis propria adenoca prsténčité bb 40x 1.Muscularis propria 2. Signet-ring cells infiltrating the muscularis propria 2 1 j0305257 Signet-ring cells in detail adenoca prsténčité bb 200x j0305257 Signet-ring cells in detail adenoca prsténčité bb 200x 01 j0305257 Hepatocellular carcinoma û 5th worldwide the most common malignancy in males, 8th in females û Makro: ð multinodular form: • multiple circular bearings in both lobes ð massive form: • large bulky node with small satellite deposits • ð difusse form: • multiple small deposits pervading almost the entire liver j0305257 Hepatocellular carcinoma û Micro: ð architecture: • trabecular • acinar +/- pseudoglandular • solid • ð cytology tumors cells: • enlarged nuclei + nucleoli • ↑ mitotic activity, atypias • eosinophilic – pale cytoplasm • ð Possible steatosis, bile production ð j0305257 Hepatocellular carcinoma – massive form jatra1 j0305257 Hepatocellular carcinoma – difusse form 60mr j0305257 Hepatocellular carcinoma – trabecular arrangement HCC 100x j0305257 Hepatocellular carcinoma – trabecular arrangement HCC 200x j0305257 Clear cell carcinoma ûcommon form of renal cell carcinoma ðderived from the epithelium of proximal tubules û ûeponym: Grawitz tumor û ûGross: ð variable form, commonly well-demarcated ð variegated on cut section: •yellow (lipids) •red (hemorrhage) •grey (fibrous tissue) û û û ð ð û j0305257 Clear cell carcinoma ûMicro: ðvariable architecture: •compact-alveolar, trabecular, tubular, cystopapillary ð ðpolygonal cells with clear (watery) cytoplasm •glycogen and lipid deposits, dissolved during processing ð ðround nuclei •Fuhrman nuclear grading (I-IV) • ðdistinctive cell membrane (plant-like) ð ðlow amount of fibrovascular stroma û j0305257 Clear cell carcinoma grawitz 1.Tumor 2.Residual renal parenchyma 3.Tumor invading the renal vein 1 2 3 j0305257 Clear cell carcinoma caledvinyY j0305257 Clear cell carcinoma Tumor cells Vessels RCC 100x j0305257 Clear cell carcinoma 200x Tumor cells Capillaries j0305257 Mammary carcinoma, NOS û most common û û former name – invasive ductal carcinoma û û gross: ðfirm lesion, irregular border ð û micro: ðcohesive (E-cadherin+) tumor cells • tubules, trabeculae, solid clusters • variable grade of nuclear pleomorphism, mitotic activity (gr. I-III) ðloss of outer myoepithelial cell layer (p63-, SMA-) ðdense fibrotic stroma, desmoplasia ðinfiltrative growth, commonly adjacent DCIS û j0305257 Mammary carcinoma, NOS 1 cohesive tumors infiltrate with sporadic tubules ojedinělými tubuly 2 infiltration of adipose tissue 1 2 j0305257 Mammary carcinoma,NOS Tumorous infiltrate with irregular small tubules j0305257 Neuroendocrine neoplasms û epithelial tumors with neuroendocrine differentiation û represent a heterogeneous group of tumors û characterized by the production of biogenic amines or hormones and mediators of hormonal effect ð e.g.serotonin, neuropeptide,… û approximately 1/4 with endocrine function ð carcinoid syndrome û secretory granules in the cytoplasm of tumor cells: ð detection mostly by immunohistochemistry! •serotonin, chromogranin, S100, NSE, CD56 ð silver impregnation method (Grimelius) û û j0305257 Neuroendocrinne neoplasms û new classification according ENETS (European Neuroendocrine Tumor Society) 2011 û û differentiation by mitotic and proliferative activity : ð neuroendocrine tumors (carcinoid) G1 • proliferation index Ki67 ≤ 2 % • mitotic index ≤ 2 mitoses per 10 high resolution visual fields • ð neuroendocrine tumors G2 • proliferation index Ki67 to 3 - 20 % • mitotic index 2 – 20 mitoses per 10 high resolution visual fields • ð neuroendocrine carcinomas G3 (small cell or large cell type) • proliferation index Ki67 >20 % • mitotic index > 20 mitoses per 10 visual fields high resolution • • j0305257 Carcinoid of the appendix û by WHO classification 2010: ð neuroendocrine tumor G1 (NET G1) ð û by WHO classification 2000: ð well differentiated neuroendocrine tumor ð û Gross: ðsmall, round-shaped, flat nodules of yellowish colour, infiltrating the wall to different depth, ðsuperficially ulcerated or covered with normal mucosa, ðsometimes exophytic û ð û Micro: ðtrabecular, glandular structures - tubules, palisading or compound structure ðregular cells with clear cytoplasm and round or oval-shaped nucleus; slight nuclear polymorphism ðlow mitotic activity ðchromogranin A in cytoplasm ð j0305257 Carcinoid of the appendix karcinoid appendixu 40x 1 Tumor cells 2 Appendiceal mucosa 1 2 j0305257 Carcinoid of the appendix karcinoid appendixu 100x 1 Tumor cells 2 Appendiceal mucosa 3 Stroma of the tumor 1 2 3 j0305257 Small-cell carcinoma ûundifferentiated neuroendocrine carcinoma ûthe most malignant variety of lung carcinoma û ûMicro: ðsmall blue cells with hardly noticeable, scant cytoplasm ð ðsmall, elongated, hyperchromatic nuclei without distinctive nucleoli ð (oat-cell carcinoma) ð ðsolid architecture ð ð neuroendocrine secretory cytoplasmic granules •chromogranin, synaptophysin û û j0305257 Small-cell lung carcinoma malobb ca 100x 1. Solid infiltration with small tumor cells 2. Necrosis 3. Fibrous stroma 1 1 2 3 j0305257 Small-cell lung carcinoma malobb ca 200x 1. Tumor cells 2. Fibrous sroma 1 2 j0305257 û û û û2. Mesenchymal tumors j0305257 2. Mesenchymal tumors û almost any localisation possible û û highly heterogenous group of tumors û û most of tumors arise de novo û û risk factors variable, among others: ðchemical carcinogens (eg herbicides containing dioxin) ð scars ð implants containing PVC ð irradiation ð viruses (HHV8 and Kaposi sarcoma) ð inheritance (hereditary multiple lipomas) û û • j0305257 2.Mesenchymal tumors û biological behavior: ðbenign tumors •fibroma, lipoma, hibernoma, myxoma, hemangioma, lymfangioma, leiomyoma, rhabdomyoma, chondroma, osteoma,… ð ð intermediate tumors •locally aggressive, rarely metastasize •fibromatosis • ð malignant tumors (sarcomas) •higher metastatic potential • û benign tumors more common (mal:ben ~ 1:100) ð ð • û ð • û j0305257 Mesenchymal tumors û û classifed according to the default parent tissue û basic histological feature without typical epithelial formations, absence of mutual cell cohesiveness û intercellular substance generally surrounds the individual tumor cells j0305257 Mesenchymal tumors ûimmunohistochemical positivity of vimentin ûco-expression of other tissue-specific markers: û ðS-100 (lipid tissue) ð ðalpha-actin and/or desmin (muscle tissue) ð ðfactor VIII and CD31 (endothelium) û j0305257 Fibroma ûalmost any localisation possible ðskin ðmucous membranes ðovary ð ûalways benign û ûcommonly reactive non-neoplastic lesion û j0305257 Fibroma ûGross: ðwell circumscribed, spherical ðgrey to pink on cut section ðfascicular (bundled) structures ðtough consistency ð ûMicro: ðaccumulation of fibrous tissue ðneoplastic fibroblasts •pointed nucleus, inconspicious cytoplasm ðproduction of collagenous intercellular matrix ðlow cellularity û j0305257 Fibroma fibrom, 100x Collagenous fibrous tissue with only few cells j0305257 Fibroma fibrom, 200x 1.Fibroblasts 2.Collagene fibers 1 2 j0305257 Undifferentiated pleomorphic sarcoma û former name malignant fibrous histiocytoma MFH û û high-grade sarcoma û û 30% of all soft tissue sarcomas û û often in the thigh region (deep soft tissues) û û mostly in older males û û diagnosis per exclusionem after elimination of any other poorly differentiated mesenchymal or neuroectodermal tumor û û û j0305257 Undifferentiated sarcoma û gross: ðwhitish tumor, „ fish-flesh“ appearance on cut section ð û micro: ð excessive pleomorphism of tumor cells and cellular architectonics ðbizarre multinucleate cells ð frequent mitotic activity, necrosis ðvariants: • spindle cell • small round cell • epithelioid • pleomorphic • NOS û ð ð j0305257 Undifferentiated sarcoma NEO078 Pleomorphic nuclei of neoplastic cells j0305257 Undifferentiated sarcoma maligní fibrózní histiocytom Pleomorphic nuclei of neoplastic cells Mitosis j0305257 Giant-cell tumor of bone ûunknown histogenesis of tumor cells û ûformer name osteoclastoma (osteoclast-type multinuclear giant cells) û ûGross: ðred-brown large tumor in the epiphysis of long bones, destructive ð ûMicro: 2 population of cells: ðsmaller oval mononuclear cells ðgiant multinuclear cells (up to 100 nuclei) j0305257 Giant-cell tumor of bone OBN2, 200xsuper.jpg 1.Multinuclear (osteoclast-like) tumor cells 2.Oval tumor cells 1 1 2 2 j0305257 Giant-cell tumor of bone OBN2, 400xsuper.jpg 1.Multinuclear (osteoclast-like) tumor cells 2.Oval tumor cells 1 2 j0305257 Chondrohamartoma of the lung ûHAMARTOMA = pseudoneoplastic lesion: ðcomposed of mature tissue elements normally found at that site, but non-functional and growing in a disorganized mass ûcomposed of cartilage, adipose and fibrous tissue, smooth muscle, respiratory epithelium û ûcartilage usually prevails û j0305257 Chondrohamartoma of the lung chondrohamartom 20x 01 1.Cartilage 2.Adipose tissue 3.Tubular structures with respiratory epithelium 1 2 3 j0305257 Chondrohamartoma of the lung chondrohamartom 100x 03 1. Cartilage 2. Adipose tissue 3. Fibrous tissue 4. Tubular structures 1 2 3 4 j0305257 Leiomyoma ûbenign smooth muscle tumor, most common mesenchymal tumor û ûGross: ðwell-circumscribed spheric nodule ðoften with regressive changes, fibrosis, calcification ð ûMicro: ðinterlacing or whorling bundles of spindle cells with inconspicious eosinophilic cytoplasm ðcigar-shaped nuclei ðno coagulative necrosis, low grade of reactive cytonuclear atypia possible û û ð j0305257 Uterus myomatosus 1.Portio vaginalis of the cervix 2.Endocervix 3.Body of the uterus 4.Submucosal leiomyoma 5.Intramural leiomyoma 6.Subserous leiomyoma leiomyom5 Copy j0305257 Leiomyoma leiomyom Bundles of spindle cells j0305257 Leiomyoma leiomyom3 Bundles of spindle cells j0305257 Gastrointestinal stromal tumors (GISTs) û û cells of the origin: ðPacemakers GIT (Cajal cells) controlling peristalsis ð û immunohistochemistry: ð CD 34 and CD 117 (c-kit) positivity û origin anywhere in the GIT: predominantly in the stomach and small intestine û ûextragastrointestinal stromal tumors (EGIST) existing ð e.g. in the pancreas, retroperitoneum, mesenterium of the small intestine, spleen, or pelvis ðextremely rare ð ð j0305257 Gastrointestinal stromal tumors û Gross: ð nodule in the wall, protruding into the lumen ð mucosa over the tumor intact or ulcerated ð û Micro: ð elongated and/or epithelioid cells ð û prediction of biological behavior: ðmitotic count ð size ð localization ð û j0305257 Gastrointestinal stromal tumors – low malignant GIST 100x j0305257 Gastrointestinal stromal tumors – highly malignant GIST maligní 100x 01 j0305257 Gastrointestinal stromal tumors – highly malignant GIST maligní 400x j0305257 Hemangioma ûbenign tumor of blood vessels û ûseveral subtypes according to vessels` calibre and architecture û û3 basic types: ðcapillary hemangioma ðcavernous hemangioma ðarteriovenous hemangioma û û j0305257 Capillary hemangioma ûoften in the skin, subcutaneous tissues and mucosa û ûGross: ðbright red to blue patches or nodules ð ð ûMicro: ðaggregates of thin-walled capillaries ðusually filled with blood, possible empty , compressed, thrombosed lumina ðusually supplied with only 1 artery » regressive changes: •oedema •hemorrhage •fibrosis •hemosiderin deposition after hemorrhage û û ð û j0305257 Capillary hemangioma of the skin Capillaries Erytrocytes Endothelium j0305257 Capillary hemangioma of the skin kaphemang400 Endothelium Erytrocytes Capillaries j0305257 Cavernous hemangioma ûGross: ðred to blue nodule ðcan be of large size ðmostly in the liver, less often in the spleen and skin ûMicro: ðlarge, dilated vascular spaces, filled with blood, separated by fibrous septa (similar to corpora cavernosa) ð ûrisk of rupture with intraperitoneal hemorrhage ð û û û j0305257 Cavernous hemangioma of the liver Blood-filled spaces with endothelial lining Fibrous septa kavernózní ham Kopie j0305257 Osteosarcoma ûyoung adults under the age of 25 (primary) û ûmostly arises in the metaphyseal region of the long bones û û70% occuring in the region of knee (distal femur and proximal tibia) û ûMicro: ðproduces tumorous bone matrix (osteoid) – essential for diagnosis ð pleomorphic sm. spindle cells, high mitotic activity ðsubtypes: •fibroblastic, osteoblastic, chondroblastic û j0305257 Osteosarcoma OSA1, 100x.jpg 1Osteoid 2Tumorous osteoblasts 3Bone trabeculae 1 2 3 j0305257 Osteosarcoma OSA3, 200x.jpg 1Osteoid 2Tumorous osteoblasts 3Bone trabeculae 3 1 2 j0305257 Osteosarcoma P0073.jpg Tumorous osteoblasts j0305257 û û û û3. Neuroectodermal tumors j0305257 Neuroectodermal tumors ûtumors of the central nervous system û ûperipheral neuroectodermal tumors û ûtumors of the autonomous nervous system û ûmelanocytic tumors j0305257 Selected tumors of the CNS ûAstrocytic tumors: ðpilocytic astrocytoma (Grade I of WHO class.): •two components: –solid areas with bipolar tumorous astrocytes – cells with long, thin, hair-like processes, eosinophilic Rosenthal fibers –microcystic areas, less cellular, with multipolar tumor cells with eosinophilic granular bodies •calcification and small foci of necrosis may occur •low mitotic activity, nuclear pleomorphism and hyperchromasia mostly absent •glomerulus-like vascular proliferation • û j0305257 Pilocytic astrocytoma Hermanova_OBR4B (1) Bipolar cells with eosinophylic granular bodies and Rosenthal fibers j0305257 Pilocytic astrocytoma Hermanova_OBR4A Microcystic area with multipolar tumor cells j0305257 Selected tumors of the CNS ûAstrocytic tumors: ðglioblastoma (WHO Grade IV): •most aggressive malignant primary brain tumor in adults • •pleomorphic cells with marked cellular and nuclear atypia, high mitotic activity • •prominent microvascular proliferation and/or necrosis • •pseudopalisading pattern of cells on the periphery of necrosis • • regional tumor heterogeneity: –atypical pleomorphic areas may alternate with regions of more regular structure • • • • • û j0305257 Glioblastoma 20 j0305257 Glioblastoma glioblastom 40x 02 Pseudopalisading cells (1) around the necrosis (2) 1 2 j0305257 Glioblastoma multiforme glioblastom 100x 01 Pseudopalisading cells (1) around the necrosis (2) 1 2 1 j0305257 Glioblastoma multiforme glioblastom 100x 03 Atypical pleomorphic tumor cells j0305257 Selected tumors of the CNS ûEmbryonal tumors: ðmedulloblastoma e.g.: •predominantly occurs in children, in the cerebellum • •extremely cellular: small, round or spindle tumor cells • •hyperchromatic nuclei with high mitotic activity • •characteristic neuroblastic Homer-Wright rosettes: –groups of tumor cells arranged in a circle around a mesh of cytoplasmic processes • • û j0305257 Medulloblastoma mbl, 200x.jpg j0305257 Medulloblastoma C:\Documents and Settings\jirka\Plocha\dejavu - mbl, paragangliom\MBL\Brož\BrožHE.jpg j0305257 Tumors of meninges ûMeningioma (WHO Grade I): ðGross: •different size, well-circumscribed, often spheric •attached to the dura •compresses underlying brain tissue • ðMicro: •spindle cells arranged in whorls, bands, nodules •frequent psammoma bodies: –basophilic, concentric, lamellated calcified structures ð j0305257 Meningioma 27 1.Nodule of meningioma 2.Flat meningiomas 3.Dura mater 4.Falx cerebri 1 2 3 4 j0305257 Meningioma meningiom 40x 01 1.Meningiocytes arranged in whorling formations 2.Psammoma bodies 3.Vessels 1 2 3 j0305257 Meningioma meningiom 100x 01 1.Whorling formations of meningiocytes 2.Psammoma bodies 1 2 j0305257 Meningioma meningiom 200x 01 Whorling formations of meningiocytes j0305257 Selected peripheral neuroectodermal tumors ûschwannoma (neurinoma, neurilemmoma) ðbenign nerve sheath tumor ðarise from Schwann cells in peripheral nerves or intracranially ð ðMicro: •cellular areas with nuclear palisading and nuclear-free zones (Antoni A pattern) • •less cellular areas, often oedematous, with loose cell arrangement (Antoni B pattern) û û û û j0305257 Schwannoma j0305257 Schwannoma 1.Antoni A 2.Antoni B 3.Palisading 1 neurinom 100x 01 2 1 3 j0305257 Schwannoma neurinom 40x 03 1.Antoni A 2.Antoni B 3.Palisading 1 2 3 j0305257 Schwannoma neurinom 100x 02 1.Antoni A 2.Palisading 1 2 j0305257 Selected peripheral neuoectodermal tumors ûneurofibroma: ðnerve sheath tumor ð2 forms: •cutaneous neurofibroma – in the dermis and subcutaneous fat, demarcated •plexiform neurofibroma – anywhere along/expanding a nerve, potential for malignant transformation • ðMicro: •spindle cells with S-shaped nuclei ð •highly collagenized stroma in cutaneous n. •myxoid background in plexiform n. ð û j0305257 Neurofibroma Spindle-like cells in the collagenized stroma neurofibrom1 j0305257 Neurofibroma Wavy looking S-shaped nuclei neurofibrom2 j0305257 Melanocytic lesions ûBenign: ðfreckles (ephelides) ðbenign solar lentigo ðmelanocytic nevi ðSpitz nevus ðdysplastic nevus ûMalignant melanoma: ðnodular ðsuperficial spreading ðlentigo maligna ðacral lentiginous melanoma û j0305257 Melanocytic nevus ûbenign tumor, most types with rare malignant transformation û ûGross: ðtan to brown, small, solid foci in the skin ð ðflat or elevated, with well-defined borders ð ðcongenital commonly larger in size û j0305257 Melanocytic nevus ûMicro: ðjunctional nevus •nests of melanocytes in the border between epidermis and dermis (junction zone) • ðcompound nevus •groups of melanocytes both in the junction zone and underlying dermis, arranged in nests or cords • ðintradermal nevus •the most mature stage of melanocytic nevus •no epidermal nests, groups of melanocytes in dermis only j0305257 Melanocytic nevus nevi-pigmentosi-detail j0305257 Intradermal melanocytic nevus nevus-id-7463-00-he-2,5x 1.Melanocytes 2.Papillary layer of the corium separating nests of melanocytes and epidermis 1 1 2 j0305257 Intradermal melanocytic nevus nevus-id-7463-00-he-10x 1.Melanocytes 2.Papillary layer of the corium separating nests of melanocytes and epidermis 1 1 2 j0305257 Compound melanocytic nevus nevus-comp-9629-92-he-10x 1.Intradermal part of the nevus 2.Junctional part of the nevus 1 1 2 2 j0305257 Malignant melanoma ûArise: ðmalignization of nevi (dysplastic) ðde novo ûOrigin: ðskin ðmucous membranes ðmeninges ðeye ð û j0305257 Malignant melanoma ûGross: ðin early stages similar to nevus ðABC - Asymetry ðirregular Borders ðvariegated Color ðulceration and possible darkening in late stages ûMicro: ðatypical pleomorphic epitheloid or spindle-like cells ðlarge hyperchromatic nuclei with prominent nucleoli ðmitoses ðasymmetric pigment deposition •completely non-pigmented forms too ðimmunoprofile: •Melan A, S-100, HMB-45 ð ð • j0305257 Malignant melanoma – radial growth phase DSCN1896 j0305257 Malignant melanoma – radial growth phase ssm-4852-96-he-10x 1. Nests of tumor cells in the junction zone 2. Single melanocytes in the epidermis 3. Lymphocytic infiltrate 4. Invasion into the papillary dermis 1 2 3 4 j0305257 Melanoma w. nodularity DSCN1899 j0305257 Nodular melanoma mm-nodul-799-93-he-1,25x 1.Large tumor invading the subcutaneous adipose tissue 2.Melanin production 1 1 2 j0305257 MM2, 100x.jpg Local melanin production Nodular melanoma j0305257 Nodular melanoma mm-nodul-799-93-he-2,5x 1.Atypical melanocytes 2.Intraepidermal part of the tumor 3.Low inflammatory response 1 2 3 j0305257 MM3, 400x.jpg MM4, 400x.jpg Atypical melanoblasts, prominent nucleoli Nodular melanoma j0305257 û û û û4. Germ cell tumors j0305257 Germ cell tumors ûusually in the gonads (ovary, testis) û ûpossible extragonadal localisation ðanterior mediastinum, retroperitoneum, pineal gland ð ûcongenital origin ðsacrococcygeal teratoma e.g. û ð j0305257 Germ cell tumors ûclassification: ðtumors with one histologic type •seminoma •non-seminomatous tumors –choriocarcinoma –embryonal carcinoma –yolk sac tumor –teratomas »mature »immature »with malignant transformation of somatic elemenets – ðmixed germ-cell tumors (with more than one histologic type) û j0305257 Primordial germ cell Differentiation along gonadal lineages (gonocyte, spermatogonium), without further differentiation potential - Seminoma Totipotential cell Undifferentiated cell - Embryonal carcinoma Extra-embryonic differentiation - Yolk sac tumor - Choriocarcinoma Differentiation along somatic cell lines -Teratoma (mature, immature, with malignant transformation of somatic elements) - (Polyembryoma) Histogenesis of germ-cell tumors j0305257 Seminoma ûabout 50% of germ-cell neoplasms ûhistologically identical to ovarian dysgerminomas ûGross: ðlarge, soft, well-circumscribed, homogenous, gray-pink in cut, with foci of necrosis ð ðdestructive growth, often affects large areas of the testis ð ðusually intratesticular growth only ð ðlate stages invade rete testis, epididymis testis, funiculus spermaticus, scrotal sac û û j0305257 Seminoma ûMicro: ðsolid growth •exceptionally microcystic, solid-alveolar, tubular or cribriform ð ðlarge, uniform cells with distinct cell borders ð ðclear, glycogen-rich cytoplasm ð ðlarge nuclei with one or two conspicuous nucleoli ð ðstroma of thin fibrovascular septa with lymphocytic infiltrate, reactive granuloma formation ð ð ð j0305257 Classic seminoma Solid structures of the seminoma Fibrovascular septa with lymphocytic infiltrate seminom1 j0305257 Classic seminoma Tumor cells with clear cytoplasm Fibrous septa with lymphocytic infiltrate seminom2 j0305257 Nonseminomatous tumors ûgerm cell differentiated into totipotential / extraembryonal cell lineage: –embryonal carcinoma –choriocarcinoma –yolk sac tumor û ûdifferentiation along somatic cell lineage: –teratomas û j0305257 Teratomas ûdifferentiation of neoplastic germ cell along somatic cell lines ûcontains tissues of one / two / three primitive germ cell layers (endo-, meso-, ectoderm) ûGross: ðcystic (usually benign) ðsolid ûMicro: ðdifferent tissue types: •brain, teeth, epithelial structures, neural tissue, endocrine organs, muscles, cartilage, bone… •often epidermoid or dermoid cysts with hairs û j0305257 Teratomas û3 histologic variants according to the maturity of particular structures: ðmature (organoid) ð ðimmature (embryonal/fetal tissues) ð ðwith malignant transformation of somatic elements » j0305257 Dermoid cyst (mature teratoma) 14 1.Lumen of the cyst with keratinized epithelial cells 2.Epidermis 3.Sebaceous glands 4.Hair follicles 5.Adipose tissue 1 3 2 4 5 j0305257 Dermoid cyst (mature teratoma) 16-2 1.Lamellar bone 2.Cartilage 3.Hematopoietic bone marrow 4.Striped muscle 5.Neural tissue 1 2 3 4 5 j0305257 Immature teratoma WHO-OvarianTumours_097 1.Immature neuroectodermal-like epithelium 2.Glial cells 3.Yolk-sac-like structures 1 2 3 j0305257 û û û û5. Mixed tumors j0305257 Mixed tumors û consist of two or more tissue components of identical or different histogenesis and identical or different biological nature: ð mixed mesenchymal tumors • angiofibroma, angioleiomyolipoma, … ð ð mixed mesenchymal/epithelial tumors •fibroadenoma, adenosarcoma, carcinosarcoma ð ð mixed malignant epithelial tumors • e.g. adenosquamous carcinoma • ð mixed germinal tumors • e.g. combination of seminoma and teratoma in one tumor j0305257 Fibroadenom mammy û most common breast tumor in young females û û benign û û gross: ð circumscribed, mobile ð û micro: ð proliferating ducts ð ð increased amount of stroma (edematous or hyalinised) ð ð 2 types: • pericanalicular, intracanalicular growth (no practical significance) j0305257 Fibroadenoma Slit-like newly formed ducts compressed by edematous stroma