j0305257 Systematic pathology Genital system pathology Breast pathology j0305257 Male genital tract pathology j0305257 ûProstate ûPenis, scrotum ûTestis, epididymis û ðcongenital defects ðcirculatory disorders ðinflammations ðtumors û j0305257 Prostate gland j0305257 Prostate gland ûinborn defects uncommon û ûcirculatory disorders: ðinfarction •in the setting of benign hyperplasia •regenerative + reparative processes adjacent to the infarction focus may mimic a malignant lesion (esp. in needle biopsy) ð j0305257 Prostate gland ûinflammations: ðbacterial (acute purulent or chronic) •systemic symptoms, dysuria, frequency, local pain •ascendent, iatrogennic (cathetrisation, surgery, …) •E. coli, Klebsiella, Proteus, enterobacter… •tb – most common tb presentation in the male genital system – local spread or isolated metastasis of lung tb –diff. dg. x reactive or idiopathic granulomatous prostatitis ðabacterial •most common, chronic pain or asymptomatic •Chlamydia trachomatis, ureaplasma… û j0305257 Prostate gland ûpseudotumors, tumors: ðBenign prostatic hyperplasia ðCarcinoma •Acinar •Ductal •Squamous cell •Adenosquamous •Transitional cell •Neuroendocrine ðSecondary tumors •local ca infiltration from adjacent organs (bladder, rectum) •haematogennous metastases (lung ca, malignant melanoma, ..) • • û j0305257 www.nature.com Zonal predisposition of prostate diseases prostata schéma.jpg j0305257 Benign prostatic hyperplasia ûepidemiologic factors: ðage (BPH prevalence rising with age, 70% by age 60, 90% by 80) ðgeographic/racial (low in Asia, more common in W Europe) • ûpathogenesis: ðnot completely clear ðhormonal dysbalance, dihydrotestosteron induced growth factors → stromal proliferation + ↓ death of glandular cells ûgross nodular hyperplasia: ðperiurethral (transition zone) mostly affected→ urethral compression + obstruction → dysuria ûconsequences: ðlower urinary tract symptoms, acute/chronic urinary retention, cystitis ðbladder hypertrophy + diverticula, hydroureter + -nephrosis, pyelonephritis ð j0305257 Benign prostatic hyperplasia ûmicro: ðnodular structure ðglands: •hyperplastic, uneven size, common cystic dilatation •bi-layered epithelium – external myoepithelial (!x invasive ca), inner secretory (sm. papillary proliferation) •inspissated luminal secretions → corpora amylacea ðstroma: •hyperplastic, common purely stromal fibromuscular nodules •disperse chronic inflammatory reaction • • j0305257 Benign prostatic hyperplasia hyperplazie prostaty 20x j0305257 Benign prostatic hyperplasia hyperplazie prostaty 40x hyperplazie prostaty 200x j0305257 Prostatic adenocarcinoma û↑ incidence ð1st – 3rd of the most common male malignancies (prostate – lungs – colorectal) ð ûperipheral zone of prostate, dorsal part (per rectum!) û ûdg.: ðneedle biopsy (most common, by suspicion) ðtransurethral resection ( BHP treatment – accidental) ðsuprapubic prostatic resection j0305257 Prostatic adenocarcinoma ûProstatic intraepithelial neoplasia (PIN) ðLow-grade •more numerous acinar cells, without significant nuclear atypias • ðHigh-grade •significant cytonuclear atypia of acinar cells (enlarged nucleus, prominent nucleolus) •commonly in proximity of acinar adenocarcinoma – precursor lesion j0305257 Acinar prostatic adenocarcinoma ûmicro: ðneoplastic cells with round nuclei and prominent nucleoli ð ðsmaller crowded glands without detectable layer of basal cells •immunohistochemistry: HMW CK, p63 negative •neoplastic acini infiltrating between normal glands •intraluminal crystaloids (pale eosinophilic substance) • ð perineural and/or extraprostatic propagation possible ð j0305257 Acinar prostatic adenocarcinoma Small neoplastic acini (1) growing between prostatic glands (2) 1 1 2 j0305257 Acinar prostatic adenocarcinoma Nucleoli (arrows). Missing basal layer. j0305257 Acinar prostatic adenocarcinoma ûGleason histologic grading (WHO modification): ð • grade of glandular differentiation, growth pattern • combined score - dominant + secondary pattern in 5-grade system • grade 1 similar to normal prostatic tissue (uncommon in ca) • grade 5 with solid, dissociated pattern • final combined score, commonly Gleason score 7 (4+3) j0305257 Acinar prostatic adenocarcinoma incidencce ca prostaty j0305257 Acinar prostatic adenocarcinoma ûspread ðlocal (per continuitatem) •into periprostatic soft tissues, seminal vesicles, urinary bladder (!x transitional cell ca, may be both in the same patient) ðvia lymphatics •into regional LN ðvia blood •into bones – osteoblastic/osteosclerotic metastases (pelvis, vertebrae, ribs, long bones) •later into liver, lungs… ð ûprognosis ðdepend on the clinical stage (TNM), Gleason score, pre-operative PSA level in serum j0305257 Penis, scrotum j0305257 Penis, scrotum ûcongenital defects ðhypospadia, epispadia •commonly + cryptorchidism •in complex somatosexual disorders ð ðphimosis ð ûcirculatory disorders ðchronic venoous congestion ðoedema ðcorpora cavernosa thrombosis, gangrene (uncommon) j0305257 Penis, scrotum ûinflammations ðbalanoposthitis (glans + inner surface of the prepuce) •STD (gonorrhoea, genital herpes, lymphogranuloma venereum, syphilis …) •risk factors: –phimosis, chronic mechanical/chemical irritation –streptococi, staph., coliforms; candidas (DM)… • ðbalanitis xerotica obliterans = lichen sclerosus •epithelial hyperkeratosis, atrophy, inflammatory infiltrate • j0305257 Penis, scrotum ûtumors, pseudotumors: ðPeyronie‘s disease – penile fibromatosis ð ðbenign epithelial tumors •condyloma accuminatum – HPV 6, 11 ð ðmalignant epithelial tumors •carcinoma in situ –Bowen‘s disease / erythroplasia of Queyrat on the glans –bowenoid papulosis (multiple, HPV 16, non-progressive) – •invasive squamous cell carcinoma –geography (Latin America, East Asia) –circumcision - protective factor (↓HPV, carcinogenes in smegma) –risk factor – smoking, occupational (mineral oil, tar) j0305257 Testis, epididymis j0305257 Testis, epididymis ûcongenital defects ðcryptorchidism (undescended testis) ð ûcirculatory and regressive changes ðnecrosis (haemorrhagic infarction) – typical due to testicular torsion, ! emergency ðatrophy – senile involution, vascular, hormonal… ðintrascrotal swelling •hydrocele (serous fluid in tunica vaginalis) •haematocele (haemorrhage into tunica vaginalis) •varicocele (varicose veins) •spermatocele (cystic dilatation of epididymis ducts) j0305257 Testis, epididymis inflammations ûepididymis >>> testis û ûusually ascending from urinary tract and/or prostate û ûcaused by ðgramnegative bacteria (children) ðchlamydias, gonococcus (adults) ðE. coli (older adults) j0305257 Testis, epididymis inflammations ûBacterial ðpurulent→ abscess, non-specific orchitis/epididymitis û ûInterstitial non-purulent orchitis ðmumps in adults ðinterstitial oedema + lymphocytes, plasma cells, macrophages û ûGranulomatous orchitis ðmay be posttraumatic, v.s. autoimmune inflammation ðnon-caseating tuberculoid granulomas centered on tubules ðfirmer testicular mass (diff. dg. x tumor) ð ûSpermatocytic granuloma ðin the head of epididymis due to rupture of tubules ðreactive tuberculoid granulomas around spermatozoa j0305257 Granulomatous orchitis Tuberculoid granulomas. j0305257 Granulomatous orchitis Tuberculoid granulomas. Poorly recognisable original seminiferous tubule j0305257 Testicular tumors ûGerminal ðfrom germ cell ð ûSex cord-stromal ðfrom specialized mesodermal gonadal stroma ð ûMixed germ cell – sex cord stromal tumors û ûOther primary tumors ûMetastatic (secondary) tumors û j0305257 Testicular tumors : histopatological report ûgross picture (incl. size) û ûhistological type û ûpresence of vascular / lymphatic propagation û ûtumor staging (TNM classification) ûpresence of intratubular germ cell neoplasia (ITGCN - in situ germ cell lesion) j0305257 Germ cell tumors û~90 % of primary testicular tumors û ûcryptorchidism ð3-5x ↑ risk of malignancy in undescended testis ð ûoncogenic markers: ðαFP, hCG, PLAP, CEA, LDH ðdetection in serum, tissues ðimportant in diagnosis, monitoring the response to therapy, patient check-up after therapy û û j0305257 Age structure of testicular tumors patients j0305257 Germ cell tumors ûintratubular germ cell neoplasia ðITGCN - in situ germ cell lesion ðcommon precursor lesion of germ cell tumors û ûbasic classification: ðseminoma ðnon-seminomatous tumors û ûgerm cell tumors of 1 histologic type – 60 % ûmixed germ cell tumors – 40 % û ûmetastases into LN (paraaortal LN), via blood (most commonly into lungs) j0305257 Germ cell tumors histogenesis Original primitive germ cell Undifferentiated cell Embryonal carcinoma Totipotent cell Differentiation along gonadal line (gonocyte, spermatogonia) without further differentiation potential. Seminoma Extraembryonal differentiation Yolk sac tumor Choriocarcinoma Intraembryonal differentiation Teratoma (mature, immature, with malignisation of somatic elements) Polyembryoma j0305257 Germ cell tumors classification ûtumors of single histologic type ðSeminoma (+ variants) ð ðNon-seminomatous germ cell tumors •Embryonal carcinoma •Yolk sac tumor •Choriocarcinoma •Teratomas –mature –immature –with malignisation of somatic elements j0305257 Germ cell tumors classification ûmixed germ cell tumors ðtumors with >1 histogenetic type • • ûSpermatocytic seminoma ðseparate clinical and pathological entity (different morphology/prognosis) j0305257 Germ cell tumors Characteristics û age marker structure ûSeminoma 30-50 10% HCG solid, clear cells, lymphocytic stroma û ûEmbryonal 20-30 90% HCG/AFP undiff. cells, organoid, necrosis ûcarcinoma ûYolk sac <3 90% AFP variable û ûChoriocarcinoma 20-30 100% HCG cyto- + syncitiotrophoblast û ûTeratoma no predilection possible HCG,AFP variable structures of >1germ û layer ûMixed tu 15-30 possible HCG,AFP variable structures û j0305257 Seminoma ûclassical ðmorphological variants: •seminoma with high mitotic rate (anaplastic), same treatment •seminoma with syncytiotrofoblastic cells (↑ HCG) ðmostly age 25 - 45 years ðtumor cells •in solid nests •large cell, clear cytoplas (glycogen), distinctive cellular membrane, large nuclei with 1-2 nucleoli ðfibrovascular septa •with lymphocytic infiltrate (event. + granulomas) ðimmunohistochemistry: PLAP+ ðmarker – 10% HCG ðradio- and chemosensitive (usuallly good prognosis) j0305257 Seminoma 1 Tumor cells 2 Fibrotic septa with lymphocytic infiltrate 1 2 j0305257 Seminoma seminom1, 200x j0305257 Seminoma ûSpermatocytic ðquite distinctive tumor, not a part of mixed germ cell tumors ðonly in the testis, older M, rare •locally aggressive, no metastases ðtumor cells •variable size (≈early stages of spermatogenesis) •no glycogen, no association with intratubular germ cell neoplasia ðfibrovascular septa without lymphocytic reactive infiltrate ðIHC: PLAP- j0305257 Spermatocytic seminoma Mixture of polymorphic tumor cells (~ early stages of spermatogenesis): large cells with lacy chromatin, middle-sized cells with round nuclei, small lymphocyte-like cells. Fibrotic septa without lymphocytic infiltrate j0305257 Embryonal carcinoma ûundifferentiated tumor, cells of epithelial appearance ûcommonly as part of mixed germ cell tumors ðworse prognosis ûmicro: ðsolid, trabecular, abortive tubular formations ðlarge cells, high mitotic activity ðstroma without lymphatic reaction j0305257 Embryonal carcinoma Testes_GCT_EC1 j0305257 Yolk sac tumor û~ yolk sac structures, extraembryonal mesodermal tissues û ûin pure form in infants, young (<3 yrs) children, better prognosis ûin adults a component of mixed germ cell tumors, worse prognosis ûά-fetoprotein (AFP) secretion – IHC, serum û ûmicro: ðmicrocystic, reticular, papillary formation, variable patterns ðglomeruloid structures (Schiller-Duval bodies) •stalk with capillary lined on the surface by layer of tumor cells ðtumor cells •flat, polygonal or cuboidal • j0305257 Yolk sac tumor Schiller-Duval body (glomeruloid formation) j0305257 Choriocarcinoma ûmixture of syncytiotrophoblast, cytotrophoblast, intermediate trophoblast cells û ûpure very rare, more commonly as component of mixed germ cell tumors, HCG ↑ û ûgross/ micro: ðhaemorrhagic + necrotic tumor ðvariable patterns of syncytiotrophoblast with admixture of larger polygonal cells of cytotrophoblast event. + intermediate trophoblast j0305257 Choriocarcinoma 1 syncytiotrophoblast 2 cytotrophoblast 3 necroses 1 1 2 2 3 j0305257 Choriocarcinoma 1 syncytiotrophoblast 2 cytotrophoblast 1 2 j0305257 Teratoma ûintraembryonal differentiation ðterminal differentiation into 3, 2 or 1 germ layers (monodermal teratoma) û ûmature uncommon in testis (x ovary); pure in children û ûhistologic classification ðdifferentiated mature t. •completely maturated tissues with organoid structure •commonly cystic, containing serous fluid, mucus, keratin ðdifferentiated immature t. •immature tissues of embryonal/fetal appearance (neuroectoderm) ðt. with somatic type malignancy •sarcoma, carcinoma, PNET û j0305257 Differentiated mature teratoma (dermoid cyst) 1 cyst with keratin 2 epidermis 3 skin adnexa 4 fat tissue 2 1 3 3 4 j0305257 Differentiated mature teratoma 2 1 5 3 4 1 nervous tissue 2 compact lamellar bone 3 bone marrow 4 cartilage 5 striated muscle j0305257 Differentiated immature teratoma Primitive fetal tissues (neuroectodermal) j0305257 Extragonadal germ cell tumors (EGT) ûprimary germ cell tumors arising in extragonadal localisation û ûmore common in males û ûorigin unclear: ðfrom primordial germ cells? ðfaulty migration? ðfaulty localisation of totipotent cells? ðectopic germ cells in healty people? û û j0305257 Extragonadal germ cell tumors (EGT) ûlocalisation: ðin midline structures (pathway of germ cells descensus into gonadal blastema): •brain (pineal, suprasellar) sacrococcygeal, anterior mediastinum, retroperitoneum,…, thymus, prostate, stomach,…… • ûseminomas, non-seminomatous ûpure or mixed û ûgeneral prognosis worse, except EGT seminoma û û j0305257 Female genital system pathology j0305257 ûvulva ûvagina ûexocervix, endocervix ûuterine body ðendometrium ðmyometrium ûfallopian tubes ûovaries j0305257 Pathology ðinborn defects ðcirculatory disorders ðinflammations ðtumors û j0305257 Vulva j0305257 Vulvar inflammations ûcandida ðmycotic vulvovaginitis (DM, post-ATB) ûHPV ðcondyloma accuminatum, vulvar intraepithelial neoplasia - dysplasia (VIN I-III) ð ûHSV, type 2, 1 ðvesicles → ulcers, primoinfection + systemic signs ûNeisseria gonorrhoeae ðpurulent inflammation (gonorrhea) in glands – periurethral, Bartholin, … ûTreponema pallidum ðlues (chancre) j0305257 Non-neoplastic epithelial disorders ûgross appearance of leukoplakia – white plaque ûmostly in peri-, postmenopausal women ûinflammatory dermatoses (psoriasis, chronic dermatitis), pre- malignant lesions (VIN, ca), disorders of unknown etiology û ûLichen sclerosus ðepithelial atrophy + hyperkeratosis ðsuperficial dermis – band of oedema + hyalinisation ðperivascular mononuclear inflammatory cell infiltrate ð → → stenosis of vaginal orifice (craurosis vulvae) ð ûLichen simplex chronicus – squamous cell hyperplasia ðepithelial hyperplasia + marked hyperkeratosis ðnot a precancerosis • j0305257 Vulvar neoplasia ûcondyloma accuminatum ðlow-risk HPV (6, 11) ðsquamous cell papilloma with koilocytar epithelial transformation û ûvulvar intraepithelial neoplasia - VIN ðhigh-risk HPV (16) ðVIN II , III –high risk of progression into SCC û ûcarcinoma ðsquamous ca (90 %) •precursor lesions: –VIN II, III –lichen sclerosus (in older females) ðadenocarcinoma, basal cell carcinoma ð ûmalignant melanoma j0305257 Condyloma accuminatum Papilomatous architecture j0305257 Condyloma accuminatum Koilocytes (arrows) j0305257 Vagina j0305257 Vaginal inflammation ûcolpitis commonly concurrent with cervicitis, catarrhal or purulent inflammation û ûSTD:Trichomonas vaginalis; Neisseria gon.; bacterial vaginosis (gardnerella + anaerobes); candidosis, … û j0305257 Vaginal tumors and pseudotumors ûfibroepithelial polyps, glandular cysts ûHPV lesions concurrent with cervical/vulvar ðcondyloma accuminatum, vaginal intraepithelial neoplasia (VaIN I-III) → squamous carcinoma û ûembryonal rhabdomyosarcoma (sarcoma botryoides) ðgross – soft polypoid tumor protruding into vaginal lumen ðgirls <5 years ð û j0305257 Embryonal rhabdomyosarcoma Rhabdomyoblasts (arrows) j0305257 Cervix (endocervix, exocervix) j0305257 Cervicitis ûcommonly with colpitis, non-specific ðsimilar microbial causes ð ûchronic cervicitis may lead to mucosal hyperplasia → endocervical polyp û û j0305257 Cervical squamous metaplasia ûtransformation zone (squamo-columnar junction) ðeversion of columnar epithelium into vagina (ectopy, ectropium) ðreserve cell hyperplasia → immature squamous metaplasia → mature metaplasia ð ûclosure of endocervical glands by overgrowth of squamous epithelium → ovulosis (cystic dilatation of the glands) û j0305257 Cervical squamous metaplasia Image063 j0305257 Squamous metaplasia, ovulosis. 2 1 Exocervical squamous epithelium. 2 Endocervical mature columnar epithelium. 3 Reserve cell hyperplasia covered by residual columnar cells 4 Dilated endocervical glands 3 4 4 j0305257 Cervical preneoplastic changes + intraepithelial lesion ûLR (low-risk) HPV (6,11) →→ koilocytic atypia of squamous cells ðreplication + cytopathic viral effect, productive infection ðnuclear atypia, cytoplasmic perinuclear halo ûCervical dysplasia – intraepithelial neoplasia associated with HR (high-risk) HPV: ðHR HPV: • 16, 18, 31, 33, 35 ð deregulation of the cell cycle, ↑ proliferation, ↓ or arrested maturation • û • û û j0305257 Cervical preneoplastic changes û risk factors ðHPV •early sexual activity (<16 years of age) •number of sexual partners ðother STD (HSV, chlamydia) ðcigarette smoking ðearly age of first pregnancy ðcombined oral contraceptives ðimmunosuppression j0305257 Cervical intraepithelial neoplasia ûOlder classification ðCIN I (mild dysplasia): •koilocytic atypia + changes in the lower third of epithelium: –anisokaryosis –nuclear enlargement, hyperchromasia –loss of cell polarity –nuclear superposition ð ðCIN II (moderate dysplasia): •changes in the lower 2/3 of epithelial thickness, progressive atypia, expansion of the immature basal cells ð ðCIN III (severe dysplasia): •changes in the whole epithelium, diffuse atypia, almost complete loss of maturation û û j0305257 Cervical intraepithelial lesion û2 categories, according to the risk of progression and clinical management: ðLSIL (low-grade squamous intraepithelial lesion) ð = CIN I, exophytic or flat condylomatous lesion •mostly self-limited (viral clearance), productive infection, lower rate of progression ð ðHSIL (high-grade squamous intraepithelial lesion) ð = CIN II/III + ca in situ •majority persists or progresses to carcinoma û j0305257 Cervical cytology: LSIL screening of cervical carcinoma cytology (Bethesda System) + colposcopy koilocytes with dyskaryotic nuclei j0305257 Cervical intraepithelial lesion LSIL (CIN I) mild cytonuclear atypia in the parabasal layers koilocyte j0305257 Cervical intraepithelial lesion HSIL (CIN II) Cytonuclear atypia in the lower 2/3 of the epithelium j0305257 Cervical intraepithelial lesion HSIL (CIN III) Diffuse cytonuclear atypia. Mitotic figures incl. atypical. j0305257 Invasive cervical squamous cell carcinoma ûalmost always by HSIL progression û ûmostly starts in the transformation zone û ûgrowth: ðlocal progression •size + depth of the invasive component •direct invasion into adjacent organs, fistulae •regional LN metastases ðdistant metastases via blood (lung, liver, bone marrow) û↑ incidence, but mostly lower stages (if screened), ↓ mortality j0305257 Other cervical carcinomas û Adenocarcinoma ð cervical glandular intraepithelial lesion ð adenocarcinoma in situ ð ! diff. dg. x endometrial ca û Adenosquamous carcinoma ûNeuroendocrine cervical carcinoma j0305257 Uterine corpus j0305257 Endometritis ûrather uncommon û ûacute inflammation mostly in association with ðpregnancy (delivery, abortion) ðinstrumentation (curretage,…) ðlong-term IUD in situ (actinomycosis) ð ûchronic inflammation (+ acute exacerbation) ðchlamydia, chronic gonorrhoea ðtb (miliary, or per continuitatem from the fallopian tubes) j0305257 Endometriosis ûfoci of functional endometrium (glands + stroma) in an ectopic localisation ðovaria, cavum Douglasi, fallopian tubes, peritoneum, bladder, umbilical skin, … lung, bones …) ðcyclical changes during MC •haemorrhagic (chocolate) cysts, hemosiderin pigmentation ðpain, pelvic inflammatory disease + adhesions, infertility ðpossible source of endometrioid adenocarcinoma • • ðadenomyosis: •endometrial diverticula (outpouchong of basalis into myometrium, mostly no functional hormonal changes) j0305257 Endometrium, menstrual cycle 25 1 2 3 4 1 Early proliferation 2 Late proliferation 3 Early secretion 4 Late secretion j0305257 Dysfunctional endometrium ûUsual clinical presentation – abnormal bleeding ûHormonal dysbalance, variable origin ûNon-secretory ← abnormal estrogenic stimulation ð↓ E → hypoproliferative → atrophic endometrium ð↑ E → hyperproliferative → hyperplastic endometrium (anovulatory cycle) ðunopposed ↑ E by missing progestogenes → hyperplastic endometrium û ûSecretory ← abnormal progestogenes ð↓ P → hyposecretory endometrium (luteal phase insufficiency) ð↑ P exogennous (contraception) - stroma-glandular dissociation – pseudo-decidualized stroma + atrophic glands ð↑ P → hypersecretory endometrium (similar to gestational); Arias-Stella phenomenon (!GEU) ð ûIrregular, mixed ← E+P dysbalance ðirregular shedding – mixed secretory + menstrual + proliferative ð j0305257 Endometrial hyperplasia ûincreased glandular proliferation - ↑ gland-to-stroma ratio ûclassification according to architecture, cytological atypia ûsimple – dilated irregular glands, epithelial stratification, „swiss cheese“ ðwithout atypia, almost no progression to adenocarcinoma, ðwith atypia → cytologic atypia present, low progression, rare ð ûcomplex – irregular branching crowded glands, ↓ stroma (back-to-back) ðwithout atypia ðwith atypia → round nuclei + nucleoli, commonly monoclonal – neoplastic – high grade of progression, commonly (1/4-1/2) concurrent ca present; û j0305257 Endometrial hyperplasia 1 Endometrial hyperplasia 2 Polypous endometrial hyperplasia 43 1 1 2 j0305257 Simple hyperplasia Cystic transformation of endometrial glands Stromal hyperplasia j0305257 Complex hyperplasia Image059 j0305257 Complex hyperplasia 1 Abnormal glandular crowding 1 1 j0305257 Complex hyperplasia with atypia Stratification of epithelial cells, vesicular nuclei, visible nucleoli j0305257 Endometrial polyp û sessile/pedunculated, solitary/multiple exophytic endometrial focus ðabnormal bleeding common ðfunctional/hyperplastic/atrophic endometrium ðstromal fibrosis, thick-walled arteries ðmay be in association with endometrial hyperplasia, possible progression to atypical hyperplasia → adenocarcinoma û j0305257 Endometrial polyp - hyperplastic korp-polyp-hyperpl-40-k j0305257 Endometrial polyp – cystic atrophic polyp endometria_web j0305257 Endometrial adenocarcinoma ûMost common malignant tumor of female genital ð2. cervical ca, 3. ovarian tumors ûAbnormal bleeding ð ûtype I: perimenopause û ðRisk factors: ðunopposed estrogennic stimulation – endo-/exogenous ðDM, obesity, early menarche - late menopause ðprecursor atypical endometrial hyperplasia ðbetter prognosis, lymphatic spread possible j0305257 Endometrial adenocarcinoma ûhistologic forms: ðtype I •endometrioid adenocarcinoma •mucinous •tubal (ciliated) •squamous cell •adenosquamous • ðbez souvislosti s estrogeny, při mutaci p53 (→ velmi agresivní průběh) •serózní papilární karcinom •světlobuněčný karcinom û j0305257 Endometrial adenocarcinoma û Type II ðpostmenopausal ðwithout estrogenic stimulation, p53 mutation (→ aggressive; intraperitoneal, lymphatic spread) ðin the setting of atrophic endometrium ðpoorly differentiated (serous, clear cell) ðundifferentiated (metaplastic carcinoma) j0305257 Endometrial adenocarcinoma gbp420 j0305257 Endometrioid adenocarcinoma cribriform glands j0305257 Endometrioid adenocarcinoma Epithelial stratification, cellular atypias, mitotic activity j0305257 Serous adenocarcinoma j0305257 Metaplastic carcinoma müll-carsar100-k j0305257 Mesenchymal tumors ûLeiomyoma ðmost common benign female tumor (usual in later reproductive age) ðsize: mm - cca 20 cm ðsymptoms due to localisation/topography (bleeding, infertility, compression of adjacent organs) ðuterus myomatosus (multiple leiomyomas) ðcommon regressive changes (oedema, fibrosis, hyalinisation, calcification) j0305257 Uterine leiomyomas 44 2 1 3 2 1 Subserous leiomyoma 2 Intramural myoma 3 Submucosal myoma 4 „Nascent“ submucosal myoma 4 j0305257 Leiomyoma Fascicular structure j0305257 Mesenchymal tumors ûStromal tumors ðorigin from endometrial stroma ðStromal nodule (benign) ðStromal sarcoma •Low-grade •High-grade j0305257 Stromal nodule j0305257 LG stromal sarcoma j0305257 Pathology of pregnancy ûectopic pregnancy ûspontaneous abortion (placental disorders incl. placentation abnormalities, vascular lesions, inflammation – ascending, hematogenous; umbilical cord pathology) ûpre-eclampsia – systemic endothelial dysfunction; hypertension + oedema + proteinuria, hypercoagulative state; may→ eclampsia (CNS – convulsion, coma) ð ûGestational trophoblastic disease j0305257 Gestational trophoblastic disease ûproliferation of gestational trophoblast with progressive malignant potential or frankly malignant ûhydatidiform mole ðpartial, complete - benign; ðinvasive – uncertain biol. potential ð from abnormal conception ðabnormal placenta with villous hydrops and variable degree of trophoblastic proliferation ûtrophoblastic tumors – choriocarcinoma, etc. j0305257 Hydatidiform mole ûComplete ð„empty“ (aneuclear) egg fertilised by 1 normal sperm with duplication of haploid genome (23,X → 46,XX), or 2 normal sperm - 46,XX or 46,XY; paternal genome only ðgross: •grape-like formations ðmicro: •cystic chorionic villi – extensive stromal oedema, central cistern – empty space •circumferential trophoblastic proliferation, atypias • ûPartial ðnormal egg fertilised by 1 diploid sperm (46,XY) or 2 haploid sperm → triploid 69,XXX or 69,XXY ðgross: •mixture of smaller grape-like villi, parts of embryo possible ðmicro: •mixture of oedematous and fibrotic villi •less marked trophoblastic proliferation j0305257 Image078 Hydatidiform mole - complete may persist or recur 10% → invasive m. 2,5% → chorioca -partial no progression, may persist or recur - invasive invasion of myometrium by villi, risk of perforation locally destructive, embolisation of villi into distant organs (lungs) j0305257 Gestational choriocarcinoma ûsubsequent to molar pregnancy (50%), abortion (25%), normal gestation (22,5%), ectopic pregnancy (2,5%) ûatypical syncytio- and cytotrophoblast, no villi, minimal stroma, no angiogenesis; foci of haemorrhage, necrosis present ûearly haematogenous spread (lung, vagina, brain, liver…) ûhighly elevated HCG ûchemosensitive (x germ cell tumor – low response to therapy, bad prognosis) û û j0305257 Fallopian tubes j0305257 Salpingitis ûmostly ascending inflammation from uterus ûpossible secondary (appendicitis) û ûrisk of mucosal adhesions ðinfertility ðectopic tubal pregnancy ð ûpart of pelvic inflammatory disease („adnextumor“) ðinflammatory pseudotumor with abscessi ðpyosalpinx j0305257 Tumors ûparatubal cysts û û intraepithelial serous adenocarcinoma (possible precursor of ovarian adenoca), invasive adenocarcinoma û ûpseudotumors ðinflammatory pseudotumor ðendometriosis û j0305257 Ovary j0305257 Ovarian inflammation ûpart of pelvic inflammatory disease (salpingo-oophoritis), tubo-ovarian abscess „adnextumor“ ûcommon bacterial infections ûactinomycosis j0305257 Ovarian cysts ûnon-neoplastic ð inclusion c. (mesothelial, epithelial) ðfunctional c. (follicular, luteal, polycystic ovary syndrome, ovarian hyperstimulation syndrome) ðendometriosis ûneoplastic ðsurface epithelial tumors, ðgerm cell tumors ðsex-cord stromal tumors ðmetastatic tumors ðothers û j0305257 Image086 Ovarian tumors j0305257 Germ cell tumors ûcounterpart to germ cell testicular tumors û ûdysgerminoma – ovarian „seminoma“ û ûmost common female germ cell tumor: ðbenign mature (differentiated) teratoma, usually in the form of dermoid cyst j0305257 gbp5100 Dermoid cyst – mature cystic teratoma j0305257 Sex cord-stromal tumors ûGranulosa-theca cell tumors •granulosa cell tumor (adult type) – Call-Exner bodies; malignant potential, estrogen production •granulosa cell tumor (juvenile type) •thecoma •fibrothecoma •fibroma •fibrosarcoma û ûSertoli-Leydig cell tumors û ûSteroid cell tumors •resemble steroid hormone-secreting cells •possible androgenic secretion j0305257 Granulosa cell tumor 1 Call-Exner bodies 1 j0305257 Granulosa cell tumor Call-Exner bodies j0305257 Other tumors ûMixed germ cell sex cord-stromal tumors ð ûPrimary ovarian mesothelioma, adenomatoid tumor ûSoft tissue tumors not specific to the ovary ûMalignant lymphomas û…. û ûSecondary ovarian tumors ðKrukenberg tumor (metastatic mucinous adenocarcinoma) ðpseudomyxoma peritonei,… j0305257 Surface epithelial-stromal tumors ûCoelomic epithelium (mesothelium with the ability of transformation into Müllerian epithelium ) → hyperplasia and metaplasia of the surface epithelium → neoplastic transformation û ûBiologic potential ûBenign ðcommonly in form of cystadenoma ûLow malignant potential ðborderline malignancy – moderate atypias, mitotic activity, architectonic changes (multilayering, irregular papillary budding), ! no invasion, but non-invasive peritoneal implants possible ûMalignant û j0305257 Surface epithelial-stromal tumors ûEpithelial type ûSerous ûMucinous, endocervical-like and intestinal-type ûEndometrioid ûClear cell tumors ûTransitional cell tumors ûMixed tumors of müllerian epithelium j0305257 Surface epithelial-stromal tumors ûForm of growth ûCystic ûPapillary incl. inverted ûSolid ûIncreased amount of neoplastic stroma, mixed tumor (adenofibroma, adenosarcoma, etc.) j0305257 Serous cystadenoma (cystadenofibroma) Columnar ciliated epithelium j0305257 06 04 WHO-OvarianTumours_009 WHO-OvarianTumours_013 Serous cystadenoma Serous borderline tumor Serous cystadenocarcinoma j0305257 Mucinous cystadenoma WHO-OvarianTumours_017 WHO-OvarianTumours_018 Columnar mucinous epithelium j0305257 Mucinous cystadenocarcinoma Mucinous borderline tumor Mucinous cystadenoma j0305257 Endometrioid adenocarcinoma 1 1 2 1 Endometrioid epithelium 2 Glandular structures j0305257 Surface epithelial-stromal tumors û Serous adenocarcinoma ð60-80%, 30-50% bilateral ð usually smaller size, rapid growth ð common psammoma bodies û Mucinous adenocarcinoma ð5-15%, 10-20% bilateral ðlarge size, slow growth û Endometrioid adenocarcinoma ð10-30%, 10-30% bilateral ð slow growth, haemorrhagic content ðsquamous metaplasia common ð ð j0305257 Pathology of the breast j0305257 ûSkin ûNipple and areola ûMammary gland ûSoft tissues û ðinborn defects ðcirculatory disorders ðinflammations ðnon-neoplastic lesions ðtumors j0305257 Nipple and areola j0305257 Paget‘s carcinoma of the nipple ûsingle neoplastic cells dispersed in the squamous cell epithelium of the nipple û ûusually concurrent with DCIS (ductal carcinoma in situ) or invasive breast carcinoma û ûgross: eczema-like (erythema, oozing/ ulcerated lesion) j0305257 Paget‘s carcinoma of the nipple Single neoplastic cells (arrows) dispersed in squamous cell epithelium www.mamma.cz j0305257 Mammary gland j0305257 Fertile mammary gland - histology 1 terminal ductal-lobular unit (TDLU = intralobular duct + acini + intralobular stroma) 2 interlobular duct 3 interlobular stroma 4 adipous tissue 1 2 3 4 j0305257 TDLU IHC anti-SMA 1 luminal glandular cells 2 myoepithelial cells (SMA+) 1 2 j0305257 Mammary gland ûselected inflammations: ðAcute pyogenic mastitis •during first weeks of breastfeeding •nipple fissures + infection (i.e. Staphylococcus aureus) → purulent inflammation / abscess formation ðPeriductal mastitis •strongly associated with smoking •squamous metaplasia in the distal parts of ducts → keratin plug → cystic dilatation / duct rupture → chronic /granulomatous periductal inflammation ðLymphocytic (diabetic) mastopathy •type I. DM, autoimmune thyreoiditis •periductal + perilobular sclerosis + dense lymphocytic infiltrate j0305257 Benign epithelial lesions ûbenign alterations in ducts and lobules ûcommon lesions û ðpalpable irregularities (lumps, granularity), +/-tender ðetiology: •hormone dependent •inflammation-associated ðdiff. dg.: malignant tumors j0305257 Benign epithelial lesions û classification according to the risk of developing subsequent breast carcinoma û non-proliferative breast changes – fibrocystic change ðcysts +/- apocrine metaplasia ðfibrosis ðadenosis j0305257 Benign epithelial lesions ûproliferative breast disease without atypia ðproliferation of ductal epithelium +/-stroma ðusually in combination ðcalcification common (mammography) ðepithelial hyperplasia (usual ductal hyperplasia – simple, florid) ðsclerosing adenosis ðpapillomatosis ðcomplex sclerosing lesion ð j0305257 Benign epithelial lesions û proliferative breast disease with atypia ð atypical ductal hyperplasia ðatypical lobular hyperplasia ð j0305257 Fibrocystic change ûpalpable „lumpy“ firmer tissue ûmicro: ðextensive fibrosis ð+ cysts (apocrine metaplasia) ð+ adenosis (lobulocentric proliferative lesion = increased number of acini in a lobule, preserved lobular architectonics) ðcommonly + ductal and/or lobular hyperplasia û ûno increased risk of malignant transformation (unless atypical epithelial hyperplasia present) ð j0305257 Cysty+duktektázie Fibrocystic change 1 cystic dilated ducts, +/- luminal secretion 2 apocrine metaplasia 3 fibrosis 1 1 1 2 3 j0305257 Sclerosing adenosis Sklerozující adenóza6 1 2 3 1 acini 2 myoepithelial cells 3 irregular fibrosis (sclerosis) j0305257 Benign epithelial tumors ûrather uncommon ûimportant in diff. dg. of malignant tumors ûselected entities: ðIntraductal, intracystic papilloma ðLactational adenoma (?exaggered focal response) ðTubular adenoma ðDuctal adenoma j0305257 Intraductal papilloma kopie z webpathology.com j0305257 Proliferative breast disease with atypia / in situ neoplasia û relatively common û potential progression into invasive carcinoma – precursor lesion ðAtypical ductal hyperplasia (ADH) ðAtypical lobular hyperplasia (ALH) ðDuctal carcinoma in situ (DCIS) •non- high grade •high grade ðLobular carcinoma in situ (LCIS) û û û j0305257 Diagnosis Morphology • Focal fibrosis • Cysts • Florid adenosis • Sclerosing adenosis • focal increase of TDLU stroma • dilated ducts • increased number of acini • increased number of acini + TDLU fibrosis • Ductal hyperplasia • Lobular hyperplasia • Ductal papillomatosis • Fibroadenomatoid hyperplasia • ductal epithelium proliferation • acinar epithelium proliferation • epithelial proliferation in dilated ducts • ductal epithelial + TDLU stromal proliferation • Atypical ductal hyperplasia • Atypická lobulární hyperplázie • ductal epithelium proliferation + atypias • acinar epithelium proliferation + atypias • DCIS, non-high grade • LCIS • intraductal ca in situ with mild nuclear pleomorphism • lobular ca in situ • DCIS, high grade • intraductal ca in situ with severe nuclear atypias Proliferative epithelial lesions and in situ neoplasia j0305257 DCIS cribriform structure of DCIS j0305257 DCIS 1 luminal cells with mild nuclear pleomorphism = non-HG DCIS 2 myoepithelial cells 1 2 j0305257 LCIS Expanded acini filled by mildly pleomorphic cells, intact basement membrane j0305257 Malignant epithelial tumors ûBreast carcinoma ûcommonest maligancy in females in high-income countries û ûrising incidence û ûfalling mortality ðscreening + better diagnostics ðknown modifiable risk factors ðmore effective therapy û ûmetastases ðlymphatic spread – regional LN (mostly axillary) ðhematogenous spread (bones, lung, liver, brain…) j0305257 Malignant epithelial tumors ûSporadic carcinomas (≈95%) ðaccidental sequential mutations ðmostly perimenopausal/postmenopausal, old age (50-75) ð ûFamilial carcinomas (≈ 5%) ðhereditary mutations in some TSG (BRCA1, BRCA2…) ðtypical in young females (after age of 20) ðpossible multicentric, bilateral → prophylactic mastectomy ð↑ risk of ovarian carcinomas ð j0305257 Age incidence věková struktura ZN mammy.png j0305257 WHO classification of carcinomas ûInvasive ca, no special type (NST) = ductal ca, NOS ûInvasive lobular carcinoma û ûTubular ca ûInvasive cribriform ca ûMedullary ca ûMucin producing ca ûNeuroendocrine tumors ûInvasive papillary ca ûInvasive micropapillary ca ûApocrine ca ûMetaplastic ca ûLipid-rich ca ûSecretory ca ûOnkocytic ca ûAdenoid-cystic carcinoma ûAcinic cell ca ûGlycogen-rich clear cell ca ûSebaceous ca ûInflammatory ca û ûBilateral carcinoma j0305257 Invasive ductal carcinoma û most common û gross: ðfirm lesion, irregular border 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 j0305257 Image059 Invasive ductal carcinoma j0305257 Invasive ductal carcinoma 1 kohezivní nádorový infiltrát s ojedinělými tubuly 2 infiltrace tukové tkáně 1 2 j0305257 Invasive ductal carcinoma 1 2 1 DCIS 2 invasive part of ductal carcinoma j0305257 Invasive ductal carcinoma Tumorous infiltrate with irregular small tubules j0305257 Invasive lobular carcinoma û častěji roste multicentricky û mikro: ðnádorové buňky ztratily soudržnost (E-cadherin-) • řadí se do různě dlouhých pruhů – „husí pochod“, „indiánské péro“ • pruhy nádorových buněk jsou uspořádány naznačeně koncentricky kolem dilatovaného vývodu • buňky mají jádra se světlejším chromatinem ðchybí myoepiteliální vrstva (SMA-) ðstroma denzní, vazivové ðinfiltrativní růst, často v blízkosti LCIS j0305257 Invasive lobular carcinoma Image060 j0305257 Invasive lobular carcinoma 1 dyscohesive tumor cells in single file (Indian file) 1 1 j0305257 Myoepithelial lesions û myoepithelial cells proliferation, (sm. + luminal cells) û uncommon û classification: ðAdenomyoepithelial hyperplasia ðAdenomyoepithelioma ðMyoepithelioma ðMyoepithelial carcinoma j0305257 Mesenchymal tumors û rare in the breast û i.e.: ðhaemangiomas, leiomyoma, lipoma, schwannoma ðangiosarcoma, leiomyosarcoma, liposarcoma j0305257 Fibroepithelial (mixed) tumors û very common û Fibroadenoma (FA) ð most common breast tumor in young females ðbenign, circumscribed, mobile, rubbery ð proliferating ducts + increased amount of stroma (edematous or hyalinised) ð pericanalicular, intracanalicular growth j0305257 Fibroadenoma Slit-like newly formed ducts compressed by edematous stroma j0305257 Fibroepithelial (mixed) tumors û Phyllodes tumor ðrare (<1% of all breast tumors) ðgross – leaflike structure and cysts (cystosarcoma phyllodes) ðmicro similar to FA, increased stromal cellularity • stromal component benign / with atypias / malignant (sarcoma) • biologic behaviour: – benign – broderline – malignant j0305257 Phyllodes tumor Hypercellular stroma compressing ducts kopie z webpathology.com j0305257 Male breast pathology û gynecomastia ð most common • up to 30% adult males, commonly bilateral ðenlarged subareolar gland ðhyperthyroidism, liver cirrhosis, CHRI, chronic respiratory failura, hypogonadism, hormone therapy. û û carcinoma ðrare, hereditary risk possible (BRCA2) ðworse general prognosis (usually late dg.)