| Disease | Epidemiology | Path | diansosis | Histo | Gross | Tx | ||
| Renal disease (definitions and clinical presentations) | 1) Azotemia (elevated BUN and creatinine; dec. GFR), 2) uremia (azotemia w/ excretory failure, metabolic/endocrine changes, and other system affects | 1) acute nephritic syndrome (hematuria, proteinuria, HTN; caused by glomerulonephritis) | 1) Nephritic syndrome inflammatory rupture of glomerular capillaries (heavy proteinuria w/ low serum albumin and lipiduria; caused by GFR failure) | Chronic glomerulonephritis - progressive glomeruli hyaline obliteration (masson trichrome stain for collagen) | Nephrotic syndrome - increased permeability of GBM w/ proteinuria (albumin) | |||
| Acute renal failure | auria or oligouria with recent onset of azotemia often caused by circulatory failure | |||||||
| Chronic renal failure | Prolonged uremia caused by persistent renal disease | |||||||
| Renal tubular defects | Reabsorption failure with polyuria,nocturia, and abnormal serum electrolytes | |||||||
| KIDNEY (CYSTIC) | ||||||||
| Cystic renal dysplasia | 1) may present as unilateral mass and if opposite kidney is preserved is excellent prognosis post surgery, 2) bilateral often fatal | 1) Abnormality in metanephric differentiation is characterized by abnormla mesenchyme, cartilage, and immature ducts, 2) Assd w/ ureteropelvic obstruction | disorganized architecture, dilated tubules w/ cuffs of primitive stroma, and an island of cartilage (right) | Enlarged kidney with irregular variable cysts | ||||
| Autosomal dominant polycystic kidney disease (ADPKD) | 1) AD w/ high penetrance, 2) 5-10% of chronic renal disease, 3) renal failure in 30-40s, 4) Sx: mimic renal masses w/ hematuria and tend to have extrarenal abnormalities also (40% liver cysts, other organ cysts, intracranial aneurysms, mitral valve prolapse) | 1) There are mutations in at least two membrane proteins (polycystin 1&2). Polycystin 1 (PKD1) is more common and severe, only expressed in distal tubule, where #2 exrpessed in all segments and othe organs., 2) Abnormal proteins = abnormal extracellular matrix (cell-cell interaction) resulting in cyst formation, enlargement and eventual renal failure | Cystic change in tubules and glomeruli w/ dilation of bowman's space | marked enlargement w/ numerous dilated cysts | ||||
| Autosomal recessive polycystic kideny disease (ARPKD) | 1) AR (rare), 2) perinatal and infantile typically renal failure, 3) juvenille onset develop hepatic fibrosis, portal HTN, and splenomegaly | The membrane protein, Fibrocystin (PKHD1 gene), is normally highly expressed in adult fetal kidney, liver, and pancreas/ | cylindrical dilation of collecting tubules | spong-like appearance with dilated channels at right angles to the cortical surface | ||||
| Medullary sponge kidney | 1) common (innocuous disease of adults), 2) may have secondary complications, | 1) Cystic dilatation of collecting ducts of medulla only (particularly papillae), 2) Caclifications in ducts, hematuria, infection, and stones are common complications | ||||||
| Medullary cystic disease | 1) progressive, childhood onset (most common genetic childhood renal failure), 2) Multiple forms: Sporadic (20%), Familial juvenille nephronophthisis (AR, 50%), renal-retinal dysplasia (AR, 15%), Adult onset (AD, 15%) | 1) Distal tubule injury w/ BM disruption, fibrosis, and progressive atrophy, 2) Results in tubular concentration failure (polyuria, polydipsia, salt wasting), 3) At least five genes: Juvenille (AR; NPH1-3), Adult (AD, MCKD1&2, progress to renal failure in adulthood) | 1) intersitial fibrosis, 2) tubular basement membrane duplication | cysts at corticomedullary junction | ||||
| GLOMERULI | ||||||||
| Glomerular syndrome definitions | Azotemia - elevated BUN and creatinine related to decreased GFR | Acute nephritic syndrome - hematuria, azotemia, variable proteinuria, oliguria, edema, & HTN | Rapidly progressive glomerulonephritis - acute nephritis w/ proteinuria and renal falure (GFR < 20%) | Nephrotic syndrome - >3.5gm proteinuria, hypoalbuminemia, hyperlipidemia, lipiduria, and edema | ||||
| Minimal change disease | 1) Children (65% of nephrotic syndrome) | 1) An immune dysfunction (Tcells) results in liberation of cytokines and damage to podocytes that allow GBM to leak proteins | 1) Clinically suspect kidney disease (albumin proteinuria), 2) LM is unremarkable, but EM shows diffuse effacement of foot processes | Effacement or flattening of podocyte foot processes | Histo: normal podocyte | Corticosteroids (responds well) | ||
| Membranous glomerulopathy | 1) Adults (30% of nephrotic syndrome), 2) 80-85% primary or idiopathic, 3) 2ndary (HepB/C, neoplasms, SLE, drugs- captopril, NSAID, gold, penicillamine), 4) 30-50% leads to chronic GN | 1) Primary: antibodies against glomerular antigens , 2) 2ndary: circulating antigen-Ab complexes, 3) NO visible inflammatory cells, 4) Immune complexes are laid b/w foot processes (subepithelial) followed by membrane deposition b/w deposites (spikes) then process effacement (flattening) | LM: Diffuse thickening of capillary wall with spikes | IF: Positive-granular pattern | EM: subepithelial and intramembranous deposits | Silver stain w/ spikes[1] | ||
| Focal segmental glomerulosclerosis | 1) 35% of NS in adults (most common), 2) 50-80% leads to chronic GN | 1) Sclerosis affecting <50% of glomeruli (focal) and involving segments of each glomerulus, 2) Primary or secondary (HIV, heroin, reflux), 3) Renal mass reduction (unknown cause) results in intraglomerular HTN with mesangial hypertrophy and epithelial/endothelial damage which presents as proteinuria and leads to sclerosis (mac TGF-B) anf further renal mass red. | LM: Focal segmental collapse of loops with hyalin drops | IF; Unremarkable | EM: Effacement of foot processes (see minimal change EM) | ACE inhibitors (Captopril) - dec. glomerular capillary pressure w/ ameolioration of FSGC progression | ||
| Membranoproliferative glomerulonephritis | 1) 10% of NS in children and adults, 2) associated w/ Hep C (strongly) and Hep B (weak), SLE, chronic bacterial infections, malignancies - lymphomas/leukemias), 3) 50% leads to chronic GN | Two types: 1) Type I: Immune complex activating both classic and alt. complement, 2) Type II: Dense-deposit (alternative pathway C3bBb activation w/ C3 nephritic factor Ab blocking degradation) w/ hypocomplementemia | Px present w/ hematuria, proteinuria, and/or hypocomplementemia | LM: mesangial cell proliferation (lobular glomerulus) with diffuse (>50%) glomerular involvement & leukocyte infiltration | LM: GBM splitting (double contour) | IF: Positive granular pattern (C3, no IgG) | EM (type I): subendothelial deposits | EM (type II): ribbon like dense deposits |
| Poststreptococcal (acute proliferative) glomerulonephritis | 1) most common in children (6-10yo), 2) 1-4wk post strep, 3) leads to chronic GN (1-2%) | 1) Immune complex mediated deposition (granular) due to nephritogenic strains of group A beta hemo strep | 1) Acute nephritis (hematuria, red cell casts, azotemia, oliguria, HTN), 2) ASO titer, 3) biopsy | LM: Proliferative glomerulonephritis = Diffuse hypercellularity (endo, mesangial proliferation + neutrophilic infiltrate) | IF: Positive-granular pattern (see MGP) | EM: subepithelial hump-like deposits | ||
| Post infectious (acute proliferative) glomerulonephritis | 1) Bacterial (staph endocarditis, pneumococcal, meningiococcal), 2) Viral (Hep B, hepC, memps, HIV, zoster, HBV), 3) parasitic (malaria, toxo) | 1) Immune complex mediated | ||||||
| Rapidly Progressive (Crescentic) Glomerulonephritis Type I | 1) >50% survival w/ plasmapheresis, 2) 66% have goodpasture's syndrome (renal and pulmonary disease) w/ 33% only renal, 3) 90% to chronic GN | Tyoe I(Anti-GBM Ab), - Anti-Goodpasture antigen Ab cross reacts w/ pulmonary and renal BM (linear IgG deposits w/ C3). GP antigen is peptide in alpha-3 chain of type IV collagen | 1) Acute nephritis w/ proteinuria, 2) rapid progressive renal function loss, 3) Type I: Goodpasture syndrome (pulmonary & renal) present coughing blood with elevated creatinine (10, n=1) | LM: crescents involving >50% of glomeruli (crescents form following glomerular capsule rupture which fills bowman space causing a rxn to blood and cytokines with subsequent parietal cell proliferation and fibrin deposition) | IF: linear deposits (IgG, C3 in GBM) | Plasmapheresis | ||
| Rapidly Progressive (Crescentic) Glomerulonephritis Type II | 90% to chronic GN | Type II (Immune complex) - due to complication of poststrep, SLE, IgA | IF: Granular pattern | Plasmapheresis not beneficial, must treat underlying disease | ||||
| Rapidly Progressive (Crescentic) Glomerulonephritis Type III | 1) may be idiopathic, 2) 90% to chronic GN | Type III (Pauci-Immune) -lack of anti-GBM or complexes w/ ANCAs commonly assd w/ wegeners or micro PAN | IF: NEGATIVE!! | |||||
| IgA Nephropathy (Berger's disease) | 1) Most common glomerular disease worldwide, 2) one of the most common causes of recurrent hematuria, 3) children and young adults, 3) 30-50% leads to chronic GN | Increased IgA1 glomerular deposition results in the production of cytokines, proliferation of mesangial cells, and glomerular sclerosis. In contrast a systemic disorder (renal, skin, GI, joint), Henoch-Schonlein purpura, is also an IgA disorder affecting children. | 1) Sx: gross/microscopic hematuria, proteinuria, 2) IF w/ IgA (diagnostic) | LM: Mesangial hypercellularity | IF: Mesangial depositoin of IgA (diagnostic) | EM: mesangial electron dense deposits | ||
| Alport syndrome | 1) hereditary in boys | defective GBM formation results in thin membrane disease | isolated hematuria | none | ||||
| Diabetic Glomerulosclerosis | 1) Most common cause of ESRD, 2) | Biochemical alteration of GBM (increased collagen/fibronectn + dec. heparan sulfate) caused by metabolic defect and HTN | LW: Mesangial sclerosis with acellular PAS positive Kimmelstiel-Wilson nodules | IF: NEGATIVE!! | EM: thick basement membrane, increased mesangial matrix, and thickened bowmans capsule | |||
| Renal SLE | 1) 40-50% is proliferative (acute nephritic or RPGN), 2) 15-20% is membranous nephropathy | LM: Proliferative diffuse hypercellularity w/ WIRE LOOP | IF: IgG,A,M deposition in every location | |||||
| Amyloid nephropathy | 1) Associated with chronic inflammatory disease (RA, myeloma) | 1) Nephritic syndrome | LM: amyloid deposits in mesangial and subendothelial | Congo red positive w/ green polarization (diagnostic for amyloid deposits) | EM: haphazardly arrangeed amyloid fibrils | |||
| TUBULES & INTERSTITIUM | ||||||||
| Acute Pyelonephritis | 1) one of the most common diseases of kidney, 2) Acute (bacterial, viral- polyoma in transplant) and chronic (bacterial, reflux), 3) 85% are G- bacilli (EC, proteus, Klebsiella, Enterobacter), 4) Females (shorter urethra) | 1) Ascending bacterial infection proceeds to bladder, gains access to ureter through deranged vesicoureteral jnct w/ reflux (risks = obstruction (prostate, tumors), bladder dysfnct (paraplegia, diabetes), instrumentation (cath)), 2) Hematogenous is less common often associated with infective endocarditis & bacteremia | Acute complications: 1) papillary necrosis (bilateral in DM), 2) Pyonephrosis (suppurative exudate fills & obstructs pelvis), 3) Perinephric abscess | 1) PMN interstitial and tubule infiltration (Plugs) with edema | Discrete yellow raised abscesses on kidney surface | |||
| Chronic Pyelonephritis | Chronic inflammation w/ irreversible scarring of calyceal-pelvic area. 2 Forms: 1) Reflux nephropathy (non-obstructive), 2) Chronic pyelonephritis (obstructive) | 1) Tubular atrophy (hallmark) - dilation of tubules w/ epi atrophy and pink, glassy casts (colloid casts), 2) Inflammation and scarring of interstitium (lymphocytes and plasma) | Reflux: scarring in kidney poles; Obstruction: calyceal scarring | |||||
| Xanthogranulomatous pyelonephritis | 1) unusual form of chronic pyelonephritis associated with Proteus | Foamy macs, lymphocytes, and plasma cells | sclerosis with stones | |||||
| Drug induced interstitial nephritis | 1) onset 2wks post drug (methicillin, ampicillin+B26 NSAID, thiazides), 2) Acute renal failure in 40-50% | A type I (IgE mediated) and type IV (delayed hypersensitivity) rxn due to drug acting as a hapten while bound to cytoplasmic or tubular component (tubular cells become immunogenic) | 1) Interstitial inflammation (Eos, plasma, PMN, lympho), 2) tubulitis, 3) granulomatous inflammation | Drug w/draw leads to recovery | ||||
| Analgesic Nephropathy | 1) long term analgesic ingestion (phenacetin, aspirin, acetominophen, caffeine, codeine) | 1) Acetominophen causes injury by covalent binding and oxidative damage, 2) Aspirin inhibits prostoglandin synthesis (papilla ischemic injury) | Chronic interstitial nephritis | Papillary tip necrosis | ||||
| Acute Tubular Necrosis (Ischemic) | 1) Most common cause of acute renal failure, 2) Ischemic (hypotension, rhabdomyolysis, hemolysis), 3) Toxic (aminoglycosides, radiocontrast, mercury, carbon tetrachloride) | Oxygen and toxin sensitive tubular epithelia become ischemic (dec. ATP) decreasing Na reabsorption resulting in intrarenal vasoconstriction (Renin-Ang feedback - more endothelin and less NO & PGI2). Ischemic cells undergoe apoptosis, express adhesion molecules, and eventually detach occluding tubule lumen and increasing interstitial pressure and permeability resultng in reduced GFR and urine output + interstitial edema | Tubule dilation due to injury and sloughing off of cells.into tubule lumen | |||||
| Acute Tubular Necrosis (Toxic) | ||||||||
| VESSELS | ||||||||
| Benign arterionephrosclerosis | 1) Hyalinization and initimal fibrosis of renal arterioles and small arteries (renal parenchyma ischemia) | 1) Arteries: Intimal fibrosis and smooth muscle hyperplasia results in decreased lumen size and reduplication of internal elastic lamina; 2) Arterioles: Hyanline accumulation under endothelial layer in afferent arterioles | 1) normal or decrease in size, 2) Cortical surface becomes finely granular with simple cysts and thinned cortex | |||||
| Malignant arterionephrosclerosis | 1) superimposed w/ 1-5% of pre-existing HTN, 2) Young AA males | Edothelial injury results in fibrinoid necrosis with fibrinogen/platelet deposition, intimal swelling, and thrombosis | 1) Fibrinoid necrosis of arterioles and interlobular arteries, 2) Arteriolar onion-skinning, 3) Endothelial injury | Petechial hemorrhages on cortical surface ("flea-bitten") | histo: pink = fibrinoid necrosis in wall; endothelial injury | |||
| Renal artery stenosis | 1) uncommon cause of HTN, 2) curable in 80% of cases | 1) 70% have atheromatous plaque at origin of renal artery, 2) Intimal, medial, or adventitial fibrous/fibromuscular hyperplasia (Fibromuscular dysplasia) typically in middle or dital artery | Fibrous thickening of media layer and adventitia (elasting stain) | |||||
| Thrombotic microangiopathies | 1) Hemolytic uremic syndrome ( childhood EC 0157:H7, adult, familial) and idiopathic thrombotic thromboctopenic purpura | 1) Endothelial cell injury (shiga toxin, neuraminidase, anti-endothelial Ab, cyclosporine, mitomycin, cytokine), 2) Platelet aggregation | thrombosis in capillaries and arterioles | |||||
| Systemic vasculitis | 1) Large vessel w/ rare renal involvement (Giant cell, takayasu), 2) Medium-sized (PAN, kawasaki), 3) Small vessel (Wegeners, micro PAN, Churg-strauss) | circulating ANCA w/ vascular IF staining | 1) Crescents, 2) Periglomerular and perivasclar granulomas (WG), 3) Eosinophils (Churg-Strauss) | |||||
| Atheroemboli (cholesterol emboli) | 1) occurs frequently following cardiac/vascular surgery or cath (1 wk post) | Bun, creatinine, eosinophilia,hematuria, proteinuria, decreased complement | 1) empty needle like clefts w/in arterioles wich contain cholesterol, 2)PMN infiltrate, Eos, lymphocytes, ATN, 3) small cortical infarcts | |||||
| Difuse cortical necrosis | 1) Post obstetric emergency, shock, surgery | pale pink w/o nuclei (left side) | Ischemic necrosis of cortex | |||||
| Renal infarcts | 1) most due to emboli (mural LA thrombosis, veg endocarditis, aortic aneurysm/atherosclerosis) | End-organ ischemic infarct in kidney | Wedge shaped infarct | |||||
| OBSTRUCTIVE UROPATHY | ||||||||
| Urolithiasis | 1) 5-10% of ameicans, 2) 20-30yo, 3) heriditary associated w/ gout, cystinuria, and primary hyperoxaluria, 4) 70% calcium oxalate and phosphate; 15-20% Magnesium ammonium phosphate; 5-10% Uric acid | 1) Calcium oxalate stones (hyperparathyroidism, diffuse bone disease, sarcoidosis), 2) Magnesium ammonium phosphate (post urea-splitting bacterial infection such as proteus which produce ammonia from urea; large stones - staghorn caculi b/c shape of pelvis; precipiate due to pH drop), 3) uric acid (gout, leukemias) | Note: urinary tract obstruction incrases susceptibility to infection and stone formation leading to permanent renal atrophy and irreversible obsruction. Only some causes are surgically correctable | |||||
| Hydronephrosis | Outflow obstruction results in dilation of renal pelvis and calyces with interstital inflammation leading to fibrosis | 1) kidney becomes enlarged with blunting of pyramids and thinnngof cortex. The ureters may also be dialted | ||||||
| KIDNEY TUMORS | ||||||||
| Renal Cell Carcinoma | 1) Malignant (85-90% of all renal malignancies), 2) 60-70s, 3) cigarette smoker, 4) 95% is sporadic (not familiial) | arise from tubular cells - adenocarcinoma | Classification: 70-80% clear cell tye; 10-15% papillary type; 5% chromophobe; 1% collecting duct carcinoma | Clear cell RCC: cytoplasm filled with glycogen ad lipid thus appearing clear | 1) large spherical masses, yellow-gray-white w/ focal hemorrhage, 2) may invade the renal vein or extend up into the heart (IVC) | histo: Papilary growth | histo: Collecting duct carcinoma - look more anaplastic and large forming glands | histo: chromophobe type - cells with prominent cell membranes, pale eosinophilic cytoplas with a halo around nucleus |
| von Hipel-Lindau syndrome | 1) familial RCC, 2) | Hemangioblastomas of CNS and retina , 2) bilateral and mucltiple RCCs | ||||||
| Urothelial carcinoma of renal pelvis | originates from urotelium or renal pelvis and may block urinary outflow | Papillae lined by malignant urothelium | ||||||
| Wilms Tumor | 1) Most common pediatric renal tumor(except during 1st 3 mo), 2) Peak incidence 2-5yo w/ 400/yr | 1) WAGR ( Wilms, Aniridia, Genital anomalies, Retardation), 2) Beckwith-Wiedemann syndrome (increased risk of Wilm's tumor) | Favorable: lacks anaplasia | Triphasic histology: 1) Blastemal (primitive oval cells w/o differentiation-right), 2) Stromal (immature spindles to diverse tissues like muscle, adipose, bone - center), 3) Epithelial (tubule forming - lower center) | Soft, friable mass often with necrosis and hemorrage | Unfavorable histo: anaplasia (enlarged hyperchromatic nuclei, mitotic figures) - very rare (25/yr in US) | ||
| Mesoblastic Nephroma | 1) Almost all occur in 1st year of life and diganosed in 3 mo, 2) 2-3% of ped. Renal tumors w/ 25/yr | 1) t(12;15) ETV6-NTRK3 translocation (cellular shares w/ infantile fibrosarcoma), 2) There are both cellular (majority) and classic histological pattern | Fetal ultrasound | Classic pattern: Bland spindled cells with low density and tongues of tumor infiltrating the renal sinus parenchyma | Unicentric, usually arises near renal sinus; may be firm and whorled | Resection is usually curative w/ 5% relapse or metastasis rate | Cellular pattern: densely packed spindle cells with high mitotic activity | |
| Clear cell sarcoma (kidney) | 1) 2-3yo peak incidence, 2) 4-5% ped ren tumors, 3) metastasis common (bone, brain, soft tissue) | monomorphous polygonal cells lacking distinct borders | Unicentric, with distinct tumor/kidney junction, glistening, gelatinous surface | |||||
| Rhabdoid tumor (kidney) | 1) Infants (median age 13mo), 2) rare (2% ped ren tum), 3) very malignant (75% dies w/in 1st yr), 4) 15% have concurrent midline brain tumor | 1) there is an association wth the loss of INI1 gene exrpession, 2) may have hypercalcemia with excess PTH or PGE2 secretion | tumor cells are large, round, polygonal with pink cytoplasm containing rhabdoid inclusions (characteristic) | |||||
| Childhood Renal cell carcinoma | 1) Rare, 2) similar to adult type | Xp11.2 renal carcinoma translocation | ||||||
| URETER | ||||||||
| Ureter: Congenital Anomalies | doublle ureters: no clinical significance | Ureteropelvic junction (UPJ) obstruction: most common cause of hydronephrosis in infants and children | Diverticula: sacular outpouching of ureteral wall due to infections or calculi b/c of urine collection for a time | Hydroureter or megaloureter: dilated ureter (either congeital or acquired) | ||||
| Idiopathic retroperitoneal fibrosis | Rare obstructive disease | Dense stromal fibrosis that entraps retroperitoneal sructures (ureter) and causes hydronephrosis. Uknown etiology (Ormond disease - no associated tumor) | Dense fibrosis and chronic inflammation | |||||
| BLADDER | ||||||||
| Bladder diverticula | 1) most are asymptomatic, 2) may be a source of infection or calculi (stasis), 3) rarely cause carcinomas | 1) Congenital (musculature defect) or acquired (benign prostatic hyperplasia), | ||||||
| Bladder exstrophy | Long term effects include colonic metaplasia, risk of adenocarcinoma. | Defect in the anterior ab wall and blader allows bladder to communicate with body surface | Surgery | |||||
| Vesicoureteral reflux | 1) Renal infection and scarring risk | |||||||
| Cystitis | 1) Bacteria (EC, proteus, klebsiella, enterobacter), 2) parasitic (Schistosoma predisposes to SCC) | |||||||
| Hemorrhagic cystitis | bloody urine due to either chemotherapy (cyclophosphamide) and radiation | |||||||
| Intersitial cystits | women | chronic cystitis w/ an unknown etiology | ||||||
| Malcoplakia | commonly associated w/ chronic EC | Histocytic (foamy mac) accumulation w/ impaired intraphagosomal digestion (undigested bacterial products) | sheets of histiocytes (Von Hansemann cells) w/ classic inclusions (Michaelis-Gutmann Bodies) (diagnostic)[2] | |||||
| Metaplastic lesions of bladder | Von Brunn nests (transitional epithelium grows into lamina propria) | Cystitis Cystica (transitional epithelium transform into cystic space lined by urothelium) | Cystitis cystica glandularis (transitional epithelium transform into columnar epithelium) | Cystitis cystica glandularis with intestinal metaplasia (risk for adenocarcinoma) | ||||
| Nephrogenic metaplasia (adenoma) | benign proliferative lesion due to urothelium injury | mixed papillary and tubular morphology. Fingers lined by single layer of small cells. Underneath there are tubules lines by epithelial cells. | ||||||
| Papillary Urothelial neoplasm | compare w/ adenoma; multple cells layers | nephrogenic adenoma (comparison) | ||||||
| Bladder: obstruction | Causes: BPH, cystocele (herniated bladder), narrowing of urethra (stricture, tumor), innervation injury (neruogenic bladder) | We may see post-obstructive hypertrophy trabeculation of bladder due to BPH | ||||||
| URETHRA | ||||||||
| Urethra | Urethritis: Gonococcal or EC, chlamydia, and mycoplasma | Reiter syndrome (arthritis, conjunctivitis, urethritis) | Tumor-like: Urethral caruncle (reactive inflammatory lesion at the urethral meatus seen more commonly in female adults; histo- mixture of inflammtory cells and ulcerated epithelium | |||||
| Urotheiial carcinoma in-situ | 1) precusor to invasive carcinoma | flat urothelium colonized by neoplastic cells w/ marked nuclear pleomorphism and hyperchromasia (nay or may not have architectural disorder or obvios mitosis) | histo: normal urothelium | |||||
| BLADDER TUMOR | ||||||||
| Urothelial Papilloma | Urothelial Carcinoma 1) more common in younger px than other urothelial tumors, 2) M>F 50-80yo, 2) Risk factors (Smoking, industrial arylamines, LT analgesics & cyclophosphamide, radiation), 3) survival depends on stage | papillary tumor lined by normal urothelium | Staging: non-invasive = pT0 | papillae lined by normal urothelium | ||||
| Papillary Urothelial Neoplasm of Uncertain Malignant Potential (PUNLMP) | lined by hyperplastic urothelium | papillary tumor lined by hyperplastic (tall) urothelium | ||||||
| Papillary urotheilal carcinoma (low grade) | disorganized urotheilum that does not show the marked nuclear changes of carcinoma in-situ | papillary tumor lined by disorganized urothelium | ||||||
| Papillary Urotheilal carcinoma (high grade) | tumor lined cells with hyperplastic nucear changes | Invasion of lamina propria (pT1) and invasion of mucularis propria (pT2) | papillary tumor lined by disorganized urothelium with mitosis | we see nests invading the lamina propria | histo: carcinoma invaded M propria | cystectomy | ||
| Sqamous cell carcinoma | 1) 3-7% US bladder cancer, 2) Risk factors: schistosomiasis, keratinizing squamous metaplasia, & squamous dysplasia, 3) poor response to chemo and XRT | Chronic bladder irritation and infection. 2) Can be both pure SCC (no urothelia) or mixed (urothelial + SCC) which is much more common | histo: Squamous dysplasia | Pure SCC: Squamous neoplasia with squamous pearls and intercellular bridges | Histo: squamous keratinzing metaplasia | Invasive fungating tumors | ||
| Pure Adenocarcinoma (bladder) | 1) rare, 2) signet-ring cell carcinoma & mixed adenocarcinoma are highly malignant | 1) invasive gland forming neoplasm, 2) arise from the wall rather than mucosal and extend toward umbilicus | Primary vesical adenocarcinoma | Primary signet ring adenocarcinoma | ||||
| Sarcomatoid carcinoma | 1) The can make any CT cell, 2) very dim prognosis | De-differentiation of a carcinoma into a neoplasm resembling a sarcoma | Urothelial cells become spindled cells which are pleomorphic and hyperchromatic | |||||
| Leiomyoma[3] | 1) Adult, 2) Sx: Hematuria and bladder mass | Benign smooth muscle neoplasm | fascicles look like school of fish swimmin in same direction | |||||
| Leiomyosarcoma | 1) Adult, 2) Sx: hematuria, bladder mass, lung metastases | Malignant smooth muscle neoplasm | Pleomorphic cells (diagnostic) | |||||
| Rhabdomyosarcoma (embryonal) | 1) most common bladder tumor in children, 2) may bulge out urethra, 3) excellent prognosis | Botryoid type: associated with mucosal surface with subepithelial condensation of tumor cells (cambium layer) | Immunohistochemistry - Desmin (muscle origin) and confirmation w/ myogenin or MyoD-1 | Botryoid Rhabdomyosarcoma: Cambium layer of pleomorphic cells | Fungating polypoid bladder mass | Chemotherapy (curable) | ||
| Inflammatory Myofibroblastic tumor | 1) Any age, 2) Anaplastic lymphoma kinase (ALK) translocation, 3) benign, locally recurring | Mural based bladder mass may occur following a transurethral procedure | sm with mixoid (blue) b/w muscle cells | partial cystectomy (not metastatic, but recurring) | ||||
| Fibroepithelial polyp (bladder) | 1) children and adolescents more common, 2) Sx: hematuria, 3) benign, non-recurring | Borad papillae which looks like a leaf | ||||||
| Urothelial neoplasms (urethra) | 1) proximal urethra | Papillary proximal | classification identical to urinary bladder | |||||
| Squamous neoplasms (urethra) | 1) distal urethra | Squamous distal | classification identical to urinary bladder | |||||
| INFECTIONS | ||||||||
| Herpes | 1) HSV1/2, 2) 60 mil americans, | 1) acute infection followed by latency (LATs) and recurrent infections, 2) gingivostomatitis (HSV1), 3) HSV2 transmitted during birth, 4) corneal lesions and encephalitis | histo: intranuclear inclusions | 1) Cowdry type A (multinucleated giant cells) | ||||
| Syphilis | 1) Primary (3 weeks): firm non-tender chancre, 2) Secondary (2-10wks post primary): rash on palms, soles, and white oral lesions w/ lymphadenopathy, fever, arthritis, 3) tertiary: aortic aneurysm (scarring of tunica media), neurosyphilis (meingovascular, tabes dorsalis, paresis), gummas, 4) congenital: Hutchinsons triad (interstitial keratitis, 8th CN deafness, teeth) | 1) silver stain, dark field examination and by IF, 2) Non-treponmenal (VDRL) - neg in early phase, 3) Direct (ab against T. pallidum, FTA-ABS, microhemaggulination assay); Indirect (Ab to cardiolipin - VDRL (15% false pos. during acute, lupus, drug addiciton, pregnancy, HIV), rapid plasma reagin) | 1) obliterative endarthritis (plasma cell rich mononuclear infiltrate) | |||||
| Chlamydia | Infections: Veneral urethritis, Lymphogranuloma venereum (endimic in asia, africa, caribbean, & South Am.), trachoma, inclusion conjunctivitis, and reiter syndrome | Serology (serotype D-K) | ||||||
| Gonorrhea | 1) 700,000 cases/yr US, | 1) protease cleaves IgA, 2) Can cause urethritis, proctitis, and pharyngitis w/ purulent exudate and granulation tissue formation, 3) inflammatory process may cause urthral stricture and insterility in men and tubo-ovarian abscess and acute peritonitis in women , 4) Urethritis - peptidoglycan & endotoxin induce TNF-alpha causing shock and multiorgan failure, 5) pelvic inflammatory disease | ||||||
| Chancroid (soft chancre) | 1) Hemophilus ducreyi | An acute ulcerative infection causing painful irregular ulcers which are not indurated and which may lead to enlarged lymph nodes which erode the skin | ||||||
| Human papilloma virus | 1) 1mill/yr infected, 2) High risk for cervical cancer= 16, 18, 31, 33 | |||||||
| Trichomoniasis | 1) 3mil/yr infected | Anaerobic flagellated protozoan infection may be asymptomatic or cause itching with profuse vaginal discharge, polyuria, dysuria, mucosal reddening and edema (fishy smell) | ||||||
| OVARIES | ||||||||
| Follicle and Luteal cysts of ovaries | 1) very common, 2) usually small and occasionally rupture causing pain and intraperitoneal bleeding, 3) Corpus luteal cyst common in 1st trimester | 1) Follcle cyst: Originate in follicles and are lined by granulosa cells (produce estrogen) with transparent membrane, | Luteal cyst:: corpus luteal cyst lined by fat with large cell and abundant cytoplasm (produce progesterone) | |||||
| Polycystic (sclerocystic) ovaries : Stein-leventhal syndrome | 1) 3-6% rep. age women, 2)chronic anovulation, 3) obesity, DM II, hirsutism, and rarely virilism | Ovaris have multiple follicular cysts (estrogen producing granulosa cells) resultin in continued endometrial proliferation and anovulation. However, follicles continue to grow so ovarian hypertrophy results. Also abnormal androgen synth = hirsutism and virilism | ultrasound | lots of cysts | ||||
| Stromal hyperthecosis | 1) postmenopause | stomal hypertheosis w/ elevated estrogen = endometrial hyperplasia = increase adenocarcinoma risk | ||||||
| Serous Tumors (ovary) | 1) Single most comon group of ovarian tumor, 2) benign & borderline (60%, 20-50yo; 100% @ 5yr), malignant (25/%, 40-60yo, 70% @ 5yr), 3) size = 5-40cm, 4) bilateral, 5) CA 125, 6) peritoneal seeding (1st step to malig) | Borderline: papillae on surface are characterized by papillary tufting w/o stroma invasion but with ab adhesions and multicentric growth which accounts for morbidity and mortality | Malignant (serous cystadenocarcinoma): shed cells which implant on peritoneal surface and produce ascites (borderline can do this also) & they invade stroma and metastasize | Uni/multilocular containing serous fluid. Benign shows smooth glistening surface, but malignant is multinodular | ||||
| Mucinous tumors | 1) 30-50yo, 2) Most common tumor during pregnancy (besides corpus luteum cyst), 3) most often associated w/ acute ab due to torsion, 4) unilateral, 80% benign, 5) 5% pseudomyxoma pertonei (glue organs) | Large multiloculated mucinous tumors with endocervix or intestine-like lining cells. Spillin of mucin into cavity mats the viscera together (pseudomyxoma peritonei) requiring repeated surgeries | Benign: multilocular (cyst inside a cyst) intestinal type (goblet-like cells) with a "single" layer of epithelial | Low malignant potential: looks very angry with multiple layers of epithelium but not invasive | multilocular | Mucinous Carcinoma: Destructive stromal invasion | ||
| Endometroid tumors | 1) the benign are usually unilateral in elderly (> 57yo), 2) second most common ovarian epithelial malignancy (behind serous), 3) leading mortality rate in female GU (late diagnosis & tx), 4) CA 125, 5) peritoneal seeding (1st step to malig) | |||||||
| Endometroid adenocarcinoma (ovary) | 1) 50-60yo, 2) Can arise from enometriotic cyst in young women, 3) stage I: 75% @ 5yr | endometriosis px are at risk (15% associated w/ similar endometrial lesion) | ||||||
| Clear cell tumor | 1) benign (rare), low malignant potential (rare), malignant(assd w/ endometriosis, endometriod adenocarcinoma, hypercalcemia) | Carcinoma: very aggressive | carcinoma (board): nucleus comes to surface and cytoplasm becomes clear (big head and thin body) | solid with areas of hemorrhage and necrosis | ||||
| Brenner tumor | 1) 95% diagnosed b/w 30-70yo, 2) unilateral and benign, 3) found incidentaly | islands of tumor cells w/ a background of fibrosis | ||||||
| Mature Cystic Teratoma | 1) Most common germ cell tumor, 2) benign, 3) 10% bilateral, 4) young women (late 20s) w/ asx ovarian mass, 5) 15% torsion, 6) 1% squamous cell carc. Transformation | cysts lined by epidermis with tissue formation from bone, cartilage, thyroid, tooth, bronchi, gut, brain, ect. | Hair, teeth, and opened cystic structure | |||||
| Immature teratoma | immature neural elements w/ neuroepithelila tubules | large solid or partially cystic masses (resemble brain tissue) | ||||||
| Specialized teratoma | 1) struma ovarii can cause hyperthyroidism | Thyroid follicles produce thyroid hormone hence the hyperthyroidism | thyroid follicles | |||||
| Dysgerminoma | 1) 20-30yo, 2) almost all unilateral, 3) malignant but only 1/3 aggressive and spread, 4) radiosensiive w/ 80% cure, 5) phen femal w/ gonadal dysgenesis, 6) Most common malignant germ cell tumor (but only 2% all ovarian tumors) | Sheets and cords of large cleared cells separated by scant fibrous strands. Lymphocytes in stroma and central located nuclei (polygonal) | solid small or large gray mass | |||||
| Endodermal Sinus Tumor (Yolk Sac Tumor) | 1) young adults, 2) aggressive, 3) survival: stage I (70-90%), higher stage (30-50%), 4) AFP, 5) 2nd most common malignant germ cell tumor | fibroblast core with schiller duval bodies | ||||||
| Fibroma | 1) any age, 2) unilarteral, 3) rarely malignant | They are te only stromal tumor which is hormonally inactive. Meigs syndrome is hydrothorax and ascites w/ fibroma | pink cytoplsm | |||||
| Thecoma | 1) any age, 2) unilarteral, 3) rarely malignant | Theca cell origin results in occasional estrogen secretion resulting in hirsutism and hyperplasia of endometrium (adenoma risk) | ||||||
| Granulosa cell tumor | 1) any age, 2) adult and juvenille form, 2) 5-25% adult form malignant, 3) juvenille benign w/ good prognosis, 4) Inhibin | Granulosa cells convert testosterone (from theca) to estrogen. Juvenille form (young child) presents w/ precociuos puberty. Adult shows endometrial hypeplasia w/ adenoma risk. | histo: diffuse patttern w/ elongated nuclear grooves | cystic structure resembling graffian follicle (Exner bodie) | <--- Call-Exner bodies | |||
| Sertoli Leydig Cell Tumor | 1) any age, 2) unilateral, small, 3) few malignant | Leydig cells produce androgens resulting in virilization. | Crystals of Reinke----------------> | Tubuli w/ cords and plump pink leydig cells w/ "Crystals of Reinke" (diagnostic) | Gray to yellow brown (due to high lipid content) | |||
| Krukenberg tumor | 1) 5% ovarian tumors | Stomach adenocarcinoma metastisizing to ovary replacing them bilaterally | Signet Ring ---> | Characterized by signet ring mucin producing cells | ||||
| Metastasis | Breast, lung, GI most common | |||||||
| PENIS | ||||||||
| Hypospadias | Urethra on ventral surface, may cause stricture, urinary stasis and infection | |||||||
| Epispadias | urthera on dorsal surface | |||||||
| Phimosis | 1) cogenital or due to repeated infection of scarring | foreskin too small to permit normal retraction | ||||||
| Parphimosis | phimosis w/ foreced retraction with swelling and edema | |||||||
| TESTICULAR | ||||||||
| Cryptorchidism | 1) Associated withTesticular atropy and sterility with a risk of carcinoma development (seminoma and embryonal carcinoma), 2) 75% unilateral, 3) correct by 2 yo b/c irreversible changes | 1) Undescended testes, 2) most inguinal cryptorchid testes descend spontaneously during first year of life, if not surgically corrected | ||||||
| Testicular Atrohy | regressive testicular change characterized by loss of spermatogenesis and gradual fibrosis, Leydig cels appear prominent | |||||||
| Non-specific epididymtis and orchitis | 1) children: GU abnormality w/ gram neg rods, 2) Sexually active men less than 35 = chlamydia or neisseria, 3) men older than 35 = EC & pseudomonas | Bilateral orchitis is most commonly Mumps. Sterility may result from atrophy of the seminiferous tubules b/c testosterone is decreased (FSH & LH increased) | Epididymitis is more common than orchitis and is casued by gonococcus, chlamydia, EC, and TB. | |||||
| Granulomatous (autoimmune) orchitis | 1) rare cause of testicular enlargement in middle aged men, 2) granulomas w/in seminiferous tubules | autoimmune | ||||||
| Gonorrhea | 1) usually non-treated disease | Extensio proceeds from urethra to prostate to seminal vesicle to epididymis progressing to involve testicle | ||||||
| Mumps | 1) systemic viral disease of school aged children, 2) 20-30% develop acute interstitial bilateral orchitis 1 wk after parotid swellin | |||||||
| TB | Begins in epididymis, but spreads to testis, due to secondary spread from prostate and seminal vesicles forming caseating granulomas. | caseating granulomas in epidydymis | ||||||
| Syphillis | 1) Testis involved before the epididymis | may damage the vessels (obliterative arteritis) | central lumen w/ plasma and lymphocytes around the vessel and invaded into lumen | |||||
| Testicular torsion | 1) 6hr = dead, so med emergency, 2) | twisting of the spermatic cord obstructing blood supply. Adult are due to anatomic defect allowing increased mobility. | ||||||
| Intrascrotal cysts | 1) hydrocele is the most common tunica vaginalis cysts (clear fluid), 2) spermatocele is most common in epididymis | |||||||
| Germ cell tumors | 1) most common in 15-34 yo, 2) excellent prognsosis w/ CURE via chemo (cisplatin), 3) RF: cryptorchidism (10%), testicular dysgenesis, 4) Genetic: i(12p) in all germ cell tumors, 5) most are malignant and 90% of testicular cancers are germ cell | 1) testicular mass, 2) Lymphatic mets most common w/ 1st (para-aortic retroperitoneal nodes) & 2nd (mediastinal and supraclavicular), 3) hematogenous most commonly to lungs, 4) >50% germ cell tumor are mixed (teratoma, embryonal, yolk sac, seminoma) | Classification: 1) Pure Seminoma, 2) Non-Seminoma: embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, 3) Spermatocytic seminoma, 2) Staging: stage I (confined), stage II (retroperitoneal below diaphragm), stage III (supradiaphragmatic nodes) | 1) Pure seminoma: radiation sensitive w/ 95% cure (least aggressive), 2) Non-seminoma: spread common, but high cure rate with cisplatin chemo or RPLND, 3) Spermatocytic seminoma: 100% cure w/ resection w/ no adjuvant (not mets) | ||||
| Intratubular Germ Cell Neoplasia (ITGCN) | Precursor to germ cell tumors in adults (not child, not spermatic seminoma) | Giant cells w/ abundant cytoplasm and hyperchromatic nuclei | ||||||
| Seminoma | 1) Most common subtype (40%), 2) B-hCG, 3) almost never in infants, usually mid-30s age group | Malignant germ cell tumor (analogous to dygerminoma in ovary) | Painless enlargement of testis | Sheets of cell w/ blood vessels forming septae b/w packets of cells. Perivascular lymphocytes & cells w/ central nucleus and abundant cytoplasm | Radiosensitive (often cured even w/ lymph mets) | |||
| Yolk sac tumor (endodermal sinus tumor) | 1) most common subtype in infants to 3yo, 2) Infants typically pure yolk sac w/ exc prog, 3) Adults typically admixed w/ embryonal carcinoma, 4) AFP | Malignant germ cell tumor (analogous to endodermal sinus tumor of ovary) | Central blood vessel with a ring of neoplstic cells around it (Schiller-Duval body) | Cisplatin sensitive (high cure rate) | ||||
| Embryonal carcinoma | 1) 2nd most common GCT (20-30%), 2) 20-30yo, 3) Adults often admixed w/ yolk sac tumor, 4) B-hCG, | Malignant germ cell tumor | Presents often with pain and metastasis, with worse prognosis than seminoma | pleomorphic cells and macronuclei w/ unclear borders (syncytium) | histo: commonly invades vascular | Cisplatin sensitive (high cure rate) | ||
| Choriocarcinoma | 1) Most aggressive subtype, w/ widespread hematogenous spread common and poor prognosis, 2) very rare, 3) B-hCG | Malignant germ cell tumor | Hyperchromatic syncytiotrophoblasts wrapped around cytotrophoblasts | Cisplatin sensitive (high cure rate) | ||||
| Testicular teratoma | 1) biologically distinct from ovarian teratoma, 2) no serum markers | mixture of tissue from any germ layer forming many tissues (gut, skin, cartilage, fat) | Prepubertal = benign; Post-pubertal = malignant | histo: skin and sebaceous | Histo: cartilage | Histo: intestinal | Cisplatin sensitive (high cure rate) | |
| Spermatocytic Seminoma | 1) >65yo, 2) Seum marker negative | 3 cell types: 1) Giant cell (characteristic), 2) intermediate, 3) lymphocyte-like | Orchiectomy (excellent prognosis w/ no adjuvant therapy or metastatic risk) | |||||
| Leydig cell (interstitial) tumor | 1) wide age range (20-60yo), 2) mass lesion or hormonal sx (gynecomastia), 3) most benign (10% malignant) | Testicular tumor derived from sex cord stroma | Typcially produces androgens but may produce estrogen & corticosteroids. Assd w/ precocious puberty and gynecomastia | PINK cytoplasm w/ crystals of Reinke (characteristic) | ||||
| Sertoli cell (Androblastoma) | cells form tubules which interconnect and branch | |||||||
| Lymphoma (testis) | 1) Most common testicular tumor in men >60yo, 2) extremely poor prognosis | Sx: testicular mass | ||||||
| Paratesticular | Lipoma (adult): very common spermatic cord benign fatty tumor | Adenoid tumor (adult): Benign mesothelial tumor of tunica vaginalis | Rhabdomyosarcoma (children): malignant skeletal musle tumor | Well-defined liposarcoma/atypical lipomatous tumor (adult): fatty tumor w/ high ris of local recurrence | ||||
| PENIS | ||||||||
| Conyloma acuminata | 1) HPV 6 & 11, 2) high risk of recurrence | Can be either Squamous cell carcinoma in-situ or invasive SCC (usual or verrucous) | We see polypoid papillary pattern at low mag and koilocytes at high mag | |||||
| Squamous cell carcinoma In-situ | 1) HPV 16 (80%), 2) invasive carcinoma precursor | LP: no invasion w/ pleomorphic dark cells w/ mitotic figures | ||||||
| Verucous type invasive SCC | 1) NOT HPV related, 2) median = 60yo, 3) excellent prognosis | Prognosis: There is a risk of recurrence and lymph node mets. Stage determines prognosis. | Border drops down into tissue but not islands or invasion w/ normal cells morphology | Superficial surface is warty | Base is sharp | |||
| Usual invasive Squamous cell carcinoma | 1) uncommon in US, but high prev in S. Am, asia, africa, 2) HPV 16 & 18, 3) smoking and uncircumcision risk factors | Metastases typically to inguinal or iliac lymph nodes | Prognosis: no metastatic potential and recurrence occurs only if incompletely excised. Excellent prognosis | invasive | ||||
| PROSTATE | ||||||||
| Benign Prostatic Hyperplasia | 1) common in men over 50yo, 2) 30% of white US males over 50, 3) Not risk factor for prostate cancer (but may coexist) | 1) Hyperplasia of prostatic glands and stroma in periurethral region (transitional zone), 2) age-related estrogen increase = DHT receptor expression, 3) Dihydrotestosterone (DHT) is mediator of prostate growth and is formed from testosterone by 5a-reductase (type 2)., 4) note that testosterone is decreased but sensitivity increased | 1) Sx: difficulty urinating, double-void, hesitancy, bladder hypertrophy (trabeculations), cystitis, kidney injury (hydroureter & hydronephrosis), 2) Increased total PSA with increased fraction of free PSA | 1) Nodules of proliferating stroma, 2) Stroma background w/ proliferation of basal cells (dark) surrounded by secretory cells (pink) | post-obstructive hypertrophy and trabeculation of bladder | 1) hormonal manipulation, 2) Transurethral resection of prostate (TURP) | ||
| Prostatic Adenocarcinoma | 1) Most common cancer in men, 2) >50yo, 3) 70% prevalence in 70-80yo, 3) Prognosis: >90% live 15yrs, 4) peripheral zone most common w/ >90% acinar, 5) osteoblastic mets (vert) 95% of time, 6) increased total PSA with decreased fraction of free PSA[4] | In acinar adenocarcinoma we see small, round glands without a basal layer (promininent nucleoli + intraluminal mucin & crystalloids) that usually infiltrates normal prostatic tissue with possible perineural invasion. | Histo: Too small and too crowded glands (buzzwords) | Lack basal cell layer (see only one cell layer). Normal has multiple layers. | Gland fusion | perineural invasion | Cytokeratin: stains basal cell layer (absent in adenocarcinoma) | |
| High-Grade Prostatic Intraepithelial Neoplasia | 1) adjacent to cancer in 80% cases, 2) Adenocarcinoma precursor | We see nuclear features of cancer (nucleomegaly, nucleoli) with normal size gland with at least a patchy basal layer | dark neuclei | |||||
| Gleason Grading | Basis: gland architecture | Stage 1&2: Well delineated (not infiltrative) in transition zone | Stage 3: Single infiltrate glands in peripheral zone | Stage 4: Fused glands (Spiderweb) with central spaces in peripheral zone | Stage 5: sheets of cells without lumen in peripheral zone | Score = primary pattern (most common) + Secondary pattern (second most common) | High risk of recurrence & metastasis: high gleasson (7-10), extraprostatic extension, and total volume of cancer | |
| VULVA | ||||||||
| Vulvar dystrophies | 2 histologic forms: 1) Lichen sclerosis and hyperplastic dystrophy (not malignant potential), 2) atypical hyperplastic dystrophy (pre-malignant) | 1) Disorder of epithelial growth presenting with leukoplakia and pruritis | ||||||
| Lichen Sclerosis | 1) Postmenopausal women, 2) painful intercourse | hyperplastic dystrophy with no malignant potential | Thinned epi hyperkeratosis, dermal fibrosis and band like superficial peivascular mono infiltration | |||||
| Lichen Simplex chronicus | 1) not a cancer precursor | Squamous hyperplasia secondary to chronic pruritis | 1) thickended ep w/ hyperkeratosis, 2) mono dermal inflammation, 3) mitotic activity, 4) leukocyte infiltration in dermis | |||||
| Condylomas | 1) condyloma accuminata: HPV 6 & 11, rarely progress to cancer | 1) condyloma lata: flat mooist minimmally invasive due to secondary syphillis, 2) Condyloma accuminataum: HPV related w/ a warty elevated appearance | Parakeratosis (nuclei) with papillary architecture. Koilocytes (infected epi, enlarged darkened nuclei, perinuclear halo) | anywhere in the anogenital region | ||||
| High Grade Vulvar Intraepithelial Neoplasia | Most common malignant tumor of vulva. HPV: 1) 3% of all female genital cancers, 2) >60yo, 3) 90% are SCC (HPV 16) and 10% adenocarcinoma (HPV 18); NON-HPV: older women, not HPV | 1) HPV related: HPV 16 & 18 (75-90%), can have both cervical and vulvar tumors at same time, there is also separate foci with different stages, 2) NON-HPV: more uniform, unifocl | VIN III: all the cells look the same with no maturation as they come to surface, very little cytoplasm with full thickness dysplasia (carcinoma in-situ) | HPV: 1) dysplasia (nuclear atypia, increased mitosis, loss of diff), 2) high grade…..; non-HPV: 1) well differentiated (keratinized cytoplasm and keratin pearls) | Invasive carcinoma: Bluer | non-HPV VIN: | non-HPV keratinizing invasive carcinoma: keratin w/ pearls | |
| Vulvar Carcinoma | Initially high grade VIN (leukoplakia-type lesion) which progresses to overt exophytic or endophytic lesion | HPV: poorly differentiated, non-HPV: differentiated (keratinized) | HPV: multifocal, warty appearance; non-HPV: unifocal | |||||
| Paget's Disease | 1) PAS pos, 2) S-100 neg, , 3) may invade locally and metastasize | Adenocarcinoma in single cells along the epidermis either singly or in clusters. | very similar to melanoma. There is carcinomatous cells w/ a lot of cytoplasm with more central nuclei w/ clear halos. Must PAS stain. | solitary or multiple well demarcated foci of red crusted areas | ||||
| Vulvar Melanoma | 1) 3-5% of vulvar malignancies, 2) metastasizes very early, 3) PAS neg and S-100 pos., 4) 5yr @ 32%, 5) prognosis = depth of invasion (lymphatic access) | big nests of cells with some have pigment. We can see them along the dermal/epidermal jnct. | Dark discoloration of vulva | |||||
| VAGINA | ||||||||
| Vaginal Intepithelial neoplasia (VAIN) | 1) uncommon, 2) elderly females (>60),3) concurrent cerviacl or vulvar neoplasia | VAIN 1: Low grad squamous intraepithelial lesion with Koilocytes | ||||||
| Sarcoma Botryoides (embryonal rhabdomyosarcoma) | 1) ant wall of vagina, 2) infants under 5yo | small round blue cell tumor accompanied with strap cell (rhabdomyoblasts) | polypoid grape like mass | |||||
| Clear cell adenocarcinoma | 1) rare, 2) secondary to DES (diethylstilbestol) an estrogen analogue used for nausea (35-90% exposed develop precursor vaginal adenosis), 3) clear cell likelihood is low <0.14%) | |||||||
| CERVIX | ||||||||
| Normal cerival epithelium (eosinopilic, round nuclei) | Squamo/columnar jnct (transition zone) - most dysplasias arise here | |||||||
| Endocervical polyp | 1) 2-5% women (pretty common), 2) premenopausal/menopausal, 3) no malignant potential | 1) Inflammatory proliferations of cervical mucosae (not neoplasm) | papillary infolding | Smooth glistening w/ highly vascular | ||||
| Cervical intraepithelial Neoplasia (CIN) and Carcinoma | 1) most frequent cancer worldwide, 2) CIN w/ mean of 30 yo and invasive carcinoma of 45yo, 3) 50% of CIN 1 regress, 20% progess to CIN 2-3, 1-5% become invasive, 4) 75% of pop exposed, 50% exposed to high risk HPV, 10% high grade CIN, 1.3% invasive, 5) RF: other STD genital infections (chlamydia, gonorrhea), 6) HPV 16, 18, 31, 33 (high risk), 7) 5% HPV neg (cigarrete smoking, genetics, carcinogens) | 1) low grade (CIN 1) = koilocytosis, 2) high grade (CIN 2 = moderate dysplasia, CIN 3 = severe dysplasia and carcinoma in-situ), 2) E6 & E7 binds and degrades p53 (cell cycle) and RB (binds TF for proliferation) | CIN 1: koilocytes | CIN 1 PAP: koilocytes with an enlarged nucleus and cytoplasmic clearing around nucleus, may be multiple nuclei | HG: full thickness dysplasia, increase N:C ration, mitotic figure up to top | HG Pap: Nuclear membranes are irregular and crinkled, the nucleus is very dark (biopsy) | ||
| Invasive carcinoma | 1) SCC 75% with adeno 20%, 2) Small cell neuroendocrine is very poor prognosis, 3) Prognosis: 5yr survival, S0 (100%), S1 (80-, S2 (75%), S3 (35%), S4 (10%) | Tumors develop in the transformation zone | 1) PAP, 2) biopsy, 3) physical exam: non-mobile cervx, 4) STAGING: 0 (in situ), 1a (microinvase carcinoma), 1a2 (invasion of stroma >3<5mm), 1b (confined to cervix), 2 (beyond cervix, not into pelvis wall, upper 2/3 vagina), 3 (into pelvic wall, fixed cervix, lower 1/3 vagina), 4 (invasion beyond true pelvis, bladder, rectum, ?) | Keratin pearls, invasion | Pap: we see necrotic debris and inflammtory cells w/ an invasive cell having a large nuclei with spindle cytoplasm | Adeno: glandular with irregular patters | Small cell Neuroendocrine Ca: | Clear cell adenocarcinoma |
| UTERUS | ||||||||
| Dysfunctional Uterine Bleeding | 1) both ends of reproductive ife | 1) Anovulation: caused by polycystic ovaries, hypothalamic-pituitary axis, thyroid, adrenal dysfnct, ovarian tumor, malnutrition, obesity, & stress resulting in proliferation till collapse with spiral artery rupture and bleeding, 2) Inadequate luteal phase: failure 4 corpus luteum maturation or premature regression, 3) Contraceptives: E:P ratio imbalance, 4) Menopausal: anovulation w/ uninterrupted E, 5) Non-hormonal: chronic endometritis | anovulatory endometrium: Proliferative endometrium with compacted stroma and bleeding | |||||
| Endometritis | 1) Acute: rare | 1) Acute: typically bacterial occuring after parturition or miscarriage due to retained products of conception, 2) Chronic: multiple causes including chronic gonorrheal pelvic disease, TB, retained conception products, and IUD | Plasma cells (clock-face chromatin) and lymphocytes in stroma with irregular disposition and proliferation of endometrial glands and hemosiderin (abnormal bleeding) | |||||
| Endometriosis | 1) 10% of reproductive age women, 2) Pelvic area most common. locations: ovaries > uterine ligaments > rectovaginal septum > pouch of Douglas > laparotomy scars > fallopian tubes > cervix, 3) Complications: Fibrosis, adhesions, severe menstrual related pain, sterility | Endometriotic glands or stroma proliferating outside of uterus w/ 3 theories: 1) Regurgitation: menstrual through fallopian tubes w/ subsequent implantation, 2) Metaplastic: coelomic epithelium metaplasia, 3) Lymphovascular dissemination: spread through lymph | Patients may present only with infertility but may also present with dysmenorrhea, dyspareuria, and pelvic pain. Cyclic bleeding is a sign of functional endometrium. | 1) endometrial glands, 2) stroma, 3) hemosiderin deposition | Chocolate cysts | |||
| Adenomyosis | 1) Common (20% of uteri) | Endometrium (glands and stroma) grows into myometrial muscle (myometrium) presenting with meorrhagia, dysmenorrhea, and/or premenstrual pain | endometrial stroma and glands within myometrium | |||||
| Endometrial Polyps | 1) Most common around menopause (may occur at any age), 2) Benign lesion | 1) Polyps result in uterine bleeding, 2) monoclonality of stromal cells with chromosome 6p21 rearrangements | Thick walled vessel (diagnostic) -----> | Normally appearing columnar epithelium with diagnostic thick-walled vessels and cystically dilated glands | Flat and sessile or pedunculated lesions projecting into endometrial cavity | |||
| Endometrial Hyperplasia | 1) Postmenopausal bleeding (most common presenting sx), 2) Endometrial carcinoma precursor (Risk varies with degree of cellular atypia) | Hyper-estrogen due to multiple causes including failure of ovulation, obesity, ovarian tumor, granulosa-theca tumor, PTEN inactivation (assd hyperplasia & cancer) | 1) Simple (cystic) Hyperplasia, 2) Complex Hyperplasia without atypia, 3) Complex Hyperplasia with atypia | thickened endometrium | Simple (cystic) hyperplasia: cystic irregular shaped glands with stromal abundance and basal nuclei (no atypia) | Complex hyperplasia with atypia: complex = more glands than stroma, atypical = nuclei changes. Also see epithelial stratification (arrows) | ||
| Endometrial Carcinoma | 1) Most frequent cancer of the female genital tract in USA, 2) 55 to 65 yo, 3) RF: obesity (estrone in fat deposits), diabetes, HTN, anovulation | There is a background of endometrial hyperplasia resulting from: 1) Hyperestrinism: HRT, E secreting ovarian tumors, 2) Endometrioid type: most common type, microsatellite instability and mutations in PTEN gene (Chr 10), 3) Papillary serous: p53 mutations, spread through fallopian tube to peritoneum, 4) Clear cell. Metastasis either invasion of bladder/rectum, lymphatic (para-aortic nodes), or hematogenous (lung, liver), | 1) Clinical: leukorrhea and postmenopausal bleeding. Enlargement of uterus and fixation to surrounding structures., 2) GRADE: 1 (well diff), 2 (int. diff), 3 (solid or poor diff; papillary serous & clear cell automatic), 3) STAGE: I (corpus), II (cervical ext), III (extension out uterus, confined to pelvis), IV (outside pelvis, or bladder/rectum), 4) Prognosis (5 yr): I (90%), II (30-50%), III (<20%) | Endometrioid Adenocarcinoma: Lots of glands sometimes with cribiform (complex) pattern | Papillary serous carcinoma: More complex papillae. The nuclei are cleared | Clear cel carcinoma: big nucleus w/ nucleoli and clearing around nucleus | ||
| Carcinosarcoma (endometrial tumor) | 1) aka malignant mixed mullerian tumor (MMT) | Originally an epithelial cancer which differentiates to a stromal tumor. It has malignant glands and sarcoma. | pic | Fleshy, bulky,polypoid mass with extensive necrosis and hemorrhage | ||||
| Adenosarcoma (endometrial tumor) | Malignant stroma and benign endometrial glands | pic | large polypoid gorwth protruding through cervical os | |||||
| Stromal tumors (endometrial tumor) | Neoplasms of endometrial stromal cells w/ two types: 1) Benign Stromal nodule: circumscribed nodule of benign endometrial stromal cells, 2) Endometrial stromal sarcoma: malignant proliferation of stromal cells w/ atypia | endometrial stromal sarcoma | ||||||
| Leiomyoma | 1) 30-50% reproductive age women, 2) AA > white | Benign smooth muscle tumor whose growth is stimulated by estrogen and therefore involues after menopause. The tumor is monoclonal (40% chromosomal abnormal) | Interlacing smooth muscle cell bundles with foci of ischemic necrosis, fibrosis, hemorhage, and calcification | 1) clinical: asx but ma y present with bleeding or progression to sarcoma (very rare) | ||||
| Leiomyosarcoma | 1) 5 yr @ 40%, 2) recurrence and metastasis not uncommon | Usually solitary tumors derived from mesenchymal myometrial cells | Mitotic figures with a big bizzare atypical nuclei | 1) bulky masses infiltrarting uterine wall, 2) poypoid lesion projecting into uterine cavity | ||||
| PREGNANCY | ||||||||
| Spontaneous Abortion | 1) 10-15% pregnancies terminate in spontaneous abortion, 2) Chromosomal abnormalities most common 1st trimester abortion, 3) Hematogenous infection most common intrauterine demise in 2nd and 3rd trimester | Abortion can be due to both fetal and maternal. | Chromosomal studies in habitual abortion or malformed fetus | |||||
| Ectopic Pregnancy | 1) 1% of all pregnancies, 2) 90% in fallopian tube, 3) Predisposing factors: PID (35-50%), peritubal adhesions, endometriosis, leiomyoma, and previous surgery | Abnormal implantation of fertilized ovum (fallopian > ovary > abdominal cavity) with a risk of rupture resulting in acute abdomen (medical emergency) and hemorrhagic shock. | ||||||
| Placenta Accreta | 1) 60% associated with placenta previa which are associated w/ C-section scars | 1) Placenta accreta: partial or complete decidual abscense resulting in placental villi adherance to myometrium, 2) Placenta increta: extends into myometrium, 3) Placenta percreta - extends through wall of uterus | Post partum bleeding is due to failure of placental separation is often life threatening. | Placenta accreta: villi adhere to myometrium | ||||
| Twin-Twin transfusion | twins share umbilicus which results in both becoming malnurished | |||||||
| Ascending Placental infection | 1) most common cause of placental inflammation and infection, 2) assd w/ premature birth and rupture of the membrane, 3) most commonly beta hemolyti Streptococcus then mycoplasma and candida. | The infection ascends up the vagina and cervix to cause chorioamnionitis and funitis (umbilical infl) predisposing to premature rupture, neonatal pneumonia (swallow amniotic fluid), sepsis and meningitis | Histo: chorioamniotitis - inflammatory cell infiltrating the chorionic membrane | Funitis - inflammatory cell infiltrate into umbilicus | Dull looking placenta | normal placenta w/ glistening | ||
| Hematogenous Infection | 1) TORCH (toxoplasma, TB, o, rubella, CMV, HIV, Herpes) | Maternal bacteremia/viremia may cause vilitis with subsequent fetal infection which can affect multiple organs (specifically hematopoetic, lymphoid, and central nervous system) | Congenital CMV infection: IGR, jaundice (hepatomegaly), anemia (hemolysis), thrombocytopenia (spleenomegaly), encephalitis, and pneumonitis | CMV induced chronic villitis: see inclusions in villi | ||||
| Toxemia of Pregnancy | 1) 5-10% of pregnancies (especially 1st preg >35yo), 2) hydatidiform mole, kidney disease, or HTN predispose to earlier peeclampsia progression | Insidious onset beginning with HTN and edema with proteinuria several days later. Possibly due to inadequate maternal blood flow to placenta due to narrowing (musculoelastic wall retention) of uteroplacental spiral arteries which predisposes to placental ischemia (infarcts), HTN (dec. placental perfusion = incr. vasconstrictors {TXA, angII, endothelin} & dec. vasodilators {PGI2, PGE2, NO}), and DIC (eclampsia). Eclampsia develope seizure and lesions (liver, kidney, heart, placenta, brain) due to DIC. | Atheromatous changes of spiral arteries in superficial placenta | |||||
| Intrauterine Growth Restriction | 1) Birth weight below 10% average | Causes: Maternal vascular diseases (30%), Chromosomal abnormalities (20%), thrombolytic disorders, autoimmune, fetal infection, metabolic disorder | ||||||
| Complete Hydatidiform Mole | 1) 1/2000 pregnancies in US (more common in Asia), 2) More common before 20 and after age of 40, 3) 2% progress to choriocarcinoma | 1) Benign, non-invasive mole, 2) All chorionic villi are abnormal, 2) Chorionic epithelial cells are typically 46XX (2 sperm + Egg w/o DNA; 90%) and ucommonly 46XY (2S + 1E noDNA; 10%) | 1) Usually discovered in 4th month by ultrasound (snowflake patterns with cysts), 2) Markedly elevated HCG | swollen villi coverd by atypical chorionic epithelium | voluminous mass of swollen cystically dilated chorionic villi ("grape-like") | |||
| Partial Hydatidiform Mole | 1) Rarely progresses to choriocarcinoma | 1) Villous edema only is some villi with focal trophoblastic proliferation, 2) Always triploid 69XXY (2S + 1E (23X)), 3) Gestational trophoblastic disease (fetus or fetal parts w/ some normal villi) | 1) Serum HCG less elevated | |||||
| Invasive Hydatiform mole | Invasive mole invades uterine wall causing possible rupture. Villi may embolize but no metastatic potential. | Hysterectomy or chemotherpy | ||||||
| Choriocarcinoma (gestastional trophoblastic disease) | 1) Very aggressive malignant tumor, 2) 1/30,000 US pregnancies (1/2000 in asia and africa), 3) 50% follow complete molar pregnancy, 25% follow abortion, 25% normal pregnancy | Tumor arises from gestational chorionic epithelium (or totipotent stem cells in gonads) composed entirely of cytotrophoblasts and syncytiotrophoblasts with widespread hematogenous dissemination (lung = 50%, vagina = 30-40%, brain, liver, kidney) | 1) Bloody, brownish discharge, 2) rising Beta-HCG | Hemorrhagic necrotic masses within uterus | Chemotherapy (methotrexate) cures ~100% (except high risk metastatic) and cured px can have normal pregnancies | |||
| Placental Site Trophoblastic Tumor | 1) Uncommon, 2) Diploid, 3) Not sensitive to chemo | Benign tumor derived from intermediate trophoblastic cells which may occasionaly cause uterine rupture | 1) HCG only slightly elevated | Placental alkaline phospatase and cytokeratin | ||||
| BREAST | ||||||||
| Mastitis | 1) Most occur during lactation (1st month), 2) Staphlococcus aureua (most common) or streptococcus pyogenes | Breast is susceptible to bacterial infection early because of risk of cracks and fissures resulting in ductal spread. | Painful breast with fever | |||||
| Perioareolar abscess | 1) >90% smokers, 2) Anaeroboes | Squamous metaplasia blocks duct and keratin builds up resulting in an abscess that may rupture and cause inflammation. Fistula often presents b/w duct and skin. | Resection of duct and fistula is usually curative | |||||
| Fat Necrosis | 1) Trauma induced (surgery or radiation), 2) Painless superficial mass | Mass with calcifications that is composed of histiocytes, hemosiderin, and inflammatory cells | Easily confused with breast cancer on mammogram | |||||
| Silicon Implant | Compications: Induration of skin, draining sinuses, deformity, hard mass development, and migration to chest wall | Causes granulomatous inflammation and fibrosis which makes it hard to see cancer | ||||||
| Fibroadenoma | 1) Most common breast tumor in adolescent and youg adults, 2) Benign, 3) not a cancer precursor | The stromal cells are neoplastic and the ductal epithelial cellsrespond to hormones so the become larger during pregnancy | 1) Presents as a firm, rubbery, painless, well-circumscribed lesion, 2) Mammogram (indistiguishable from cyst), 3) Ultrasound (TOC) | 2 diff types: 1) Intracanalicular - Stroma compresses and distorts glands into slitlike spaces, 2) Pericanalicular - glands retain round shape | 1) Well demarcated mass with smooth contour, 2) Freely moveable, 3) Wider than tall (go w/ anatomic boundaries) | |||
| Duct Ectasia | 1) 25% have a palpable mass | Serous bloody or pus-like nipple discharge with common local pain and a periarolar abscess and fistual (acute inflammatory response) | ||||||
| Fibrocystic disease | 1) most common disorder of breast, 2) most common cause of palpable breast mass (20-50yo), 3) uncommon before adolescence and post-menopausal | MECH: Due either to increased estrogen sensitivity or decreased progesterone (hence bilateral midcyle tenderness); TYPES: Nonproliferative: (Fibrosis & blue dome cyst; no cancer risk), Proliferative: Epithelial changes (epithelial lining may be flattened, show apocrine metaplasia, or be hyperplastic w/ or w/o atypia; adenosis = small duct and myoepithelial cell proliferation; sclerosing adenosis = adenosis + fibrosis); Note: hyperplastic epithelium w/ atypia & sclerosing adenosis = cancer risk | Lumpy-bumpy breast with possible axillary lymphadenopathy and midcyle tenderness due to inflammation | Duct ectasia (due to chronic inflammation and fibrosis) and cyst formation lined by apocrine metaplasia. | Non-proliferative fibrocystic changes | Epithelial (ductal) hyperplasia. Note that the cells do not respect one anothers boundaries | Tx: Heat, good bra support, and evening primrose oil | |
| Intraductal Papilloma | 1) Benign tumor of major lactiferous ducts (central breast), 2) Most common cause of bloody nipple discharge | Must distinguish from carcinoma | central fibrovascular core extends from ducal wall and papillae arborize within the lumen. Lined by myoepithelial and luminal cells | |||||
| Lobular carcinoma in situ | 1) Increases risk of invasive cancer, 2) often bilateral | Atypical lobular epithelial hyperplasia | Noeplastic cells fill and expand lobule, but the cells respect each other's space (paradoxical) | |||||
| Invasive Breast Cancer | 1) 12% lifetime risk in US, 2) 7% of total considered hereditary (AD), 3) RF: age, +FH, estrogen exposure, obesity), 4) Genetics: BRCA1 mutation (Occur in only 12% early onset brca; 85-90% risk of cancer w/ mutation), BRCA2 (37-84%), Li-Fraumeni syndrome, PTEN (cowden syn), GSTM1 (glutathione s-transferase) | Mass is growing vertically and firm, ill defined and may just be a diffuse thickening or change in breast texture. Nipple discharche and pain are infrequent in invasive carcinoma | 1) METS: axillary nodes -> bone (need bone scan) --> liver, lung, or brain; Biger stage and size bigger mets risk, 2) PROGNOSIS: 1) Estrogen receptor (VIP; good prognosis), 2) Her2 neu (amplification = poor prognosis) | Mammogram: Look for masses (stelate lesion or asymmetry) or abnormal calcification (small groups) | ||||
| Ductal carcinoma in situ | 1) Low metastatic potential (<1% mets), 2) Present in ~80% invasive breast cancers | Low grade DCIS: ductal hyperplasia respecting boundaries | High grade DCIS: Hyperplasia with comedo necrosis grossly presenting as mass lesion due to stromal rxn | |||||
| Paget's Disease (Nipple) | 1) 100% of px have DCIS w/ 35-50% having invasive carcinoma, 2) 90% tumor cells her2neu, 3) may be PAS+ | Ductal carcinoma cells invade the nipple | Single or small groups of pleomorphic cells with abundant clear cytoplasm infiltrate epidermis | erythematous nipple | ||||
| Invasive Mammary Carcinoma | 1) 2nd in female cancer mortality, 2) 50s, | Mammogram | Ductal invasion into stroma | |||||
| Tubular Carcinoma | 1) older women, 2) Grade 1: excellent prognosis (even w/ lymph mets) | Well formed tubules w/ absent myoepithelial layer | ||||||
| Mucinous Carcinoma | 1) Elderly, 2) Very good prognosis | pools of extracellular mucus surrounding clusters of tumor cells | gelatinous consistency | |||||
| Medullary Carcinoma | 1) Young women | Well circumscribed mass (similar to fibroadenoma) which may grow explosively. However syncytial growth with low mets due to adhesion overexpression | Sheets of large cells w/ pleomorphic nuclei, mitosis, and prominent nucleoli. Prominent lymphoplasmacytic infiltrate and a pushing non-infiltrating border | |||||
| Invasive Lobular Carcinoma | 1) incidence rise due to HRT | Typically express estrogen receptor (good prognosis) | Often missed on mammogram (diffusely infitrative) | Single file pattern of tumor cells | Firm to hard with irregular margin. Occasionaly diffuse thickening w/o defined mass. | |||
| Inflammatory Carcinoma | 1) High grade and aggressive, 2) 3yr @ 3-10% | Tumor cells infiltrate dermal lymphatics causing acute inflammatory response and edema | 1) Orange peel skin with inflammation and edema | Chemo before surgery | ||||
| Phyloides Tumor | Large bulky mass with variable malignancy (stromal atypia prognostic) | 1) Cystic spaces containing leaflike projections from cyst wall, 2) myxoid contents | ||||||
| Angiosarcoma | 1) Postradiation | 1) Result of longstanding edema, 2) very aggressive | histo | |||||
| Male Gynecomastia | 1) 30-40% adolescent and adult men, 2) bilateral | Enlarged ducts a result of hormones, estrogens, androgens, and many drugs | Enlarged cuts devoid of lobular units | diffuse or nodular | ||||
| Male Breast Cancer | 1) 75% painless mass, 2) 50% px w/ serous discharch and mass have cancer, 3) 95% tumors express androgen and 70% express estrogen | majority located retroperitoneal | ||||||