Kidney and Male GU Renal Vasculitis Prostatic carcinoma

Vasculitis  Inflammation and necrosis of blood vessels  Capillaries -> Aorta

Examples of Vasculitis Large blood vessels –Giant cell (Temporal) Arteritis Medium sized vessels –Polyarteritis Nodosa Small vessel vasculitis –Capillaries, venules, arterioles +/- small arteries –Systemic or one site only (skin, renal glomeruli)

Vasculitis

Vasculitis - artery in Polyarteritis Nodosa Lumen Inflammation of artery wall

Glomerulus in vasculitis: crescents, necrosis Crescent around glomerulus Necrosis and small crescent Glom CRESCENT Nec Cres

Typical of small vessel vasculitis in kidney Crescent: proliferation of cells inside Bowman’s capsule - blocks urinary space Necrosis and crescent N Cr

Vasculitis: Clinical, Serology Acute renal failure, haematuria, proteinuria Systemic signs: include rash, arthralgias, respiratory, neuromuscular symptoms Duration of illness variable ANCA (MPO, PR3) (ANA, anti-GBM antibodies)

Anti-neutrophil cytoplasmic antibodies (ANCA) Serum antibodies to enzymes in neutrophil granules, monocyte lysosomes Immunofluorescence: Cytoplasmic or Perinuclear P-ANCA (anti-myeloperoxidase) in 80% of micro polyangiitis; more often indolent, renal limited C-ANCA (anti-proteinase 3) in 90% of Wegener’s Very useful in diagnosis; follow up of disease activity in Wegener’s with C-ANCA

Crescentic GN, vasculitis: Immunofluorescence findings 65% “pauci-immune” –pauci = few or no IC 20% immune complex 15% anti-GBM...,.

Immunofluorescence, EM Pauci-immune –(little / no immunofluorescent staining) –90% of ANCA-assoc GN Electron microscopy –GBM breaks, fibrin (indicate structural damage) –Crescent cells (epithelial > macrophages/lymphocytes) –No EM deposits...,.

ANCA-Mediated Glomerulonephritis ANCA mediated, Pauci-immune Crescentic GN –Wegener’ granulomatosis –Microscopic polyangiitis –Churg-Strauss syndrome –Glomerular Pathology identical in all 3 –Pathology at other sites? Respiratory tract? –MPA may have different stage lesions, more chronic –ANCA Type PR3 or MPO –Specific diagnosis needs careful correlation –If prompt treatment: 75% 5year survival

** Scar (healing) after necrosis Scar Chronic, partly healed lesions in vasculitis **Fibrocellular crescent

Necrosis and/or Crescents in GN PAUCI-IMMUNE (90% are ANCA-positive) –Microscopic polyangiitis, Wegener’s, Churg-Strauss, (drugs) IMMUNE COMPLEX (also Electron dense deposits) –Henoch-Schlonlein purpura –Cryoglobulinemia –Lupus nephritis –Bacterial endocarditis –Drug reaction –other ANTI-GBM DISEASE –Goodpasture’s syndrome and anti-GBM nephritis

R D 28 year old male Acute renal failure Pulmonary haemorrhage N = Necrotic segment of glomerulus N

R D Crescent, necrosis, fibrin Linear staining for IgG (EM: GBM breaks, fibrin) Cres

And Your Diagnosis is: ANCA-mediated? Immune complex? Anti-GBM disease?

Prostate Surrounds bladder neck and urethra Normal weight = 20gm Enlarged prostate palpable on rectal examination CZ = Central zone PZ = Peripheral zone

Benign prostatic hyperplasia Nodules around prostatic urethra 70% men over 60 yrs Growth requires dihydrotestosterone (Leydig cells), its metabolite 3- alpha-androstanediol & estrogens, which increase DHT receptor expression in prostatic tissue –DHT converted from testosterone by 5-alpha-reductase BPH not precancerous Clinical: –(None in most) –Obstruction - compression of urethra -> frequency, nocturia, etc –Dysuria because of UTI; acute retention

Benign prostatic hyperplasia Prostate = gm Nodules vary in size, colour and texture Nodules consist of glands and / or fibromuscular stroma NODULE

Benign prostatic hyperplasia Treatment –None –Transurethral resection (TURP) –(Open prostatectomy for very enlarged prostates) –Medical treatment 5 alpha-reductase inhibitor, or Alpha adrenergic blockade

Carcinoma of the prostate Commonest cancer in males –Second leading cause of cancer deaths in men >50 –Incidence increases with age 70 >60 >50 yrs –Afro-Americans at earlier age >US whites >Asians Endocrine, genetic & environmental factors –Androgens –Susceptibility loci on chromosomes 1 and 10 (near PTEN) –Incidence in Scandinavians > Japanese –Animal fat in diet? Prostatic Intraepithelial Neoplasia (PIN) –in situ precursor of prostatic carcinoma

Clinical presentation Latent carcinoma - asymptomatic. Screening - PSA, PR +/- Transrectal Ultrasound, prostatic biopsies –PSA is a serine protease secreted by prostatic acinar cells, that liquifies the ejaculate. A single serum PSA test is not fully sensitive or specific. Advanced carcinoma - obstruction or symptoms due to local extension or metastases e.g. bone pain.

PSA in prostatic acini

Preferential sites for prostatic lesions Transverse section BPH around prostatic urethra * 70% of carcinomas are peripheral, and often posterior *

Pathology Peripheral in 70%, mostly posterior, palpable on PR Often not easily recognised on gross examination Invasion outside capsule; seminal vesicles, bladder Lymphatics; bloodstream, osteoblastic mets late Micro: Adenocarcinoma (different patterns = diff grades) –Grading: Gleason grade 1 ( virtually normal glands -> Gleason grade 5 (poorly differentiated). –Gleason score: add two predominant grades –Score = 6 predicts a good prognosis; 8-10 a poor prognosis –Immunostaining: PSA+, loss of HMW keratin staining

Prostatic carcinoma - microscopic Gleason Grade 3 Gleason G 5

Capsular & perineural invasion (L) and bone metastasis (R) Nerve

Prostatic carcinoma stage, prognosis Staging: clinical, PR, U/S, CT/MRI, bone scan, pathological stage in prostatectomy –T1, T2 - both treated by radical prostatectomy or radiotherapy –T3 locally invasive - radiotherapy –T4 metastatic - hormonal therapy Prognosis: –Slow growing cancers –Stage and Gleason score –90% 10 yr survival for T1, T2 –10-40% for T4