Kidney and Male GU 2010.3

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

GlomCRESCENT

Nec

Cres

Typical of small vessel vasculitis in kidney

• Crescent: proliferation of cells inside Bowman’s capsule - blocks urinary space

• Necrosis and crescent

NCr

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 = 40 - 200 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