GU and Kidney Flashcards
Benign Mimics of Prostate Cancer
Normal Anatomy
Cowpers glands
Seminal vesicles / ejaculatory ducts
Paraganglia
Atrophy
Partial atrophy
Post atrophic hyperplasia
Benign Proliferations
Adenosis (AAH)
Sclerosing adenosis
Hyperplasia and Metaplasia
Basal cell hyperplasia
Clear cell cribriform hyperplasia
Verumonatum gland hyperplasia
Neophrogenic metaplasia
Mucinous metaplasia
Inflammation / Reactive
Malakoplakia
Granulomatous prostatitis
Staging of Prostate Cancer
AJCC 8th ed. (adenocarcinomas and histologic variants; NEC & other types)
pT Staging
pT2 = organ confined
pT3a = extraprostatic extension or bladder neck invasion
pT3b = seminal vesicle invasion
pT4 = tumour fixed or invades adjacent structures other than seminal vesicles e.g. bladder, rectum, levator muscles, external sphincter and pelvic wall
pN Staging
Regional lymph nodes
pM Staging
pM1a Non regional lymph nodes
pM1b Bone
pM1c Other sites with or without bony disease
Reporting Elements for Radical Prostatectomy
Specimen type, weight and size of prostate gland
Histologic subtype of carcinoma
Histologic grade (Gleason Grade & ISUP Grade Group)
Presence of intraduct carcinoma (+ whether has been included in grading)
Volume of prostate involved by cancer - % and as site, size and location of dominant nodule
Perineural and lymphovascular space invasion
Extraprostatic extension (+ location of EPE)
Bladder neck invasion
Seminal vesicle invasion
Margin status and if EPE is present at positive margin
Nodal status (if included)
Reporting Elements of Prostate Core Biopsy
Specimen site, number of cores, length of cores
If cancer is present / absent
Histologic subtype of cancer (acinar, ductal, mixed, neuroendocrine)
Gleason Grade and ISUP Grade Group
Number of cores involved and length of tissue involved (mm)
Presence of intraduct carcinoma
Perineural invasion
Extraprostatic extension
Comment / Other findings as needed
Staging of Testicular Cancer
AJCC 8th ed. (Germ Cell Tumours & Sex Cord Stromal Tumours).
pT Staging
pT0: No evidence of primary tumour
pTis: Germ cell neoplasia in situ only
pT1: Limited to testis (incl rete testis invasion) without lymphovascular space invasion
pT1a & b: Substaging for pure seminoma based on size < or > 3cm
pT2: Tumour limited to testis (incl rete testis invasion) with lymphovascular space invasion, or tumour invading hilar soft tissue or epididymis or through visceral mesothelial layer of tunica albuginea with or without lymphovascular space invasion
pT3: Tumour directly invades spermatic cord, with or without lymphovascular space invasion
pT4: Tumour directly invades scrotum, with or without lymphovascular space invasion
pN Staging
Regional lymph node metastases, number involved and size of lymph node mass (2, 5cm cut offs)
pM Staging
pM1a: non-retroperitoneal nodal or pulmonary metastases
pM1b: non-pulmonary viasceral metastases
Reporting Elements Testicular Cancer
Reporting Elements in Testicular Cancer
Clinical: pre and post serum markers
Site / Laterality of tumour
Focality (uni versus multi focal tumour)
Size of tumour
Histologic subtype (s) of tumour - GCT (and %), sex-cord stromal tumour
Extent of Invasion - rete testis, hilar soft tissue, epididymis, tunica albuginea, spermatic cord, scrotum
Lymphovacscular space invasion
Margin Status
Other findings: GCNIS, Tumour regression, Atrophy, Sertoli cell nodules etc.
Retroperitoneal lymph nodes
Gleason Grading of Prostate Cancer
Five tier grading system based on architecture (cytologic features not included).
Reported as sum of most prevalent pattern (primary) and second most prevalent pattern (secondary) to give a combined Gleason score.
Gleason patterns 1 & 2 are exceedingly, usually seen on TURP specimens
Gleason Pattern 3:
Clearly infiltrative glands
Glands vary in shape and size
All glands are distinct and separated by stroma
Microcystic, atrophic, branching and pseudohyperplasitc glands are all considered pattern 3.
Gleason Pattern 4:
Glands no longer seen as separate - fused, poorly defined, cribiform or glomeruloid
Ductal adenocarcinoma and intraduct carcinoma (without necrosis) considered pattern 4.
Gleason Pattern 5:
Cells in solid nests and sheets, rosettes, cords or single cells with virtually no glandular differentiation
Nest of tumour with central comedonecrosis also classed as pattern 5.
ISUP Grade Groups (Prostate Cancer)
Why? ISUP Grade Groups
- ease of communication of cancer diagnosis to patient
- with grade groups best prognostic group is “1” not “3 + 3 = 6” which is clearly confusing
- easier to compare outcomes in cancer research if grouped
ISUP Grade Groups
GG1: Gleason score 6 (3 + 3)
GG2: Gleason score 7 (3 + 4)
GG3: Gleason score 7 (4 + 3)
GG4: Gleason score 8 (4 + 4, 3 + 5, 5 + 3)
GG5: Gleason scores 9 & 10
WHO / ISUP Grading of Renal Cell Carcinoma
Grade.Nucleoli (400x).Nucleoli (100x).
- Absent / inconspicuous. Absent.
- Conspicuous & eosinophilic. Visible but not prominent.
- Prominent. Conspicuous and eosinophilic.
- Prominent. Prominent.
Only clear cell renal cell carcinoma and papillary renal cell carcinoma are graded
Tumours are graded by the worst area, however focal
Collecting duct carcinoma is considered ISUP grade 3 - 4
Grade 4 = marked nuclear pleomorphism, multi nucleated tumour giant cells, sarcomatoid and rhabdoid features.
Staging Bladder Cancer
AJCC 8th ed. (urothelial carcinoma & variants, Adenocarcinoma, SCC, NEC, sarcomatoid carcinoma)
m= multiple, r = recurrent, y = post treatment
pT Staging
pT0 No evidence of primary tumour
pTa Non-invasive papillary carcinoma
pTis Urothelial carcinoma in situ
pT1 Tumour invades lamina propria
pT2a Tumour invades superficial muscularis propria
pT2b Tumour invades deep muscularis propria
pT3a Tumour invades perivesical tissue microscopically
pT3b Tumour invades perivesical tissue macroscopically
pT4a Extravesical tumour invades directly into prostate stroma, uterus or vagina
pT4b Extravesical tumour invades pelvic wall or abdominal wall
pN Staging
pN1 Single regional lymph node metastasis in true pelvis
pN2 Multiple regional lymph node metastases in true pelvis
pN3 Lymph node metastasis to common iliac nodes
pM Staging
pM1a Distant metastases limited to lymph nodes beyond the common iliacs
pM1b Non lymph node metastases
Tumours Arising in GCNIS
Seminoma
Embryonal carcinoma
Choriocarcinoma
Post-pubertal teratoma
Post-pubertal Yolk Sac Tumour
Tumours Not Arising in GCNIS
Spermatocytic tumour
Pre pubertal teratoma
Post pubertal teratoma
Non- Germ cell tumours e.g
Sex-cord stromal tumours
Mesenchymal tumours (eg RMS)
Haematolymphoid
Reporting Elements of Renal Cell Carcinoma
Procedure and laterality
Focality (uni vs. multi)
Site and size of tumour
Histologic subtype
Histologic grade (ISUP grade for ccRCC and papillary)
Tumour extent: perinephric fat, Gerotas fascia, adrenal, renal sinus fat, pelvicalyceal systema, renal vein, IVC, adjacent organs.
Sarcomatoid and rhaboid features
Lymphovascular space invasion (excl. major vessels)
Tumour cell necrosis and %
Lymph nodes (regional and non-regional)
Margin status
Metastases
Staging System for Renal Cell Carcinomas
Based on size of tumour and extent of invasion
SIZE CUT OFFS = 4, 7, 10cm
pT1 = limited to kidney: pT1a < 4cm, pT1b 4 - 7 cm
pT2 = limited to kidney: pT2a 7 - 10cm, pT2b >10cm
pT3a = sinus fat, pelvicalyceal, renal vein, perinephric fat
pT3b/c = IVC above or below diphragm
pT4 = beyond Gerotas fascia including direct adrenal
DDx of Paediatric Renal Tumours
Embryonal Neoplasms
Nephrogenic rests
Paediatric cystic nephroma (DICER1)
Nephroblastoma & cystic partially differeniated nephroblastoma
Mesenchymal Tumours
Ossifying renal tumour of infancy
Congenital mesoblastic nephroma (classic & cellular)
Rhabdoid tumour
Clear cell sarcoma of kidney
WHO 2022 Tumours of Renal Tubular Origin
Clear cell tumours:
ccRCC, multilocular cystic renal neoplasm LMP
Papillary RCC
(NB: papillary adenoma <15mm, pRCC > 15mm)
Oncocytic and chromophobe
Collecting duct carcinoma
Other:
Clear cell papillary renal cell tumour
Mucinous tubular and spindled RCC
Tubulocystic RCC
ACD of kidney- associated RCC
Molecularly Defined Tumours:
SDH deficient RCC
FH deficient RCC
ALK rearranged
SMARCB1 deficient renal medually carcinoma
TFE3-rearranged RCC
TFEB-rearranged RCC
ELOC mutated RCC
WHO 2022 Kidney Tumours - Not of renal tubule origin
Metanephric Tumours
Metanephric adenoma
Metanephric adenofibroma
Metanephric stromal tumour
Mixed Epithelial and Stromal Tumour
Adult Renal Mesenchymal Tumours
AML and eAML
Renal haemangioblastoma
Juxtaglomerular cell tumour
Renomedullay interstitial cell tumour
Reporting Elements for Paediatric Kidney Tumour
Procedure and Laterality
Nephrectomy Weight - grams
Tumour Focality (uni or multi)
Histologic Type of Tumour (and Anaplasia in Wilns)
Tumour Size
Integrity of Gerotas Fascia
Renal Sinus Involvement
Renal Vein Involvement
Extension beyond Renal Capsule
Direct Extension into Adjacent Organs
Nephrogenic Rests
Posttherapy Histologic Classification (Int Soc Paed Onc)
(how much tumour is viable, percentage of blastema)
Margins
Lymph Nodes
Metastases
Pathologic Stage : COG Staging System (not for RCC)
How to Cut Up Kidney for Wilms Tumour
PPE, 3 points of ID, orient specimen.
Check MDM (site, size, pre or post treatment).
Weigh and measure in 3D. Measure ureter and vessels.
Photograph and ink.
Bivalve. Take fresh tissue for tumour banking or rapid H&E if pre treatment. Then fix for 24 - 48 hours.
Shave margins of ureters and vessels. Check renal vein.
Measure kidney and adrenal gland. Slice thinly and photograph for blocking diagram.
Measure tumour in 3D, described cut surface and relationship to structures and margins.
Describe background kidney - look for nephrogenic rests.
Block renal sinus fat and several further blocks of edge of tumour to closest margins / perinephic fat / adjacent structures. Block background kidney / rests. Document on photo blocking diagram.
Lymph nodes.
Processing Renal Biopsies
Native Kidney
1 core in formalin, 1 core in MIM (Michels Transport Medium)
Core in MTM is examined under dissecting microscope to identify the gloms. This end of core is taken and split for EM (glutaraldehyde) and DIFL (into fridge).
Formalin fixed tissue is processed as per usual then cut
Thin (1-2 micron) slides for:
H&E x 3
PAS x 3
Jones Silver x 3
Masson trichrome x 3
+/- Sirius Red (thick, 6 microns)
DIFL uses antibodies against:
IgG, IgA, IgM, C3, fibrin. Kappa and lamba also available as DIFL.
Special Stains in Medical Kidney
- PAS: BMs, glycogen, mucopolysaccharides, some mucins, sclerosis, amyloid (weakly +)
- Jones Silver: BMs, membrane spikes, sclerosis, K-W nodules
- Masson Trichrome: nuclei = blue / black, collagen = blue / green, cytoplasm, muscle and RBC’s red. Shows fibrosis and collagen deposition (black), fibrin thrombi (dark red).
Plus Sirius Red or Congo Red for amyloid.
Cresenteric GN
Severe form of GN in which >50% or more of the glomeruli are affected by epithelial crescents.
Clinical syndrome = RPGN, rapid decline in eGFR with haematuria, red cell casts, variable proteinuria and oliguria.
Causes:
1. Anti GBM Nephritis
- serum anti-GBM antibodies, linear IgG in GBM on DIFL, no EDD on EM, may have lung involvement (Goodpastures)
2. Pauci-Immune GN
- ANCA associated, no IF staining or EDD on EM. May have vasculitis. Associated with GPA, EGPA, MPA.
3. Immune Complex Mediated
- Associated with GN e.g IgA nephropathy, lupus, post-infectious, MPGN, cryoglobulinemic - findings depend on underlying cause
Amyloidosis in Kidney
Eosinophilic homogenous pink stuff in GBM, TBM, mesangium and capillary walls
Congo Red positive, weakly PAS positive, pale grey / blue on Trichrome
Linear non branching fibrils 6 - 10nM on EM
Need to kappa and lambda ISH or DIFL to exclude AL amyloid
Causes of amyloid:
Neoplasm associated (AL, AH)
Chronic inflammation associated (AA)
Hereditary or Mutation associated (ATTR, AAPO)
Other: sporadic / aging related, dialysis related, alzheimer’s
Diabetic Nephropathy
Diffuse thickening of GBM and vascular BM
Insudative lesions (fibrin caps, capular drops, arteriolar hyalinosis)
Microaneurysms of capillary loops
Segmental mesangial Kimmelstiel-Wilson nodules
DDx: nodular glomeruolsclerosis i.e. KW nodules = amyloid and light chain deposition disease
