Uropathology 2022

FRCPath Part 1 Uropathology Dr J Stevenson Consultant Cellular Pathologist St Helens & Knowsley Teaching Hospitals

Topics 

RCC – staging, grading

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Familial RCC syndromes

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Malakoplakia

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Prostate carcinoma – staging and Gleason grading

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Testicular tumours – classification of germ cell tumours, staging

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Bladder cancer - staging

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Penile tumours

Urological Tumours 

       

Rules for classification with the procedures for assessing T, N and M categories; additional methods may be used when they enhance the accuracy of appraisal before treatment Anatomical sites and subsites where appropriate Definition of the regional lymph nodes Distant metastasis TNM Clinical classification pTNM Pathological classification G Histopathological grading where applicable Stage grouping Summary

Pathological staging of Renal carcinoma – 8th Edition   

Tx – Primary tumour cannot be assessed T0 – No evidence of primary tumour T1 – Tumour 7.0 cm or less, limited to kidney

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T2 – Tumour more than 7.0 cm, limited to kidney

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T3 – Tumour directly invades into perinephric tissues (not beyond Gerota’s fascia) or extends into major veins

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◦ T1a: Tumour 4cm or less ◦ T1b: Tumour 4-7cm

◦ T2a – Tumour more than 7cm but not more than 10cm ◦ T2b – Tumour more than 10cm limited to the kidney

◦ T3a: Tumour directly invades perinephric tissues (perirenal fat, renal sinus fat) ◦ T3b: Tumour grossly extends into vena cava below diaphragm ◦ T3c: Tumour infiltrates vena cava above diaphragm

T4 – Tumour directly invades beyond Gerota’s fascia or into ipsilateral adrenal gland

Pathological staging of Renal carcinoma   

Nx – Regional lymph nodes cannot be assessed N0 – No regional lymph node metastasis N1 – Metastasis in regional lymph node(s)

Regional lymph node groups – Hilar, abdominal para-aortic, pre-aortic, pre-caval, retro-caval and retro-aortic nodes.

Select the appropriate pathological tumour stage from the options for each of the renal tumours described. Each option may be used once, more than once or not at all.

A. B. C. D. E. F. G. H. I. J.

pT0 pT1a pT1b pT2a pT2b pT3a pT3b pT3c pTx pT4

1. Tumour 3 cm confined to the kidney.

2. Tumour 5cm, invasion into perinephric fat.

3. Tumour 4 cm with direct extension into the renal sinus fat. The major tributaries of the renal vein show macroscopic tumour invasion.

4. Tumour 7cm with invasion of the adrenal gland.

5. Tumour 6 cm with invasion beyond Gerota’s fascia.

1. Tumour 3 cm confined to the kidney – pT1a 2. Tumour 5cm, invasion into perinephric fat – pT3a 3. Tumour 4 cm with direct extension into the renal sinus fat.

The major tributaries of the renal vein show macroscopic tumour invasion – pT3a 4. Tumour 7cm with invasion of the adrenal gland – pT4 5. Tumour 6 cm with invasion beyond Gerota’s fascia – pT4

Stage grouping of renal carcinoma    

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Stage Grouping Stage I: T1 N0 M0 Stage II: T2 N0 M0 Stage III ◦ T3 N0 M0 ◦ T1, T2, T3 N1 M0 Stage IV ◦ T4 N0, N1 M0 ◦ Any T N2 M0 ◦ Any T Any N M1

T stage and 5 year survival rates    

Stage Stage Stage Stage

I – 60% to 80% II – 40% to 70% III – 10% to 40% IV - < 5%

Summary Kidney T1 - ≤7cm; limited to the kidney T1a - ≤4cm T1b - >4cm T2 - >7cm; limited to the kidney T2a - >7 to 10cm T2b - >10cm T3 – Major veins, perinephric fat T3a – Renal vein, perinephric fat T3b – Vena cava below diaphragm T3c – Vena cava above diaphragm T4 – Beyond Gerota fascia, ipsilateral adrenal N1 – Regional mets

T stage and prognosis in renal carcinoma   

Prognostic difference between T1 and T2 tumours?

Tumour size matters only if size less than 4 cm or more than 10 cm.

Recurrence and survival for T1N0M0 and T3aN0M0 tumours are equivalent.

Fuhrman’s grading of Renal Carcinoma Nuclear shape

Nucleoli

Grade 1

Round, Uniform

None

Grade 2

Slightly irregular

Visible at x400 magnification

Grade 3

Very irregular outlines

Visible at x100 magnification

Grade 4

Bizarre, multilobed or spindle

Prominent

WHO/ISUP grading

(Based on highest grade that occupies a high power field.

Validated in clear cell and papillary RCC only) G1 - Nucleoli absent or inconspicuous and basophilic at x400 magnification G2 - Nucleoli conspicuous and eosinophilic at x400 magnification but inconspicuous at x100 magnification G3 - Nucleoli conspicuous and eosinophilic at x100 magnification G4 - Marked nuclear pleomorphism and/or multinucleate giant cells and/or rhabdoid and/or sarcomatoid differentiation

A renal tumour on histology shows solid sheets of clear cells with a prominent vascular network. The majority of the tumour cells have slightly irregular nuclei with nucleoli visible at X400 magnification. A focal area with spindled, highly pleomorphic cells is also noted. What is the ISUP grade of the tumour?

A. Grade 1 B. Grade 2 C. Grade 3 D. Grade 4 E. Grade2 and Grade 3

A renal tumour on histology shows solid sheets of clear cells with a prominent vascular network. The majority of the tumour cells have slightly irregular nuclei with nucleoli visible at X400 magnification. A focal area with spindled, highly pleomorphic cells is also noted. What is the ISUP grade of the tumour?

A. Grade 1 B. Grade 2 C. Grade 3 D. Grade 4 E. Grade2 and Grade 3

Familial Renal Carcinoma 

Most (>95%) renal tumour sporadic, but… ◦ ◦ ◦ ◦ ◦



Von Hippel–Lindau disease Hereditary leiomyomatosis and renal cell carcinoma Hereditary papillary renal cell carcinoma Birt-Hogg Dube’ syndrome Tuberous sclerosis

Multiple tumours, FH, young pts

Familial renal cell carcinoma  

Type of renal carcinoma distinct in each inherited syndrome Regular screening of carriers mandatory

Von Hippel-Lindau disease 

Germline mutations of VHL tumour suppressor gene (3p25-26)

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VHL protein associated with cell cycle regulation and angiogenesis

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Renal manifestations – Clear cell renal carcinomas, renal cysts

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Extra-renal manifestations – Retinal and CNS haemangioblastomas, phaeochromocytomas, pancreatic cysts, neuroendocrine tumours

Von Hippel-Lindau disease 

Type I – With phaeochromocytoma

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Type II – Without phaeochromocytoma ◦ IIa: Renal cell carcinoma present ◦ IIb: No renal cell carcinoma

Hereditary papillary renal carcinoma 

Mutations of the met oncogene (7q31)

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Multiple type I papillary renal carcinomas

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Usually before 55 years of age

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No known extra-renal manifestations.

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Hereditary leiomyomatosis and renal cell cancer (HLRCC)

Mutations in the FH (fumarate hydratase) gene (1q42-43)

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Renal manifestations – Type II papillary renal cell carcinomas

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Extra–renal manifestations – Cutaneous leiomyomas, uterine leiomyomas and leiomyosarcomas.

Birt-Hogg-Dubé syndrome 

BHD gene (17p11.2), folliculin

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Renal manifestations – Chromophobe carcinomas, clear cell carcinomas, oncocytoma

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Extra-renal manifestations – Benign skin lesions including fibrofolliculomas, trichodiscomas and acrochordons.

Tuberous Sclerosis 

TSC1 (9q34) and TSC2 (16p13) genes

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Renal – angiomyolipomas, lymphangioleiomyomatosis

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Extra-renal: Subungual fibromas, cutaneous angiofibromas, cardiac rhabdomyomas, SEGA (subependymal giant cell astrocytoma), adenomatous polyps

A 30 year old male presents with bilateral renal clear cell carcinoma. Investigations also reveal a posterior fossa CNS tumour with histological appearances of a haemangioblastoma. Abnormalities of which of the following chromosomes leads to this condition?

A. 7q31 B. 3p25 C. 17p11.2 D. 9q34 E. 1q42

A 30 year old male presents with bilateral renal clear cell carcinoma. Investigations also reveal a posterior fossa CNS tumour with histological appearances of a haemangioblastoma. Abnormalities of which of the following chromosomes leads to this condition?

A. 7q31 B. 3p25 C. 17p11.2 D. 9q34 E. 1q42

A 56 year old female undergoes cystoscopy for investigation of haematuria. Multiple nodular thickenings of the mucosa are seen near the trigone, which are biopsied. Histology reveals sheets of CD68+ cells with intracytoplasmic concentrically layered inclusions. Which of the following histochemical stains demonstrates these inclusions?

A. Alcian blue B. Rubeanic acid C. Orcein D. Von Kossa E. PTAH

A 56 year old female undergoes cystoscopy for investigation of haematuria. Multiple nodular thickenings of the mucosa are seen near the trigone, which are biopsied. Histology reveals sheets of CD68+ cells with intracytoplasmic concentrically layered inclusions. Which of the following histochemical stains demonstrates these inclusions?

A. Alcian blue B. Rubeanic acid C. Orcein D. Von Kossa E. PTAH

Malakoplakia

Von Hansemann histiocytes, Michaelis Gutmann bodies

Malakoplakia     

Inflammatory condition Unknown aetiology Infections? Gram negative coliform bacilli Causes defective function of histiocytes; chronic inflammatory state; fibrosis and scarring Intracellular deposition of iron and calcium – Michaelis-Guttman bodies

A.pT1a

B. pT1b

C. pT1C

D. pT2a

E. pT2b

F. pT2C

G. pT3a

H. pT3b

I. pT4 1.

2.

3.

4.

5.

A 73 year old male with PSA levels of 8.4. Histology shows adenocarcinoma invading into the right seminal vesicle.

A 62 year old male undergoes radical prostatectomy for cancer. On histology, the carcinoma extends beyond the prostate into the periprostatic fat.

A 68 year old male with elevated PSA levels has a normal prostate on clinical and radiological examination. Needle core biopsies from both lobes however, reveal an adenocarcinoma.

A 52 year old male with obstructive symptoms undergoes radical prostatectomy. On histology, an adenocarcinoma involving both lobes, but confined to the prostate is seen.

A 58 year old male with obstructive symptoms and a PSA of 38, undergoes a CT scan of the pelvis, which reveals a prostatic tumour extending into the levator muscles.

Prostate – Rules for Classification

The classification applies only to adenocarcinomas.

Transitional cell carcinoma of the prostate is classified as a urethral tumour.

There should be histological confirmation of the disease.

Pathological staging of prostate cancer 

Tx – Primary tumour cannot be assessed



T0 - No evidence of primary tumour

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T1 – Clinically inapparent tumour ◦ T1a: Incidental tumour <5% of total tissue ◦ T1b: Incidental tumour >5% of total tissue ◦ T1c: Tumour identified by needle biopsy

Pathological staging of prostate cancer 





T2 – Tumour confined to the prostate

◦ T2a: Tumour involving not more than one half of one lobe ◦ T2b: Tumour involving more than one half of one lobe ◦ T2c: Tumour involving both lobes

T3 – Tumour with extra-prostatic extension

◦ T3a: Extracapsular extension (including bladder neck) ◦ T3b: Tumour invades seminal vesicle(s)

T4 – Tumour invades adjacent structures other than seminal vesicles (ie. external sphincter, rectum, levator muscles and/or pelvic wall)

Pathological staging of Prostate cancers

Pathological Staging of Prostate Cancer N – Regional Lymph Nodes NX – No regional lymph node metastasis N0 – No regional lymph node metastasis N1 – Regional lymph node metastasis M – No distant metastasis* M1 – Distant metastasis M1a – Non-regional lymph node(s) M1b – Bone(s) M1c – Other site(s) Note: *When more than one site of metastasis is present, the most advanced category is used. pM1c is the most advanced category.

1. A 73 year old male with PSA levels of 8.4. Histology shows adenocarcinoma invading into the right seminal vesicle 2. A 62 year old male undergoes radical prostatectomy for cancer.

On histology, the carcinoma extends beyond the prostate into the peri-prostatic fat 3. A 68 year old male with elevated PSA levels has a normal prostate on clinical and radiological examination. Needle core biopsies from both lobes however, reveal an adenocarcinoma 4. A 52 year old male with obstructive symptoms undergoes radical prostatectomy. On histology, an adenocarcinoma involving both lobes, but confined to the prostate is seen 5. A 58 year old male with obstructive symptoms and a PSA of 38, undergoes a CT scan of the pelvis, which reveals a prostatic tumour extending into the levator muscles

1. A 73 year old male with PSA levels of 8.4. Histology shows adenocarcinoma invading into the right seminal vesicle – pT3b 2. A 62 year old male undergoes radical prostatectomy for cancer.

On histology, the carcinoma extends beyond the prostate into the peri-prostatic fat – pT3a 3. A 68 year old male with elevated PSA levels has a normal prostate on clinical and radiological examination. Needle core biopsies from both lobes however, reveal an adenocarcinoma pT1c 4. A 52 year old male with obstructive symptoms undergoes radical prostatectomy. On histology, an adenocarcinoma involving both lobes, but confined to the prostate is seen - pT2c 5. A 58 year old male with obstructive symptoms and a PSA of 38, undergoes a CT scan of the pelvis, which reveals a prostatic tumour extending into the levator muscles – pT4

A 66 year old man undergoes radical prostatectomy for a needle core detected adenocarcinoma. The tumour predominantly shows raggedly infiltrating single and separate glands of varying sizes.

Approximately 5% of the carcinoma also shows rounded tumour masses with central necrosis. Which of the following best represents the grade of the tumour?

A. Gleason’s 3 + 3 = 6 B. Gleason’s 3 + 4 = 7 C. Gleason’s 4 + 3 = 7 D. Gleason’s 3 + 5 = 8 E. Gleason’s 4 + 5 = 9

Introduction 

In the 1960’s and 1970’s, Donald F Gleason and collaborators characterised various architectural patterns of prostatic cancer and grouped them into 5 grades or patterns, thus establishing the Gleason grading system  More than 4 decades since its introduction, the Gleason system still remains the key prognostic factor in patients with prostatic cancer

Gleason’s grading

Original Gleason diagram

Modified ISUP diagram

Intro contd... 

Thus, a 2005 ISUP modified Gleason system was proposed, outlining the morphological patterns 15, which were accompanied by a modified diagram, similar to the original Gleason system  It was reiterated that GP1 and GP2 are quite rare on biopsy and

prostatectomy. The most significant modifications pertained to patterns 3 and 4  GP3 was restricted to discrete glandular units and to smoothly

circumscribed but only small cribriform tumour nodules

Intro contd... 

Pattern 4 included fused glands and large cribriform glands or cribriform glands with border irregularities, as well as hypernephromatoid glands  Additionally, a category of ill-defined glands or glands containing

poorly formed glandular lumina was introduced under GP4  GP5 was reserved for cancers containing essentially no glandular

differentiation, composed of solid sheets, cords, and single cells.

Comedocarcinoma with central necrosis was also retained in pattern 5

2014 ISUP Modified Gleason System Pattern 3: Discrete glandular units Infiltrates in and amongst nonneoplastic prostate acini Marked variation in size and shape Pattern 4: Fused microacinar glands Ill-defined glands with poorly formed glandular lumina Cribriform glands Hypernephromatoid Pattern 5: Essentially no glandular differentiation, composed of solid sheets, cords, or single cells Comedocarcinoma with central necrosis surrounded by papillary, cribriform, or solid masses

Cribriform prostate cancer with perineural invasion.

Cribriform glands with round border (arrow) Cribriform glands with irregular border (arrowhead) – both now Gleason 4

Gleason score 4 + 4 = 8 adenocarcinoma Fused Glands

Large irregular cribriform

Gleason pattern 5 cancer with cribriform gland containing central comedonecrosis

Gleason’s grading 

Prostatectomy:

◦ Grade obtained by adding the most prevalent (primary) and the second most prevalent (secondary) pattern +/- any tertiary pattern (if 4 or 5)*

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Needle biopsy:

◦ Grade obtained by adding the most prevalent (primary) and the highest

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Gleason’s grading tutorial – pathology.jhu.edu/prostate

*A pattern is secondary if it accounts for at least 5% of the tumour, and tertiary if it is < 5% of the tumour

A 66 year old man undergoes radical prostatectomy for a needle core detected adenocarcinoma. The tumour predominantly shows raggedly infiltrating single and separate glands of varying sizes. Approximately 5% of the carcinoma also shows rounded tumour masses with central necrosis. Which of the following best represents the grade of the tumour?

A. Gleason’s 3 + 3 = 6 B. Gleason’s 3 + 4 = 7 C. Gleason’s 4 + 3 = 7 D. Gleason’s 3 + 5 = 8 E. Gleason’s 4 + 5 = 9

Gleason grade groups

Testis – germ cell tumours The classification applies to germ cell tumours of the testis. There should be histological confirmation of the disease and division of cases by histological type. Histopathological grading is not applicable.

The presence of elevated serum tumour markers, including alphafetoprotein (AFP), hCG and LDH, is frequent in this disease. Staging is based on the determination of the anatomic extent of disease and assessment of serum tumour markers.

Testis Serum tumour markers are obtained immediately after orchidectomy and if elevated, should be performed serially after orchidectomy according to the normal decay for AFP (half-life 7 days) and hCG (half-life 3 days).

The serum level of LDH (but not its half-life levels) has prognostic value in patients with metastatic disease and is included for staging.

Choose the WHO classification category from the options for each of the testicular tumours described below. Each option may be used once, more than once or not at all.

A. B. C.

D. E. F. G. H. I.

Embryonal carcinoma Seminoma Teratoma with somatic transformation Spermatocytic tumour Mixed germ cell tumour Dermoid cyst Mature teratoma Yolk sac tumour Choriocarcinoma

1.

2.

3.

4.

5.

Nests of tumour cells separated by fibrous septae, infiltrated by lymphocytes. A few syncytiotrophoblast like cells are seen.

Diffuse sheets of anaplastic cells, positive for CD30 A child with a cystic lesion containing keratin and lined by squamous epithelium. The wall contains cutaneous adnexal structures.

Haemorrhagic tumour showing admixture of atypical syncitio and cytotrophoblastic cells.

Diffuse sheets of CD30 + anaplastic cells admixed with areas showing well differentiated glandular structures and islands of mature cartilage

Classification of testicular germ cell tumours 2004 WHO classification

BTTP classification

Tumours of one histological type Seminoma

Seminoma

With syncytiotrophoblastic giant cells Spermatocytic seminoma

Spermatocytic seminoma

Embryonal carcinoma

Malignant teratoma, undifferentiated

Yolk sac tumour

Yolk sac tumour (pure neoplasms only)

Choriocarcinoma

Malignant teratoma, trophoblastic

Other trophoblastic tumours Monophasic choriocarcinoma Placental site trophoblastic tumour Teratoma

Teratoma, differentiated

Dermoid cyst Monodermal teratoma Teratoma with somatic transformation Tumours of more than one histological type Embryonal carcinoma/yolk sac and teratoma

Malignant teratoma, intermediate

Choriocarcinoma and other non-seminoma

Malignant teratoma, trophoblastic

Seminoma and non-seminoma

Combined tumour seminoma/non-seminoma

Classification of testicular germ cell tumours   



WHO system based on identification of different germ cell components BTTP ‘lumps’ some non-seminomatous tumours into single entities.

All teratomas in adults are potentially malignant with the exception of dermoid cyst.

J Clin Pathol 2008;61:20-24

Choose the BTTP classification category from the options for each of the testicular tumours described below. Each option may be used once, more than once or not at all.

A. B. C.

D. E. F. G. H. I.

Embryonal carcinoma Seminoma Teratoma with somatic transformation Spermatocytic tumour Mixed germ cell tumour Dermoid cyst Mature teratoma Yolk sac tumour Choriocarcinoma

1.

2.

3.

4.

5.

Nests of tumour cells separated by fibrous septae, infiltrated by lymphocytes. A few syncytiotrophoblast like cells are seen. B Diffuse sheets of anaplastic cells, positive for CD30. A A child with a cystic lesion containing keratin and lined by squamous epithelium. The wall contains cutaneous adnexal structures. F Haemorrhagic tumour showing admixture of atypical syncytio and cytotrophoblastic cells. I Diffuse sheets of CD30 + anaplastic cells admixed with areas showing well differentiated glandular structures and islands of mature cartilage E

pTNM Pathological Classification

pTx - Primary tumour cannot be assessed pT0 – No evidence of primary tumour (e.g. histological scar in testis) pTis – Germ cell neoplasia in-situ (carcinoma in-situ) pT1 – Tumour limited to testis and epididymis without vascular/lymphatic invasion; tumour may invade tunica albuginea but not tunica vaginalis pT2 – Tumour limited to testis and epididymis with vascular/lymphatic invasion, or tumour extending through tunica albuginea with involvement of tunica vaginalis pT3 – Tumour invades spermatic cord with or without vascular/lymphatic invasion pT4 – Tumour invades scrotum with or without vascular/lymphatic invasion

pTNM Pathological Classification

pNx – Regional lymph nodes cannot assessed pN0 – No regional lymph node metastasis pN1 – Metastasis with a lymph node mass 2cm or less in greatest dimension and 5 or fewer positive nodes, none more than 2cm in greatest dimension pN2 – Metastasis with a lymph node mass more than 2cm but not more than 5cm in greatest dimension; or more than 5 nodes positive, none more than 5cm; or evidence of extranodal extension of tumour pN3 – Metastasis with a lymph node mass more than 5cm in greatest dimension

pTNM Pathological Classification

pM – Distant Metastasis pM1 – Distant metastasis microscopically confirmed Note: *pM0 and pMX are not valid categories S – Serum Tumour Markers SX – Serum marker studies not available S0 – Serum marker study levels within normal limits LDH Hcg (Miu/ML) AFP (ng/ml) S1 <1.5xN and <5000 and <1000 S2 - 1.5-10xN or 5000-50000 or 100010000 S3 - >10xN or >50000 or >10000 Note: N indicates the upper limit of normal for the LDH assay

Stage Grouping Stage Stage Stage Stage Stage Stage Stage

0 I IA IB IS II IIA

Stage IIB Stage IIC Stage III Stage IIIA Stage IIIB Stage IIIC

pTis N0 pT1-T4 N0 pT1 N0 M0 pT2-T4 N0 Any pT/TX N0 Any pT/TX N1-N3 Any pT/TX N1 Any pT/TX N1 M0 Any pT/TX N2 Any pT/TX N2 M0 Any pT/TX N3 Any pT/TX N3 M0 Any pT/TX Any N Any pT/TX Any N Any pT/TX Any N Any pT/TX N1-N3 Any pT/TX Any N Any pT/TX N1-N3 Any pT/TX Any N Any pT/TX Any N

M0 M0 S0 M0 M0

S0, SX SX

S0 S1-S3 M0 SX M0 S0 S1 M0 S0 S1 M0 S0 S1 M1a SX M1a S0 M1a S1 M0 S2 M1a S2 M0 S3 M1a S3 M1b Any S

A biopsy of a cryptorchid testis shows atrophy with a few seminiferous tubules containing atypical germ cells with clear cytoplasm. These cells are positive for PLAP. Which other immunostain is routinely used to confirm the diagnosis?

A. B. C. D. E.

EMA CD30 C-Kit AFP Inhibin

A biopsy of a cryptorchid testis shows atrophy with a few seminiferous tubules containing atypical germ cells with clear cytoplasm. These cells are positive for PLAP. Which other immunostain is routinely used to confirm the diagnosis?

A. B. C. D. E.

EMA CD30 C-Kit AFP Inhibin

Germ cell neoplasia in-situ Can be seen in  Residual testis harbouring germ cell tumour  Contralateral testis  Undescended testis Specific types:  Intratubular seminoma  Intratubular embryonal carcinoma

PAS

PLAP Germ cell neoplasia insitu (GCNIS)

Summary - Testis pTis – Intratubular pT1 – Testis and epididymis, no vascular / lymphatic invasion pT2 – Testis and epididymis with vascular / lymphatic invasion or tunica vaginalis pT3 – Spermatic cord pT4 – Scrotum N1 - ≤2cm pN1 ≤2cm & ≤5 nodes N2 - >2cm to 5cm pN2 >2cm & 5cm or > 5 nodes or extranodal extension N3 - >5cm pN3 >5cm M1a – Non-regional lymph nodes or lung M1b – Other sites

Urinary Bladder TNM Clinical Classification

T – Primary Tumour The suffix (m) should be added to the appropriate T category to indicate multiple tumours. The suffix (is) may be added to any T to indicate presence of associated carcinoma in situ.

TNM Clinical Classification TX – Primary tumour cannot be assessed T0 – No evidence of primary tumour Ta – Non-invasive papillary carcinoma Tis – Carcinoma in situ: ‘flat tumour’ T1 – Tumour invades subepithelial connective tissue T2 – Tumour invades muscle T2a – Tumour invades superficial muscle (inner half) T2b – Tumour invades deep muscle (outer half) T3 – Tumour invades perivesical tissue: T3a – microscopically T3b – macroscopically (extravesical mass) T4 – Tumour invades any of the following: prostate stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall T4a – Tumour invades prostate stroma, seminal vesicles, uterus or vagina T4b – Tumour invades pelvic wall or abdominal wall

TNM Clinical Classification N – Regional Lymph Nodes NX – Regional lymph nodes cannot be assessed N0 – No regional lymph node metastasis N1 – Metastasis in a single lymph node in the true pelvis (hypogastric, obturator, external iliac, or presacral) N2 – Metastasis in multiple lymph nodes in the true pelvis (hypogastric, obturator, external iliac, or presacral) N3 – Metastasis in a common iliac lymph node(s) M – Distant Metastasis M0 – No distant metastasis M1 – Distant metastasis

TNM Bladder Classification Stage Grouping Stage Stage Stage Stage Stage

0a Ta N0 M0 0is Tis N0 M0 I T1 N0 M0 II T2a, b N0 M0 III T3a, b N0 M0 T4a N0 M0 Stage IV T4b N0 M0 Any T N1, N2, N3 M0 Any T Any N M1

Urinary Bladder - Summary Ta – Non-invasive papillary Tis – In situ: ‘flat tumour’ T1 – Subepithelial connective tissue T2 – Muscularis T2a – Inner half T2b – Outer half T3 – Beyond Muscularis T3a – Microscopically T3b – Extravesical mass T4 – Prostate, uterus, vagina, pelvic wall, abdominal wall T4a – Prostate, uterus, vagina T4b – Pelvic wall, abdominal wall N1 – Single (pelvic) N2 – Multiple (pelvic) N3 – Common iliac

Penis Anatomical Subsites 1.

Prepuce 2.

Glans penis 3.

Body of penis Regional Lymph Nodes The regional lymph nodes are the superficial and deep inguinal and the pelvic nodes

Penis - TNM Clinical Classification T – Primary Tumour TX – Primary tumour cannot be assessed T0 – No evidence of primary tumour Tis – Carcinoma in situ Ta – Non-invasive verrucous carcinoma1 T1 – Tumour invades subepithelial connective tissue T1a – Tumour invades subepithelial connective tissue without lymphovascular invasion (or PNI) and is not poorly differentiated or undifferentiated T1b – Tumour invades subepithelial connective tissue with lymphovascular invasion (or PNI) or is poorly differentiated or undifferentiated T2 – Tumour invades corpus spongiosum or cavernosum T3 – Tumour invades urethra T4 – Tumour invades other adjacent structures Note: 1. Verrucous carcinoma not associated with destructive invasion

Penis TNM Clinical Classification

N – Regional Lymph Nodes NX – Regional lymph nodes cannot be assessed N0 – No palpable or visibly enlarged inguinal lymph nodes N1 – Palpable mobile unilateral inguinal lymph node N2 – Palpable mobile multiple or bilateral inguinal lymph nodes N3 – Fixed inguinal nodal mass or pelvic lymphadenopathy unilateral or bilateral

M – Distant Metastasis M0 – No distant metastasis M1 – Distant metastasis

G Histological Grading GX – Grade of differentiation G1 – Well differentiated G2 – Moderately differentiated G3-4 – Poorly differentiated/undifferentiated

Stage 0

Stage Grouping Ta

Tis

N0

M0

N0 M0 Stage I T1a N0 M0 Stage II T1b N0 M0 T2 N0, N1 M0 T3 N0 M0 Stage IIIa T1, T2, T3 N1 M0 Stage IIIB T1, T2, T3 N2 M0 Stage IV T4 Any N M0 Any T N3 M0 Any T Any N M1

Summary - Penis Tis – Carcinoma in situ Ta – Non-invasive verrucous carcinoma T1 – Subepithelial connective tissue T2 – Corpus spongiosum, cavernosum T3 – Urethra T4 – Other adjacent structures N1 – Single palpable mobile unilateral inguinal pN1 – Single inguinal N2 – Palpable mobile multiple or bilateral inguinal pN2 – Multiple/bilateral inguinal N3 – Fixed inguinal or pelvic pN3 – Pelvic or extranodal

THANK YOU FOR LISTENING. ANY QUESTIONS ?