FRCPath Part 1 Uropathology
Dr J Stevenson ST6 Histopathology Whiston Hospital
Topics
RCC – staging, grading
Familial RCC syndromes
Malakoplakia
Prostate carcinoma – staging and Gleason grading
Testicular tumours – classification of germ cell tumours, staging
Bladder cancer - staging
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 th carcinoma – 8 Edition
Tx – Primary tumour cannot be assessed T0 – No evidence of primary tumour T1 – Tumour 7.0 cm or less, limited to kidney
T2 – Tumour more than 7.0 cm, limited to kidney
T3 – Tumour directly invades into perinephric tissues (not beyond Gerota’s fascia) or extends into major veins
◦ 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
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 100x 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) VHL protein associated with cell cycle regulation and angiogenesis Renal manifestations – Clear cell renal carcinomas, renal cysts
Extra-renal manifestations – Retinal and CNS haemangioblastomas, phaeochromocytomas, pancreatic cysts, neuroendocrine tumours
Von Hippel-Lindau disease
Type I – With phaeochromocytoma Type II – Without phaeochromocytoma ◦ IIa: Renal cell carcinoma present ◦ IIb: No renal cell carcinoma
Hereditary papillary renal carcinoma
Mutations of the met oncogene (7q31)
Multiple type I papillary renal carcinomas
Usually before 55 years of age
No known extra-renal manifestations.
Hereditary leiomyomatosis and renal cell cancer (HLRCC)
Mutations in the FH (fumarate hydratase) gene (1q42-43) Renal manifestations – Type II papillary renal cell carcinomas Extra–renal manifestations – Cutaneous leiomyomas, uterine leiomyomas and leiomyosarcomas.
Birt-Hogg-Dubé syndrome
BHD gene (17p11.2), folliculin Renal manifestations – Chromophobe carcinomas, clear cell carcinomas, oncocytoma Extra-renal manifestations – Benign skin lesions including fibrofolliculomas, trichodiscomas and acrochordons.
Tuberous Sclerosis
TSC1 (9q34) and TSC2 (16p13) genes
Renal – angiomyolipomas, lymphangioleiomyomatosis
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
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
T3 – Tumour with extra-prostatic extension
◦ 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 ◦ 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 – 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 diagram
Modified ISUP
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
TABLE 3. 2005 ISUP Modified Gleason System (Patterns 1+2 removed)
Pattern 3: Discrete glandular units Typically smaller glands than seen in Gleason pattern 1 or 2 Infiltrates in and amongst nonneoplastic prostate acini Marked variation in size and shape Smoothly circumscribed small cribriform nodules of tumour
Pattern 4: Fused microacinar glands Ill-defined glands with poorly formed glandular lumina Large cribriform glands Cribriform glands with an irregular border 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:
Needle biopsy:
Gleason’s grading tutorial – pathology.jhu.edu/prostate
◦ Grade obtained by adding the most prevalent (primary) and the second most prevalent (secondary) pattern +/- any tertiary pattern (if 4 or 5)* ◦ Grade obtained by adding the most prevalent (primary) and the highest
*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
Appendix C
Reporting proforma for transurethral resections of prostate
Surname
Forenames
Date of birth
Hospital
Hospital no
NHS no
Date received
Date reported
Report no
Pathologist
Surgeon
Review
Yes
□
Nature of specimen(s) and core macroscopic items TURP
□ Weight: g
Proportion sampled:
Enucleation
□ Weight: g
Dimensions
x
x
mm
No
□
Core microscopic items Tumour type
Microacinar
Percentage of tumour if clinically unsuspected tumour Gleason score
pT category (TNM 2002) Vascular invasion
Primary grade
□
Other (please specify)
(number positive/total x100) Secondary grade
□ No tertiary grade pT1a □ Incidental carcinoma in 5% or less of tissue resected pT1b □ Incidental carcinoma over 5% of tissue □ Absent resected □ Present
SNOMED codes T
M
T
M
Signature of pathologist…………………………………………
Date………….………..
Appendix D
Reporting proforma for radical prostatectomies
Surname
Forename s
Date of birth
Hospital
Hospital no
NHS no
Date received
Date reported
Report no
Pathologist
Surgeon
Review
Nature of specimen(s) and core macroscopic items Prostate
Weight:
g
Fasciae/connective tissue Surgical incisions Seminal vesicles
Right
N/A
□
Present
□
D i m e n s i o n s
Yes
□ No
□
Core microscopic items Tumour type
Microacinar
Gleason score (prevalence)
Primary grade No terti ary gra de
N o t u m o u r □
□
Organ confined
Yes
□
Beyond the outline of the prostate
Yes
□
Into seminal vesicle(s).
Yes
□
Into bladder neck
Yes
□
Nodal status
No nodes present
□
Node negative
□
Number
Right side
Node positive
□
Number (positive nodes/total)
Right side
pTNM stage 2002
Left side /
Left side
/
SNOMED codes
pT
pN
□ pT2 (organ confined) □ pT3a (EPE) □ pT3b (SV positive) □ pT4 (other organs involved)
□ pNx □ pN0 □ pN1
pM
T
M
T
M
Signature of pathologist…………………………………………
Date………….………..
Appendix E Reporting proforma for prostatic biopsies Surname
Forenames
Date of birth
Hospital
Hospital no
NHS no
Date received
Date reported
Report no
Pathologist
Surgeon
Review Yes
□ No
□
Nature of specimen(s) and core macroscopic items Right side (specific locations below if applicable)
Number
Length Left side (specific locations below if applicable)
Number
Length
Core microscopic items Tumour type
Microacinar
Gleason score
Primary grade
No tertiary grade
Number of cores positive/total
/
Other estimates of Greatest percentage of cancer tumour extent SNOMED codes (single most involved core) Side: Right □ Left □ Both □
T
M
T
M
Perineural invasion
%
N/A
Invasion into adipose tissue
N/A
Vascular invasion
N/A
Signature of pathologist………………………………………… Non prostatic tissues N/A Present
Date………….………..
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 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. 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 1000-10000 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
pT1-T4
Any Any Any
Any Any Any Any
pTis
N0
N0
pT1 pT2-T4 Any pT/TX Any pT/TX Any pT/TX pT/TX N1 Any pT/TX pT/TX N2 Any pT/TX pT/TX N3 Any pT/TX Any pT/TX pT/TX Any Any pT/TX pT/TX Any Any pT/TX pT/TX Any pT/TX Any
N0 N0 N0 N1-N3 N1
N2 N3
N N N N
Any N Any N N1-N3 N1-N3
M0
M0 M0 M0
M1a M1a M1a M1b
M0 SX M0 M0 M0 M0 M0 S1 M0 S1 M0 S1 M1a M1a S1 M0 S2 M0 S3 Any S
S0, SX S0 S0 S1-S3 SX S0
S0 S0 SX S0 S2 S3
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
RCPath REPORTING PROFORMA FOR TESTICULAR CANCER Surname……………………… Forenames………………….… Hospital………….…………… Hospital no……………….…... Date of receipt………….……. Date of reporting………..…..... Pathologist……….…………... Surgeon………………….…… Nature of specimen/procedure and core macroscopic items
Biopsy
Righ t
Left
Orchidectom y
Right
Left
Partia l Nodes
Yes
Date of birth………… NHS no…………….... Report no…………….
Retroperitoneal lymph node dissection
Tumour location ………………….. Maximum tumour size ……………(mm)
No
Please specify origin……………………. Surgical margins
Negative
Positive
Site(s)………………
Sex…
Core microscopic items Tumour type/s (one or more)
Germ cell tumour
Non germ cell
Classical seminoma
Leydig cell tumour
Spermatocytic seminoma
Sertoli cell tumour
Undifferentiated teratoma/embryonal carcinoma
Undifferentiated sex cord/stromal
Yolk sac tumour
Other
Malignant teratoma trophoblastic/choriocarcinoma
Please specify:………………………….
Teratoma differentiated/teratoma
Other
Please specify:…………………………………………
No evidence of primary tumour (e.g. scar in testis, pT0)
Yes
No
Intratubular germ cell neoplasia only (pTis)
Yes
No
Tumour limited to testis/epididymis without vascular invasion, invasion of tunica albuginea but not vaginalis (pT1)
Yes
No
Tumour limited to testis/epididymis but tunica vaginalis involvement (pT2)
Yes
No
Tumour limited to testis/epididymis with vascular invasion (pT2)
Yes
No
Tumour invades spermatic cord with or without vascular invasion (pT3)
Yes
No
Tumour invades scrotum with or without vascular invasion (pT4)
Yes
No
Margins
BTTP classification
N/A
Negative
Positive
If seminoma, invasion into rete
Site(s)………………
Yes
No
pTNM stage: pT ……… pN……… pM……. SNOMED codes T……………….. M…………………. T……………….. M…………………. Signature of pathologist…………………………………………Date…………………..………..
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 0a Stage 0is Stage I M0 Stage II M0 Stage III M0 Stage IV
Ta Tis
T1
N0 N0
N0
T2a, b
N0
T3a, b
N0
T4a T4b Any T Any T
N0 N0 N1, N2, N3 Any N
M0 M0
M0 M0 M0 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 M0
Stage I M0 Stage II M0 Stage IIIa Stage IIIB Stage IV
Stage Grouping Tis
Ta T1b T2
T1a
N0
N0
N0
N0 N0, N1
T3 N0 T1, T2, T3 N1 T1, T2, T3 N2 T4 Any N Any T N3 Any T Any N
M0 M0 M0 M0 M0 M0 M0 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
Core microscopic items Tumour subtype
Squamous carcinoma, usual type
Grade 1
Papillary squamous carcinoma
Grade 2
Basaloid squamous carcinoma
Grade 3
Warty squamous carcinoma
Associated carcinoma in situ
Yes
No
Verrucous squamous carcinoma
Vascular invasion
Yes
No
Sarcomatoid squamous carcinoma
Margins clear
Yes
No
Other:
If no, specify margins involved: ……………………………………..
Please specify…………………
Differentiation
Carcinoma in situ only (pTis)
Yes
No
Cannot assess
Invasion into lamina propria (pT1)
Yes
No
Cannot assess (pTx)
Invasion into corpus spongiosum (pT2)
Yes
No
Cannot assess (pTx)
Invasion into corpus cavernosum (pT2)
Yes
No
Cannot assess (pTx)
Invasion into urethra or prostate (pT3)
Yes
No
Cannot assess (pTx)
Invasion of adjacent organs (pT4)
Yes
No
Cannot assess (pTx)
Node type, right
N/A
Node type, left
Sentinel/Cloquet’s
Sentinel/Cloquet’s
Superficial inguinal
Superficial inguinal
Deep inguinal
Deep inguinal
Pelvic
Pelvic
Extracapsular spread
Total
No. positive
Yes
No
N/A
Total
No. positive
N/A
pTNM stage: pT ……… pN……… pM……. SNOMED codes: T...…... M………. T…….. M………. Signature of pathologist………………………………………… Date………….………..
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