Genitourinary Flashcards
What are 3 benign tumours of the kidney
Benign papillary adenoma
Angiomyolipoma
Oncocytoma
What are the two most common invasive malignancies of the kidney
Renal cell carcinoma
Wilms tumour
How common are benign papillary adenomas of the kidney at autopsy
Found in 7-22%
How do renal papillary adenomas differ from low grade papillary renal cell carcinoma histologically
No difference
Often size criteria used; >3cm much greater risk of spread
What is the most common subtype of renal cell carcinoma. What are it’s histological features
Clear cell
-non papillary
-clear or granular cytoplasm
-mutation of VHL/ chromosome 3 short arm deletions
What are the most common variants of renal cell carcinoma
Clear cell
Papillary
What is the gross presentation of the two most common types of renal cell carcinoma
Most commonly affect poles of kidneys
Clear cell: solitary tumour
Papillary: multifocal
What are the most common sites of metastasis of renal cell carcinoma. What are the rates of metastasis at diagnosis
Present in 15% at diagnosis
Lungs and bone most common site
What is the most common malignancy of the renal pelvis
Urothelial (transitional) carcinoma
What are the two precursor lesions to invasive urothelial carcinoma
Papilloma
Flat carcinoma in situ
Invasion of what layer of the bladder wall defines a T1 urothelial carcinoma. What layer defines T2a/b
T1: lamina propria (deep to basement membrane)
T2a: invasion of muscular is propria (less that half of thickness)
T2b: invasion of muscular is propria (more than half of thickness)
What 2 genetic mutations are frequently implicated in flat cis of the bladder
P53, Rb
What percentage of urothelial CIS proceeds to invasive cancer if left untreated
50-75%
What is the most common type of malignancy of the testis
Germ cell tumour
What are the two categories of germ cell tumour of the testis
Seminomatous
Non-seminomatous
What tumour markers should be checked in testicular cancer that for part of staging
B-hcg (choriocarcinoma)
AFP (embryonal carcinoma, yolk sac, +/-teratoma)
LDH (seminoma)
What are the main histological types of non seminomatous germ cell tumour
Mixed germ cell tumour (with components of multiple types below, and also seminomatous)
Embryonal carcinoma
Yolk sac (post pubertal type)
Choriocarcinoma
Teratoma (post pubertal type)
What is the usual CK7/CK20 profile for prostate cancer
Both negative
What are the two IHC markers most useful for RCC
PAX8 (uniformly positive in RCC)
CAIX (strong positivity in clear cell RCC (increased expression as a result of VHL mutation), most other variants of RCC negative)
What IHC tests can be used to distinguish RCC from adrenocortical neoplasms and pheochromocytoma
RCC: positive: PAX8, broad spectrum CK (AE1/AE3, cam 5.2). EMA (usually positive whereas CKs are variable)
Adrenocortical: positive: SF1, melan-A (other melanoma markers negative), inhibin, synaptophysis frequently positive. Negative: S100, chromogranin, cytokeratins
Pheo: neuroendocrine markers (synaptophysin, chromogranin, CD56), S100, SOX10, GATA3. Negative: SF1, CKs
What are the microscopic features of prostate adenocarcinoma
Loss of basal layer of glands
Invasion through basement membrane
Prominent nucleoli enlarged nuclei. Round nuclei.
Loss of gland formation with higher grade
Mitoses
Stromal desmoplasia
Glomerularions (glands that look like glomeruli)
Various intraluminal contents
What are the microscopic differences between benign and malignant prostate gland appearances
Benign: large, regularly spaced glands. No nucleoli, small nuclei. Abundant apical clear cytoplasm
Malignant: small glands with haphazard spacing. Large nuclei with prominent nucleoli.
What are the rules for Gleason grading
Primary pattern: always the most common pattern
Secondary pattern: must be present >5% if primary pattern is higher grade. If primary grade is lower then report any presence of highest grade
Tertiary: only reported for prostatectomy specimens. Other rules still apply
Epidemiology of bladder cancer
Common (4th male, 8th female)
Median age 70
M>F 3:1
Risk factors for bladder cancer
Smoking
Chemical exposure (industrial, hair dyes)
Medications: some analgesics, cyclophosphamide
Schistosomiasis (associated with SqCC)
Chronic inflammation
Radiation exposure
Lynch syndrome
What are the two hypothesis of the development of multi focal bladder cancer
1) clonogenic: arises from a single transformed cell, but malignant cells spread through urothelial tract via intraepithelial migration or seeding
2) Field change: multiple areas of urothelial mucosa exposed to same (chronic) carcinogen and independent malignant cells arise resulting in multiple tumours
Deletion of what chromosome is strongly associated with urothelial carcinoma
Chromosome 9
What are the two main pathways of development of urothelial carcinoma and their associated gene abnormalities.
1. Hyperplasia (most common pathway, 70-80%): chromosome 9 loss results in hyperplasia and superficial (non muscle invasive tumours). Associated with HRAS/FGFR3. 70% recurrence rate, 15% will progress to muscle invasive
2. Dysplasia (20-30%) chromosome 9 loss results in dysplasia then progression to muscle invasive tumour. Associated with p53 and Rb abnormalities. Invasive urothelial cancer associated with loss of e-cadherin
How is bladder CiS distinguished from dysplasia
HMWCK stains full thickness in CiS, but only the basal layer will stain in dysplasia
What is the importance of grading in non-invasive papillary carcinoma (Ta) bladder.
Low grade: CSS 98%
High grade: CSS 40%
What IHC stains are positive in urothelial carcinoma
CK7, CK20, HMWCK, GATA3, p63
What features of cytological atypia are used to distinguish low from high grade urothelial carcinoma
Mitotic rate
Nuclear size/pleomorphism, hyperchromatism
What is the most common precipitant of SqCC of the bladder
Chronic inflammation. (Eg recurrent uti, schistosomiasis, recurrent bladder calculi)
What is the macro and micro appearance of bladder SqCC
Whitish appearance, necrosis
Keratin pearls, intercellular bridges, CK5/6+. Adjacent squamous meta plasma/dysplasia
What are the differentials for a bladder mass
Pre-invasive
Cis
Ta
Malignant:
Urothelial carcinoma
SqCC
Adenocarcinoma
Small cell carcinoma
Sarcoma
Lymphoma
Melanoma
Metastasis
What are the epidemiological patterns of prostate cancer
Male gender
Increasing age
Family history
African American race
What are the microscopic features of each Gleason grade of prostate cancer
Grade 1- closely packed glands, larger than grade 3 glands. Abundant cytoplasm
Grade 2- some irregularity of glands, but still large, abundant cytoplasm
Grade 3- abundant small glands, variable in size and shape
Grade 4- fused glands, cribriform glands, glomerulations
Grade 5- sheets of cells, loss of glands. Comedo necrosis
IHC staining prostate adeno vs urothelial cancer
Opposite patterns
Urothelial: (positive) p63, HMWCK, GATA3, CK7/20
Prostate: AMACR, NKX3.1, PSA, PSMA. (In benign prostate tissue p63, HMWCK both positive)
What is the significance of the presence of intraductal carcinoma of the prostate in biopsies of adenocarcinoma
Associated with high grade, high volume disease. Early biochemical recurrence and metastatic disease.
What are the microscopic features of intraductal carcinoma of the prostate
Large calibre glands
Preservation of basal cell layer (p63 and HMWCK positive in basal layer of glands
Significant nuclear atypia
Comedo necrosis often present
What IHC stains would be useful in a general panel for testicular tumours
AE1/AE3 (neg lymphoma, spermatocytic)
SALL4 (non specific, but positive most germ cell tumours)
OCT3/4 (seminoma and embryonal carcinoma only)
B-hcg (choriocarcinoma)
CD45 (lymphoma)
CD30 (embryonal carcinoma)
CD117/ckit (multiple)
AFP
Glypican 3
Sox 2
What is the most aggressive germ cell tumour
Choriocarcinoma. Frequent hemorrhagic Mets
What chromosomal abnormality is commonly associated with testicular seminoma and embryonal carcinoma
Isochrome 12p
Ie, loss of the q arm of chromosome 12, and the 12p arm gets mirrored.
What is the microscopic appearance of seminoma
Large polygonal cell with clear cytoplasm
Distinct cell membranes
Prominent nucleoli
Nested architecture
Lymphocyte infiltrate
What is the difference in behaviour of post pubertal testicular teratoma and ovarian teratoma
Testicular usually malignant, ovarian usually benign
What are the two main types of sex cord stromal tumours
Leydig cell tumour - may secrete testosterone and cause precocious puberty
Sertoli cell tumour
What are the subtypes of seminomatous germ cell tumour
Classical
Anaplastic
Spermatocytic
Aside from germ cell tumours and sex cord stromal tumours, what other tumours are associated with the testis
Lymphoma
Mesothelioma (of tunica vaginalis)
Sarcomas (eg liposarcoma, rhabdomyosarcoma)
What are the 3 WHO categories of testicular tumours (not including lymphoma, sarcomas)
Type 1: Germ cell tumours derived from GCNIS (most of the common types including postpubertal teratoma). Associated with isochrome 12p
Type 2: Germ cell tumours unrelated to GCNIS (spermatocytic, pre-pubertal yolk sac and teratoma)
Type 3: Sex cord stromal tumours (serotonin cell, leydig cell + others)
What is the S component of staging for testicular germ cell tumours
Serum tumour marker levels (AFP, bHCG, LDH)
S0= all not elevated.
S1-3 depending on exact levels they are raised to
At a basic level what is represented by the different stages of testicular germ cell tumour
Stage 1a: T1
Stage 1b: T2-4
Stage 2a-c: N1-3
Stage 3: M+
How are is the primary staged for testicular cancer (ie T1-4)
T1: not invading tunica vaginalis
T2: invading tunica vaginalis
T3: invading spermatic cord
T4: invading scrotum (risk of node spread to inguinal/ext iliac)
What is the microscopic appearance of testicular embryonal carcinoma
Large crowded pleomorphic cells (giving purple appearance to slide)
Vesicular nuclei, prominent nucleoli
Variable architecture (nests, sheets, papillae, glands)
What is the microscopic appearance of testicular choriocarcinoma
Cytotrophoblasts and trophoblasts (mononuclear with light cytoplasm)
Syncytiotrophoblasts (multinucleated with deeply eosinophilic cytoplasm- giving red colour to slide)
Abundant haemorrhage
Associated with haemorrhagic metastasis
What is the typical microscopic appearance of testicular post pubertal yolk sac tumours
Usually part of a mixed germ cell tumour
Most commonly reticular/microcytic architecture (honeycomb mesh work)
Hypocellular myxoid areas
Other distinctive features (see Kurt’s notes)
