kidney & urothelial tumours

8/9/2019 Kidney & Urothelial Tumours

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KIDNEY TUMOURS & UROTHELIAL TUMOURS

Speaker : Dr. Joram Khopey

Moderator : Dr. Sushma Kh.

Asstt. Professor

WHO histological classification of tumours of the kidney

I. Renal cell tumours

a. Clear cell renal cell carcinoma

b. Multilocular clear cell renal cell carcinoma

c. Papillary renal cell carcinoma

d. Chromophobe renal cell carcinoma

e. Carcinoma of the collecting ducts of Bellini

f. Renal medullary carcinoma

g. Xp11 translocation carcinomas

h. Carcinoma associated with neuroblastoma

i. Mucinous tubular and spindle cell carcinoma

j. Renal cell carcinoma, unclassified

k. Papillary adenoma

l. Oncocytoma

II. Metanephric tumours

a. Metanephric adenoma

b. Metanephric adenofibroma

c. Metanephric stromal tumour

III. Nephroblastic tumours

a. Nephroblastomab. Nephrogenic rests

c. Cystic partially differentiated

nephroblastoma

IV. Mesenchymal tumours

1. Occurring Mainly in Children

a. Clear cell sarcoma

b. Rhabdoid tumour

c. Congenital mesoblastic nephroma

d. Ossifying renal tumour of infants

2. Occurring Mainly in Adults

a. Leiomyosarcoma (including renal vein)b. Angiosarcoma

c. Rhabdomyosarcoma

d. Malignant fibrous histiocytoma

e. Haemangiopericytoma

f. Osteosarcoma

g. Angiomyolipoma

Occuring mainly in adults (contd)

i. Leiomyoma j. Haemangioma

k.Lymphangioma

l. Juxtaglomerular cell tumour

m. Renomedullary interstitial cell tumour

n. Schwannoma

o. Solitary fibrous tumour

V.Mixed mesenchymal and epithelial tumours

Cystic nephroma

Mixed epithelial and stromal tumour

Synovial sarcoma

VI.Neuroendocrine tumours

CarcinoidNeuroendocrine carcinoma

Primitive neuroectodermal tumour

Neuroblastoma

Phaeochromocytoma

VII.Germ cell tumours

TeratomaChoriocarcinoma

VIII.Metastatic tumours

,p53 overexpression

Renal cell neoplasms : putative cell of origin, classification, and genetic correlates

Renal Cell Carcinoma

Def: Renal cell carcinoma is a group of malignancies arising from

the epithelium of the renal tubules.

- Usually occurs in adults ( most common at 5th & 6th decades of

- Male: female 2:1

- Bilateral in 1% cases

Classification of RCC

Benign Malignant1. Oncocytoma 1. Clear cell RCC

2. Papillary adenoma 2. Papillary RCC

3. Chromophobe RCC

4. Collecting duct Ca* Renal medullary Ca

5. Xp11 translocation Ca

6. Ca asso. with neuroblastoma

7. mucinous tubular & spindle cell Ca8. Renal cell Ca , unclassified

Aetiology

Cigarette smoking causes 39% in males

Exposure to carcinogenic arsenic compounds

Exposure to asbestos, cadmium, pesticides, fungal toxins over

prolonged periods Oestrogen implicated in over wt. persons

Genetics:

- terminal deletion of short arm of chr. 3, beginning at 3p13

seen in non-papillary carcinoma of all types except in

oncocytic & papillary types

- overexpression of p53, loss Rb gene function

- Well delineated & centred on the cortex- May arise in any portion of kidney but occurs commonly in the

poles esp upper pole

- Solid golden-yellow separated from surrounding tissue bypseudocapsule

- Occurrence of haemorrhage,necrosis, calcification & cystic

changes give the tumour a variegated appearance

characteristic of this neoplasm

Renal cell carcinoma developing in the adult

form of polycystic renal disease

Gross appearance of renal cell carcinoma

Tumor is relatively well circumscribed and variegated, with a combination of

cystic, solid, and hemorrhagic areas.

Renal cell carcinoma well circumscribed and relatively

homogeneous

Involves almost the entire kidney and extends into the renal vein

Microscopic

- tumour cells are large, cytoplasmic appearance ranging fromoptically clear with sharp boundaries to deeply granular with

many transitional forms according to the type

1. Clear cell carcinoma2. Papillary carcinoma

3. Chromophobe renal carcinoma

4. Collecting duct carcinoma

5. Renal medullary carcinoma6. Sarcomatoid renal cell carcinoma/spindle cell carcinoma

Renal cell carcinoma, clear cell type.

Diffuse pattern of growth.

Clear cell typeThe most common type > 70-80%

Most are sporadic , in familial type it occurswith VHL disease

loss of sequences in the short arm of chr. 3

by deletion or translocation

Histologic patterns:

a. solid (most common)

b. glandular

c. papillary

d. spindled

- have a network of small, delicate, blood

vessels of uniform calibre that invest

alveolar clusters of ca cells ( this vascularpattern unique to CCRCC )

- prone to the formation of small & large

Cell morphology:

a. clear cells are polygonal, cuboidal or

columnar with distinct cell borders

High-power view showing optically clear cytoplasm and sharply outlined cell membrane

Papillary type

accounts for 10-15% of renal cancers

occurs in familial & sporadic forms

characterised by papillary growth

pattern cytogenetic abnormalities:

a. trisomies of 3q,7,8,12,16,17 & loss of Y in

males pts. in sporadic form

b. trisomy 7 in familial form

has better prognosis than conventional RCC

Papillae are compressed, imparting the tumora trabecular growth pattern.

Papillary renal cell carcinoma

The cells have a well-defined cell membrane,

faintly granular cytoplasm, and perinuclear

clear halo. The pattern of growth is solid.

Chromophobe type

- accounts for 5% of all cases

- nesting arrangement of tumour cells

- tumour cells have sharp borders &

abundant cytoplasm

- cytoplasm has pale, acidophilic quality

with a clear perinuclear region due to

+nce of cytoplasmic vesicles that stain for

Hales colloidal iron ( acidic mucin +nt)

- has better prognosis than conventional

RCC, can metastasize to lungs,liver

- can undergo a sarcomatoid change that is

prognostically unfavourable

Positive Hales colloidal iron stain in chromophobe carcinoma.

Collecting duct carcinoma

Tumour centered in the medullary portion of

the kidney and extends into the renal pelvis.

- contributes 1-2% of all cases, common in males

- thought to arise from intercalated cells

-lesions centred in the medullary region &

surrounded by desmoplastic reaction (tic clue)

-aggressive behaviour with distant mets at time of presentation

- mucin stain is +ve in contrast to conventional RCC

-Vinculin is immunohistochemical marker of choice

- genetics:Monosomies of chr. 1,6,14,15,22 have

been documented

Collecting duct carcinoma

Cellular stroma

Tubules

A cellular stroma separates the well-differentiated tubules

Collecting duct carcinoma showing branching

tubules lined by cuboidal cells.

Medullary Renal cell carcinoma

- is rare & occurs in young blacks with sickle cell disease

- very aggressive behaviour with very poor outcome

Oncocytoma

- adds ~7% of all primary non-urothelial epithelial renalneoplasms

- are solid & mahogany brown

- has a central stellate scar- may acquire huge size & invade renal capsule & vein

Central stellate( fibrous) scar

Microscopic- composed of cells with abundant

eosinophilic granular cytoplasm

growing in nesting or tubular fashion

- nuclei are round with small clumps of

chromatin & nucleoli

- mitotic figures absent or rarely present

- cytoplasm filled with mitochondria

(EM view)

* Chromophobe RCC (Eosinophilic variant)+ Oncocytoma tumour cells ve for CK7 or

express CK7 in scattered single cells or small

clusters of cells while Chromophobe RCC

express CK7 in almost all cells

++ CK20 is always negative

+++ No reactivity for vimentin (contrast to Conv.

-also c/a sarcomatoid renal cell carcinoma,

anaplastic carcinoma or carcinosarcoma

- makes up ~1% of all renal tumours in adults

-composed of spindle or pleomorphic tumour

giant cells-Is an extremely aggressive neoplasm &

extrarenal mets present during operation

Spindle cell RCC

Spindle cells

Pleomorphic giant cell appearance

Prognostic criteria in RCC

1. Staging

2. Nuclear grading

ROBSON SYSTEM TNM SYSTEM

Stage 1

Confined within renal capsule

T1 - confined by renal capsule & 70 µm

T1a - 40 µmT1b - 40 µm but 70 µm

T2 confined by renal capsule & 70 µm

Stage 2

Confined by Gerotas fascia

T3a - Invasion of adrenal or fat within Gerotas

fascia

T3b - Gross extension into veins or vena

cava below diaphragm

Stage 3

A- Grossly visible extension into renal vein or

vena cava

B- Lymphatic metastasis

C- both vascular extension & metastasis to nodes

T3c - Intravascular extension above

diaphragm or invades wall of vena cava

N1 - Single regional node

N2 - More than 1 regional node

Stage 4

Invasion of adjacent organ(xcept T4 Adrenal)

Haematogenous metastasis

Extension beyond Gerotas fascia

M1 -Distant metastasis

Staging of Renal cell carcinoma

5 Year survival rates following nephrectomy for RCC

Stage I ----- 60-80%

Stage II ----- 40-70%

Stage III ----- 10-40%

Stage IV ----- 5%

FUHRMAN NUCLEAR GRADING OF RCC

Grade Nuclear contour Size of nucleus Nucleoli

I Round, uniform ~10 µm Minute or absent

II Slightly irregular ~15 µm Visible at 400X

III Moderate to markedly ~20 µm Large, visible at 100X

irregular

IV Same as in III

multilobular,multiple or bizrre with heavy clumping of chromatin

Correlates the nuclear features with survival

Mesenchymal tumors

Clear cell sarcoma of kidney

- originally c/a Bone-metastasizing renal tumour of childhood

- highly malignant neoplasm resistant to conventional therapy

for Wilms tumour, responsive to doxorubicin-containingregimens

- occurs in same age range as Wilms tumour - at 12-36 months

- comprises 6% of paediatric renal tumours with male

preponderance (66%)- high potential for skeletal metastasis esp. to skull

Gross :

- c/s variable with homogenous,

grayish & lobular or variegated

appearances

- may produce mucin giving a

slimy glistening appearance

- well circumscribed

Microscopic :

- monotonous diffuse array of

small cells with round normo-

chromatic nuclei

- nuclei contain finely dispersed

chromatin & small nucleoli- cytoplasm is light-staining or

vacoulated with indistinct

borders

- branching array of small blood

vessels are present

THE MASQUERADES

Despite the name, the cytoplasm of MOST of the cells in clear

cell sarcoma of kidney is much less clear than that of CCRCC

(20% are clear)

These lesions are in no way related to clear cell sarcoma of soft

tissue

Distinguishing features of Clear cell sarcoma from Wilms tumour

1. No blastema foci seen

2. No non-renal elements

3. Are unilateral

4. Typical vascular pattern on microscopy

5. No specific genetic abnormalities detected

Angiomyolipoma

Def: is a benign mesenchymal tumour composed of a variable

proportion of adipose tissue, smooth muscle & abnormal

thick-walled blood vessels.

- has a female:male ratio of 4:1

- mostly are adults of age 45-55 yrs at sis

- Angiomyolipoma pts. suffer from Tuberous sclerosis also

Localization

- may arise in the cortex or medulla of kidney

- lesions may be multifocal & if so indicates a presumptive sis of

- tumours are golden yellow but colour variesaccording to the proportion of smooth muscle,

fats & blood vessels

- though well demarcated, are not encapsulated

- may resemble a lipoma

Microscopic

- shows mature adipose tissue, tortousthick-walled blood vessels with

eccenterically placed or very small lumen,

lack elastic lamina

- bundles of smooth muscles seem to

emanate from the vessel wall

- +ve for smooth muscle actin/or desmin,HMB45/or MelanA

. Lipoma

. Sarcomatoid RCC

. Malignant fibrous histiocytoma

Surgical excision is usually curative

Renal cell carcinoma, unclassified

- is a diagnostic category

- assigned to renal ca that do not fit into any category

Qualifying criteria or features of tumour for RCC , unclassified

+nce of :1. apparent composites of recognized types

2. sarcomatoid ca without recognizable epithelial elements

3. production of mucin

4. mixtures of epi. & stromal elements5. unrecognizable cell types

Nephroblastic tumours

Nephroblastoma

Synonymns: Wilms Tumour, embryoma, carcinosarcoma, adenosarcoma,adenomyosarcoma

Def: is a malignant embryonal neoplasm derived from nephrogenic blastemal

cells that both replicates the histology of developing kidneys and often

showing divergent patterns of differentiation.

- Accounts for 20% of all malignant tumours in children but can occur inadults also

- Mean age at sis is 37 & 43 months for & respectively

- No particular inclination for either sex

- Race : Blacks > Orientals > Whites

- Both kidneys equally affected - synchronous or metachronous bilat.involvement being 5-10%

Clinically

Abdominal mass

Abdominal pain or acute abd. crisis

Haematuria

Hypertension

Anaemia Polycythemia

A. For pretreated cases

I. Low risk tumours

¥ Cystic partially differentiated

nephroblastoma

¥ Completely necrotic nephroblastoma

II. Intermediate risk tumours

¥ Nephroblastoma epithelial type

¥ Nephroblastoma stromal type

¥ Nephroblastoma mixed type

¥ Nephroblastoma regressive type

¥ Nephroblastoma focal anaplasia

III. High risk tumours

¥ Nephroblastoma blastemal type

¥ Nephroblastoma diffuse anaplasia

B. For Primary nephrectomy cases

I. Low risk tumours

¥ Cystic partially differentiated

nephroblastoma

II. Intermediate risk tumours

¥ Non-anaplastic nephroblastoma

and its variants

¥ Nephroblastoma-focal anaplasia

III. High risk tumours

¥ Nephroblastoma diffuse anaplasia

Revised SIOP Working Classification of Nephroblastoma

Syndromes asso. c increased risk of nephroblastoma

1. WAGR syndrome

2. Beckwith-Wiedmann syndrome

3. Hemihypertrophy

4. Denys-Drash synd.

5. Familial nephroblastoma

6. Bloom synd.

7. Klippel-Trenaunay syndrome

Wilms tumour(variegated appearance)

- are solitary, well circumscribed, soft consistency

- variable size

- c/s may show areas of cystic changes, necrosis

& haemorrhage

Microscopic

3 major components

1. Undifferentiated blastema

2. Mesenchymal tissue

3. Epithelial tissue

in varying proportions

1. Blastematous area

- extremely cellular- composed of small round to oval primitive cells with scanty

cytoplasm

- growth pattern nodular, diffuse or cord-like

2. Mesenchymal area

- have a spindle cell fibroblast-like configuration or may showdifferentiation towards smooth muscle & skeletal muscle

3. Epithelial component

- characterised by +nce of tubules of various maturity or

glomeruloid structures- arranged haphazardly or in lobules separated by scant

mesenchymal component

Wilms tumor

Low-power view showing blastema, stroma, and immature tubular formations

Wilms tumor

High-power microscopic view showing a combination

of blastema, stroma, epithelial tubular formation, and

immature glomeruli.

Histochemical & Immunohistochemical properties

1. Blastematous elements focal +tivity for vimentin

2. Epithelial elements react for keratin, EMA, lectins

3. Mesenchymal elements myogenin & desmin

Genetics

- genetic loci predisposing to Wilms tumour are WT1 & WT2

- WT1 located at 11p13

- WT2 located at 11p15.5

Metastasis

- Locally to perirenal soft tissue adrenals, bowel,liver, vertebrae

- Distant mets to liver, lungs, peritoneum & CNS

Staging of Wilms tumour

Stage I - Tumour confined to kidney & completely resected

Stage II - Tumour extends locally outside the kidney but is

completely resected

Stage III - Residual tumour confined to the abd. without

haematogenous spread

Stage IV -Blood-borne metastasis or spread beyond abdomen

Stage V - Tumours present in both kidneys

1. Favourable histology - absence of anaplasia - Better response to chemotherapy2. Unfavourable histology - +nce of anaplasia - Poor response to chemotherapy

Anaplasia

- def as combination of cells with very large hyperchromaticnuclei & multipolar mitotic figures

- enlarged nuclei to be atleast 3 times as large as typical

blastemal nuclei in both axes with obvious hyperchromasia

- hyperdiploid mitotic figures must be present

Aniridia in a child associated with Nephroblastoma

UROTHELIAL TUMOURS

- renal pelvis, ureter & urinary bladder are lined by transitional

(urothelial) epithelium

- transitional epithelium is a stratified epithelium composed of

many layers of cells

- are better suited to cope with stretching , act as osmotic barrier

Transitional cell carcinoma of bladder

- 90% of primary tumour of bladder is of transistional cellcarcinoma

-Aetiological factors

* Cigarette smoking

* Exposure to aniline dyes (benzidine & -naphthylamine)* Long term use of phenacetin containing analgesics

* Cyclophosphomide

* Shistosoma haematobium infection

Age: Occurs in persons >50 yrsSex: Males> Females

Cytogenetic abnormalities

- monosomy of chr. 9

- deletion of 9p,9q,17p,13q,11p,14q

Sites of occurences in bladder

1. Lateral walls - 37%

2. Posterior wall - 18%

3. Trigone - 12%

4. Neck - 11%

5. Ureteric orifice - 10%

6. Dome - 8%

7. Anterior wall - 4%

May present as:

a. exophytic - adopts a papillary or solid appearanceb. endophytic - clusters of tumour in lamina propria

c. both

Grading of Urothelial tumours

WHO/ISUP Grades

I. Urothelial papilloma

II. Urothelial neoplasm of low malignant potential

III. Papillary urothelial carcinoma, low grade

IV. Papillary urothelial carcinoma, high grade

Pathologic staging of primary urothelial tumours

AJCC/UICC Depth of invasion

Non-invasive, papillary Ta

Carcinoma in-situ (Noninvasive,flat) Tis

Lamina propria invasion T1

Muscularis propria T2

Microscopic extravesicle invasion T3a

Grossly apparent extra vesicle invasion T3b

Invades adjacent structures T4

-extent of invasion is of prognostic value

Normal urothelial lining

Low grade urothelial neoplasm with

increased cell lining & scattered

hyperchromatic nuclei , cell order &cohesiveness maintained

Low grade carcinoma-in-situ with slight loss of cell cohesiveness & enlarged pleomorhic

High grade urothelial ca

* Loss of polarity

* Loss of cohesiveness

* Nuclear atypia

* Mitotic figures

Exophytic and papillary pattern of growth of a

transitional cell carcinoma arising in a bladder

Transtional cell ca of renal pelvis

Papillary tumors fill and distort the renal

pelvis

Thank You

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