Renal Cell Carcinoma & Other Solid renal lesions

Dr Charles Chabert

POW

May 2005

Epidemiology

• 12th most common site in men /17th female

• Low amongst Asian & African

• Highest in Czech Republic: 20/10 per 100,000

WHO 2004

Epidemiology

• Increase in all groups till mid ’80s

• Increase in incidence after age 40 years

• Decrease after age 75 years

• Male more commonly affectedWHO 2004

Aetiology

Environmental • Tobacco smoking• Carcinogenic arsenic• Asbestos, cadmium, organic solvents, fungal

toxins• Body Mass Index• Hypertension• Phenacetin

WHO 2004

Genetic Basis For RCC

• von Hippel-Lindau (VHL)

• Birt-Hog-Dube (BHD)

• Hereditary Papillary renal CA

• Hereditary Leiomyomatosis & RCC Syndrome

Pavlovich et at Urol Clin N Am 30,2003 437-454

von Hippel-Lindau

• First described by opthalmologists

• Autosomal dominant inherited

• VHL gene located at 3p25

• pVHL = Tumour suppressor genePavlovich et at Urol Clin N Am 30,2003 437-454

von Hippel-Lindau

Manifestations

• Renal cysts, Clear cell RCC

• Haemangiomas of retina & CNS

• Phaeochromocytoma

• Pancreatic cysts

• Endolymphatic sac

• Epididymal papillary cystadenomasPavlovich et at Urol Clin N Am 30,2003 437-454

von Hippel-Lindau

Type 1

No phaeochromocytoma

Type2a

Phaeochromocytoma

CNS & Retina haemangioblastomas

Type2b

+ pancreatic involvementPavlovich et at Urol Clin N Am 30,2003 437-454

Clinical Features

• Retinal lesions occur first

• Mean onset 25 years

• CNS haemangiomas later- 30years

• Renal lesions – 37 years

Clinical Diagnosis

• Haemangioblastoma of CNS or retina & extraneuronal lesion

• + Family History

• Any one lesion

Pavlovich et at Urol Clin N Am 30,2003 437-454

Birt-Hog-Dube

• Autosomal dominant

• Fibrofolliculomas

• Pulmonary cysts (90%)

• Spontaneous pneumothorax (20%)

• Renal neoplasms (25%)– hybrid oncocytic RCC

Pavlovich: J Urol, 173(5). May 2005 1482-1486

http://gateway.ut.ovid.com/gw1/ovidweb.cgi?View+Image=00005392-200505000-00012%7CFF2&S=IDNJHKJOKDBMAP00D&WebLinkReturn=Full+Text%3DL%7CS.sh.15.16.18.40%7C0%7C00005392-200505000-00012

http://gateway.ut.ovid.com/gw1/ovidweb.cgi?View+Image=00005392-200505000-00012%7CFF3&S=IDNJHKJOKDBMAP00D&WebLinkReturn=Full+Text%3DL%7CS.sh.15.16.18.40%7C0%7C00005392-200505000-00012

Hereditary Papillary RC

• Autosomal dominant - 50% penetrance

• Papillary RCC

• Late onset, bilateral & multiple

• Gene location 7q31 - mutations MET

Hereditary Papillary RC

• MET: proto-oncogene

• Induces mitogenesis, morphogenesis and cellular migration

• No documented extrarenal manifestations

Hereditary Leiomyomatosis & RCC

• Aggressive PRCC

• Uterine leiomyomas/ leiomyosarcomas/ cutaneous nodules

• Single lesions & early metastasis

Clinical Features of RCC

• Classic triad

• Incidental finding

• Systemic symptoms

• Paraneoplastic syndromes – 30%

Paraneoplastic Syndromes

• Haematological:

• Anaemia

• Raised ESR

• Stauffer syndrome

• Fever

• Amyloidosis: 8%

• Hypercalcaemia: 5-13%

• Erythrocytosis: 3-10%

• Hypertension: 10-40%

Paraneoplastic Syndromes

Histologic Subtype

• Clear cell RCC: 70%

• Multilocular RCC Reduced mets & LR

• Papillary: 15%

less aggressive

2 subtypes; type 2 more aggressiveLeibovich et al Uro Clin Am 30 (2003) 481-497

Clear Cell RCC

Clear Cell RCC

•

Clear Cell RCC

•

Papillary RCC

•

Histology

• Chromophobe RCC: 5%Excellent prognosis

Mets rare- propensity for liver

• Collecting Duct RCC: <1%

Aggressive

Rapid mets

Leibovich et al Uro Clin Am 30 (2003) 481-497

Chromophobe RCC

•

Grading

• Fuhrman System: 4 grades

• Features assessed:

• Nuclear size, contour, nucleoli

• Grade 1: 86% 5 yr survival

• Grade 4: 24% 5yr survival

Staging

• AJCC TNM 2002

• Changes from 1987-1997:stage T1 cutoff

• 2002: T1 substratified into T1a & T1b

• Validated by Salama et al: J Urol 173(5) May 2005.1492-1495

Management

• Radical nephrectomy

• Does Lap nephrectomy reproduce open technique?

• Issues:1. Early vascular control2. LN dissection3. Adrenal gland

Lymph Node Dissection

• LN dissection unnecessary, if node –ve on imaging

• No difference in 5yr survival.

• 2% node positive – correlates with EORTC 1%

Minervini et al BJU Int 2001;88:169-72

Adrenelectomy

• Large upper pole tumour or involved on CT

• Overall Incidence 5.7%

• T1-2 0.6%

• T4 40%

Tsui et al J Urol 2000:163;437-41

Oncological Outcome

• 5 year recurrence free & CA specific survival 92% & 98%

Portis et al J Urol 2002;167:1257-62

Conclusion

• Laparoscopic approach mirrors open

• New gold standard

Other Solid lesions

• Oncocytoma

• Aniomyolipoma

• Adenoma

Oncocytoma

• Benign epithelial neoplasms

• Mitochondria-rich, eosinophilic cytoplasm

• 5% renal neoplasms

• Centrally placed scar, spoke-wheel pattern

Oncocytoma

Angiomyolipoma

• Benign mesenchymal tumour

• Adipose tissue, smooth muscle & abnormally thickened blood vessels

• Independently or in association with TS

Metanephric Adenoma

• Rare condition recently diagnosed

• Benign course

• Histopathological diagnosis

Conclusion

• AML can be distinguished radiologically

• Others managed accordingly