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Renal tumours adults

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overview of kidney tumors in adults

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Renal tumours adults

  1. 1. Urology Series – Mon. 09th .May.2016, 07am: part I & - Mon. 16th .May. 2016, 07am: part II RENAL NEOPLASMS IN ADULTS Dr. K.J. Mburu MMed Urology II Moderators: Dr. Owilla/ Dr. Monda 1
  2. 2. Introduction-Renal Masses • Renal masses are a biologically heterogeneous group of tumors ranging from benign masses to cancers that can be indolent or aggressive. • The true incidence of renal masses (including benign lesions) is unknown, but benign lesions comprise approximately 20 percent of surgically resected tumors. • Renal masses can be malignant, benign, or inflammatory as classified by Barbaric (1994) • They can be classified based on radiographic appearance (simple cystic, complex cystic, fatty tumors, and others) • WHO, 2004, histological classification 2
  3. 3. Benign Renal Masses • Simple cyst • Angiomyolipoma • Oncocytoma • Renal adenoma • Metanephric adenoma • Cystic nephroma • Mixed epithelial/ stromal tumor • Reninoma (JG cell  tumor) • Leiomyoma • Fibroma • Hemangioma • Vascular – Renal artery  aneurysm – Arteriovenous  malformation • Pseudotumor 3
  4. 4. Malignant Renal Masses • Renal cell carcinoma – Clear cell – Papillary – Chromophobe – Collecting duct • Urothelium based – Transitional cell  carcinoma – Squamous cell  carcinoma – Adenocarcinoma • Sarcoma – Leiomyosarcoma – Liposarcoma – Angiosarcoma – Hemangiopericytoma – Malignant fibrous  histiocytoma – Synovial sarcoma – Osteogenic sarcoma – Clear cell sarcoma – Rhabdomyosarcoma • Wilms tumor • Primitive neuroectodermal  tumor • Carcinoid • Lymphoma • Leukemia Metastasis • Invasion by adjacent  neoplasm 4
  5. 5. Inflammatory Renal Masses • Abscess • Focal pyelonephritis • Xanthogranulomatous pyelonephritis • Infected renal cyst • Tuberculosis • Rheumatic granuloma 5
  6. 6. Renal Masses Classified by  Radiographic Appearance • Simple Cystic – Cyst – Multiple cysts – Peripelvic cysts – Calyceal diverticulum – Hydronephrosis • Complex Cystic – Cystic nephroma  – Cystic renal cell carcinoma      – Hemorrhagic cyst  – Infected cyst  – Renal abscess  • Fatty Tumors – Angiomyolipoma – Lipoma – Liposarcoma • All Others – Renal cell carcinoma    – Sarcomas – Lymphoma,leukemia – Metastases – Oncocytoma – Renal adenoma  – Metanephric adenoma  – Reninoma (JG cell tumor)      – Leiomyoma – Fibroma – Hemangioma – Carcinoid – Primitive neuroectodermal tumor    6
  7. 7. WHO,2004, Histological Classification Of Tumours Of The Kidney 1. Renal cell tumors 2. Metanephric tumors 3. Nephroblastic tumors 4. Mesenchymal tumors 5. Mixed mesenchymal and epithelial tumors 6. Neuroendocrine tumors 7. Haematopoietic and lymphoid tumors 8. Germcell tumors 9. Metastatic tumors 7
  9. 9. Benign Renal Masses • Are non-cancerous growths of the kidney that do not metastasize to other sites in the body • They are not life-threatening but they can cause complaints if they exert pressure effects on adjacent structures. • As there is universal increase in the use of radiological imaging, benign renal masses are being detected more frequently . 9
  10. 10. Renal cysts • Most common benign renal lesions – Represents more than 70% of asymptomatic renal masses • Can be solitary or multiple, unilateral or bilateral (terada et al, 2002) • Sporadic or familial 10
  11. 11. Renal cysts • Risk factors for development of sporadic renal cyst; (tarada et al, 2004) – Increasing age – Male gender – Presence of hypertension – Presence of renal insufficiency • End stage renal disease - dialysis 11
  12. 12. Bosniak Classification ( Israel & Bosniak,2005; Warren & McFarlane,2005) • Most useful and widely employed method for characterizing renal cystic lesions – and for assessing the likelihood of the presence of a concomitant malignancy within the cyst 12
  13. 13. 13
  14. 14. 14
  15. 15. Bosniak Class III & IV Lesions • associated higher risk of malignancy • Definitive therapy – surgical excision, • ablative therapiesof cystic masses have been reported(Raman et al 2009) – cryotherapy – radio frequency ablation 15
  16. 16. Clinical presentation • Benign cystic lesions of the kidney can grow to such a large size that they can cause pain or other symptomatology, including hypertension (porpigia et all, 2009; zerem et al, 2009) • Symptoms can also occur as a result of – hemorrhage within the cyst or spontaneous/traumatic cyst rapture, (hughes et all, 1995; rainio et all, 2006; ishikawa et al,2008; vaidyanathan et al, 2008) – Cyst infection, abscess formation, and/or sepsis – Erythrocytosis/polycythemia – Calcification in or around cysts 16
  17. 17. Therapeutic interventions cho et al,2008;ham et al,2008;baysal&soylu,2009;canguven et al,2008;choi et al, 2009;porpigilia et al,2009 • Aspiration • Surgical resection • Cyst decortications • Sclerotherapy 17
  18. 18. Renal cortical/ Papillary adenoma • a benign renal neoplasm arising from the renal tubular epithelium and almost always located within the cortex.  – considered one of the commonest of renal epithelial neoplasms. (renshaw,2002) • Epidemiology – They have been reported in 7% of nephrectomy specimens and 10-40% of autopsies. – In autopsy series, the lesions are more common in older patients (10% of patients <40 years; 40% in those >70 years). 18
  19. 19. Renal cortical/ Papillary adenoma • cytogenetics – Loss of the Y chromosome, and combined trisomy of both chromosomes 7 and 17 are early changes in renal papillary neoplasms. – small papillary lesions show these changes only, while PRCC show these, as well as gains of chromosomes 12, 16, and 20. 19
  20. 20. Renal cortical/ Papillary adenoma • Incidence of renal adenomas increases with age and male gender • these tumors also have been associated with acquired renal cystic disease that result in end stage renal failure (leroy et al,2001;denton et al,2002;snyder et al,2006;ferda et al,2007). 20
  21. 21. Renal cortical/ Papillary adenoma • Antemortem pathologic diagnosis of renal adenoma is much less common – No reliable histopathological, ultrastructural, or immunohistochemical criteria • Renal adenomas have been suggested to be a premalignant precussor of Papillary RCC (Wang et al; Brunnelli et al,2003) – Histologic and genetic abnormalities of renal adenomas are indistinguishable from papillary RCCs. 21
  22. 22. Clinical presentation, management and prognosis • Asymptomatic • Undetectable radiographically because of their small size(less than 1 cm) • Require no further therapy • Prognosis – Renal papillary adenomas theoretically have no metastatic potential. 22
  23. 23. Metanephric adenoma • Most common benign renal parenchymal tumor • Reported in 1995 by Davis & Colleagues – 50 cases of an unusual and novel renal mass lesion with distinctive histological features and benign clinical course despite occasional symptomatic presentation and large tumor size (5-15cm) – Half the patients presented with flank pain, gross haematuria, or a palpable mass – Six patients presented with polycythemia, and hypercalcemia 23
  24. 24. Metanephric adenoma • Female predominance (2:1) (jones et al,1995;snyder et al,2006;bastide et al,2009) • Incidental presentation most common • Peak incidence in 5th -6th decade (renshaw,2002) 24
  25. 25. Metanephric adenoma • Polycythemia seen in 10% of patients, – production of erythropoeitin and other cytokines by the tumor (yoshioka et al,2007;bastide et al,2009) • Radiographically, these tumors can have peripheral or central calcifications and may be hypovascular on contrast-enhanced CT and hyperechoic on ultrasonography (bastide et al,2009) 25
  26. 26. Metanephric adenoma • Ultrasound –Metanephric adenoma appears as an expansile hypoechoic or hyperechoic mass on sonography.  26
  27. 27. Metanephric adenoma • CT – appear as heterogeneous, hypovascular masses with frequent foci of hemorrhage and necrosis. – Calcification is seen in 20% of cases.  27
  28. 28. Metanephric adenoma • Positive staining for wilms tumor protein, WT1,(muir et al,2001;bosco et al,2007) – mutations or deletions in the WT1 gene on 11p13  – Suggests histogenic relationship with wilms tumor • Alternative theory for origin of metanephric adenoma,(Brown & associates,1997), – Gain of chromosomes 7&17 – Suggests histogenic relationship with pRCC 28
  29. 29. Metanephric adenoma • Varius histologic stains have been evaluated to distinguish metanephric adenoma from other renal neoplasms – Wilms tumor marker WT1, is frequently expressed in metanephric adenoma,(muir et al,2001;bosco et al,2007) – Alpha methylacylcoa racemace is poorly expressed in metanephric adenoma but highly expressed in papillary RCC – S-100 is highly expressed in metanephric adenoma, weak in wilms tumor, and absent in papillary RCC.(azabdaftari et al,2008) 29
  30. 30. summary • Rare • Lack of highly predictive clinical or radiographic criteria • Remains a pathological diagnosis • Radiologic findings raise the index of suspicion • percutaneous core biopsy with FNA prove helpuful • Observation • Nephron sparing treatment 30
  31. 31. Angiomyolipoma • Originally described in 1911 by Fischer, and current name given by Morgan in 1951 • Accounts for less than 10% of renal tumors • Consist of thick walled aneurysmal vessels, smooth muscles and fat (tamboli et al,2000;nelson et al,2002;bissler et al,2004) • Present in 25-50% of patients with tuberous sclerosis (lesions in cerebral cortex-epilepsy & mental retardation, skin abnormalities) • 2 distinct histologic subtypes – Classic – Monotypic epitheliod 31
  32. 32. Angiomyolipoma • Initially considered to be a harmatoma or choriostoma • Recent evidence suggests neoplastic origin with evidence of a monoclonal, rather than polyclonal, source (green et al 1996;sepp et al,1996;katter et al,1999) • Considered to be of neurocrest origin,possibly derived from perivascular epitheliod cells 32
  33. 33. Angiomyolipoma • Tumor strongly expresses estrogen receptor-beta and androgen receptor – Pedominantly found in females, Rarer before puberty (boorjian et al,2008) • Sporoadic or associated with TSC 33
  34. 34. Angiomyolipoma • Typical sporadic presentation is of a middle aged woman with single asymptomatic tumor • Sporadic angiomyolipomas have a slow growth rate,detected incidentally • Angiomyolipoma is the most common neoplasm associated with spontaneous perirenal hemorrhage,closely followed by RCC (zhang et al,2003) 34
  35. 35. Angiomyolipoma • 20-30% of angiomyolipomas are in patients with TSC – and ~50% of patients with TSC develop angiomyolipomas (eble,1998; neumann et al,1998;tamboli et al,200; lendvay et al,2003, minor et al,2003) • TSC associated angiomyolipomas typically present – at a younger age (mean age 30yrs), – f:m=2:1, – with multiple,bilateral, and symptomatic tumors(eble,1998 neumann et al,1998; lendvay et al,2003) • TSC Classical triad of seizures,adenoma sebaceum&mental retardation may not be present (steiner et all,1998) 35
  36. 36. Angiomyolipoma • Wunderlich syndrome – Reported in 10% of patients – Massive spontaneous retroperitoneal hemorrhage • Angiomyolipoma followed by RCC – Most significant complication of renal angiomyolipoma – Significant morbidity and potential mortality if not promptly treated (oesterling et al,1986;steiner et al,1993;eble,1998) – Pregnancy increases risk of hemorrhage (eble,1998) 36
  37. 37. Angiomyolipoma • Angiomyolipoma is the only benign renal tumor that is confidently diagnosed with CT scan on cross-sectional imaging – Presence of fat within renal lesion is considered diagnostic hallmark (jinzaki et al,1997;lemaitre et al,1997; bosniak et al,1998; simplfendorfer et al,2009) 37
  38. 38. 38
  39. 39. Angiomyolipoma • Utrasonography – Well-circumscribed,highly echogenic lesion with shadowing (siegel et al,1996; lemaitre et al,1997) • Angiography (ct angiography) – Aneursysmal dilatation in 50% of angiomyolipomas – Size of aneurysms correlate with risk of rapture (yamakado et al, 2002) 39
  40. 40. 40
  41. 41. Angiomyolipoma • Radiological ddx – Retroperitoneal Liposarcoma (very rare) in the setting of large angiomyolipoma • On CT, they compress or only extrinsically push the renal parenchyma (clark &novick,2001;wang et al, 2002) – Fat containing RCC, may contain calcifications, usually almost never seen in angiomyolipomas (henderson et al,1997;lemaitre et al,1997;roy et al,1998) 41
  42. 42. Angiomyolipoma • Percutaneous biopsy • Core biopsy – Eminently accurate in the diagnosis of angiomyolipoma (lebret et al,2007; silverman et al,2007) 42
  43. 43. Angiomyolipoma-Invariably benign • Extrarenal occurrences – Hilar lymph nodes – Retroperitoneum – Liver – Direct extension into venous system (Eble 1998;turker koskal et al,2000;gogus et al,2001;nelson and sanda,2002;lin et al,2003;bissler and kingswood,2004;ackali et al,2006;haritharan et al,2006;blick et al,2008;schade et al,2008) • Benign clinical course still follows • Indicates, multicentric origin, rather than malignancy with metastases 43
  44. 44. Angiomyolipoma • Pathological ddx – Many angiomyolipomas exhibit regions of Cellular atypia Fibrosarcoma Leiyomyosarcoma Liposarcoma • Positive immunoreactivity for HMB-45,a monoclonal antibody, is characteristic of angiomyolipoma – Differentiate angiomyolipoma from other sarcomas (eble1998) 44
  45. 45. Epitheliod angiomyolipoma(eble and colleagues,1997) • Predominant epitheliod component • Can metastasize • In patients with/without TSC (Pea et al,1998;l’hostis et al,1999;martignomi et al,2000;cibas et al,2001; mene et al,2001;nelson and sanda,2002;saito et al,2002;bissler and kingswood,2004;huang et al,2007;limaiem et al,2008;matsuyuma et al 2008;moudouni et al 2008;zanelli et al,2008;kato et al,2009) • This phenotype is characterized by epitheliod cells that are cytokeratin negative and HMB-45 positive 45
  46. 46. Angiomyolipoma-Optimal treatment • Treatment must be individualized • Management should take into account – the size of tumor; cut point=4cm (steiner et al,1993;nelson and sanda,2002) – presence of symptoms, (pain, bleeding) – and patients factors. • Asymptomatic small tumors – Observed expectantly – Imaging, 6-12 months, this define growth rate and clinical siginificance (oesterling et al,1986;De luca et al,1999; martin et al,2008 ) 46
  47. 47. Angiomyolipoma • Intervention – Large tumors, particularly if patient is symptomatic – Taking into account • Patients age • Comorbidities • Women of child bearing age • Access to surveillance or emergency care – Nephron spearing approach,either by; • Selective embolization • Open/laparoscopic/robotic partial nephrectomy- wedge resection or enucleation even in solitary kidney (fazeli-matin and novick,1998;boorjian et al,2007; minervin et al,2007) 47
  48. 48. Angiomyolipoma- Selective embolization • Preferred modality (nelson and sanda,2002;harabayashi et al,2004) • Considered as 1st line, in patients with acute or potentially life threatening hemorrhage - surgical exporation in this setting result in total nephrectomy (pappas et al,2006;chang et al,2007) • Overall complications is 10%,similar to rates of partial nephrectomy (boorjian et al,2007) – Hemorrhage – Abscess formation – Sterile liquifaction of tumor, which may require; • Percutaneous drainage • Surgical intervention 48
  49. 49. Angiomyolipoma-Ablative therapies • Include: – radiofrequency ablation (reduce pain) (prevoo et al,2008) – and cryoablation (destroy tissue) (bachman et al,2005;bryd et al,2006; littrup et al,2007; caviezel et al,2008) • Best for treatment of patients – with TSC who have multicentric angiomyolipomas – Older patients with co-morbidities who require treatment and are not candidates for embolization 49
  50. 50. Oncocytoma • The first case of renal oncocytoma was reported by Zippel in 1942. • Renal Oncocytoma (RO) is a benign renal epithelial neoplasm that accounts for 3%- 7% of kidney tumours (morra and Das 1993) • Embryologic origin – Many investigators have suggested that these tumors originate from intercalated cells of the collecting system. 50
  51. 51. Oncocytoma • Etiology – Renal oncocytomas can present in familial or sporadic forms. – Familial RO • Oncocytomas are the most frequent renal tumors in patients with Birt-Hogg-Dube syndrome (BHD) caused by mutations in the folliculin gene (FLCN). – The etiology of sporadic RO is not known 51
  52. 52. Oncocytoma • Genes involved and Proteins –Mutations in folliculin gene (FLCN, 17p11.2) cause Birt-Hogg-Dube (BHD) syndrome • rare inherited genodermatosis • characterized by –hair follicle hamartomas, – kidney tumors, –and spontaneous pneumothorax. 52
  53. 53. Oncocytoma • Cytogenetics – Complete or partial loss of chromosome 1 is the most common cytogenetic abnormality reported in approximately 40% of cases (lindgren et al,2004; paner et al,2007). – Other frequent changes include loss of Y (15%) and monosomy 14q (15%). (Lindgren et al, 2004; Philips et al, 2001) – Trisomy 7 has been reported as the most common chromosomal gain in up to 5% of patients. – Structural rearrangements involving 11q12-13 have been reported. – Approximately 50% of tumors show no chromosomal abnormalities. (schwerdtle et al,1997;chao et al,2002; pollascik et al, 2002; lindgren et al, 2004) 53
  54. 54. Oncocytoma pathology • Renal oncocytomas generally occur and are contained within a well-defined fibrous capsule • The tumors are usually solitary and unilateral, although several bilateral cases and multiple oncocytomas occurring simultaneously (oncocytomatosis) have been reported (Tickoo et al, 1999). • Tan to mahogany brown, homogenous, well encapsulated • May achieve large size upto 12cm in diameter • Metastasis is extremely rare though invasion of the lymphovascular spaces has been observed. 54
  55. 55. Oncocytoma • 1/3 of cases, – hemorrhage, – extension into perinephric fat, – cellular atypia, – prominent nucleoli,and pleomorphism • may be seen, yet clinical behaviour in this cases is is within what is expected with a benign course (amin et al,1997;perez-ordonez et al,1997). 55
  56. 56. Diagnosis of Oncocytoma • predominantly pathologic because there are – no reliable distinguishing clinical characteristics. • Gross hematuria and flank pain occur in <20% of patients. Males more than Females, peak 70 years • No characteristic features of the tumors appear on CT, ultrasound (US), intravenous urography (IVU), or MRI. • Angiographic features include the “spokewheel” appearance of tumor arterioles, the “lucent rim sign” of the capsule, and a homogeneous capillary nephrogram phase. – Unfortunately, these findings are not invariable, and similar findings have been reported in patients with renal cell carcinoma (RCC). 56
  57. 57. 57
  58. 58. Oncocytoma • In most cases the treatment options are isolated to – observation, particularly for the older or sicker patient, – and surgical resection, particularly for the younger healthier patient. • nephron-sparing approach is preferred given the benign nature of these lesions and the very low probability of recurrence (Licht, 1995; Romis et al, 2004; Gudbjartsson et al, 2005). • Thermal ablation, although sometimes reported as a treatment option, – commits the patient to long-term radiographic surveillance, – lower success rates of these procedures – unknown longterm outcomes, 58
  59. 59. Cystic Nephroma • Cystic nephroma is a characteristic renal lesion with bimodal age distribution and benign clinical course (tamboli et al,2000) – Diagnostic peak primarily in the first 2-3 years of life • Predominantly in Males – 4th and 5th decades • Female prevalence, significant 8:1 (madwell et al,1983; upadhyay and neely,1989; castillo et al,1991; stamatiou et al,2008; kuzgunbay et al,2009) • Familial cases have been reported in literature • Reported cases of sarcomas and clear cell carcinoma arising from cystic nephroma (bal et al,2005;omar et al,2006; raj et al,2006;ashley and reinberg,2007) 59
  60. 60. Cystic Nephroma • Clinical presentation – Abdominal mass – pain – Haematuria • Majority are Incidental findings (madwell et al,1983;kuzgunbay et al,2009) 60
  61. 61. Cystic Nephroma • Radiologically (madwell et al,1983; turbiner et al,2007) – Solitary – Centrally located – Widely variable in size (mean 9 cm) – Demonstrate culvilinear calcifications – Herniatiation into the renal collecting system – Septal enhancement • NB: radiological differentiation between cystic nephroma and cystic RCC in adults and wilms in children is not possible (vujanic et 61
  62. 62. Cystic Nephroma 62
  63. 63. Cystic Nephroma • Immunohistochemical studies – Affinity for epithelial component for cytokerratins – Stromal components frequently stain positive for • CD10, • calretinin,I • nhibin, • estrogen, and progesterone receptor (turbiner et al,2007; montironi et al,2008) 63
  64. 64. Cystic Nephroma • Management – Children, concern for cystic wilms? • Radical nephrectomy – Adults, • Nephron spearing approach with partial nephrectomy 64
  65. 65. MIXED EPITHELIAL STROMAL TUMOR (MEST) • Rare benign adult renal neoplasm • Made of epithelial and mesenchymal components (adsey et al,2000) 65
  66. 66. MEST - occurence • Female predominance (6:1) • 4th decade • Adsay et al,2000, showed that; – majority of women diagnosed with MEST had estrogen replacement therapy – The Only male patient in the largest MEST series had androgen deprivation therapy for prostate cancer 66
  67. 67. MEST - presentation • Similar to those of cystic nephroma – Abdominal mass – pain – Haematuria • Majority detected incidentally (adsay et al,2000;turbiner et al,2007;montironi et al,2008) 67
  68. 68. MEST - Radiologic appearance • CT scan – Complex cystic renal mass, indistinguishable from cystic RCC (adsay et al,2000) • MRI – Involvement of renal hilum – Compression of pelvicalyceal system – Gross infiltration of adjacent renal parenchymal is NOT seen 68
  69. 69. MEST • Summary – A preoperative diagnosis of MEST should be considered in perimenopausal women receiving hormone therapy; – Radiological differentiation from rcc is not reliable – surgical intervention, preferably with a nephron sparing approach should be offered to appropriately selected patients 69
  70. 70. LEIOMYOMA • Rare,benign tumors that may arise from smooth muscle cells anywhere along the genitourinary tract (tamboli et,2000) • Kidney – Tumors arise from renal capsule – Renal pelvis and renal vein sites of origin also reported (wells et al,1981;steiner et al,1990;o’brien et al,1992;rao et al,2001) • Majority are Incidental findings during CT-abdomen (romero et all,2005; derche et al,2008) • 15 % detectable clinically (romero et al,2005) 70
  71. 71. Leiomyoma CT SCAN • Small exophytic renal mass with/without enhancement arising from smooth-muscle- containing areas of the kidney including the renal capsule and renal pelvis. • Radiological differentiation from rcc is not possible (steiner et al,1990; derchi et al,2008) 71
  72. 72. Leiomyoma • Gross – Well encapsulated – Range from purely cystic to mixed solid/cystic or solid in appearance • Histologically – Reveales intersecting fascicles of smooth muscles – No evidence of hypercellularity, pleormophism, mitotic activity or necrosis (steiner et al,1990; tamboli et,2000) – Calcification uncommon 72
  73. 73. Leiomyoma • Immunohistochemical stains – Confirm smooth muscle nature of the tumor – Strong diffuse positive staining for smooth muscle markers desmin and caldesmon (romero et al,2005) • Management – Nephron sparing approaches should be considered for peripherally located small lesions 73
  74. 74. Other benign renal tumors  Reninoma – Benign tumor of renal juxtaglomerular cell apparatus (wong et al,2008) – Females in 3rd and 4th decade are most commonly affected (martin et al,2001; rubenstein et al,2002; wong et al,2008) – Clinical presentation, dominated by hypersecretion of renin (schonfeld et al,1991; rubenstein et al,2002) • Hypertension • Hypokalaemia – Associated symptoms • Polydipsia • Polyurea • Myalgia • Headache 74
  75. 75. 75
  76. 76. Other benign renal tumors  Reninoma • The diagnosis is confirmed by Selective renal vein renin sampling with lateralization – It has been suggested that renin lateralization ratio (LRR)>1.5    maximizes the specificity of this investigation • Radiologic appearance – Small (less than 3cm), solid hypovascular renal mass • Management – Surgical excision,sparing remaining renal parencyma. (dunnick et al,1983; schonfeld et al,1991; tanabe et al,2001) • Rapid decline of plasma renin levels • Normalization of blood pressure • Resolution of associated symptoms 76
  77. 77. Other benign renal tumors  Reninoma • Histological examination • Sheets of polygonal to spindle-shaped cells with indistinct cell borders,abundant eosinophilic cytoplasm,and minimal atypia (martin et al,2001) • Immunohistochemistry • For factor VIII and factor VIII-related antigens is characteristic • Confirms deviation from endothelial cell lineage (sanfilippo et al,1982) • NB/ only one case of malignant reninoma has been documented in literature (duan et al,2004) 77
  78. 78. Other benign renal tumors Hemangiomas • small vascular tumors occurring in the kidney • Multiple lesions in one kidney occur in approximately 12% of cases • rarely bilateral. • source of hematuria in an otherwise well-evaluated patient. • Risk factors associated with Kidney Hemangioma include: – Individuals with Sturge-Weber-Krabbe syndrome (encephalotrigeminal angiomatosis) or von Hippel Lindau (vHL) disease may be at an increased risk of developing Kidney Hemangiomas – Hemangiomas of the bowel, liver, bone, or brain may also increase the risk • The diagnosis may be determined by CT angiography, MR angiography, or by direct visualization by endoscopy (Ekelund and Gothlin, 1975). • Treatment methods for Kidney Hemangiomas may include: – Radiation therapy -Laser-assisted ablation – Endoscopic surgery - Nephron sparing surgery ? Radical nephrectomy 78
  79. 79. 79
  80. 80. 80
  81. 81. 81
  82. 82. Fibroma • Fibromas are tumors of the fibrous tissue on, in, or surrounding the kidney. • They are rare and are more common in women. • Their cause is unknown and most do not cause symptoms. • Usually they grow on the periphery of the kidney and can become large before becoming clinically obvious. • While generally benign, these tumors have no special characteristics to differentiate them from malignant tumors of the kidney. • Because of this uncertainty of diagnosis, – observation – partial or radical nephrectomy is the standard treatment. • Good prognosis 82
  83. 83. Other benign renal tumors Renal lipomas • very uncommon deposits of mature adipose cells without evident mitosis that arise from the renal capsule or perirenal tissue. • They are seen primarily in middle-aged females • owing to the characteristic CT differentiation of fat, are best detected radiographically on CT scanning. • Nephrectomy? Partial? radical 83
  84. 84. … end of part I thankyou. 84
  85. 85. References 1. Campbell Walsh Urology 10th Edition; 1413-1505 2. Smith and Tanagho’s General Urology 18th Edition; 330-349 3. AUA guidelines 4. EUA guidelines 5. Pub Med Health 6. http://www.uonbi.ac.ke/ Digital Repository 7. http://www.emedicine.medscape.com 85
  87. 87. Renal Cell Carcinoma (RCC) EPIDEMIOLOGY • Accounts for 2% - 3% of all adult malignant neoplasms – 90-95% of neoplasms arising from the kidney. • 35 patients during the period 1983 to 1997. – Clinical presentation and management of renal cell carcinoma, (Oliech JS: East Afr Med J. 1998 Oct;75(10):594-7), • The tissue of origin for RCC is the proximal renal tubular epithelium.  • 6th and 7th decades of life (pantuck et al,2001wallen et al,2007) • Male predominanace; 1.5: 1 87
  88. 88. RCC OCCURRENCE – sporadic , Majority – familial (lipworth et al,2006) , 2-3% – RCC in children is uncommon, • represent 2.3-6.6% of all renal tumors in chidren (castellanos et al,1974;chan et al,1983;freedman et al,1996,asanuma et al,1999;broeker,2000) • Mean age at presentation in children is 8-9 years • similar incidence in boys and girls 88
  89. 89. RCC - ETIOLOGY I. TOBACCO EXPOSURE – Cigarette smoking is considered a causal risk factor for renal cell cancer by the International Agency for Research on Cancer (IARC)  – Risk increases with cummulative dose or pack years (kantor,1977;la vecchia et al,1990; Mclaughlin et al,1995;mclaughlin and lipworth,2000;dhote et al,2004;lindblad,2004;lipwort et al,2006;carrisoza and godley,2009) – Relative risk is directly related to duration of smoking and begins to fall after cessation, supporting a cause-and-effect relationship (la vecchia et al,1990; Mclaughin et al1995; parker et al2003) – Account for 20-30% of cases of RCC in men and 10-20% in women (mclaughin et al,1995;mclaughlin et al,1995;mclaughlin and lipworth,2000) – Cigarette smoking is hypothesized to increase renal cell cancer risk through chronic tissue hypoxia due to carbon monoxide exposure – higher level of DNA damage in their peripheral blood lymphocytes induced by a tobacco-specific N-nitrosamine 89
  90. 90. RCC - ETIOLOGY II. OBESITY – major risk factor for RCC – Excess body weight has been estimated to account for over 40% of renal cell cancers in the United States and over 30% in Europe – Incresed relative risk for each unit of rising body mass index (chow et al,2000; bergstrom et all,2001;bjorge et al 2004; calle and kaaks, 2004;reeves et al,2007) – Potential mechanism linking obesity to RCC (kasiske et al,1992; huang et al,1998; gago-dominguez et al,2002;calle and kaaks,2004) • Lipid peroxidation leading to DNA adducts • Increased insulin like growth factor-1 expression, • increased circulating estrogen levels, • Increased arterionephrosclerosis and local inflammation 90
  91. 91. RCC - ETIOLOGY III. HYPERTENSION – Certain types of renal tumors and cancer treatment have been shown to cause hypertension. – there is sufficient evidence to demonstrate that hypertension predisposes to renal cell cancer development. (tumor-promoting effect for hypertension) – 3rd major etiological factor – Proposed mechanisms (lipworth et al, 2006) • Hypertension induced renal injury and inflammation • Metabolic or functional changes in renal tubules that may increase susceptibility to carcinogens – chronic renal hypoxia and lipid peroxidation with formation of reactive oxygen species. • Users of diuretics and other anti-hypertensive medications also were associated with an elevated risk of renal cell cancer 91
  92. 92. RCC - ETIOLOGY IV. OCCUPATION & ENVIRONMENT • Trichloroethylene exposure – classified in Group 2A (probable carcinogens)by the IARC (International Agency for Research on Cancer) – Widely used as a metal degreaser and chemical additive, – Relative risks ranging from twofold to sixfold (vamvaka et al,2000;mandel,2001;moyad,2001;bruning et al,2003,;lipworth et al,2006,lock and reed,2006) • Asbestos, cadmium, uranium, arsenic, nitrate, and radon (colonel,1976;pesch et al,2000moyad,2001;hu et al,2002;dhote et al,2004;lindblad,2004;lipworth et al ,2006;carrizosa and godley,2009) – Workers in the metal, chemical, rubber, mining and printing industries • Low socioeconomic status and Urban background (kantor,1977;goodman et al,1986;muscat et al,1995;youan et al,1998) 92
  93. 93. RCC - ETIOLOGY V. DIET AND BEVERAGES • Diets rich in fruits and vegetables are inversely related to renal cell cancer  – associations with antioxidant nutrients common in fruits and vegetables, such as vitamins A, C, and E, and carotenoids, are mixed. • Acrylamide, a substance classified by the IARC as Group 2A  in commonly consumed fried and baked foods. • Alcohol consumption has been inversely associated with renal cell cancer risk in a dose-response manner in prospective studies, – with an estimated 28% reduction in risk among those who drank ≥15 gram/day, equivalent to slightly more than one alcoholic drink per day 93
  94. 94. RCC -ETIOLOGY VI. FAMILY HISTORY OF RCC – Increased RR for individuals with a first-or-second degree relative (gago-dominguez et al,2001) VII. IATROGENIC CAUSES – Thorotrast (used as contrast in the past) – Radiation therapy (vogelzang and colleagues(1998) • reported 4 cases of RCC developing in a previously irradated field • slightly increased incidence of RCC has been rported in men who received retroperitoneal irradation for the treatment of testicula cancer.(wenz,1967;romanenko et al,2000) 94
  95. 95. RCC - ETIOLOGY VIII. Survivors of childhood WILMS TUMOR also appear to be at increased risk for RCC, – possibly related to prior radiation therapy or chemotherapy (cherullo eat al,2001) IX. Increased incidence of RCC observed in patients with ESRD and certain FAMILIAL SYNDROMES (ishikawa et al,1990;bjornsson et al,1996;neumann and zbar,1997) X. A history of diabetes mellitus has been linked to renal cell cancer risk in several cohort studies XI. Compared to nulliparous women, risk increased 40% to 90% among women who had given birth and rose with increasing number of births (highest risk among women who gave multiple births at a relatively young age) XII. Physical activity has been shown to reduce body weight and blood pressure, improve insulin sensitivity, and reduce chronic inflammation and oxidative stress, changes that could contribute to reducing renal cell cancer risk. 95
  96. 96. RCC - TYPES • Histological subtypes – Clear cell RCC (ccRCC) – 75% – Papillary RCC (pRCC) – 15% • Type basic types • Type II • Type III - oncocytic – Chromophobe (chRCC) - 5% • Others – Collecting duct carcinoma – Renal medullary carcinoma – Sarcomatoid differentiation – Unclassified RCC 96
  97. 97. Familial RCC syndromes 97
  98. 98. VON HIPPEL-LINDAU DISEASE, VHL GENE, AND GENETICS OF ccRCC • The familial form of clear cell RCC is von Hippel-Lindau disease. • This is a relatively rare autosomal dominant disorder that occurs with a frequency of 1 per 36,000 population. • RCC develops in about 50% of patients with von Hippel- Lindau disease – and is distinctive for its early age at onset and for its bilateral and multifocal involvement (Horton et al, 1976; Go et al, 1984; Green, 1986; Jennings et al, 1988; Lamiell et al, 1989; Maher et al, 1990; Neumann and Zbar, 1997; Vira et al, 2007; Nathanson and Stephenson, 2009). – often in the 3rd , 4th , or 5th decade of life 98
  99. 99. Manifestations of the von Hippel-Lindau Syndrome (Horton et al, 1976; Go et al, 1984; Green, 1986; Jennings et al, 1988; Lamiell et al, 1989; Maher et al, 1990; Neumann and Zbar, 1997; Hansel and Rini, 2008; Nathanson and Stephenson, 2009). 99
  100. 100. RCC - VHL Gene • This gene, which is located at chromosome 3p25-26 • its a tumor suppressor gene for both the sporadic and the familial forms of clear cell RCC (Gnarra et al, 1994; Linehan et al, 1995; Zbar, 1995; Furge and Teh, 2009; Nathanson and Stephenson, 2009). • As with most tumor suppressor genes, both alleles of the VHL gene must be MUTATED or INACTIVATED for development of the familial RCC(2-3%). 100
  101. 101. RCC - VHL Gene • sporadic clear cell RCCs – harbor mutations or other genetic mechanisms, such as hypermethylation, that inactivates both alleles of the VHL gene (Zbar, 1995; Linehan et al, 2003; Nathanson and Stephenson, 2009) • accounts for 70% to 80% of all RCCs, (Störkel et al, 1997; Eble et al, 2004; Rini et al, 2009). – exhibit venous tumor extension than any other subtype of RCC (Rabbani et al, 2004). – worse prognosis compared with papillary or chromophobe RCC (Lau et al, 2002; Cheville et al, 2003; Beck et al, 2004) 101
  102. 102. RCC - VHL Gene • The function of the VHL protein complex is to target the hypoxia-inducible factors 1 & 2 (HIF-1 and HIF-2) – The HIFs are intracellular proteins that play an important role in regulating cellular responses to hypoxia, starvation, and other stresses. • Inactivation or mutation of the VHL gene leads to dysregulated expression of the HIFs and they begin to accumulate in the cell. (Maxwell et al, 1999; Yu et al, 2001) – This, in turn, leads to a severalfold upregulation of the expression of vascular endothelial growth factor (VEGF), the primary angiogenic growth factor in RCC, contributing to the pronounced neovascularity associated with clear cell RCC (Gnarra et al, 1996; Iliopoulos et al, 1996; Gunningham et al, 2001; Igarashi et al, 2002; Linehan et al, 2003; Sudarshan and Linehan, 2006; Vira et al, 2007). 102
  103. 103. RCC - VHL protein • HIFs also upregulate the expression of –tumor growth factor-α, –platelet-derived growth factor (PDGF), –glucose transporter (Glut 1) –erythropoietin –carbonic anhydrase IX (CA-IX),(a tumor- associated antigen with specificity for clear cell RCC) (Zbar et al, 1999; Wykoff et al, 2000; Turner et al, 2002; Wiesener et al, 2002; Linehan et al, 2003; Grabmaier et al, 2004; Sudarshan and Linehan, 2006; Vira et al, 2007). 103
  104. 104. . • The von Hippel-Lindau (VHL) gene encodes a tumor suppressor protein (pVHL) that interacts with a hypoxia-inducible factor (HIF) that is a "master regulator" of many genes . • Mutations in the VHL gene can therefore alter intracellular signaling • When HIF dissociates from pVHL, it becomes stabilized and induces expression of hypoxia-induced target genes, including vascular endothelial growth factor (VEGF), which stimulates angiogenesis; platelet-derived growth factor (PDGF), which enhances endothelial stabilization; and transforming growth factor-alpha (TGF- alpha), which stimulates cell replication 104
  105. 105. 105
  106. 106. Hereditary Papillary RCC and Genetics of type 1 Papillary RCC • Papillary RCC, – In 1995, Zbar and colleagues described familial syndrome of RCC—hereditary papillary RCC (HPRCC) – designated chromophilic RCC in previous classification schemes, – is the second most common histologic subtype (Störkel et al, 1997; Eble et al, 2004; Pignot et al, 2007; Gontero et al, 2008). – It represents 10% to 15% of all RCCs, – it is more commonly found in patients with end-stage renal failure and acquired renal cystic disease (Ishikawa and Kovacs, 1993; Störkel et al, 1997). – characterized by trisomy for chromosomes 7 and 17 and loss of chromosome Y as well as abnormalities on chromosomes 1, 12, 16, 20, (Störkel et al, 1997; Oyasu, 1998; Pavlovich et al, 2003). 106
  107. 107. Type 1 Papillary Renal Cell Carcinoma • Two Basic variants of papillary RCC have been described (Renshaw et al, 1997; Störkel et al, 1997; Oyasu, 1998; Delahunt et al, 2001; Eble et al, 2004; Yang et al, 2005;Rosner et al, 2009) – Type 1 papillary RCC, • the more common form, • hereditary papillary RCC syndrome, multifocal, bilateral renal tumors • mutations of the c-MET proto-oncogene located on chromosome 7 (Schmidt et al, 1997; Pavlovich and Schmidt, 2004). • Better prognosis (Moch et al, 2000; Lau et al, 2002; Amin et al, 2002; Beck et al, 2004; Zhou, 2009). – Type 2 papillary RCC • more aggressive variants • hereditary leiomyomatosis and RCC syndrome (Delahunt et al, 2001; Amsellem-Ouazana et al, 2002; Leroy et al, 2002; Renshaw, 2002; Choyke et al, 2003; Gunawan et al, 2003; Pignot et al, 2007). • Fumarate hydratase mutation 107
  108. 108. Hereditary Papillary RCC and Genetics of type 1 Papillary RCC • HPRCC demonstrate an autosomal dominant mode of transmission, similar to all of the familial RCC syndromes – inciting event is activation of a proto-oncogene, rather than inactivation of a tumor suppressor gene (Missense mutations of the c-MET proto- oncogene at 7q31) • tumors in HPRCC are tend to be less aggressive than their sporadic counterparts, some can metastasize (Schmidt et al, 2004; Vira et al, 2007). 108
  109. 109. Hereditary Papillary RCC and Genetics of type 1 Papillary RCC • Unlike von Hippel-Lindau disease, most patients with HPRCC do not develop tumors in other organ systems (Czene and Hemminki, 2003; Pfaffenroth and Linehan, 2008; Nathanson and Stephenson, 2009) • CT is the preferred imaging modality for patients with HPRCC – it has the greatest sensitivity for detecting the small, hypovascular lesions that are common in this syndrome (Sudarshan and Linehan, 2006; Pfaffenroth and Linehan, 2008; Nathanson and Stephenson, 2009). 109
  110. 110. Type 1 Papillary Renal Cell Carcinoma • VHL mutations are rare in papillary RCC, – confirm distinct genetic pathways to tumorigenesis (Kenck et al, 1996; Zambrano et al, 1999; Linehan et al, 2003; Rosner et al, 2009). • Papillary RCC is more likely to be hypovascular – owing to the lack of VHL mutations that regulate VEGF, the primary proangiogenic molecule in RCC (Blath et al, 1976; Herts et al, 2002; Kim JK et al, 2002). 110
  111. 111. Hereditary Leiomyomatosis and Type 2 papillary RCC • described In 2001, Launonen and colleagues; patients develop – cutaneous and uterine leiomyomas and – type 2 papillary RCC (Choyke et al, 2003; Kiuru and Launonen, 2004; Pavlovich and Schmidt, 2004; Sudarshan and Linehan, 2006; Sudarshan et al, 2007) • Mean age at diagnosis is in the early 40s (Hansel and Rini, 2008; Nathanson and Stephenson, 2009). • Collecting duct RCC, another highly malignant variant of RCC, has also been observed in this syndrome 111
  112. 112. Hereditary Leiomyomatosis and RCC • Prompt surgical management of the renal tumors is recommended in this syndrome – tendency toward invasive and aggressive behavior (Linehan et al, 2003; Grubb et al, 2005b, 2007; Sudarshan and Linehan, 2006; Vira et al, 2007; Coleman, 2008). – This is in contrast to other familial syndromes of RCC, for which management tends to be more conservative, as discussed later (Grubb et al, 2007; Vira et al, 2007; Pfaffenroth and Linehan, 2008). 112
  113. 113. Birt-Hogg-Dubé Syndrome • is named after three Canadian physicians who first described the cutaneous lesions in 1977(Toro et al, 1999; Linehan et al, 2003; Pavlovich et al, 2003, 2005; Pavlovich and Schmidt, 2004; Adley et al, 2006; Hansel and Rini, 2008). • patients develop – cutaneous fibrofolliculomas, (Any of a group of neoplasms formed by proliferation of the fibrous sheath of the hair follicle) – lung cysts, – spontaneous pneumothoraces, – and a variety of renal tumors primarily derived from the distal nephron, 113
  114. 114. Birt-Hogg-Dubé Syndrome • renal tumors typically include – chromophobe RCC, – oncocytomas, – and hybrid or transitional tumors that exhibit features of both of these entities. – other forms of RCC, including a substantial proportion of clear cell RCC, have been observed in this syndrome (Pavlovich et al, 2002; Adley et al, 2006). • Overall penetrance for renal tumors is 20% to 40%, but when they occur they are often bilateral and multifocal (Pavlovich et al, 2002; Linehan et al, 2003; Pavlovich and Schmidt, 2004: Pfaffenroth and Linehan, 2008; Toro et al, 2008) 114
  115. 115. Birt-Hogg-Dubé Syndrome • Average age at renal tumor diagnosis is approximately 50 years (Pavlovich et al, 2005). • Most renal tumors in Birt-Hogg-Dubé syndrome have limited biologic aggressiveness, although metastatic behavior and lethality have been reported (Pavlovich et al, 2005) 115
  116. 116. Chromophobe Renal Cell Carcinoma • first described by Theones and colleagues in 1985, • Chromophobe RCC is seen in the Birt-Hogg-Dubé syndrome, but most cases are sporadic (Pavlovich et al, 2002). • derived from the cortical portion of the collecting duct (Störkel et al, 1997). • It represents 3% to 5% of all RCCs (Oyasu, 1998; Eble et al, 2004; Klatte et al, 2008). • Genetic analysis has revealed multiple chromosomal losses, most frequently the whole chromosomes 2, 10, 13, 17, and 21 (Schwerdtle et al, 1996; Bugert et al, 1997; Iqbal et al, 2000; Polascik et al, 2002). • increased incidence of TP53 mutations and upregulated expression of the c-KIT oncogene (type of receptor tyrosine kinase and a type of tumor marker) has also been reported (Contractor et al, 1997; Yamazaki et al, 2003; Pan et al, 2004; Petit et al, 2004; Huo et al, 2005). 116
  117. 117. Collecting Duct Carcinoma • Carcinoma of the collecting ducts of Bellini • Is a rare subtype of RCC, accounting for less than 1% of all RCCs (Kennedy et al, 1990; Rumpelt et al, 1991; Carter et al, 1992; Störkel et al, 1997; Srigley and Eble, 1998; Swartz et al, 2002). • Many reported cases in younger patients, – often in the third, fourth, or fifth decades of life (Carter et al, 1992). • Most patients are symptomatic at presentation, – and up to 50% have metastatic disease at the time of detection (Tokuda et al, 2006). • Deletions on chromosome 1q and monosomy of chromosomes 6, 8, 11, 18, 21, and Y have been reported (Fuzesi et al, 1992; Steiner et al, 1996; Polascik et al, 2002). • patients with advanced collecting duct RCC have responded to cisplatin- or gemcitabine-based chemotherapy (Milowsky et al, 2002; Peyromaure et al, 2003; Kobayashi et al, 2008). 117
  118. 118. Renal Medullary Carcinoma • Subset of RCC that occurs almost exclusively in association with the sickle cell trait. • arise from the calyceal epithelium near the renal papillae but is often highly infiltrative (Davidson et al, 1995; Davis et al, 1995). • typically diagnosed in young African-Americans, – often in the third decade of life, – many cases are both locally-advanced and metastatic at the time of diagnosis (Davis et al, 1995b; Polascik et al, 2002; Swartz et al, 2002; Zhou, 2009). – Most patients do not respond to therapy and succumb to their disease in a few to several months (Davis et al, 1995b; Herring et al, 1997; Figenshau et al, 1998; Polascik et al, 2002). 118
  119. 119. Sarcomatoid Differentiation • found in 1% to 5% of RCCs, – most commonly in association with clear cell RCC or chromophobe RCC, but variants of most other subtypes of RCC have been described (Weiss et al, 1995; Störkel et al, 1997; Oyasu, 1998; Delahunt, 1999; dePeralta-Venturina et al, 2001; Kuroda et al, 2003e; Cheville et al, 2004; Zhou, 2009). • believed that sarcomatoid lesions represent poorly differentiated regions of other histologic subtypes of RCC rather than independently derived tumors (DeLong et al, 1993; Oyasu, 1998; Delahunt, 1999; Eble et al, 2004). • rare to find a truly pure sarcomatoid renal mass (Delahunt,1999). • Characterized by infiltrative growth pattern, aggressive local and metastatic behavior, and poor prognosis (Ro et al, 1987; DeLong et al, 1993; Cangiano et al, 1999; Eble et al, 2004). • Invasion of adjacent organs is common, and median survival has been less than 1 year in most series (Ro et al, 1987; Cangiano et al, 1999; Escudier et al, 2002a; Mian et al, 2002; Nanus et al, 2004; Dall’Oglio et al, 2005; Zhou, 2009). 119
  120. 120. Clinical Presentation - RCC • Because of the location of the kidney within the retroperitoneum, – many renal masses remain asymptomatic and nonpalpable until they are advanced. – more than 50% of RCCs are now detected incidentally (Pantuck et al, 2000). • Haematuria, abdominal pain, fever of unknown origin and abdominal mass were the commonest presenting features.  – Clinical presentation and management of renal cell carcinoma, (Oliech JS: East Afr Med J. 1998 Oct;75(10):594- 7) 120
  121. 121. …Clinical Presentation - RCC • Incidental • Local Tumor Growth – Hematuria – Flank pain  • due to hemorrhage and clot obstruction, • also occur with locally advanced or invasive disease – Abdominal mass  – Perirenal hematoma  • most often AML or RCC. • Metastases – Persistent cough  – Bone pain  – Cervical lymphadenopathy  – Constitutional symptoms  – Weightloss/fever/malaise • Obstruction of the Inferior Vena Cava – Bilateral lower extremity edema – Nonreducing or right-sided  varicocele • Paraneoplastic Syndromes – Hypercalcemia – Hypertension – Polycythemia – Stauffer’s syndrome 121
  122. 122. Incidence of Systemic Syndromes Associated with RCC • Elevated erythrocyte sedimentation rate - 55.6% • Hypertension - 37.5% • Anemia - 36.3 % • Cachexia, weight loss - 34.5 % • Pyrexia - 17.2 % • Abnormal liver function - 14.4% • Hypercalcemia - 4.9 % • Polycythemia - 3.5 % • Neuromyopathy - 3.2 % • Amyloidosis - 2.0% 122
  123. 123. Paraneoplastic syndromes in RCC • found in 20% of patients with RCC, • Secondary to Pathological production of: – 1,25 dihydroxycholecalciferol, – renin, – erythropoietin, – various prostaglandins, – parathyroid hormone–like peptides, – lupus-type anticoagulant, – human chorionic gonadotropin, – insulin – various cytokines and inflammatory mediators (Sufrin et al, 1989; Gold et al, 1996; Ather et al, 2002; Elias, 2005; Altundag et al, 2005; Elias, 2005) 123
  124. 124. Paraneoplastic syndromes in RCC • Hypercalcemia has been reported in up to 13% of patients with RCC and can be due to – either paraneoplastic phenomena (Calcitriol) – or osteolytic metastatic involvement of the bone (Sufrin et al, 1989; Gold et al, 1996; Magera et al, 2004; Klatte et al, 2007d; Pepper et al, 2007; Schwarzberg and Michaelson, 2009). • The production of parathyroid hormone–like peptides is the most common paraneoplastic etiology, although tumor derived 1,25-dihydroxycholecalciferol and prostaglandins may contribute in a minority of cases (Goldberg et al, 1964; Mangin et al, 1988; Sufrin et al, 1989; Gold et al, 1996; Walther et al, 1997b; Magera et al, 2004; Massfelder et al, 2004; Klatte et al, 2007d; Pepper et al, 2007). • patients with RCC who present with hypercalcemia have a compromised prognosis 124
  125. 125. Paraneoplastic syndromes • The signs and symptoms of hypercalcemia are nonspecific – nausea, anorexia, fatigue, and decreased deep tendon reflexes. • Medical management includes – vigorous hydration – followed by diuresis with furosemide – selective use of bisphosphonates, corticosteroids, or calcitonin (Gold et al, 1996; Coleman, 2004; Pepper et al, 2007; Schwarzberg and Michaelson, 2009). – Indomethacin has also proved useful in a minority of cases (Gold et al, 1996; Walther et al, 1997). – nephrectomy and ?metastasectomy, depending on the clinical circumstances. – focused radiation therapy for hypercalcemia related to osteolytic metastases if limited sites of involvement can be identified (Gold et al, 1996). 125
  126. 126. Paraneoplastic syndromes (Moein and Dehghani, 2000) • Hypertension associated with RCC secondary to i. increased production of renin directly by the tumor; ii. compression or encasement of the renal artery or its branches, effectively leading to renal artery stenosis; iii. or arteriovenous fistula within the tumor (Robertson et al, 1967; Sufrin et al, 1989). iv. Less common causes include polycythemia, hypercalcemia, ureteral obstruction, and increased intracranial pressure associated with cerebral metastases (Sufrin et al, 1989). • Polycythemia associated with RCC can be due to – increased production of erythropoietin, either directly by the tumor or by the adjacent parenchyma in response to hypoxia induced by tumor growth (Gross et al, 1994; Wiesener et al, 2007). 126
  127. 127. Stauffer syndrome • Also referred to as non - metastatic hepatic dysfunction • reported in 3% to 20% of cases (Stauffer, 1961; Rosenblum, 1987; Giannakos et al, 2005; Moria et al, 2006; Young et al, 2008). • Almost all patients with Stauffer syndrome have; i. an elevated serum alkaline phosphatase level, ii. 67% have elevated prothrombin time or hypoalbuminemia, iii. 20% to 30% have elevated serum bilirubin or transaminase levels (Sufrin et al, 1989). iv. Other common findings include thrombocytopenia and neutropenia, and v. Elevated serum levels of IL-6 (Blay et al, 1997). • Typical symptoms include fever and weight loss, – many patients are found to harbor discrete regions of hepatic necrosis (Sufrin et al, 1989; Gold et al, 1996). 127
  128. 128. Stauffer syndrome, • Hepatic function normalizes after nephrectomy in 60% to 70% of cases. • Persistence or recurrence of hepatic dysfunction – indicative of the presence of viable tumor – represents a poor prognostic finding (Sufrin, 1989). 128
  129. 129. Other paraneoplastic syndromes • Cushing syndrome, • hyperglycemia, • galactorrhea, • neuromyopathy, amyotrophic lateral sclerosis • clotting disorders, • cerebellar ataxia (Ather et al, 2002; Kamra et al, 2002; Hagel et al, 2005; Mohammed et al, 2006; Ammar et al, 2008). • Treatment of paraneoplastic syndromes associated with RCC – surgical excision or – systemic therapy and, – except for hypercalcemia, medical therapies have not proved helpful. 129
  130. 130. Laboratory findings • FHG – polycythemia – Anemia occurs in about 30% of RCC patients – Normochromic Anaemia • Serum iron and TIBC – Low (anemia of chronic illness) • Urinalysis – Hematuria- gross or microscopic • ESR – An elevated erythrocyte sedimentation rate is also commonly seen, with a reported incidence as high as 75% • RFTs • LFTs – Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 130
  131. 131. Imaging and Radiological findings • Ultrasonography – Although ultrasound is very frequently requested to assess the renal tract, it is not as sensitive or specific as CT or MRI.   – The tumour pseudocapsule can sometimes be visualised with ultrasound as a hypoechoic halo. Although this is a relatively specific sign, it is not particularly sensitive – Contrast-enhanced ultrasound  demostrates the lesion to be heterogenously hypervascular in the arterial phase with early wash out in the delayed phase. 131
  132. 132. Imaging and Radiological findings • CT Scanning – On non-contrast CT the lesions appear of soft tissue attenuation. Larger lesions frequently have areas of necrosis. Approximately 30% demonstrate some calcification – becomes enhanced with the use of intravenous contrast media. – CT scanning is also the method of choice in staging the patient • visualizing the renal hilum, perinephric space, renal vein and vena cava, adrenals, regional lymphatics, and adjacent organs. – Evaluation of metastases – Spiral CT with 3-dimensional reconstruction has become useful for evaluating tumors before nephron- sparing surgery • delineate the 3-dimensional extent of the tumor • outline the vasculature, • aid the surgeon in preventing positive surgical margins (Holmes et al, 1997). 132
  133. 133. Imaging and Radiological findings Renal Angiography • markedly diminished utility in the diagnostic evaluation of RCC • clinical situations in which angiography may be useful; – for example, guiding the operative approach in a patient with an RCC in a solitary kidney when attempting to perform a partial nephrectomy may be indicated – CT angiography or MR angiography can give better information with less risk to the patient. 133
  134. 134. Imaging and Radiological findings Radionuclide Imaging • Bone metastases • NB/patients without bone pain and with a normal alkaline phosphatase level have a very low incidence of bone metastases (Henriksson et al, 1992), and thus a routine bone scan is not necessary in such 134
  135. 135. Imaging and Radiological findings  Magnetic Resonance Imaging • Its primary advantage is in the evaluation of patients with suspected vascular extension. • superior to CT in assessing inferior vena caval involvement (Kabala et al, 1991) • also able to suggest the likely histology, on the grounds of T2 differences. – T1: often heterogeneous due to necrosis, haemorrhage and solid components – T2: appearances depend on histology 6 • clear cell RCC: hyperintense • papillary RCC: hypointense – T1 C+ (Gd): often shows prompt arterial enhancement 135
  136. 136. Imaging and Radiological findings  Positron Emission Tomography (PET) and Targeted Imaging • allows the measurement of systemically administered biochemical agents such as 18- fluoro-2- deoxyglucose (FDG), which can accumulate in the kidney. • useful in monitoring response to systemic therapy in those with metastatic disease (Hoh et al, 1998). • FDG-PET may also be more accurate than routine CT scanning in detecting disease recurrence or progression 136
  137. 137. Fine-needle aspiration in diagnosis of renal lesions • Indications – in patients with clinically apparent metastatic disease who may be candidates for nonsurgical therapy. – establishing a diagnosis in patients who are surgical candidates – differentiating a primary RCC from a renal metastasis in patients with known primary cancers of nonrenal origin, – evaluating some radiographically indeterminate lesions – to confirm the diagnosis of a neoplasm particularly in patients who may undergo observation or percutaneous ablative therapy (Shah et al, 2005). • The accuracy of fine needle aspiration cytology of renal masses is reported to be slightly lower mainly because of lower sensitivity. Specificity can still be high and close to 100%. 137
  138. 138. core needle biopsies • accurately diagnose malignancy in up to 100% of cases >4 cm and 95% of cases <4 cm, (Wunderlich et al, 2005). – utilized in patients with metastatic disease in order to guide appropriate targeted systemic therapy (prior to or instead of cytoreductive nephrectomy), • since the choice of systemic therapy can be influenced by the specific RCC histology. – seeding of the needle tract have been reported but the risk of seeding is reported to be <0.01% (Volpe et al, 2007). – The accuracy of needle core biopsies is reported to be >90% with sensitivity ranging between 70–100% and specificity of 100% (Volpe et al, 2007). 138
  139. 139. Instrumental and Cytologic Examination • cystoscopy – Patients presenting with hematuria. – Blood effluxing from the ureteral orifice identifies the origin of bleeding from the upper tract. • endoscopic evaluation – Most renal pelvis tumors – bladder, ureters, and renal pelvis • urine cytologic – cytologic study of urine with renal pelvis washing is frequently diagnostic in renal pelvis tumors. 139
  140. 140. TUMOR STAGING • The ultimate goal of staging – is select appropriate therapy and obtain prognostic information. • Appropriate studies for a complete clinical staging evaluation include – history and physical examination, – complete blood count, – serum chemistries (renal and hepatic function), – urinalysis, – chest x-ray (chest CT scan for an equivocal exam), – CT scan of abdomen and pelvis, – and a radionuclide bone scan (with x-rays of abnormal areas). • The original staging system by Robson (1963) does not relate directly to prognosis and hence it is no longer commonly used. • The tumor- node-metastasis (TNM) system more accurately classifies the extent of tumor involvement and is currently most often used. – The TNM classification system for RCC has undergone multiple revisions with the most recent edition being the 2010 version 140
  141. 141. Staging 141
  142. 142. RCC Stage grouping Stage 1 T1 NO MO Stage 2 T2 NO MO Stage 3 T1, T2, T3 T3 N1 N0 MO MO Stage 4 T4 ANY T ANY N ANY N MO M1 142
  143. 143. grading • Grading has been based primarily on nuclear size and shape and the presence or absence of prominent nucleoli. Fuhrman’s System has been most generally adopted and is now recognized as an independent prognostic factor for RCC generally and for clear cell RCC in particular (Fuhrman et al, 1982; Pantuck et al, 2001a; Lang et al, 2005; Lohse et al, 2005; Zhou, 2009). 143
  144. 144. Prognostic Factors for RCC ANATOMIC • Tumor size • Venous involvement • Extension into contiguous  organs • Adrenal involvement  (direct or metastatic) • Lymph node metastases • Distant metastases • Metastatic burden of      disease CLINICAL • Perfomance status (karnofsky,ECOG,WHO) • Systemic symptoms  (cachexia,loss of >10% of body  weight) • Symptomatic vs incidental  presentation • Anemia • Hypercalcemia • Elevated lactate  dehydrogenase • Elevated erythrocyte  sedimentation rate • ElevatedC-reactiveprotein • Thrombocytosis • Elevated alkaline phosphatase 144
  145. 145. Prognostic Factors for RCC HISTOLOGIC • Fuhrman Nuclear grade • Histologic subtype • Presence of sarcomatoid  features • Presence of histologic  necrosis • Vascular invasion • Invasion of perinephric or renal sinus fat  • Collecting system  invasion • Surgical margin status MOLECULAR • Hypoxia inducible factors: – CA-IX, IGF-1, VEGF, VEGFRs,        CA-XII, CXCR3, CXCR4, HIF      • Costimulatory molecules:  – B7-H1, B7-H3 (tumor      cell/vascular), B7-H4, PD-1    • Cell cycle regulators:    – PTEN, TP53, Bcl2, Cyclin A, CDKN1B, Skp2  • Adhesion molecules: – EpCAM, EMA, E-Cad, α- catenin,Cad-6 • Other factors:  – Ki-67, XIAP, Survivin, EphA2, Smac/DIABLO, PCNA,  Caveolin-1, AR,CD44, AnnexinII,Gelsolin, Vimentin, CA-  125),aberrant DNA methylation, Na+,K+ATPase  α1 subunit, vitamin D receptor, retinoidX receptor  145
  146. 146. Management of localized RCC  T1-2, NO, MO • Nephron Sparing Surgery (NSS) – Open, pure laparoscopic, robot-assisted – Unsuitable in; • Locally advanced tumor growth • Partial resection is not feasible due to unfavourable tumor location • Significant deterioration in patient health • Laparoscopic Radical nephrectomy for patients with T2 tumors and localised masses not treatable by PN – en bloc removal of the kidney and its enveloping fascia (Gerota’s) including the ipsilateral adrenal, proximal one-half of the ureter, and lymph nodes up to the area of transection of the renal vessels • Ipsilateral adrenalectomy is not recommended if no clinical evidence of invasion of the adrenal gland • LND is not recommended in localized tumor without clinical evidence of LN invasion 146
  147. 147. Management of localized RCC • Laparoscopic/robotic radical nephrectomy is being used increasingly for patients with localized renal tumors. – This approach results in quicker recovery compared to open radical nephrectomy – approach of choice in appropriate patients with <10 cm tumors and without local extension or a renal vein or caval thrombus (Gill et al, 2001; Portis et al, 2002). • Partial nephrectomy (NSS) and wedge resection with an adequate margin of normal parenchyma – standard primary surgical therapy for patients with tumors <4 cm in size, even in the presence of a normal contralateral kidney. – Local recurrence of tumor in the same kidney ranges from 0% to 10%, and it is between 0% and 3% for tumors <4 cm in size (Hafez et al, 1997; Morgan and Zincke, 1990; Uzzo and Novick, 2001). 147
  148. 148. Management of localized RCC • Non-surgical management – Tumors less than 4 cm – Older and frail patients (more than 75 years) – Active surveillance (initial monitoring of tumor size by serial abdominal imaging with delayed intervention reserved for tumors showing clinical progression during follow-up) • Ablative therapies – Cryoablation, percutaneous or laparoscopic – Radiofrequency ablation, laparoscopic or percutaneous – Other ablative therapies in trial, • Microwave ablation • Laser ablation • High – intensity focussed US ablation 148
  149. 149. Management of localized RCC • use of cryoablation, high-intensity focused US, and radiofrequency ablation (Murphy and Gill, 2001). – for the treatment of small, incidentally discovered renal lesions – liquid nitrogen or argon gas, either percutaneously using MRI guidance or via laparoscopic probes – in patients with single or multiple small lesions or in – older individuals with many co morbidities. – Bleeding, scarring of renal pelvis, and urine leak are among the commonly reported complications with the ablative therapies. 149
  150. 150. Management of locally advanced RCC • Clinically positive lymph nodes (cN+) – LND is justified • Locally advanced unresectable RCC – Embolization can control symptoms(hematuria, frank pain) • RCC with venous thrombus – Excision of kidney tumor and caval thrombus is recommended in non-metastatic RCC • No evidence for the use of adjuvant therapy VEGF-R or mTOR inhibitors 150
  151. 151. Management of locally advanced RCC • Preoperative renal artery embolization (angioinfarction) as a surgical adjunct to facilitate radical nephrectomy, – decreases blood loss or facilitates surgery, – patients with very large tumors in which the renal artery may be difficult to reach early in the procedure. – useful to palliate patients with nonresectable tumors and significant symptoms such as hemorrhage, flank pain, or paraneoplastic syndromes. • Radiation therapy has been advocated as a neoadjuvant (preoperative) or adjuvant method to radical nephrectomy, – no evidence that postsurgical radiation (adjuvant) therapy to the renal bed, whether or not residual tumor is present, contributes to prolonged survival. 151
  152. 152. Management of advanced/metastatic RCC Local therapy of advanced/metastatic RCC 1. Cytoreductive nephrectomy – palliative – Systemic treatments necessary (immunotherapy e.g. INF-a/ target therapy e.g sunitinib, sorafenib) – Indications of cytoreductive nephrectomy – Mrcc patients with good PS – Large primary tumors – Low metastatic volume 152
  153. 153. Management of advanced/metastatic RCC Local therapy of advanced/metastatic RCC 2. Embolisation of primary tumor – In patients unfit for surgery, or with non- resectable disease – Control symptoms (haematuria or flank pain) 153
  154. 154. Management of advanced/ metastatic RCC Local therapy for metastases in mRCC • Metastasectomy (complete/no/incomplete) – With exceptionof brain and possibly bone metastases, metastasectomy remains by default the most appropriate local treatment for most sites. • The decision to resect metastases has to be taken for each site, and on a case-by-case basis; performance status, risk profiles, patient preference and alternative techniques to achieve local control, must be considered. 154
  155. 155. Management of advanced/ metastatic RCC Local therapy for metastases in mRCC • Radiotherapy to bone and brain metastases from RCC can induce significant relief from local symptoms (e.g. pain). • In individual cases, stereotactic radiotherapy for bone metastases, and stereotactic radiosurgery for brain metastases can be offered for symptom relief. 155
  156. 156. Systemic therapy for advanced/metastatic RCC CHEMOTHERAPY RCC resistant to chemotherapy • Chemotherapy is moderately effective only if 5- fluorouracil (5-FU) is combined with immunotherapeutic agents (INF-a, IL-2) • In patients with clear-cell mRCC, chemotherapy is not considered effective. 156
  157. 157. Systemic therapy for advanced/ metastatic RCC IMMUNOTHERAPY • INF-a monotherapy and combined bevacizumab • Conflicting results exist for IFN-a in ccmRCC • IFN- may only be effective in some patient subgroups,α including patients with ccRCC, favourable-risk criteria, as defined by the Memorial Sloan-Kettering Cancer Center (MSKCC) and lung metastases only 157 RISK FACTORS* CUT-OFF POINT USED Karnofsky PS < 80 Time from diagnosis to treatment < 12 months Haemoglobin < Lower limit of laboratory reference range LDH > 1.5 times the upper limit of laboratory range Corrected serum calcium > 10.0 mg/dL (2.4 mmol/L)
  158. 158. Systemic therapy for advanced/ metastatic RCC • The interferons ,INF alpha – are natural glycoproteins with antiviral, antiproliferative, and immunomodulatory properties. – These agents have a direct antiproliferative effect on renal tumor cells in vitro, stimulate host mononuclear cells, and enhance expression of major histocompatibility complex molecules. • IL-2 – Is a T-cell growth factor and activator of T cells and natural killer (NK) cells. – IL-2 affects tumor growth by activating lymphoid cells in vivo without affecting tumor proliferation directly. – High-dose interleukin-2 (IL-2) can induce durable long-term remission in 10% of patients with advanced kidney cancer, and must be considered for robust patients with excellent cardiopulmonary reserve – The major toxic effect of high-dose IL-2 is a sepsislike syndrome,(progressive decrease in systemic vascular resistance and an associated decrease in intravascular volume due to capillary leak). Other toxic effects are fever, chills, fatigue, infection, and hypotension. 158
  159. 159. Systemic therapy for advanced/ metastatic RCC • Use of several antiangiogenic agents and inhibitors of tyrosine kinase and other cell cycle activators in RCC. • Bevacizumab – is a monoclonal antibody that binds and inactivates VEGF A. – delay disease progression, and improve survival in patients with advanced renal cancer (Yang et al, 2003). • Anti-VEGF TKIs (Sorafenib, Sunitinib, and Pazopanib) – orally bioavailable. – Sunitinib and pazopanib have significant activity in the first-line setting with higher response rates and longer progression-free survival compared to IFN or placebo (Motzer et al, 2007; Sternberg et al, 2010). – Sorafenib was shown to have activity in patients who had previously received cytokine immunotherapy. (Escudier et al, 2009). – Toxicities • hypertension, diarrhea, rash, handfoot skin reactions, cardiac abnormalities, and many others. 159
  160. 160. Systemic therapy for advanced/ metastatic RCC • mTOR inhibitors (Temsirolimus, Everolimus ) – Temsirolimus,first line therapy, prolong survival in patients with advanced renal cancer who present with poor risk or multiple sites of metastases (Hudes et al, 2007). – Everolimus prolong progression-free survival as second-line therapy for patients with metastatic clear-cell RCC (Motzer et al, 2010). – Toxiicities of mTOR inhibitors • mouth sores, • fatigue, pneumonitis, • hypertriglyceridemia • among other side effects. 160
  161. 161. FOLLOW-UP AFTER RADICAL NEPHRECTOMY OR PARTIAL NEPHRECTOMY OR ABLATIVE THERAPIES FOR RCC • Surveillance after treatment for RCC allows the urologist to monitor or identify: – Postoperative complications – Renal function – Local recurrence after PN or ablative treatment – Recurrence in the contralateral or ipsilateral (after PN) kidney – Development of metastases • stage T1 disease – yearly chest x-rays – liver and renal function tests. • Those with stage T2 or T3 disease – least 3-month or 6-month intervals in the early postoperative period. – Repeat CT scans of the abdomen, especially in those who have undergone partial nephrectomy, to rule out local recurrence. 161
  162. 162. FOLLOW-UP AFTER RADICAL NEPHRECTOMY OR PARTIAL NEPHRECTOMY OR ABLATIVE THERAPIES FOR RCC • metastatic disease who are not undergoing therapy – need continued follow-up to provide appropriate supportive care. • Prognosis – The prognosis of patients is most clearly related to the stage of disease at presentation. – stage T1–T2 disease in the 80–100% range, – stage T3 in the 50–60% range. – metastatic disease have a poorer prognosis, with only a 16–32% 5-year survival rate. 162
  163. 163. Sarcomas of the Kidney • Sarcomas represent 1% to 2% of all malignant renal tumors in adults • peak incidence in the fifth decade of life (Srinivas et al, 1984; Russo, 1991; Spellman et al, 1995; Frank et al, 2000). • Renal sarcoma is less common but more lethal than sarcoma of any other genitourinary site, including the prostate, bladder, and paratesticular region (Russo, 1991; Russo et al, 1992). • Differentiation of renal sarcoma from sarcomatoid RCC is often difficult on the basis of – clinical presentation, – radiographic findings, and, in some cases, – pathologic analysis. 163
  164. 164. Sarcomas of the Kidney • The common signs and symptoms associated with renal sarcoma in adults – include palpable mass, abdominal or flank pain, and hematuria and are similar to those seen with large, rapidly growing RCCs (Economou et al, 1987). – Renal sarcoma should be suspected in any of these circumstances or in any patient with a very large or rapidly growing renal mass 164
  165. 165. Sarcomas of the Kidney • Abdominal CT typically demonstrates – a large soft tissue mass involving or derived from the kidney, a finding that is again similar to that associated with many sarcomatoid RCCs (Farrow et al, 1968; Shirkhoda and Lewis, 1987; Russo, 1991). – Specific findings suggestive of sarcoma rather than of RCC include • apparent origin from the capsule or perisinuous region, • growth to large size in the absence of lymphadenopathy, • presence of fat or bone suggestive of liposarcoma or osteosarcoma, and • hypovascular pattern on angiography, although one notable exception is the hemangiopericytoma, which is highly vascular (Smullens et al, 1982; Shirkhoda and Lewis, 1987). • MRI can be useful for preoperative planning by defining tissue planes and proximity to vital structures. 165
  166. 166. Sarcomas of the Kidney • These tumors are derived from mesenchymal components – thus free of the natural barriers to dissemination that confine other tumor types. • They are typically surrounded by a pseudocapsule that is readily identifiable – cannot be relied on for surgical dissection because it is often infiltrated with cancer cells, which can extend for some distance into the surrounding tissues – In many cases this cannot be recognized macroscopically, – it is often manifested in the form of local recurrences, which are common after surgical extirpation, even when a wide excision has been performed. 166
  167. 167. Sarcomas of the Kidney • This is primarily a surgical disease, and wide excision is the goal with intraoperative monitoring of margin status – The initial resection is the key event because, for many patients, this is their best chance for a long-term cure. – this often mandates radical nephrectomy along with en bloc excision of adjacent organs (Srinivas et al, 1984; Brescia et al, 2008). • Chemotherapeutic agents that have demonstrated activity against metastatic sarcomas – include doxycycline and ifosfamide, Antman et al, 1993). • most important prognostic factors for sarcomas are margin status and tumor grade. • High-grade sarcomas often metastasize – Saitoh and colleagues (1982) defined the common sites of metastases of renal sarcomas: lung first and foremost but also lymph nodes and liver. • Low-grade sarcomas tend to pursue a more indolent course, – local recurrences often require repeat resection to prolong survival and minimize morbidity. 167
  168. 168. Sarcomas of the Kidney • The combination of radiation therapy and chemotherapy, – effective in an adjuvant setting for the management of sarcomas of the extremity, – not much benefit for renal or retroperitoneal sarcomas (Russo, 1991). 168
  169. 169. 1. Leiomyosarcoma of the Kidney • is the most common histologic subtype • accounting for 50% to 60% of such tumors. • The cell of origin is the smooth muscle cell of the capsule or other perinephric structures (Moudouni et al, 2001; Deyrup et al, 2004). • female predominance; • most patients presented in the fourth through sixth decades of life. • Renal leiomyosarcoma, tends to displace rather than invade the parenchyma, and is characterized by rapid growth rate, frequent metastasis, and high local and systemic recurrence rates (Pollack et al, 1987; Deyrup et al, 2004). 169
  170. 170. 2. Renal Liposarcoma • readily distinguished from RCC because of the – presence of adipose tissue, but it is often confused with AMLs or with large, benign renal lipomas (Frank et al, 2000). – Renal liposarcoma typically develops in the fifth and sixth decades of life and often grows to extremely large size (Economou et al, 1987). – Response to radiation therapy and cisplatin- based chemotherapy in an adjuvant setting has been reported (Belldegrun and deKernion 1987) 170
  171. 171. Osteogenic sarcoma of the Kidney • is a rare but distinctive form of renal sarcoma that contains calcium and is often rock hard (Micolonghi et al, 1984; Leventis et al, 1997). – Extensive calcification in a large, hypovascular tumor should suggest the diagnosis. – The appearance on plain films can mimic a staghorn calculus, but the readily evident mass effect should suggest xanthogranulomatous disease or, more rarely, osteogenic sarcoma. – prognosis is poor; most patients die of disease progression within a few years after diagnosis 171
  172. 172. Malignant hemangiopericytomas • present at a mean age of 40years, which is younger than most other renal sarcomas, – notable for their extensive vascularity (Argyropoulos et al, 2005; Chaudhary et al, 2007; Brescia et al, 2008). – Preoperative angioembolization has been described and may simplify surgical excision (Smullens et al, 1982). 172
  173. 173. Other Sarcomas of the Kidney • Less common histologic subtypes include – Rhabdomyosarcoma, – Fibrosarcoma, – Carcinosarcoma, – Malignant Fibrous Histiocytoma, – Synovial Sarcoma, – Schwannoma, – Angiosarcoma, (Raghavaiah et al, 1979; Weiss et al, 1984; Mordkin et al, 1997; Tsuda et al, 1997; Cerilli et al, 1998; Merchant et al, 1998; Chieng et al, 1999; Koyama et al, 2001; Bella et al, 2002; Chen et al, 2003; Shannon et al, 2005; Khan et al, 2006; Leggio et al, 2006; Hung et al, 2008; Mirza et al, 2008) 173
  174. 174. Renal Lymphoma and Leukemia • Renal involvement with hematologic malignant neoplasms, which include the lymphomas and leukemias, is common – found at autopsy in approximately 34% of patients dying of progressive lymphoma or leukemia. • uncommonly seen in clinical practice – often silent and generally occur only as a late manifestation of systemic disease (Richmond et al, 1962; Pollack et al, 1987; McVary, 1991). • Renal involvement is more common with non-Hodgkin’s lymphoma than with Hodgkin’s disease, (Richmond et al, 1962; Pollack et al, 1987; Yasunaga et al, 1997; O’Riordan et al, 2001). • Primary renal lymphoma is rare, given the relative paucity of lymphoid tissue in the normal renal parenchyma. • Hematogenous dissemination most common and is thought to occur in 90% of cases; – direct extension from retroperitoneal lymph nodes accounts for the remainder. 174
  175. 175. Renal Lymphoma and Leukemia • lymphomas are more common in patients with iatrogenic immune suppression, acquired immunodeficiency syndrome (AIDS), autoimmune diseases, or graft-versus-host disease and in patients with a history of radiation therapy (McVary, 1991). • Renal lymphoma should be suspected in patients with massive retroperitoneal lymphadenopathy, splenomegaly, or lymphadenopathy in other regions of the body or atypical regions within the retroperitoneum (Jafri et al, 1982; Dimopoulos et al, 1996). • The CT scan is the radiographic modality of choice for the diagnosis of renal lymphoma and for monitoring response to therapy (Jafri et al, 1982; Pollack et al, 1987; Sheeran and Sussman, 1998; Urban and Fishman, 2000). – Renal lymphoma can present as multiple distinct renal masses; – as a solitary renal mass, which can be difficult to differentiate from RCC; – as diffuse renal infiltration; – or as direct invasion of the kidney from enlarged retroperitoneal nodes (Cohan et al, 1990; Heiken et al, 1991; Eisenberg et al, 1994; Sheeran and Sussman, 1998; Sheth et al, 2006). 175
  176. 176. Renal Lymphoma and Leukemia • The main landing zones for RCC should be kept in mind – the interaortocaval region for right RCC – and para-aortic region for left RCC – and lymphadenopathy centered outside of these areas should raise suspicion for lymphoma. • A hypovascular pattern on angiography is typical for renal lymphoma (Pollack et al, 1987). • Any patient with a prior history of lymphoma and a renal mass should also be evaluated for renal recurrence rather than for RCC. 176
  177. 177. Renal Lymphoma and Leukemia • Renal involvement related to leukamia – more common children, paralleling the demographics of the disease – commonly due to lymphocytic leukemia than the myelogenous forms (Araki, 1982; Pollack et al, 1987). – Leukemia typically involves the kidney in a diffusely infiltrative pattern – often represents a late manifestation of systemic disease. • Both renal lymphoma and leukemia are commonly silent – can be associated with hematuria, flank pain, or progressive renal failure. Fever, weight loss, and fatigue, (B symptoms )(Yasunaga et al, 1997; Zomas et al, 2004). – Renal failure can be due to extensive replacement of the functioning parenchyma or bilateral ureteral obstruction associated with enlarged retroperitoneal lymph nodes (McVary, 1991). – renal failure in such patients is more often related to medical causes, such as hypercalcemia or urate nephropathy, that can develop during systemic treatment of advanced disease. 177
  178. 178. Renal Lymphoma and Leukemia • If lymphoma or leukemic renal involvement is suspected, – percutaneous biopsy to obtain a pathologic diagnosis; – and if exploratory surgery is necessary, intraoperative biopsy and frozen-section analysis should take priority. • Truong and colleagues (2001) have demonstrated the utility of fine- needle aspiration in the diagnosis of renal lymphoma • If lymphoma or leukemia is confirmed, – the kidney should be spared and complete staging of the neoplasm should be performed to preclude the need for a secondary procedure (McVary, 1991). • Extirpative surgery should be avoided if renal lymphoma and leukemia are suspected – treatment of these processes is generally systemic chemotherapy with or without radiation therapy. 178
  179. 179. Renal Lymphoma and Leukemia • The classic chemotherapy regimen for non-Hodgkin’s lymphoma – CHOP protocol, which includes cyclophosphamide, doxorubicin, vincristine, and prednisolone (Colevas et al, 2000). • Nephrectomy is seldom indicated – except in patients with severe symptoms, such as uncontrollable hemorrhage. – The other notable exception is the extremely rare patient with primary renal lymphoma in whom a combination of nephrectomy and systemic chemotherapy may represent optimal therapy (Okuno et al, 1995; Garcia et al, 2007). • E.g marginal zone B-cell lymphoma (MALT) localized to the kidney have been described with some apparently cured by surgery alone (Garcia et al, 2007). 179
  180. 180. Carcinoid tumors • arise from Primitive stem cells within the kidney or retained neural crest tissue (Krishnan et al, 1997; Begin et al, 1998). • This is thus a rare renal malignant neoplasm with fewer than 60 cases reported in the English literature (Kawajiri et al, 2004; Mufarrij et al, 2005; Romero et al, 2006; Hansel et al, 2007; Lane et al, 2007b; Canacci et al, 2008). • A correlation with horseshoe kidneys • stain positive for markers of neuroendocrine tissue such as neuron-specific enolase and chromogranin (Kulke and Mayer, 1999; Lane et al, 2007b). 180
  181. 181. Carcinoid tumors • Presentation of carcinoid syndrome (Jensen and Doherty, 2001; Romero et al, 2006; Lane et al, 2007b). – Median age at diagnosis is 49 years (Romero et al, 2006). – episodic flushing, – wheezing, – and diarrhoea • diagnosis – Measurement of urinary or plasma serotonin or its metabolites can be diagnostic (Kulke and Mayer, 1999). – renal carcinoids, metastases were found in 46% of patients at diagnosis (Romero et al, 2006) – CT findings are nonspecific, and many renal carcinoids are small and nonaggressive. 181
  182. 182. Carcinoid tumors • Management – Surgical excision is the mainstay of treatment (Kawajiri et al, 2004). – Nephron-sparing surgery is preferred if the diagnosis is suspected preoperatively. • prognosis – Prognosis is good, particularly when associated with a horseshoe kidney (Krishnan et al, 1997; Begin et al, 1998; Lowrance et al, 2006). – Significant adverse prognostic factors include (Romero et al, 2006). • age older than 40 years, • tumor size greater than 4 cm, • high mitotic rate, • purely solid gross morphology, • metastasis at initial diagnosis, • and tumor extending through the renal capsule 182
  183. 183. NEUROENDOCRINE TUMORS • include – small cell carcinoma and – large cell neuroendocrine carcinoma • can occur in the kidney but are even less common than renal carcinoids (Gonzales-Lois et al, 2001; Majhail et al, 2003; Lane et al, 2007). • Presentation – flank pain or hematuria is common (Majhail et al, 2003; Mirza et al, 2007). – Many small cell carcinomas of the kidney are locally advanced or metastatic at presentation, and • Positive staining for neuron-specific enolase, chromogranin, and synaptophysin is characteristic (Akkaya et al, 2003). 183
  184. 184. Neuroendocrine Tumors • Preoperative differentiation from RCC is difficult, although a – relatively hypovascular pattern may be an indication. • Multimodal therapy – with nephrectomy or tumor debulking combined with platinum-based chemotherapy regimens is advocated for extrapulmonary small cell carcinoma in general and may also be useful for the renal manifestation of this malignant neoplasm (Majhail et al, 2003; Mirza et al, 2007). • prognosis – Long-term survivors are described but rare 184
  185. 185. Metastatic Tumors • most common malignant neoplasms in the kidney, outnumbering primary renal tumors – Autopsy studies have shown that 12% of patients dying of cancer have renal metastases, making the kidney one of the most common sites for metastatic dissemination (Pollack et al, 1987). • The profuse vascularity of the kidney makes it a fertile soil for the deposition and growth of cancer cells. – Almost all renal metastases develop through a hematogenous route of spread; – only a small minority are caused by direct invasion of tumors derived from adjacent organs such as the pancreas, colon, and adrenal gland. 185
  186. 186. Metastatic Tumors • The most common sources of renal metastases include lung, breast, and gastrointestinal cancers; malignant melanoma; and the hematologic malignant neoplasms (Klinger, 1951; Choyke et al, 1987; Pollack et al, 1987; Aron et al, 2004; Martino et al, 2004; Sánchez-Ortiz et al, 2004b; Stage et al, 2005). • renal metastases consists of multiple small nodules that are often clinically silent, – can lead to hematuria or flank pain in exceptional circumstances (Walther et al, 1979; Pollack et al, 1987). 186
  187. 187. Metastatic Tumors • Renal metastases should be suspected in – any patient with multiple renal lesions – widespread systemic metastases – history of nonrenal primary cancer. • If there is any uncertainty about the diagnosis, – a CT- or ultrasound-guided percutaneous renal biopsy usually provides pathologic confirmation (Gattuso et al, 1999; Sánchez-Ortiz, 2004a). – CT is the primary diagnostic modality for renal metastases and typically demonstrates isodense masses that enhance only moderately after administration of intravenous contrast material (Pollack et al, 1987; Ferrozzi et al, 1997). • Most patients with renal metastases are managed – with systemic therapy – or placed on a palliative care pathway, depending on the clinical circumstances. – Nephrectomy is almost never required except in extenuating circumstances, such as uncontrollable renal hemorrhage. 187
  188. 188. References 1. Campbell Walsh Urology 10th Edition; 1413-1505 2. Smith and Tanagho’s General Urology 18th Edition; 330-349 3. AUA guidelines 4. EUA guidelines, 2015 5. http://www.uonbi.ac.ke/ Digital Repository 6. http://www.emedicine.medscape.com 7. http://radiopaedia.org/articles/renal-cell-carcinoma 188
  189. 189. …the end thankyou. 189