Renal tumors.pptx

Renal tumors -- Renal cell carcinoma

1. Renal Parenchymal Neoplasms Lara Masri

2. Renal Cell Carcinoma Renal cell carcinoma (RCC) accounts for 2–5% of adult cancers Constitutes approximately 70% of all primary malignant renal tumors RCC occurs most commonly in the sixth to seventh decades Male:female ratio of 2:1 Arises mostly from the upper pole

3. Etiology Most renal cell carcinomas (RCCs) occur sporadically . Approx. 4% of renal cell carcinomas are associated with hereditary factors . Both forms show structural alterations of the short arm of chromosome 3 (3p) and subsequent alterations of the VHL gene . Risk factors for sporadic RCC   Male Smoking  twofold increase in risk  major risk factor for RCC Obesity Sickle cell disease   Renal Medullary Carcinoma Acquired cystic kidney disease   Renal pelvic stones Hypertension Immunodeficiency Chronic hepatitis C infection Occupational exposure to: Asbestos, solvents, cadmium

4. The risk of developing RCC has been estimated to be >30 times higher in patients receiving dialysis who have cystic changes in their kidneys than in the general population. RCC occurs in 3–9% of patients with acquired cystic disease of the kidneys. Renal cell carcinoma is associated with a wide spectrum of paraneoplastic syndromes, including polycythemia, thrombocytosis, hypercalcemia, cachexia, pyrexia, hypertension, and hepatic dysfunction Hypercalcemia is the most common paraneoplastic complication in renal cell carcinoma  13%  due to production of a parathyroid hormone-related peptide ( PTHrP ) Stauffer syndrome  is a constellation of signs and symptoms of liver  dysfunction that arises due to presence of renal cell carcinoma

5. Hereditary renal cell  carcinomas Von Hippel-Lindau syndrome :  is a familial cancer syndrome Approx . 40% of patients with VHL syndrome develop renal cell carcinomas ( usuallyclear cell RCC). central nervous system (CNS) hemangiomas, retinal agniomas , and pheochromocytom a Tuberous sclerosis 5 % of people with tuberous sclerosis develop renal cell carcinomas (usually clear cell RCC). RCC occurs more commonly in women . Associated with AMLs, Seizures, Development Delay. Birt -Hogg- Dube syndrome Inherited autosomal dominant condition caused by a mutation in the folliculin ( FLCN ) gene  on chromosome  17. Characterized by Skin  lesions: fibrofolliculomas , benign hamartomatous tumors of hair follicles Lung cysts  , spontenous pneumothorax Renal cell carcinoma (usually chromophobic ceal cell RCC or  oncocytic RCC)

6. Succinate dehydrogenase kidney cancer (SDH-RCC) Autosomal Dominant caused by a mutation in any of three succinate dehydrogeanse subunits, B, C, or D. Patients develop clear cell RCC, chromophobe RCC, type 2 papillary RCC, and oncocytomas , paragangliomas ,  pheochromocytomas . Hereditary leiomyomatosis and renal cancer syndrome  (HLRCC) Autosomal dominant condition caused by a mutated fumarate dehydrogenase gene (FH) located on chromosome 1  Characterized by cutaneous and uterine leiomyomas 15% develop type 2 papillary  RCC Hereditary papillary renal cell carcinoma  (HPRCC) Autosomal dominant condition with a high penetrance Caused by activating mutations of the MET proto-oncogene located on the long arm of chromosome 7 Usually associated with type 1 papillary RCC  

7. Clinical features Usually asymptomatic in the early stages Patients become symptomatic when the tumor has reached a large size (usually > 10 cm) and/or if metastases are present.  Constitutional symptoms  Weight loss, fatigue, Fever , night sweats  , Anemia Symptoms caused by primary  tumor  7-10% of pts Hematuria   60% of RCC patients Flank pain  Palpable renal mass  Patients may also present with dyspnea, cough, and bone pain that are typically symptoms secondary to metastases.

8. Pathogenesis Renal cell carcinomas are vascular tumors that tend to spread either by direct invasion through the renal capsule into perinephric fat and adjacent visceral structures . direct extension into the renal vein. Approximately 20–25% of patients show evidence of metastatic disease at presentation. The most common site of distant metastases is the lung . However, liver, bone (osteolytic), ipsilateral adjacent lymph nodes and adrenal gland, brain, the contralateral kidney, and subcutaneous tissue are frequent sites of disease spread

9. ▶ Tumor Staging and Grading

10. Pathology Renal cell carcinomas are adenocarcinomas that usually arise from the  epithelial cells of the proximal convoluted tubule . Clear Cell Renal Cell Carcinoma: Relative frequency : 70% Cell of origin : Proximal convuoluted tubule Etiology : Sporadic or inherited mutation of VHL gene on chromosome 3p Macroscopic appearance : Yellow or golden due to high intracellular lipid concentration Microscopic appearance: Clear cells  Polygonal cells arranged as cords or tubules (non-papillary growth) Clear, glycogen and/or lipid-filled cytoplasm Unifocal , unilateral growth Prognosis : Depending on tumor stage  

11. Papillary RCC ( Chromophilic) Relative frequency : 10-15% Cell of origin : Proximal convuoluted tubule Etiology : Trisomy 7, 17, Loss of Y chromosome Macroscopic appearance : Yellow or golden due to high intracellular lipid concentration Microscopic appearance: Cuboidal, low columnar cells Cells grow in papillary formations  Bilateral, multifocal growth possible Prognosis : Type 1 papillary RCC: better than type 2 papillary RCC Type 2 papillary RCC: aggressive tumor with a poor prognosis   

12. Chromophobe RCC Relative frequency : 5% Cell of origin : cortical  collecting duct Etiology : Hypodiploidy , Birt -Hogg- Dube syndrome Macroscopic appearance : Yellow or golden due to high intracellular lipid concentration Microscopic appearance: Large polygonal cells with a prominent cell membrane Eosinophilic cytoplasm Perinuclear halo Prognosis : Excellent

13. Oncocytic RCC Relative frequency : 1% Cell of origin : cortical collecting duct Etiology : unknown Macroscopic appearance : Yellow or golden due to high intracellular lipid concentration Microscopic appearance: Originate from oncocytomas Similar to chromophobic RCC, but without perinuclear halo Cells occur as tumor nests Prognosis : Excellent

14. Collecting duct carcinoma (Bellini duct carcinoma) Relative frequency : 1% Cell of origin : Medullary Collecting duct Etiology : unknown Macroscopic appearance : Yellow or golden due to high intracellular lipid concentration Microscopic appearance: Hobnail pattern: irregularly arranged malignant glandular cells within a fibrous stroma Medullary duct carcinoma: A variant that is associated with sickle cell disease Prognosis : Aggressive with poor prognosis

15. Diagnostics Laboratory studies and urinalysis Urinalysis Can show frank and microscopic hematuria  Measure  albumin: creatinine ratio if proteinuria is detected.  Laboratory studies   CBC Abnormal  hemoglobin levels   normochromic anemia in 30% ↑ WBC and/or ↑ platelets   ↓ serum iron, TIBC ↑ ESR in 75%, ↑CRP ( could be prognostic of recurrence) CMP Hypercalcemia  ↑ AST, ALT, and/or ALP  ↑  BUN:creatinine ratio  

16. Imaging Imaging Classification for Renal Lesions

17. Workup based on imaging findings  Findings Next steps Bosniak I and II cystic mass Follow-up is usually not required Bosniak IIF cystic mass Repeat imaging at 6 and 12 months, then yearly for a total of 5 years. Refer to urology if there is any change in appearance or > 3 mm growth per year. Bosniak III or IV cystic mass Solid mass > 1 cm with no fat Obtain CBC, BMP, and urinalysis.   Refer to urology for consideration of further investigations (e.g., staging, biopsy).

18. Ultrasonography 98% accurate in distinguishing simple cysts from solid lesions. Strict ultrasonographic criteria for a simple cyst include through transmission, a well-circumscribed mass without internal echoes, and adequate visualization of a strong posterior wall Contrast-enhanced ultrasound using microbubbles, rather than a contrast agent, can better visualize renal parenchyma and blood flow within and around the tumor. This is useful in patients who may not receive contrast because of a severe allergy or chronic kidney disease. Intraoperative ultrasonography is also often used to confirm the extent and number of masses in the kidney at the time of performing a partial nephrectomy

19. CT scanning A typical finding of RCC on CT is a mass that is enhanced with contrast media. In general, RCC exhibits an overall decreased density in hounsfield units compared with normal renal parenchyma. Identify macroscopic fat in a renal mass Stage the patient by visualizing the renal hilum, perinephric space, renal vein and vena cava, adrenal glands, regional lymph nodes, and adjacent organs. A CT scan of the chest is indicated in patients with equivocal chest x-ray findings. Patients who present with symptoms consistent with brain metastases should be evaluated with either head CT or MRI.

20. MRI R enal masses are isointense to moderately hypointense on T1-weighted phases H yperintense on T2-weighted phases. Its primary advantage is in the evaluation of patients with suspected macroscopic fat or renal vein and vena cava involvement with tumor thrombus The use of gadolinium-based contrast in MRI can avoid the risks of contrast nephropathy . However, in those with severe renal insufficiency ( eGFR < 30 mL/min), there is a significant risk of nephrogenic systemic fibrosis with gadolinium. The primary disadvantage of MRI is higher cost, longer duration, and patient discomfort during the study

21. Biopsy of Renal Masses Renal mass biopsy should be considered if a mass is concerning for metastatic, hematologic, infectious, or inflammatory etiology Should not be considered in otherwise young and healthy patients that would undergo intervention anyway or older, frail patients that are not planning to undergo intervention Establishing a diagnosis in patients who are not surgical candidates, selecting patients undergoing active surveillance for small renal masses, and evaluating radiographically indeterminate lesions. Biopsy should be considered primarily in those patients in whom the results would change management. Core biopsy is more sensitive and specific than fine-needle aspiration and is preferred.

22. Treatment Approach Local or locoregional disease : curative treatment intent   Standard of care: nephrectomy (partial or radical)  Consider adrenalectomy, lymph node dissection, and adjuvant therapy with sunitinib Metastatic disease : mostly palliative treatment intent but may be curative for patients with a solitary metastasis or  oligometastatic disease  Targeted and/or immunotherapy In selected patients, surgery (i.e., cytoreductive  nephrectomy,  metastasectomy ) or other local therapies (e.g., embolization ) Consider active surveillance  for patients with:  Solid masses < 2 cm Complex masses that are predominantly cystic limited life expectancy High surgical risk

23. Medical therapy Targeted Therapy VEGF receptor tyrosine kinase inhibitor  Pazopanib , Sunitinib , Sorafenib , Cabozantinib , Tivozanib , Axitinib , Lenvatinib Anti-VEGF antibodies  Bevacizumab mTOR inhibitors  Everolimus , Temsirolimus Immunotherapy Anti-PD-1 antibodies  Pembrolizumab , Nivolumab , Avelumab Anti-CTLA-4 antibodies  Ipilimumab Cytokines  Interleukin 2 , Interferon alpha

24. Surgery   The following applies to patients with solid renal masses or renal cysts with Bosniak classification III or IV. The approach may be open, robotic, or laparoscopic. Partial  nephrectomy:  Absolute indications: patients with a T1a renal mass , a solitary kidney, bilateral masses, familial RCC, preexisting chronic kidney disease, or proteinuria  Relative indications: patients who are young and/or have a longer life expectancy, multifocal masses, or comorbidities that impact renal function  Radical nephrectomy Removal of the entire kidney along with the adrenal gland and surrounding perinephric fat, with or without lymph node dissection Preferred in patients with increased oncological risk 

25. Radiochemotherapy Radiation therapy is not typically used because RCC is usually radioresistant .   Conventional chemotherapy is not used to treat RCC because RCC is highly resistant to most chemotherapeutic agents.  Local therapies   Thermal ablation (e.g.,  cryoablation ): may be appropriate for patients with tumors ≤ 3 cm and/or high surgical risk Embolization of the primary tumor and/or metastases: for symptom control in patients with nonresectable disease   

26. Complications caused by paraneoplastic syndromes Secondary hypercortisolism : due to ectopic ACTH release Secondary polycythemia : due to ectopic erythropoietin (EPO) secretion Hypertension : due to the release of renin Hypercalcemia : due to the release of PTHrP  (parathyroid hormone-related protein) Leukemoid reaction : due to bone marrow stimulation Limbic encephalitis   Memory loss Psychosis Depression Complications caused by local spread Varicocele Rare, classically associated with left-sided RCC Malignant cells grow inside the left renal vein and occlude the ostium of the left gonadal vein.  Budd-Chiari syndrome : caused by involvement of the IVC Lower limb edema Ascites Hepatic dysfunction  

27. Complications caused by metastatic  disease Spread beyond the renal capsule affects the lymph nodes of the renal hilum and para-aortic nodes. Hematogenous spread occurs via renal vein and IVC . Pulmonary metastases : most common site of metastases Hemoptysis Dyspnea Bone metastases : second most common site of metastases Bone pain Pathological fractures Reactive amyloidosis  RCC accounts for 25 to 42% of all reported AA amyloidosis cases caused by solid organ malignancies . Clinical features Nephrotic syndrome  Primary adrenal insufficiency Hepatosplenomegaly Malabsorption

28. Angiomyolipoma   Definition : benign renal tumors that arise from perivascular epithelioid cells and consist of blood vessels, smooth muscle, and mature fat cells Most common benign renal  tumor, F > M (4:1) Etiology Sporadic   usually unilateral Associated with : Tuberous sclerosis (TSC)   45-80%  bilateral , asymptomatic Sporadic  lymphangioleiomyomatosis  

29. Diagnostics   Abdominal ultrasound: round, well-circumscribed, highly echogenic (similar echogenicity to renal pelvis) renal tumor often located near the renal capsule (cause bulging )  Abdominal CT Tumor with macroscopic fat deposits  No calcification Treatment : Surgical resection of the tumor is indicated for  angiomyolipomas  that measure > 4 cm in diameter AND symptomatic If < 4 cm  follow up with yearly CT or US If > 4cm asymptomatic  follow up semiannual US

30. Oncocytoma Definition : benign epithelial tumor arising from the intercalated tubular cells in the collecting duct, 3-5% of renal masses, males > females May occur in adrenal, thyroid, salivary, parathyroid gland. Pathology Macroscopy: smooth, clearly defined brown tumor with central stellate  scar  Microscopy Large acidophilic cells  Excessive amount of mitochondria → acidophilic, granular eosinophilic  cytoplasm  ( oncocytes ) Treatment Often resected in order to exclude RCC Surveillance Nephrectomy in case of increase in tumor size  Prognosis : Oncocytomas are not invasive, but they may transform into a malignant  oncocytic RCC