Renal Tumors PDF: Types, Symptoms, and Treatment

Renal Tumors Axel Baez Torres, M.D.  Objectives Describe the pathogenesis, epidemiology, clinical presentation, clinical course, pathology, tumor grading, tumor staging and treatment of renal cell carcinoma Describe the epidemiology, clinical presentation, clinial course,...

Renal Tumors Axel Baez Torres, M.D.  Objectives Describe the pathogenesis, epidemiology, clinical presentation, clinical course, pathology, tumor grading, tumor staging and treatment of renal cell carcinoma Describe the epidemiology, clinical presentation, clinial course, pathology and treatment of urothelial carcinoma of renal pelvis Define and use in proper context: Goodpasture Syndrome, heart failure cell  Renal Tumors Nephroblastoma (Wilm’s tumor) Renal cell carcinoma Urothelial carcinoma of renal pelvis  Wilm’s Tumors Malignant neoplasm of embryonic nephrogenic elements Constitutes the most frequent abdominal solid tumor in children, the most common primary renal tumor in children and the fourth most common pediatric malignancy  Wilm’s Tumors Occurs primarily in children (50% of cases before 3 years and 90% before age 6) In 90% of cases a palpable abdominal mass is the initial sign. Hematuria, abdominal pain and hypertension may be present  Wilm’s Tumors In 90% of cases the tumor is sporadic and unilateral. In 5% of cases the tumor arises in the context of three different congenital malformation syndromes: WAGR syndrome Denys-Drash syndrome Beckwith-Wiedeman syndrome  Wilm’s Tumors Tumor development in some cases has been linked with two distinct chromosomal loci (putative tumor suppressor genes); the Wilm’s tumor- associated genes WT1 and WT2, both located on the short arm of chromosome 11  Wilm’s Tumors Macroscopic – Large, solitary, well circumscribed renal mass  Wilm’s Tumors Microscopic – The classic combination of embryonic blastemal, stromal and epithelial elements is observed in the vast majority of cases  Wilm’s Tumors The treatment and clinical course of patients with Wilm’s tumor depends on tumor stage and histologic category (presence or absence of anaplasia)  Wilm’s Tumors Stage I: Tumor confined to kidney and completely resected Stage II: Tumor extends locally beyond kidney but is completely resected Stage III: Residual tumor confined to abdomen without hematogenous spread Stage IV: Hematogenous metastasis or involvement of lymph nodes beyond renal drainage region Stage V: Bilateral renal tumors  Wilm’s Tumors Anaplasia – Presence of enlarged hyperchromatic nuclei that are at least three times the size of nuclei of the same cell type and abnormal (multipolar) mitotic figures  Wilm’s Tumors The majority of Wilm’s tumor are low-stage, have favorable histology (absent anaplasia), and have excellent prognosis For these patients the treatment includes nephrectomy, double- agent chemotherapy without radiotherapy Actually, the estimated overall long-term survival rate is 90%  Renal Cell Carcinoma The most common primary cancer of the kidney Arises from renal tubular epithelium Occur most often in older individuals, with peak incidence in the sixth decade The most important etiologic factor in tobacco smoking  Renal Cell Carcinoma Most cases are sporadic, but about 5% are inherited and occurs in the context of three distinct syndromes: – Von-Hippel Lindau syndrome – Hereditary clear cell carcinoma – Hereditary papillary carcinoma  Renal Cell Carcinoma The most common initial symptoms are hematuria (60%), flank pain (50%) or an abdominal mass (33%); symptoms often indicative of an advance stage of disease at diagnosis  Renal Cell Carcinoma Systemic metastasis are identified in 25% to 30% of patients at initial evaluation The most common sites of distant metastases include lung, bone, liver, adrenal gland and brain  Renal Cell Carcinoma Tumors may produce a diversity of systemic symptoms and paraneoplastic effects attributable to ectopic hormone production including: – Polycythemia(erythropoietin) – Hypertension(renin) – Hypercalcemia(parathormone- related peptide) – Maculinization or Feminization(steroid hormones)  Table 16-17 Categories of Renal Cell Carcinoma Category Frequency(%) Clear cell type 70-80 Papillarytype 10-15 Chromophobe type 5 Collecting duct type 1  RCC Clear Cell Type Most common type of renal cell carcinoma accounting for 70-80% of cases In 98% of these tumors there is loss of sequences on the short arm of chromosome 3.Three particular loci are disproportionaly affected: 3p14, 3p21.3 and 3p25.3 (the location of the VHL gene)  RCC Clear Cell Type Most tumors appear centered on the cortex and usually solitary and unilateral Typical cross sections shows a yellowish spherical mass which may contain hemorrhagic or cystic areas  RCC Clear Cell Type Tumor cells have characteristic transparent cytoplasm in formalin-fixed sections The most common architectural patterns and alveolar, trabecular, tubular and microcystic  RCC Papillary Type Accounts for 10-15% of renal cell carcinomas Not associated with 3p deletion The most common cytogenetic abnormalities are trisomies 7, 16 and 17 and loss of Y in male patients in the sporadic form and trisomy 7 associated to mutation of MET proto-oncogene in the familial form.  RCC Papillary Type Multifocality and bilaterality are more common than in clear cell type Most common type occurring in association to dialysis-related acquired cystic disease  RCC with Xp11.2 Translocation Most often arises in children and young adults Distinctive appearance with alveolar and papillary architecture, clear cells and psammoma bodies. Characterized by the Xp11.2 translocation which can be detected by molecular testing. The gene product of the Xp11.2 locus is the TFE-3 protein. The Xp11.2 translocation may be shared with multiple partners, particularly with loci at chr. 1 and 17  RCC Cell Carcinoma Clinical Course: – Tumor stage and grade are the most important determinants of clinical outcome  RCC Cell Carcinoma Grading: – Grade I: Round uniform nuclei, nucleoli not visible – Grade 2: Irregular large nuclei, small nucleoli present – Grade 3: Irregular larger nuclei, prominent nucleoli – Grade 4: Pleomorphic nuclei, prominent nucleoli  RCC Cell Carcinoma Staging: – Stage I: Tumor confined within renal capsule – Stage II: Tumor confined by Gerota’s fascia – Stage III: Involvement of renal vein, vena cava or regional lymph nodes – Stage IV: Invasion of adjacent organs or distant metastasis  RCC Cell Carcinoma Treatment: – Radical nephrectomy is the standard therapy for localized RCC – Present systemic chemotherapeutic agents have little effect against RCC – Immunotheraphy protocols are still under study – Radiotherapy is of no value in the treatment of disseminated disease  RCC Cell Carcinoma Clinical Course: – The average 5-year survival rate is about 45% and up to 70% in the absence of distant metastasis – With the renal vein invasion or extension into the perinephric fat, the 5-year survival rate is reduced to approximately 15% to 20% Urothelial Carcinoma of Renal Pelvis Accounts for about 5-10% of renal cancers in adults. Peak incidence occurs in the sixth to seventh decade of life  Urothelial Carcinoma of Renal Pelvis Epidemiologic risk factors are the same for development of urinary bladder carcinoma including tobacco use, occupational exposure to arylamines, radiation, chronic inflammation and calculi Analgesic abuse is an important risk factor Urothelial Carcinoma of Renal Pelvis Painless gross hematuria is the most common initial symptom (70% to 80% of patients) Depending on their location, large tumors may cause urinary outflow obstruction and hydronephrosis Urothelial Carcinoma of Renal Pelvis Renal pelvis urothelial carcinomas are commonly associated with multifocal tumors, synchronous or metachronous cancer involving the ipsilateral or contralateral ureter, renal pelvis, or urinary bladder are identified in about 40% to 50% of patients Urothelial Carcinoma of Renal Pelvis Macroscopy – Most commonly exophytic papillary masses with frond- like growth on the mucosal surface – Tumors may extend down the ureter, or invade the renal medulla and cortex Urothelial Carcinoma of Renal Pelvis Microscopy – Most tumors have a papillary growth pattern – Tumors may be invasive or non-invasive  Urothelial Carcinoma of Renal Pelvis Grading – Tumors are graded in terms of cytologic features Grade I: Slight nuclear enlargement, without pleomorphism or mitotic activity Grade II: Moderate pleomorphism, prominent nucleoli, readily identified mitoses Grade III: Marked pleomorphism, prominent nucleoli and frequent mitoses Urothelial Carcinoma of Renal Pelvis Treatment – Nephoureterectomy with bladder cuff is the standard therapy for pyeloureteral urothelial carcinoma – Adjuvant chemotherapy and radiation therapy may used in the treatment of advanced disease. Urothelial Carcinoma of Renal Pelvis Clinical Course – Approximately 75% of renal pelvis urothelial carcinomas are low-grade and low-stage – Muscle invasion and metastasis to regional lymph nodes are adverse prognosis factors Urothelial Carcinoma of Renal Pelvis Patients with high-grade / high-stage lesions usually die within 2 years of diagnosis Overall 5-year survival rate after radical surgery ranges from 20% to 45% Urothelial Carcinoma of Renal Pelvis Poorest prognosis factor is the presence of distant metastasis. Common sites include lung, liver, bone and peritoneum