Renal Tumors Pathology PDF

Prof. Nazik Elmalaika O.S. Husain, MBBS, MD, MSc, MHPE, PhD. Pathology Department, FMHS, Omdurman Islamic University, Sudan. 1 Outlines The World Health Organization (WHO) 2022 classification of urinary and male genit...

Prof. Nazik Elmalaika O.S. Husain, MBBS, MD, MSc, MHPE, PhD. Pathology Department, FMHS, Omdurman Islamic University, Sudan. 1 Outlines The World Health Organization (WHO) 2022 classification of urinary and male genital tumors (5th edition). Diagnostic criteria, molecular correlates and nomenclature have been updated. Selected tumors. The WHO (2022) of Kidney tumors A. Renal cell tumors 1. Clear cell renal tumors 2. Papillary renal tumors 3. Oncocytic and chromophobe renal tumors. 4. Collecting duct tumors 5. Other renal tumors 6. Molecularly defined renal carcinomas. B. Metanephric tumors C. Mixed epithelial and stromal renal tumors D. Renal mesenchymal tumors E. Embryonal neoplasms of the kidney F. Miscellaneous renal tumors. * Classification of Renal tumors: Oncocytoma. Clear cell renal cell carcinoma. Nephroblastoma (Wilms tumor). 4  General information With the exception of oncocytoma, benign tumors rarely cause clinical problems. Malignant tumors, on the other hand, are of great importance clinically and deserve considerable emphasis. By far the most common of these malignant tumors is renal cell carcinoma that affects adults, followed by Nephroblastoma (Wilms tumor), which is found in children.  Renal oncocytoma * Clinical Features: 5 - 9% of renal tumors M:F = 2:1 Most cases are asymptomatic, although flank pain may be a presenting complaint; hematuria may be seen. CT or MRI may identify a central scar. 6  Renal oncocytoma: Pathophysiology Benign neoplasms are believed to arise from renal intercalated cells and are packed with respiration-defective mitochondria. Often possess pathogenic mitochondrial mutations; it is suggested that the defective mitochondria activates a metabolic checkpoint leading to autophagy impairment and mitochondrial accumulation. Some cases have hybrid morphologies and Multiple tumors can be associated with syndromic conditions.  Renal oncocytoma: Pathophysiology 2 main molecular variant events associated with oncocytomas: rearrangements of CCDN1 (11q13 translocations) or aneuploidy manifested mostly in losses of chromosome Y and 1. Also suggested that in some oncocytomas (the ones that harbor aneuploidy losses of chromosome 1 and Y), additional p53 mutations may allow for progression to eosinophilic chromophobe renal cell carcinoma. Renal oncocytoma * Gross Pathology: Well-circumscribed, homogeneous cortical tumor. Mahogany-brown cut surface. Often shows a central, irregular fibrous scar. Bilateral or multicentric in 2% to 3% of cases. 9 10  Renal oncocytoma On microscopic examination: Well circumscribed lesion; usually no pseudocapsule. Composed of large round eosinophilic cells (oncocytes) with dense granular cytoplasm; nuclei are round and regular with even chromatin; small but conspicuous nucleoli are present. The cells are arranged in nests separated by edematous and hyalinized fibrous stroma. 11 Renal oncocytoma Positive stains: CD117 / KIT, E-cadherin, S100A1, PAX8 Low molecular weight keratin (CAM 5.2) and pancytokeratin. Negative stains: CK7 negative or scattered rare positive cells, AMACR, CAIX, Vimentin, HMB45, melanA, CK20, Hale colloidal iron. 14 15 * Epidemiology: Renal cell carcinomas represent about 1% to 3% of all visceral cancers and account for 85% of renal malignancy in adults. The tumors occur most often in older individuals, usually in the sixth and seventh decades of life, showing a male preponderance in the ratio of 2:1. Most renal cancer is sporadic, but unusual forms are a familial. 16  * Risk factors 1. Cigarette smoking is the most significant risk factor. 2. Obesity (particularly in women). 3. Hypertension. 4. Unopposed estrogen therapy. 5. Exposure to asbestos, petroleum products, and heavy metals. 6. Acquired polycystic kidney disease secondary to dialysis. 17  * Clinical presentation Silent 1. Hematuria. 2. Flank pain. 3. Flank lump. This triad is seen in only 10% of cases. The most reliable of the three is hematuria, but it is usually intermittent and may be microscopic; thus, the tumor may remain silent until it attains a large size. 18  Renal cell carcinoma tends to produce a diversity of systemic symptoms not related to the kidney termed paraneoplastic syndromes, ascribed to abnormal hormone production including; Polycythemia (erythropoietin):: Hct > 60%. Hypercalcemia (PTH like hormone). Hypertension. 19  Hepatic dysfunction. Feminization or masculinization (↑ gonadotrophin). Cushing syndrome. Leukemoid reactions. Amyloidosis. 20  One of the common characteristics of this tumor is its tendency to metastasize widely before giving rise to any local symptoms or signs. In 25% of patients with renal cell carcinoma, there is radiologic evidence of metastases at the time of presentation. The most common locations of metastasis are the lungs (more than 50%) and bones (33%), followed in order by the regional lymph nodes, liver and adrenals, and brain. 21 * Classification 22  This is the most common type, accounting for 70% to 80% of RCT. * Gross Pathology: Solitary renal cortical mass. Bilaterality and multifocality more common in familial cases. Well-circumscribed, lobulated with golden-yellow cut surface. Cystic change, hemorrhage, necrosis, and calcification often present. 23 24  * Histopathology: Nests of clear cells interspersed by delicate vascular network. 25  Cancer cells with clear cytoplasm. It contain glycogen. PAS +ve. 26 Positive stains: PAX8 and PAX2. CAIX: diffuse, membranous in 75 - 100% of clear cell RCC. Generally, CD10 (proximal tubular marker), RCC, vimentin and epithelial markers including AE1 / AE3, CAM 5.2, EMA. Negative stains: CK20, inhibin, MelanA / MART1, calretinin, TTF1, CEA.  Metastasis: Lung and bone Bone: produce osteolytic lesion and cause pathological fracture. Marker of bone mets.: ↑alkaline phosphatase. 28 Nephroblastoma (Wilms tumor) 29 Nephroblastoma (Wilms tumor) Nephroblastoma (or Wilms tumor) is a malignant embryonal tumor originating from nephrogenic blastema, which imitates the histology of developing kidney. Primarily occurs in children. Named after the German surgeon Max Wilms (who is often wrongly attributed to be the first one describing this entity). Nephroblastoma: Epidemiology Most common: 3 - 4 years of age. European and North American rates are about the same (8 per million). More common in Africans; least common in East Asian population. Congenital Wilms tumors very rare. Rare adult cases. Slight female preponderance. Majority of patients with Wilms tumor are nonsyndromic. 10 - 15% associated with syndromes and congenital anomalies. 1 - 2% familial. Relapses occur in ~15% of children, the majority within 2 years of diagnosis. Nephroblastoma: Etiology Thought to develop from persistent metanephric tissue or nephrogenic rests. Believed to be due genetic alterations of embryological development of the genitourinary tract. WT1 gene at chromosome 11p13 implicated in tumorigenesis. WT2 gene at chromosome 11p15 is a second locus.  Nephroblastoma: Clinical features Usually presents as abdominal mass with no associated symptoms. Other signs or symptoms (present in 20 - 30% of cases): Abdominal pain Hematuria Hypertension Anemia. Most common predisposition syndromes and conditions with different risk (high, moderate, low).  Nephroblastoma associated syndromes WAGR syndrome A = aniridia, G = genital abnormality, R = mental retardation Denys-Drash Syndrome Gonadal Dysgenesis and renal abnormality. Beckwith-widemann Enlargement of Individual organ Syndrome (macroglossia). Enlargement of entire body segment (hemihypertrophy). Enlargement of adrenal cortical gland. 34 Nephroblastoma Gross: lobulated, tan mass Micro: Tumor consists of blastemal, epithelial and stromal elements (triphasic) which can be present in variable amounts, and may show different lines and degrees of differentiation (from poor to well differentiated). Excellent, long-term survival 90%. Nephroblastoma (Wilms tumor): Morphology Small blue blastemal cells 36 Blastemal component composed of undifferentiated cells, arranged in small nodules.  Classification of Renal tumors (WHO 2022). I. Oncocytic and chromophobe renal tumors: Oncocytoma. II. Clear cell renal tumors: Clear cell renal cell carcinoma. III. Embryonal neoplasms of the kidney: Nephroblastoma (Wilms tumor). THANKS