Renal oncocytoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2] Shanshan Cen, M.D. [3]

Renal oncocytoma is a relatively rare and benign tumor. The incidence of is approximately 3% to 7% of solid renal resected tumors and it is more common in male patients. The majority of patients with renal oncocytoma are asymptomatic. Symptoms of renal oncocytoma include hematuria, flank pain, abdominal or flank mass and weight loss. Physical examination of patients with renal oncocytoma is usually normal. An abdominal or flank mass may be palpayed during physical examination. Surgery is the mainstay of treatment for renal oncocytoma. Although the nature of renal oncocytoma is benign and the prognosis is excellent, since the definite diagnosis can not be obtained before operation, surgical resection is a choice of treatment.

Renal oncocytoma was first discovered by Zippel, in 1942 and Klein and Valensi were the first to demonstrate the pathologic characteristics of renal oncocytoma as “proximal tubular adenoma with oncocytic features” in 1976.

There is no established system for the classification of renal oncocytoma.

The exact pathogenesis of renal oncocytoma is not completely understood. Although some mechanisms are suggested in the pathogenesis of this disease that include, lossing of chromosome 1 and dysfunction of mitochondrial enzymes which is caused by alterations in the mitochondrial DNA. DNA diploidy is seen in 96% of patients with renal oncocytomas. The development of renal oncocytoma is the result of multiple genetic mutations such as deletion of chromosome 1, deletion of the sex chromosome, translocation of chromosome 11q13, sporadic or no chromosomal alteration. Renal oncocytoma can be associated with familial renal oncocytoma or Birt-Hogg-Dube syndrome. On gross pathology, tan to brown surface color , well-encapsulated with a thick, well-defined, fibrous capsule, central scar, and homogeneous appearance without any hemorrhage or necrosis inside it in the tumor cut are characteristic findings of renal oncocytoma. On microscopichistopathological analysis, renal oncocytoma characterized by “oncocytes”. They are large, round to polygonal neoplastic cells accompanied by eosinophilicgranular cytoplasm and are organized in nested or organoid pattern. Although, renal oncocytoma is benign, atypia, prominent nucleoli, and pleomorphism may seen in microscopic examination.

There are no established causes for renal oncocytoma.

Renal oncocytoma must be differentiated from other diseases that cause abdominal mass, abdominal pain and hematuria such as wilms tumor, renal cell carcinoma, rhabdoid kidney disease, polycystic kidney disease, and other urogenital mass.

The incidence of renal oncocytoma is approximately 3% to 7% of solid renal resected tumors. Patients of all age groups may develop renal oncocytoma. The age of patients can be differ from 10 to 94 years. The incidence of renal oncocytoma increases with age; the median age at the time of surgery is 62 to 68 years. Males are more commonly affected by renal oncocytoma than females. The male to female ratio is approximately 2 to 1.

Patients with tuberous sclerosis complex and Birt-Hogg-Dube syndrome are at an elevated risk of developing renal oncocytomas (often bilateral).

There is insufficient evidence to recommend routine screening for renal oncocytoma.

The median age at the time of surgery is 62 to 68 years. In 10% to 32% of patients with renal oncocytoma, coexcitente RCC are seen. Prognosis is generally excellent, There are only two cases of metastatic renal oncocytoma were reported. Since the definite diagnosis is maintain just after surgery, most of patients are undergone operation.

The majority of patients with renal oncocytoma are asymptomatic. Symptoms are seen in almost only 17% to 21% of patients with renal oncocytoma. Symptoms of renal oncocytoma include hematuria, flank pain, abdominal or flank mass and weight loss.

Physical examination of patients with renal oncocytoma is usually normal. An abdominal or flank mass may be palpayed during physical examination.

Some patients with renal oncocytoma may have hematuria, in their urine analysis.

X-ray is rarely done for the diagnosis of renal oncocytoma.

Abdominal CT scan may be helpful in the diagnosis of renal oncocytoma. Findings on CT scan suggestive ofrenal oncocytoma include solid renal lesion, centralscar (stellate scar), hypervascularity, hypodenseity ( most of the time), and homogenous enhancements.

Renal MRI may be helpful in the diagnosis of renal oncocytoma. Findings on MRI suggestive of renal oncocytoma include central scar, satellite pattern, pseudo-capsule, hypointensity in T1 and hyperintensity in T2 weighted images. Although, none of these characteristics can differentiate between renal oncocytoma and RCC.

Renal ultrasound in renal oncocytoma patients may show: solid mass ( help to distinguish solid from cystic mass), central scarring, calcification, central necrosis which none of them characteristics for indicating a specific renal lesion.

Renal angiography may be helpful in the diagnosis of renal oncocytoma. The “spoke-wheeled” appearance, lucent rim sign, homogeneous capillary flush in the nephrogram phase, lack of wild neoplastic vessels,and both hypovascular or hypervascular may seen on angiography of patients with renal oncocytoma. Although, none of them are specific for renal oncocytoma and they also may seen in RCCs.

Renal mass biopsy may be helpful in the diagnosis of renal oncocytoma. However, distinguishing between oncocytoma and RCC by biopsy is difficult. Since this method only reserved for patients who are at high risk for an operation like very elderly or extremely sick patients. Some complications may happen during renal mass biopsy which are perirenal hemorrhage, pneumothorax ( during biopsy of upper pole tumors) and tumor seeding.

The mainstay of therapy for renal oncocytoma is surgery.

Surgery is the mainstay of treatment for renal oncocytoma. Although the nature of renal oncocytoma is benign and the prognosis is excellent, since the definite diagnosis can not be obtained before operation, surgical resection is a choice of treatment. Best option for surgery differs based on the mass characteristics, partial nephrectomy is done in polar lesions smaller than 4 cm in a normal contralateral kidney while, large solid renal masses which destroy most part of renal tissue or patients who have not candidate for nephron-sparing surgery are reserved for total nephrectomy.

There are no established measures for the primary prevention of renal oncocytoma.

There are no established measures for the secondary prevention of renal oncocytoma.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]

Renal oncocytoma was first discovered by Zippel, in 1942 and Klein and Valensi were the first to demonstrate the pathologic characteristics of renal oncocytoma as “proximal tubular adenoma with oncocytic features” in 1976.

• Renal oncocytoma was first discovered by Zippel, in 1942.^[1]
• In 1976, Klein and Valensi were the first to demonstrate the pathologic characteristics of renal oncocytoma as “proximal tubular adenoma with oncocytic features”.^[2]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]

There is no established system for the classification of renal oncocytoma.

There is no established system for the classification of renal oncocytoma.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2] Shanshan Cen, M.D. [3]

The exact pathogenesis of renal oncocytoma is not completely understood. Although some mechanisms are suggested in the pathogenesis of this disease that include, lossing of chromosome 1 and dysfunction of mitochondrial enzymes which is caused by alterations in the mitochondrial DNA. DNA diploidy is seen in 96% of patients with renal oncocytomas. The development of renal oncocytoma is the result of multiple genetic mutations such as deletion of chromosome 1, deletion of the sex chromosome, translocation of chromosome 11q13, sporadic or no chromosomal alteration. Renal oncocytoma can be associated with familial renal oncocytoma or Birt-Hogg-Dube syndrome. On gross pathology, tan to brown surface color , well-encapsulated with a thick, well-defined, fibrous capsule, central scar, and homogeneous appearance without any hemorrhage or necrosis inside it in the tumor cut are characteristic findings of renal oncocytoma. On microscopic histopathological analysis, renal oncocytoma characterized by “oncocytes”. They are large, round to polygonal neoplastic cells accompanied by eosinophilic granular cytoplasm and are organized in nested or organoid pattern. Although, renal oncocytoma is benign, atypia, prominent nucleoli, and pleomorphism may seen in microscopic examination.

• The exact pathogenesis of renal oncocytoma is not completely understood.
• The mechanisms which are suggested in the pathogenesis of renal oncocytoma include:^[1][2][3][4]
  • Lossing of chromosome 1
  • Dysfunction of mitochondrial enzymes which is caused by alterations in the mitochondrial DNA

DNA diploidy is seen in 96% of patients with renal oncocytomas.^[5][6][7]

The development of renal oncocytoma is the result of multiple genetic mutations such as:^{[8][9][10][1][2][11]}

• Deletion of chromosome 1
• Deletion of the sex chromosome
• Translocation of chromosome 11q13
• Sporadic or no chromosomal alteration

Conditions associated with renal oncocytoma include:^[12][13]

• Familial renal oncocytoma
• Birt-Hogg-Dube syndrome

Note: Birt-Hogg-Dube syndrome is an autosomal dominant syndrome which is presented with different types of dermatologic diseases and renal epithelial tumors such as renal oncocytoma and RCCs.

On gross pathology, tan to brown surface color , well-encapsulated with a thick, well-defined, fibrous capsule, central scar, and homogeneous appearance without any hemorrhage or necrosis inside it in the tumor cut are characteristic findings of renal oncocytoma.^{[14][15][16][17][18][19]}

On microscopic histopathological analysis, renal oncocytoma characterized by “oncocytes”. They are large, round to polygonal neoplastic cells accompanied by eosinophilic granular cytoplasm and are organized in nested or organoid pattern. Although, renal oncocytoma is benign, atypia, prominent nucleoli, and pleomorphism may seen in microscopic examination.^{[20][21][22][23][24]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]

There are no established causes for renal oncocytoma.

There are no established causes for renal oncocytoma.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2] Shanshan Cen, M.D. [3]Sargun Singh Walia M.B.B.S.[4]

Renal oncocytoma must be differentiated from other diseases that cause abdominal mass, abdominal pain and hematuria such as wilms tumor, renal cell carcinoma, rhabdoid kidney disease, polycystic kidney disease, and other urogenital mass.

Renal oncocytoma must be differentiated from other diseases that cause abdominal mass, abdominal pain and hematuria such as Wilms tumor, renal cell carcinoma, rhabdoid kidney disease, polycystic kidney disease, and other urogenital mass..

Genetic differentiation between renal oncocytoma and RCC subtypes

Common chromosomal alteration

1. Deletion of chromosome 1 and X/Y 2. A balanced translocation involving 11q13 3. Sporadic or no chromosomal alterations

Loss of heterozygosity chromosome 1, 2, 6, 10, 13,17, and 21

Additional copies of chromosomes 7, 12, and 17

Loss of heterozygosity chromosome 3p

Oncocytoma

chromophobe RCC

Papillary RCC

Nonpapillary RCC

Renal oncocytomas should be differentiated from other diseases that cause abdominal pain, hematuria and headache. The differentials include the following:^{[1][2][3][4][5][6][7][8][9]}

S.No.	Disease	Symptoms			Signs		Diagnosis			Comments
		Abdominal Pain	Hematuria	Headache	Abdominal mass	Abdominal tenderness	Ultrasonography	CT scan	Histology
1.	Renal oncocytoma	+/-	+ /-	–	+/-	+/-	Renal ultrasound in renal oncocytoma patients may show: Solid mass ( help to distinguish solid from cystic mass) Central scarring Calcification Central necrosis note: None of these characteristics are indicating for a specific renal lesion.	Abdominal CT scan may be helpful in the diagnosis of renal oncocytoma. Findings on CT scan suggestive of renal oncocytoma include: Solid renal lesion Central scar (stellate scar) Hypervascularity Hypodenseity ( most of the time) Homogenous enhancements	Wilms tumor has a triphasic appearance. It is comprised of 3 types of cells: Stromal Epithelial Blastemal All the 3 types are not required for the diagnosis of Wilms tumor. Primitive tubules and glomeruli are often seen comprised of neoplastic cells. Beckwith and Palmer reported in NWTS the different histopathologic types of Wilms tumor to categorize them based on prognosis. Spindled cell stroma surrounding abortive tubules and glomeruli is characteristic. The stroma may include: Striated muscle cartilage bone Fat tissue Fibrous tissue.
2.	Wilms tumor	+	+	–	+	+	It is the best initial diagnostic study used in cases suspected with Wilms tumor. Ultrasonography can help identify the mass as a kidney mass. It can distinguish tumor mass from other causes of renal swelling like hydronephrosis. Doppler ultrasonography can help to detect invasion of renal vein and IVC by the tumor.	Findings on CT scan which can be suggestive of Wilms tumor include: Heterogeneous soft-tissue density masses These masses have frequent areas of calcification (~10%) and fat-density regions Lymph node metastasis CT scan of the renal mass can further reveal: Invasion of surrounding organs Thrombus in or occlusion of the renal vein and/or the inferior vena cava Abdominal lymph nodes and contralateral involvement	Wilms tumor has a triphasic appearance. It is comprised of 3 types of cells: Stromal Epithelial Blastemal All the 3 types are not required for the diagnosis of Wilms tumor. Primitive tubules and glomeruli are often seen comprised of neoplastic cells. Beckwith and Palmer reported in NWTS the different histopathologic types of Wilms tumor to categorize them based on prognosis.[10] Spindled cell stroma surrounding abortive tubules and glomeruli is characteristic. The stroma may include: Striated muscle cartilage bone Fat tissue Fibrous tissue.
3.	Renal cell carcinoma	+	+	+/-	+	–	Ultrasound (US) may be helpful when CT scan results are equivocal. It is noteworthy to mention that not all renal cell carcinomas are detectable on ultrasound.	Both CT and MRI may be used to detect neoplastic masses that may define renal cell carcinoma or metastasis of the primary cancer. CT scan and use of intravenous (IV) contrast is generally used for work-up and follow-up of patients with renal cell carcinoma.	The histological pattern of renal cell carcinoma depends whether it is papillary, chromophobe or collecting duct renal cell carcinoma.
4.	Rhabdoid kidney disease	+	+	–	+	–	Ultrasound shows a complex cystic mass.	CT scan may be diagnostic of malignant rhabdoid tumor. Findings on CT scan suggestive of malignant rhabdoid tumor include a large, heterogenous, centrally located mass, which is lobulated with individual lobules separated by intervening areas of decreased attenuation, relating to either previous hemorrhage or necrosis. Enhancement is similarly heterogeneous. Calcification is relatively common, observed in 20-50% of cases and is typically linear and tends to outline tumor lobules.	Malignant rhabdoid tumor is characterized by the round blue tumor cells of high cellularity composed of atypical cells with eccentric nuclei, small nucleoli, and abundant amounts of eosinophilic cytoplasm with frequent mitotic figures.
5.	Polycystic kidney disease	+	+	+ (from hypertension)	+	–	Ultrasound may be helpful in the diagnosis of polycystic kidney disease. Findings on an ultrasound diagnostic of polycystic kidney disease include: At least three unilateral or bilateral cysts in patients 15 – 39 years old Atleast two cysts in each kidney in patients 40 – 59 years old Atleast four cysts in each kidney in patients 60 years of age or older	Renal CT scan may be helpful in the diagnosis of polycystic kidney disease. Findings on CT scan diagnostic of ADPKD include: Numerous renal cysts of varying size and shape with little intervening parenchyma with water attenuation and very thin wall. Reduction in sinus fat due to expansion of the cortex Occasional complex cysts with hyperdense appearance, with possible septations or calcifications Multiple homogeneous and hypoattenuating cystic lesions in the liver in patients with liver involvement	On microscopic histopathological analysis, interstitial fibrosis, tubular atrophy, thickening and lamellation of tubular basement membranes, microcysts and negative immunofluorescence for complement and immunoglobulin are characteristic findings of ADPKD.
6.	Pheochromocytoma	–	–	+ (as a part of the hypertension paroxysm)	–	–	CT is the preferred imaging modality for the diagnosis of pheochromocytoma.	The following findings may be observed on CT scan: Most common extra-adrenal locations are superior and inferior abdominal paraaortic areas, the urinary bladder, thorax, head, neck and pelvis. In sporadic pheochromocytoma, CT and MRI are good choices. The choice depends on availability and cost. In patients with the multiple endocrine neoplasia type 2 (MEN2) syndrome, CT may miss the tumors.	On microscopic pathology, Pheochromocytoma typically demonstrates a nesting (Zellballen) pattern on microscopy. This pattern is composed of well-defined clusters of tumor cells containing eosinophilic cytoplasm separated by fibrovascular stroma.
7.	Burkitt lymphoma	+/- (in non-endemic or sporadic form of the disease)	–	–	–	–	Abdominal ultrasonography may show splenomegaly and ascites.	Chest, abdomen, and pelvis CT scan may be helpful in the diagnosis of Burkitt’s lymphoma but it is not done routinely.	On microscopic histopathological analysis, characteristic findings of Burkitt’s lymphoma include: Medium-sized (~1.5-2x the size of a RBC) with uniform size (“monotonous”) — key feature (i.e. tumor nuclei size similar to that of histiocytes or endothelial cells) Round nucleus Small nucleoli Relatively abundant cytoplasm (basophilic) Brisk mitotic rate and apoptotic activity Cellular outline usually appears squared off “Starry-sky pattern”: The stars in the pattern are tingible-body macrophages (macrophages containing apoptotic tumor cells. The tumour cells are the sky
8.	Intussusception	+	–	–	+/-	+	Ultrasound is the gold standard imaging modality used to diagnose intussusception Target or doughnut sign Edematous intussuscipien forms an external ring around the centrally located intussusceptum Target sign is usually seen in right lower quadrant Layers of intussusception forms pseudo-kidney appearance on the transverse view	CT scan may be helpful in the diagnosis of intussusception. CT scan maybe used when other image modalities like x-ray and ultrasound have not given positive results but suspicion of intussusception is high.	Intussusception occurs if there is an imbalance between the longitudinal and radial smooth muscle forces of intestine that maintain its normal structure. This imbalance leads to a segment of intestine to invaginate into another segment and cause entero-enteral intussusception. Etiology of intussusception is either idiopathic or pathologic (lead point).
9.	Hydronephrosis	+	+/-	–	–	+ (CVA tenderness in case of pyelonephritis)	Ultrasound allows for visualization of the ureters and kidneys and can be used to assess the presence of hydronephrosis and/or hydroureter.	In the case of renal colic (one sided loin pain usually accompanied by a trace of blood in the urine) the initial investigation is usually an intravenous urogram. This has the advantage of showing whether there is any obstruction of flow of urine causing hydronephrosis as well as demonstrating the function of the other kidney. Many stones are not visible on plain x ray or IVU but 99% of stones are visible on CT and therefore CT is becoming a common choice of initial investigation.	The kidney undergoes extensive dilation with atrophy and thinning of the renal cortex.
10.	Dysplastic kidney	N/A	N/A	N/A	N/A	N/A	MCDK is usually diagnosed by ultrasound examination before birth. Mass of non-communicating cysts of variable size. Unlike severe hydronephrosis, in which the largest cystic structure (the renal pelvis) lies in a central location and is surrounded by dilated calices, in multicystic dysplastic kidney the cyst distribution shows no recognizable pattern. Dysplastic, echogenic parenchyma may be visible between the cysts, but no normal renal parenchyma is seen.	MCKD can be discovered accidentally on CT scan. CT scan shows myltiple cysts with absence of renal parenchyma.	MCKD is the result of abnormal differentiation of the renal parenchyma.
11.	Pediatric Neuroblastoma	+	–	–	+/-	+/-	On ultrasound, neuroblastoma is characterized by a heterogeneous echogenicity due to the vascular, necrotic, and calcified content of the mass.	CT scan is the investigation of choice for the diagnosis of neuroblastoma. On CT scan, neuroblastoma is characterized by: Heterogeneous mass Calcification Necrosis Compression of the surrounding vessels Invasion of the psoas muscle or kidneys Swollen lymph nodes	On microscopic histopathological analysis the presence of round blue cells separated by thin fibrous septa are characteristic findings of neuroblastoma. Other findings of neuroblastoma on light microscopy may include: Homer-Wright rosettes (rosettes with a small meshwork of fibers at the center) Neuropil-like stroma (paucicellular stroma with a cotton candy-like appearance) On electron microscopy neuroblastoma is characterized by: Dendritic processes with longitudinally oriented microtubules Membrane bound electron-dense granules that contain catecholamines Presence of desmosomes Absence of glycogen
12.	Pediatric Rhabdomyosarcoma	+	+/-	+/-	–	+/-		On CT scan, rhabdomyosarocma is characterized by: Soft tissue density Some enhancement with contrast Adjacent bony destruction (over 20% of cases)	Rhadbomyosarcoma has an appearance similar to the other round blue cell tumors such as Ewing sarcoma and small cell osteoblastoma.
13.	Mesoblastic nephroma	+	+	–	+	–	Ultrasound may be helpful in the diagnosis of mesoblastic nephroma. Mesoblastic nephroma may presents as a well-defined mass with low-level homogeneous echoes. The presence of concentric echogenic and hypoechoic rings can be a helpful diagnostic feature of mesoblastic nephroma.	CT scan may be helpful in the diagnosis of mesoblastic nephroma. Findings on CT scan suggestive of mesoblastic nephroma include: Solid hypoattenuating renal lesion Variable contrast enhancement No calcification	Template:WH Template:WS

References

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2] Shanshan Cen, M.D. [3]

The incidence of renal oncocytoma is approximately 3% to 7% of solid renal resected tumors. Patients of all age groups may develop renal oncocytoma. The age of patients can be differ from 10 to 94 years. The incidence of renal oncocytoma increases with age; the median age at the time of surgery is 62 to 68 years. Males are more commonly affected by renal oncocytoma than females. The male to female ratio is approximately 2 to 1.

• The incidence of renal oncocytoma is approximately 3% to 7% of solid renal resected tumors.^[1][2]

• Patients of all age groups may develop renal oncocytoma. The age of patients can be differ from 10 to 94 years.^[3][4][5]
• The incidence of renal oncocytoma increases with age; the median age at the time of surgery is 62 to 68 years.^[6][7][8]

• Males are more commonly affected by renal oncocytoma than females. The male to female ratio is approximately 2 to 1.^[9]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2] Shanshan Cen, M.D. [3]

Patients with tuberous sclerosis complex and Birt-Hogg-Dube syndrome are at an elevated risk of developing renal oncocytomas (often bilateral).

Patients with tuberous sclerosis complex and Birt-Hogg-Dube syndrome are at an elevated risk of developing renal oncocytomas (often bilateral).

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2] Shanshan Cen, M.D. [3]

There is insufficient evidence to recommend routine screening for renal oncocytoma.

There is insufficient evidence to recommend routine screening for renal oncocytoma.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2] Shanshan Cen, M.D. [3]

The median age at the time of surgery is 62 to 68 years. In 10% to 32% of patients with renal oncocytoma, coexcitente RCC are seen. Prognosis is generally excellent, There are only two cases of metastatic renal oncocytoma were reported. Since the definite diagnosis is maintain just after surgery, most of patients are undergone operation.

• The median age at the time of surgery is 62 to 68 years. ^[1]
• In 10% to 32% of patients with renal oncocytoma, coexcitente RCC are seen.^[2][3]

• Prognosis is generally excellent, There are only two cases of metastatic renal oncocytoma were reported.^[4][5]
• Since the definite diagnosis is maintain just after surgery, most of patients are undergone operation.^[6][1][7]

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