Two11 96 Benign Renal Tumors

They are not connected to any part of the nephron, although they may originate initially from a portion of the nephron

• Discovered incidentally on imaging
• Abdominal mass or pain
• Hematuria secondary to rupture into the pelvicalyceal system
• Hypertension secondary to segmental ischemia
• Cysts can cause calyceal or renal pelvic obstruction

• (1) absence of internal echoes 
• (2) presence of a sharply defined, thin, distinct wall with a smooth and distinct margin,
• (3) good transmission of sound waves through the cyst with consequent acoustic enhancement behind the cyst, and
• (4) a spheric or slightly ovoid shape

In CT, the density ranges from −10 to +20 HU, similar to the density of water, and no enhancement should occur after the intravenous injection of contrast medium.

• When the cyst fluid is hyperdense (i.e., between 20 and 90 HU), the cyst still is likely to be a simple cyst if
• - no enhancement
• - other criteria of CT and ultrasonography are met
• - size (the lesion should be 3 cm or smaller)
• - location (at least one-fourth of the cyst’s circumference should extend beyond the renal contour so that the smoothness of a good portion of the cyst can be evaluated)

High density is due to old, degenerated clotted blood therefore the CT attenuation of their contents is increased. 

Because cysts have no blood vessels and do not communicate directly with nephrons, they should not enhance; enhancement therefore implies vascular tissue or contrast medium mixing with fluid. Enhancement of any nodular areas on the wall of the cyst or of a thickened septum within the cyst is taken as proof of vascularity within the lesion, and thus there should be a high index of suspicion for neoplasm.

Two percent of simple cysts and 10% of RCCs contain calcium deposits, but calcification in simple cysts appears to be peripheral, whereas in tumors it is more central

• When the cysts are numerous and bilateral, differentiation from ADPKD may be difficult if liver cysts are not also found.
• Because of the obvious implications, it is important to avoid a diagnosis of ADPKD in questionable cases unless a familial history consistent with autosomal dominant transmission can be documented or the diagnosis confirmed by genetic testing.

It is important not to overdiagnose unilateral simple cyst disease, because the entity itself is rare, and when first identified in an individual it is more likely to represent a unilateral asymmetrical presentation of ADPKD.

• I
• - no septa 

• II
• - few hairline septa or fine calcification, no enhancement, infection
• - high density (>20HU), size <3cm, no enhancement

• IIF
• - multiple hairline septa, no enhancement
• - high density, size >3cm or totally intrarenal, no enhancement 

• III
• - Septa with measurable enhancement 

• IV
• - enhancing soft tissue components

• Risk of malignancy - minimal - minimal - 10% - 50% - 90%. 
• Counselling is very important while doing excision of complex cysts. For example, in Cat III, the chance of specimens being benign is 50%, and patient party should understand this. 

III might be due to infection, trauma (hemorrhage) - always ask history - if no such history - always explore

A major differentiating factor for complex renal cysts is the presence of unequivocal contrast enhancement, which is not seen in Bosniak 2 and 2F lesions.

• Originally devised using CT scan, can be used with MRI. 
• MRI can make septa appear thicker, II looks like IIF and IIF looks like III

Preliminary data imply that CEUS may perform at least as well as or better than CECT and CEMR in the diagnosis of renal masses. However, the evidence base is limited, and more high-quality, well-designed, adequately powered, and sampled studies are needed to reach definitive conclusions. - Metaanalysis, European urology

I and II - simple renal cyst

IIF, III and IV - complex renal cyst

Thinned out renal parenchyma, get enhancement, looks like the Bosniak III cyst

Multiloculated varient of clear cell RCC is most common, then only Papillary RCC

• Pain 
• HTN 
• Complex cyst

First-line therapy - percutaneous image-guided aspiration and sclerosing agents placement. care to be taken for peripelvic cysts - may cause fibrosis 

Decorticaion, marsupialization, or unroofing 

Surviellence not required for I and II hypodense cysts, is required for II hyperdense cysts and IIF cysts 

If complex (III/IV) - partial or radical nephrectomy

Similar immunohistochemical staining (α- methylacyl CoA racemase [AMACR] positivity) and cytogenetic changes (such as trisomy 7 and 17) of papillary adenoma and papillary RCC

[@ Papi AMAR lai sadhe 7 ko dasha] 

In 2004 the  WHO defined papillary adenoma as a low-grade (grade 1–2), well-circumscribed cortical lesion measuring less than 0.5 cm

Metanephric adenoma is a rare, benign enhancing renal mass. Symptoms are present in approximately 50% of patients, with a female predisposition.

Metanephric adenoma may exist on a continuum with Wilms tumors and papillary RCC, and can be distinguished based on histology and immunohistochemical staining. 

• Metanephric adenomas stain positive for WT1 and CD57 and negative for α- methylacyl CoA racemase (AMACR)
• Papillary RCC stains oppositely
• S100 expression is very high in metanephric adenoma, weak in Wilms tumour, and absent in papillary RCC

Polycythemia has been identified in metanephric adenoma due to tumour production of erythropoietin, IL-6, IL8, G-CSF, and GM-CSF

• Similar age of presentation - 7th decade 
• Both are derived from DCT 
• The eosinophilic variant of chromophobe and oncocytoma are  diffusely eosinophilic 
• Both are associated with Birt Hogg Dube syndrome 
• Hypervascularity and Spoke wheel pattern

Oncocytoma can be associated with perirenal fat invasion and renal vein invasion—findings that carry prognostic significance in RCC but do not in oncocytoma and should not be interpreted as an aggressive pathology

Abundance of Mitochondrial - Eosinophilic

Oncocytic tumor of adrenal or salivary glands also have similar feature

Frozen section cannot differentiate between oncocytoma and chromophobe RCC - should not be used to guide surgical strategy

• Radiological
• - In chromophobe - Enhancement in the corticomedullary phase
• - In Oncocytoma - in nephrogenic phase, the maximum enhancement

• Immunohistochemistry
• - cytokeratin-7 is rarely positive in oncocytoma, whereas chromophobe RCC tends to be diffusely positive and is recommended by the ISUP to distinguish these entities
• - Colloid iron staining is negative for oncocytoma and diffuse reticular staining in chromophobe RCC

[@ Corticomedullary, Cytokeratin, Colloid iron for Chromophobe]

99mTc Sestamibi SPECT/CT is used to differentiate renal oncocytoma from renal cell carcinoma, which can lessen invasive surgical exploratory resection

Sestamibi is taken up by mitochondria, which are in abundance in oncocytomas and hybrid oncocytic/chromophobe tumors, and a strong signal is suggestive of these histologies

• Derived from perivascular epitheloid cells, called as PEComas
• Can occur sporadically or as part of genetic syndromes: most commonly tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM).
• Lymphangioleiomyomatosis (LAM) is associated with cystic lung lesions, lymphangioleiomyomas, and chylous effusions [@ AML LAM]

• TSC arises from mutations in either TSC1 (encoding hamartin) on chromosome 9q34 or TSC2 (encoding tuberin) on chromosome 16p13. 
• Inheritance is autosomal dominant
• Hamartin and tuberin dimerize to inhibit mTOR, and therefore inactivating mutations of these proteins result in unregulated mTOR activation.
• Downstream, this results in protein synthesis, cellular growth, and angiogenesis

Massive retroperitoneal hemorrhage in AML

Melanocyte markers HMB-45 and Melan-A are important immunohistochemical stains to aid in the diagnosis when in doubt

Presence of fat - NCCT -20 HU or less 

Aneurysmal dilatation is found in around 50% of AML 

Tumors with calcification associated with fat are uncommon but are almost always malignant RCC. In this setting the fat is thought to be a reactive process related to tumor necrosis. Calcification is virtually never seen in association with AML. 

MRI - T1 and T2 hyperintensity, enhancement on gadolinium administration, hypointensity on T1 fat-suppressed sequences , and the presence of a dark boundary on in-phase/opposed-phase imaging that is also called an “India ink artifact”

Liposarcoma - As AML arises from the parenchyma, an indentation in the parenchyma can be observed from this site  of origination, whereas liposarcomas begin in the  retroperitoneum and subsequently envelop and compress the renal parenchyma

Fat Rich RCC - AML Never contain calcification, Fat rich RCC may have calcification

Fat poor AML - difficult to differentiate from RCC, treat as RCC, if any suspicion - biopsy - HMB 45 positive in AML, negative in RCC.

Epithelioid variant

• The main indications for active treatment of AML were as follows:
• (1) increased tumour size, The average size of the actively treated AMLs (that did not bleed) in the largest AS  series was 8 cm, keeping 4 cm cutoff value - we might be overtreating the AML. intralesional aneurysm larger than 5 mm - needs intervention 
• (2) presence of symptoms (bleeding and pain), and
• (3) suspicion of cancer  on imaging

• European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guidelines Panel 2020
• https://euoncology.europeanurology.com/article/S2588-9311(19)30054-9/pdf

There are four mainstays

• Surgical resection - NSS especially for TSC cases, bilateral nephrectomy before transplantation owing to the risk of life-threatening haemorrhage and development of RCC
• Thermal ablation
• Embolization - for active bleeding cases. Most patients with acute or potentially life-threatening hemorrhage will require total nephrectomy if exploration is performed, and if the patient has TSC, bilateral disease, preexisting renal insufficiency, or other medical or urologic disease that could affect renal function in the future, selective embolization should be considered. 
• Everolimus is indicated for the management of larger, multifocal AMLs in patients with TSC and lymphangioleiomyomatosis (LAM)

Patients with multiple or large AMLs should be warned about the potential risk of pregnancy and estrogen administration. 

Everolimus is indicated for the management of larger, multifocal AMLs in patients with TSC and LAM



10mg Everolimus Tablets - INRs 12,800/strip

Lymphangiomas are known to present with cystic extrinsic compression of the kidney due to aberrant lymphatic development in the perirenal lymphatics.

Reninoma or Juxtaglomerular tumor (JGCT), a benign tumour of the renal juxtaglomerular cell apparatus, is an important but rare cause of secondary hypertension and hypokalemia.