Episode 105: Renal Cell Carcinoma. 

Manpreet and Jon-Ade explain how to diagnose renal cell carcinoma. Introduction about age and kidney transplant by Dr. Arreaza and Dr. Yomi. 

[Due to technical difficulties this episode was not posted as scheduled, so it had to be reposted on 9/9/2022] 

Introduction: Too old for a new kidney?
By Hector Arreaza, MD. Discussed with  Timiiye Yomi, MD.

Today we will be talking about the kidneys, those precious bean-shaped organs that detoxify your blood 24/7. Amazingly, we can live normal lives with one kidney, but when the kidney function is not good enough to meet the body’s demands, patients need to start kidney replacement therapy. Modern medicine has made a lot of advances with dialysis, but the perfection of a kidney has not been outperformed by any machine yet. That’s why kidney transplant is the hope for many of our patients with end-stage kidney disease.

The need for a kidney transplant is growing, likely due to increasing chronic diseases such as diabetes and hypertension, and also because of an increase in elderly population. About 22% of patients on the kidney transplant waiting list are over age 65. 

A cut-off age to receive kidney transplant has not been established across the globe. Different countries use different criteria for the maximum age for transplant. The American Society of Transplantation’s guidelines states “There should be no absolute upper age limit for excluding patients whose overall health and life situation suggest that transplantation will be beneficial.” So, if your patient is older than 65 and needs a kidney, they may qualify for a transplant, and age should not be an absolute contraindication to receive it. Actually, older patients may have lower risk of rejection due to a theoretically weaker immune system. A live donor is likely to be a better option for elderly patients. 

A condition that would make your elderly patient a poor candidate for kidney transplant would be frailty. Common contraindications to kidney transplant include active infections or malignancy, uncontrolled mental illness, ongoing addiction to substances, reversible kidney failure, and documented active and ongoing treatment nonadherence.

So, remember to take these factors into consideration when deciding if you need to refer your elderly patients for a kidney transplant, there is no such thing as being too old for a new kidney if your patient meets all the criteria for a transplant.

This is Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care physician for additional medical advice.

 

Renal Cell Carcinoma. 

By Manpreet Singh, MS3, Ross University School of Medicine, and Jon-Ade Holter, MS3 Ross University School of Medicine. Moderated by Hector Arreaza, MD.

 

Definition:

Renal cell carcinoma is a primary neoplasm arising form the renal cortex. 80-85 percent of renal tumors are renal cell carcinomas followed closely by transitional cell renal cancer and Wilms tumor. 

 

Epidemiology: 

In 2022, 79,000 new cases of kidney cancer were diagnosed with almost 14,000 mortalities. 

There is a 2:1 male to female ratio and the average age is 64 and normally 65-74. African Americans and American Indians have a higher prevalence rate compared to other racial groups. The lifetime risk for developing kidney cancer in men is about 1 in 46 (2.02%) and 1 in 80 (1.03%) in women. 

 

Risk Factors associated with RCC: 

Anything that causes assault to the kidneys and affects its function would cause increased demand, injury, and inflammation. This assault can lead to cell derangement and lead to cancer. The risk factors that have been associated with RCC are smoking, obesity, HTN, family history of kidney cancer, Trichloroethylene (a metal degreaser used in large manufacturing factories), acetaminophen, and patients with advanced kidney disease needing dialysis.

 

Patients with syndromes that cause multiple types of tumors: 

• VHL (von Hippel-Lindau) deficiency, a tumor suppressor, gives rise to clear cell renal cell carcinoma. Familial inheritance of VHL deficiency is mostly found in patients that have RCC at a very young age, before 40 y/o. Other tumors can be found in the eye, brain, spinal cord, pancreas, and pheochromocytomas.
• Hereditary leiomyoma-renal cell carcinoma due to FH gene mutations causing women who have leiomyomas to have a higher risk of developing papillary RCC.
• Birt-Hogg-Dube (BHD) syndrome mutation in FLCN gene who develop various skin and renal tumors.
• Cowden syndrome is a mutation in the PTEN gene giving rise to cancers associated with breast, thyroid , and kidney cancers.
• Tuberous sclerosis causes benign tumors of the skin, brain, lungs, eyes, kidneys, and heart. Although kidney tumors are most often benign, occasionally they can be clear cell RCC.

 

Screening For RCC:

Screening is unnecessary because of the low prevalence of this cancer in the general population, though certain groups require annual repeat imaging via US, CT, or MRI. 

• Inherited conditions that are associated with RCC such as VHL syndrome or Tuberous Sclerosis
• ESRD patients who have been on dialysis for 3-5 years
• Family history of RCC
• Prior kidney irradiation

 

Clinical Picture: 

Most patients with RCC are asymptomatic until cancer grows large enough to cause disruption of local organs, such as the kidney, bladder, or renal vein, and dysregulates other organs via metastasis. Therefore, it’s important to look at other signs and symptoms caused by RCC. 

 

The patient most likely will be an older male who presents with the classic triad of: 

• Flank pain: caused by rapid expansion and stretching of the renal capsule.
• Hematuria: occurs from the invasion of the neoplasm into the collecting duct.
• Palpable abdominal mass: mass tends to be homogenous and mobile with respirations.

 

Though this presents only in 9% of patients during the presentation, having physical symptoms is a sign of advanced disease and 25% of patients with these signs tend to have distant metastasis. 

 

• Anemia: normally associated with anemia of chronic disease. It precedes the disease by at least 8 months to 1 year.

 

• Males can develop varicoceles because of decreased emptying due to neoplasm obstruction. Patients normally develop varicoceles on the left due to the spermatic vein emptying in the higher resistance left renal vein, which causes backup of the blood in the pemphigus plexus. Though a right-sided varicocele should raise a higher suspicion of obstruction due to the spermatic vein draining directly into the IVC which is lower in resistance. A right-sided varicocele is seen in approximately 11 percent of patients.

 

The paraneoplastic syndrome can also arise from RCC

• Epo: Erythrocytosis with symptoms of weakness, fatigue, headache, and joint pain.
• PTHrP: PTH-related peptide acts like PTH which gives rise to hypercalcemia with the prevalent symptoms of arthritis, osteolytic lesions, confusions, tetany, ventricular tachycardia, shortened QTc, and nausea and vomiting.
• Renin: overproduction from the juxtaglomerular cells can cause disarrangement of the RAAS system causing hypertension.
• Others also like ACTH and beta-HCG.

 

Other disorders present include hepatic dysfunction, cachexia, secondary amyloidosis, and thrombocytosis.

 

Workup 

If a patient comes in with painless hematuria, then the first test should be abdominal CT or abdominal ultrasound. A CT is more sensitive than the US but it can quickly indicate if the abdominal mass felt can be a cyst or a solid tumor. 

 

US of kidneys should show if it’s a simple cyst:

-The cyst is round and sharply demarcated with smooth walls

- It’s anechoic – appears solid black

-There is a strong posterior wall echo

-Use the Bosniak classification to classify mass 

 

Bosniak I: benign simple cyst with thin wall less than equal to 2mm, no septa or calcifications. No future workup is needed.

 

Bosniak II: benign cyst, <1mm septa with thin calcification, high attenuation due to contents other than simple water in cyst. No further workup needed.

 

Bosniak IIF: Minimally complex cyst with multiple hairline thin septa with thickened walls, calcification present, and high attenuation lesions >3 cm diameter, requires f/u with US/CT/MRI at 6 months, 12 months, and annually for the next 5 years. Chance of malignancy: 5%. 

 

Bosniak III: indeterminate cystic mass with thick, irregular or smooth walls. This requires nephrectomy or radiofrequency ablation. Chance of malignancy: 55% 

 

Bosniak IV: Clearly a malignancy its grade III with enhancing soft tissue components that its independent from the wall or septum. Requires total or partial nephrectomy. Chance of malignancy 100%. 

 

CT of the kidneys for a neoplasm should show:

-Thickened irregular walls or septa 

-Enhancement after contrast injection are suggestive of malignancy

-CT can also help detect invasion in local tissue areas such as renal vein and perinephric organs 

 

MRI is used if the patient cannot use contrast or kidney function is poor. MRI can also evaluate the growth of the cancer.

 

Other imaging studies:Other imaging studies that may be useful for assessing for distant metastases include bone scan, CT of the chest, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT.

 

Treatment and staging 

Nephrectomy, partial or total, will be used as the initial tissue collection for pathology. If the patient is not a surgical candidate, you can also obtain a percutaneous biopsy. The nephrectomy is preferred because first, it serves as a definitive treatment option, but also it allows for definitive staging of the cancer with tumor and nodal staging. Regardless of the size, any solid mass may indicate malignancy and point towards RCC, requiring resection. 

 

 

TNM staging

 

Stage I: Tumor is 7cm across or smaller and only in the kidney with no lymph nodes or distant mets. T1N0M0

 

Stage IIa: Tumor size is larger than 7cm but still in the kidney but no invasion of lymph node or mets. T2N0M0

 

Stage IIb: Tumor is growing into the renal vein or IVC, but not into neighboring organs such as adrenals or Gerota’s fascia and still lacks lymph node invasion and mets. T3N0M0. 

 

Stage III: Tumor can be any size but has not invaded outside structures such as adrenals, though nearby lymph node invasion is present but not distant. There is no distant mets. T3N1M0.

 

Stage IV:  The main tumor is beyond the Gerota’s fascia and may grow into the adrenal gland . It may or may not spread to the lymph nodes or may not have distant mets. Stage IV also consists of any cancer that has any number of distant mets. T4

 

Adjuvant therapy can be done with immune therapy.

 

Conclusion: Now we conclude our episode number 105 “Renal cell carcinoma.” This type of cancer may be asymptomatic until it is large enough to cause symptoms. Keep it on your list of differentials on patients with hematuria, flank pain, weight loss, and abnormal imaging. Keep in mind the features of simple kidney cysts vs complex cysts when assessing kidney ultrasounds. Your patient will be grateful for an early diagnosis of RCC and a prompt treatment. Even without trying, every night you go to bed being a little wiser.

This week we thank Hector Arreaza, Timiiye Yomi, Manpreet Singh, Jon-Ade Holter. 

Thanks for listening to Rio Bravo qWeek Podcast. If you have any feedback, contact us by email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. Audio edition: Suraj Amrutia. See you next week! 

 

Bibliography:

 

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1. American Cancer Society. “Key Statistics About Kidney Cancer”. Cancer.Org, 2022, https://www.cancer.org/cancer/kidney-cancer/about/key-statistics.html.

 

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1. Leslie SW, Sajjad H, Siref LE. Varicocele. [Updated 2022 Feb 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448113/.

 

1. Maguire, Claire. “Understanding Endoscopic Ultrasound and Fine Needle Aspiration.” Educational Dimension, Educational Dimensions, 1 Jan. 2007, educationaldimensions.com/eLearn/aspirationandbiopsy/eusterm.php.

 

1. Maller, V., Hagir, M. Renal cell carcinoma (TNM staging). Reference article, Radiopaedia.org. (accessed on 20 May 2022) https://doi.org/10.53347/rID-4699.

 

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