What Is Chromophobe Renal Cell Carcinoma

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Outcomes Of Metastatic Chromophobe Renal Cell Carcinoma In The Targeted Therapy Era: Results From The International Metastatic Renal Cell Cancer Database Consortium

Article type: Research Article

Authors: Yip, Steven M.a | Ruiz Morales, Jose M.b | Donskov, Fredec | Fraccon, Annad | Basso, Umbertoe | Rini, Brian I.f | Lee, Jae Lyung | Bjarnason, Georg A.h | Sim, Hao-Weni | Beuselinck, Benoitj | Kanesvaran, Ravindrank | Brugarolas, Jamesl | Koutsoukos, Kostasm | Fu, Simon Yuen Fain | Yuasa, Takeshio | Davis, Ianp | Alva, Ajjaiq | Kollmannsberger, Christianr | Choueiri, Toni K.s | Heng, Daniel Y.C.t; *

Correspondence: Correspondence to: Daniel Y.C. Heng, Tom Baker Cancer Center, University of Calgary, 1331 29 St NW, Calgary, AB, T2N 4N2, Canada. Tel.: +1 403 521 3166; Fax: +1 403 283 1651; E-mail: .

Keywords: Metastatic, renal, chromophobe, international, targeted

DOI: 10.3233/KCA-160002

Journal: Kidney Cancer, vol. 1, no. 1, pp. 41-47, 2017

Abstract

Background: Treatment outcomes are poorly characterized in patients with metastatic chromophobe renal cell cancer , a subtype of renal cell carcinoma.

Objective: This retrospective series aims to determine metastatic chrRCC treatment outcomes in the targeted therapy era.

Methods: A retrospective data analysis was performed using the IMDC dataset of 4970 patients to determine metastatic chrRCC treatment outcomes in the targeted therapy era.

What Causes Renal Cell Carcinoma

Cancer occurs when abnormal cells begin to grow or divide uncontrollably. The abnormal cells crowd out normal cells, causing problems at the site where the cancer started. Cancer can sometimes spread to other organs as well. RCC beings in one or both kidneys.

The kidneys are bean-shaped organs that filter blood and create urine to dispose of the waste. Renal cell cancer affects the lining of small tubules in the kidneys, where the filtration takes place.;

Most people have two kidneys one on each side of the lower spine, near the hips. However, its possible to live a healthy life with just one kidney. RCC usually involves one tumor in one kidney, but it also may involve multiple tumors in both kidneys.

Certain factors and lifestyle choices affect your risk of getting RCC. You may have an increased risk of RCC if you:

• smoke

• have;high blood pressure

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Genetic Syndrome Associated With Chromophobe Rcc

BHD syndrome is an autosomal dominant disorder that includes: benign skin tumor , renal epithelial neoplasms and spontaneous pneumothorax. Renal tumors are often multifocal and bilateral. BHD gene encodes potential tumor suppressor protein – folliculin on 17p11 .

ChRCCs is characterized by length polymorphism such as loss of chromosomal material involving chromosomes: 1, 2, 3p, 6, 10, 13, 17p, 17q and 21 . It may be helpful in distinguishing between clear, papillary and chromophobe subtypes of RCC.

Papillary Renal Cell Carcinoma

Papillary renal cell carcinoma cells have small finger-like projections that stick out of the tumor. This type is also called chromophilic;RCCbecause the cells easily absorb color from stains. Stains applied to cells in the lab help scientists see cell details and make a diagnosis. About 10% of renal cell carcinomas are this type.

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Patient Population And Histology

A retrospective data analysis was performed using the International mRCC Database Consortium dataset to characterize mRCC treatment outcomes in the targeted therapy era. Twenty-seven international cancer centres in Canada, the USA, Denmark, Greece, South Korea, Australia, New Zealand, Japan, Singapore, Belgium, and Italy provided consecutive patient data collected from hospital and pharmacy records using uniform database software and templates. Data were collected between 2005 and May 2016. Institutional review board approval was obtained from each participating centre.

All patients with metastatic ccRCC and chrRCC, who were treated with one or more lines of VEGF inhibitor or mTOR targeted therapy , were included. Patients with mixed subtype RCC were excluded from analysis. Tumour histology was recorded using pathology reports generated by pathologists as part of routine patient diagnosis, prior to and independent of this study.

Clinical And Histomorphological Features

Prognosis in ChRCC is better than in other types of RCC. Five- and 10-year DFS for chromophobe RCC was 83.9% and 77.9%, respectively . The median time from nephrectomy to metastasis detection, and from metastasis detection to death were twice as long for ChRCC than for other subtypes of RCC .

In univariate analysis: sarcomatoid change , microscopic necrosis , tumor size , pT stage , broad alveolar growth , vascular invasion , and Fuhrman nuclear grade were associated with aggressive ChRCC behavior. Independent predictors of aggressive ChRCC included: pT stage , sarcomatoid change and microscopic necrosis . Other factors like: age, sex, histologic subtyping by clear, eosinophilic or mixed cell types, tubulocystic pattern, degenerate or symplastic atypia were not predictors of chromophobe RCC behavior.

The patients with aggressive phenotype of chromophobe RCC may be candidates for adjuvant therapies as they become available .

ChRCCs are hyperechogenic in ultrasound examination, CT imaging or MRI demonstrate homogeneous enhancement. A spoke-wheel pattern of contrast enhancement is characteristic for ChRCC and for onkocytoma . Most of ChRCCs are sporadic, but sometimes they are associated with BHD syndrome .

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How Is Renal Cell Carcinoma Treated

Based on the type and stage of RCC, your doctor will recommend a treatment plan. The plan may include one or more of the following approaches:;

• Surgery: This is the most common treatment for kidney cancer. Surgery can often cure early-stage RCC.;

• Radiation therapy: Also called radiotherapy, this treatment uses beams of intense energy to kill cancer cells;or stop them from growing.;

• Thermal ablation: Your doctor inserts a needle into the tumor and applies heat to kill cancer cells.

• Cryosurgery: Cold liquid nitrogen is delivered directly to the tumor through a needle kill cancer cells

• Immunotherapy: Leading-edge immunotherapy drugs prompt your own immune system to fight the cancer.

• Targeted therapy: Thesemedications attack specific parts of cancer cells to stop them from growing and multiplying.

• Chemotherapy: Oral or intravenous medications stop cancer cells from growing.

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How Does It Spread

If a cancerous tumor is discovered in one of your kidneys, the usual treatment is to surgically remove part or all of the affected kidney.

If the tumor is not removed, its more likely that the cancer will spread to either your lymph nodes or other organs. The spread of cancer is called metastasis.

In the case of RCC, the tumor can invade a large vein leading out of the kidney. It can also spread to the lymph system and other organs. The lungs are especially vulnerable.

Management Of Rare Rcc Subtypeschromophobe Renal Cell Carcinoma

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Chromophobe Renal Cell Carcinoma

What is chromophobe renal cell carcinoma?

Chromophobe renal cell carcinoma is a type of kidney cancer. The tumour develops from the very small tubules in the kidney. Chromophobe renal cell carcinoma is the third most common type of kidney cancer in adults. These tumours generally have an excellent prognosis except when sarcomatoid or rhabdoid cells are found.

The kidneys

The kidneys are two bean-shaped organs located near the back of your body just below the rib cage on both the left and the right side. The kidneys are composed of a complex network of millions of microscopic tubules.; These tubules act to filter your blood by removing waste products and toxins.; The result of this filtration process is the production of urine.; After the tubules in your kidneys produce urine, it travels through a thin tubular structure called the ureter.; The ureter acts as a connection between the kidney and the urinary bladder.; Urine is stored in the bladder before being excreted during urination.

How is this tumour normally found and diagnosed?

Many chromophobe renal cell carcinomas are found incidentally at the time of abdominal imaging for other reasons.; Patients with these tumours may occasionally experience pain in their back or side or notice blood in their urine. The tumour will appear as a kidney mass;on MRI or CT scan of the abdomen.

Syndromes associated with chromophobe renal cell carcinoma

What to look for in your report after the tumour is removed

Tumour size

Number of tumours

Genetic Alterations Of Her Genes In Chromophobe Renal Cell Carcinoma

This article is mentioned in:

Abstract

Introduction

Chromophobe renal cell carcinoma is thethird most common subtype of kidney cancer and accounts for ~5% ofall RCC cases. The 5-year disease-free survival rate of chRCC isreported to be increased compared with that of other RCC subtypes,including clear cell, sarcomatoid and papillary renal cellcarcinoma . Although theoutcomes of chRCC are typically more favorable compared with thoseof other subtypes, the disease still demonstrates a 67%probability of tumor progression and metastasis .

Histologically, chRCC consists of large polygonalcells with a slightly reticulated cytoplasm, and with clear and/oreosinophilic cells . The similarities between the histologicalfeatures of chRCC and oncocytoma, a benign tumor of the kidney, maylead to the misdiagnosis of chRCC .

The roles of other HER family genes, including HER1,HER3 and HER4, have not been well studied in chRCC. The presentstudy aimed to investigate the abnormalities of the HER family andassess a potential association with chRCC.

Materials and methods

Tissue specimens

Table;I.

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How Is Stage Determined

The staging system most often used for kidney cancer is the American Joint Committee on Cancer TNM system. The TNM system is based on 3 key pieces of information:

• The size and extent of the main tumor : How large is the tumor? Has it has grown into nearby areas?
• The spread to nearby lymph nodes : Has the cancer spread to nearby lymph nodes?
• The spread to distant sites : Has the cancer spread to other organs such as the bones, brain, or lungs?

Numbers or letters after T, N, and M provide more details about each of these factors. Higher numbers mean the cancer is more advanced. Once a persons T, N, and M categories have been determined, this information is combined in a process called stagegrouping to assign an overall stage. To learn more, see Cancer Staging.

The system described below is the most recent version of the AJCC system, effective as of January 2018.

Kidney cancer is typically given a clinical stage based on the results of a physical exam, biopsy, and imaging tests . If surgery is done, the pathologic stage is determined by examining tissue removed during the operation.

Kidney cancer staging can be complex. If you have any questions about your stage, please ask your doctor to explain it to you in a way you understand.

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Chromophobe Renal Cell Carcinoma Symptoms

Most people with chromophobe RCC dont have any symptoms at all when they are diagnosed. Instead, the cancer may be discovered on imaging scans done for another reason.;

If symptoms are present, they may include the following:

• Pain in your lower back
• Blood in your urine

You might experience different symptoms if your cancer has already traveled to other places in your body . In this case, some possible symptoms include:

• Bone pain
• Swelling of your legs

Types Of Kidney Cancer

Chromophobe renal cell carcinoma falls into a broader group of kidney cancers called renal cell carcinoma . Renal means kidney. Carcinoma is a word for cancers that begin in the cells that line the internal organs. About 90% of cancers that start in the kidney are classified as renal cell carcinoma.

Scientists eventually learned that certain kidney cancers behave somewhat differently than others. That is, if someones cancer cells looked a certain way under a microscope, they classified them into different categories. And those cancers seemed to share certain similarities, like how well they responded to specific treatments.

Chromophobe renal cell carcinoma is a subtype of renal cell carcinoma. About 5% of people with renal cell carcinoma have this subtype. Compared to people with some other more common subtypes, people with chromophobe renal cell carcinoma are more likely to be female.;

People with the chromophobe subtype also tend to be diagnosed at an earlier stage than people with some of the other subtypes. That is, their cancer isnt as advancedhasnt grown and spread as muchcompared to people with other subtypes.

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Tcga’s Study Of Chromophobe Renal Cell Carcinoma

What is chromophobe kidney cancer?

Chromophobe renal cell carcinoma is a rare type of kidney cancer that forms in the;cells;lining the small tubules in the kidney. These small tubules help filter waste from the blood, making urine. As the;different;types of;kidney cancer;are very distinct, characterizing and understanding each type is important.1;

In 2012, it was estimated that there would;be 64,770 new cases of kidney cancer and 13,570 deaths as a result of this disease.2;Chromophobe kidney cancer accounts for 5% of these cases. This rare type of cancer can run in families as part of a rare;genetic;disorder called Birt-Hogg-Dubé;syndrome.3;The disorders genetic nature has allowed researchers a small window of opportunity to study it; however, very little is known about the genetic basis of sporadic chromophobe kidney cancer. TCGA studied the sporadic cases of this type of kidney cancer. Although rare, this cancer is a serious disease. At the time of this study, the only treatment option for patients with chromophobe kidney cancer is surgery.4;Additional information on kidney cancer.

What have TCGA researchers learned about chromophobe kidney cancer?

Adjuvant And Neoadjuvant Therapy

Adjuvant therapy, which refers to therapy given after a primary surgery, has not been found to be beneficial in renal cell cancer. Conversely, neoadjuvant therapy is administered before the intended primary or main treatment. In some cases neoadjuvant therapy has been shown to decrease the size and stage of the RCC to then allow it to be surgically removed. This is a new form of treatment and the effectiveness of this approach is still being assessed in clinical trials.

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