Sandy T. Liu, MD1,4,5, Karlton Wong, MD1,
Gavin Hui, BA2, Kristen Kelley, MD3,
Allan J. Pantuck, MD4,5, Alexandra Drakaki, MD, PhD1,4,5
Kidney Cancer Journal 17
The Classification and Treatment of
Non-Clear Cell Renal Cell Carcinoma
Sandy T. Liu, MD Allan J. Pantuck, MD Alexandra Drakaki, MD, PhD
1Division of Hematology-Oncology, Department of Medicine, David Geffen
School of Medicine at University of California Los Angeles, Los Angeles, California
2David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California
3Division of General Internal Medicine, Department of Medicine, David Geffen
School of Medicine at University of California Los Angeles, Los Angeles, California
4Institute of Urologic Oncology, Department of Urology, David Geffen
School of Medicine at University of California Los Angeles, Los Angeles, California
5Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at
University of California Los Angeles, Los Angeles, California
Introduction/Epidemiology
Renal cell carcinoma (RCC) is the 8th most common cancer
in the United States with an estimated incidence of
63,990 causing 14,400 deaths in 2017 according to the
National Cancer Institute’s Surveillance, Epidemiology,
and End Result (SEER) program data.1 From 1975 to 2014,
the incidence of RCC increased from 7 to 15 per 100,000
people. This finding is likely due in part to the increased
use of imaging studies leading to the detection of small,
asymptomatic renal tumors. Recently, Welch and colleagues
found that hospital referral regions that utilized
computerized tomography (CT) with greater frequency
also experienced higher rates of nephrectomy, presumably
reflecting the increased rate in detection of incidental
renal masses.2
Cigarette smoking, increased body mass index (BMI),
and high blood pressure are all established risk factors for
the development of renal cell carcinoma. Smoking cessation
and also possibly treatment of hypertension are
associated with a reduction in risk.3 Increased risk of developing
RCC has also been observed in some studies in
patients with diabetes mellitus4, increased parity5, and in
patients with history of trichloroethylene exposure.6
Conversely, an inverse relationship has been suggested
between physical activity and alcohol consumption and
the development of RCC. The study of the relationship
between diet and RCC has yielded conflicting results with
some data suggesting a protective effect from a diet rich
in fruits and vegetables and increased risk associated with
high fat diets or intake of processed meats.7 RCC affects
males twice as often as females and typically affects older
adults with a median age at diagnosis of 64.8 Higher incidence
is found among Blacks, American Indians, Alaska
Natives, Whites, and Hispanics as compared to Asians
and Pacific Islanders.9
Among all malignant renal neoplasms, renal cell carcinoma
(RCC) represents 90% of cases.10 RCC itself is a
heterogeneous group of malignant epithelial neoplasms
that is further categorized based on histopathologic, genetic
features and clinical behavior ranging from indolent
to highly aggressive. RCC is primarily comprised of
clear cell type, representing about 75%, while non-clear
cell RCC represents approximately 25%.11 Non-clear cell
renal carcinomas can be further subdivided into, papillary
(10-15%), chromophobe (5%), collecting duct (1%),
medullary (<1%), translocation (1-3%), and unclassified
(5% ) types.11-12 A clear understanding of the different
characteristics of these subtypes of non-clear cell RCC is
critical for prognostication and for identification of suitable
treatments.
Classification of Non-Clear Cell RCC
Non-clear cell RCC subtypes are classified according to
cell of origin, histology, immunohistochemical staining,
molecular biology, and tumor genetics (Table 1). The
main subtypes of non-clear cell RCC include papillary,
chromophobe, collecting duct, medullary, translocation,
and unclassified. Sarcomatoid features, once thought to
Key Words: Non-clear cell renal cell carcinoma; classification, subtypes,
papillary, chromophobe, collecting duct, medullary,translocation,
unclassified, treatment, VEGF receptor inhibitor, mTOR
inhibitor.
Corresponding author: Allan J. Pantuck, MD, MS, FACS,Department
of Urology, David Geffen School of Medicine at UCLA,Wasserman
Building, Third Floor, 300 Stein Plaza, Los Angeles, CA 90095
Email: apantuck@mednet.ucla.edu
link