AJR:204, May 2015 1031
medullary, and unclassified. Clear cell RCC
is the most common histologic type, ac-
counting for approximately 70–75% of RCCs
[8, 10, 11]. Clear cells, which arise from the
proximal convoluted tubular epithelium, are
grossly yellow-tan owing to lipid content but
appear clear after staining owing to their gly-
cogen-rich content [8]. Granulosa and spin-
dle cells may also be present in clear cell
RCCs [8]. The vascular appearance of this
cancer subtype is due to its characteristic
network of small, thin-walled, sinusoidlike
blood vessels [10, 11]. The multilocular cys-
tic form of clear cell RCC consists of septat-
ed, variably sized cysts lined by a monolayer
of epithelial cells that contain serous or hem-
orrhagic fluid [10, 11].
The papillary histologic subtype accounts
for 10–15% of RCCs [10, 11]. Within these
tumors, the papillae have fibrovascular cores
with foamy macrophages and associated
cholesterol crystals [11, 12]. Papillary RCCs
are subclassified into two subtypes—baso-
philic type I and eosinophilic type II [13].
These subtypes have similar clinical and his-
topathologic patterns, except that type I has
a substantially higher cancer-specific surviv-
al rate than does type II [14–16]. This may
be explained by the higher frequency of lym-
phovascular invasion associated with type II
papillary RCC [16]. Macroscopically, pap-
illary RCCs exhibit hemorrhagic, necrotic,
and cystic degeneration [10, 11].
The chromophobe subtype comprises ap-
proximately 4–6% of RCCs [11]. Chromo-
phobe cells are thought to arise from the in-
tercalated cells of the collecting system [17].
Diagnostic Approach to Hereditary
Renal Cell Carcinoma
Shiva Gupta
1
Hyunseon C. Kang
Dhakshina Moorthy Ganeshan
Tharakeswara Kumar Bathala
Vikas Kundra
Gupta S, Kang HC, Ganeshan D, Bathala TK,
Kundra V
1
All authors: Department of Diagnostic Radiology,
University of Texas M. D. Anderson Cancer Center, Unit
1473, 1515 Holcombe Blvd, Houston, TX 77030. Address
correspondence to S. Gupta (sgupta6@mdanderson.org).
Genitourinary Imaging • Review
AJR 2015; 204:1031–1041
0361–803X/15/2045–1031
© American Roentgen Ray Society
R
enal cell carcinoma (RCC) is the
third most common urologic can-
cer and accounts for 2–3% of
adult malignancies [1, 2]. In the
United States, incidence of kidney and renal
pelvis cancer is on the rise, with an estimated
63,920 new cases and 13,860 new deaths by
these cancers in 2014. [1, 3, 4]. Hereditary re-
nal cancer syndromes account for approxi-
mately 2–5% of RCCs [5–7]. The autosomal
dominant inheritance in most of these syn-
dromes results in a predisposition to the devel-
opment of renal tumors [2, 5]. Several heredi-
tary renal cancer syndromes occur equally in
men and women, but some syndromes occur
more often in women. These renal tumors
tend to be multiple and distributed bilaterally
and occur at a relatively young age [2].
Understanding the ontogeny, histopatho-
genesis, and biologic behavior of these he-
reditary RCCs has led to improvements in di-
agnosis, treatment plans, and prognosis [8].
We provide an up-to-date discussion of these
characteristics. We also introduce a pattern-
based approach to the diagnosis of heredi-
tary RCC syndromes that focuses on the pre-
dominant histologic RCC subtype for each
syndrome (adapting the Heidelberg classifi-
cation of renal cell tumors [9]) and the asso-
ciated renal and extrarenal imaging findings.
Histopathologic Subtypes of
Renal Cancers
According to the 2004 World Health Or-
ganization classification of renal tumors, his-
tologic subtypes of RCC include clear cell,
papillary, chromophobe, collecting duct,
Keywords: chromophobe renal cell carcinoma, clear cell
renal cell carcinoma, hereditary renal cell carcinoma
syndromes, medullary renal cell carcinoma, papillary
renal cell carcinoma, renal cell carcinoma
DOI:10.2214/AJR.14.13514
Received July 18, 2014; accepted without revision
August 20, 2014.
Based on a presentation at the Radiological Society of
North America 2013 annual meeting, Chicago, IL.
OBJECTIVE. The purpose of this article is to discuss the histopathologic features, genet-
ics, clinical presentation, and imaging of hereditary renal cancer syndromes.
CONCLUSION. Hereditary renal cell carcinoma syndromes can be diagnosed with a
pattern-based approach focused on the predominant histologic renal cell carcinoma subtype
and associated renal and extrarenal features of each syndrome.
Gupta et al.
Hereditary Renal Cell Carcinoma
Genitourinary Imaging
Review
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