Malignant Renal Mass

ZIGMUND BRYAN CORTEZA, MD

 Renal masses can be malignant, benign, or inflammatory
 They can be classified based on radiographic appearance
 simple cystic, complex cystic, solid.
 Malignant renal tumors include RCC, urothelial-based malignancies, sarcomas,
embryonic or pediatric tumors, lymphomas, and metastases.
 Renal Cell Carcinoma (RCC) includes a number of distinct subtypes derived from
the various parts of the nephron, each with a unique genetic basis and tumor
biology
Imaging and Clinical Risk Stratification of
Renal Masses
 The strongest predictors of malignancy are male sex and increasing tumor size
 When considering tumor size, 20% to 30% of renal masses less than 4 cm and
40% of renal masses less than 2 cm are benign
 The likelihood of malignancy increases per centimeter of tumor diameter
RADIOGRAPHIC EVALUATION OF
RENAL MASSES
 Radiographic evaluation of a renal mass remains the strongest predictor of
malignancy and metastatic potential
 Current guidelines recommend multiphase, cross-sectional imaging
Ultrasonography

 Noninvasive and relatively inexpensive modality that can differentiate cystic

versus solid renal masses.
 Strict ultrasonographic criteria for simple cysts have been defined
 a smooth cyst wall,
 a round or oval shape without internal echoes, and
 through-transmission with strong acoustic shadowing posteriorly.
 A renal mass that is not clearly a simple cyst by strict ultrasound criteria should be
evaluated further with multiphasic, cross-sectional imaging
Evaluation of Cystic Renal Lesions
RENAL CELL CARCINOMA

 RCC, which accounts for 2% to 3% of all adult malignant neoplasms, is the most
lethal of the common urologic cancers
 Primarily a disease of older adults, with typical presentation between 55 and 75
years of age
 The majority of cases of RCC are sporadic; only 4% to 6% are believed to be
familial
 The incidence of RCC has increased since the 1970s by an average of 3% per
year, largely related to more prevalent use of ultrasonography and CT for the
evaluation of a variety of nonspecific abdominal complaints
Etiology

 RCCs arise primarily from the proximal convoluted tubule for the clear cell and
papillary variants.
 Other histologic subtypes of RCC, such as chromophobe RCC and collecting duct
carcinoma, are derived from the more distal components of the nephron.
 Risk Factors
 Tobacco exposure (1.4-2.5)
 Obesity (1.07)
 Hypertension
Familial Renal Cell Carcinoma Subtypes

 Von Hippel-Lindau disease (VHL)

 Hereditary papillary renal carcinoma (HPRC)
 Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)
 Succinate dehydrogenase-deficient RCC (SDH-RCC)
 Birt-Hogg-Dube syndrome (BHD)
 PTEN hamartoma tumor syndrome (Cowden Syndrome)
 Tuberous sclerosis (TSC)
 BAP 1 tumor predisposition syndrome
 MiTF-associated cancer syndrome
von Hippel-Lindau Disease

 The familial form of clear cell RCC is von Hippel-Lindau Disease

 Major manifestations include the development of RCC, pheochromocytoma,
retinal angiomas, and hemangioblastomas of the brainstem, cerebellum, or spinal
cordn Hippel-Lindau (VHL) disease
 RCC develops in about 50% of patients with VHL disease
Hereditary Leiomyomatosis and Renal
Cell Carcinoma
 Renal tumors in this syndrome are unusual for familial RCC in that they are often
solitary and unilateral, and they are more likely to be aggressive than other forms
of familial RCC.
 Collecting duct carcinoma, another highly malignant variant of RCC, has also
been observed in this syndrome, which was named hereditary leiomyomatosis and
renal cell carcinoma (HLRCC) syndrome
 Prompt surgical management of the renal tumors is recommended in individuals
with HLRCC, given their tendency toward aggressive behavior
Succinate Dehydrogenase RCC

 Another syndrome that shares features with HLRCC is SDH-RCC. Affected

individuals present with bilateral, multifocal, early onset (<40 years) renal tumors,
often along with pheochromocytomas and head and neck paragangliomas
Birt Hogg Dube Syndrome

 Birt-Hogg-Dube (BHD) syndrome, in which patients can develop cutaneous

fibrofolliculomas, lung cysts, spontaneous pneumothoraces
 A variety of renal tumors primarily derived from the distal nephron The renal
tumors typically include chromophobe RCC, oncocytomas, and hybrid oncocytic
tumors that exhibit features of both of these entities
 Most renal tumors in BHD syndrome have limited biologic aggressiveness,
although metastatic behavior and lethality have been reported
Cowden Syndrome

 Cowden syndrome is one of several syndromes that result from germline

mutations of the phosphatase and tensin homolog (PTEN) tumor suppressor gene,
which together are termed PTEN hamartoma tumor syndrome
 Individuals with Cowden syndrome carry a 50% lifetime risk of female breast
cancer, 34% lifetime risk of RCC, and 10% lifetime risk of epithelial thyroid
carcinoma RCC in this syndrome is most often of papillary histology, although
chromophobe and clear cell histology have also been reported
Tuberous Sclerosis Complex

 Autosomal dominant disorder that manifests with characteristic tumors in multiple

organ systems
 Major features include AML, cortical tubers, subependymal nodules or
subependymal giant cell astrocytomas (SEGA), pulmonary
lymphangioleiomyomatosis (LAM), cardiac rhabdomyomas, and facial
angiofibromas.
 Renal AML are typically multifocal, bilateral, and often large, occasionally
requiring angioembolization or partial nephrectomy (PN) to treat or prevent
bleeding from larger (>5 cm) tumors
Pathology
 Most RCCs are round to ovoid and circumscribed by a pseudocapsule of
compressed parenchyma and fibrous tissue rather than a true histologic capsule.
 A new four-tiered grading system developed by the World Health Organization
and International Society of Urological Pathology has been validated for clear cell
and papillary RCC
Clear Cell Renal Cell Carcinoma
 Clear cell RCC accounts for 70% to 80% of all RCCs, representing the garden
variety of RCC
 On microscopic examination, clear cell RCC can include clear cells, granular or
eosinophilic cells, or mixed types
Papillary Renal Cell Carcinoma

 Papillary RCC, which was previously designated chromophilic

 RCC, is the second most common histologic subtype (10%–15%)
 of all RCCs
 Type 1 papillary RCC, the more common form, consists of basophilic cells with
scant cytoplasm
 Type 2 papillary RCC includes potentially more aggressive variants with
eosinophilic cells and abundant granular cytoplasm
 Current evidence suggests that type 1 papillary RCC carries a better prognosis
than clear cell RCC, whereas type 2 papillary RCC is similar or worse than clear
cell RCC
Chromophobe Renal Cell Carcinoma

 Represents 3% to 5% of all RCCs and appears

to be derived from the distal convoluted tubules
 Perinuclear clearing or “halo” is typically found
and electron microscopic findings consist of
numerous 150- to 300-nm microvesicles, which
are the single most distinctive and defining
feature of chromophobe RCC
Collecting Duct Carcinoma

 Carcinoma of the collecting ducts of Bellini is a relatively rare subtype of RCC,

with a predictably poor prognosis
 Most reported cases of collecting duct carcinoma have been high grade, advanced
stage, and unresponsive to conventional therapies
Renal Medullary Carcinoma

 Renal medullary carcinoma is an uncommon subtype of RCC that occurs almost

exclusively in patients with sickle cell trait.
 Many cases are locally advanced and metastatic at the time of diagnosis
 Thought to arise from the calyceal epithelium near the renal papillae but is often
highly infiltrative. The site of origin (renal papillae) and association with sickle
cell trait suggest that a relatively hypoxic environment may contribute to
tumorigenesis
 Clinical Presentation

 Many renal masses remain asymptomatic and

nonpalpable until they are locally advanced
 With the more pervasive use of noninvasive imaging for
the evaluation of a variety of nonspecific symptom
complexes, more than 60% of RCCs are now detected
incidentally
 Symptoms associated with RCC can be due to local
tumor growth, hemorrhage, paraneoplastic syndromes,
or metastatic disease
 The classic triad of flank pain, gross hematuria, and
palpable abdominal mass is now rarely seen
Screening and Clinical
Associations
 Most important, RCC remains primarily a
surgical disease requiring early diagnosis to
optimize the opportunity for cure
 For these reasons, the focus of screening for RCC
must be on well-defined target populations, such
as patients with end-stage renal disease and
acquired renal cystic disease, tuberous sclerosis,
and familial RCC
STAGING

 The recommended staging system for RCC is the eighth

edition of the AJCC TNM classification, which was
released in 2016
Imaging

 MRI can be reserved primarily for patients with locally advanced malignant
disease, equivocal venous involvement, or allergy to intravenous contrast material
 MRI is still the premier study for evaluation of invasion of tumor into adjacent
structures and for surgical planning in these challenging cases
 The sensitivities of CT for detection of renal venous tumor thrombus and IVC
involvement are 78% and 96%, respectively
 Metastatic evaluation in all cases should include a routine chest radiograph,
systematic review of the abdominal and pelvic CT or MRI, and liver function tests
PROGNOSIS

 Overall, tumor-related factors such as pathologic stage, tumor size, nuclear grade,
and histologic subtype have the greatest individual predictive ability.
 Clinical findings that suggest a compromised prognosis in patients with presumed
localized RCC include symptomatic presentation, unintended weight loss of more
than 10% of body weight, and poor performance status
 Pathologic stage has proved to be the single most important prognostic factor for
RCC
PROGNOSIS

 Other important prognostic factors for patients with systemic metastases include
performance status, number and sites of metastases, anemia, hypercalcemia,
elevated alkaline phosphatase or lactate dehydrogenase levels, thrombocytosis,
and sarcomatoid histology
Radical Nephrectomy

 Prototypical RN encompasses the basic principles of early ligation of the renal

artery and vein, removal of the kidney with primary dissection external to Gerota
fascia, excision of the ipsilateral adrenal gland, and performance of an extended
lymph node dissection (LND)
 RCC metastasizes through the bloodstream independent of the lymphatics in
many patients, and the lymphatic drainage of the kidney is highly variable.
 Therefore even an extensive retroperitoneal LND may not remove all possible
sites of metastasis.
Partial Nephrectomy

 Nephron-sparing surgery entails complete local resection of the tumor while

optimally preserving normal functioning parenchyma within the involved kidney
 Indications
 RN would render the patient anephric or at high risk for ultimate need of dialysis
 comprised patients with bilateral RCC
 RCC involving a solitary functioning kidneys
 In patients with bilateral synchronous RCC, the general approach has been to
perform bilateral PNs whenever feasible, usually as staged procedures,
particularly if the tumors are relatively large. When a locally extensive tumor on
one side precludes nephron sparing surgery, an RN is performed on the more
involved side along with a contralateral PN
Tumor Enucleation
 Tumor enucleation (TE) is
well-established for patients
with familial kidney cancer,
although its role for sporadic
RCC remains controversial
 TE entails blunt dissection
along the pseudocapsule,
thereby reducing the amount
of normal parenchyma
removed with the tumor
 review of the TE literature
suggests that this
 approach is reasonable for
many patients, but selection
criteria are not well defined.
Thermal Ablative Therapies

 TA, including renal cryosurgery and radiofrequency ablation (RFA), are now
established as alternate nephronsparing treatments for patients with localized RCC

 Both can be administered percutaneously and thus offer the potential for reduced
morbidity

 In general, long-term efficacy of TA is still not as well established as surgical

excision, and local recurrence rates with primary TA are somewhat higher than
those reported for traditional surgical approaches
Thermal Ablative Therapies

 The traditional candidates for TA have been patients with reasonable life
expectancy despite advanced age or significant comorbidities who prefer a
proactive approach but are not optimal candidates for conventional surgery
 Tumor size is another important factor in patient selection
 Success rates appear to be highest for tumors smaller than 2.5 to 3.0 cm, and
complication rates are also lower in this setting
Active Surveilance

 Studies suggest that patients with small, solid renal

lesions, who are elderly or have increased surgical
risk, can safely be managed with observation and
serial renal imaging at 6-month or 1-year intervals
Locally Invasive

 Complete excision of the tumor, including resection of the involved bowel,

spleen, distal pancreas, or abdominal wall muscles, is the aim of therapy
 The presence of lymph node metastasis is an important prognostic factor and
defines a highrisk subset of patients with advanced RCC.
 Although lymphadenectomy for RCC provides accurate staging, the therapeutic
benefits of routine lymphadenectomy are controversial. Even in patients with
radiographic adenopathy, only 30% to 43% of clinically enlarged lymph nodes
contain metastatic disease
Locally Invasive

 Local recurrences of RCC can occur after RN and nephron-sparing surgery and
present unique challenges.
 Local recurrence of RCC after RN, which includes recurrence in the renal fossa,
ipsilateral adrenal gland, renal vein stump or adjacent IVC, or ipsilateral
retroperitoneal lymph nodes, is an uncommon event, occurring in 2% to 4% of
cases
 Risk factors include locally advanced or nodepositive disease and adverse
histopathologic Features
 Surgical resection of isolated local recurrence of RCC after RN should be
considered, because it can provide long-term cancer-free status for 30% to 40% of
patients
 Local recurrence in the remnant kidney after PN for RCC has been reported in
1.4% to 10% of patients, and the main risk factors are advanced T stage or high
tumor grade