Renal Cell Carcinoma

Overview

Definition

Renal cell carcinoma (RCC), also called hypernephroma and renal cell adenocarcinoma, is a type of cancer that originates from the lining of the small tubules of the renal cortex.

Epidemiology

• Accounts for 80%–85% of all primary renal neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is highest in North America and the Czech Republic:
  • In North America, RCC is responsible for 76,000 new cases and 14,000 deaths each year.
  • In the United States, the incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is highest in the White, Black, Hispanic, and American Indian populations and lowest in the Asian American and Pacific Islander populations.
• Approximately twice as common in men as in women
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is highest in the 6th to 8th decade of life, with a median age of 64.

Etiology

• Most cases of RCC occur sporadically.
• Only 4% of cases are associated with a genetic component.
• Risk factors:
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases (associated with a higher incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency and more advanced disease)
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity (risk increases with ↑ BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity)
  • CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease, especially individuals with cystic Cystic Fibrocystic Change disease of the kidney acquired through dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Peritoneal Dialysis and Hemodialysis
  • Occupational exposure (e.g., cadmium, asbestos, petroleum by-products)
  • Prolonged ingestion of analgesic combinations (e.g., aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs), NSAIDs NSAIDS Primary vs Secondary Headaches, and acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen)
  • Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics: several hereditary diseases have been associated with RCC:
    • Inherited polycystic disease 
    • Von Hippel-Lindau syndrome (approximately 40% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop RCC)
    • Tuberous sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor (approximately 5% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop RCC)
    • Hereditary leiomyomatosis and renal cancer syndrome (HLRCC)
    • Hereditary papillary renal cell carcinoma (HPRCC)
  • Cytotoxic Cytotoxic Parvovirus B19 chemotherapy Chemotherapy Osteosarcoma
  • Chronic hepatitis C Hepatitis C Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C Virus infection
  • Kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
  • Sickle cell disease Sickle cell disease Sickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage. Sickle Cell Disease

Pathologic Classification

The difference between benign Benign Fibroadenoma and malignant masses in the kidney is determined by histologic criteria. According to the morphology, growth pattern, cell of origin, and histochemical and molecular basis, RCCs are classified into several types:

• Clear cell (most common) 
• Papillary
• Chromophobe 
• Oncocytic 
• Collecting duct (very rare)
• Translocation RCC (very rare)

Clear cell carcinoma

• 75%–85% of all renal tumors
• Etiology: 
  • Most commonly sporadic Sporadic Selective IgA Deficiency
  • Genetic mutations Genetic Mutations Carcinogenesis:
    • Deletion of 3p (seen in up to 94% of clear cell tumors)
    • Gain of 5q
    • Monosomy Monosomy The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2n-1. Types of Mutations or partial loss of 14q
  • Genetic pathway alterations:
    • VHL gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics
    • PBRM1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics
    • BAP1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics
    • Inactivation of histone-modifying genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure
    • Ubiquitin-mediated proteolysis pathway
    • Abnormalities in cellular division ( Ras RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis, p53)
• Pathology/histologic appearance:
  • Arises from clear cells in the proximal tubular epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology
  • Mostly well differentiated
  • Large areas of gray-white necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage and foci of hemorrhagic discoloration
  • Can have a trabecular (cordlike) or tubular growth pattern with cells of rounded or polygonal shape and granular or clear cytoplasm
  • May show cystic Cystic Fibrocystic Change and/or solid areas
  • May show cellular atypia Atypia Fibrocystic Change
• Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas:
  • Depends on the stage at diagnosis
  • Poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas with higher nuclear grade and/or sarcomatoid pattern

Papillary carcinoma

• 10%–15% of cases
• Etiology: 
  • Most commonly sporadic Sporadic Selective IgA Deficiency (majority associated with trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 7, trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 17, and the loss of Y in males)
  • MET MET Preoperative Care gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations
  • FH gene mutation Gene Mutation Myotonic Dystrophies
• Pathology/histologic appearance: 
  • Can arise from the proximal or distal convoluted tubules
  • Can be multifocal Multifocal Retinoblastoma and/or bilateral
  • Usually hemorrhagic and cystic Cystic Fibrocystic Change, especially if large
  • Made of cuboidal or low columnar cells that are arranged in papillary formations
  • Interstitial foam cells Foam cells Lipid-laden macrophages originating from monocytes or from smooth muscle cells. Atherosclerosis and psammoma bodies Psammoma Bodies Cellular Accumulations may be present.
• Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas: 
  • Type 1 Type 1 Spinal Muscular Atrophy papillary RCC (slow growth) has a favorable prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.
  • Type 2 Type 2 Spinal Muscular Atrophy papillary RCC (aggressive course) has a poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.

Chromophobe carcinoma

• 5%–10% of cases
• Etiology: 
  • Hypodiploid number of chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure
  • Up-regulated KIT oncogene
  • Up-regulated TERT gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics
• Pathology/histologic appearance: 
  • Arises from intercalated cells Intercalated cells Tubular System of the collecting ducts
  • Made up of pale, eosinophilic cells arranged in solid sheets around blood vessels
  • Perinuclear halos can be seen
• Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas: 
  • Favorable prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas (more than clear cell RCC)
  • Possibly due to presentation at an earlier stage

Oncocytic carcinoma/oncocytomas

• 3%–7% of cases
• Etiology: 
  • Genetic abnormalities, including:
    • Loss of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 1 and chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics Y
    • Rearrangement of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 11q13 (contains CCND1 CCND1 Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin d1 is the result of bcl-1 rearrangement, a t(11; 14) translocation, and is implicated in various neoplasms. Lentigo Maligna)
  • Associated with:
    • Birt-Hogg-Dubé syndrome
    • Tuberous sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor
• Pathology/histologic appearance: 
  • Arises from intercalated cells Intercalated cells Tubular System of the collecting ducts
  • Composed of oncocytes, well-differentiated neoplastic cells with highly eosinophilic cytoplasm due to numerous mitochondria Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. The Cell: Organelles
• Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas: 
  • Favorable prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas
  • Behave as benign Benign Fibroadenoma tumors
  • Rarely invasive or metastatic

Collecting or Bellini duct tumors

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: very rare
• Etiology: usually due to genetic abnormalities
• Pathology/histologic appearance: 
  • Composed of irregular channels Channels The Cell: Cell Membrane 
  • Epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology is very atypical, with a hobnail pattern.
• Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas: 
  • Poor
  • Commonly associated with metastatic and/or advanced disease

Translocation renal cell carcinoma

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 
  • Very rare
  • Occurs at a younger age and predominantly in women
• Etiology: 
  • Due to a fusion of the TFE3, TFEB, or MITF MITF Lentigo Maligna genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure to a number of other genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure, including ASPSCR1, PRCC, SFPQ, and NONO
  • Presents in children with previous chemotherapy Chemotherapy Osteosarcoma, autoimmune disorders, or bone marrow transplant Bone marrow transplant Transfer of hematopoietic stem cells from bone marrow or blood between individuals within the same species (homologous transplantation) or transfer within the same individual (autologous transplantation). Hematopoietic stem cell transplantation has been used as an alternative to bone marrow transplantation in the treatment of a variety of neoplasms. Organ Transplantation conditioning
• Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas: 
  • Much worse prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas than most other types of RCC because symptoms develop at a later stage
  • Resistant to targeted therapies

Clinical Presentation

Many cases present asymptomatically, leading to further progression of the diseases. Symptoms arise when the tumor Tumor Inflammation has reached a significant size, invaded adjacent structures, or developed distant metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis.

• Classic triad of flank pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, hematuria, and palpable abdominal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast (present in only 9% of cases)
• Other symptoms:
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Muscle wasting Muscle Wasting Duchenne Muscular Dystrophy
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia 
  • Secondary polycythemia Secondary Polycythemia Polycythemia Vera
  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • Scrotal varicocele Varicocele A condition characterized by the dilated tortuous veins of the spermatic cord with a marked left-sided predominance. Adverse effect on male fertility occurs when varicocele leads to an increased scrotal (and testicular) temperature and reduced testicular volume. Varicocele, Hydrocele, and Spermatocele, usually left-sided
  • Involvement of the inferior vena cava Inferior vena cava The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy ( IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy):
    • Lower-extremity edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
    • Hepatic dysfunction
    • Pulmonary emboli
  • Paraneoplastic syndrome, which can lead to increased levels of the following hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types:
    • Erythropoietin Erythropoietin Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology
    • Parathyroid Parathyroid The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands: Anatomy hormone-related protein
    • Gonadotropins
    • Human placental lactogen
    • Adrenocorticotropic hormone Adrenocorticotropic hormone An anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids. Acth is a 39-amino acid polypeptide of which the n-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotropic activity. Upon further tissue-specific processing, acth can yield alpha-msh and corticotropin-like intermediate lobe peptide (clip). Adrenal Hormones–like substance
    • Renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation
    • Glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions
    • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin
  • Hypercalcemia Hypercalcemia Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Hypercalcemia due to:
    • Lytic bone lesions Bone Lesions Multiple Myeloma
    • Parathyroid Parathyroid The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands: Anatomy hormone-related protein
    • Elevated prostaglandins Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Eicosanoids that promote bone resorption Bone resorption Bone loss due to osteoclastic activity. Bones: Remodeling and Healing

Diagnosis and Staging

Diagnosis

• 1st-line: CT scan of the abdomen and pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy to show characteristics of RCC, as opposed to a simple renal cyst:
  • Thickened, irregular or smooth wall
  • Septations
  • Enhancement after contrast injection
• Ultrasonography may also be performed.
• MRI used if CT and/or ultrasonography inconclusive
• A biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is performed after the imaging diagnosis and must be evaluated for the extent of local invasion and metastatic disease prior to surgery.

Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis

RCCs vary greatly in the extent of disease at presentation.

• Localized to the kidney: 65%
• Regional ( lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy): 17%
• Metastatic disease: 16%
• Unstaged: 3%

Management and Prognosis

Management

• Localized, nonmetastatic disease requires surgery, which is curative in stages I–III. 
  • Partial nephrectomy
  • Radical nephrectomy
  • Enucleation
  • Thermal ablation
• Metastatic disease: 
  • If metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis has already developed, the disease is usually unresectable.
  • Immunotherapy with or without molecularly targeted therapy Targeted Therapy Targeted therapy exerts antineoplastic activity against cancer cells by interfering with unique properties found in tumors or malignancies. The types of drugs can be small molecules, which are able to enter cells, or monoclonal antibodies, which have targets outside of or on the surface of cells. Targeted and Other Nontraditional Antineoplastic Therapy:
    • Nivolumab Nivolumab A genetically engineered, fully humanized immunoglobulin g4 monoclonal antibody that binds to the pd-1 receptor, activating an immune response to tumor cells. It is used as monotherapy or in combination with ipilimumab for the treatment of advanced malignant melanoma. It is also used in the treatment of advanced or recurring non-small cell lung cancer; renal cell carcinoma; and Hodgkin’s lymphoma. Melanoma plus ipilimumab 
    • Pembrolizumab Pembrolizumab Squamous Cell Carcinoma (SCC) plus axitinib 
    • Nivolumab Nivolumab A genetically engineered, fully humanized immunoglobulin g4 monoclonal antibody that binds to the pd-1 receptor, activating an immune response to tumor cells. It is used as monotherapy or in combination with ipilimumab for the treatment of advanced malignant melanoma. It is also used in the treatment of advanced or recurring non-small cell lung cancer; renal cell carcinoma; and Hodgkin’s lymphoma. Melanoma plus cabozantinib 
    • Molecularly targeted therapy Targeted Therapy Targeted therapy exerts antineoplastic activity against cancer cells by interfering with unique properties found in tumors or malignancies. The types of drugs can be small molecules, which are able to enter cells, or monoclonal antibodies, which have targets outside of or on the surface of cells. Targeted and Other Nontraditional Antineoplastic Therapy: vascular endothelial growth factor Vascular endothelial growth factor A family of angiogenic proteins that are closely-related to vascular endothelial growth factor a. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells. Wound Healing (VEGF) tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase inhibitors (e.g., cabozantinib, lenvatinib plus everolimus Everolimus A derivative of sirolimus and an inhibitor of tor serine-threonine kinases. It is used to prevent graft rejection in heart and kidney transplant patients by blocking cell proliferation signals. It is also an antineoplastic agent. Immunosuppressants, nivolumab Nivolumab A genetically engineered, fully humanized immunoglobulin g4 monoclonal antibody that binds to the pd-1 receptor, activating an immune response to tumor cells. It is used as monotherapy or in combination with ipilimumab for the treatment of advanced malignant melanoma. It is also used in the treatment of advanced or recurring non-small cell lung cancer; renal cell carcinoma; and Hodgkin’s lymphoma. Melanoma) 

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• Depends on:
  • Type of renal cell carcinoma
  • Extent and size of the tumor Tumor Inflammation at the time of detection
• Sarcomatoid appearance indicates poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.
• The 5-year survival rate of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with kidney cancer has increased in recent years because of advancements in technology allowing for the detection of more tumors incidentally and at smaller sizes:
  • Localized: 93%
  • Regional: 70%
  • Distant metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis: 13%
  • Combined survival rate: 75%

Differential Diagnosis

• Benign Benign Fibroadenoma renal tumor Tumor Inflammation:
  • Angiomyolipoma Angiomyolipoma A benign tumor containing vascular, adipose, and muscle elements. It occurs most often in the kidney with smooth muscle elements (angiolipoleiomyoma) in association with tuberous sclerosis. Tuberous Sclerosis: appears on imaging as an enhancing mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast containing macroscopic fat and no calcifications. Small angiomyolipomas with minimal fat are difficult to characterize on imaging and often require further evaluation. Associated with tuberous sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor, especially if bilateral. 
  • Metanephric adenoma: rare, benign Benign Fibroadenoma lesions that are more common in women than in men. Often discovered incidentally, but can present with pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, hematuria, or a palpable mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast. Can be difficult to differentiate on histology from papillary RCC or epithelial-predominant Wilms tumor Tumor Inflammation.
• Metastatic disease: cancer from another source that spreads to the kidney. Metastatic disease often presents with multiple renal lesions with borderline enhancement and widespread metastatic disease.
• Lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum: hematologic malignancy Malignancy Hemothorax that can involve the kidney. Percutaneous biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma should be done to differentiate lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum from RCC. Renal involvement in hematologic malignancies is found at autopsy in about ⅓ of terminal lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum or leukemia patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship. Renal involvement should be suspected in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with massive retroperitoneal Retroperitoneal Peritoneum: Anatomy lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy, splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly, or lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy elsewhere in the body or in atypical retroperitoneal Retroperitoneal Peritoneum: Anatomy regions. 
• Renal abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease or focal pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess: a variety of infectious and inflammatory conditions can mimic RCC, including acute and chronic pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess and renal abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease. Axial Axial Computed Tomography (CT) imaging often shows perineal inflammatory changes. Clinical symptoms, such as chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, flank pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, or pyuria Pyuria The presence of white blood cells (leukocytes) in the urine. It is often associated with bacterial infections of the urinary tract. Pyuria without bacteriuria can be caused by tuberculosis, stones, or cancer. Urinary tract infections (UTIs) aid in the diagnosis. Renal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma or aspiration with drain placement can aid in the diagnosis. Serial imaging to demonstrate the resolution of the mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast may also be required after the treatment.