PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
In the more advanced stages, the staging features relate to the patterns of spread to the surrounding anatomy and, to a degree, criteria of resectability.
PERSPECTIVE AND PATTERNS OF SPREAD
Renal cancers are of obscure etiology. Painless hematuria is the most common symptom but by itself is nonspecific and ca occur with other genitourinary tumors. An estimated 20,000 new cases are diagnosed annually; 40% of these individuals are destined to die from the disorder. An unusual aspect of this highly angioinvasive malignancy is its ability to metastasize widely and its peculiarity to undergo spontaneous regression. It has triggered intensive investigation into both specific an nonspecific immunobiologic effects for diagnostic and therapeutic purposes. The challenge to contain and cure this neoplasm remains unmet.
In contrast, Wilms’ tumor was the first pediatric tumor success story of the multimodal era. A unique neoplasm of the renal parenchyma, the nephroblastoma is most often seen in children. Abdominal mass is the presenting complaint, and there is a tendency to develop metastases. There have been interesting hypotheses relating Wilms’ tumor to doubling times and cancer curability using mathematical modeling. The addition of effective chemotherapy to radiation therapy and extirpative surgery stimulated the combined modality approach to other pediatric and adult tumors. Within three decades, what was a relatively incurable malignancy has become 90% curable through carefully organized clinical trials. More effective treatment has become less intensive to reduce toxicity and late effects in the process of optimization. Currently, therapy reduction tailored to each stage of the tumor's advancement is under study in clinical protocols.
Figure 35.1| Kidney cancer is not a single disease. It is made up of a number of different types of cancers that occur in the kidney, each with a different histology, a different clinical course, and a different causative gene.
Figure 35.2 | A. Coronal. B. Transverse. Patterns of spread (cancer crab) of renal cancer are color coded for stage: T0, yellow; T1, green; T2, blue; T3, purple; and T4, red. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six-directional pattern (SIMLAP, Table 35.2).
In the early stages, tumor size is the dominant criterion for renal cancer (Fig. 35.1) whereas in the more advanced stages, the staging features relate to the patterns of spread to the surrounding anatomy and, to a degree, criteria of resectability (Fig. 35.2; Table 35.2).
PATHOLOGY
Renal cell cancers (RCCs) are mainly sporadic, but 5% are inherited. They tend to be bilateral and multifocal, and the risk for family members is heightened fivefold. The main categories are clear cell (20% to 80%) and papillary (10% to15%): (Fig. 35.1 and Table 35.1).
• Clear cell RCC is the most common type and arises from proximal tubular epithelial cells. Cells are arranged as round and elongated collections.
• Papillary cancers are arranged as fibrovascular stalks
• Chromophobe renal cell carcinoma shows a mixture of acidophilic granular cells and pale, transparent cells with prominent cell borders, which impart a plant cell–like appearance. The cytoplasm contains numerous vesicles fille with a distinctive mucopolysaccharide that can be stained with the Hale colloidal iron technique. In the pale cells, these vesicles displace other organelles to the periphery, causing a central cytoplasmic pallor. Chromophobe RCC appears to arise from the intercalated cells of renal collecting ducts.
• Collecting duct carcinoma is a rare variety that arises from medullary collecting ducts but may extend into the cortex. Histologically, it is composed of tubular and papillary structures lined by a single layer of cuboidal cells that may have a hobnail appearance. Renal medullary carcinomas are a variant of collecting duct carcinomas that develop almost exclusively in African Americans with sickle cell trait or disease.
TNM STAGING CRITERIA
The kidney has a distinct capsule separating renal parenchyma from its surrounding of perirenal fat, which in turn on its posterior surface has the perirenal fat separated by fascia (Gerota's) and lumbar quadratus muscle, 12th rib, and posterior diaphragmatic surface. Superiorly it can spread into the adrenal gland. Once the tumor penetrates the capsule it has access to regional nodes. Due to renal cancer's hypervascularization, a path of least resistance is into renal veins and the inferior vena cava. Lung metastases are very common.
Renal adenocarcinomas arise in the renal parenchyma mainly from the proximal renal tubule, in contrast to transitional cell cancers from the renal pelvis and its intrarenal collecting system. Their incidence ratio is 90% and 10%, respectively. A number of different histopathologic types of renal cancer have been identified, with subtypes clear cell and granular cell cancer or a mixture (Table 35.1; Fig. 35.1).
TNM STAGING CRITERIA
In the seventh edition of the AJCC Cancer Staging Manual, T2 lesions are divided into T2a (>7 to 10 cm) and T2b (>10 cm). Justification of relating cancer size to survival relates to new data from the National Cancer Data Base (Table 35.3A). Renal vein involvement is changed from T3b to T3a. Adrenal gland involvement is changed from T3a to T4 if spread is contiguous and M1 if it is not. Nodal criteria are simply N1 independent of number in the regional nodal station.
In the early stages, tumor size is the dominant criterion for renal cancer (Fig. 35.1), whereas in the more advanced stages, the staging features relate to the patterns of spread to the surrounding anatomy and, to a degree, criteria of resectability. The TNM staging has been undergoing subtle changes reflect ing the advances in imaging hypernephromas because the radiologic appearance is virtually pathognomic. Renal cancers show a supervascularity when computed tomography (CT) with contrast is used that is characteristic when compared to cysts. In the first to third editions of AJCC Cancer Staging Manual (1978 to 1980), T1 was distinguished from T2 by absence of deformity in the contour of pelvis calyces structures and T3 from T4 by a medial venous spread to the renal vein and/or renal pelvis invasion compared to lateral spread through the renal capsule into perirenal fat versus penetrating to Gerota's fascia. With the fourth edition in 1992, the tumor size and more specific patterns of invasion were defined modify stage III into substages A, B, and C (Fig. 35.3A).
T2 tumors measure >7 cm and are limited to the kidney or have no renal capsule invasion. T3 cancers are subdivided according to patterns of spread. Once the renal capsule is penetrated, T3a means the cancer has spread into perirenal fat laterally or adrenal gland superiorly. T3b cancers invade medially into the renal vein and inferior vena cava, and T3c cancers extend into the vena cava above the diaphragm. T4 cancer applies to posterior and lateral invasion beyond Gerota’ s fascia. With a few exceptions, stage reflects the primary categories.
SUMMARY OF CHANGES SEVENTH EDITION AJCC
The following changes in the definitions of TNM and the stag grouping for kidney cancer have been made since the sixth edition (Fig. 35.3A):
• T2 lesions have been divided into T2a (greater than 7 cm but less than or equal to 10 cm) and T2b (>10 cm).
• Ipsilateral adrenal involvement is reclassified as T4 if contiguous invasion and M1 if not contiguous.
• Renal vein involvement is reclassified as T3a
• Nodal involvement is simplified to N0 vs. N1
The TNM Staging Matrix is color coded for identification o Stage Group once T and N stages are determined (Table 35.3B). T stage determines group stage.
KIDNEY
Figure 35.3A | TNM renal cancer diagram. Renal cancers are well vascularized. When invasive, stage III, T3a, 3b, 3c (purple), they are resectable; when stage IV (red), T4, they are unresectable; and when stage IV, they are also metastatic. Vertically arranged with T definitions on the left and stage groupings on the right. Color bars are coded for stage: stage I, green; II, b ue; III, purple; IV, red; and metastatic, black.
ADRENAL GLAND
The new inclusion of adrenal cell carcinoma neurologic tumors rests on its anatomic relationship to the kidney.
• Anatomy: The adrenal glands are located at the superior poles of the kidney and are surrounded by Gerota’ s fascia and separated from the renal parenchyma by the renal capsule which consists of two distinct layers of connective tissue. The outer layer of fibroblasts and collagen fibers and cellular inner layer of myofibroblasts embryologically th cortex is derived from the mesoderm and medulla from the neural crest. Each adrenal gland consists of an outer cortex and inner medulla.
• Histology: The adrenal cortex exhibits 3 concentric zones (Fig. 35.4A):
1. Zone glomerulosa (15% volume) is a thin zone inferior to the capsule and consists of cells in ovoid clumps.
2. Zone fasciculate (80%) is the intermediate zone. The thickest and arranged in vertical columns, one-cell thick adjacent to capillaries.
3. Zone reticularis (5%) is innermost zone arranged in cords.
Figure 35.4A | The structural organization and general location in the body of the thyroid gland, parathyroid gland, and adrenal gland. Figure 35.4C | Major clinical manifestations of Cushing's syndrome.
Figure 35.4B | Adrenal cortical carcinoma. Left. The bulky tumor on section is yellow to tan with areas of necrosis and cystic degeneration. Right. A microscopic section demonstrates marked anisocytosis and nuclear pleomorphism.
• Physiology: Each zone produces essential hormones:
1. Zone glomerulosa: mineral corticoids
2. Zone fasciculate: glucocorticoids
3. Zone reticularis: androgens
• Pathology: Both adrenal gland cortical adenomas and carcinomas can be functioning and produce Cushing's syndrome. Eighty percent of carcinomas are functional, occur more frequently in women, and carry a poor prognosis (Fig. 35.4B).
• Clinical presentation: Cushing's syndrome can vary in intensity and severity depending on the levels of corticoids and duration. Typically there is the onset of moon face, buffalo humpback, and obesity of abdomen with wasting of limbs (Fig. 35.4C).
• Staging system is straightforward, based on tumor size (T15 cm, T2>5 cm) and T3 invades perinephric fat but not Gerota's fascia, vs. T4 relates to whether there is invasion of adjacent organs i.e. kidney vs. diaphragm, great vessels, pancreas, spleen, liver. Nodal spread is to paraortic and paracaval nodes in juxtaposition to tumor. Metastatic spread is to lung and liver or distant nodes in mediastinum and retroperitoneal area (Fig. 35.3B).
Figure 35.4C | Major clinical manifestations of Cushing's syndrome.
ADRENAL ADENOCARCINOMA
Figure 35.3B | TNM adrenal adenocarcinoma diagram. When invasive, stage III, T3a, 3b, 3c (purple), they are resectable; when stage IV (red), T4, they are unresectable; and when stage IV, they are also metastatic. Vertically arranged with T definitions n the left and stage groupings on the right. Color bars are coded for stage: stage I, green; II, blue; III, purple; IV, red; and metastatic, black.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR ONCOANATOMY
The isocenter of the kidney is the renal bed, which consists of Gerota's fascia and overlies the psoas major muscle and the quadratus lumborum musculature. The superior poles of both kidneys also lie in contact with the diaphragm. Usually, the 12th rib overlies the superior portion of the kidneys and is the only bone that is intimate anatomically. The kidney also lies opposite the transverse processes of T12 to L3 (Fig. 35.5).
T-oncoanatomy
The T-oncoanatomy is displayed in three planar views. A. Coronal, B. Sagittal, C. Transverse axial (Fig. 35.6).
• Coronal: There are many structures that overlie the kidney; however, they are of little concern oncologically because the peritoneal lining essentially excludes the visceral structures it contains from direct invasion. Nevertheless, it is important to recognize the intimate relationships of the stomach, on the left, and the duodenum, on the right, and the location of the hepatic and splenic flexures of the colon in relation to the midportions of the kidneys. The lung overlies the upper poles of both kidneys owing to the low insertion of the diaphragm, particularly during deep inspiration. One should be aware of the position of the pancreas, particularly of its head and tail and in regard to the right and left hila of the kidneys, respectively (Fig. 35.5). The course of the ureter is such that it is first crossed anteriorly by the rena artery and vein and then the spermatic artery and vein in males or the ovarian artery and vein in females. In its continued descent retroperitoneally, the ureter passes anterior to the major iliac vessels.
• Sagittal: The kidney is encased by a fibrous capsule and is surrounded by perinephric fat. The kidney is composed of the cortex, which includes glomeruli; convoluted tubules; and the medulla, which consists of the pyramids of converging tubules and the loops of Henle. The exterior third of the kidney substance is the cortex, in contrast to the inner two thirds, which is the medulla. The medulla contains 8 to 18 striated pyramids that send finge -like rays into the cortex and end in the minor calices. The minor calices unite and form the major calices that drain into the renal pelvis. The hilus of the kidney has the pelvis, ureter, and renal artery and veins.
• Transverse: Before its insertion in the bladder, the vesical arteries and veins, as well as the uterine artery and vein, pass anteriorly to the ureter (“water under the bridge”). There are considerable variations in the anatomic relationships of the renal ureters with renal arteries and veins owing to normal anatomic variations of embryologic development that lead to different locations of the kidneys. In addition, anomalies in their development are common and include multiple renal arteries, fetal lobulations of the kidney, deflected and bifid ureters and pelves, and horseshoe an pelvic kidneys.
Figure 35.5 | Orientation of T-oncoanatomy. The anatomic isocenter for three-planar anatomy of the kidney is at the T12 to L3 level. A. Coronal. B. Sagittal.
Figure 35.6 | T-oncoanatomy. Connecting the dots: Structures are color coded for cancer stage progression. The color code for the anatomic sites correlates with the color code for the stage group (Figs. 35.3A and 35.3B) and patterns of spread (Fig. 35.2) and the SIMLAP table (Table 35.2). Connecting the dots in similar colors will provide an appreciation for the three-dimensional oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
The regional nodes are anterior to and surround the renal artery and vein and at the midline, para-aortic and paracaval in location. It is important to note the left testis drains to the left hilar area of the kidney and the right testis drains to paracaval nodes at the lower pole on the right. The cisterna chyli is located on the right side near the upper pole.
There are considerable variations in the anatomic relationships of the renal ureters with renal arteries and veins owing to normal anatomic variations of embryologic development that lead to different locations of the kidneys. In addition, anomalies in their development are common and include multiple renal arteries, fetal lobulations of the kidney, deflected an bifid ureters and pelves, and horseshoe and pelvic kidneys (Fig. 35.7A; Table 35.4A). For the adrenal gland lymph node drainage, see Table 35.4B.
M-ONCOANATOMY
Common metastatic sites reflect the vascular drainage of th kidney. As noted in the patterns of spread, invasion in the renal vein and inferior vena cava is common. Pulmonary spread is very common. With continued circulation of tumor cells through the left heart, metastases to bone, brain, and liver become possible. Unfortunately, remote metastases frequently occur with this tumor owing to the rich neovascularization. The T3 stage is divided according to the venous drainage of the kidney: T3a invasion into renal vein, T3b invasion into inferior vena cava infradiaphragmatic, T3a is supradiaphragmatic.
Renal pelvis transitional cell cancers are characterized similarly to transitional cell cancers of uroepithelium of bladder in their ability to “seed” throughout the urinary tract. Endoscopic assessment is important to determine when renal pelvis cancer is a primary or part of a disseminated urological cancer (Fig. 35.7B).
REGIONAL LYMPH NODES
The regional lymph nodes, illustrated in Figure 35.7A, are as follows:
Renal hilar
Caval (paracaval, precaval, and retrocaval)
Interaortocaval
Aortic (para-aortic, preaortic, and retroaortic)
The primary landing zone for right-sided tumors is the interaortocaval zone and for left-sided tumors is the aortic region. The more extended landing zone for RCC are analogous to those for right and left testicular tumors, respectively, although patterns of spread are somewhat more unpredictable. Lymph nodes outside of these templates should be considered distal (metastatic) rather than regional.*
*Preceding passage from Edge SB, Byrd DR, and Compton CC, et al. AJCC Cancer Staging Manual, 7th edition. New York: Springer, 2010, p. 480.
Figure 35.7 | A. N-oncoanatomy. Renal hilar (para-aortic) and paracaval. B. M-oncoanatomy. The renal veins drain into the inferior vena cava, which is arbitrarily divided into infradiaphragmatic and supradiaphragmatic.
STAGING WORKUP
RULES OF CLASSIFICATION AND STAGING
Clinical Staging and Imaging
Clinical examination is limited, and reliance on imaging is critical. Fortunately, modern imaging is superb and includes CT, magnetic resonance imaging (MRI), and selective arteriography. If the primary tumor is advanced, CT of chest for lung and mediastinal nodal metastases is advised. An intravenous pyelogram and routine laboratory studies are worthwhile (Table 35.5; Fig. 35.8).
Pathologic Staging
Careful assessment of resected primary, which includes primary tumor, kidney, appropriate lymph nodes contained within the renal (Gerota’ s) fascia, perirenal fat, and renal vein/artery, is needed. Partial nephrectomy needs careful study for margins.
Oncoimaging Annotations
• Renal carcinomas are more conspicuous in the CT nephrogram phase than in the early arterial or corticomedullary phase of imaging.
• Cross-sectional imaging is essential in staging and in guiding treatment.
• Although the reported staging accuracy for CT and MRI is similar, CT is used as a primary imaging approach; MRI complements CT and is most useful in defining the presenc and extent of intravenous tumor extension.
• Doppler ultrasonography is also recommended for the evaluation of vascular invasion.
• Pretreatment use of chest radiography versus chest CT is controversial. The use of chest CT is recommended when there is renal-vascular tumor extension, the patient has chest symptoms, or a suspicious nodule is seen on the chest film
PROGNOSIS AND CANCER SURVIVAL
PROGNOSIS
The limited number of prognostic factors are listed in Table 35.6.
CANCER STATISTICS AND SURVIVAL
When considered together, the genital and urinary systems in males are the major sites of malignancy. Prostate cancer alone accounts for 200,000 new patients annually. There are 100,000 new urinary tract cancers and 2.5-fold more male genital cancers: 250,000 cases annually (see Tables 35.7 and 35.8).
The dramatic gains in survival are due to multidisciplinary achievements in screening, early detection, precise diagnoses, and effective multimodal therapies. The cancer statistics reveal perhaps the greatest gains in survival in oncology over the last five decades. In local stage I, male genitourinary tumors are 90% to 100% curable according to the latest Surveillance Epidemiology and End Results data: kidney, 90%; bladder, 94%; testes, 99%; and prostate, 100% (Table 35.7). Death and mortality rates are declining. Pediatric Wilms’ tumor was the first malignancy in childhood to be cured, achieving>90% long-term survival and heralding the success of multimodal treatment that would be achieved in adult tumors in urology (see Fig. 35.9).
Figure 35.8 | Axial CTs of L1 and L2 level correlate with the T-oncoanatomy transverse section (Fig. 35.6C). Oncoimaging with CT is commonly applied to staging cancers, often combined with PET to determine true extent of primary cancer and involved lymph nodes. 1. Superior mesenteric vein. 2. Superior mesenteric artery. 3. Left renal artery 4. Right renal vein. 5. Inferior vena cava. 6. Pancreas. 7. Descending colon. 8. Ascending colon. 9. Duodenum. GB, gallbladder; J, jejunum; LK, left kidney; RK, right kidney.
Figure 35.9 | Five-year observed survival rate for kidney cancer. (Data from Edge SB, Byrd DR, Compton CC, et al., AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010, p. 480.)