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Genitourinary pathology includes specimens from the kidney, ureters, bladder, prostate, testis, and penis (see separate chapter for the latter). The kidney may undergo biopsy as part of the evaluation of renal function, the testes may be biopsied for interfertility issues, the prostate may be excised for urinary symptoms, and the vas deferens may be resected for sterilization. Otherwise, genitourinary specimens are generally biopsied or excised for neoplastic disease.
Relevant clinical history, in addition to gender and age, is often necessary or helpful to interpret specimens from the kidney ( Table 17.1 ).
HISTORY RELEVANT TO ALL SPECIMENS | HISTORY RELEVANT FOR KIDNEY SPECIMENS |
Organ/tissue resected or biopsied | Urinalysis: presence and quantity of protein (spot urine protein to urine creatinine ratio, 24-hour quantification); blood; amount and type of casts (e.g., red blood cells, white blood cells, muddy brown) |
Purpose of the procedure | Renal function tests (BUN and creatinine) and time frame of changes |
Gross appearance of the organ/tissue/lesion sampled | Systemic conditions: connective tissue and autoimmune diseases, acute or chronic infections, hemoglobinopathies, hypertension, obesity, diabetes mellitus, antiphospholipid syndrome, myeloma, vasculitis, hemolytic uremic syndrome (HUS) |
Any unusual features of the clinical presentation | |
Any unusual features of the gross appearance | |
Prior surgery/biopsies—results | Results of serology (e.g., anti-GBM antibodies, ANCA, ANA, C3, C4, cryoglobulins, hepatitis B and C) |
Prior malignancy | |
Prior treatment (radiation therapy, chemotherapy, drug use that can change the histologic appearance of tissues) | Drug use (analgesics, penicillamine, hydralazine, chemotherapeutic agents, antihypertensives, ACE inhibitors, angiotensin receptor blockers) |
Compromised immune system | Blood pressure |
Edema | |
Glucose values and hemoglobin A1c | |
Urine culture results | |
Serum and urine protein electrophoresis (SPEP and UPEP) | |
Radiographic findings (symmetry, obstruction, etc.) | |
For transplants: duration of transplant, donor information (living, deceased, related, unrelated, “expanded criteria,” polyoma serology, history of prior transplants, results of prior transplant biopsies, relevant interventions (e.g., changes in immunosuppressive therapy), serum levels of immunosuppressive therapy |
“Medical” renal biopsies are typically performed for evaluation of renal function or urinary abnormalities and are assessed in the context of the clinical presentation of the patient, with particular attention to the results of serological tests and urinalysis. Small renal masses are frequently biopsied to determine if the mass is benign or malignant. Large kidney masses are occasionally biopsied because for the tumor subtype will affect the choice of treatment. Occasionally biopsies will be performed on kidneys with tumors that will be treated with cryotherapy or before a kidney is used for transplantation. Unresectable tumors are usually diagnosed by fine needle aspiration or core biopsy of a primary tumor or metastasis if present.
A medical kidney biopsy is usually performed by a nephrologist in conjunction with a radiologist, under ultrasound guidance. Occasionally, the radiologist may perform a percutaneous biopsy under CT guidance, or a transjugular biopsy in the angiography suite. After each pass, the core needle biopsy (ideally 15-gauge) is examined unfixed under stereomicroscopy by the renal pathologist to assess the adequacy of the specimen and to determine the need for additional biopsies ( Fig. 17.1 ). The consensus classification for adequacy of a transplant biopsy recommends there must be 10 or more glomeruli and two arteries.
Biopsies are examined and divided for light microscopy, immunofluorescence (IM), and electron microscopy (EM), which are performed routinely on every medical renal biopsy. The amount of needed tissue and type (cortex or medulla) will differ for each situation and depends on the clinical differential diagnosis, the focality of the expected disease process, pathologist’s experience, patient tolerance of the procedure, and any complications (e.g., bleeding).
Clean forceps must be used when allocating tissue for light microscopy, IF, and EM! Minute amounts of formalin or glutaraldehyde can destroy the antigenicity of the tissue allocated for IF and glutaraldehyde can create problems in interpreting tissue for light microscopy.
Representative cortex and, if available, medulla (for evaluation of casts), are allocated for IF by placement in Zeus transport solution (Michel’s solution).
A few viable glomeruli are usually sufficient for placement in Karnovsky’s glutaraldehyde/paraformaldehyde fixative for EM.
The remaining tissue is fixed in formalin. Each core is placed separately in a nylon biopsy tissue bag. Institutions will have protocols for routine studies.
Nephrectomies are commonly performed for tumors (usually renal cell carcinoma [RCC], less frequently for urothelial cell carcinoma [UCC] of the renal pelvis), or to remove nonfunctioning grafts. Native nonfunctioning kidneys are also sometimes removed. Partial nephrectomies (also referred to as nephron sparing surgery) are becoming more common to resect tumors if the other kidney is absent or nonfunctioning or if the primary tumor is small (e.g., a tumor found incidentally on CT scan or ultrasound examination).
The evaluation of the non-neoplastic kidney is important to recognize other diseases that elevate the patient’s risk for progressive renal failure.
If a kidney is removed as part of a larger resection (e.g., a retroperitoneal resection for a sarcoma), sections of cortex should always be submitted for EM and IF and evaluated for medical renal diseases.
The section for light microscopy to evaluate the nontumorous kidney must include both cortex and medulla and must be located away from the tumor and scarred areas.
H&E, PAS, Jones’ silver methenamine, and trichrome stains are typically ordered.
The section for IF must include both cortex and medulla and must be located away from the tumor and scarred areas. Using a clean pair of forceps and clean blade (without having touched formalin), remove a small section of cortex and further cut it into smaller fragments measuring 0.5 × 0.2 cm in thickness. Place the tissue into a vial labeled with the patient information and containing Zeus transport solution (Michel’s solution). Shake the vial to make sure all the tissue fragments are covered by fixative.
The section for EM must include cortex only and must be located away from the tumor and scarred areas. Using a clean pair of forceps and clean blade (without having touched formalin) remove a small section of cortex and further cut it into smaller fragments measuring 0.5 × 0.2 cm in thickness. Place the tissue into a vial labeled with the patient information and containing glutaraldehyde/Karnovsky’s fixative. Shake the vial to make sure all of the tissue fragments are covered by fixative.
Renal grafts are transplanted to the pelvis with a short vascular pedicle connected to the inguinal vessels. The specimen usually consists simply of the kidney, without surrounding soft tissue, and vessels cut flush with the hilum. Transplant failure may be due to pre-existing disease in the allograft, vascular insufficiency (e.g., thrombosis or plaque), rejection, or recurrence of the patient’s original renal disease.
Weigh the kidney (normal is 125–170 g for males and 115–155 g for females) and record the measurements. Record the length and diameter of the hilar vessels and ureter. Look for patency or obstruction of vessels (thrombosis, intimal proliferation, atherosclerotic plaques).
Describe the renal parenchyma including color (tan/red, gray/green), thickness of cortex, shape of calyces and papillae (normal or blunted), state of pelvis and ureter, vessels, infarcts (size and location), hemorrhage, and necrosis.
Submit four cassettes including cortex and medulla, hilar vessels, and any lesions. Allocate tissue for EM and IF microscopy.
Nonfunctioning kidneys may be removed due to hypertension refractive to medical therapy, persistent pyelonephritis, severe renal protein loss, polycystic kidneys, or in patients with bilateral renal tumors. A native kidney may also be removed to provide a native ureter for the allograft.
Acquired cystic kidney disease occurs in over 30% of patients with end-stage renal disease and the incidence increases over time. Papillary hyperplasia is commonly present in the walls of the cysts and is thought to be a precursor lesion for carcinomas. Adenomas are frequently found in this population (about 25%) and are typically multiple and bilateral.
RCCs develop in 5–10% of patients of patients with end-stage kidney disease, and 70–80% of these patients will have acquired cystic kidney disease. Carcinomas are more likely to be multifocal (50%) and 25% of patients have bilateral tumors. Although many are small and incidental, some do metastasize for an overall 5-year survival rate of 35%. Different types of renal tumors occur in this population. About one third are acquired cystic disease (ACD)-associated RCC. These cancers increase in incidence with long-term hemodialysis. They usually occur within a cyst in a background of other cysts. Clear cell, papillary, chromophobe, and clear cell papillary RCC (CCPRCC) also occur in these patients.
The incidence of urothelial carcinomas is increased in patients with long-term use of analgesics, especially phenacetin. The cortex is examined as for a diagnostic renal biopsy to identify the etiology of the renal failure.
Weigh the kidney (normal is 125–170 g for males and 115–155 g for females) and record the measurements. Record the length and diameter of the hilar vessels and ureter. Look for patency or obstruction of vessels (thrombosis, intimal proliferation, atherosclerotic plaques).
Describe the renal parenchyma including color (tan/red, gray/green), thickness of cortex, shape of calyces and papillae (normal or blunted), state of pelvis and ureter, vessels, infarcts (size and location), hemorrhage, and necrosis. The number and size of cysts are recorded.
The entire kidney is thinly sectioned and carefully examined. The lining of cysts is examined for any areas of thickening or irregularities as these may be neoplastic. Solid lesions are also suspicious for neoplasia. Allocate tissue for EM and IF microscopy.
Submit four cassettes including cortex and medulla and hilar vessels.
Additional cassettes are submitted to evaluate any solid or cystic areas suspicious for carcinoma (1 tissue section per 1 cm of suspected tumor).
Routine PAS, Jones’ methenamine silver, and trichrome stains on the normal renal cortex may be ordered.
Radical nephrectomies consist of the kidney, the majority of the ureter, renal vein and artery, perinephric fat, and surrounding Gerota’s fascia. An adrenal gland may or may not be present. Recommendations for the sampling of these specimens with RCCs have been published.
Uninvolved tissue from the cortex and medulla should also be taken to evaluate the kidney for medical renal diseases (see above). Examination of the non-neoplastic kidney reveals significant disease in over half of patients. This information is important to identify the patients most likely to develop chronic renal disease in order to implement early preventative therapy and treatment.
Weigh the entire specimen and record its dimensions. Examine the hilum carefully and identify the ureter, renal vein, and renal artery. The vessels and ureter will usually be tied off with sutures or stapled.
It is useful to determine if renal vein invasion was seen on preoperative radiologic studies prior to gross evaluation to aid in specifically documenting this finding. Involvement of the renal vein and segmental branches changes the T classification to pT3a and is important for staging and prognosis.
Tumor involvement of the renal vein may be obvious grossly and has the appearance of a smoothly surfaced projection of tumor extending out from the hilum. The vessel wall often retracts around a tumor thrombus that is not attached to the wall, resulting in the intravascular tumor being present at the “margin.” However, the vein margin is only considered positive when the tumor is adherent to the vessel wall at the margin. This finding must be carefully evaluated and documented.
Take en face cross sections of the margins (vein, artery, and ureter) and place in a labeled cassette.
Inspect the outer portion of the specimen. The kidney is surrounded by perirenal fat. Surrounding this fat, the kidney, and the adrenal gland is within a renal fascia (“Gerota’s fascia”).
Ink the outer surface of the specimen including perirenal fat and areas of exposed kidney.
A probe placed in the ureter and renal vessel (vein if unobstructed by tumor; artery if minimally atherosclerotic) assists in making a cut through the center of the kidney. Cut along the probes to bisect the ureter and vein and extend the cut to divide the kidney. This method facilitates the complete evaluation of the urothelium in cases of UCC. The kidney is bivalved with a single longitudinal cut. Cut the kidney completely through into two separate halves. If the mass is not well visualized with the central slide, cut additional slices parallel to the first. Photograph one half of the kidney with the mass. The color of the tumor and gross appearance can help with subtyping and staging, respectively.
Describe all lesions including size, number (both RCC and UCC may be multifocal), appearance, necrosis, location (with respect to the upper and lower pole, cortex, medulla, pelvis), distance from margins (Gerota’s fascia, vascular, ureteral), involvement of calyceal or pelvic mucosa (open completely with scissors), gross invasion of capsule or into perirenal soft tissue, gross involvement of the sinus, and involvement of adjacent structures (renal vein, adrenal). It is important to note if the tumor demonstrates direct extension into the adrenal gland (pT4) or is present as a separate mass in the adrenal gland (M1). Make additional cuts (horizontal or perpendicular to the original cut) as necessary to assess the entire parenchyma.
Renal sinus adipose tissue is located between the pelvicalyceal system and the renal parenchyma. The main lymphovascular supply of the kidney is located here and invasion into this tissue is important to document. Invasion of hilar adipose tissue also upstages the tumor to pT3. Multiple blocks of tissue may be submitted if the tumor is close to this area but tumor invasion into fat is uncertain.
Describe the uninvolved renal parenchyma including color, thickness of the cortex, corticomedullary junction (well defined, effaced), shape of the papillae (blunted, necrotic), calyces, renal pelvis (dilation, petechiae, mucosa), presence of calculi, and types of cysts (simple are usually benign; complex cysts may be neoplastic). Note any tan/yellow or white nodules in the cortex that might be a cortical “adenoma” or additional foci of tumor.
Palpate the hilar region for any lymph nodes and save in a labeled cassette. Typically, hilar lymph nodes are only found in about 22% of patients.
A section of normal cortical and medullary tissue located away from the tumor and scarring is taken for light microscopy and possible IF and the cortex is sampled for possible EM (see above). Routine PAS, Jones and silver stains on the non-neoplastic tissue block may be ordered. Examination of the non-neoplastic kidney reveals significant disease in over half of patients. This information is important to identify the patients most likely to develop chronic renal disease in order to implement early preventative therapy and treatment.
Fix the entire specimen in formalin overnight. Large tumors should be bivalved with additional parallel slices as needed. Formalin-soaked gauze is placed between the slices to wick formalin around the sections.
The following day sections of the tumor (at least 1 per cm), margins, and kidney are taken. Grossly different areas should be sampled, including an interface between any areas that are grossly different in appearance (i.e., yellow vs. brown vs. fleshy/tan). Pay special attention to white fleshy areas as these may represent areas of sarcomatoid transformation; document in the gross description the approximate amount (in percent) of white/fleshy tumor.
The adrenal gland may be present at the upper pole. Free the gland from the surrounding fat and describe including color, size, nodularity (see Chapter 8 ). Section the gland carefully looking for evidence of tumor metastasis (nodules). If abnormal, weigh the gland and/or focal lesions.
Carefully section through the remainder of the fat looking for lymph nodes. Any nodes present are usually near the renal hilum.
Sample the tumor showing the closest approach to the renal capsule.
Sample perirenal and hilar adipose tissue, including tumor if it is close to this tissue.
Rarely, a portion of rib may be submitted with the nephrectomy specimen. See Chapter 11 for instructions on processing.
One full-thickness section including both cortex and medulla, located away from the tumor, is taken. Routine PAS, Jones’ methenamine silver, and trichrome stains may be ordered on this section for evaluation of renal disease.
Renal tumors often have distinctive appearances and can be distinguished grossly ( Fig. 17.2 ).
Renal cell carcinoma: The most common type is clear cell (conventional) carcinoma (75% of cases), followed by papillary carcinoma (10%), chromophobe carcinoma (5%), and other rare types. Some RCC’s arising in kidneys with ACD may be quite subtle and can have the appearance of an irregular area of papillary projection within a cyst (ACD-associated RCC).
Clear cell (conventional) RCC is the most common type of renal carcinoma. This carcinoma is usually golden yellow to red, spongy to firm, and occurs in discrete nodules with pushing borders. An older term for this cancer, hypernephroma, refers to the gross resemblance of the color of this tumor (“canary yellow”) to the adrenal gland cortex, as both are composed of cells with abundant cytoplasmic lipid. The tumor may appear brown if the cytoplasm is granular. Prominent thin-walled blood vessels and blood lakes are typical. Necrosis may be present. Cysts may be absent or quite prominent. The tumor may bulge out beyond the contour of the renal capsule and sometimes will invade through the capsule into adipose tissue. Invasion may occur into the renal sinus adipose tissue where there is no capsule.
Papillary RCC is a well-circumscribed tumor with a fibrous pseudocapsule (papillary adenomas lack a fibrous capsule). The tumors are soft and friable because of the papillary architecture. The color ranges from brown (due to hemosiderin) to tan/yellow (due to abundant foamy macrophages). Some appear to be necrotic due to the soft texture and some are actually necrotic. Hemorrhage and cystic areas are common. Some are multifocal, although small tumors (up to 1.5 cm) may be classified as papillary adenomas.
Chromophobe RCC is usually a small to large well-circumscribed solitary tumor without a surrounding capsule. A central scar is present in about 15%. The color is pale tan to dark brown associated with cytoplasmic iron. Necrosis or hemorrhage is seen in about a third of cases. Cystic change is uncommon.
Collecting duct carcinomas occur in the renal medulla and have a hard gray/white appearance. The borders are typically irregular and tumor typically infiltrates between glomeruli and tubules. The majority invade into the renal sinus and perinephric adipose tissue. Necrosis, hemorrhage, and cystic change are frequent.
ACD-associated carcinomas occur in the setting of cystic disease associated with renal failure and long-term hemodialysis. The tumor grows in a cystic space in a background of other cysts. The cancers are well circumscribed and can be multifocal and bilateral. They are tan to yellow brown and can have areas of necrosis and hemorrhage. Long-term hemodialysis (>10 years) is a risk factor for developing an ACD-associated RCC.
Clear cell tubulopapillary renal cell carcinoma occurs in patients with and without end-stage renal disease. The cancers are usually small and well circumscribed with a tumor capsule and may be cystic. No hemorrhage or necrosis is seen.
Sarcomatoid differentiation has the appearance of gray/white firm to fleshy areas detected in cancers of other histologic types. Any area of this appearance should be documented (give overall percent of tumor) and sampled. Hemorrhage and necrosis are common.
Urothelial cell carcinoma is usually a tan/pink friable mass with a minute villous architecture. There may be a rather small base, compared to the size of the tumor, attached to the renal pelvic urothelium. However, some tumors have a broad base and involve the majority of the urothelium of the renal pelvis. The tumor can have retrograde growth up collecting tubules or directly invade the renal parenchyma. The ureter may also be involved.
Renal cortical adenomas are usually well circumscribed, unencapsulated gray or yellow benign tumors present below the renal capsule. They are typically an incidental finding and are less than 1.5 cm in size. They are sometimes associated with long-term hemodialysis or chronic pyelonephritis and are most frequently papillary in architecture.
Metanephric adenomas are well-circumscribed benign tumors but can range in size from 1 to 15 cm. The color is fleshy tan/yellow and hemorrhage or necrosis should not be present.
Oncocytomas are usually deep red/brown, soft, and well-circumscribed benign tumors, without areas of necrosis, located in the cortex. Central “scarring” is present in about half of cases, especially in larger tumors.
Other types of neoplasia: Rare renal tumors include fumarate hydratase-deficient RCC, succinate dehydrogenase-deficient RCC, translocation (Xp11.2) RCC, mucinous tubular and spindle cell carcinoma, tubulocystic carcinoma, malignant perivascular epithelioid neoplasm (PEComa), mixed epithelial and stromal cell tumor, primary sarcoma, and others.
Pediatric tumors: The types of renal tumors occurring in children are quite different than those seen in adults and include nephroblastoma (Wilms tumor), clear cell sarcoma, rhabdoid tumor, mesoblastic nephroma, lymphoma, and neural tumors, as well as RCC, and angiomyolipoma. The College of American Pathologists (CAP) “Protocol for the Examination of Resection Specimens from Patients with Wilms and Other Pediatric Renal Tumors” has additional information on the sampling and reporting of these tumors (available at https://www.cap.org ). The Childrens Oncology Group Staging System can be used for Wilms tumors ( Table 17.5 ). There is not an AJCC staging system for Wilms tumors.
Nephrectomy weight in pediatric kidney tumors is used as an eligibility factor for some clinical trials and is important to document. The specimens may be processed as above but additional sections should be taken to document the relationship of the tumor to the normal kidney (to identify the invasive pattern of the tumor), the relationship of the tumor to the renal sinus and sinus vessels (important to define stage 2 disease), and to evaluate the relationship of the tumor to the capsule. Normal appearing cortex should also be sampled. Because these tumors tend to be more heterogeneous in appearance, at least 1 section per cm of greatest tumor dimension should be taken including all areas of differing appearance. If there is more than one tumor nodule, each nodule should be sampled. It is important to document the location of each section taken on a diagram or photograph to appropriately classify these tumors. Some treatment protocols require that the patient have negative lymph nodes. Therefore, all hilar tissue should be examined microscopically.
Tissue should also be taken for special studies:
Snap-frozen: The National Wilms Tumor Study Protocols (see www.nwstg.org ) require snap-frozen tissue (in liquid nitrogen or cold isopentane) from all pediatric renal tumors and adjacent normal tissue (preferably 1 g or a minimum of 100 mg in two or more vials along with a separate portion of normal kidney in at least one vial). Nephrogenic rests may also be frozen. Adjacent tissue should be sampled for formalin fixation for histologic correlation.
EM: EM may occasionally be of use.
Touch preparations : Fixed in 95% alcohol. Can be used for some studies (such as in situ hybridization) if other tissue is not available for these studies.
Flow cytometry: In some cases flow cytometric analysis of ploidy, S-phase fraction, or surface markers (i.e., for lymphomas) may be requested.
Genetics: Genetic studies may be useful for classification and prognosis as some tumors have specific genetic alterations:
Cellular mesoblastic nephromat(12;15)
Malignant rhabdoid tumor22q11.2 deletion
Wilms tumordel 11p13
Nephroblastoma (Wilms tumor): This is the most common type of pediatric renal tumor (80% of total) and occurs in children from 1 to 6 years of age. Most are well-circumscribed lobulated masses with a variegated appearance from gray to pink. Extensive necrosis and hemorrhage are common. If there are multiple nodules, each should be sampled. Cysts may be present. The tumor may invade into the renal vein, ureter, or adipose tissue.
The weight of the kidney may be used as an eligibility factor for clinical protocols and must be determined accurately.
At least 1 section per cm of tumor should be taken, as tumors can be quite heterogeneous. Most sections should be taken from the periphery to evaluate the relationship to the capsule, the renal sinus, the normal kidney, and possible vascular involvement.
The renal sinus (the hilum of the kidney occupied by the renal pelvis, hilar vessels, and fat) should be well sampled as tumors often involve vessels at this point. The renal cortex lacks a capsule at this point. The tumor often involves the renal vein as a tumor thrombus. The vein may retract around a tumor thrombus. This should not be interpreted as a positive margin if the thrombus is not transected.
If the patient has been treated, the response to treatment is classified according to the percent of residual viable tumor. It is important to document the location of sections and to sample the entire tumor bed in order to make this determination.
Nephrogenic rests: These are areas of persistent embryonal tissue and are found in more than one third of cases of Wilms tumor. They are found in <5% of pediatric kidneys removed for other reasons. The rests appear as grossly pale areas and are often subcapsular. Nephroblastomatosis is defined as multiple or diffusely distributed rests. The presence of nephrogenic rests and the type of rests (perilobar or intralobar) are associated with the probability of a syndrome and involvement of the contralateral kidney ( Table 17.2 ). Renal lobes are more easily seen in the kidneys of infants and children. Clear cell sarcoma: These make up 4% of renal tumors in children and occur between the ages of 1 and 3. Thirty percent present with metastases to lymph nodes. The tumor is usually a large well-circumscribed gray/white mass with pushing borders into the adjacent renal parenchyma. Focal necrosis and hemorrhage may be present.
FEATURE | PERILOBAR REST | INTRALOBAR REST |
Site in renal lobe | Periphery (including subcortical) | Random; cortex, medulla, sinus |
Margins | Clearly demarcated | Poorly demarcated |
Relation to nephrons | No nephrons within rest | Dispersed between nephrons |
Composition | Blastemal or tubular; stroma scanty or sclerotic | Tubules, blastema, cysts; stroma usually predominates |
Number | Usually numerous | Often single |
Wilms tumor associations | Blastemal or epithelial predominant | Early-onset, stromal predominant or tumors showing divergent (teratomatous) differentiation |
Syndrome associations | Beckwith–Wiedemann syndrome, Perlman syndrome, and hemihypertrophy | WAGR syndrome and Denys–Drash syndrome |
* Modified from Sternberg’s Diagnostic Surgical Pathology, 2004.
Rhabdoid tumor: Most are well defined and fleshy in appearance with frequent necrosis and hemorrhage. The renal pelvis is usually involved. These tumors are most common in infants below the age of 1 and rare in children older than 5.
Congenital mesoblastic nephroma (CMN): These are rare tumors (2% of pediatric renal tumors) that occur in children from birth to 2 (most are less than 3 months old). The tumor is an irregular gray/white to tan mass often of large size. Cysts, necrosis, or hemorrhage are unusual. These tumors can involve the renal vein and the vessels at the hilum and this is an important prognostic factor. This area should be thoroughly sampled.
There are three types:
Classic CMN (24% of cases) corresponds to infantile fibromatosis.
Cellular CMN (66% of cases) corresponds to infantile fibrosarcoma and often have a t(12;15) or other variant translocation resulting in a fusion product. All relapses are of this type or mixed.
Mixed CMN (10%) has features of both histologic types. Some of these tumors have EFGR activating mutations.
Lymphoma: A well-defined homogenous gray to white mass involving the cortex or medulla.
Cystic kidney disease: Genetic (presenting at birth or as an adult), sporadic, and acquired (due to long-term hemodialysis) forms of cystic kidney disease occur. The location and size of the cysts vary among the different types of cystic renal disease ( Table 17.3 ). Because of the increased risk of RCC in ACD, all cysts must be carefully examined for mural nodules or papillary projections. Xanthogranulomatous pyelonephritis: Appears as single or multiple golden yellow nodules in and around the pelvis and calyces. The nodules may rarely be found in the renal capsule or in adjacent fat. The gross appearance can mimic a RCC.
CYSTIC KIDNEY DISEASE | ||||
DISEASE | KIDNEY SIZE | LOCATION OF CYSTS | SIZE OF CYSTS | CLINICAL CORRELATIONS |
Infantile polycystic kidney disease | Massively enlarged | Cortex and medulla, radially arranged and oriented perpendicular to renal capsule | Small | Autosomal recessive Can also affect liver (congenital hepatic fibrosis—Caroli disease) Usually fatal at birth |
Medullary sponge kidney | Normal | Arise in collecting ducts and found in medullary pyramids and renal papillae | Small <0.5 cm | Most sporadic—rarely hereditary Rarely progress to renal failure, associated with urolithiasis |
Medullary cystic kidney disease | Small, contracted, granular surface | Corticomedullary junction | Small <2 cm | Autosomal dominant Two types—gout often develops in type 2 Renal failure develops from 30 to 70 years |
Nephronophthisis/medullary cystic kidney disease | Small, contracted, granular surface | Corticomedullary junction | Small <2 cm | Autosomal recessive Four types—renal failure develops from 1 to 19 years 15% develop retinal disease |
Adult polycystic kidney disease | Normal to marked increase | Cortex and medulla | Small to very large (several centimeters) | Autosomal dominant Liver cysts may be present About half progress to renal failure in adulthood |
Acquired cystic disease | Small | Cortex | Variable—small to very large | Occurs after long-term hemodialysis. There is an increased risk of RCC |
Angiomyolipoma : These tumors consist of dystrophic vessels, smooth muscle (gray/white), and adipose tissue (yellow) in varying proportions. The tumor is usually circumscribed with a variable appearance depending on the components of the tumor. Smooth muscle predominant tumors resemble leiomyomas and adipose predominant tumors resemble lipomas. The radiologic appearance is often diagnostic due to the presence of adipose tissue and vessels within the tumor. The vascular component is often associated with hemorrhage. The tumor may be confined to the kidney or extend through the capsule. Rare cases may involve the renal vein or regional lymph nodes. The gross appearance can closely mimic a RCC and some tumors are associated with RCC. This is a very common tumor in patients with tuberous sclerosis (in this setting they can be multifocal and bilateral), but the majority of tumors occur in patients without this disease.
Tumor | One section per cm of tumor with varying appearance, relationship to adjacent uninvolved tissue, invasion of adjacent structures (such as perinephric or perihilar fat). If involvement of the renal vein is known or suspected, representative sections should be submitted of the vein. Include sampling of hilar and perinephric adipose tissue. |
Margins | Radial margin in perirenal fat, vascular margins, and ureter margin |
Other lesions | Cysts, infarcts, adenomas, etc. One section of each. |
Normal kidney | At least one cassette of uninvolved normal appearing cortex and medulla. If an underlying disease is suspected that could affect the other kidney, tissue for EM and IF microscopy and special stains may be indicated. |
Adrenal (if present) | At least one cassette demonstrating normal adrenal. Additional cassettes to demonstrate lesions. |
Lymph nodes | Submit all lymph nodes found. |
Part A, received fresh and labeled with the patient’s name, medical record number, and “right kidney” consists of a radical nephrectomy specimen (296 g, 12.3 × 11.9 × 3.2 cm) including ureter (12.3 cm long, 0.3 cm in diameter), renal vein (2.1 cm long, 2.0 cm in diameter), renal artery (0.9 cm long, 0.3 cm in diameter), kidney proper (15.6 × 8.2 × 4.1 cm), and perirenal adipose tissue (up to 3.1 cm thick). Adrenal is not identified. The outer surface is inked blue.
There is a well-demarcated, variegated yellow–red to brown, solid hemorrhagic mass (4.1 × 3.5 × 2.7 cm) in the mid–upper pole involving approximately 20% of the kidney. The mass is 3.1 cm to the renal vein margin, 2.5 cm to the renal artery margin, 13.6 cm to the ureter margin, and 3.0 cm to the inked outer surface. The mass does not involve the renal vein, distorts but does not grossly invade the renal sinus, and is confined to the kidney without involvement of the perirenal adipose tissue. The remainder of the kidney contains a well-defined corticomedullary junction and a unilocular cortical cyst (0.6 cm in greatest dimension) filled with clear serous fluid in the lower pole.
Gross photographs are taken. Representative mass and normal is submitted for tissue bank and research. Representative normal kidney cortex is allocated for EM/IF on hold. Representative sections are submitted for microscopic evaluation.
Micro A1: Ureter, artery, and vein margins en face, three fragments.
Micro A2–A3: Mass to sinus, two fragments.
Micro A4–A5: Mass to inked radial margin, two fragments.
Micro A6: Mass with normal kidney and pelvis, one fragment.
Micro A7: Parenchyma and cortical cyst, two fragments.
Micro A8: Uninvolved parenchyma, one fragment.
A partial nephrectomy is performed for a radiologically indeterminate mass, a tumor in a solitary kidney (the contralateral nephrectomy may have been performed for prior tumor), or underlying disease expected to affect renal function (e.g., diabetes). Process as above with the following exceptions:
Examine the cut surface of the kidney for areas suspicious for tumor. Ink this parenchymal resection margin. Often, the surgeon will indicate the resection margin using a surgical suture. Because orientation and evaluation of this margin is very important, contact the surgeon for orientation if necessary. Ink the capsule a second color. Serially section through the specimen. Describe the distance of the tumor from the cut renal resection margin.
No major vessels or the ureter will be present.
Always photograph the cut surface of specimen to include the mass.
Take multiple sections demonstrating the relationship of the tumor to the renal resection margin as well as to the deep (perirenal fat) margin.
Minimally invasive surgery to remove a kidney for tumor or other indications is reported to result in shorter hospital stays, decreased blood loss, more rapid recovery, and improved cosmesis. The kidney is placed in a bag intraoperatively, prior to removal. If removed intact, the kidney can be processed according to standard procedures. Alternatively, the specimen may be morcellated within the bag in order to remove it through a small (typically 1–1.2 cm) incision. The ability to evaluate tumor size, tumor margins, renal vein involvement, and renal sinus involvement is very limited, or impossible, in these specimens. Tumor type and grade can be determined.
The entire specimen is weighed.
The fragments are separated into groups based on the gross appearance:
Suspicious for tumor or cyst wall
Suspicious for hilar structures—vessels or ureter
Normal appearing renal parenchyma
The probability of sampling a tumor in a given number of cassettes is related to the size of the tumor and the size of the kidney. The tumor-to-kidney volume ratio is defined as the volume of the tumor divided by the volume of the kidney. 17
The volume of the tumor is calculated using the radius (half the largest dimension by imaging) and assuming the tumor is a solid sphere. Thus, the volume of a 3 cm tumor (i.e., the radius is 1.5 cm) is:
4/3 × 3.14 (Pi) × 1.5 3 = 14.13 cm 3 .
The volume of the kidney is approximated by the weight.
Thus, if the kidney weighs 200 g, the tumor-to-kidney volume ratio is 14.13/200 = 0.071.
The probability of sampling this 3 cm tumor is 75% if 10 blocks are submitted, 90% if 16 blocks are submitted, and 99.99% if 32 blocks are submitted. 17
However, in one study of morcellated kidneys, the fragments containing cancer could be grossly identified in all cases.
If a tumor was suspected by imaging, and the initial samples do not show tumor, additional tissue should be evaluated.
Procedure | Partial nephrectomy, total nephrectomy, radical nephrectomy, nephroureterectomy (partial or complete), ureterectomy |
Specimen Laterality | Right, left |
Tumor Site | RCC: Upper pole, middle, lower pole, hilum, medulla, cortex |
UCC: ureter, renal pelvis, ureter and renal pelvis, kidney | |
Tumor Size | RCC: Greatest dimension (4 cm, 7 cm, and 10 cm are used for staging), if multiple tumors, give the size of the largest tumor |
UCC: Greatest dimension (other sizes can be provided) | |
Focality | Unifocal, multifocal |
Tumor Extension | RCC: Limited to kidney, extension into perinephric tissue (beyond renal capsule), renal sinus, extension beyond Gerota’s fascia, extension into major vein (renal vein or its segmental branches, inferior vena cava), into pericalyceal system, extension into adrenal (direct invasion is classified as T4, noncontiguous involvement is classified as M1), extension into other organ(s)/structure(s) |
UCC: Into or through renal pelvis into parenchyma or invades into peripelvic fat | |
Ureter: Involvement of lamina propria, muscularis propria, periureteric soft tissue | |
Histologic Type | Clear cell (conventional) RCC, papillary RCC (types), chromophobe RCC, collecting duct carcinoma, renal medullary carcinoma, translocation carcinoma (Xp11 and others), UCC, oncocytoma, Wilms tumor, other rare types. The WHO classification is recommended. |
Sarcomatoid Features | RCC: Not identified, present (give percentage of sarcomatoid element) |
Rhabdoid Features | RCC: Not identified, present |
Tumor Necrosis | RCC: Not identified, present (give percentage of necrosis) |
Histologic Grade | WHO/International Society for Urological Pathology (ISUP) system (validated for clear cell and papillary RCC) |
Margins | Involved or not involved, renal vein, ureter, perinephric fat, renal sinus soft tissue margin, Gerota’s fascial margin, renal parenchyma (for partial nephrectomies), renal capsular margin (for partial nephrectomies) |
Lymphovascular Invasion | Not identified, present. This does not include the renal vein and its segmental branches or the inferior vena cava. Involvement of these vessels is reported separately. |
Regional Lymph Nodes | Metastases present or absent, number of involved nodes, number of nodes examined, size of largest metastasis, extracapsular invasion, size of largest involved lymph node |
Additional Pathologic Findings | Glomerular disease, tubulointerstitial disease, vascular disease, cysts, tubular (papillary) adenomas, urothelial papilloma, papillary urothelial neoplasm (low malignant potential—PUNLMP), urothelial dysplasia, cystitis cystica et glanularis, keratinizing squamous metaplasia, intestinal metaplasia |
For Wilms tumor—nephrogenic rests (intralobar or perilobar). | |
Distant Metastasis | If present. If distant metastasis is not present on pathologic examination, the M category is a clinical classification. |
AJCC Classification | T, N, and M classifications should be provided, when possible ( Tables 17.4 – 17.6 ). cM0 is conferred after clinical assessment; there is no pM0 category. |
Information needed for AJCC (8th edition) classification | ||
Group | Features | Comments |
T | Size: ≤ 4 cm, > 4 cm to ≤ 7 cm, > 7 cm to ≤ 10 cm, > 10 cm | Gross evaluation is necessary to determine the tumor size |
Extent: limited to the kidney, extends into major veins or perinephric tissues, invades the pericalyceal system, invades perirenal and/or renal sinus fat, extends into the vena cava below the diaphragm, extends into the vena cava above the diaphragm, invades the wall of the vena cava, invades beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland) | ||
N | Metastases: absent, present | |
M | Distant metastases | Usually determined clinically or with a separate biopsy of a metastatic site. |
Stage I | Tumor limited to the kidney and completely resected |
Renal capsule intact | |
Tumor not ruptured or biopsied before removal | |
No residual tumor apparent beyond margins of resection | |
Renal vein and renal sinus vessels contain no tumor (intrarenal vessel involvement may be present) | |
No lymph node involvement or distant metastasis | |
Stage II | Tumor extends beyond kidney but is completely resected |
Regional extension of tumor (vascular invasion outside the renal parenchyma or within the renal sinus, extensive renal sinus soft tissue invasion, and/or capsular penetration with negative excision margin) | |
Stage III | Nonhematogenous metastases confined to the abdomen (e.g., tumor in regional lymph nodes), including tumor implants on or penetrating the peritoneum |
Gross or microscopic tumor remains postoperatively (tumor at margins of resection) | |
Tumor spill before or during surgery not confined to flank | |
Piecemeal excision of the tumor (removal in more than one piece) | |
Operative tumor rupture | |
Tumor biopsy before surgery | |
Stage IV | Hematogenous metastases or lymph node metastases outside the abdominopelvic region (beyond renal drainage system, e.g., lung or liver) |
Stage V | Bilateral renal involvement at diagnosis (each slide should also be staged separately, according to above criteria, as I through IV) |
Information needed for AJCC (8th edition) classification | ||
Group | Features | Comments |
T | Papillary noninvasive carcinoma, carcinoma in situ, invasive carcinoma | Determined by microscopic evaluation but often evident on gross examination. |
Extent: invasion into subepithelial connective tissue, invasion into the muscularis, invasion into peripelvic fat or renal parenchyma (if in renal pelvis), invasion into periureteric fat (if in ureter), invasion into adjacent organs, invasion through the kidney into the perinephric fat | ||
N | Metastases: absent, present | |
Size: ≤ 2 cm, > 2 cm | ||
Number: single, multiple | ||
M | Distant metastases | Usually determined clinically or with a separate biopsy of a metastatic site. |
This checklist incorporates information from the CAP Cancer Committee protocols for reporting on cancer specimens (see www.cap.org/ ) as well as other resources. The specific details of reporting the elements may vary among institutions.
There is a separate CAP Cancer Protocol for the reporting of pediatric Wilms tumor (see “Cancer Protocols and Checklists” at www.cap.org ).
UCC is the most common tumor of the bladder. Other tumors at this site are rare (e.g., squamous cell carcinoma or adenocarcinoma).
In addition to age and gender, relevant clinical history is often necessary or helpful for the interpretation of specimens ( Table 17.7 ).
HISTORY RELEVANT TO ALL SPECIMENS | HISTORY RELEVANT FOR BLADDER SPECIMENS |
Organ/tissue resected or biopsied | Renal or bladder stones |
Purpose of the procedure | Recent urinary tract infections |
Gross appearance of the organ/tissue/lesion sampled | Recent urinary tract procedures |
Any unusual features of the clinical presentation | Obstruction |
Any unusual features of the gross appearance | Infections |
Prior surgery/biopsies—results | Lynch syndrome (Hereditary Non-Polyposis Colon Cancer or HNPCC syndrome)—can be associated with carcinomas of the ureter |
Prior malignancy | |
Prior treatment (radiation therapy, chemotherapy, drug use that can change the histologic appearance of tissues) | Systemic or intravesical chemotherapy, immunotherapy with BCG, or radiation |
Analgesic nephropathy, with papillary necrosis—may increase the risk of renal pelvic tumors | |
Compromised immune system |
The bladder muscularis mucosae (small bundles of smooth muscle) are poorly defined (not unlike the gallbladder!) and incomplete. Therefore, the term lamina propria is used and “submucosa” is not used. Invasion is reported as being into the lamina propria or deeper into the muscularis propria (large, thick bundles of smooth muscle)
Bladder biopsies are processed as small biopsies (see Chapter 10 ). Transurethral resections of bladder tumors (TURBT) sometimes result in specimens with grossly recognizable papillary tumors. However, the specimens generally cannot be oriented. Diathermy loop specimens are generally larger (0.6 cm) than cold-cup biopsy specimens (0.2–0.3 cm). The clinician can provide important information for interpretation by specifying if the biopsy is from the exophytic portion of the tumor, the base of the tumor, or is from adjacent mucosa. Random biopsies may also be taken.
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