Large renal masses in young adults

LARGE RENAL MASSES IN YOUNG ADULTS GERALD H. JORDAN, M.D. DAVID S. HARTMAN, M.D. LEOPOLD

E. LADAGA, M.D.

PAUL F. SCHELLHAMMER,

M.D.

From the Department of Urology, Portsmouth Naval Hospital, and Departments of Radiologic Pathology, Urology, and Pathology, Eastern Virginia Medical School, Norfolk, Virginia

Case Presentation

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GERALD H. JORDAN,M.D.*: The first patient, a twenty-eight-year-old white male, presented with acute onset abdominal pain on the right side. He complained of anorexia without nausea or vomiting. He admitted to a similar episode six months earlier. An annual physical examination shortly after the first episode found him in good health, and all of his screening laboratory test results were normal. His past medical history was otherwise negative. Physical examination revealed mild tenderness over the entire right side of the abdomen. He was seen by the general surgery service and was admitted to the hospital with a diagnosis of “rule out appendicitis.” He had a slight anemia and leukocytoses. His LDH was not available at the time of his admission but subsequently was found to be elevated. An examiner after admission questioned the diagnosis of appendicitis. An intravenous pyelogram was ordered. Radiologic findings The plain film demDAVID S. HARTMAN,M.D.t: onstrates a large mass on the right which distorts the kidney and psoas (Fig. 1A). The mass is somewhat inhomogenous but appears to contain a lucent area which could be indicative of fat. Radiologic difThe opinions or assertions herein are the private views of the authors and are not to be construed as official or as reflecting the view of the Department of the Navy or the Department of Defense. *Department of Urology, Portsmouth Naval Hospital, and Assistant Professor of Urology, Eastern Virginia Medical School. tchairman, Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, D.C.

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ferential diagnosis of a fatty abdominal mass includes liposarcoma, angiomyolipoma, lipoma, teratoma, and adrenal myelolipoma. Rarely, children with Wilms tumor will demonstrate intratumoral fat. The angiomyolipoma and well-differentiated liposarcoma represent the 2 most common large fatty abdominal masses. Lipomas are rare and usually are homogenously lucent. Extragonadal teratoma usually is seen in young children and is uncommon in this age group. Myelolipoma is an uncommon adrenal tumor comprised of fat and myeloid elements and may be inhomogenous but rarely will be this large. Excretory urography is helpful in defining the relationship of the mass to the kidney. The urogram demonstrates that the mass is inseparable from the kidney and is a renal cell carcinoma until proved otherwise (Fig. 2A). A renal sonogram confirms that the mass is solid and intrarenal (Fig. 3A). Although the tumor echogenicity is mixed, there is a discrete hypoechoic area near the base of the mass which may be indicative of necrosis, hemorrhage, an intratumoral cystic space, or an aneurysm. To this point, malignancy cannot be excluded. Computed tomography is helpful in confirming the presence of fat, recognizing any complications of the tumor, determining the relationship of the tumor to the Gerota fascia, and evaluating lymph nodes and vascular structures for tumor spread (Fig. 4A-D) . The unenhanced scan demonstrates discrete low-density areas ( - 68 HU) within the tumor indicative of fat. There are also areas within the tumor that are denser than unenhanced normal renal parenchyma which correspond to foci of relatively acute intratumoral hemorrhage. The most common

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FIGURE 1. Plain films of renal mases (A) Case 1, and (B) Case 2.

FIGURE 2. Intravenous urograms of renal mases (A) Case 1, and (B) Case 2.

fat-containing renal mass in an adult is the angiomyolipoma. Rarely, a liposarcoma arising within the perinephric space may invade the kidney and result in similar radiographic findings. Liposarcomas usually are seen in older patients and are uncommon in this age group.

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Angiography may be helpful in differentiating these two tumors, since most liposarcomas are hypovascular and most angiomyolipomas are hypervascular and contain macroaneurysms (Fig. 5A). Angiography in this case demonstrates an intrarenal neoplasm with a large aneurysm. These findings are

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FIGURE 3. Ultrasonograms of renal masses (A) Case 1, and (B) Case 2.

most suggestive for a renal angiomyolipoma containing a large aneurysm and complicated by intratumoral hemorrhage. DR. JORDAN: We were comfortable with the preoperative diagnosis of angiomyolipoma and planned our surgery with the goal of saving the kidney. Exploration through a right thoracoabdominal incision showed an upper pole renal mass which exhibited mostly extraparenchymal growth. An upper pole partial nephrectomy was performed which included the mass. Dr. Ladaga will discuss the histologic findings. Pathologic findings

FIGURE4. Computed tomograms (A-D) Case 1, and (E-H) Case 2.

*Assistant Professor, Department nia Medical School.

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of renal masses

of Pathology, Eastern Virgi-

LEOPOLD E. LADAGA, M.D.*: We have a tumor which is composed mostly of fatty tissues. A large area of hemorrhage and a cystic area also are appreciated. Microscopically, we see a classic angiomyolipoma. There are areas of fatty tissue, smooth muscle, and blood vessels; hence, the name angiomyolipoma. The fat tissue is composed of normal fat cells. The cellular area, if there is one, is composed of myoblasts. Abnormal blood vessels usually are numerous and have a thick fibrous wall which lacks the normal elastic lamina. This feature accounts for the presentation of spontaneous hemorrhage seen with this tumor. Often, the smooth muscle tissue surrounds the blood vessels, and these cells can be pleomorphic in appearance. The tumor has been confused in the past with a malignant neoplasm, but malignant angiomyolipomas are rare, if they exist at all. The tumor is considered by some to be a hamartomatous lesion. Others, however, emphasize that normally fatty tissue does not exist in the renal parenchyma. The association with other hamartomatous lesions in the lung, pancreas, spleen, and lymph nodes has been confused as metastasis. These lesions represent multiple lesions rather than metastasis. Again, the diagnosis is angiomyolipoma.

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FI GURE 5. Angi0gram.s of Tenal masses (A) Case 1, and (‘B) Case 2.

Case Presentation

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The next patient, a twenty-sixDR. JORDAN: year-old white female, presented at another institution complaining of recurrent right abdominal and flank pain of six months’ duration. There were episodes when she was free of symptoms interspersed with episodes of acute flank pain. Her diagnosis at that institution was recurrent acute pyelonephritis. She had polio as a child which accounts for the bony asymmetric findings that you will see on the radiologic studies. Six months after her initial presentation, she was referred to us. She was noted to be slightly anemic, her urinalysis revealed microhematuria and minimal pyuria, and her urine culture was negative. She presented with an IVP which had been performed at the other institution. Radiologic findings DR. HARTMAN: The plain film of the abdomen demonstrates pelvic asymmetry due to polio and several punctate calcifications adjacent to the right psoas muscle (Fig. 1B). The excretory urogram shows that these calcifications are within a lower pole intrarenal mass (Fig. 2B). The mass is lobulated, although it is roughly spherical. The sonogram confirms that the mass is intrarenal and clearly shows that it is solid (Fig. 3B). Unenhanced and enhanced CT scans reveal a large heterogeneous, calcified mass without a central scar (Fig. 4 E-H). Although areas within the tumor have low density (OHU), no clear areas of fat are appreciated. No adenopathy or tumor thrombus is identified. The angiogram demonstrates a moderately vascular lower pole mass which contains a large aneurysm (Fig. 5B). The radiologic differential diagnosis of a solid, calcified, vascular tumor in a twenty-eight-year-old

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woman is extensive and includes renal cell carcinoma, angiomyolipoma, and oncocytoma. Renal cell carcinoma is the most common tumor with these findings and is the diagnosis which must be excluded. Rarely, the fatty component of an angiomyolipoma will be sparse or obliterated by intratumoral hemorrhage and not be detected on CT. Although aneurysms are seen frequently with angiomyolipoma, this finding by itself is nonspecific. Angiomyolipomas without demonstrable fat cannot be confidently diagnosed by radiologic criteria alone. The renal adenoma with oncocytic features (oncocytoma) is an uncommon benign tumor originating from tubular epithelium. Radiologic findings suggestive of this tumor include: the presence of a central scar in an otherwise homogenous tumor, a “spokewheel” arterial supply, and a homogenous tumor blush. While this tumor could be an oncocytoma, the diagnosis cannot be strongly considered based only on its radiographic features. The juxtaglomerular tumor is a rare, benign neoplasm of the juxtaglomerular cells. While the radiographic findings are nonspecific, patients have a very typical clinical presentation: hypertension with hyperreninism. These clinical features were not present in this patient; therefore, a juxtaglomerular tumor should not be considered. Metastasis to the kidney, benign and malignant mesenchymal tumors of the kidney, and Wilms tumor are other uncommon solid renal masses which may have findings similar to those in this patient. While they must be considered in our differential diagnosis, a specific radiographic diagnosis is not possible. The diagnosis of angiomyolipoma DR. JORDAN: was considered. The patient was the correct age. The mass was of relatively low density, in the zero

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Houndsfield unit range. The angiogram certainly lacks some of the “characteristics” of a renal cell carcinoma, and it was suggested that parenchymalsparing surgery could be performed on this patient. However, as Dr. Hartman has pointed out, the unequivocal presence of fat needed for the real preoperative diagnosis of angiomyolipoma was not present. A radical nephrectomy was performed. The mass occupied virtually the entire kidney A few interesting gross features were noted. The mass did not have the characteristic yellow color of an angiomyolipoma. The diagnosis of oncocytoma was suggested because the mass had a stellate central scar; however, the characteristic mahogany color was not present. The classic gross features of a renal adenocarcinoma were not present. There was very little hemorrhage. Most renal cell carcinomas do not have a central area of scarring. Dr. Ladaga will discuss the microscopic findings. Pathologic findings DR. LADAGA: The most obvious gross feature is the large central scar which is seen in the center of oncocytomas, especially large ones. Under low power, one notes a (monotonous) pattern of cells with very eosinophilic cytoplasm and relatively large nuclei. Renal cell carcinomas usually are composed of two types of cells: clear cells and dark cells. The next field shows dark cells compatible with a renal cell carcinoma. These cells demonstrate many features of oncocytes. True oncocytes, however, have abundant eosinophilic cytoplasm with small regular nuclei. The nuclei in this tumor are large, and the cells are pleomorphic. In a true oncocytoma, the cells are more uniform and the cytoplasm more abundant. The cells’ borders are sharply demarcated and often suggest a tubular pattern. Another field of the tumor removed from this patient is examined. Cells with more clear cytoplasm and pleomorphic nuclei are seen. These are the clear cells of renal cell carcinoma. The diagnosis is renal cell carcinoma with areas of oncocytic features.

Discussion of Cases DR. JORDAN: Let us discuss why these two particular cases were presented together. It appears that one case is a clear-cut angiomyolipoma, and the second case certainly appears to be a relatively clearcut renal cell carcinoma until we compare the radiographs of each case side-by-side. In all of the comparisons, the angiomyolipoma is on the left side and the renal cell carcinoma on the right side. What can we expect a KUB film to tell us (Fig. 1, Table I)? A mass effect is certainly not a specific finding.

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Calcification is again nonspecific. One can have calcification in both tumors. A suggestion of radiolucency in the area of the renal unit is a hard call to make at best. Is it bowel gas? Is it retroperitoneal air? There is nothing on the KUB film that allows for a confident decision to be made for performing parenchymal-sparing surgery. Let us move on to the urograms. There is no difference between these two urograms (Fig. 2). What can we expect from the urogram (Table I)? A mass effect again is nonspecific. Displacement of the collecting system is also nonspecific. Occasionally, one sees nonfunction of the renal unit in renal cell carcinoma, but there can be areas of diminished uptake within the angiomyolipoma and, again, nonfunction of that unit. Occasional renal pelvis filling defects also are nonspecific. There is nothing evident on this urogram for one to be able to make a diagnosis of angiomyolipoma. One characteristic of angiomyolipoma on the sonogram is that of a highly echogenic mass (Table I). In fact, the renal cell carcinoma in this case was more echogenic than the classic angiomyolipoma (Fig. 3). What does the ultrasound tell us? Again, there is absolutely nothing specific from the ultrasound study which allows for a confident preoperative diagnosis. The angiograms in these cases are confusing because of the large macro-aneurysms on both studies (Fig. 5). What can the angiogram tell us (Table I)? The potential for information is abundant, but again all findings are nonspecific. Whatever one sees in an angiomyolipoma one sees in renal cell carcinoma. If present, one feature on the angiogram can be helpful. Angiomyolipoma does not usually contain arteriovenous malformations, and usually there is no evidence of early venous filling. These features are more characteristic of renal cell carcinoma. Both patients underwent surgery and both surgical procedures were correct for each respective clinical situation. All of the studies presented thus far were suggestive but not diagnostic. The CT scan allowed for a confident preoperative diagnosis in the first case but caused confusion in the second case. First, let us discuss the concept of CT averaging since this caused the confusion in the case of the renal cell carcinoma. The low density was explained as being caused by CT averaging. The CT scan presents 0.5-l.O-cm thick section through the tumor. That section is then examined by the CT computer. It either looks at the density that occupies the complete section or, if that section happens to be in an area of differing densities, it will average the two densities. As demonstrated, sections of completely

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TABLE

Radiographic

I.

Radiograph

features of angiomyolipoma

Renal Cell Carcinoma

Angiomyolipoma

KUB

IVP

Ultrasonography

Angiography

~1srenal cell carcinoma

Mass Calcifications rare Suggestion of radiolucency in renal unit Mass, irregular outline Displaced collecting system Areas of diminished uptake of contrast medium Occasional nonfunction of unit Rare renal pelvis filling defect Mass, solid Frequently highly echogenic Calcifications rare Usually hypervascular Irreg./dist. vessels with puddling of contrast medium Can be hypovascular Classic “berry-like” macroaneurysms Blood supply, mostly renal artery Can have parasitic vessels

Mass Calcifications

lo-15 %

Mass, irregular outline Displaced collecting system

Occasional nonfunction of unit Occasional renal pelvis filling Mass, usually solid Variable echogenicity Calcifications lo-15 % Usually hypervascular Irreg./dist. vessels with puddling of contrast medium Can be hypovascular Can be micro/macroaneurysms Blood supply, mostly renal artery Frequently has parasitic Vessels

“Increased” blush with epinephrine; can have renal vein/caval tumor thrombus Often prolonged arterial phase with no A/V malformations Mass, usually well-defined/ heterogeneous Does not enhance normally Calcifications rare Can show nodal involvement Can show tumor involvement of liver and/or spleen Shows areas of fat density *

CT

“Increased” blush with epineprhine; often has renal vein/caval tumor thrombus Often early venous filling with A/V malformations Mass, usually well-defined/ heterogeneous Does not enhance normally Calcifications 10-15 % Can show nodal involvement Can show visceral metastases Can have low-density areas

‘No reported case of renal cell carcinoma with fat or fat density.

different composition can appear virtually the same on CT scan (Fig. 6). One cannot plan therapy for a patient when there is a suspicion of angiomyolipoma based on the assumption of CT averaging. As shown by the second case (Fig. 4B), that approach could lead to surgery which is not in the best interest of the patient. The CT scan can be confusing in other areas (Table I). The findings of enlarged hilar nodes, thrombosis in the renal vein or inferior vena cava, and tumor in the spleen are all compatible with renal cell carcinoma or angiomyolipoma. There is, however, one finding that is absolutely specific to angiomyolipoma and that is the clear demonstration of areas of fat density.

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Angiomyolipoma is not an easy diagnosis to make. It cannot be diagnosed 100 per cent of the time as the literature suggests. It is a diagnosis which, if one sees fat on the CT scan, allows renal parenchymasparing surgery. If that feature is absent, the diagnosis is malignancy until proved otherwise. Summary PAUL E SCHELLHAMMER, M.D.*: The clinical, radiologic, and pathologic correlations have been discussed clearly and in great detail. I would like to ask a question of Dr. Hartman with regard to the central *Professor, Department School.

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of Urology, Eastern Virginia Medical

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CT averaging: density measurements on CT scan represent average of densities of tissues represented in “CT slice.” Zjdensity of tissues is constant throughout slice (slices 1, 2, and S), then CT density will be accurate measurement of tissue density. Zj density of tissue varies throughout slice (slices 3 and 4), then CT density will be average of actual tissue densities. FICURE~.

scar that one may see on the CT scan. Is this a sign that requires contrast enhancement for identification? While the central scar has been described on gross inspection of oncocytoma, I was not aware that it actually could be identified on CT scan. Is this a common feature of oncocytoma on CT scan? DR. HARTMAN: Some recent work shows that oncocytomas often demonstrate a stellate scar on CT scan. It can be seen on either unenhanced or enhanced CTs, and usually the scar does not enhance as much as the parenchyma and is quite obvious. Differentiating the scar from an area of necrosis is difficult. Oncocytomas usually do not have areas of necrosis. An area of necrosis is often circular, whereas the scar is oftentimes linear and stellate. DR. SCHELLHAMMER: I wish to make some comments with regard to the evolving changes in renal mass evaluation. Certainly the CT scanner has revolutionized the urologist’s approach to the renal mass just as the arteriogram did when it was first introduced in the 1950s. The distinct advantage of CT scanning is its unique ability to measure tissue densities, thereby making possible in some cases a histologic diagnosis prior to pathologic histologic examination. We are all familiar with the attenuation values expressed clinically as Houndsfield numbers. These range as follows: - 500 for air; - 50 for fat; 0 for fluid; 15-25 for parenchymal organs; and + 500 for calcification or bone. In addition to the attenua-

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tion values obtained on the nonenhanced scan, the attenuation value after contrast injections (enhancement) further characterizes a mass in a parenchymal organ. The vascular extent of a mass is demonstrated by an increase in Houndsfield numbers between 20 and 30 units above baseline after contrast injection. With this information, I will review the possibilities in diagnosis of a renal mass containing fat as demonstrated by Houndsfield numbers in the - 50 to - 60 range. Such a mass may be an angiomyolipoma, a liposarcoma, an atypical Wilms tumor, or, rarely, a teratoma. As noted previously, renal cell carcinoma never contains fat and, therefore, never records negative Houndsfield numbers. This may seem inconsistent since the histologic appearance of the clear renal adenocarcinoma cell is characterized by a central nucleus surrounded by a large amount of relatively clear cytoplasm. We might ask why such a clear cell tumor does not register negative Houndsfield numbers when the fat cell, also with a central or peripheral nucleus and clear cytoplasm, registers a negative number? In spite of its clear appearance, the “clear cell” of renal cell carcinoma does contain abundant cytoplasmic material which generates a positive rather than a negative number. A pure lipogenic or lipomatous liposarcoma will be associated with negative Houndsfield numbers. A myxomatous liposarcoma, however, may have positive Houndsfield numbers for much the same reason that a renal cell carcinoma has positive numbers, namely an abundance of intercytoplasmic material. Thus, some liposarcomas cannot be diagnosed definitively by CT scan. The negative Houndsfield lipomatous or lipogenic liposarcoma is differentiated from the angiomyolipoma in that it is an avascular or hypovascular lesion with negligible enhancement on the CT scan. This finding aids in distinguishing it from the hypervascular and enhancing angiomyolipoma. Atypical Wilms tumor may have areas of fat and present difficulty in differential diagnosis. The Wilms tumor may have epithelial, endothelial, and mesenchymal elements associated with it. Most Wilms tumors do have some element of fat, but it is minimal and not often noted on CT scan. However, occasionally a Wilms tumor (thus far only in children) may have a rather large compartment of fat which will register negative Houndsfield numbers. In differentiating this entity from an angiomyolipoma, it is important to note that this latter entity is rare in the pediatric age group unless it is associated with tuberous sclerosis. Thberous sclerosis syndrome is readily identified by the association with other features, namely central nervous system lesions, dermatologic lesions, and retinal lesions. In

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FIGURE7.

Follow-up intravenous urogram of Case

1. the absence of tuberous sclerosis, a fat-containing mass in the child should be considered an atypical Wilms carcinoma. Renal teratoma is rare. Dr. Jordan has discussed the preservation of renal parenchyma, if possible, when the definitive diagnosis of angiomyolipoma is made. Angiomyolipoma is a benign lesion, although histologic examination may demonstrate invasion of vessels, invasion of renal vein and vena cava, involvement of nodes, and angiomyolipoma in extrarenal sites (i.e., the spleen or liver). These findings do not represent

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metastases but represent a multifocal origin of the process. Follow-up IVP in Case 1 reveals a virtually normal right kidney and is a good demonstration of the exophytic growth of the angiomyolipoma (Fig. 7). In the past, angiomyolipoma has been treated with nephrectomy because of the misconception that angiomyolipoma was a malignant neoplasm. Most, if not all of the cases of malignant angiomyolipoma, were truly misdiagnoses representative of a multifocal process. Many large lesions also were treated with adjuvant radiotherapy if the size of the mass made resection difficult. Now that a preoperative diagnosis of angiomyolipoma is made with confidence, a partial nephrectomy often can be performed. There is also a case at this institution that was treated by infarction of a feeding vessel to an angiomyolipoma. Some might ask, “why treat these benign lesions at all? Many of them become huge without causing any symptoms.” According to Mostofi and other series, 25 to 50 per cent of these tumors can present with life-threatening hemorrhage. This case did not present in shock, but angiomyolipomas may bleed and cause shock. Since 40 per cent of people with angiomyolipoma have the tuberous sclerosis complex, all such patients are investigated for the stigmata suggestive of tuberous sclerosis. The problem of the tuberous sclerosis patient who may have multiple bilateral angiomyolipomas must be considered differently. In the patient with tuberous sclerosis, one should not operate unless forced to do so by a potentially life-threatening situation. These patients are watched very closely; and should surgical intervention become necessary, every effort is directed to preservation of renal parenchyma. Clinical

and Anatomic Diagnoses

Case 1. Angiomyolipoma. Case 2. Renal cell carcinoma cocytic features.

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with areas of on-

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