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Neurilemoma of the kidney
NEURILEMOMA
OF THE KIDNEY
ADAM J. SINGER, AND KARL H. ANDERS
ABSTRACT Neurilemomas are neoplasms that originate from Schwann cells of the central and peripheral nervous systems. Thirteen case reports of neurilemomas involving the kidney have been described in the English literature. We r-e port the fifth case of a neurilemoma within the renal sinus and review the previous casesof renal neurilemoma. This neoplasm is usually found incidentally. Presenting signs are nonspecific and radiographic features are highly variable. These factors make a preoperative diagnosis extremely difficult. Accurate identification relies heavily on detailed pathologic evaluation. Wide local excision is the treatment of choice, since malignancy is found in up to 30% of casesand there is a tendency for local recurrence and distant metastasis.UFxOLCGY@47: 575-58 1, 1996.
n 1910, Verocayl reported the first case of a nerve sheath tumor and called it a neurinoma. In 1932, Masson’ described a tumor that originated in Schwann cells and assigned the term “schwannoma.” Stout3 proposed the nomenclature, neurilemoma, as a compromise between these two terms in 1953. Subsequently, schwannoma, neurilemoma, solitary neurofibroma, and perineural fibroblastoma have been used interchangeably to describe neoplasms arising from the Schwann cell of the nerve sheath. Herein, the fifth case of a neurilemoma of the renal sinus is presented with a review of the English literature of the remaining 13 cases involving the kidney.4-‘6
I
CASE REPORT A 70-year-old Caucasian woman was referred for a left renal mass. A computed tomography (CT) scan was done because the serum carcinoembryonic antigen (CEA) was elevated at 7.5 ng/mL (normal, less than 3 ng/mL); it was repeated after the CT scan and was 3.0 ng/mL. She had a partial left colectomy for an incidentally found focal adenocarcinoma of the appendix, which was performed for acute appendicitis in 1983. Her other medical problems included essential hypertension, hypercholesterolemia, hypothyroidism, cholecystectomy, and Bell’s palsy of the left facial nerve with full recovery. She smoked a half pack of cigFrom the Department of Urology, and the Department of Pathology, Kaiser Permanente Medical Center, Woodland Hills, California; and the Departments of Pathology and Laboratory Medicine, University of California, Los Angeles School of Medicine, Los Angeles, California Reprint requests: Adam Singer, M.D., Department of Urology, Kaiser Permanente Medical Center, 5601 De Soto Avenue, Woodland Hills, CA 91365 Submitted: August 1, 1995, accepted (with revisions): October 24, 1995 UROLOGY@ 47 (4), 1996
arettes per day for 50 years. Her medications were verapamil 130 mg orally three times daily, clonidine 0.2 mg orally three times daily, metoprolo125 mg orally twice daily, gemfibrozil 600 mg orally every morning, levothyroxine 0.5 mg orally every morning, and potassium chloride 10 mEq orally twice daily. Physical examination was unremarkable. A complete blood count, serum electrolytes, blood urea nitrogen, creatinine, calcium, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, urinalysis, urine culture, voided urine cytologic examination, and chest x-ray film were within normal limits. Cystourethroscopy was normal. An excretory urogram showed extrinsic compression of the upper and middle infundibula of the left kidney without obstruction. An abdominal CT scan showed a 4.5 X 2.7 X 3.0-cm soft tissue mass of the left kidney with extension into the renal sinus (Fig. lA,B). The lesion was isodense (33 HU) compared with normal renal parenchyma before intravenous contrast medium and showed enhancement following the administration of contrast medium, but was hypodense (72 HU) compared with the kidney. Prior to referral, a fine needle aspiration biopsy of the mass was performed in an effort to make a tissue diagnosis. CT-guided fine needle aspiration yielded scanty, monomorphic, cohesive cells with round to oval nuclei suggestive of a neoplasm, but of insufficient cellularity for complete assessment. Magnetic resonance imaging (MRI) was done to determine if there was extension of tumor into either the renal vein or inferior vena cava, since the CT scan was indeterminate in ruling out tumor thrombi. A precontrast MRI demonstrated the mass to be slightly hypointense on T,-weighted images and slightly hyperintense on the T,weighted images (Fig. lC,D>. The mass enhanced 575
FIGURE 1. [A) Computed tomography (CT) scan [no contrast) shows a 4.5 x 2.7 x 3.0-cm (33 HU) left kidney soft tissue mass extending into the renal sinus (arrows). A simple cyst (15 HU) of the right kidney (arrowheads) is also observed. (B) CT scan (contrast) demonstrates enhancement (72 HU) of the left renal tumor (arrows). The right renal cyst shows no enhancement (arrowheads). (C) Magnetic resonance imaging [MRI; T,-weighted image) demonstrates hypointense left renal mass [arrow). Two simple cysts of right kidney are seen. (D) MRI (T,-weighted image) shows slightly hyperintense left renal tumor (arrow). Simple cysts of right kidney are present. on Tr-weighted images after the injection of gadolinium. The patient underwent a left radical nephrectomy through a left subcostal incision without postoperative complications. She is without evidence of recurrent disease at 18 months. Her serum CEA is 2.9 ng/mL. PATHOLOGICEVALUATION The nephrectomy specimen showed a 6.0-cm well-demarcated, lobulated, pale tan tumor that compressed the renal pelvis and parenchyma. His576
tologic sections showed a well-circumscribed neoplasm effacing the kidney (Fig. 2A). Two distinct cellular patterns, Antoni A and Antoni B, were present. The Antoni A pattern predominated and consisted of cellular regions of interlacing fascicles of oval to spindle cells in a hyalinized stroma (Fig. 2B). Tumor nuclei were mostly uniform and showed wavy contours with focal palisading (Verocay) bodies. Focal atypia and hyperchromasia were also demonstrated (Fig. 2C), but mitotic figures were not identified. This atypia, without mitosis, was thought to represent degenerative rather uR0LocY~ 47 (41,1996
FIGURE 2. (A) Intermediate magnification shows a cellular spindle cell neoplasm [left) with a well-demarcated, noninfiltrative border. It compresses the renal medulla and exhibits intense immunoreactivity for S- 100 protein. (S100 protein peroxidase-antiperoxidase, x 100.) [BJ Antoni A pattern demonstrates nuclei that are round to oval, often wavy, and focally clustered to form Verocay bodies (arrows). (hematoxylin-eosin, x400.) (C) Antoni A pattern containing focal areas with atypical nuclei (arrows) that are significantly enlarged and hyperchromatic. Cellular atypia in neurilemoma is not indicative of malignant behavior in the absence of mitotic figures, an infiltrative border, or metastasis. (hematoxylin-eosin, x400.) [D) Antoni B pattern is far less cellular and orderly, with spindle and oval cells appearing randomly arranged in a loose myxoid stroma. (hematoxylin-eosin, x400.) UROLOGYe 47 (41, 1996
577
TABLE
I.
Neurilemoma
involving
the kidney:
review
of the literature
Age/Sex
Tumor Location Right renal capsule
Presentation Microhematuria
Surgery Right radical nephrectomy
51/F
Right renal pelvis
Right nephrectomy
45/F
Left renal pelvis
51/F
Left renal hilum
Recurrent pyelonephritis, right flank tenderness, palpable mass, and pyuria without hematuria Nonfunctioning right kidney (UPJ obstruction from tuberculosis). Left solitary kidney, bilateral CVA tenderness: normal urinalysis Microhematuria
21/M
Right renal pelvis
Gross hematuria following kick to right flank
51/M
Left renal hilum
Upper abdominal pain, fever, acute epididymitis. Normal urinalysis
Right nephrectomy, transurethral resection of incidental bladder tumor Excision of mass
67/M
Right kidney and right renal pelvis Right renal capsule
Epigastric
Asymptomatic
50/F
Left kidney with invasion into the lung and diaphragm
Left upper abdominal discomfort x3 mos. Loss of appetite, 1O-pound weight loss, anemia, and nontender mass
56/M
Left renal hilum
52/M
Right renal capsule. Metastasis to bone, liver, colon, mesentery, and retroperitoneum
Fever and chills x5 yrs. Left flank pain and mass, 45-pound weight loss x2 yrs, anemia, normal urinalysis Flank pain, fever, mass, anemia, leukocytosis
55/F
Left kidney
50/F
Right renal hilum
70/F
Left renal hilum
74/F
KEY: IVTJ = intravenous inferior vena am.
ur”gram.
UPJ = ureteropelvic
Left nephrectomy
Right radical nephrectomy
pain for 2 weeks mass
Excision of mass
Routine IVU for evaluation of uterine myoma; normal urinalysis Palpable mass, microhematuria
CT scan for elevated carcinoembryonic and history of adenocarcinoma of the appendix; normal urinalysis junction,
CVA = costovertebral
than malignant change. In contrast, the rare foci of Antoni B pattern were characterized by low cellularity and myxoid stroma (Fig. 2D). Sections of the renal pelvis and surgical margins were benign. Immunohistochemical stains were performed using a peroxidase-antiperoxidase technique with antisera specific for vimentin, S-100 protein, and muscle-specific actin (MSA). The tumor cells showed intense diffuse cytoplasmic positivity with both vimentin and S-100 protein antisera (Fig. 2A), but staining was not observed with MSA. This 578
Left partial nephrectomy
angle,
CT = computed
Left radical nephrectomy. Wide local excision with partial resection of lung and diaphragm. Regional lymphadenectomy Left nephrectomy
Right radical nephrectomy with regional lymphadenectomy
Left radical nephrectomy Excision of mass
antigen
tomography,
Left radical nephrectomy
MR, = magnetic
resonance
imaging,
IVC =
staining pattern, coupled with the histopathologic features, are diagnostic of renal neurilemoma. COMMENT Neurilemomas are neurogenic tumors that arise from Schwann cells of the nerve sheath. They are common to large nerves of the peripheral and central nervous systems (acoustic neuromas), but rarely involve the kidney Including the present report, only 14 evaluable casescan be found in the English literature, of which 5 originated in the UROLOGY’
47 (4), 1996
TABLE
1.
Neurilemoma
Pathology Malignant
Status Alive at 5 mos
Malignant
Alive
Benign
Alive
involving
the kidney:
review
of the literature
(continued)
Radiographic Findings IVU: lower pole renal mass. Arteriogram: neovascular tumor IVU: Kidney displacement, pyetectasis and calicectasis
Ref.# 4 5
IVU: Nonfunctioning right kidney. Left inferior-medial mass pressing on calices and ureter.
6
Arteriogram: neovasculartumor Not specified
Not specified
Alive at 1 year
IVU: extrinsic compression left pelvo-caliceal system. CT: tumor of left renal pelvis sinus. Arteriogram: avascular tumor IVU: mass within right renal pelvis. Ultrasound; 3-cm isoechoic mass protruding into renal pelvis and incidental bladder tumor IVU: extrinsic compression of pelvis with hydronephrosis. Ultrasound: hypoechoic mass arising from renal hilum. Arteriogram: avascular tumor with displaced vessels. MRI: T,-isointense; T,-high signal intensity IVU: suspicious for carcinoma. Ultrasound: renal enlargement
Not specified
Not specified
Not specified
Not specified
Benign
10
Benign
Not specified
IVU: right renal mass. Arteriogram:
11
Malignant tumor: regional lymphnodes negative
Died at 15 mos with metastases
CT: left renal mass with invasion into diaphragm. enhancement without central enhancement
Benign
Not specified
IVU: hilar mass with renal displacement
13
Malignant: regional lymph nodes negative
Died at 3 mos with metastases
14
Not specified
Alive at 18 mos
IVU: mass upper pole mass with caudal displacement. Ultrasound: hypoechoic mass. CT: cystic necrotic renal tumor with colon and liver metastasis. Barium enema: colon metastasis. Cavogram: deformed IVC without invasion. Arteriogram: avascular mass IVU: upper pole mass. Arteriogram: avascular mass
Benign
Not specified
16
Benign
Alive at 18 mos
IVU: right lower pole mass with displaced kidney. Ultrasound: complex mass. CT: cystic, necrotic hemorrhagic mass. Arteriogram: hypovascular mass IVU: extrinsic compression of upper and middle infundibuli. CT: enhancing mass of renal sinus. MRI: T,-hypointense; T,-hyperintense
KEY: IVU = intravmous
ur~gram,
UPJ = ureteropelvic
junction,
CVA = costovert&d
angle,
CT = computed
separated
t~mog@y,
stretched
vessels
Peripheral
hfm = mopetic
12
15
Present case
TcSonanCe imaging,
IVC =
inferiorwnacava.
renal sinus (Table I).4-16 Six were in men and 8 were in women. Patients ranged in age from 21 to 74 years. Tumors were equally distributed between left and right. These neoplasms arose from the kidney capsule in 3,4,11,14renal sinus in 5,7,9,13,15 renal pelvis in 3,5,6,8renal parenchyma in 2,12J5 and both the kidney and pelvis in 1 patientlo In retrospect, neurilemomas were usually found incidentally and the presenting clinical information was generally not helpful. For example, neurilemomas were discovered during the evaluation of recurrent pyeloUR~LCGY~47 (41,19%
nephritis5 following ureteropelvic junction obstruction from tuberculosis in a solitary functioning kidney,6 on the investigation of gross hematuria following a kick to the flank,8 during the workup of epididymitis9 on the evaluation of nonspecific epigastric pain, l”,12 fever and chills,13J4 and by routine urography for a uterine myoma.15 In our experience, it was discovered as an incidental finding on a CT scan. With respect to the classic triad of pain, palpable mass, and hematuria found in renal neoplasms, pain was noted in 85,6,a-10,12-14; a 579
palpable mass was identified in 6,5,11-14nj and hematuria was seen in 4 patients.4,7sJ6 In the present case, the initial serum CEA was elevated. This was considered a false-positive value, since it was normal 2 weeks following the CT scan and prior to surgery It remained relatively unchanged 18 months following surgery Serum CEA, therefore, does not appear to be a valuable tumor marker in this disorder. The radiographic findings of renal neurilemomas were highly variable. Excretory urography showed space-occupying lesions causing distortion of the normal anatomy Tumors were isoechoic,8J0 hypoechoic,g necrotic,14 and complex cysti on ultrasonography. CTs showed enhancing and nonenhancing lesions, with or without necrosis. 14,16 Arteriography was done in 8 cases and showed neovascularity in 2,4,6 avascularity in 1,' displacement or stretching of surrounding vessels in 2,g,11 and hypovascularity in 4.10,14-16 MRIs were described in one previous report.g Isointensity on T,- and high signal intensity on T,weighted images were observed. Conversely, hypointensity on T, and slight hyperintensity on T, images were found in the present case. We suggest that this difference may be related to the variable cellular and vascular composition of these tumors. In light of these findings, an unequivocal diagnosis of neurilemoma cannot be made solely on a clinical basis without tissue. Unfortunately, we did not find fine needle aspiration to be definitive. Neurilemomas have unique pathologic features. They are slow growing encapsulated tumors that are usually solitary and characterized by varying quantities of Antoni A and Antoni B cellular patterns. Gross inspection reveals a tan to yellow-gray cut surface. Areas of hemorrhage and cystic degeneration may be found, especially if the tumor is large. The Antoni A pattern consists of cellular regions of interlacing fascicles with oval to spindle cells in a hyalinized stroma. Antoni B pattern is characterized by areas of low cellular density and myxoid stroma. Although most neurilemomas do not show significant nuclear atypia, some may demonstrate nuclear enlargement, hyperchromasia, and multinucleation. These nuclear changes may suggest malignancy, but neurilemomas rarely degenerate into a malignant neoplasm. In the absence of mitosis, an infiltrative border, or evidence of metastatic disease, a diagnosis of malignant neurilemoma should not be rendered.17 We suspect that 2 of 4 previously reported cases of malignant schwannoma of the kidney may represent degenerative neurilemomas rather than malignancies.4v5 The current nomenclature for neurilemomas is confusing. Most pathologists use the terms neurilemoma or schwannoma interchangeably The presence of encapsulation, bimorphic Antoni A and An580
toni B histologies, and the uniformly intense immunostaining for the S-100 protein are diagnostic of neurilemoma. This constellation of features distinguishes it from neurofibroma and other spindle cell neoplasms, such as leiomyomas, leiomyosarcomas, malignant fibrous histiocytomas, and spindle cell renal cell carcinoma. l8 Our case is the fourth renal neurilemoma to document this intense S-100 immunopositivity (Fig. 2A) .g,10,12 Benign neurilemomas can be eradicated by complete surgical excision. Wide excision is also recommended for malignant neurilemomas, since they respond poorly to irradiation and chemotherapy The 5-year survival of malignant retroperitoneal neurilemomas ranges from 47% to 66% in those without distant metastasis.12 Recurrences have been observed from 10 to 15 years following surgical remission.12 The 2-year survival is 5% in the presence of metastasis.12 Distant metastasis is uncommon, but usually occurs hematogenously rather than by the lymphatic system. This is supported on review of the 2 cases of unequivocal malignant renal neurilemomas depicted in Table I.12,14 Both cases demonstrated bulky renal tumors, local and distant metastasis, but negative regional lymph nodes. Surgical treatment for the previously reported cases was radical nephrectomy in 5,4JoJ2J4J5 nephrectomy in 4,5,7*8J3 partial nephrectomy in 1,6 and tumor excision in 3.g211916Four were reportedly malignant,4*5~12~14 5 were benign,6J0J1J3J6 but the histopathology was not stated in 4. The status and duration of follow-up were available in 7 of 13 patients Five were alive4-‘,15 and 2 died of metastasis in 3 and 15 months.12J4 Our patient is alive and without evidence of recurrent disease at 18 months. In conclusion, clinicians should be cognizant that the clinical presentation of neurilemomas involving the kidney, although rare, is highly variable and likely to be a serendipitous finding. Radiographic studies cannot reliably differentiate neurilemomas from other renal neoplasms, which makes the correct preoperative diagnosis difficult. In addition, the sensitivity and specificity of percutaneous aspiration and cutting needle biopsy are still unknown. Although ours was the only case wherein needle aspiration had been performed, we found it nondiagnostic and of limited utility due to the inadequate cellular yield. Furthermore, distinguishing malignant and benign neurilemomas on a limited sample is highly problematic. The treatment of choice for neurilemoma involving the kidney is wide local excision. REFERENCES 1. Verocay J: Zur Kenntnis der “Neurofibrome.” Beitr Path Allg Path 48: 1, 1910. 2. Masson P: Experimental and spontaneous schwannomas. Am J Path01 8: 367, 1932.
uRoLoGYm 47 (4), 1996
3. Stout AP: The peripheral manifestations of the specific nerve sheath tumor (neurilemmoma). Am J Cancer 24: 751, 1953. 4. Bair ED, Woodside JR, Williams WL, and Borden TA: Perirenal malignant schwannoma presenting as renal cell carcinoma. Urology 11: 510-512, 1978. 5. Fein RL, and Hamm FC: Malignant schwannoma of the renal pelvis: a review of the literature and a case report. J Urol 94: 356, 1965. 6. Freund ME, Cracker DW, and Harrison JH: Neurofibroma arising in a solitary kidney. J Uro198: 318-321, 1967. 7. Inoue Y, Nakamura H, Yamaguchi S, Yamazaki K, and Osafune M: Benign non-parenchymal renal tumors: radiological appearances. Clin Imaging 15: 113-117, 1991. 8. Le Cheong L, Khan AN, and Bisset RA: Sonographic features of a renal pelvic neurofibroma. J Clin Ultrasound 18: 129-131, 1990. 9. Kitagawa K, Yamahana T, Hirano S, Kawaguchi S, Mikawa I, Masuda S, and Kadoya M: MR imaging of neurilemoma arising from the renal hilus. J Comput Assist Tomogr 14:830-832,199O.
10. Ma KF, Tse CH, and Tsui MS: Neurilemmoma of kidney-a rare occurrence. Histopathology 17: 378-380, 1990.
UROLOGYfi 47 (41, 1996
11. Myerson D, Rosenfield AT, and Itzchak Y: Renal capsular tumors: the angiographic features. J Urol 121: 238-241, 1979. 12. Naslund MJ, Dement S, and Marshall FF: Malignant renal schwannoma. Urology 38: 477-479, 1991. 13. Phillips CA, and Baumrucker G: Neurilemmoma (arising in the hilus of left kidney). J Urol 73: 671-673, 1955. 14. Romics I, Bach D, and Beutler W: Malignant schwannoma of kidney capsule. Urology 40: 453-455, 1992. 15. Somers WJ, Terpenning B, Lowe FC, and Romas NA: Renal parenchymal neurilemoma: a rare and unusual kidney tumor. J Urol 139: 109-110, 1988. 16. Steers WD, Hodge GB, Johnson DE, Chaitin BA, and Charnsangavej C: Benign retroperitoneal neurilemoma without Von Recklinghausen’s disease: a rare occurrence. J Urol 133: 8466848, 1985. 17. Harkin JC, and Reed RJ: Solitary benign nerve sheath tumors, in: Tumors of the Peripheral Nervous System, Washington, Armed Forces Institute of Pathology (Fascicle), 1968 (2nd series), pp 29-51. 18. Enzinger FM, and Weiss SW: Benign tumors of peripheral nerves, in: Soft Tissue Tumors, 3rd ed. St. Louis, Mosby-Year Book, 1995, pp 829-842.
581
OF THE KIDNEY
ADAM J. SINGER, AND KARL H. ANDERS
ABSTRACT Neurilemomas are neoplasms that originate from Schwann cells of the central and peripheral nervous systems. Thirteen case reports of neurilemomas involving the kidney have been described in the English literature. We r-e port the fifth case of a neurilemoma within the renal sinus and review the previous casesof renal neurilemoma. This neoplasm is usually found incidentally. Presenting signs are nonspecific and radiographic features are highly variable. These factors make a preoperative diagnosis extremely difficult. Accurate identification relies heavily on detailed pathologic evaluation. Wide local excision is the treatment of choice, since malignancy is found in up to 30% of casesand there is a tendency for local recurrence and distant metastasis.UFxOLCGY@47: 575-58 1, 1996.
n 1910, Verocayl reported the first case of a nerve sheath tumor and called it a neurinoma. In 1932, Masson’ described a tumor that originated in Schwann cells and assigned the term “schwannoma.” Stout3 proposed the nomenclature, neurilemoma, as a compromise between these two terms in 1953. Subsequently, schwannoma, neurilemoma, solitary neurofibroma, and perineural fibroblastoma have been used interchangeably to describe neoplasms arising from the Schwann cell of the nerve sheath. Herein, the fifth case of a neurilemoma of the renal sinus is presented with a review of the English literature of the remaining 13 cases involving the kidney.4-‘6
I
CASE REPORT A 70-year-old Caucasian woman was referred for a left renal mass. A computed tomography (CT) scan was done because the serum carcinoembryonic antigen (CEA) was elevated at 7.5 ng/mL (normal, less than 3 ng/mL); it was repeated after the CT scan and was 3.0 ng/mL. She had a partial left colectomy for an incidentally found focal adenocarcinoma of the appendix, which was performed for acute appendicitis in 1983. Her other medical problems included essential hypertension, hypercholesterolemia, hypothyroidism, cholecystectomy, and Bell’s palsy of the left facial nerve with full recovery. She smoked a half pack of cigFrom the Department of Urology, and the Department of Pathology, Kaiser Permanente Medical Center, Woodland Hills, California; and the Departments of Pathology and Laboratory Medicine, University of California, Los Angeles School of Medicine, Los Angeles, California Reprint requests: Adam Singer, M.D., Department of Urology, Kaiser Permanente Medical Center, 5601 De Soto Avenue, Woodland Hills, CA 91365 Submitted: August 1, 1995, accepted (with revisions): October 24, 1995 UROLOGY@ 47 (4), 1996
arettes per day for 50 years. Her medications were verapamil 130 mg orally three times daily, clonidine 0.2 mg orally three times daily, metoprolo125 mg orally twice daily, gemfibrozil 600 mg orally every morning, levothyroxine 0.5 mg orally every morning, and potassium chloride 10 mEq orally twice daily. Physical examination was unremarkable. A complete blood count, serum electrolytes, blood urea nitrogen, creatinine, calcium, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, urinalysis, urine culture, voided urine cytologic examination, and chest x-ray film were within normal limits. Cystourethroscopy was normal. An excretory urogram showed extrinsic compression of the upper and middle infundibula of the left kidney without obstruction. An abdominal CT scan showed a 4.5 X 2.7 X 3.0-cm soft tissue mass of the left kidney with extension into the renal sinus (Fig. lA,B). The lesion was isodense (33 HU) compared with normal renal parenchyma before intravenous contrast medium and showed enhancement following the administration of contrast medium, but was hypodense (72 HU) compared with the kidney. Prior to referral, a fine needle aspiration biopsy of the mass was performed in an effort to make a tissue diagnosis. CT-guided fine needle aspiration yielded scanty, monomorphic, cohesive cells with round to oval nuclei suggestive of a neoplasm, but of insufficient cellularity for complete assessment. Magnetic resonance imaging (MRI) was done to determine if there was extension of tumor into either the renal vein or inferior vena cava, since the CT scan was indeterminate in ruling out tumor thrombi. A precontrast MRI demonstrated the mass to be slightly hypointense on T,-weighted images and slightly hyperintense on the T,weighted images (Fig. lC,D>. The mass enhanced 575
FIGURE 1. [A) Computed tomography (CT) scan [no contrast) shows a 4.5 x 2.7 x 3.0-cm (33 HU) left kidney soft tissue mass extending into the renal sinus (arrows). A simple cyst (15 HU) of the right kidney (arrowheads) is also observed. (B) CT scan (contrast) demonstrates enhancement (72 HU) of the left renal tumor (arrows). The right renal cyst shows no enhancement (arrowheads). (C) Magnetic resonance imaging [MRI; T,-weighted image) demonstrates hypointense left renal mass [arrow). Two simple cysts of right kidney are seen. (D) MRI (T,-weighted image) shows slightly hyperintense left renal tumor (arrow). Simple cysts of right kidney are present. on Tr-weighted images after the injection of gadolinium. The patient underwent a left radical nephrectomy through a left subcostal incision without postoperative complications. She is without evidence of recurrent disease at 18 months. Her serum CEA is 2.9 ng/mL. PATHOLOGICEVALUATION The nephrectomy specimen showed a 6.0-cm well-demarcated, lobulated, pale tan tumor that compressed the renal pelvis and parenchyma. His576
tologic sections showed a well-circumscribed neoplasm effacing the kidney (Fig. 2A). Two distinct cellular patterns, Antoni A and Antoni B, were present. The Antoni A pattern predominated and consisted of cellular regions of interlacing fascicles of oval to spindle cells in a hyalinized stroma (Fig. 2B). Tumor nuclei were mostly uniform and showed wavy contours with focal palisading (Verocay) bodies. Focal atypia and hyperchromasia were also demonstrated (Fig. 2C), but mitotic figures were not identified. This atypia, without mitosis, was thought to represent degenerative rather uR0LocY~ 47 (41,1996
FIGURE 2. (A) Intermediate magnification shows a cellular spindle cell neoplasm [left) with a well-demarcated, noninfiltrative border. It compresses the renal medulla and exhibits intense immunoreactivity for S- 100 protein. (S100 protein peroxidase-antiperoxidase, x 100.) [BJ Antoni A pattern demonstrates nuclei that are round to oval, often wavy, and focally clustered to form Verocay bodies (arrows). (hematoxylin-eosin, x400.) (C) Antoni A pattern containing focal areas with atypical nuclei (arrows) that are significantly enlarged and hyperchromatic. Cellular atypia in neurilemoma is not indicative of malignant behavior in the absence of mitotic figures, an infiltrative border, or metastasis. (hematoxylin-eosin, x400.) [D) Antoni B pattern is far less cellular and orderly, with spindle and oval cells appearing randomly arranged in a loose myxoid stroma. (hematoxylin-eosin, x400.) UROLOGYe 47 (41, 1996
577
TABLE
I.
Neurilemoma
involving
the kidney:
review
of the literature
Age/Sex
Tumor Location Right renal capsule
Presentation Microhematuria
Surgery Right radical nephrectomy
51/F
Right renal pelvis
Right nephrectomy
45/F
Left renal pelvis
51/F
Left renal hilum
Recurrent pyelonephritis, right flank tenderness, palpable mass, and pyuria without hematuria Nonfunctioning right kidney (UPJ obstruction from tuberculosis). Left solitary kidney, bilateral CVA tenderness: normal urinalysis Microhematuria
21/M
Right renal pelvis
Gross hematuria following kick to right flank
51/M
Left renal hilum
Upper abdominal pain, fever, acute epididymitis. Normal urinalysis
Right nephrectomy, transurethral resection of incidental bladder tumor Excision of mass
67/M
Right kidney and right renal pelvis Right renal capsule
Epigastric
Asymptomatic
50/F
Left kidney with invasion into the lung and diaphragm
Left upper abdominal discomfort x3 mos. Loss of appetite, 1O-pound weight loss, anemia, and nontender mass
56/M
Left renal hilum
52/M
Right renal capsule. Metastasis to bone, liver, colon, mesentery, and retroperitoneum
Fever and chills x5 yrs. Left flank pain and mass, 45-pound weight loss x2 yrs, anemia, normal urinalysis Flank pain, fever, mass, anemia, leukocytosis
55/F
Left kidney
50/F
Right renal hilum
70/F
Left renal hilum
74/F
KEY: IVTJ = intravenous inferior vena am.
ur”gram.
UPJ = ureteropelvic
Left nephrectomy
Right radical nephrectomy
pain for 2 weeks mass
Excision of mass
Routine IVU for evaluation of uterine myoma; normal urinalysis Palpable mass, microhematuria
CT scan for elevated carcinoembryonic and history of adenocarcinoma of the appendix; normal urinalysis junction,
CVA = costovertebral
than malignant change. In contrast, the rare foci of Antoni B pattern were characterized by low cellularity and myxoid stroma (Fig. 2D). Sections of the renal pelvis and surgical margins were benign. Immunohistochemical stains were performed using a peroxidase-antiperoxidase technique with antisera specific for vimentin, S-100 protein, and muscle-specific actin (MSA). The tumor cells showed intense diffuse cytoplasmic positivity with both vimentin and S-100 protein antisera (Fig. 2A), but staining was not observed with MSA. This 578
Left partial nephrectomy
angle,
CT = computed
Left radical nephrectomy. Wide local excision with partial resection of lung and diaphragm. Regional lymphadenectomy Left nephrectomy
Right radical nephrectomy with regional lymphadenectomy
Left radical nephrectomy Excision of mass
antigen
tomography,
Left radical nephrectomy
MR, = magnetic
resonance
imaging,
IVC =
staining pattern, coupled with the histopathologic features, are diagnostic of renal neurilemoma. COMMENT Neurilemomas are neurogenic tumors that arise from Schwann cells of the nerve sheath. They are common to large nerves of the peripheral and central nervous systems (acoustic neuromas), but rarely involve the kidney Including the present report, only 14 evaluable casescan be found in the English literature, of which 5 originated in the UROLOGY’
47 (4), 1996
TABLE
1.
Neurilemoma
Pathology Malignant
Status Alive at 5 mos
Malignant
Alive
Benign
Alive
involving
the kidney:
review
of the literature
(continued)
Radiographic Findings IVU: lower pole renal mass. Arteriogram: neovascular tumor IVU: Kidney displacement, pyetectasis and calicectasis
Ref.# 4 5
IVU: Nonfunctioning right kidney. Left inferior-medial mass pressing on calices and ureter.
6
Arteriogram: neovasculartumor Not specified
Not specified
Alive at 1 year
IVU: extrinsic compression left pelvo-caliceal system. CT: tumor of left renal pelvis sinus. Arteriogram: avascular tumor IVU: mass within right renal pelvis. Ultrasound; 3-cm isoechoic mass protruding into renal pelvis and incidental bladder tumor IVU: extrinsic compression of pelvis with hydronephrosis. Ultrasound: hypoechoic mass arising from renal hilum. Arteriogram: avascular tumor with displaced vessels. MRI: T,-isointense; T,-high signal intensity IVU: suspicious for carcinoma. Ultrasound: renal enlargement
Not specified
Not specified
Not specified
Not specified
Benign
10
Benign
Not specified
IVU: right renal mass. Arteriogram:
11
Malignant tumor: regional lymphnodes negative
Died at 15 mos with metastases
CT: left renal mass with invasion into diaphragm. enhancement without central enhancement
Benign
Not specified
IVU: hilar mass with renal displacement
13
Malignant: regional lymph nodes negative
Died at 3 mos with metastases
14
Not specified
Alive at 18 mos
IVU: mass upper pole mass with caudal displacement. Ultrasound: hypoechoic mass. CT: cystic necrotic renal tumor with colon and liver metastasis. Barium enema: colon metastasis. Cavogram: deformed IVC without invasion. Arteriogram: avascular mass IVU: upper pole mass. Arteriogram: avascular mass
Benign
Not specified
16
Benign
Alive at 18 mos
IVU: right lower pole mass with displaced kidney. Ultrasound: complex mass. CT: cystic, necrotic hemorrhagic mass. Arteriogram: hypovascular mass IVU: extrinsic compression of upper and middle infundibuli. CT: enhancing mass of renal sinus. MRI: T,-hypointense; T,-hyperintense
KEY: IVU = intravmous
ur~gram,
UPJ = ureteropelvic
junction,
CVA = costovert&d
angle,
CT = computed
separated
t~mog@y,
stretched
vessels
Peripheral
hfm = mopetic
12
15
Present case
TcSonanCe imaging,
IVC =
inferiorwnacava.
renal sinus (Table I).4-16 Six were in men and 8 were in women. Patients ranged in age from 21 to 74 years. Tumors were equally distributed between left and right. These neoplasms arose from the kidney capsule in 3,4,11,14renal sinus in 5,7,9,13,15 renal pelvis in 3,5,6,8renal parenchyma in 2,12J5 and both the kidney and pelvis in 1 patientlo In retrospect, neurilemomas were usually found incidentally and the presenting clinical information was generally not helpful. For example, neurilemomas were discovered during the evaluation of recurrent pyeloUR~LCGY~47 (41,19%
nephritis5 following ureteropelvic junction obstruction from tuberculosis in a solitary functioning kidney,6 on the investigation of gross hematuria following a kick to the flank,8 during the workup of epididymitis9 on the evaluation of nonspecific epigastric pain, l”,12 fever and chills,13J4 and by routine urography for a uterine myoma.15 In our experience, it was discovered as an incidental finding on a CT scan. With respect to the classic triad of pain, palpable mass, and hematuria found in renal neoplasms, pain was noted in 85,6,a-10,12-14; a 579
palpable mass was identified in 6,5,11-14nj and hematuria was seen in 4 patients.4,7sJ6 In the present case, the initial serum CEA was elevated. This was considered a false-positive value, since it was normal 2 weeks following the CT scan and prior to surgery It remained relatively unchanged 18 months following surgery Serum CEA, therefore, does not appear to be a valuable tumor marker in this disorder. The radiographic findings of renal neurilemomas were highly variable. Excretory urography showed space-occupying lesions causing distortion of the normal anatomy Tumors were isoechoic,8J0 hypoechoic,g necrotic,14 and complex cysti on ultrasonography. CTs showed enhancing and nonenhancing lesions, with or without necrosis. 14,16 Arteriography was done in 8 cases and showed neovascularity in 2,4,6 avascularity in 1,' displacement or stretching of surrounding vessels in 2,g,11 and hypovascularity in 4.10,14-16 MRIs were described in one previous report.g Isointensity on T,- and high signal intensity on T,weighted images were observed. Conversely, hypointensity on T, and slight hyperintensity on T, images were found in the present case. We suggest that this difference may be related to the variable cellular and vascular composition of these tumors. In light of these findings, an unequivocal diagnosis of neurilemoma cannot be made solely on a clinical basis without tissue. Unfortunately, we did not find fine needle aspiration to be definitive. Neurilemomas have unique pathologic features. They are slow growing encapsulated tumors that are usually solitary and characterized by varying quantities of Antoni A and Antoni B cellular patterns. Gross inspection reveals a tan to yellow-gray cut surface. Areas of hemorrhage and cystic degeneration may be found, especially if the tumor is large. The Antoni A pattern consists of cellular regions of interlacing fascicles with oval to spindle cells in a hyalinized stroma. Antoni B pattern is characterized by areas of low cellular density and myxoid stroma. Although most neurilemomas do not show significant nuclear atypia, some may demonstrate nuclear enlargement, hyperchromasia, and multinucleation. These nuclear changes may suggest malignancy, but neurilemomas rarely degenerate into a malignant neoplasm. In the absence of mitosis, an infiltrative border, or evidence of metastatic disease, a diagnosis of malignant neurilemoma should not be rendered.17 We suspect that 2 of 4 previously reported cases of malignant schwannoma of the kidney may represent degenerative neurilemomas rather than malignancies.4v5 The current nomenclature for neurilemomas is confusing. Most pathologists use the terms neurilemoma or schwannoma interchangeably The presence of encapsulation, bimorphic Antoni A and An580
toni B histologies, and the uniformly intense immunostaining for the S-100 protein are diagnostic of neurilemoma. This constellation of features distinguishes it from neurofibroma and other spindle cell neoplasms, such as leiomyomas, leiomyosarcomas, malignant fibrous histiocytomas, and spindle cell renal cell carcinoma. l8 Our case is the fourth renal neurilemoma to document this intense S-100 immunopositivity (Fig. 2A) .g,10,12 Benign neurilemomas can be eradicated by complete surgical excision. Wide excision is also recommended for malignant neurilemomas, since they respond poorly to irradiation and chemotherapy The 5-year survival of malignant retroperitoneal neurilemomas ranges from 47% to 66% in those without distant metastasis.12 Recurrences have been observed from 10 to 15 years following surgical remission.12 The 2-year survival is 5% in the presence of metastasis.12 Distant metastasis is uncommon, but usually occurs hematogenously rather than by the lymphatic system. This is supported on review of the 2 cases of unequivocal malignant renal neurilemomas depicted in Table I.12,14 Both cases demonstrated bulky renal tumors, local and distant metastasis, but negative regional lymph nodes. Surgical treatment for the previously reported cases was radical nephrectomy in 5,4JoJ2J4J5 nephrectomy in 4,5,7*8J3 partial nephrectomy in 1,6 and tumor excision in 3.g211916Four were reportedly malignant,4*5~12~14 5 were benign,6J0J1J3J6 but the histopathology was not stated in 4. The status and duration of follow-up were available in 7 of 13 patients Five were alive4-‘,15 and 2 died of metastasis in 3 and 15 months.12J4 Our patient is alive and without evidence of recurrent disease at 18 months. In conclusion, clinicians should be cognizant that the clinical presentation of neurilemomas involving the kidney, although rare, is highly variable and likely to be a serendipitous finding. Radiographic studies cannot reliably differentiate neurilemomas from other renal neoplasms, which makes the correct preoperative diagnosis difficult. In addition, the sensitivity and specificity of percutaneous aspiration and cutting needle biopsy are still unknown. Although ours was the only case wherein needle aspiration had been performed, we found it nondiagnostic and of limited utility due to the inadequate cellular yield. Furthermore, distinguishing malignant and benign neurilemomas on a limited sample is highly problematic. The treatment of choice for neurilemoma involving the kidney is wide local excision. REFERENCES 1. Verocay J: Zur Kenntnis der “Neurofibrome.” Beitr Path Allg Path 48: 1, 1910. 2. Masson P: Experimental and spontaneous schwannomas. Am J Path01 8: 367, 1932.
uRoLoGYm 47 (4), 1996
3. Stout AP: The peripheral manifestations of the specific nerve sheath tumor (neurilemmoma). Am J Cancer 24: 751, 1953. 4. Bair ED, Woodside JR, Williams WL, and Borden TA: Perirenal malignant schwannoma presenting as renal cell carcinoma. Urology 11: 510-512, 1978. 5. Fein RL, and Hamm FC: Malignant schwannoma of the renal pelvis: a review of the literature and a case report. J Urol 94: 356, 1965. 6. Freund ME, Cracker DW, and Harrison JH: Neurofibroma arising in a solitary kidney. J Uro198: 318-321, 1967. 7. Inoue Y, Nakamura H, Yamaguchi S, Yamazaki K, and Osafune M: Benign non-parenchymal renal tumors: radiological appearances. Clin Imaging 15: 113-117, 1991. 8. Le Cheong L, Khan AN, and Bisset RA: Sonographic features of a renal pelvic neurofibroma. J Clin Ultrasound 18: 129-131, 1990. 9. Kitagawa K, Yamahana T, Hirano S, Kawaguchi S, Mikawa I, Masuda S, and Kadoya M: MR imaging of neurilemoma arising from the renal hilus. J Comput Assist Tomogr 14:830-832,199O.
10. Ma KF, Tse CH, and Tsui MS: Neurilemmoma of kidney-a rare occurrence. Histopathology 17: 378-380, 1990.
UROLOGYfi 47 (41, 1996
11. Myerson D, Rosenfield AT, and Itzchak Y: Renal capsular tumors: the angiographic features. J Urol 121: 238-241, 1979. 12. Naslund MJ, Dement S, and Marshall FF: Malignant renal schwannoma. Urology 38: 477-479, 1991. 13. Phillips CA, and Baumrucker G: Neurilemmoma (arising in the hilus of left kidney). J Urol 73: 671-673, 1955. 14. Romics I, Bach D, and Beutler W: Malignant schwannoma of kidney capsule. Urology 40: 453-455, 1992. 15. Somers WJ, Terpenning B, Lowe FC, and Romas NA: Renal parenchymal neurilemoma: a rare and unusual kidney tumor. J Urol 139: 109-110, 1988. 16. Steers WD, Hodge GB, Johnson DE, Chaitin BA, and Charnsangavej C: Benign retroperitoneal neurilemoma without Von Recklinghausen’s disease: a rare occurrence. J Urol 133: 8466848, 1985. 17. Harkin JC, and Reed RJ: Solitary benign nerve sheath tumors, in: Tumors of the Peripheral Nervous System, Washington, Armed Forces Institute of Pathology (Fascicle), 1968 (2nd series), pp 29-51. 18. Enzinger FM, and Weiss SW: Benign tumors of peripheral nerves, in: Soft Tissue Tumors, 3rd ed. St. Louis, Mosby-Year Book, 1995, pp 829-842.
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