RENAL LEIOMYOSARCOMA: PLEA FOR AGGRESSIVE THERAPY

RODNEY DAVIS, M.D. JOHN A. VACCARO, M.D. GEORGE E HODGES, M.D. WILLIAM D. BELVILLE, M.D. VICTOR KIESLING, JR., M.D.

From the Departments of Surgery (Urology Service) and Pathology, Madigan Army Medical Center, Tacoma, Washington

ABSTRACT- We report a case of renal leiomyosarcoma arising from the renal pelvis with immunohistochemical confirmation of the diagnosis. Treatment was extirpative surgery for both primary and metastatic lung lesions as well as adjunctive radiation and chemotherapy. This patient remains disease-free twelve months following treatment.

Sarcomas of the kidney account for only 3 per- cent of all renal tumors, the most common be- ing leiomyosarcoma. l-l1 Other renal sarcomas such as liposarcoma, rhabdomyosarcoma, he- mangiosarcoma, and malignant fibrous his- tiocytoma are rare. 1,11,12 Herein we present a typical case and review current diagnostic and therapeutic concepts to include the use of im- munohistochemistry for definitive diagnosis.

Case Report

A forty-one-year-old white man presented with a two-week history of intermittent gross hematuria, crampy lower abdominal pain, and dysuria. There was no history of urolithiasis or trauma, and he denied weight loss. Physical ex- amination was unremarkable except for mild right lower quadrant tenderness. Urinalysis showed red blood cells too numerous to count, and complete blood cell count (CBC) disclosed mild normocytic normochromic anemia.

Excretory urography and retrograde pyelog- raphy showed high-grade obstruction of the ureteropelvic junction by an inferior pole renal mass. A thickened right renal pelvis and a solid

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflect- ing the views of the Department of the Army or of the Depart- ment of Defense.

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FIGURES. Solid right renal pelvis mass with hydro- nephrosk

hilar mass were demonstrated by computed to- mography (CT) (Fig. 1). Chest x-ray film and liver function tests were negative.

A right radical nephrectomy was performed disclosing a well-circumscribed, 6.5 x 4 x 35 cm white-tan nodular mass arising from the re- nal pelvis. There was no gross evidence of renal parenchyma involvement (Fig. 2). The histo- pathologic examination of the tumor disclosed a spindle cell malignancy showing two patterns of growth. While the majority of the tumor was dedifferentiated, resembling malignant fibrous

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FICURE~. Bisected nephrectomy specimen demon- strating large, well-delineated tumor arising from the renal pelvis (original magnijication x 120).

histiocytoma (Fig. 3A), there were broad in- terlacing fascicles of spindle cells with elon- gated nuclei more suggestive of leiomyosar- coma (Fig. 3B). Large regions of the tumor in the undifferentiated areas were necrotic, and occasional large bizarre cells and multinu- cleated cells were present. The mitotic index was high, ranging from 6 to 38 per 10 high- power fields. The tumor was contiguous with the smooth muscle around the renal pelvis and the renal vein. There was no microscopic evi- dence of renal parenchymal involvement. The resection margins were free of tumor.

Immunohistochemical stains including anti- bodies to vimentin and two muscle markers, muscle-specific actin and desmin, were strongly positive. Cytokeratin antibody stains were neg- ative. Electron microscopy disclosed anaplastic cells with no differentiated features. The diagnosis of leiomyosarcoma was confirmed by the Armed Forces Institute of Pathology, Geni- tourinary Branch.

FIGURE 3. Microscopic sections demonstrate high degree of pleomorphism and biphasic pattern of growth exhibited by tumors. (A) Less-dijjerentiated areas demonstrated highly anaplastic spindled cells and numerous multinucleated giant ceils, and (B) other areas consisted of densely cellular spindled cells in jascicular growth pattern suggestive of leiomyosarcoma (original magnijications x 120).

The patient’s convalescence was uneventful, and he received radiation (5,000 rad) to the right renal bed. Three months later, chest x-ray film disclosed a 7 x g-mm mass in the left lung. A left thoracotomy and wedge resection con- firmed the presence of metastatic leiomyosar- coma. At this time he was treated with five courses of cyclophosphamide (Cytoxan) and doxorubicin hydrochloride (Adriamycin), 1,400 mg and 70 mg per course, respectively. He has remained without evidence of disease twelve months after chemotherapy.

Comment Ninety-four cases of leiomyosarcoma of the

kidney have been reported since Berry2 described the first case in 1919. Renal leiomy- osarcomas have a very poor prognosis with most patients dead within two years.Q,lo There are, however, isolated survivals of three, six, and six- teen years. 1.5 The majority of these tumors oc- cur between the fifth and eighth decades. The

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right kidney is involved twice as often as the left, and there is a slightly greater frequency in females (1.4:l). 3,6,8 Approximately 7 percent of tumors are bilateral9

Renal leiomyosarcomas may arise from the renal capsule or from the smooth muscle fibers of the renal pelvis or vasculature.r3J4 They may be encapsulated or nonencapsulated, and they may invade the adjacent tissue.

The presenting symptom in more than half of all cases is flank pain. Other symptoms in de- creasing order of frequency include hematuria, flank mass, weight loss, and gastrointestinal disturbances.

Excretory urography may demonstrate a mass effect in the area of the collecting system or distortion of the renal outline. Ultrasound or CT usually reveals a solid lesion. Angiography commonly shows a hypervascular lesion with a nonspecific pattern. ‘s8 Local recurrences are frequent, and metastases can occur in the lung, bone, liver, and mesentery. 3*9~10~13

Renal leiomyosarcoma may be confused with sarcomatoid renal cell carcinoma since both contain large numbers of spindle cells.12 The use of immunohistochemical staining for in- termediate filaments is valuable in these cases to differentiate the two entities. Negative stain- ing with antibodies to cytokeratins and positive staining with antibodies to desmin and muscle- specific actin indicate a mesenchymal neoplasm of muscle origin. 15-18 Vimentin antibody stain- ing is not particularly helpful since it may be positive in both sarcomas and sarcomatoid re- nal cell carcinomas.1g Electron microscopy also can be helpful in distinguishing between these two neoplasms, but was noncontributory in this case because of the undifferentiated nature of the area sampled.eO

The primary treatment of renal leiomyosar- coma historically has been surgery with or without adjunctive radiation or chemotherapy. Of the 21 cases treated with surgery alone as reported by Tolia, Hajdu, and Whitmore only 5 were alive twelve months or longer. They also reported treating 1 patient unsuccessfully with adjunctive 5 fluorouracil (5-FU) following nephrectomy. Crabtree reported excision of multiple abdominal recurrences with pro- longed survival lasting five years.

Helmbrecht and Cosgrove’ described the use of adjunctive radiation and chemotherapy in 2 patients. One received preoperative radiation plus additional postoperative radiation and doxorubicin with cyclophosphamide for local

bone recurrence. The second patient received radiation (5,000 rad) and actinomycin postop- eratively before refusing additional chemother- apy. Both of these individuals were alive at thirty and twelve months.

Beccia, Elkort, and Kraneg used adjunctive chemotherapy consisting of actinomycin D, cy- clophosphamide, and vincristine following sur- gery. Their patient was alive and tumor-free af- ter forty-eight months.

Rakowsky et aLlo reported a patient whose tumor recurrence thirteen months following nephrectomy showed a partial response to dox- orubicin, cyclophosphamide, vincristine, and dacarbazine. That remission lasted eight months and the patient succumbed to an ab- dominal tumor recurrence.

In summary, renal leiomyosarcomas are ag- gressive neoplasms with a very poor prognosis. Immunohistochemical staining for intermedi- ate filaments must be used to differentiate this disease process from sarcomatoid renal cell car- cinoma. The paucity of reported cases makes the therapeutic decision process very difficult. This review suggests that adjunctive radiation and chemotherapy produce better survival than surgery alone. Most reports utilized approxi- mately 5,000 rad adjunctive radiotherapy to contain local disease. The most effective chemotherapeutic agents are doxorubicin or ac- tinomycin D in combination with cyclophos- phamide and vincristine. There seems to be a place for excision of local tumor recurrences, and this case report also hints that there may be a place for excision of distal metastases in this disease process.

Urology Service Madigan Army Medical Center

Tacoma, Washington 984315302 (DR. VACCARO)

ACKNOWLEDGMENT. To Dr. Allan Gown, University of Washington, Seattle, for immunohistochemical analysis, and Dr. I. Sesterhenn, Armed Forces Institute of Pathol- ogy, Genitourinary Branch, for the consultative opinion.

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