BILATERAL RENAL CELL CARCINOMA WITH METASTASIS TO THYROID M'LISS A. HUDSON, M.D. LOUIS R. KAVOUSSI, M.D. WILLIAM J. CATALONA, M.D. From the Jewish Hospital, Washington University Medical Center, St. Louis, Missouri
ITRACT--A case o] bilateral synchronous renal cell carcinomas with metastases to the' regional ph nodes and later to the thyroid gland was treated with aggressive surgical extirpation and ~vant gamma inter]eron. The patient continues to have an excellent per]ormance status sixteen tths after initial diagnosis despite a large tumor burden at presentation.
al cell carcinoma is known for its unusual des of presentation, frequent association filth paraneoplastic syndromes, relative resistiiee to standard radiation and chemotherapy, ~d wide variability in its clinical course. One urd of patmnts with renal cell carcinoma ~esent with metastatic disease at the time of i~gnosls and only 10 percent of these patients ii!I survive one year, with an average survival enod of only four months.. Metastases from real cell carcinoma spread with equal fre! ~ n c y through the regional lymphatics or hei~togenously to distant sites 3 The most comii~0n sites of distant metastases for renal cell inoma include lung, liver, subcutaneous tisi ~ i and the central nervous system. Unusual ~t~ for metastatic spread of renal cell car~:+,~ tn0ma have also been reported, including the ii~h~oid gland. 4-8 +:i~Bflateral renal cell carcinomas have been reed in only 1.8-3.5 percent of renal tumors 2 ~!in~the maioritv have been associated with Von ~J~i~pel-Linclau syndrome Survival rates again !~+~++: ~ higher in patients with synchronous as opnetachronous renal tumors2 we report a case of bilateral synchro.1 cell carcinomas with documented to the lymph nodes of the porta hesubsequent metastasis to the thyroid th a multimodal approach to therapy,
l~ ~
FIGURE 1. IVU demonstrating bilateral distortion o] collecting systems. Medial ureteral deviation on right is due to lower pole mass.
/ FEBRUARY1991 / VOLUMEXXXVII,NUMBER2
145
FIGURE 2. (A) Preoperative abdominal CT scan demonstrates bilateral renal masses and retroperitonea~ adenopathy. (13) Photomicrograph of renal carcinoma consisting o] pleomorphic cells with abundant cle~i cytoplasm and moderate to severe nuclear atypia (hematoxylin and eosin reduced from x 300). (C) CT sb~ o] abdomen sixteen months after initial surgery demonstrating persistent retroperitoneal adenopathy. ( ~ Photomicrography o] thyroid metastasis histiologically identical to primary renal tumor (hematoxylin d ~ eosin reduced from x 300). our patient is active and well sixteen months after initial diagnosis. Case Report A sixty-year-old white w o m a n had a single episode of gross hematuria treated empirically with antibiotics. Four months later she was hospitalized after a syncopal episode. Her abdomen was tender to palpation, and an ultrasound of the abdomen revealed bilateral solid renal masses and retroperitoneal adenopathy. L a b o r a t o r y studies i n c l u d e d a s e r u m creatinine of 1.0 mg/dL, hematocrit of 32 percent, and urinalysis showed 2-3 red blood cells/ high-power field. Urine culture was sterile. Liver function tests and coagulation parameters were normal. An intravenous pyelogram demonstrated an 8 x 15 cm left: lower pole renal mass, a 4 x 4.5 cm right upper pole mass, and a 7 x 8 em right lower pole renal mass (Fig. 1). Computerized tomography (CT) of the abdomen confirmed these solid renal masses and a 3 × 3 cm mass believed to be adenopathy near the head of the 146
pancreas (Fig. 2A). Bone scan and CT of t head and chest were negative for metastatic d ease. Fine-needle aspiration of the left rer mass revealed clear cell renal adenocarcinom The patient was referred to our institution fl ,i an experimental t r e a t m e n t p r o g r a m Wl! gamma interferon. To enhance the prospects t a favorable response it was elected to reduce t tumor burden as much as possible by surgii excision. At laparotomy, the patient was found to ha' two right renal masses involving the upper ai lower poles, respectively, and a left lower pi'J~ renal mass. The liver and small-bowel mesc! tery appeared free of tumor. Impressive ~cf nopathy was noted in the region of the pol hepatis while the para-aortic and paraca~ nodes appeared normal. Findings on frozen sc tion biopsy of the nodes near the porta hepa! were positive for malignant cells. The patient u n d e r w e n t right lower pole partial nephrectomies an, ical nephrectomy. The adenopathy hepatis was deemed unresectable.
UROLOGY / FEBRUARY1991 / VOLUMEXXXV
t-Ier recovery was uneventful and her postoperative serum ereatinine was 1.8 mg/dL. Patho10~e examination of the specimens revealed d~ar cell renal adenoearcinoma in all three re~ tumors and the lymph node from the porta ~patis (Fig. 2B). S h e entered an experimental protocol and received intravenous infusions of gamma interferOn (1 mg/mm 2) three times per week on alternate weeks. Her retroperitoneal adenopathy has remained stable (Fig. 2C). T h i r t e e n months after her initial diagnosis the patient noted a 1.5 cm painless firm mass on : ~ left anterior aspect of her neck. Thyroid iunetion studies were within normal limits. She ~i~h3erwent a neck exploration and was found to ~i,e a solitary mass in the left lobe of the thyr0id. A left hemithyroidectomy was performed. ~thologie examination revealed metastatic re~ cell carcinoma with clear cell histology, confined to the thyroid (Fig. 2D). The patient has ;eeovered and continues to hve an active life ~thout restrictions sixteen months after her ~Nal diagnosis of renal cell carcinoma. No Other new areas of metastatic disease have devel0ped to date. Comment Renal cell carcinoma has been estimated to affect approximately 18,000 people in the U~ited States per year. 1° It usually presents in thesixth decade of life and the male to female fall0 is approximately 2:1. The classic presenta~6n includes hematuria, pain, and a flank ~Ss. Approximately one third of patients with re~al cell carcinoma present with metastases at thetime of diagnosis and in another third metaStatic disease develops after nephreetomy for ~)arently localized disease. ~ ....Bilateral renal tumors occur in about 1.8-3.5 percent of reported eases of renal cell car~n0ma. 2 The majority of bilateral renal tumors ~e associated with the Von Hippel-Lindau syndrome. Smith et al. 1' reported approximately half of these patients had synchronous bilateral ,re~al tumors and the other half had metaehroa0Us bilateral renal tumors. Whether these tu~:n~isrepresent two separate tumors arising de n0vo in the same patient or metastatic disease !r0m one renal tumor to the opposite kidney is U~nown. Unfortunately, adjuvant therapy for metatic renal cell carcinoma has been uniformly appointing' Renal tumors have proved relatively resistant to radiation therapy. 2 Single
~
~/ItOLOGY /
FEBRUARY 1991
/
agent chemotherapy and hormonal therapy both have shown low response rates of approximately 15 percent. 12 Although some encouraging results have been noted with interferon treatment, the overall response is at most 31 percent for patients with metastatic renal cell carcinoma, la Because of isolated reports of spontaneous regression of metastatic renal carcinomas and the lack of adjuvant therapy for this disease, adjuvant nephreetomies have been performed with the hope of inducing a spontaneous remission. 14 In several large series, however, the incidence of spontaneous regression after nephreetomy appears to be only about 0 . 3 - 0 . 4 percent. 12 Because the morbidity and mortality rates of nephreetomy are much higher (2-15%) than the expectation of a spontaneous remission (0.03 % ) adjuvant nephreetomy cannot be justified for all patients. H Nevertheless, some authors have attempted to identify a select group of patients with metastatic renal cell carcinoma who might benefit from an aggressive surgical approach. Maldazys and de Kernion 15 in studying 181 eases of metastatic renal carcinoma found improved survival correlated with long interval free of disease between nephreetomy and discovery of metastases, normal performance status, metastases limited to the lung parenehyma, and removal of the primary tumor. In their series, patients with lung metastases only who were free of disease for greater than six months after nephreetomy achieved a 37 percent five-year survival rate. Based on these data, they advocated nephreetomy in patients with metastatic renal cell carcinoma who had a good performance status, limited metastases, particularly if limited to the lung, who are candidates for trials of systemic adjuvant therapy. Similarly, Golimbu and associates 16 performed radical nephreetomy and excision of m e t a s t a s e s in 21 patients with metastatic renal cell carcinoma. Of their patients, 8 who had metastases at the time of diagnosis survived an average of fifty-four months with a 50 percent five-year survival. Survival in their series was influenced by interval free of disease, tumor aggressiveness, and completeness of surgical resection. Overall, patients in their series with synchronous metastases survived longer (average 54 months) than those with asynchronous metastases (average 38 months). Bilateral renal carcinoma in the past was thought to have a poor prognosis. 17 However,
VOLUME XXXVII, NUMBER 2
147
when treated with curative resection, Jacobs, Berg, and Lawson ~s found a 69 percent fiveyear survival in patients with synchronous bilateral renal tumors. Sehiff, Bagley, and Lytton ~9 noted a 77 percent survival rate in a combined series of bilateral renal tumors and tumors in solitary kidneys treated aggressively with an average 45.7-month follow-up period. Smith et al. 11 found 9 of 13 patients with bilateral synchronous renal cell carcinomas survived a mean of 25.6 months after surgical intervention, although 2 of these patients later died of metastatic disease. These authors concluded that survival rates for bilateral renal cell carcinoma treated with an aggressive surgical approach approximated those of unilateral radical nephrectomy for renal cell carcinoma in patients with a normal contralateral kidney. Although tumor metastases to the thyroid gland are relatively uncommon in clinical practice (0.07% in the Mayo Clinic series), renal cell carcinoma is the most commonly reported primary tumor to metastasize to the thyroid gland. 6 Since the first report of thyroid metastasis from a primary renal tumor in 1891 by Leva, ~° approximately 100 such cases have been described. 4-s Thyroid metastases from renal cell carcinoma may be found in association with diffusely disseminated tumor, or, more rarely, may present as a solitary metastasis many years after the initial nephrectomy. In the absence of other known sites of metastatic disease, surgical extirpation has been advocated for solitary thyroid metastases from renal cell carcinoma. 4,
ITRACT--A case o] bilateral synchronous renal cell carcinomas with metastases to the' regional ph nodes and later to the thyroid gland was treated with aggressive surgical extirpation and ~vant gamma inter]eron. The patient continues to have an excellent per]ormance status sixteen tths after initial diagnosis despite a large tumor burden at presentation.
al cell carcinoma is known for its unusual des of presentation, frequent association filth paraneoplastic syndromes, relative resistiiee to standard radiation and chemotherapy, ~d wide variability in its clinical course. One urd of patmnts with renal cell carcinoma ~esent with metastatic disease at the time of i~gnosls and only 10 percent of these patients ii!I survive one year, with an average survival enod of only four months.. Metastases from real cell carcinoma spread with equal fre! ~ n c y through the regional lymphatics or hei~togenously to distant sites 3 The most comii~0n sites of distant metastases for renal cell inoma include lung, liver, subcutaneous tisi ~ i and the central nervous system. Unusual ~t~ for metastatic spread of renal cell car~:+,~ tn0ma have also been reported, including the ii~h~oid gland. 4-8 +:i~Bflateral renal cell carcinomas have been reed in only 1.8-3.5 percent of renal tumors 2 ~!in~the maioritv have been associated with Von ~J~i~pel-Linclau syndrome Survival rates again !~+~++: ~ higher in patients with synchronous as opnetachronous renal tumors2 we report a case of bilateral synchro.1 cell carcinomas with documented to the lymph nodes of the porta hesubsequent metastasis to the thyroid th a multimodal approach to therapy,
l~ ~
FIGURE 1. IVU demonstrating bilateral distortion o] collecting systems. Medial ureteral deviation on right is due to lower pole mass.
/ FEBRUARY1991 / VOLUMEXXXVII,NUMBER2
145
FIGURE 2. (A) Preoperative abdominal CT scan demonstrates bilateral renal masses and retroperitonea~ adenopathy. (13) Photomicrograph of renal carcinoma consisting o] pleomorphic cells with abundant cle~i cytoplasm and moderate to severe nuclear atypia (hematoxylin and eosin reduced from x 300). (C) CT sb~ o] abdomen sixteen months after initial surgery demonstrating persistent retroperitoneal adenopathy. ( ~ Photomicrography o] thyroid metastasis histiologically identical to primary renal tumor (hematoxylin d ~ eosin reduced from x 300). our patient is active and well sixteen months after initial diagnosis. Case Report A sixty-year-old white w o m a n had a single episode of gross hematuria treated empirically with antibiotics. Four months later she was hospitalized after a syncopal episode. Her abdomen was tender to palpation, and an ultrasound of the abdomen revealed bilateral solid renal masses and retroperitoneal adenopathy. L a b o r a t o r y studies i n c l u d e d a s e r u m creatinine of 1.0 mg/dL, hematocrit of 32 percent, and urinalysis showed 2-3 red blood cells/ high-power field. Urine culture was sterile. Liver function tests and coagulation parameters were normal. An intravenous pyelogram demonstrated an 8 x 15 cm left: lower pole renal mass, a 4 x 4.5 cm right upper pole mass, and a 7 x 8 em right lower pole renal mass (Fig. 1). Computerized tomography (CT) of the abdomen confirmed these solid renal masses and a 3 × 3 cm mass believed to be adenopathy near the head of the 146
pancreas (Fig. 2A). Bone scan and CT of t head and chest were negative for metastatic d ease. Fine-needle aspiration of the left rer mass revealed clear cell renal adenocarcinom The patient was referred to our institution fl ,i an experimental t r e a t m e n t p r o g r a m Wl! gamma interferon. To enhance the prospects t a favorable response it was elected to reduce t tumor burden as much as possible by surgii excision. At laparotomy, the patient was found to ha' two right renal masses involving the upper ai lower poles, respectively, and a left lower pi'J~ renal mass. The liver and small-bowel mesc! tery appeared free of tumor. Impressive ~cf nopathy was noted in the region of the pol hepatis while the para-aortic and paraca~ nodes appeared normal. Findings on frozen sc tion biopsy of the nodes near the porta hepa! were positive for malignant cells. The patient u n d e r w e n t right lower pole partial nephrectomies an, ical nephrectomy. The adenopathy hepatis was deemed unresectable.
UROLOGY / FEBRUARY1991 / VOLUMEXXXV
t-Ier recovery was uneventful and her postoperative serum ereatinine was 1.8 mg/dL. Patho10~e examination of the specimens revealed d~ar cell renal adenoearcinoma in all three re~ tumors and the lymph node from the porta ~patis (Fig. 2B). S h e entered an experimental protocol and received intravenous infusions of gamma interferOn (1 mg/mm 2) three times per week on alternate weeks. Her retroperitoneal adenopathy has remained stable (Fig. 2C). T h i r t e e n months after her initial diagnosis the patient noted a 1.5 cm painless firm mass on : ~ left anterior aspect of her neck. Thyroid iunetion studies were within normal limits. She ~i~h3erwent a neck exploration and was found to ~i,e a solitary mass in the left lobe of the thyr0id. A left hemithyroidectomy was performed. ~thologie examination revealed metastatic re~ cell carcinoma with clear cell histology, confined to the thyroid (Fig. 2D). The patient has ;eeovered and continues to hve an active life ~thout restrictions sixteen months after her ~Nal diagnosis of renal cell carcinoma. No Other new areas of metastatic disease have devel0ped to date. Comment Renal cell carcinoma has been estimated to affect approximately 18,000 people in the U~ited States per year. 1° It usually presents in thesixth decade of life and the male to female fall0 is approximately 2:1. The classic presenta~6n includes hematuria, pain, and a flank ~Ss. Approximately one third of patients with re~al cell carcinoma present with metastases at thetime of diagnosis and in another third metaStatic disease develops after nephreetomy for ~)arently localized disease. ~ ....Bilateral renal tumors occur in about 1.8-3.5 percent of reported eases of renal cell car~n0ma. 2 The majority of bilateral renal tumors ~e associated with the Von Hippel-Lindau syndrome. Smith et al. 1' reported approximately half of these patients had synchronous bilateral ,re~al tumors and the other half had metaehroa0Us bilateral renal tumors. Whether these tu~:n~isrepresent two separate tumors arising de n0vo in the same patient or metastatic disease !r0m one renal tumor to the opposite kidney is U~nown. Unfortunately, adjuvant therapy for metatic renal cell carcinoma has been uniformly appointing' Renal tumors have proved relatively resistant to radiation therapy. 2 Single
~
~/ItOLOGY /
FEBRUARY 1991
/
agent chemotherapy and hormonal therapy both have shown low response rates of approximately 15 percent. 12 Although some encouraging results have been noted with interferon treatment, the overall response is at most 31 percent for patients with metastatic renal cell carcinoma, la Because of isolated reports of spontaneous regression of metastatic renal carcinomas and the lack of adjuvant therapy for this disease, adjuvant nephreetomies have been performed with the hope of inducing a spontaneous remission. 14 In several large series, however, the incidence of spontaneous regression after nephreetomy appears to be only about 0 . 3 - 0 . 4 percent. 12 Because the morbidity and mortality rates of nephreetomy are much higher (2-15%) than the expectation of a spontaneous remission (0.03 % ) adjuvant nephreetomy cannot be justified for all patients. H Nevertheless, some authors have attempted to identify a select group of patients with metastatic renal cell carcinoma who might benefit from an aggressive surgical approach. Maldazys and de Kernion 15 in studying 181 eases of metastatic renal carcinoma found improved survival correlated with long interval free of disease between nephreetomy and discovery of metastases, normal performance status, metastases limited to the lung parenehyma, and removal of the primary tumor. In their series, patients with lung metastases only who were free of disease for greater than six months after nephreetomy achieved a 37 percent five-year survival rate. Based on these data, they advocated nephreetomy in patients with metastatic renal cell carcinoma who had a good performance status, limited metastases, particularly if limited to the lung, who are candidates for trials of systemic adjuvant therapy. Similarly, Golimbu and associates 16 performed radical nephreetomy and excision of m e t a s t a s e s in 21 patients with metastatic renal cell carcinoma. Of their patients, 8 who had metastases at the time of diagnosis survived an average of fifty-four months with a 50 percent five-year survival. Survival in their series was influenced by interval free of disease, tumor aggressiveness, and completeness of surgical resection. Overall, patients in their series with synchronous metastases survived longer (average 54 months) than those with asynchronous metastases (average 38 months). Bilateral renal carcinoma in the past was thought to have a poor prognosis. 17 However,
VOLUME XXXVII, NUMBER 2
147
when treated with curative resection, Jacobs, Berg, and Lawson ~s found a 69 percent fiveyear survival in patients with synchronous bilateral renal tumors. Sehiff, Bagley, and Lytton ~9 noted a 77 percent survival rate in a combined series of bilateral renal tumors and tumors in solitary kidneys treated aggressively with an average 45.7-month follow-up period. Smith et al. 11 found 9 of 13 patients with bilateral synchronous renal cell carcinomas survived a mean of 25.6 months after surgical intervention, although 2 of these patients later died of metastatic disease. These authors concluded that survival rates for bilateral renal cell carcinoma treated with an aggressive surgical approach approximated those of unilateral radical nephrectomy for renal cell carcinoma in patients with a normal contralateral kidney. Although tumor metastases to the thyroid gland are relatively uncommon in clinical practice (0.07% in the Mayo Clinic series), renal cell carcinoma is the most commonly reported primary tumor to metastasize to the thyroid gland. 6 Since the first report of thyroid metastasis from a primary renal tumor in 1891 by Leva, ~° approximately 100 such cases have been described. 4-s Thyroid metastases from renal cell carcinoma may be found in association with diffusely disseminated tumor, or, more rarely, may present as a solitary metastasis many years after the initial nephrectomy. In the absence of other known sites of metastatic disease, surgical extirpation has been advocated for solitary thyroid metastases from renal cell carcinoma. 4,
