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Sarcomatoid Renal Carcinoma
0022-534 7/83/1304-0657$02.00/0 Vol. 130, October
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1983 by The Williams & Wilkins Co.
SARCOMATOID RENAL CARCINOMA KEVIN M. TOMERA, GEORGE M. FARROW
AND
MICHAEL M. LIEBER*
From the Departments of Urology and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Sarcomatoid renal carcinoma made up 1 per cent of renal parenchymal tumors resected from 1967 to 1980. The majority of patients with this aggressive type of renal carcinoma were symptomatic and had a palpable renal mass at the time of diagnosis. Only 2 of 13 patients had tumor confined within the renal capsule at the time of operation. One of these patients survived and 12 of 13 died rapidly of metastatic renal carcinoma, with a median survival of 6.3 months from the time of diagnosis. This distinctive histologic variant of renal carcinoma has a highly malignant biological behavior and, as effective adjuvant treatment for renal carcinoma becomes available, should be one of the tumor types treated vigorously. In 1968 Farrow and associates described 37 cases of a unique renal mixed malignancy that they called sarcomatoid renal carcinoma. 1 This tumor consists of renal cell carcinoma associated intimately with a more pleomorphic spindle cell or giant cell malignancy resembling sarcoma in which foci of transition between carcinoma cells to pleomorphic sarcomatoid cells usually can be demonstrated. We herein report the clinical, pathological and survival features of patients who underwent resection of sarcomatoid renal cell carcinoma between 1967 and 1980. MATERIALS AND METHODS
We reviewed the histologic diagnoses of all renal tumors resected between 1967 and 1980. Cases in the pathologic tissue registry with a description containing spindle-like, sarcomatoid, sarcomatous, high grade or grade IV renal carcinoma were identified, and received detailed clinical and pathologic review. From among 1,303 cases of renal carcinoma resected during this period 39 were so identified in the tissue registry. Since our study pathologist (G. M. F.) has had long-standing interest in renal sarcomas and sarcomatoid tumors it is believed that few renal tumors containing sarcomatous elements would not be identified as such in our institutional tissue registry. Of these 39 tumors current histologic review by the study pathologist identified 13 cases that fit strict criteria for sarcomatoid renal carcinoma. The histologic appearance of these mixed, bimorphic tumors depends on the area examined. Histologic examination of the area of adult renal carcinoma reveals the usual granular cell, clear cell or mixed pattern of varying cellular differentiation that has been well described previously. Examination of the sarcomatoid element reveals a more pleomorphic neoplasm composed predominantly of spindle fibrogenic cells, often with bizarre and multinucleated forms. Although there is some overlap of features among the cases the 13 tumors fell into 2 groups based on resemblance of the sarcomatoid element to recognized categories of true sarcoma. The most common group (11 tumors) showed a predominance of spindle or fibroblastic cells arranged in a whorled or storiform pattern with variable amounts of fibrous stroma (fig. 1). Many of these tumors also featured bizarre multinucleated giant neoplastic cells. These histologic features are indistinguishable by light microscopy from a distinctive type of soft tissue sarcoma called malignant fibrous histiocytoma. 2 •3 Because of the large bizarre neoplastic
cells, which at one time were believed to represent neoplastic muscle cells, many cases of malignant fibrous histiocytoma were classified in the past as pleomorphic rhabdomyosarcoma. The 2 remaining renal tumors displayed a monomorphic spindled fibrogenic component similar to fibrosarcoma. RESULTS
A total of 13 patients with renal tumors showing a typical pattern of sarcomatoid renal carcinoma underwent resection between 1967 and 1980 (13 of 1,303 or 1 per cent of all renal tumors resected). There were 11 men and 2 women in this group. Patient age ranged from 34 to 78 years, with a median age of 56 years (fig. 2). Seven tumors occurred in the right kidney and 6 in the left kidney. There were no instances of bilateral tumors. The majority of patients had symptoms related to the renal tumor: two-thirds had either flank pain or gross hematuria, 7 (54 per cent) had a palpable mass and 2 (15 per cent) reported preoperative fever. Seven patients (54 per cent) reported that they were cigarette smokers. No patient had a family history of renal carcinoma or of diseases, such as von Hippel-Lindau disease or tuberous sclerosis, known to be associated with the development of renal neoplasms. A total of 3 patients (27 per cent) had arterial hypertension, 10 (73 per cent) had microscopic hematuria on admission urinalysis, 4 (31 per cent) had the hepatic dysfunction syndrome, 6 (46 per cent) had increased erythrocyte sedimentation rate and 7 (54 per cent) had anemia. Of the patients 12 underwent radical nephrectomy and 1 underwent open biopsy only. Tumors of this type were relatively large and ranged from 6 to 17 cm. in diameter, with a median of 10 cm. The size distribution of the resected tumors is shown in figure 3. Tumor stage was advanced by the time of operation. Two patients had stage I tumors confined within the renal capsule, 5 had stage II tumors (perinephric fat invasion), 1 had regional lymph node metastases (stage III) and 5 had distant metastases (stage IV) (fig. 4). Survival experience for these 13 patients was discouraging. Only 1 patient with a stage I tumor is alive without evidence of disease 49 months after resection. The remaining patients are dead of metastatic renal carcinoma, with a median postoperative survival of 6.3 months (range 1 to 14 months). DISCUSSION
Accepted for publication March 31, 1983. * Requests for reprints: Department of Urology, Mayo Clinic, Rochester, Minnesota 55905. Read at annual meeting of North Central Section, American Urological Association, Marco Island, Florida, October 17-23, 1982.
Of the patients with primary renal tumors resected at our institution from 1967 to 1980, 1 per cent had the mixed malignancy of renal carcinoma associated with sarcomatoid elements that has been called sarcomatoid renal carcinoma. In the earlier
658
TOMERA, FARROW AND LIEBER
study of 2,286 renal tumor specimens seen here from 1906 to 1966 sarcomatoid renal carcinomas made up 1.5 per cent of the samples studied. 1 Sarcomatoid renal carcinomas were advanced at the time of diagnosis, with a majority of patients having a palpable flank mass and 11 of 13 (85 per cent) having stages II through IV tumors at the time of diagnosis. The poor prognosis observed in the earlier decades of this century (1 of 37 patients alive) also was seen in our series, in which only 1 patient (who had disease limited to within the renal capsule) appeared to be a moderately long-term survivor. The remaining 12 patients died of metastatic disease, with a median survival of 6.3 months. Thus, sarcomatoid renal cell carcinoma is a highly aggressive malignancy with a dismal prognosis even at the present time. If and when active cytotoxic drugs or other effective systemic treatment for renal cell carcinoma becomes available, then this histologic variant would be a primary candidate for preemptive treatment, since <1 patient in 10 is likely to be a long-term survivor with standard surgical treatment. Malignant fibrous histiocytoma is a term used to describe a
No. of patients
30
40
60
50
70
80
Age FIG. 2. Age distribution of patients with sarcomatoid renal carcinomas.
No. of patients
1-3
4-7
8-11
12-15
16-19
19-22
Tumor diameter (cm)
FIG. 3. Tumor size distribution of sarcomatoid renal carcinomas
FIG. 4. Pathologic stage of sarcomatoid renal carcinomas m 13 patients.
FIG. 1. A, typical histologic appearance of sarcomatoid renal carcinoma. Poorly differentiated area of renal cell carcinoma is adjacent to area of sarcomatous-appearing spindle cells. B, representative histologic section from sarcomatous area of sarcomatoid renal carcinoma, which has histologic appearance similar to malignant fibrous histiocytoma.2·3 Reduced from Xl60.
wide spectrum of tumors, particularly in the somatic soft tissues.2·3 These tumors are of uncertain histogenesis. Considerable histopathologic heterogeneity is exhibited, leading to a classification that includes several subtypes featuring fibrous, myxoid, giant cell, histiocytic, inflammatory and angiomatoid variants. Since the histopathological findings of this neoplasm overlap considerably with other neoplastic types, and particularly anaplastic carcinomas, such tumors in various sites may simulate closely ~1 of the variants of malignant fibrous histiocytoma by standard light microscopy and even by electron microscopy in many instances. Ultrastructural studies of such tumors occurring in the kidney may be necessary to distinguish between sarcomatoid renal cell carcinoma of epithelial origin and malignant fibrous histiocytoma. Desmosomal junctions
659 ultrs.str:~tctu.rai studies of sarcornatoid ::.,enal carcir10~T1a confirrn studies may be of ings may be in which confusion with a Certain authorities have grading and detailed classification for as,se:ss1ng of patients with renal parenchymal carcinomas. However, we continue to believe that careful histologic assessment of renal tumors can yield useful information. At one extreme are so-called renal oncocytomas which, although they have been considered previously to be malignant neoplasms, appear to have a nonaggressive biologic behavior. 6 Fo:r more renal cell carcinomas our experience suggests that based on criteria can be of general predictive value. Finally, sarcomatoid renal cell carcinomas are at the most aggressive extreme among adults with renal parenchymal tumors and have a uniform dismal prognosis to dateo VVe believe that assigning renal parenchymal tumors to such histologic categories can be of use in assessing prognosis and may be helpful in the future to indicate the need for adjuvant treatment. Most renal tumors believed to be renal sarcomas have proved to be sarcomatoid renal cell carcinomas.' Since these tumors make up about 1 per cent of renal tumors seen in our institutional experience they are not really rare but merely uncom~·~~.LHN'>L~
WLU~.uuuv,.~
15,,000 nevv cases of :renal ceil carcinoma each year in the United 100 to 200 nevl cases oE sarscmatoid renal carcinonJ.a PYnC•r•tpfj 88.Ch year. 8
REFERENCES
L Farrow) G. ]\;l., Harriso11 Eo G., Jr. and Utz, D. C.: Sarcomas and sarcomatoid and mixed malignant tumors of the kidney in III. Cancer, 22: 556, 1968. 2. and Enzinger, F. M.: ""m,;HG
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1983 by The Williams & Wilkins Co.
SARCOMATOID RENAL CARCINOMA KEVIN M. TOMERA, GEORGE M. FARROW
AND
MICHAEL M. LIEBER*
From the Departments of Urology and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Sarcomatoid renal carcinoma made up 1 per cent of renal parenchymal tumors resected from 1967 to 1980. The majority of patients with this aggressive type of renal carcinoma were symptomatic and had a palpable renal mass at the time of diagnosis. Only 2 of 13 patients had tumor confined within the renal capsule at the time of operation. One of these patients survived and 12 of 13 died rapidly of metastatic renal carcinoma, with a median survival of 6.3 months from the time of diagnosis. This distinctive histologic variant of renal carcinoma has a highly malignant biological behavior and, as effective adjuvant treatment for renal carcinoma becomes available, should be one of the tumor types treated vigorously. In 1968 Farrow and associates described 37 cases of a unique renal mixed malignancy that they called sarcomatoid renal carcinoma. 1 This tumor consists of renal cell carcinoma associated intimately with a more pleomorphic spindle cell or giant cell malignancy resembling sarcoma in which foci of transition between carcinoma cells to pleomorphic sarcomatoid cells usually can be demonstrated. We herein report the clinical, pathological and survival features of patients who underwent resection of sarcomatoid renal cell carcinoma between 1967 and 1980. MATERIALS AND METHODS
We reviewed the histologic diagnoses of all renal tumors resected between 1967 and 1980. Cases in the pathologic tissue registry with a description containing spindle-like, sarcomatoid, sarcomatous, high grade or grade IV renal carcinoma were identified, and received detailed clinical and pathologic review. From among 1,303 cases of renal carcinoma resected during this period 39 were so identified in the tissue registry. Since our study pathologist (G. M. F.) has had long-standing interest in renal sarcomas and sarcomatoid tumors it is believed that few renal tumors containing sarcomatous elements would not be identified as such in our institutional tissue registry. Of these 39 tumors current histologic review by the study pathologist identified 13 cases that fit strict criteria for sarcomatoid renal carcinoma. The histologic appearance of these mixed, bimorphic tumors depends on the area examined. Histologic examination of the area of adult renal carcinoma reveals the usual granular cell, clear cell or mixed pattern of varying cellular differentiation that has been well described previously. Examination of the sarcomatoid element reveals a more pleomorphic neoplasm composed predominantly of spindle fibrogenic cells, often with bizarre and multinucleated forms. Although there is some overlap of features among the cases the 13 tumors fell into 2 groups based on resemblance of the sarcomatoid element to recognized categories of true sarcoma. The most common group (11 tumors) showed a predominance of spindle or fibroblastic cells arranged in a whorled or storiform pattern with variable amounts of fibrous stroma (fig. 1). Many of these tumors also featured bizarre multinucleated giant neoplastic cells. These histologic features are indistinguishable by light microscopy from a distinctive type of soft tissue sarcoma called malignant fibrous histiocytoma. 2 •3 Because of the large bizarre neoplastic
cells, which at one time were believed to represent neoplastic muscle cells, many cases of malignant fibrous histiocytoma were classified in the past as pleomorphic rhabdomyosarcoma. The 2 remaining renal tumors displayed a monomorphic spindled fibrogenic component similar to fibrosarcoma. RESULTS
A total of 13 patients with renal tumors showing a typical pattern of sarcomatoid renal carcinoma underwent resection between 1967 and 1980 (13 of 1,303 or 1 per cent of all renal tumors resected). There were 11 men and 2 women in this group. Patient age ranged from 34 to 78 years, with a median age of 56 years (fig. 2). Seven tumors occurred in the right kidney and 6 in the left kidney. There were no instances of bilateral tumors. The majority of patients had symptoms related to the renal tumor: two-thirds had either flank pain or gross hematuria, 7 (54 per cent) had a palpable mass and 2 (15 per cent) reported preoperative fever. Seven patients (54 per cent) reported that they were cigarette smokers. No patient had a family history of renal carcinoma or of diseases, such as von Hippel-Lindau disease or tuberous sclerosis, known to be associated with the development of renal neoplasms. A total of 3 patients (27 per cent) had arterial hypertension, 10 (73 per cent) had microscopic hematuria on admission urinalysis, 4 (31 per cent) had the hepatic dysfunction syndrome, 6 (46 per cent) had increased erythrocyte sedimentation rate and 7 (54 per cent) had anemia. Of the patients 12 underwent radical nephrectomy and 1 underwent open biopsy only. Tumors of this type were relatively large and ranged from 6 to 17 cm. in diameter, with a median of 10 cm. The size distribution of the resected tumors is shown in figure 3. Tumor stage was advanced by the time of operation. Two patients had stage I tumors confined within the renal capsule, 5 had stage II tumors (perinephric fat invasion), 1 had regional lymph node metastases (stage III) and 5 had distant metastases (stage IV) (fig. 4). Survival experience for these 13 patients was discouraging. Only 1 patient with a stage I tumor is alive without evidence of disease 49 months after resection. The remaining patients are dead of metastatic renal carcinoma, with a median postoperative survival of 6.3 months (range 1 to 14 months). DISCUSSION
Accepted for publication March 31, 1983. * Requests for reprints: Department of Urology, Mayo Clinic, Rochester, Minnesota 55905. Read at annual meeting of North Central Section, American Urological Association, Marco Island, Florida, October 17-23, 1982.
Of the patients with primary renal tumors resected at our institution from 1967 to 1980, 1 per cent had the mixed malignancy of renal carcinoma associated with sarcomatoid elements that has been called sarcomatoid renal carcinoma. In the earlier
658
TOMERA, FARROW AND LIEBER
study of 2,286 renal tumor specimens seen here from 1906 to 1966 sarcomatoid renal carcinomas made up 1.5 per cent of the samples studied. 1 Sarcomatoid renal carcinomas were advanced at the time of diagnosis, with a majority of patients having a palpable flank mass and 11 of 13 (85 per cent) having stages II through IV tumors at the time of diagnosis. The poor prognosis observed in the earlier decades of this century (1 of 37 patients alive) also was seen in our series, in which only 1 patient (who had disease limited to within the renal capsule) appeared to be a moderately long-term survivor. The remaining 12 patients died of metastatic disease, with a median survival of 6.3 months. Thus, sarcomatoid renal cell carcinoma is a highly aggressive malignancy with a dismal prognosis even at the present time. If and when active cytotoxic drugs or other effective systemic treatment for renal cell carcinoma becomes available, then this histologic variant would be a primary candidate for preemptive treatment, since <1 patient in 10 is likely to be a long-term survivor with standard surgical treatment. Malignant fibrous histiocytoma is a term used to describe a
No. of patients
30
40
60
50
70
80
Age FIG. 2. Age distribution of patients with sarcomatoid renal carcinomas.
No. of patients
1-3
4-7
8-11
12-15
16-19
19-22
Tumor diameter (cm)
FIG. 3. Tumor size distribution of sarcomatoid renal carcinomas
FIG. 4. Pathologic stage of sarcomatoid renal carcinomas m 13 patients.
FIG. 1. A, typical histologic appearance of sarcomatoid renal carcinoma. Poorly differentiated area of renal cell carcinoma is adjacent to area of sarcomatous-appearing spindle cells. B, representative histologic section from sarcomatous area of sarcomatoid renal carcinoma, which has histologic appearance similar to malignant fibrous histiocytoma.2·3 Reduced from Xl60.
wide spectrum of tumors, particularly in the somatic soft tissues.2·3 These tumors are of uncertain histogenesis. Considerable histopathologic heterogeneity is exhibited, leading to a classification that includes several subtypes featuring fibrous, myxoid, giant cell, histiocytic, inflammatory and angiomatoid variants. Since the histopathological findings of this neoplasm overlap considerably with other neoplastic types, and particularly anaplastic carcinomas, such tumors in various sites may simulate closely ~1 of the variants of malignant fibrous histiocytoma by standard light microscopy and even by electron microscopy in many instances. Ultrastructural studies of such tumors occurring in the kidney may be necessary to distinguish between sarcomatoid renal cell carcinoma of epithelial origin and malignant fibrous histiocytoma. Desmosomal junctions
659 ultrs.str:~tctu.rai studies of sarcornatoid ::.,enal carcir10~T1a confirrn studies may be of ings may be in which confusion with a Certain authorities have grading and detailed classification for as,se:ss1ng of patients with renal parenchymal carcinomas. However, we continue to believe that careful histologic assessment of renal tumors can yield useful information. At one extreme are so-called renal oncocytomas which, although they have been considered previously to be malignant neoplasms, appear to have a nonaggressive biologic behavior. 6 Fo:r more renal cell carcinomas our experience suggests that based on criteria can be of general predictive value. Finally, sarcomatoid renal cell carcinomas are at the most aggressive extreme among adults with renal parenchymal tumors and have a uniform dismal prognosis to dateo VVe believe that assigning renal parenchymal tumors to such histologic categories can be of use in assessing prognosis and may be helpful in the future to indicate the need for adjuvant treatment. Most renal tumors believed to be renal sarcomas have proved to be sarcomatoid renal cell carcinomas.' Since these tumors make up about 1 per cent of renal tumors seen in our institutional experience they are not really rare but merely uncom~·~~.LHN'>L~
WLU~.uuuv,.~
15,,000 nevv cases of :renal ceil carcinoma each year in the United 100 to 200 nevl cases oE sarscmatoid renal carcinonJ.a PYnC•r•tpfj 88.Ch year. 8
REFERENCES
L Farrow) G. ]\;l., Harriso11 Eo G., Jr. and Utz, D. C.: Sarcomas and sarcomatoid and mixed malignant tumors of the kidney in III. Cancer, 22: 556, 1968. 2. and Enzinger, F. M.: ""m,;HG