RENALTUMORSINYOUNGADULTS" MAJ. WILLIAM H. BOYKIN, MC (USA) CAPT. KEVIN E. BRIGHT, MC (USA) MAJ. ERIC J. ZEIDMAN, MC (USA) MAJ. IAN M. THOMPSON, MC (USA)
From the Urology Service, Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas ABSTRACT-Primary renal malignancies are relatively rare in young adults. Eighteen patients between the ages of twenty and forty years underwent nephrectomy for renal tumors at OUTinstitution between 1947 and 1989. Data were reviewed in this group regarding method of presentation, duration of symptoms, tumor histology, pathologie stage, and survival. Tumor histology parallels that of older patients, the majority being adenocarcinoma (78 %). The duration of symptoms prior to seeking medical attention was long, averaging eighty-four weeks. The overall survival rate, excluding nontumor deaths, was 50 percent. NO patient with nodal OTdistant metastases survived, regardless of histology.
Primary renal malignancies comprise a heterogenous group of neoplasms which may arise from renal parenchyma, collecting system or capsule. The most common renal neoplasm in adults, renal adenocarcinoma (renal cel1 carcinema), constitutes approximately 85 percent of al1 primary aenal malignancies.’ Renal cel1 carcinoma is generally a disease of older adults with the peak incidence occurring in the sixth decade and is approximately twice as common in males as in females.2 Renal adenocarcinoma is rare in young adults with only 3.4 percent occurring in patients less than forty years of age.3 Other histologie types of primary renal tumors follow a similar age distribution, but data in the literature regarding such tumors in young individuals are scarce and are mainly case reports. 4,5 The two largest series reviewing malignancies in young adults report only survival and prognostic variables associated with renal adenocarcinoma .6,7 Anecdotally, primary renal malignancies in young adults are believed to be characterized
by unusual histopathology and poor prognosis. We reviewed our experience with renal tumors in young adults, ages twenty to forty years, to assess the relative frequency of the various renal tumors, modes of presentation, pathologie stage, and survival.
*The opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army or the Department of Defense.
The average age of patients in this series was 28.3 years (Fig. 1). There were 13 men (72%) and 5 women (2.6: 1 ratio).
UROLOGY
/
DECEMBER
1992
/
VOLUME 40, NUMBER 6
Material and Methods Three hundred seventy-one cases of renal tumors from the Brooke Army Medical Center Tumor Registry from 1947 to 1989 were reviewed, and 18 patients between ages twenty and forty years at the time of diagnosis were identified. In this group presenting signs and symptoms, duration of symptoms, laboratory abnormalities, and method of diagnosis were recorded. Clinical stage was assessed (according to Robson) and corroborated by pathologie evaluation as al1 patients underwent explorationlnephrectomy. Complete follow-up to July 1989 was available for al1 patients in this study. Results
503
TABLE1.
Presenting signshymptoms
Diagnosis
TABLE 111.
Sign/Symptom
No. of Patients
Diagnosis
No.
Gross hematuria Flank pain Mass Infection Weight loss Hypertension Anemia Incidental
10 9 2 1 1 1 1 1
Adenocarcinoma Transitional cel1 CA Squamous cel1 CA Nephroblastoma (adult Wilms’) Angiomyolipoma
14 1 1 1
TABLE 11.
TOTAL
No. 6 3 3 1 1
IVP alone IVP + RPG IVP + arteriogram RPG alone IVP + CT IVP + CT + arteriogram IVP + US + CT CT alone CT + US
1
1 1 1 18
TOTAL
KEY:IVP = intravenous pyelography; RPG = retrograde pyelography; CT = computerized tomography; US = ultrasonogra-
20-2s
26-30 AGE
FIGURE
1.
31-35
36-40
IN VEARS
Age at diagnosis.
The presenting signs and symptoms are summarized in Table 1. The patients exhibited essentially the same spectrum of clinical signs and symptoms as did older patients, with the vast majority complaining of hematuria and/or flank pain. The average duration of symptoms prior to diagnosis was eighty-four weeks. Because of the
504
-K
TABLE IV.
Screening modality
Screening Modality
1
Stage at nephrectomy of patients with renal adenocarcinoma -Survival 5 Year
No. of Pts.
Stage
1 11 111 IV *‘lXvo deaths not
7 2 3 2
(%)10 Year
100 100 33 0
attributable
70* 50 0 0
to renal cel1 carcinoma.
constellation of presenting signs, symptoms, and laboratory abnormalities and their lack of specificity, the preoperative detection of renal masses remains primarily a radiologie diagnosis. Sixteen of eighteen renal masses (89 %) were suspected by abnormalities noted on pyelography (intravenous or retrograde) which remains the initial screening modality for patients presenting with hematuria at our institution. As the majority of the patients were diagnosed and treated prior to the late 197Os, computerized tomography (CT) and ultrasound had minima1 diagnostic impact in this series, In fact, only 5 of 18 patients (22 % ) had diagnostic confirmation with CT and/or ultrasound; al1 of whom were diagnosed after 1983 (Table 11). Tumor histology is presented in Table 111. None of the 14 cases of renal adenocarcinoma were noted to have adverse histology (spindle cel1 or sarcomatoid) .
Pathologie stage and survival of the 14 patients with renal cel1 carcinoma are summarized in Table IV. Both patients with undifferentiated squamous cel1 carcinoma and poorly differentiated transitional cel1 carcinema presented with metastases and succumbed to their disease. The patients with adult Wilms’ tumor and angiomyolipoma are both alive and well. The overall five-year surviva1 in this series is 70 percent. Excluding nontumor deaths, overall ten-year survival is 50 percent. UROLOGY
/
DECEMBER
1992
/
VOLUME 40. NUMBER 6
The prognosis in other types of renal tumors cannot be assessed in this series due to the smal1 numbers represented. The question remains whether or not nonadenocarcinoma renal tumors tend to be more aggressive than similar histologie types in older age groups. We conclude that renal cel1 carcinoma may exhibit a more benign prognosis in young adults when diagnosed at a low stage. Higher stages seem to possess a biologie potential similar to that seen in older adult patients. It should be emphasized that renal neoplasms must be considered in the differential diagnosis in young adults with hematuria to avoid delayed diagnosis and possible increased mortality.
Comment The differential diagnosis of gross hematuria in a seemingly healthy young adult may center on a variety of non-malignant conditions to include various nephritides, urolithiasis, hemoglobinopathies and intrarenal vascular malformations. Patients aged twenty to forty years constituted 4.8 percent of al1 renal tumors diagnosed at our institution during this period. Though other series have focused only on patients in this age group with renal adenocarcinema, the incidence may range as high as 7 to 9 percent3,’ A review of 890 cases of renal adenocarcinoma from M.D. Anderson suggests a significant increase in incidence in the forty to forty-nine-year-old age group.s Renal tumors are not often diagnosed early in their course because there are no characteristic early symptoms and signs. In this series, the average delay in diagnosis is particularly excessive at eighty-four weeks. The majority of patients (72 %) prasented with one or more of the classic triad symptoms: gross hematuria, flank pain, and mass. The histology of renal tumors in young adults mimics that found in older patients with a significant preponderance of renal adenocarcinema (78%). Of the tumors that were renal adenocarcinoma, the majority were of clear cel1 origin and none were noted to have unfavorable histology. Overall prognosis in patients with rena1 adenocarcinoma was excellent in low-stage disease (Stages 1 and 11) with only 1 patientdeath related to tumor, and survival at ten years of 85 percent (6/7). This compares with fiveand ten-year survival of 65 percent and 56 percent in Stage 1 disease and 44 percent and 26 percent in Stage 11 disease in Skinner’s series9 Young adults with metastatic disease at presentation (Stages 111 and IV) did as poorly as older patients with a 20 percent five-year survival and with none surviving ten years.
UROLOGY
i
DECEMBER
1992
/
VOLUME
40, NUMBER
Urology Service Department of Surgery Brooke Army Medical Center Fort Sam Houston, Texas 78234-6200 (DR. BOYKIN) References 1. Pritchett TR, Lieskovsky G, and Skinner DG: Clinical manifestations and treatment of renal parenchymal tumors, in Skinner DG, and Lieskovsky G (Eds): Diagnosis and Management of Genitourinary Cancer, Philadelphia, PA, WB Saunders Co, 1988, chap 19, p 337. 2. Bel1 ET: Renal Diseases, 2nd ed, Philadelphia, Lea and Febiger, 1983, p 435. 3. Kantor ALF, Meigs JW, Heston JF, and Flannery FT: Epidemiology of renal cel1 carcinoma in Connecticut 1935-1973, J Nat1 Cancer Inst 57: 495 (1976). 4. Jordan GH, Hartman DS, Ladaga LE, and Schellhammer PF: Large renal masses in young adults, Urology 28: 330 (1986). 5. Liber MM, et al: Innominate bone and renal masses in a young man, J Urol 120: 607 (1978). 6. Lieber MM, Tomera FM, Taylor WF, and Farrow CM: Renal adenocarcinoma in young adults: survival and variables affecting prognosis, J Urol 125: 164 (1981). 7. Schiff M, Herter G, and Lytton B: Renal adenocarcinoma in young adults, Urology 25: 357 (1985). 8. Noronha RFX, Johnson DE, Gainee VF, and Bourlase BC: Changing patterns in age distribution of renal carcinoma patien& Urology 13: 12 (1979). 9. Skinner DG, et al: Diagnosis and management of renal cel1 carcinoma. A clinical and pathological study of 309 cases, Cancer 28: 1165 (1971).
6
505
From the Urology Service, Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas ABSTRACT-Primary renal malignancies are relatively rare in young adults. Eighteen patients between the ages of twenty and forty years underwent nephrectomy for renal tumors at OUTinstitution between 1947 and 1989. Data were reviewed in this group regarding method of presentation, duration of symptoms, tumor histology, pathologie stage, and survival. Tumor histology parallels that of older patients, the majority being adenocarcinoma (78 %). The duration of symptoms prior to seeking medical attention was long, averaging eighty-four weeks. The overall survival rate, excluding nontumor deaths, was 50 percent. NO patient with nodal OTdistant metastases survived, regardless of histology.
Primary renal malignancies comprise a heterogenous group of neoplasms which may arise from renal parenchyma, collecting system or capsule. The most common renal neoplasm in adults, renal adenocarcinoma (renal cel1 carcinema), constitutes approximately 85 percent of al1 primary aenal malignancies.’ Renal cel1 carcinoma is generally a disease of older adults with the peak incidence occurring in the sixth decade and is approximately twice as common in males as in females.2 Renal adenocarcinoma is rare in young adults with only 3.4 percent occurring in patients less than forty years of age.3 Other histologie types of primary renal tumors follow a similar age distribution, but data in the literature regarding such tumors in young individuals are scarce and are mainly case reports. 4,5 The two largest series reviewing malignancies in young adults report only survival and prognostic variables associated with renal adenocarcinoma .6,7 Anecdotally, primary renal malignancies in young adults are believed to be characterized
by unusual histopathology and poor prognosis. We reviewed our experience with renal tumors in young adults, ages twenty to forty years, to assess the relative frequency of the various renal tumors, modes of presentation, pathologie stage, and survival.
*The opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army or the Department of Defense.
The average age of patients in this series was 28.3 years (Fig. 1). There were 13 men (72%) and 5 women (2.6: 1 ratio).
UROLOGY
/
DECEMBER
1992
/
VOLUME 40, NUMBER 6
Material and Methods Three hundred seventy-one cases of renal tumors from the Brooke Army Medical Center Tumor Registry from 1947 to 1989 were reviewed, and 18 patients between ages twenty and forty years at the time of diagnosis were identified. In this group presenting signs and symptoms, duration of symptoms, laboratory abnormalities, and method of diagnosis were recorded. Clinical stage was assessed (according to Robson) and corroborated by pathologie evaluation as al1 patients underwent explorationlnephrectomy. Complete follow-up to July 1989 was available for al1 patients in this study. Results
503
TABLE1.
Presenting signshymptoms
Diagnosis
TABLE 111.
Sign/Symptom
No. of Patients
Diagnosis
No.
Gross hematuria Flank pain Mass Infection Weight loss Hypertension Anemia Incidental
10 9 2 1 1 1 1 1
Adenocarcinoma Transitional cel1 CA Squamous cel1 CA Nephroblastoma (adult Wilms’) Angiomyolipoma
14 1 1 1
TABLE 11.
TOTAL
No. 6 3 3 1 1
IVP alone IVP + RPG IVP + arteriogram RPG alone IVP + CT IVP + CT + arteriogram IVP + US + CT CT alone CT + US
1
1 1 1 18
TOTAL
KEY:IVP = intravenous pyelography; RPG = retrograde pyelography; CT = computerized tomography; US = ultrasonogra-
20-2s
26-30 AGE
FIGURE
1.
31-35
36-40
IN VEARS
Age at diagnosis.
The presenting signs and symptoms are summarized in Table 1. The patients exhibited essentially the same spectrum of clinical signs and symptoms as did older patients, with the vast majority complaining of hematuria and/or flank pain. The average duration of symptoms prior to diagnosis was eighty-four weeks. Because of the
504
-K
TABLE IV.
Screening modality
Screening Modality
1
Stage at nephrectomy of patients with renal adenocarcinoma -Survival 5 Year
No. of Pts.
Stage
1 11 111 IV *‘lXvo deaths not
7 2 3 2
(%)10 Year
100 100 33 0
attributable
70* 50 0 0
to renal cel1 carcinoma.
constellation of presenting signs, symptoms, and laboratory abnormalities and their lack of specificity, the preoperative detection of renal masses remains primarily a radiologie diagnosis. Sixteen of eighteen renal masses (89 %) were suspected by abnormalities noted on pyelography (intravenous or retrograde) which remains the initial screening modality for patients presenting with hematuria at our institution. As the majority of the patients were diagnosed and treated prior to the late 197Os, computerized tomography (CT) and ultrasound had minima1 diagnostic impact in this series, In fact, only 5 of 18 patients (22 % ) had diagnostic confirmation with CT and/or ultrasound; al1 of whom were diagnosed after 1983 (Table 11). Tumor histology is presented in Table 111. None of the 14 cases of renal adenocarcinoma were noted to have adverse histology (spindle cel1 or sarcomatoid) .
Pathologie stage and survival of the 14 patients with renal cel1 carcinoma are summarized in Table IV. Both patients with undifferentiated squamous cel1 carcinoma and poorly differentiated transitional cel1 carcinema presented with metastases and succumbed to their disease. The patients with adult Wilms’ tumor and angiomyolipoma are both alive and well. The overall five-year surviva1 in this series is 70 percent. Excluding nontumor deaths, overall ten-year survival is 50 percent. UROLOGY
/
DECEMBER
1992
/
VOLUME 40. NUMBER 6
The prognosis in other types of renal tumors cannot be assessed in this series due to the smal1 numbers represented. The question remains whether or not nonadenocarcinoma renal tumors tend to be more aggressive than similar histologie types in older age groups. We conclude that renal cel1 carcinoma may exhibit a more benign prognosis in young adults when diagnosed at a low stage. Higher stages seem to possess a biologie potential similar to that seen in older adult patients. It should be emphasized that renal neoplasms must be considered in the differential diagnosis in young adults with hematuria to avoid delayed diagnosis and possible increased mortality.
Comment The differential diagnosis of gross hematuria in a seemingly healthy young adult may center on a variety of non-malignant conditions to include various nephritides, urolithiasis, hemoglobinopathies and intrarenal vascular malformations. Patients aged twenty to forty years constituted 4.8 percent of al1 renal tumors diagnosed at our institution during this period. Though other series have focused only on patients in this age group with renal adenocarcinema, the incidence may range as high as 7 to 9 percent3,’ A review of 890 cases of renal adenocarcinoma from M.D. Anderson suggests a significant increase in incidence in the forty to forty-nine-year-old age group.s Renal tumors are not often diagnosed early in their course because there are no characteristic early symptoms and signs. In this series, the average delay in diagnosis is particularly excessive at eighty-four weeks. The majority of patients (72 %) prasented with one or more of the classic triad symptoms: gross hematuria, flank pain, and mass. The histology of renal tumors in young adults mimics that found in older patients with a significant preponderance of renal adenocarcinema (78%). Of the tumors that were renal adenocarcinoma, the majority were of clear cel1 origin and none were noted to have unfavorable histology. Overall prognosis in patients with rena1 adenocarcinoma was excellent in low-stage disease (Stages 1 and 11) with only 1 patientdeath related to tumor, and survival at ten years of 85 percent (6/7). This compares with fiveand ten-year survival of 65 percent and 56 percent in Stage 1 disease and 44 percent and 26 percent in Stage 11 disease in Skinner’s series9 Young adults with metastatic disease at presentation (Stages 111 and IV) did as poorly as older patients with a 20 percent five-year survival and with none surviving ten years.
UROLOGY
i
DECEMBER
1992
/
VOLUME
40, NUMBER
Urology Service Department of Surgery Brooke Army Medical Center Fort Sam Houston, Texas 78234-6200 (DR. BOYKIN) References 1. Pritchett TR, Lieskovsky G, and Skinner DG: Clinical manifestations and treatment of renal parenchymal tumors, in Skinner DG, and Lieskovsky G (Eds): Diagnosis and Management of Genitourinary Cancer, Philadelphia, PA, WB Saunders Co, 1988, chap 19, p 337. 2. Bel1 ET: Renal Diseases, 2nd ed, Philadelphia, Lea and Febiger, 1983, p 435. 3. Kantor ALF, Meigs JW, Heston JF, and Flannery FT: Epidemiology of renal cel1 carcinoma in Connecticut 1935-1973, J Nat1 Cancer Inst 57: 495 (1976). 4. Jordan GH, Hartman DS, Ladaga LE, and Schellhammer PF: Large renal masses in young adults, Urology 28: 330 (1986). 5. Liber MM, et al: Innominate bone and renal masses in a young man, J Urol 120: 607 (1978). 6. Lieber MM, Tomera FM, Taylor WF, and Farrow CM: Renal adenocarcinoma in young adults: survival and variables affecting prognosis, J Urol 125: 164 (1981). 7. Schiff M, Herter G, and Lytton B: Renal adenocarcinoma in young adults, Urology 25: 357 (1985). 8. Noronha RFX, Johnson DE, Gainee VF, and Bourlase BC: Changing patterns in age distribution of renal carcinoma patien& Urology 13: 12 (1979). 9. Skinner DG, et al: Diagnosis and management of renal cel1 carcinoma. A clinical and pathological study of 309 cases, Cancer 28: 1165 (1971).
6
505
