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Retroperitoneal Mass in a 58-Year-Old Man
0022-534 7/79 / 1224-0535$02.00/0
V oL 122, October Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
Clinicopathologi cal Conference RETROPERITONEAL MASS IN
58-YEAR-OLD MAN
CHARLES B. BRENDLER, * JOHN E. DEES,t ROBERT A. OLDER,:j: BERNARD F. FETTER§ JAMES F. GLENNII
AND
From the Departments of Urology; Radiology and Pathology, Duke University Medical Center, Durham, North Carolina
afebrile, white blood count remained within normal limits and urine remained microscopically clear. On the third a repeat IVP disclosed no with pers1st(mt obstmction of the left upper ureter 1). n·,,th,-en""'rm,c examination disclosed a normal bladder and ureteral orifices. A 6F mOno,Hn h~ureteral up the left ureter to the level of the encou1c,tenr1g no resistance or obstruction, and a drip of was obtained. The catheter was indwelling, the sym.ptoms resolved completely and the ureteral catheter was removed 48 hours later only to incite recurrence of colicky left flank pain. At this point a third IVP was obtained and again disclosed obstruction of the upper left ureter without evidence of definite ureteral stone. An upper gastrointestinal series and a barium enema were within normal limits. Surgical exploration was elected.
Dr. Charles B. Brendler. A '"'·-"''",.-"'''"' white man was in 1965 with a 12-hom of intermittent left flank unassociated with any constitutional or symptoms. He denied any diffiand been in excellent general health except for an episode of gouty arthritis 8 years He had experienced no further difficulty with gout, was on no medication and was unaware of any chemical abnormalities. Pre-admission urinalysis revealed rare white blood cells, no bacteria, but 8 to 10 red blood cells per high power field in the spun urinary sediment. A plain x-ray of the abdomen was unremarkable, with no evidence of urinary calculL Excretory urography (IVP) disclosed a normal right kidney and an intrinsically normal but slightly lateral right ureter. The bladder was unremarkable as well. However, on the left side there was delay in excretion of contrast material with dilatation of the renal pelvis and upper PREOPERATIVE DIAGNOSIS ureter down to the level of the L2, L3 intervertebral disk space. Dr. John E. Dees. Our presumptive diagnosis was a nonThe left ureter also showed a somewhat lateral position. A opaque calculus subtotally obstructing the left ureter. The presumptive diagnosis of an obstructing non-opaque ureteral · patient had a history of an attack of gouty arthritis, although calculus was entertained and the patient was hospitalized for the uric acid levels were normal. The only urinary abnormality supportive treatment and observation. was microscopic hematuria. We had no definite evidence of Physical examination disclosed a middle-aged white man in intrinsic stricture of the ureter or extrinsic to cause moderate discomfort. Vital signs included temperature ureteral obstruction. Furthermore, there was no physical or pulse 80, respirations 20 and blood pressure 160/90. Examina- radiographic evidence of an abdominal mass. tion of the head, eyes, ears, nose and throat was within normal limits. The lungs were clear to percussion and auscultation, and SURGICAL FINDINGS cardiac examination was unremarkable. Examination of the abdomen disclosed moderate obesity without masses, guarding Doctor Brendler. Exploration was accomplished through a or rebound tenderness but there was some direct tenderness in left flank 12th rib incision. When the retroperitoneal space was the left lower quadrant. Bowel sounds were normal and active. entered a large, smooth mass was encountered, which was Rectal examination disclosed a normal prostate and was oth- intimately attached to the posterior abdominal musculature erwise unremarkable. External genitalia were normal to inspec- and extended from the hilus of the kidney down to the level of tion and palpation. Extremities were unremarkable and neuro- the bifurcation of the aorta. With further exposure it was found logical examination was within normal limits. that the mass extended ac.ross the midline and involved the Clinical laboratory findings included hemoglobin 13.2 gm. per aorta and the vena cava. The ureter was encased by the mass cent, hematocrit 39.4 mg. per cent, with white blood count 9,200 at the level of the lower pole of the kidney. The tumor was and differential normal. Blood sugar was 103 mg. per cent, separate from the kidney but was deemed unresectable because blood urea nitrogen 23 mg. per cent, sodium 140 mEq./1., of its extent and involvement of major vessels. Accordingly, a potassium 4.1 mEq./1., chloride 102 mEq./l., carbon dioxide 26 left nephrectomy was accomplished and an ample biopsy of the mM./l., total protein 7.5 gm. per cent with albumin 3.4 gm. per mass was taken. Frozen section histologic evaluation disclosed cent and globulin 4.1 gm. per cent, calcium and phosphorus 9.6 anaplastic malignancy, most likely seminoma. and 2.6 mg. per cent, respectively, and uric acid 7.0 mg. per cent. These values were all normal for this laboratory. A chest DISCUSSION OF PATHOLOGY x-ray was within normal limits but was not an optimal study. Dr. Bernard F. Fetter. The surgical specimen was completely An electrocardiogram was normal. For 2 days the patient was observed, symptoms of discomfort adequate for diagnostic evaluation. Clearly malignant, the tupersisting but relieved minimal analgesia. He remained mor was composed of a single cell type with a fine, vesicular nucleus (fig. 2). The cytoplasm throughout was pale to nonstaining. Cells were arranged in nests and surrounded by a • Chief Resident in Urology. delicate stroma in which there was lymphoid infiltrate. The t Professor of Uroiogy. pattern was completely characteristic of seminoma. t Associate Professor of Radiology and Director of Uroradio!ogy. Dr. James F. Glenn. Vias the entire tumor sp,ecirr,en exam§ Pxofessor of Pathology. and 1Nere there any other cells or elerr.1.ents to suggest II Chief of 1 Case nr,,s.ent,,d at Urology R,ou?1.ds on January 1979. ~,,,-c,;,~~ nther tha11. seminorna?
536
CLINICOPATHOLOGICAL CONFERENCE
FIG. 2. Representative histologic pattern of abdominal tumor, characteristic of seminoma.
FIG. 1. IVP demonstrates moderate obstruction in left upper ureter. Both ureters are slightly lateral in position.
Doctor Fetter. Virtually the entire generous biopsy specimen of tumor was sectioned and all areas presented the same rather uniform histology, characteristic of seminoma. POSTOPERATIVE COURSE
Doctor Brendler. In view of the histologic diagnosis careful re-examination of the testes was accomplished but no abnormalities were noted. Because of some mild postoperative pulmonary symptoms a chest x-ray was repeated 10 days subsequent to the original normal film. There was now definite evidence of bilateral pulmonary nodules, presumed to be metastatic lesions (fig. 3). Radiation therapy was initiated with 3,000 rad to the abdominal area of tumor, administered during a 3-week interval. During this time there was rapid progression in the lung metastases, although the patient remained free of symptoms. Shortly after completion of radiation therapy hemoptysis and dyspnea developed and a course of 10 mg. phenylalanine mustard daily for 10 days was administered. Despite this therapy there was further deterioration with persistent abdominal mass and pulmonary and systemic symptoms. Because of rapid progression of the pulmonary lesions the patient was treated with 1,800 rad to both lung fields. Three months after the original hospitalization the patient was rehospitalized in respiratory distress with altered mental status, tachycardia and congestive failure, anemia with hemoglobin 7.4 gm. per cent and widespread pulmonary metastatic disease. He died <24 hours later. DIAGNOSTIC EVALUATION
Doctor Glenn. We have a germinal cell tumor that progressed rapidly. However, you have not mentioned the usual tumor markers that we might have used, P-subunit human chorionic gonadotropin (HCG) and a-fetoprotein (AFP), or even urinary gonadotropins. Furthermore, it seems unusual that one or more of the combination chemotherapy regimens were not used in the care of this patient.
FIG. 3. Chest film 10 days after hospitalization demonstrates pulmonary nodules thought to represent metastatic malignancy.
Doctor Dees. This patient had been seen in 1965. Since that time there have been tremendous advances in the diagnosis and management of germinal cell tumors, including the identification of appropriate tumor markers, the advent of effective lymphangiography and substantial advances in surgery and chemotherapy. It was believed that presentation of this clinical problem might provide an appropriate opportunity for discussion of these advances. Doctor Glenn. Doctor Older, can you offer any insight into
RETROPERITONEAL MASS IN 58-YEAR-OLD MAN
this malignant and fulminating process from the vantage point of radiology? Dr. Robert A. Older. The 3 IVPs obtained at different intervals preoperatively were all identical, demonstrating dilatation of the left renal pelvis and upper ureter with mild lateral deviation of the left ureter. The ureter could have been further evaluated with the use of a cross-table lateral film that might have shown some anterior deviation. As Doctor Dees stated, however, this case was done in 1965 and the x-ray tables available in the urology clinic at that time did not have the capability for cross-table lateral films. Routine lateral films in which the patient is turned on his side are not as valuable for evaluation of the ureter since the upper kidney and ureter tend to fall forward. The relative symmetry of the 2 ureters may well have diminished somewhat the consideration of their lateral position as being abnormal. If such a question were raised today and could not be resolved with a simple maneuver such as the cross-table lateral then the most appropriate study would be computerized tomography. This new modality is particularly effective in retroperitoneal lesions. Since there was no preoperative suggestion of tumor lymphangiography, which would most likely have been positive, was not performed. Although no stones could be seen on the preliminary films the possibility of a non-opaque calculus as the cause of the partial obstruction· on the left side could not be excluded totally. As far as the pulmonary metastases are concerned the sequential films showed rapid progression of the pulmonary lesions, apparently unaffected by either the brief course of chemotherapy or the pulmonary radiotherapy. The lesions simply appear as those of any type of metastatic lesion and are not distinctive.
537
Braunstein and associates." Generally, we are aware of the specificity of AFP, the a-I-globulin, which is commonly elevated in patients with testicular tumor, hepatocellular malignancies and probably other carcinomas as well. In the case under discussion here I believe that we would today find massive elevations of /3-HCG and AFP, a clinical supposition that cannot be definitely argued but is supported by the massive and rapidly progressive disease in this particular patient. Indeed, the overwhelming neoplastic process in this patient strongly suggests that this is more than seminoma. Clearly, we have observed seminoma in the biopsy specimen but the clinical course suggests that there may have been other germinal cell elements present. The rapid progression and the failure of response to either radiotherapy or chemotherapy imply that this is a highly anaplastic and virulently malignant neoplasm. Obviously, the tumor that comes to mind is choriocarcinoma, the most malignant of the germinal tumors. With these observations and our conviction that retrnperitoneal abdominal germinal malignancy is usually clinical assessment would lead to a diagnosis of mixed choriocarcinoma of the testis, primary focus obscure or obliterated, metastatic to the retroperitoneum and to the lungs. CLINICAL DIAGNOSIS
Primary retroperitoneal seminoma with metastases. DOCTOR GLENN'S DIAGNOSIS
Metastatic mixed germinal cell tumor of the testis, primary focus obscure, probably including syncytiotrophoblastic tumor (choriocarcinoma).
CLINICAL DISCUSSION
Doctor Glenn. The rapidly fulminant downhill course of this patient strongly suggests that we are treating something other than seminoma. One would not expect pulmonary metastases of seminoma to progress so rapidly and it might be anticipated that the abdominal mass would have shown at least some response to radiation had this been seminoma of the usual sort. On the other hand, we had been told that genital examination, preoperatively and again postoperatively disclosed normal testes. If we accept these observations then we are forced to speculate that we are treating an extragonadal germinal cell tumor of very malignant character, possibly anaplastic seminoma OJr perhaps an even more virulent malignancy. Wacksman and associates reviewed the patients with extragenital germinal cell neoplasms in our institution, noting the distinct difference between those patients with abdominal retroperitoneal germinal tumors compared to those with germinal cell tumors of the mediastinum. 1 Patients with mediastinal germinal tumors may, indeed, be exhibiting primary malignancies arising from the germinal ridge, as previously documented by Utz and Buscemi. 2 More often retroperitoneal and even mediastinal germinal or gonadal malignancies represent metastatic disease with occult primary lesions of the testis. Friedman and Moore documented 29 patients presenting with primary retroperitoneal germinal tumors, 15 actually representing metastatic occult testis tumor. 3 Meares and Briggs have reported specifically on occult seminoma of the testis masquerading as primary extragonadal germinal neoplasia, probably not an uncommon phenomenon. 4 Based upon our own experience it can be concluded that primary tumors of the retroperitoneum probably represent metastatic testis tumor, while germinal cell tumors arising in the mediastinum may, indeed, be primary. In the case under discussion today it would have been extremely helpful to have the advantage of the various tumor markers. More than 10 years ago we initiated use of urinary gonadotropin determinations as an index of malignant potential and progression of testicular malignancies. 5 Of course, this determination has been replaced by the more and sensitive deter1nination of JB-HCG as documented. 1
DISCUSSION OF PATHOLOGY
Doctor Fetter. At autopsy metastatic malignancy was found in the lungs, liver, right kidney, spleen, brain and para-aortic as well as hilar lymph nodes. Everywhere the tumor had similar appearance and was hemorrhagic in character. Histologically, 2 cell types could be identified: multinucleated syncytial giant cells and smaller cells with a single nucleus (fig. 4, A). The latter mononuclear cells were arranged in groups, while the multinucleated giant cells were scattered. The histology of the tumor at autopsy, consistent in all foci, was entirely different from that observed in the surgical biopsy specimen. The latter was composed of a single cell type with a fine vesicular nucleus, arranged in nests surrounded by delicate stroma with a lymphoid infiltrate, the pattern entirely compatible with seminoma. On the contrary, the tumor at autopsy is clearly choriocarcinoma. Careful examination of the testes was accomplished in an attempt to identify a primary focus of malignancy. The only abnormality found was in the hilus of the left testis where a small, firm area of approximately 3 mm. in diameter could be identified. Histologic evaluation of this area revealed a few metaplastic abnormal cells, not overly malignant and not in sufficient quantity to demonstrate a definitive pattern (fig. 4, B). The area was somewhat fibrous in character and was consistent with the "burned out" focus of primary testicular neoplasia, which is described by Mostofi and Price who state that such a focus is usually "a well-defined fibrous scar in the testis consisting of relatively acellular usually dense, but sometimes loose, connective tissue". 7 These same authors further state that "seminoma may metastasize as seminoma in 60% of cases, as embryonal carcinoma in 25%, choriocarcinoma in 9%, and teratoma in 4%". Based upon the tissue changes presented here it may be postulated that the primary tumor was either seminoma or seminoma with choriocarcinoma, that it metastasized as seminoma and choriocarcinoma based upon the surgical biopsy and the autopsy ,.,,,m.,dm,o and that the focus became Hburned ouf'. In a more Ms:o·.c,.uac1 ve:&n it seerz1s
538
CLINICOPATHOLOGICAL CONFERENCE
FIG. 4. A, autopsy specimens of metastatic malignancy exhibited multinucleated syncytial giant cells and smaller cells with single nucleus, consistent with choriocarcinoma. B, fibrous area of left testis with few metaplastic cells, consistent with "burned out" focus of testicular neoplasia. reasonable to postulate that the seminomatous elements of the metastatic process responded totally to either radiation therapy or chemotherapy or the combination of the 2, leaving behind only the more malignant and unresponsive elements of syncytiotrophoblastic tumor that progressed to the death of the patient. PATHOLOGIC DIAGNOSIS
Choriocarcinoma with "burned out" primary in left testis, possibly originating as seminoma, with widespread metastatic spread. MANAGEMENT COMMENTARY
Doctor Glenn. There is much in this case to prompt our thoughtful consideration of management of testicular malignancies. We should emphasize once again the value of the tumor markers, ,8-HCG and AFP, in the initial assessment and continuing care of patients with testis tumors, clearly appropriate today. Next, we should observe once again that seminoma has the capacity to metastasize as germinal cell elements of greater malignant potential, perhaps a compelling reason to consider retroperitoneal lymphadenectomy in even the most straightforward instances of primary seminoma of the testis. Finally, although this patient presented with an overwhelming disease, it seems likely that some response Inight have been achieved with the chemotherapeutic tools available to us today. It is apparent that this patient was beyond the realm of simple retroperitoneal lymphadenectomy or resection of tumor at primary presentation. As indicated by Lindsey and Glenn our preferential mode of treatment would be primary retroperitoneal lymphadenectomy, if possible. 8 Here, exploration disclosed that the tumor was unresectable and we would then have followed the management plan of Skinner9 with intensive
chemotherapy, possible radiation therapy and subsequent secondary surgical intervention. While beyond the realm of this discussion it certainly is obvious that the primitive nature of this tumor would prompt current use of combination chemotherapy to include cis-platinum as popularized by Einhorn and Donohue. 10 The most effective combination today would be a combination of vinblastine, actinomycin D, bleomycin and cisplatinum. REFERENCES
1. Wacksman, J., Case, G. and Glenn, J. F.: Extragenital gonadal neoplasia and metastatic testicular tumor. Urology, 5: 221, 1975. 2. Utz, D. C. and Buscemi, M. F.: Extragonadal testicular tumors. J. Urol., 105: 271, 1971. 3. Friedman, N. B. and Moore, R. A.: Tumors of the testis: a report on 922 cases. Mil. Surg., 99: 573, 1946. 4. Meares, E. M., Jr. and Briggs, E. M.: Occult seminoma of the testis masquerading as primary extragonadal germinal neoplasms. Cancer, 30: 300, 1972. 5. Wilson, J.M. and Woodhead, D. M.: Prognostic and therapeutic implications of urinary gonadotropin levels in the management of testicular neoplasia. J. Urol., 108: 754, 1972. 6. Braunstein, G.D., McIntyre, K. R. and Waldman, T. A.: Discordance of human chorionic gonadotropin and alpha-fetoprotein in testicular teratocarcinomas. Cancer, 31: 1065, 1973. 7. Mostofi, F. K. and Price, E. B., Jr.: Tumors of the male genital system. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 8, 1973. 8. Lindsey, C. M. and Glenn, J. F.: Germinal malignancies of the testis: experience, management and prognosis. J. Urol., 116: 59, 1976. 9. Skinner, D. G.: Management of nonseminomatous tumors of the testis. In: Genitourinary Cancer. Edited by D. G. Skinner and J. B. deKernion. Philadelphia: W. B. Saunders Co., chapt. 27, 1978. 10. Einhorn, L. H. and Donohue, J. P.: Improved chemotherapy in disseminated testicular cancer. J. Urol., 117: 65, 1977.
V oL 122, October Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
Clinicopathologi cal Conference RETROPERITONEAL MASS IN
58-YEAR-OLD MAN
CHARLES B. BRENDLER, * JOHN E. DEES,t ROBERT A. OLDER,:j: BERNARD F. FETTER§ JAMES F. GLENNII
AND
From the Departments of Urology; Radiology and Pathology, Duke University Medical Center, Durham, North Carolina
afebrile, white blood count remained within normal limits and urine remained microscopically clear. On the third a repeat IVP disclosed no with pers1st(mt obstmction of the left upper ureter 1). n·,,th,-en""'rm,c examination disclosed a normal bladder and ureteral orifices. A 6F mOno,Hn h~ureteral up the left ureter to the level of the encou1c,tenr1g no resistance or obstruction, and a drip of was obtained. The catheter was indwelling, the sym.ptoms resolved completely and the ureteral catheter was removed 48 hours later only to incite recurrence of colicky left flank pain. At this point a third IVP was obtained and again disclosed obstruction of the upper left ureter without evidence of definite ureteral stone. An upper gastrointestinal series and a barium enema were within normal limits. Surgical exploration was elected.
Dr. Charles B. Brendler. A '"'·-"''",.-"'''"' white man was in 1965 with a 12-hom of intermittent left flank unassociated with any constitutional or symptoms. He denied any diffiand been in excellent general health except for an episode of gouty arthritis 8 years He had experienced no further difficulty with gout, was on no medication and was unaware of any chemical abnormalities. Pre-admission urinalysis revealed rare white blood cells, no bacteria, but 8 to 10 red blood cells per high power field in the spun urinary sediment. A plain x-ray of the abdomen was unremarkable, with no evidence of urinary calculL Excretory urography (IVP) disclosed a normal right kidney and an intrinsically normal but slightly lateral right ureter. The bladder was unremarkable as well. However, on the left side there was delay in excretion of contrast material with dilatation of the renal pelvis and upper PREOPERATIVE DIAGNOSIS ureter down to the level of the L2, L3 intervertebral disk space. Dr. John E. Dees. Our presumptive diagnosis was a nonThe left ureter also showed a somewhat lateral position. A opaque calculus subtotally obstructing the left ureter. The presumptive diagnosis of an obstructing non-opaque ureteral · patient had a history of an attack of gouty arthritis, although calculus was entertained and the patient was hospitalized for the uric acid levels were normal. The only urinary abnormality supportive treatment and observation. was microscopic hematuria. We had no definite evidence of Physical examination disclosed a middle-aged white man in intrinsic stricture of the ureter or extrinsic to cause moderate discomfort. Vital signs included temperature ureteral obstruction. Furthermore, there was no physical or pulse 80, respirations 20 and blood pressure 160/90. Examina- radiographic evidence of an abdominal mass. tion of the head, eyes, ears, nose and throat was within normal limits. The lungs were clear to percussion and auscultation, and SURGICAL FINDINGS cardiac examination was unremarkable. Examination of the abdomen disclosed moderate obesity without masses, guarding Doctor Brendler. Exploration was accomplished through a or rebound tenderness but there was some direct tenderness in left flank 12th rib incision. When the retroperitoneal space was the left lower quadrant. Bowel sounds were normal and active. entered a large, smooth mass was encountered, which was Rectal examination disclosed a normal prostate and was oth- intimately attached to the posterior abdominal musculature erwise unremarkable. External genitalia were normal to inspec- and extended from the hilus of the kidney down to the level of tion and palpation. Extremities were unremarkable and neuro- the bifurcation of the aorta. With further exposure it was found logical examination was within normal limits. that the mass extended ac.ross the midline and involved the Clinical laboratory findings included hemoglobin 13.2 gm. per aorta and the vena cava. The ureter was encased by the mass cent, hematocrit 39.4 mg. per cent, with white blood count 9,200 at the level of the lower pole of the kidney. The tumor was and differential normal. Blood sugar was 103 mg. per cent, separate from the kidney but was deemed unresectable because blood urea nitrogen 23 mg. per cent, sodium 140 mEq./1., of its extent and involvement of major vessels. Accordingly, a potassium 4.1 mEq./1., chloride 102 mEq./l., carbon dioxide 26 left nephrectomy was accomplished and an ample biopsy of the mM./l., total protein 7.5 gm. per cent with albumin 3.4 gm. per mass was taken. Frozen section histologic evaluation disclosed cent and globulin 4.1 gm. per cent, calcium and phosphorus 9.6 anaplastic malignancy, most likely seminoma. and 2.6 mg. per cent, respectively, and uric acid 7.0 mg. per cent. These values were all normal for this laboratory. A chest DISCUSSION OF PATHOLOGY x-ray was within normal limits but was not an optimal study. Dr. Bernard F. Fetter. The surgical specimen was completely An electrocardiogram was normal. For 2 days the patient was observed, symptoms of discomfort adequate for diagnostic evaluation. Clearly malignant, the tupersisting but relieved minimal analgesia. He remained mor was composed of a single cell type with a fine, vesicular nucleus (fig. 2). The cytoplasm throughout was pale to nonstaining. Cells were arranged in nests and surrounded by a • Chief Resident in Urology. delicate stroma in which there was lymphoid infiltrate. The t Professor of Uroiogy. pattern was completely characteristic of seminoma. t Associate Professor of Radiology and Director of Uroradio!ogy. Dr. James F. Glenn. Vias the entire tumor sp,ecirr,en exam§ Pxofessor of Pathology. and 1Nere there any other cells or elerr.1.ents to suggest II Chief of 1 Case nr,,s.ent,,d at Urology R,ou?1.ds on January 1979. ~,,,-c,;,~~ nther tha11. seminorna?
536
CLINICOPATHOLOGICAL CONFERENCE
FIG. 2. Representative histologic pattern of abdominal tumor, characteristic of seminoma.
FIG. 1. IVP demonstrates moderate obstruction in left upper ureter. Both ureters are slightly lateral in position.
Doctor Fetter. Virtually the entire generous biopsy specimen of tumor was sectioned and all areas presented the same rather uniform histology, characteristic of seminoma. POSTOPERATIVE COURSE
Doctor Brendler. In view of the histologic diagnosis careful re-examination of the testes was accomplished but no abnormalities were noted. Because of some mild postoperative pulmonary symptoms a chest x-ray was repeated 10 days subsequent to the original normal film. There was now definite evidence of bilateral pulmonary nodules, presumed to be metastatic lesions (fig. 3). Radiation therapy was initiated with 3,000 rad to the abdominal area of tumor, administered during a 3-week interval. During this time there was rapid progression in the lung metastases, although the patient remained free of symptoms. Shortly after completion of radiation therapy hemoptysis and dyspnea developed and a course of 10 mg. phenylalanine mustard daily for 10 days was administered. Despite this therapy there was further deterioration with persistent abdominal mass and pulmonary and systemic symptoms. Because of rapid progression of the pulmonary lesions the patient was treated with 1,800 rad to both lung fields. Three months after the original hospitalization the patient was rehospitalized in respiratory distress with altered mental status, tachycardia and congestive failure, anemia with hemoglobin 7.4 gm. per cent and widespread pulmonary metastatic disease. He died <24 hours later. DIAGNOSTIC EVALUATION
Doctor Glenn. We have a germinal cell tumor that progressed rapidly. However, you have not mentioned the usual tumor markers that we might have used, P-subunit human chorionic gonadotropin (HCG) and a-fetoprotein (AFP), or even urinary gonadotropins. Furthermore, it seems unusual that one or more of the combination chemotherapy regimens were not used in the care of this patient.
FIG. 3. Chest film 10 days after hospitalization demonstrates pulmonary nodules thought to represent metastatic malignancy.
Doctor Dees. This patient had been seen in 1965. Since that time there have been tremendous advances in the diagnosis and management of germinal cell tumors, including the identification of appropriate tumor markers, the advent of effective lymphangiography and substantial advances in surgery and chemotherapy. It was believed that presentation of this clinical problem might provide an appropriate opportunity for discussion of these advances. Doctor Glenn. Doctor Older, can you offer any insight into
RETROPERITONEAL MASS IN 58-YEAR-OLD MAN
this malignant and fulminating process from the vantage point of radiology? Dr. Robert A. Older. The 3 IVPs obtained at different intervals preoperatively were all identical, demonstrating dilatation of the left renal pelvis and upper ureter with mild lateral deviation of the left ureter. The ureter could have been further evaluated with the use of a cross-table lateral film that might have shown some anterior deviation. As Doctor Dees stated, however, this case was done in 1965 and the x-ray tables available in the urology clinic at that time did not have the capability for cross-table lateral films. Routine lateral films in which the patient is turned on his side are not as valuable for evaluation of the ureter since the upper kidney and ureter tend to fall forward. The relative symmetry of the 2 ureters may well have diminished somewhat the consideration of their lateral position as being abnormal. If such a question were raised today and could not be resolved with a simple maneuver such as the cross-table lateral then the most appropriate study would be computerized tomography. This new modality is particularly effective in retroperitoneal lesions. Since there was no preoperative suggestion of tumor lymphangiography, which would most likely have been positive, was not performed. Although no stones could be seen on the preliminary films the possibility of a non-opaque calculus as the cause of the partial obstruction· on the left side could not be excluded totally. As far as the pulmonary metastases are concerned the sequential films showed rapid progression of the pulmonary lesions, apparently unaffected by either the brief course of chemotherapy or the pulmonary radiotherapy. The lesions simply appear as those of any type of metastatic lesion and are not distinctive.
537
Braunstein and associates." Generally, we are aware of the specificity of AFP, the a-I-globulin, which is commonly elevated in patients with testicular tumor, hepatocellular malignancies and probably other carcinomas as well. In the case under discussion here I believe that we would today find massive elevations of /3-HCG and AFP, a clinical supposition that cannot be definitely argued but is supported by the massive and rapidly progressive disease in this particular patient. Indeed, the overwhelming neoplastic process in this patient strongly suggests that this is more than seminoma. Clearly, we have observed seminoma in the biopsy specimen but the clinical course suggests that there may have been other germinal cell elements present. The rapid progression and the failure of response to either radiotherapy or chemotherapy imply that this is a highly anaplastic and virulently malignant neoplasm. Obviously, the tumor that comes to mind is choriocarcinoma, the most malignant of the germinal tumors. With these observations and our conviction that retrnperitoneal abdominal germinal malignancy is usually clinical assessment would lead to a diagnosis of mixed choriocarcinoma of the testis, primary focus obscure or obliterated, metastatic to the retroperitoneum and to the lungs. CLINICAL DIAGNOSIS
Primary retroperitoneal seminoma with metastases. DOCTOR GLENN'S DIAGNOSIS
Metastatic mixed germinal cell tumor of the testis, primary focus obscure, probably including syncytiotrophoblastic tumor (choriocarcinoma).
CLINICAL DISCUSSION
Doctor Glenn. The rapidly fulminant downhill course of this patient strongly suggests that we are treating something other than seminoma. One would not expect pulmonary metastases of seminoma to progress so rapidly and it might be anticipated that the abdominal mass would have shown at least some response to radiation had this been seminoma of the usual sort. On the other hand, we had been told that genital examination, preoperatively and again postoperatively disclosed normal testes. If we accept these observations then we are forced to speculate that we are treating an extragonadal germinal cell tumor of very malignant character, possibly anaplastic seminoma OJr perhaps an even more virulent malignancy. Wacksman and associates reviewed the patients with extragenital germinal cell neoplasms in our institution, noting the distinct difference between those patients with abdominal retroperitoneal germinal tumors compared to those with germinal cell tumors of the mediastinum. 1 Patients with mediastinal germinal tumors may, indeed, be exhibiting primary malignancies arising from the germinal ridge, as previously documented by Utz and Buscemi. 2 More often retroperitoneal and even mediastinal germinal or gonadal malignancies represent metastatic disease with occult primary lesions of the testis. Friedman and Moore documented 29 patients presenting with primary retroperitoneal germinal tumors, 15 actually representing metastatic occult testis tumor. 3 Meares and Briggs have reported specifically on occult seminoma of the testis masquerading as primary extragonadal germinal neoplasia, probably not an uncommon phenomenon. 4 Based upon our own experience it can be concluded that primary tumors of the retroperitoneum probably represent metastatic testis tumor, while germinal cell tumors arising in the mediastinum may, indeed, be primary. In the case under discussion today it would have been extremely helpful to have the advantage of the various tumor markers. More than 10 years ago we initiated use of urinary gonadotropin determinations as an index of malignant potential and progression of testicular malignancies. 5 Of course, this determination has been replaced by the more and sensitive deter1nination of JB-HCG as documented. 1
DISCUSSION OF PATHOLOGY
Doctor Fetter. At autopsy metastatic malignancy was found in the lungs, liver, right kidney, spleen, brain and para-aortic as well as hilar lymph nodes. Everywhere the tumor had similar appearance and was hemorrhagic in character. Histologically, 2 cell types could be identified: multinucleated syncytial giant cells and smaller cells with a single nucleus (fig. 4, A). The latter mononuclear cells were arranged in groups, while the multinucleated giant cells were scattered. The histology of the tumor at autopsy, consistent in all foci, was entirely different from that observed in the surgical biopsy specimen. The latter was composed of a single cell type with a fine vesicular nucleus, arranged in nests surrounded by delicate stroma with a lymphoid infiltrate, the pattern entirely compatible with seminoma. On the contrary, the tumor at autopsy is clearly choriocarcinoma. Careful examination of the testes was accomplished in an attempt to identify a primary focus of malignancy. The only abnormality found was in the hilus of the left testis where a small, firm area of approximately 3 mm. in diameter could be identified. Histologic evaluation of this area revealed a few metaplastic abnormal cells, not overly malignant and not in sufficient quantity to demonstrate a definitive pattern (fig. 4, B). The area was somewhat fibrous in character and was consistent with the "burned out" focus of primary testicular neoplasia, which is described by Mostofi and Price who state that such a focus is usually "a well-defined fibrous scar in the testis consisting of relatively acellular usually dense, but sometimes loose, connective tissue". 7 These same authors further state that "seminoma may metastasize as seminoma in 60% of cases, as embryonal carcinoma in 25%, choriocarcinoma in 9%, and teratoma in 4%". Based upon the tissue changes presented here it may be postulated that the primary tumor was either seminoma or seminoma with choriocarcinoma, that it metastasized as seminoma and choriocarcinoma based upon the surgical biopsy and the autopsy ,.,,,m.,dm,o and that the focus became Hburned ouf'. In a more Ms:o·.c,.uac1 ve:&n it seerz1s
538
CLINICOPATHOLOGICAL CONFERENCE
FIG. 4. A, autopsy specimens of metastatic malignancy exhibited multinucleated syncytial giant cells and smaller cells with single nucleus, consistent with choriocarcinoma. B, fibrous area of left testis with few metaplastic cells, consistent with "burned out" focus of testicular neoplasia. reasonable to postulate that the seminomatous elements of the metastatic process responded totally to either radiation therapy or chemotherapy or the combination of the 2, leaving behind only the more malignant and unresponsive elements of syncytiotrophoblastic tumor that progressed to the death of the patient. PATHOLOGIC DIAGNOSIS
Choriocarcinoma with "burned out" primary in left testis, possibly originating as seminoma, with widespread metastatic spread. MANAGEMENT COMMENTARY
Doctor Glenn. There is much in this case to prompt our thoughtful consideration of management of testicular malignancies. We should emphasize once again the value of the tumor markers, ,8-HCG and AFP, in the initial assessment and continuing care of patients with testis tumors, clearly appropriate today. Next, we should observe once again that seminoma has the capacity to metastasize as germinal cell elements of greater malignant potential, perhaps a compelling reason to consider retroperitoneal lymphadenectomy in even the most straightforward instances of primary seminoma of the testis. Finally, although this patient presented with an overwhelming disease, it seems likely that some response Inight have been achieved with the chemotherapeutic tools available to us today. It is apparent that this patient was beyond the realm of simple retroperitoneal lymphadenectomy or resection of tumor at primary presentation. As indicated by Lindsey and Glenn our preferential mode of treatment would be primary retroperitoneal lymphadenectomy, if possible. 8 Here, exploration disclosed that the tumor was unresectable and we would then have followed the management plan of Skinner9 with intensive
chemotherapy, possible radiation therapy and subsequent secondary surgical intervention. While beyond the realm of this discussion it certainly is obvious that the primitive nature of this tumor would prompt current use of combination chemotherapy to include cis-platinum as popularized by Einhorn and Donohue. 10 The most effective combination today would be a combination of vinblastine, actinomycin D, bleomycin and cisplatinum. REFERENCES
1. Wacksman, J., Case, G. and Glenn, J. F.: Extragenital gonadal neoplasia and metastatic testicular tumor. Urology, 5: 221, 1975. 2. Utz, D. C. and Buscemi, M. F.: Extragonadal testicular tumors. J. Urol., 105: 271, 1971. 3. Friedman, N. B. and Moore, R. A.: Tumors of the testis: a report on 922 cases. Mil. Surg., 99: 573, 1946. 4. Meares, E. M., Jr. and Briggs, E. M.: Occult seminoma of the testis masquerading as primary extragonadal germinal neoplasms. Cancer, 30: 300, 1972. 5. Wilson, J.M. and Woodhead, D. M.: Prognostic and therapeutic implications of urinary gonadotropin levels in the management of testicular neoplasia. J. Urol., 108: 754, 1972. 6. Braunstein, G.D., McIntyre, K. R. and Waldman, T. A.: Discordance of human chorionic gonadotropin and alpha-fetoprotein in testicular teratocarcinomas. Cancer, 31: 1065, 1973. 7. Mostofi, F. K. and Price, E. B., Jr.: Tumors of the male genital system. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 8, 1973. 8. Lindsey, C. M. and Glenn, J. F.: Germinal malignancies of the testis: experience, management and prognosis. J. Urol., 116: 59, 1976. 9. Skinner, D. G.: Management of nonseminomatous tumors of the testis. In: Genitourinary Cancer. Edited by D. G. Skinner and J. B. deKernion. Philadelphia: W. B. Saunders Co., chapt. 27, 1978. 10. Einhorn, L. H. and Donohue, J. P.: Improved chemotherapy in disseminated testicular cancer. J. Urol., 117: 65, 1977.