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Carcinoma of the Epididymis1
CARCINOMA OF THE EPIDIDYMIS 1 JAMES A. MAY
Malignant tumors of the epididymis are extremely rare and those of epithelial origin comprise a very small portion of the group. An additional case of primary carcinoma of the epididymis, in which the head of the epididymis only was involved, is reported. The histo-pathologic picture of the tumor, which made its classification difficult, and the fact that it is one of the few cases of carcinoma of the epididymis in which estimations of the gonadotropic hormone of the urine have been made, are added points of interest. Twenty-three cases of carcinoma of the epididymis have been reported to date. In a review of the literature on tumors of the epididymis, spermatic cord, and testicular tunics in 1924, Hinman and Gibson found 3 reported cases of carcinoma of the epididymis which they felt could be considered authentic. To these they added a case of their own. They also reported a case of seminoma of the epididymis which involved the testis as well; there was some doubt as to whether or not this tumor had its origin in the epididymis. In 1934, Ferrier and Foord collected a total of 14 cases of primary carcinoma of the epididymis; this number included 3 of the seminoma type. The addition of their own case of carcinoma brought the total number to 15. In 1936, Thompson added a case of seminoma reported by de Vincentiis to this number, and reported 7 additional cases. Two of these seven tumors were definitely malignant and five were comparatively benign. Of the latter, four were classified as adenocarcinoma, grade 1, and one as adenocarcinoma, grade 2. The case reported here brings the total number to 24. It is the third reported case in which the tumor involved only the head of the epididymis. The patient was a barber, aged 49 years. He was first seen at the Clinic on February 13, 1931, at which time he complained of a mass in the left side of the scrotum which he had first noticed approximately six weeks earlier. Since that time there had been a progressive increase in its size. He complained also of a soreness and dragging sensation in the left testicle and spermatic cord. There was no history of injury. An indirect inguinal hernia which was distinct from the mass had been present for seven years. Twelve 1 Read before the Urological Section of the California Medical Association at the annual meeting, Coronado, Calif., May 25-28, 1936. 391
392
JAMES A. MAY
years previously he had received urethral injections and prostatic massages for a gonorrheal infection which had subsided in ten weeks time. Epididymitis was not a complication. Otherwise his past health had been excellent. There had been no loss of weight. There was no history of cancer in his immediate family. Upon examination, the left side of the scrotum was found to contain a soft mass approximately the size of a baseball through which the testis could not be palpated accurately. This mass transmitted light and after the aspiration of 5 ounces of clear, amber-colored fluid, the scrotal contents could be palpated easily. The testis felt normal in size and consistency as did the body and tail of the epididymis. In the region of the head of the epididymis there was a hard, nodular mass approximately 3 by 2 cm. in size. Above this mass, an inguinal hernia protruded through a dilated external ring. There was no inguinal adenopathy. The right testis, epididymis and spermatic cord were considered normal. Upon rectal examination, the prostate was found to be slightly enlarged, of normal consistency and well encapsulated; its median groove was well defined. The seminal vesicles were not indurated or nodular. There was no urethral discharge. No acid-fast bacilli were found on repeated stains of the urine sediment and no malignant cells were found in the stained prostatic secretion. General physical examination revealed no pathology outside of the genitourinary system. Roentgenologic studies of the entire gastro-intestinal tract were normal and roentgenograms of the kidney, ureter and bladder areas revealed no metastatic areas in the bones. Stereoscopic roentgenograms of the lungs showed a chronic non-tuberculous pneumonitis of the left lower lung fields. The Kahn and Wassermann reactions of the blood were negative. The pre-operative diagnosis was a tumor mass in the head of the left epididymis, tuberculous or malignant in nature; a left hydrocele; and an indirect left inguinal hernia. On February 16, 1931, the scrotum was explored through a left inguinal incision, under spinal anesthesia. After the excision of the hernial sac, the testis appeared and felt normal. In the head of the epididymis a slightly nodular tumor, approximately 3 by 2 cm. in size was found. Because of the presence of the tumor, the testis and spermatic cord were removed by high excision at the level of the internal inguinal ring. Careful dissection of the operated specimen demonstrated a grayish-white solid tumor which completely replaced the head of the epididymis (figs. 1 and 2). The tumor tapered down to a point opposite the middle portion of the testis and became continuous with normal-appearing epididymis. The body and tail of the epididymis and the vas deferens appeared normal. There were no areas of caseation and, grossly, no areas of invasion of the testis. The specimen was given to Dr. H. S. Sumerlin for pathologic study. Blocks
CARCINOMA OF EPIDIDYMIS
393
of tissue for microscopic examination were taken from the junction of the tumor and body of the epididymis, from the rete, and from the testis itself. In the spaces between the ducts, there was an infiltration of small closely packed cells, the nuclei of which were highly chromatic and for the most part, fairly round (fig. 3). The cells had practically no cytoplasm, and were distributed in clusters, strands and sheets in a loose :fibrous stroma. Examination of many sections disclosed no other type of cell. Atypical mitoses were numerous. Lymphocytes were scattered throughout the tissue. Most of the ducts appeared normal; there were a few atypical ones which suggested metaplasia but definite transition was not demonstrated (:fig. 5). Sections from the rete (fig. 6) and from the testis showed no neoplastic change. Dr.
FIG. 1 FIG. 2 FIG. 1. Specimen removed at operation. Cut surface of testis and epididymis, showing carcinoma of the epididymis FIG. 2. Epididymis opened to show tumor in globus major
Sumerlin considered the growth to be an infiltrating carcinoma of a high grade of malignancy which presumably had its origin in the epididymis. Immediate post-operative irradiation, directed over the anterior and posterior aspects of the pelvis was given. For seven days,-March 16, 1931 to March 23, 1931,-daily exposure to x-rays generated at 200 kilovolts from a distance of 50 cm. through a filter of 0.5 mm. copper and 1 mm. aluminum, was made. A total of 800 roentgens was given. The patient returned to work on April 15, 1931, and was seen at monthly intervals thereafter. On September 3, 1931, he complained of soreness over the left pubic area. There was no evidence of local recurrence and roentgenograms of the kidney, ureter and bladder areas again showed no bone pathology.
394
JAMES A. MAY
December 7, 1933, twenty-two months after the operation, he noticed a tumor in the left side of the abdomen. At this time he complained also of indigestion, fatigue and loss of weight. The tumor was nodular and extended from the left costal border to the pelvic brim. In addition, a smaller tumor was palpated on the right side. Upon rectal examination a hard, nodular mass was felt above the prostate. Roentgenologic examination of the chest revealed no metastatic changes in the lung fields or the rib cage. Further irradiation was directed to all four quadrants of the abdomen, and resulted in marked diminution in the size of the abdominal tumors. A total of 2400 roentgens was given over a period of five weeks.
FIG. 3. Section through tumor showing infiltration of cells, between ducts.
(X 100)
On April 12, 1934, a nodule appeared in the right supraclavicular space. A roentgenogram of the chest showed no metastases in the lung fields. On April 19, 1934, the patient complained of pain in the right eye and right side of the head and of difficulty in walking. The findings of a neurological , examination indicated the presence of a lesion in the brain stem. Roentgen examination of the skull showed extensive metastases in the parietal, occipital and sphenoidal bones. From April 12, 1934 to May 9, 1934, irradiation was directed over the cervical region and the skull. A total of 4000 roentgens was given.
395
CARCINOMA OF EPIDIDYMIS
On June 27, 1934, approximately six weeks after his last period of irradiation, urine for the :first gonadotropic hormone determination was obtained. Quantitative estimations were made by Dr. Tracy 0. Powell of Los Angeles, to whom I am indebted for this work. Tests graduated to reveal the presence of as low a level as 200 uni ts of hormone per liter of urine were negative. On September 6, 1934, the abdominal masses were definitely larger and the patient was failing rapidly. Pyuria and pleural effusion developed and from this time until his death his course was febrile. On November 2, 1934, a
FIG.
4
FIG.
s
FIG. 4. Anaplastic cells. ( X 450) FIG. 5. Section of tumor showing atypical ducts suggesting metaplasia.
(X 100)
second specimen of urine was sent for hormone estimation. Dr. Powell reported that no hormone was present in excess of 300 units per liter. Irradiation had not been given for four months prior to this time. On November 22, 1934, the patient died of general carcinomatosis and sepsis. Autopsy was performed by Dr. Howard A. Ball of the San Diego County General Hospital. There was bilateral pleural effusion. There were numerous metastatic lesions of both parietal and visceral pleura on both sides but there was no evidence of metastases within the lung parenchyma. The
396
JAMES A. MAY
liver contained numerous metastatic nodules measuring from 2 to 5 cm. in diameter. The right kidney was hypertrophied and there was marked pyelonephritis. The left kidney was completely imbedded in a large mass of malignant tissue which had attached itself to the ligaments of the spinal column and extended from the level of the diaphragm to the brim of the pelvis. The pelvis and calyces of the kidney were so dilated from back pressure that scarcely any cortex remained. The malignant tissue was traced along the bifurcation of the iliac arteries into the posterior aspect of the pelvis. There was no gross tumor tissue along either inguinal canal. The
Frc. 6. Section through normal rete
bladder wall was not particularly thickened and no malignant changes were found inside the bladder cavity. The prostate showed no evidence of tumor formation but was surrounded by a carcinomatous mass in which the seminal vesicles were imbedded. Dr. Sumerlin examined sections from the autopsy specimens and found that the metastases in the kidneys, liver and lymph nodes reproduced the type of cells originally found in the epididymis. The cells were closely packed, in sheets, and there was practically no stroma. Sections from the prostate showed no evidence of malignancy.
CARCINOMA OF EPIDIDYMIS
397
Discussion. We believe this neoplasm to be a primary carcinoma of the head of the epididymis rather than a teratoid tumor of the testis which had grown into the epididymis. Several blocks of tissue were removed at the junction of the growth and the testis, through the rete testis and from the testis itself, and malignant tissue was found only in those sections which were taken from the tumor mass. The rete testis appeared normal. Microscopic sections of the tumor were sent to Drs. Ewing, Broders and Hinman, all of whom were kind enough to send me their opinions. Dr. Ewing reported as follows: "The tumor of the epididymis which you sent me shows a highly malignant infiltrating carcinoma. The cells are small and composed mostly of nuclei. There are no indications as to its exact origin. It does not resemble any type of carcinoma of the testis with which I am familiar and I wonder whether the tumor may not be metastatic. The majority of carcinomas of the testis arise in the rete and invade both testis and epididymis. This one seems to be entirely in the epididymis. I think you have a rare tumor and I strongly suspect that it is metastatic." Dr. Broders wrote as follows : "I agree with Dr. Sumerlin's diagnosis of carcinoma. It bears a close resemblance to adenocarcinoma of the testicle and appears to be at least of a grade 4 malignancy." Dr. Hinman considered the sections very atypical of a seminoma and thought that "they were more likely a secondary growth, possibly from the prostate or seminal vesicles." Later, after he had received the information that no malignancy was found in the prostate or seminal vesicles and had seen prints of the specimen he wrote "your case is indeed a most unusual and interesting one and from your findings of course looks like a primary carcinoma of the epididymis." Metastatic involvement of the epididymis is extremely rare and the entire clinical course of the disease in this case would indicate that the left scrotal area was the primary site of the new growth. Careful physical examination supplemented by roentgen examinations of the lungs, abdominal area, and complete gastro-intestinal tract at the time the patient was first seen failed to reveal any other pathology, and repeated examinations disclosed no malignant change in any other organ until almost two years after operation when metastases first appeared along the aortic lymph chains. Gonadotropic hormone in the urine of a patient suffering from teratoma testis was first noted by Zondek in 1929. This observation has been of great potential value to urologists in that it offers a possible THE JOURNAL OF UROLOGY, VOL,
36,
NO ,
4
398
JAMES A. MAY
method of differentiation between benign and teratoid growths of the testis and between teratoid growths of the testis and malignant tumors of other pathogenesis in adjacent organs. It offers also in cases of teratoma a possible method of detecting the presence of metastases following the removal of the tumor. By quantitative titration of the hormone in the urine, the progress of the disease following surgery or irradiation may be observed. In April, 1931, Ferguson et al. obtained positive hormone reactions in 12 cases of teratoma testis examined by them in which the malignancy was clinically active. Again, in March 1934, Ferguson reported the results of hormone determinations in 100 cases of benign lesions of the testis in which there was no excretion in excess of 100 units per liter of urine. In 117 consecutive cases of teratoma testis, the excretion of the hormone was in excess of 500 units per liter of urine in all untreated cases with the exception of those of the adult cystic type. Ferguson concludes that their results "indicate the consistent absence of the hormone in non-malignant disease of the testis" and that if the urine assay for 100 units per liter results in no reaction in cases of suspected teratoma, the probability is against the diagnosis. He warns that it does not say that "the case of adult carcinoma of the testis may not exist or that tumors involving neighboring structures not of teratoid origin are absent." Hinman and Powell conclude that "the majority of tumors of the testicle (embryonal) are associated with the presence of gonadotropic hormone in the urine and that the presence of such hormone in the urine of the patient with a tumor of the testis is presumptive evidence of testicular malignancy, and its absence is strong but not de.finite evidence against malignancy." Because of the rarity of epididymal tumors, the number of cases in which hormone estimations have been made is exceedingly small. In July, 1932, Eisenberg, Simons and Wallerstein reported one case of spheroidal cell carcinoma (seminoma) of the epididymis in which the hormone reaction was strongly positive. Sections of the tumor showed large cells with clear cytoplasm and large nuclei with considerable chromatin. The tumor was apparently not present in the testis. Ferguson, in March 1934, reported negative hormone reactions of the urine in one case of .fibrosarcoma of the epididymis, one case of carcinoma of the epididymis and one case of fibrosarcoma of the spermatic cord. In the case reported here, there was no excretion of gonadotropic hormone in the urine in excess of 200 units per liter. The last estimation was made from urine obtained sixteen days before death when the
CARCINOMA OF EPIDIDYMIS
399
metastatic growths were most extensive. Roentgen therapy had not been given for a period of four months prior to this time so that there could have been no effect of the x-rays on hormone excretion at this time. If this tumor had been of testicular origin, one would expect a high titration of gonadotropic hormone in the urine in view of our present knowledge of the hormone excretion in testicular tumors. The fact that the hormone content in our case was less than 200 units per liter of urine is further presumptive evidence that the tumor was not of testicular origin. Statistics on the length of life after operation in the reported cases of carcinoma of the epididymis are not complete. However, a review of the cases reported indicates that metastases occur early and that the prognosis 1s poor. We feel that the immediate postoperative irradiation in our case was a decided factor in lengthening the interval between operation and the development of metastases and in the prolongation of life. We believe that in all such cases high total excision followed by deep roentgen therapy should be the method of treatment. CONCLUSIONS
A case of primary carcinoma in the head of the epididymis is reported. Gonadotropic hormone in excess of 200 units per liter of urine was not found in this case. We believe that removal of the testis and epididymis by high excision of the spermatic cord, followed by intensive radiation therapy, is the method of choice in the treatment of carcinoma of the epididymis.
Rees-Stealy Clinic 2001 Fourth Avenue, San Diego, California. REFERENCES EISENBERG, A. A., SIMONS, I., AND WALLERSTEIN, H.; Case of spheroidal-cell carcinoma (seminoma) of the epididymis. Amer. Jour. Cancer, 16: 875-881, 1932. FERRIER, P. A., AND FooRD, A. G.: Primary carcinoma of the epididymis. Urol. and Cutan. Rev., 38: 646-649, 1934. FERGUSON, R. S.: Clinical evaluation of the quantitative excretion of Prolan-A in teratoma testis. Jour. Urol., 31: 397-409, 1934. - - - , DowNEs, H. R., ELLIS, E., AND NICHOLSON, M. E.: Preliminary note on a new method of differentiating the testicular tumors by biological means. Amer. Jour. Cancer, 15: 835-843, 1931. HINMAN, FRANK, AND GrnsoN, T. E.: Tumors of the epididymis, spermatic cord and testicular tunics. Arch. Surg., 8: 100-137, 1924. - - - , AND POWELL, T. 0.: The gonadotropic hormone in the urine of men with tumor of the testis. Jour. Urol., 34: 55-71, 1935. THOMPSON, G. J.: Tumors of the spermatic cord, epididymis and testicular tunics. Surg., Gynec. and Obstet., 62: 712-728, 1936.
Malignant tumors of the epididymis are extremely rare and those of epithelial origin comprise a very small portion of the group. An additional case of primary carcinoma of the epididymis, in which the head of the epididymis only was involved, is reported. The histo-pathologic picture of the tumor, which made its classification difficult, and the fact that it is one of the few cases of carcinoma of the epididymis in which estimations of the gonadotropic hormone of the urine have been made, are added points of interest. Twenty-three cases of carcinoma of the epididymis have been reported to date. In a review of the literature on tumors of the epididymis, spermatic cord, and testicular tunics in 1924, Hinman and Gibson found 3 reported cases of carcinoma of the epididymis which they felt could be considered authentic. To these they added a case of their own. They also reported a case of seminoma of the epididymis which involved the testis as well; there was some doubt as to whether or not this tumor had its origin in the epididymis. In 1934, Ferrier and Foord collected a total of 14 cases of primary carcinoma of the epididymis; this number included 3 of the seminoma type. The addition of their own case of carcinoma brought the total number to 15. In 1936, Thompson added a case of seminoma reported by de Vincentiis to this number, and reported 7 additional cases. Two of these seven tumors were definitely malignant and five were comparatively benign. Of the latter, four were classified as adenocarcinoma, grade 1, and one as adenocarcinoma, grade 2. The case reported here brings the total number to 24. It is the third reported case in which the tumor involved only the head of the epididymis. The patient was a barber, aged 49 years. He was first seen at the Clinic on February 13, 1931, at which time he complained of a mass in the left side of the scrotum which he had first noticed approximately six weeks earlier. Since that time there had been a progressive increase in its size. He complained also of a soreness and dragging sensation in the left testicle and spermatic cord. There was no history of injury. An indirect inguinal hernia which was distinct from the mass had been present for seven years. Twelve 1 Read before the Urological Section of the California Medical Association at the annual meeting, Coronado, Calif., May 25-28, 1936. 391
392
JAMES A. MAY
years previously he had received urethral injections and prostatic massages for a gonorrheal infection which had subsided in ten weeks time. Epididymitis was not a complication. Otherwise his past health had been excellent. There had been no loss of weight. There was no history of cancer in his immediate family. Upon examination, the left side of the scrotum was found to contain a soft mass approximately the size of a baseball through which the testis could not be palpated accurately. This mass transmitted light and after the aspiration of 5 ounces of clear, amber-colored fluid, the scrotal contents could be palpated easily. The testis felt normal in size and consistency as did the body and tail of the epididymis. In the region of the head of the epididymis there was a hard, nodular mass approximately 3 by 2 cm. in size. Above this mass, an inguinal hernia protruded through a dilated external ring. There was no inguinal adenopathy. The right testis, epididymis and spermatic cord were considered normal. Upon rectal examination, the prostate was found to be slightly enlarged, of normal consistency and well encapsulated; its median groove was well defined. The seminal vesicles were not indurated or nodular. There was no urethral discharge. No acid-fast bacilli were found on repeated stains of the urine sediment and no malignant cells were found in the stained prostatic secretion. General physical examination revealed no pathology outside of the genitourinary system. Roentgenologic studies of the entire gastro-intestinal tract were normal and roentgenograms of the kidney, ureter and bladder areas revealed no metastatic areas in the bones. Stereoscopic roentgenograms of the lungs showed a chronic non-tuberculous pneumonitis of the left lower lung fields. The Kahn and Wassermann reactions of the blood were negative. The pre-operative diagnosis was a tumor mass in the head of the left epididymis, tuberculous or malignant in nature; a left hydrocele; and an indirect left inguinal hernia. On February 16, 1931, the scrotum was explored through a left inguinal incision, under spinal anesthesia. After the excision of the hernial sac, the testis appeared and felt normal. In the head of the epididymis a slightly nodular tumor, approximately 3 by 2 cm. in size was found. Because of the presence of the tumor, the testis and spermatic cord were removed by high excision at the level of the internal inguinal ring. Careful dissection of the operated specimen demonstrated a grayish-white solid tumor which completely replaced the head of the epididymis (figs. 1 and 2). The tumor tapered down to a point opposite the middle portion of the testis and became continuous with normal-appearing epididymis. The body and tail of the epididymis and the vas deferens appeared normal. There were no areas of caseation and, grossly, no areas of invasion of the testis. The specimen was given to Dr. H. S. Sumerlin for pathologic study. Blocks
CARCINOMA OF EPIDIDYMIS
393
of tissue for microscopic examination were taken from the junction of the tumor and body of the epididymis, from the rete, and from the testis itself. In the spaces between the ducts, there was an infiltration of small closely packed cells, the nuclei of which were highly chromatic and for the most part, fairly round (fig. 3). The cells had practically no cytoplasm, and were distributed in clusters, strands and sheets in a loose :fibrous stroma. Examination of many sections disclosed no other type of cell. Atypical mitoses were numerous. Lymphocytes were scattered throughout the tissue. Most of the ducts appeared normal; there were a few atypical ones which suggested metaplasia but definite transition was not demonstrated (:fig. 5). Sections from the rete (fig. 6) and from the testis showed no neoplastic change. Dr.
FIG. 1 FIG. 2 FIG. 1. Specimen removed at operation. Cut surface of testis and epididymis, showing carcinoma of the epididymis FIG. 2. Epididymis opened to show tumor in globus major
Sumerlin considered the growth to be an infiltrating carcinoma of a high grade of malignancy which presumably had its origin in the epididymis. Immediate post-operative irradiation, directed over the anterior and posterior aspects of the pelvis was given. For seven days,-March 16, 1931 to March 23, 1931,-daily exposure to x-rays generated at 200 kilovolts from a distance of 50 cm. through a filter of 0.5 mm. copper and 1 mm. aluminum, was made. A total of 800 roentgens was given. The patient returned to work on April 15, 1931, and was seen at monthly intervals thereafter. On September 3, 1931, he complained of soreness over the left pubic area. There was no evidence of local recurrence and roentgenograms of the kidney, ureter and bladder areas again showed no bone pathology.
394
JAMES A. MAY
December 7, 1933, twenty-two months after the operation, he noticed a tumor in the left side of the abdomen. At this time he complained also of indigestion, fatigue and loss of weight. The tumor was nodular and extended from the left costal border to the pelvic brim. In addition, a smaller tumor was palpated on the right side. Upon rectal examination a hard, nodular mass was felt above the prostate. Roentgenologic examination of the chest revealed no metastatic changes in the lung fields or the rib cage. Further irradiation was directed to all four quadrants of the abdomen, and resulted in marked diminution in the size of the abdominal tumors. A total of 2400 roentgens was given over a period of five weeks.
FIG. 3. Section through tumor showing infiltration of cells, between ducts.
(X 100)
On April 12, 1934, a nodule appeared in the right supraclavicular space. A roentgenogram of the chest showed no metastases in the lung fields. On April 19, 1934, the patient complained of pain in the right eye and right side of the head and of difficulty in walking. The findings of a neurological , examination indicated the presence of a lesion in the brain stem. Roentgen examination of the skull showed extensive metastases in the parietal, occipital and sphenoidal bones. From April 12, 1934 to May 9, 1934, irradiation was directed over the cervical region and the skull. A total of 4000 roentgens was given.
395
CARCINOMA OF EPIDIDYMIS
On June 27, 1934, approximately six weeks after his last period of irradiation, urine for the :first gonadotropic hormone determination was obtained. Quantitative estimations were made by Dr. Tracy 0. Powell of Los Angeles, to whom I am indebted for this work. Tests graduated to reveal the presence of as low a level as 200 uni ts of hormone per liter of urine were negative. On September 6, 1934, the abdominal masses were definitely larger and the patient was failing rapidly. Pyuria and pleural effusion developed and from this time until his death his course was febrile. On November 2, 1934, a
FIG.
4
FIG.
s
FIG. 4. Anaplastic cells. ( X 450) FIG. 5. Section of tumor showing atypical ducts suggesting metaplasia.
(X 100)
second specimen of urine was sent for hormone estimation. Dr. Powell reported that no hormone was present in excess of 300 units per liter. Irradiation had not been given for four months prior to this time. On November 22, 1934, the patient died of general carcinomatosis and sepsis. Autopsy was performed by Dr. Howard A. Ball of the San Diego County General Hospital. There was bilateral pleural effusion. There were numerous metastatic lesions of both parietal and visceral pleura on both sides but there was no evidence of metastases within the lung parenchyma. The
396
JAMES A. MAY
liver contained numerous metastatic nodules measuring from 2 to 5 cm. in diameter. The right kidney was hypertrophied and there was marked pyelonephritis. The left kidney was completely imbedded in a large mass of malignant tissue which had attached itself to the ligaments of the spinal column and extended from the level of the diaphragm to the brim of the pelvis. The pelvis and calyces of the kidney were so dilated from back pressure that scarcely any cortex remained. The malignant tissue was traced along the bifurcation of the iliac arteries into the posterior aspect of the pelvis. There was no gross tumor tissue along either inguinal canal. The
Frc. 6. Section through normal rete
bladder wall was not particularly thickened and no malignant changes were found inside the bladder cavity. The prostate showed no evidence of tumor formation but was surrounded by a carcinomatous mass in which the seminal vesicles were imbedded. Dr. Sumerlin examined sections from the autopsy specimens and found that the metastases in the kidneys, liver and lymph nodes reproduced the type of cells originally found in the epididymis. The cells were closely packed, in sheets, and there was practically no stroma. Sections from the prostate showed no evidence of malignancy.
CARCINOMA OF EPIDIDYMIS
397
Discussion. We believe this neoplasm to be a primary carcinoma of the head of the epididymis rather than a teratoid tumor of the testis which had grown into the epididymis. Several blocks of tissue were removed at the junction of the growth and the testis, through the rete testis and from the testis itself, and malignant tissue was found only in those sections which were taken from the tumor mass. The rete testis appeared normal. Microscopic sections of the tumor were sent to Drs. Ewing, Broders and Hinman, all of whom were kind enough to send me their opinions. Dr. Ewing reported as follows: "The tumor of the epididymis which you sent me shows a highly malignant infiltrating carcinoma. The cells are small and composed mostly of nuclei. There are no indications as to its exact origin. It does not resemble any type of carcinoma of the testis with which I am familiar and I wonder whether the tumor may not be metastatic. The majority of carcinomas of the testis arise in the rete and invade both testis and epididymis. This one seems to be entirely in the epididymis. I think you have a rare tumor and I strongly suspect that it is metastatic." Dr. Broders wrote as follows : "I agree with Dr. Sumerlin's diagnosis of carcinoma. It bears a close resemblance to adenocarcinoma of the testicle and appears to be at least of a grade 4 malignancy." Dr. Hinman considered the sections very atypical of a seminoma and thought that "they were more likely a secondary growth, possibly from the prostate or seminal vesicles." Later, after he had received the information that no malignancy was found in the prostate or seminal vesicles and had seen prints of the specimen he wrote "your case is indeed a most unusual and interesting one and from your findings of course looks like a primary carcinoma of the epididymis." Metastatic involvement of the epididymis is extremely rare and the entire clinical course of the disease in this case would indicate that the left scrotal area was the primary site of the new growth. Careful physical examination supplemented by roentgen examinations of the lungs, abdominal area, and complete gastro-intestinal tract at the time the patient was first seen failed to reveal any other pathology, and repeated examinations disclosed no malignant change in any other organ until almost two years after operation when metastases first appeared along the aortic lymph chains. Gonadotropic hormone in the urine of a patient suffering from teratoma testis was first noted by Zondek in 1929. This observation has been of great potential value to urologists in that it offers a possible THE JOURNAL OF UROLOGY, VOL,
36,
NO ,
4
398
JAMES A. MAY
method of differentiation between benign and teratoid growths of the testis and between teratoid growths of the testis and malignant tumors of other pathogenesis in adjacent organs. It offers also in cases of teratoma a possible method of detecting the presence of metastases following the removal of the tumor. By quantitative titration of the hormone in the urine, the progress of the disease following surgery or irradiation may be observed. In April, 1931, Ferguson et al. obtained positive hormone reactions in 12 cases of teratoma testis examined by them in which the malignancy was clinically active. Again, in March 1934, Ferguson reported the results of hormone determinations in 100 cases of benign lesions of the testis in which there was no excretion in excess of 100 units per liter of urine. In 117 consecutive cases of teratoma testis, the excretion of the hormone was in excess of 500 units per liter of urine in all untreated cases with the exception of those of the adult cystic type. Ferguson concludes that their results "indicate the consistent absence of the hormone in non-malignant disease of the testis" and that if the urine assay for 100 units per liter results in no reaction in cases of suspected teratoma, the probability is against the diagnosis. He warns that it does not say that "the case of adult carcinoma of the testis may not exist or that tumors involving neighboring structures not of teratoid origin are absent." Hinman and Powell conclude that "the majority of tumors of the testicle (embryonal) are associated with the presence of gonadotropic hormone in the urine and that the presence of such hormone in the urine of the patient with a tumor of the testis is presumptive evidence of testicular malignancy, and its absence is strong but not de.finite evidence against malignancy." Because of the rarity of epididymal tumors, the number of cases in which hormone estimations have been made is exceedingly small. In July, 1932, Eisenberg, Simons and Wallerstein reported one case of spheroidal cell carcinoma (seminoma) of the epididymis in which the hormone reaction was strongly positive. Sections of the tumor showed large cells with clear cytoplasm and large nuclei with considerable chromatin. The tumor was apparently not present in the testis. Ferguson, in March 1934, reported negative hormone reactions of the urine in one case of .fibrosarcoma of the epididymis, one case of carcinoma of the epididymis and one case of fibrosarcoma of the spermatic cord. In the case reported here, there was no excretion of gonadotropic hormone in the urine in excess of 200 units per liter. The last estimation was made from urine obtained sixteen days before death when the
CARCINOMA OF EPIDIDYMIS
399
metastatic growths were most extensive. Roentgen therapy had not been given for a period of four months prior to this time so that there could have been no effect of the x-rays on hormone excretion at this time. If this tumor had been of testicular origin, one would expect a high titration of gonadotropic hormone in the urine in view of our present knowledge of the hormone excretion in testicular tumors. The fact that the hormone content in our case was less than 200 units per liter of urine is further presumptive evidence that the tumor was not of testicular origin. Statistics on the length of life after operation in the reported cases of carcinoma of the epididymis are not complete. However, a review of the cases reported indicates that metastases occur early and that the prognosis 1s poor. We feel that the immediate postoperative irradiation in our case was a decided factor in lengthening the interval between operation and the development of metastases and in the prolongation of life. We believe that in all such cases high total excision followed by deep roentgen therapy should be the method of treatment. CONCLUSIONS
A case of primary carcinoma in the head of the epididymis is reported. Gonadotropic hormone in excess of 200 units per liter of urine was not found in this case. We believe that removal of the testis and epididymis by high excision of the spermatic cord, followed by intensive radiation therapy, is the method of choice in the treatment of carcinoma of the epididymis.
Rees-Stealy Clinic 2001 Fourth Avenue, San Diego, California. REFERENCES EISENBERG, A. A., SIMONS, I., AND WALLERSTEIN, H.; Case of spheroidal-cell carcinoma (seminoma) of the epididymis. Amer. Jour. Cancer, 16: 875-881, 1932. FERRIER, P. A., AND FooRD, A. G.: Primary carcinoma of the epididymis. Urol. and Cutan. Rev., 38: 646-649, 1934. FERGUSON, R. S.: Clinical evaluation of the quantitative excretion of Prolan-A in teratoma testis. Jour. Urol., 31: 397-409, 1934. - - - , DowNEs, H. R., ELLIS, E., AND NICHOLSON, M. E.: Preliminary note on a new method of differentiating the testicular tumors by biological means. Amer. Jour. Cancer, 15: 835-843, 1931. HINMAN, FRANK, AND GrnsoN, T. E.: Tumors of the epididymis, spermatic cord and testicular tunics. Arch. Surg., 8: 100-137, 1924. - - - , AND POWELL, T. 0.: The gonadotropic hormone in the urine of men with tumor of the testis. Jour. Urol., 34: 55-71, 1935. THOMPSON, G. J.: Tumors of the spermatic cord, epididymis and testicular tunics. Surg., Gynec. and Obstet., 62: 712-728, 1936.