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Testis Tumors: Report on 250 Cases1
TESTIS TUMORS: REPORT ON 250 CASES 1 LLOYD C. LEWIS PATHOLOGY
Interpretation of the cellular structure of tumors of the testis requires not only experience with the microscopic pattern of carcinoma but also a working knowledge of embryological histology. The varied structure of testis tumors suggests that no one method of treatment would be adequate. Since 43 per cent of our 250 patients had proven metastasis on admission to Walter Reed General Hospital and in an additional 28 per cent metastasis eventually developed, it is obvious that only a few could be cured by simple orchiectomy alone. Orchiectomy plus radiation therapy has proven satisfactory only in the case of seminoma. The apparent confusion in the classification of testis tumors has come about from the use of ill-defined terminology. As a result, many urologists have treated testis tumors by simple orchiectomy and radiation therapy because the results of radical orchiectomy without radiation therapy have not been satisfactory. Chevassu wrote: "A classification is not a catalog. It does not only register, it must explain." A clinico-pathological classification of testis tumors indicates that surgical treatment should be extended and radiation therapy rationalized. Tumors of the supporting tissues of the testis, connective tissue and the blood vessels are similar to those produced in other parts of the body and will not be discussed here. No sarcomas or endotheliomas were seen in our patients of military age. Specific endocrine tumors of the testis are composed of the interstitial cells of Leydig. Two or 0.8 per cent of our cases were interpreted as benign interstitial cell tumors, occurring in marvelously well developed men of 25 and 37 years. These tumors, while usually benign, may become malignant. Fresh tissue examination after section revealed reddish-brown solid tumors occupying the entire testis without gross evidence of remaining tubular elements. The tumors consisted of proliferating interstitial cells filling the septa and compressing the testis tubules. These large eosinophilic clear cells of indefinite outline showed small oval nuclei. No mitotic figures were seen in our specimens. The diagnosis would be difficult from frozen section. Both patients after radical orchiectomy are well over 1½ years. The radical gland dissection did no harm but possibly was not indicated. The radiosensitivity of this tumor has not been studied. One of the common testicular tumors, the seminoma of Chevassu, is histologically identical to the seminoma or dysgerminoma of the ovary. It is also very similar to a tumor of the pineal body. It probably is of germ cell origin. The seminoma, dysgerminoma, spermatocytoma, or whatever name we may wish to call it, deserves special consideration because it behaves as a clinical entity, having the features of relatively slow growth, delayed metastasis, remarkable radiosensitivity and warrants a good prognosis. Its radiosensitivity simulates the lymphoma. The seminoma is a rounded or lobulated, solid grayish-white tumor which tends to compress, displace, but rarely to invade, the seminiferous 1 Read at annual meeting, Southeastern Section, American Urological Association, Palm Beach, Fla., March 28, 1947. 763
764
LLOYD G. LEWIS
tubules. This tumor can frequently be recognized on the microscopic slide without aid of the microscope by its lobulation, its dark blue basophilic staining property. It is composed of large clear polyhedral cells with small but darkly staining nuclei laid down in sheets or strands, occasionally presenting a suggestion of acinar formation. Mitoses average 2 to 3 per high power field. Any similar tumor with more evident mitosis is considered an atypical seminoma. Serial sections of the entire tumor might disclose embryonal tumor elements and we must consider this possibility. Hemorrhage into or around these tumors is exceedingly rare but tendency to spontaneous necrosis is common. The lymphoid cells seen along the fibrous septa adjacent to blood vessels in a certain percentage of seminomata are not regarded as part of the tumor. There is little difference in behavior, radiosensitivity or prognosis of seminoma with or without lymphoid stroma. That is not the differentiating factor between seminoma and the socalled embryonal carcinoma. After the tumors have been entirely destroyed by x-rays in dosage of only 600-800 r delivered in 6 to 7 days, the small areas of dead cells in areas of spontaneous necrosis remain to establish the tentative diagnosis. Seminoma occurred in 109 or 43 per cent of our cases. Metastasis was demonstrated on admission in 15 per cent, retroperitoneal metastatic nodes were removed in an additional 10 per cent. Late metastasis occurred in an additional 4 per cent following surgery. Seminoma is the common tumor of the atrophic or maldeveloped testis. Twelve of the 13 tumors in cryptorchids were seminomas. The 3 tumors occurring in patients with mumps atrophy and the 5 found in patients with traumatic or idiopathic atrophy were seminomas. At this point we might add that the incidence of testis tumors in soldiers during World War II was approximately 1 per 10,000 troops. By calculation, if we accept the incidence of cryptorchism in adults after Campbell as 0.23 per cent, the incidence of testis tumor in undescended testes is 22 per 10,000, occurring 22 times as commonly as seen in normally descended testes. Our experience paralleled Gilbert's finding that neither orchiopexy nor spontaneous descent have any lessening influence on the development of tumor in a cryptorchid. The large group of testis tumors which fall into the general category of teratoma testis, presents a difficult pathological picture for interpretation. Ewing's concept of a totipotent cell capable of producing undifferentiated tumors, tumors of one or more primitive germ layer, tumors of :immature or embryonic, mature or adult structure demands our serious consideration, for one cannot conceive of various teratomatous elements of the tumor metastasizing to distant parts as a tumor embolus. Such a migration would be expected to produce infarction and this has not been noted. In certain cases the most malignant cells of a mixed tumor may metastasize, leaving behind the less invasive structures. Classification of testis tumors according to their morphological pattern, undifferentiated carcinoma, adenocarcinoma, papillary carcinoma and teratocarcinoma may enable the pathologist to sort out his specimens but gives the clinician little aid in selection of a plan of therapy nor in prognosis. A division of this group of tumors into embryonal carcinoma and teratocarcinoma results in some benefit to the surgeon but there is no generally accepted concept as to what these terms imply. To one group of workers embryonal carcinoma implies any
TESTIS TUMORS
765
tumor with embryonic tissue; to another, the added term carcmoma signifies malignant change in the embryonic tissue. To one group, chorio-epithelioma is a clinical entity and to another, part of an embryonal carcinoma. Does teratocarcinoma imply the possibility of metastasis of mature teratoid structures of the tumor or malignant degeneration of parts of the tumor? Most distressing is the term "embryonal carcinoma-seminoma". Does that imply embryonal tUID.or with seminoma cells or a suspicion of undetected embryonic structure in addition to the obvious seminoma? The classification of testis tumors recently offered by the Army Institute of Pathology and presented by Drs. Friedman, Nathan, and Moore, Robert, meets most of our criteria. They regard seminoma as a clinical entity and have grouped under the heading "embryonal carcinoma", undifferentiated tumors and tumors of trophoblastic origin. Because of the variation in radiosensitivity and prognosis of undifferentiated carcinoma, tumors of cytotrophoblastic elements and tumors of syncytiotrophoblastic elements, we believe that the term "embryonal carcinoma" should be limited to the general classification and the type of most malignant cell recognized in the tissues be used in the diagnosis. These highly malignant elements may be seen with teratoid tumors of somatic cells. When such a complex picture is seen, the diagnosis of teratoma supplemented by a description of the most malignant cell should be made. In a limited number of cases (3.2 per cent in our series) the entire tumor is composed of somatic elements in immature or mature form. These tumors are relatively benign teratomas but the possibility of malignancy must be kept in mind. The classification which we suggest is based on embryonal form, pathological structure, radiosensitivity studies and results of combined surgical and radiation treatment carried out by Dr. Milton Friedman and myself at Walter Reed General Hospital. Classification: Tumors of Supporting Tissues of Testis 1. Cysts of tunica. albuginea 2. Fibromas 3. Fibrosarcomas 4. Fibroleiomosarcomas 5. Hemangimas 6. Endotheliomas Tumors of Interstitial Cells Tumors of Germ Cell Origin 1. Seminoma (dysgerminoma, spermatocytoma) 2. Carcinoma-(a) undifferentiated carcinoma (b) adenocarcinoma, Embryonal (c) papillary adenocarcinoma carcinoma 3. Trophocarcinoma (a) choriocarcinoma (from cytotrophoblast) _ (b) chorio-epithelioma (from syncytiotrophoblast) 4
1
l 1
Teratocarcinoma
(a) Teratoma w~th carci~oma,_ undifferentiated, adenopapillary. (b) Teratoma with chonocarcmoma (c) Teratoma with chorio-epithelioma 5. Teratoma (a) immature (b) mature (c) Rhabdomyosarcomas
766
LLOYD G. LEWIS
The fertilized ovum, after the initial stage of cell division and before the primitive germ layers are differentiated, is represented by an undifferentiated cell mass. The potentia of these cells is terrific, but lacking the normal stimulus to differentiate and to form germ layers, the improperly activated germ cell may form a tumor. The cells of undifferentiated carcinoma resemble closely the undifferentiated cells of the embryo. These primitive cells are seen in many cases of immature teratoma. They tend to form acinar patterns and the term adenocarcinoma is correctly applied by pathologists. Some embryonic cells may be arranged in definite papillary pattern. Clinically, undifferentiated carcinoma is more rapidly growing than seminoma; it is more irregular and invasion is the characteristic pattern differentiating it from the rounded or lobulated seminoma. The cell structure is unlike seminoma, and only at the periphery where seminoma cells undergo degenerative changes do they at all resemble each other. These embryonic cancer cells are irregular, tend to be spiculated, have irregular staining cytoplasm and comparatively large nuclei. Mitosis is common. This tumor varies in its radiosensitivity. Some of these tumors are destroyed with from 2000 to 3000 r. There is little tendency to spontaneous necrosis and after irradiation the diagnosis is most difficult. Tumors of embryonic tissue, for the most part in undifferentiated masses, but with a tendency to acinar formation, may differentiate into somatic and trophoblastic tissues resembling the blastocyst of the embryo as described by Peyron and by Melicow. We have observed four such tumors; one metastasized identically as described by Sabrazes and Peyron. Tumors of embryonic tissue present cystic areas lined by cells resembling embryonic entoderm or yolk sac entoderm. Certain adenoid developments of ectoderm and plates of cells in columnar form representing development of ectoderm are seen. There are evidences of embryonic connective tissue and suggestions of neural elements. Such tumors of embryonic structure we prefer to call immature teratoma with the appended term indicating its most malignant element. The undifferentiated embryonic cells having differentiated, a tumor made up of cells resembling the cytotrophoblast may develop. Chorionic tissue composed of large gray cells with large oval nuclei resembling Langhans cells are present in sheets or acinar pattern. The term choriocarcinoma is used, realizing that these cells of the cytotrophoblast are the parent cells of the syncytiotrophoblast. In many instances these chorionic cells form villus structures with a marked tendency to invade blood vessels and blood spaces. Theyresembleyoung chorionic villi and the term choriopapillary adenocarcinoma may be correctly applied. These chorionic cells over-grow the other elements of the tumor and metastasize early, making the prognosis but a little less grave than fpr chorioepithelioma. When definite syncytial cells are found with the chorionic elements described in the foregoing, the diagnosis of chorio-epithelioma is made. The transition from cytotrophoblast to syncytiotrophoblast may be obvious. These tumors tend to grow rapidly and to metastasize early. When chorioepithelioma occurs with teratoma, the teratoid elements are usually confined to the testis while the chorionic tissues metastasize to distant parts.
TESTIS TUMORS
767
These chorionic cancers and true chorio-epithelioma also appear with more mature or adult structures in teratoma. Then the term mature teratoma with the other features appended is used. Relatively benign tumors of mature structures grow very slowly, but when any tumor of this description has chorionic elements in it, rapid growth with hemorrhage into the tumor and into the hydrocele sac with or without recession in growth is common. The lethal x-ray tumor dose for chorionic cells is between 5000 and 6000 r. The lethal dose for mature teratoma cannot be reached with safety. SYMPTOMS
At the onset and for many weeks or months the testis tumor may present a painless swelling in the testis proper. Later, expansion of the capsule or trauma may produce pain. The history of acute painful swelling with redness and fever which characterizes inflammatory lesions is lacking. Hemorrhage may produce pain. Recession of the mass by absorption of blood may bring about actua1 decrease in size. Patients with chorio-epithelioma frequently present themselves with symptoms referable to metastatic involvement a:hd no testicular mass is felt. Seminoma very rarely metastasizes without a palpable testis tumor. Hormone bioassays by the modified Aschheim-Zondek technique are considered of little diagnostic value and positive findings are considered as confirmatory evidence when a testis tumor is present or metastasis obvious. The difficulty of interpretation of these tests lies in the fact that both chorionic gonadotropins and the follicle stimulating hormones are reported together. Laboratory tests using hypophysectomized animals may be used to isolate the gonadotropic hormone but that is not always practical. Thirty-five per cent of a series of control patients without testis tumor gave positive findings to the Friedman test. Thirty-four per cent of patients with seminoma who should have secreted no gonadotropins had high readings. All of the patients with chorio-epithelioma had strongly positive readings. A positive test cannot, therefore, be interpreted as evidence of testis tumor nor of metastasis. A repeatedly confirmed positive reaction from a patient with tumor indicates the likelihood of the presence of chorionic tissue in the tumor. DIAGNOSIS
The differential diagnosis of testis tumor should not be difficult. Bimanual palpation, which we must insist upon, will eliminate epididymitis, lesions of the spermatic cord, spermatoceles and lesions of the surrounding scrotum. The presence of a complicating hydrocele is the only difficult feature. Trans-illumination, tapping of the hydrocele to facilitate differentiation by palpation are indicated. Our only difficulty has been in the differentiation of thick-walled or calcified hydroceles, hematoceles and gumma. X-ray examination of the scrotum will help in the differentiation of calcified hydrocele from calcification of the testis tumor. Calcification occurs in the periphery in the hydrocle and more or less centrally in the tumor. When there is doubt, exploration of the scrotum is imperative and we are decidedly against the use of punch or needle biopsy.
768
LLOYD G. LEWIS
Seminoma can be differentiated by its radiosensitivity. We have, I believe, adequately studied this phase and upon the suspicion of testis tumor, early if not immediate orchiectomy is advised. THERAPY
Surgery. Orchiectomy, transscrotal or inguinal, should be done as early as possible. We prefer the inguinal approach so that the incision can be extended to perform the radical retroperitoneal dissection after examination of the tumor in gross. Personally, I would like to have a radical orchiectomy for any type of testis tumor. It may not be indicated for seminoma because of the radiosensitivity of that tumor, but I have in mind the possibility of inclusion of some more malignant elements unrecognized in the routine section. Radical orchiectomy may not be indicated for benign interstitial cell tumors nor for simple mature teratomata but here, too, the possibility of malignancy and lymphatic metastasis is not too remote. Chorionic tumors metastasize both by lymphatics and blood stream. The only rationale for radical surgery in chorio-epithelioma is to take the long internal spermatic vessels with the lymphatics. It is the most we can do. Radical orchiectomy consists of removal of the testis with its tunics, the epididymis, vas, entire spermatic cord and the retroperitoneal lymph chain from the inguinal ring to the renal pedicles as described by Chevassu, Young, Hinman and others. Orchiectomy with ligation of the cord at the internal inguinal ring is not radical orchiectomy. We have been fortunate in not having as high a percentage of inoperable metastases as did Young and Hinman. Crossed metastases below the renal pedicles have not been observed by us except when there is tremendous involvement of the precaval nodes from right testis tumor. Like other tumors, testicular tumors do not always involve nodes in continuity along the lymphatic chain. Metastases skip nodes, may even skip all retroperitoneal nodes and appear at the supraclavicular node on the left side. Chorio-epithelioma may invade the blood stream without lymphatic involvement. The external inguinal and femoral nodes are very rarely involved except when the tumor invades the scrotal wall. The internal iliac node at the internal inguinal ring over the external iliac artery is frequently involved. The lymphatic chain extends over the external iliac artery to a node medial to the artery distal to the bifurcation of the external iliac and hypogastric vessels. Then the lymphatic chain crosses the vessels to pass to a node lateral to the common iliac artery. On the left side the lymphatic chain and nodes lie lateral to the aorta to pass up to the nodes at the entrance of the internal spermatic vein into the left renal vein. Those nodes at the renal pedicle and medial to it are most frequently involved. On the right side the lymphatic pathways lead over the vena cava and between it and the aorta to the most frequently involved node at the entrance of the internal spermatic vein into the vena cava. Metastatic channels lead to midline inoperable nodes above the renal pedicles. I do not feel badly about removing uninvolved nodes nor does the surgeon who has the opportunity to do radical mastectomy upon a patient without lymphatic metastasis. My assistant at Walter Reed General Hospital, Dr. Carleton Smith, of Pontiac, Michigan, and
TESTIS TUMORS
769
I have performed 169 radical retroperitoneal resections without operative mortality. Sixty-six per cent of the patients had no metastatic involvement. Twentyfour per cent had operable metastatic nodes removed and we had to leave inoperable nodes in 10 per cent of our operative cases. X-ray. At Walter Reed General Hospital, Dr. Milton Friedman of New York did radiosensitivity studies on a large number of patients who presented themselves with the tumor intact. Many patients had had orchiectomy at other army installations. He found the seminoma most radiosensitive and, in fact, destroyed the tumor in 6 instances so that no tissue is available for microscopic identification. In others the tumor was diagnosed from its metastasis or from areas of spontaneous necrosis not affected by irradiation. Some embryonal tumors were markedly affected by dosage from 2000 to 3000 r. I cannot say that chorionic tumors were effectively changed by x-rays and our results in radiation of metastatic lesions of chorionic tumor -were most discouraging. X-ray therapy to be effective requires use of a full lethal tumor dose. Prophylactic irradiation of the retroperitoneal area or of other specific areas requires specific lethal tumor dosage. Using the million volt x-ray machine, there was no problem in administering the required dose, but the lethal tumor dose must be safe as far as normal tissue destruction and repair are concerned. Dr. Friedman was a pioneer in the field of million volt therapy. We soon learned that the skin is no protection to the therapist in restraining him from delivering lethal doses to the retroperitoneal tissues, nor to the gastro-intestinal tract. The patients have considerable variability in dosage resistance. However, we have found that whereas they can take large dosage and survive the immediate impact, they may develop radiation gastritis and late radionecrosis. Fourteen patients have perforated stomach and bowel 1½ to 2 years following therapy. The relatively small lethal dose for seminoma can be delivered to the retroperitoneal node area with safety. One thousand roentgens is considered adequate. It can be given in 2 weeks with the million volt machine, whereas it takes 6 weeks to deliver the same using the 200 KV machine. I do not feel it is safe to use prophylacbic irradiation for tumors which require more than 3000 r lethal tumor dose. In the presence of known metastasis, the higher dosage required is justified. Dr. Friedman agrees with me that all patients requiring more than 1000 r require radical surgery, and since the operative risk is so small, recommends it for seminoma also. PROGNOSIS
It is too early to present statistics on the value of radical surgery for testis tumor. Since only 1 patient has died from tumor after 1½ years following treatment, we may be able to estimate the trend. The cases illustrated in fig. 1 were operated upon between May 1942 and July 1946. The 2 patients with interstitial cell tumor are well. Seven patients with mature teratoma and one with immature teratoma are considered well after radical surgery without radiation therapy. Eight per cent of the patients with seminoma having radical surgery plus irradiation have died and only 9 per cent of the 109 patients with seminoma have died. We regret that 4 of these patients, who had excessive
770
LLOYD G. LEWIS
Fw. 1. (Upper left), embryonic body resembling a blastocyst composed of primitive ec toderm and entodermal cyst from a metastatic node removed from a patient whose pri mary testis tumor showed hundreds of such embryomas. (High power). (Upper ri ght), adenocarcinoma composed of large vacuolated cells wi th la rge prominent nuclei and ver y prominent nucleoli interpreted as cytotrophobl ast. This chorionic t issue was removed from a metastatic node from the same patient illustrated in the upper left photomicrograph. (High power) . (Left m iddle), papillary adenocarcinoma composed of primitive ectodermal t issue. Metastatic nodes from the same patient showed chorionic tissue. (Low power). (Right middle) , typical seminoma with sheets of seminoma cells inter spersed with lymphoid cells. There is a tendency to acinar formation. No teratoid elements were fo und in th is tumor. (Low power) . (Left lower), immature teratoma composed of embryonic ectodermal elements, entodermal cysts, embryonic connective tissue. (Low power). (Right lower). Chorio-ep ithelioma from a metastatic node illustrating hemorrhagic a reas bordered by syncytia l cells . Langhans cells a re not prominent .
771
TESTIS TUMORS
irradiation for a tumor diagnosed as embryonal carcinoma and later found to be seminoma when sections from overseas hospitals became available, died from radiation gastritis. It is to be noted that 23 per cent of seminomas had metastasis on admission; yet only 5 per cent died from cancer. Sixty per cent of the 28 patients with undifferentiated adeno- or papillary adenocarcinoma had metastasis on admission. Twenty of these patients had radical orchiectomy and 35 per cent have died. Fifty per cent of the total series of 28 have died. Seventy per cent of the 17 patients with choriocarcinoma (cytotrophoblast tumor) had metastasis on admission. Eleven were subjected to retroperitoneal gland resection and 45 per cent of these have died. Sixty-five per cent of the total series of 17 have died. All but one of our 12 patients with chorio-epithelioma had metastasis and TABLE
1.
Testis tumors
CONDITION ON ADMISSION
DIAGNOSIS
CASES
Inopeia-
ble metastases
-- --
Seminoma ... Undif. care ..... Choriocarc ... ....... Chorioepith .. .. Teratocarc. with undif. carcinoma. Teratocarc. & choriocare ...... Tera to care. & chorioepith .. .... Teratoma . .. . . . Inters tit. cell tumor . Total. ....
Operable roetastases - -
TREAT.MENT
Metasta£tasis ~-
Radical orchiec-
Simple orchiec-
tomy
tomy
-~
--
RESULTS RADICAL SERIES
Died
%
- -
- -
RESULTS TOTAL
Died
%
-- --
6 7 5 2
8 35 45 100
10 14
2
40 8 6 10
12
9 50 65 100
38%
29
5
5
17
8
24
10
75%
21
7
9
43
15
53
4 0 0
75% 0 0
7 8 2
5 0 0
6 0 0
86
11
83
109 28 17 12
15 8 8 10
10 9 4 1
23% 60% 70% 92%
69 20
34
9
4
28
11
12 8 2
5 0 0
250 - - - - 43 %
11
1----;;-1~-1~
11
0 0 - -- -- -
24
81
32
all have died from metastatic cancer. Thirty-eight per cent of 34 patients diagnosed teratoma with undifferentiated carcinoma had metastasis on admission. Twenty-nine were subjected to radical orchiectomy. Only 17 per cent of the radical series have died but 24 per cent of the total series of 34 have died. The teratoma apparently lessens the spread of the more malignant tumor cells. Seventy-five per cent of the 28 patients with teratoma and choriocarcinoma had metastasis on admission. Twenty-one of these patients were subjected to radical orchiectomy and 43 per cent of these have died. Fifty-three per cent of the total series of 28 died. Seventy-five per cent of the patients with teratoma and chorioepithelioma had metastasis on admission. Only 2 of these patients are living, 83 per cent having died. SUMi\IARY
In summary, 43 per cent of a series of 250 testis tumors had metastasis on admission. One hundred sixty-nine patients were subjected to radical orchi-
772
LLOYD G. LEWIS
ectomy. Twenty-four per cent of these have died. Eighty-one patients either had inoperable metastasis on admission or were subjected to simple orchiectomy and irradiation because of the diagnosis of seminoma. Thirty~two per cent of the total series have died, 8 of these patients having died from perforation of the stomach or bowel due to excessive irradiation. At autopsy no tumor was found. It is interesting to note that, except in the case of chorio-epithelioma, the metastasis rate was higher than the mortality rate, indicating that therapy by radiation and surgery was thorough. CONCLUSIONS
Treatment of testis tumor must be varied according to the pathology presented: For benign interstitial cell tumors, simple orchiectomy is probably sufficient. For teratomata, radical orchiectomy is indicated without radiation therapy. For seminoma, simple orchiectomy plus radiation therapy is probably sufficient. We recommend 1000 r prophylactic dose to the entire retroperitoneal lymph drainage area. Radical orchiectomy may not be indicated for seminoma but the information gained by retroperitoneal dissection aids the roentgen therapist in planning treatment. For undifferentiated carcinoma, adenocarcinoma and papillary adenocarcinoma, radical orchiectomy is indicated followed by prophylactic roentgen therapy in dosage not to exceed 3000 r. For trophoblastic tumors, choriocarcinoma and chorio-epithelioma radical orchiectomy is indicated and radiation therapy in dosage of 5000 r should not be used except when inoperable metastatic nodes remain. For teratoma with malignant embryonic elements, irradiation is only indicated when inoperable metastatic nodes are found.
1150 Connecticut Ave., Washington 6, D.C. REFERENCES CAMPBELL, H. E.: Arch. Surg., 44: 353, 1942. CHEVAssu, M.: Thesis of Paris, No. 193, 1906. FRIEDMAN, N. B. AND MooRE, R. A.: Mil. Surgeon, 99: 573, 1946. EWING, J.: Neoplastic Diseases. Philadelphia: W. B. Saunders Co., 1928, 3rd ed. GILBERT, J.B.: J. Urol., 46: 740, 1941. HINMAN, F.: Principles and Practice of Urology. Philadelphia: W. B. Saunders Co., 1935. MELICOW, M. M.: J. Urol., 44: 333, 1940. PEYRON, A.: Compt. rend. Soc. de biol., 135: 281,347,864, 1941. SABRAZES, J., AND PEYRON, A.: Compt. rend. Soc. de biol., 135: 350, 1941. YOUNG, H. H., AND DAVIS, D. M.: Young's Practice of Urology. Philadelphia: W. B. Saunders Co., 1926, vol. 2, p. 544.
Interpretation of the cellular structure of tumors of the testis requires not only experience with the microscopic pattern of carcinoma but also a working knowledge of embryological histology. The varied structure of testis tumors suggests that no one method of treatment would be adequate. Since 43 per cent of our 250 patients had proven metastasis on admission to Walter Reed General Hospital and in an additional 28 per cent metastasis eventually developed, it is obvious that only a few could be cured by simple orchiectomy alone. Orchiectomy plus radiation therapy has proven satisfactory only in the case of seminoma. The apparent confusion in the classification of testis tumors has come about from the use of ill-defined terminology. As a result, many urologists have treated testis tumors by simple orchiectomy and radiation therapy because the results of radical orchiectomy without radiation therapy have not been satisfactory. Chevassu wrote: "A classification is not a catalog. It does not only register, it must explain." A clinico-pathological classification of testis tumors indicates that surgical treatment should be extended and radiation therapy rationalized. Tumors of the supporting tissues of the testis, connective tissue and the blood vessels are similar to those produced in other parts of the body and will not be discussed here. No sarcomas or endotheliomas were seen in our patients of military age. Specific endocrine tumors of the testis are composed of the interstitial cells of Leydig. Two or 0.8 per cent of our cases were interpreted as benign interstitial cell tumors, occurring in marvelously well developed men of 25 and 37 years. These tumors, while usually benign, may become malignant. Fresh tissue examination after section revealed reddish-brown solid tumors occupying the entire testis without gross evidence of remaining tubular elements. The tumors consisted of proliferating interstitial cells filling the septa and compressing the testis tubules. These large eosinophilic clear cells of indefinite outline showed small oval nuclei. No mitotic figures were seen in our specimens. The diagnosis would be difficult from frozen section. Both patients after radical orchiectomy are well over 1½ years. The radical gland dissection did no harm but possibly was not indicated. The radiosensitivity of this tumor has not been studied. One of the common testicular tumors, the seminoma of Chevassu, is histologically identical to the seminoma or dysgerminoma of the ovary. It is also very similar to a tumor of the pineal body. It probably is of germ cell origin. The seminoma, dysgerminoma, spermatocytoma, or whatever name we may wish to call it, deserves special consideration because it behaves as a clinical entity, having the features of relatively slow growth, delayed metastasis, remarkable radiosensitivity and warrants a good prognosis. Its radiosensitivity simulates the lymphoma. The seminoma is a rounded or lobulated, solid grayish-white tumor which tends to compress, displace, but rarely to invade, the seminiferous 1 Read at annual meeting, Southeastern Section, American Urological Association, Palm Beach, Fla., March 28, 1947. 763
764
LLOYD G. LEWIS
tubules. This tumor can frequently be recognized on the microscopic slide without aid of the microscope by its lobulation, its dark blue basophilic staining property. It is composed of large clear polyhedral cells with small but darkly staining nuclei laid down in sheets or strands, occasionally presenting a suggestion of acinar formation. Mitoses average 2 to 3 per high power field. Any similar tumor with more evident mitosis is considered an atypical seminoma. Serial sections of the entire tumor might disclose embryonal tumor elements and we must consider this possibility. Hemorrhage into or around these tumors is exceedingly rare but tendency to spontaneous necrosis is common. The lymphoid cells seen along the fibrous septa adjacent to blood vessels in a certain percentage of seminomata are not regarded as part of the tumor. There is little difference in behavior, radiosensitivity or prognosis of seminoma with or without lymphoid stroma. That is not the differentiating factor between seminoma and the socalled embryonal carcinoma. After the tumors have been entirely destroyed by x-rays in dosage of only 600-800 r delivered in 6 to 7 days, the small areas of dead cells in areas of spontaneous necrosis remain to establish the tentative diagnosis. Seminoma occurred in 109 or 43 per cent of our cases. Metastasis was demonstrated on admission in 15 per cent, retroperitoneal metastatic nodes were removed in an additional 10 per cent. Late metastasis occurred in an additional 4 per cent following surgery. Seminoma is the common tumor of the atrophic or maldeveloped testis. Twelve of the 13 tumors in cryptorchids were seminomas. The 3 tumors occurring in patients with mumps atrophy and the 5 found in patients with traumatic or idiopathic atrophy were seminomas. At this point we might add that the incidence of testis tumors in soldiers during World War II was approximately 1 per 10,000 troops. By calculation, if we accept the incidence of cryptorchism in adults after Campbell as 0.23 per cent, the incidence of testis tumor in undescended testes is 22 per 10,000, occurring 22 times as commonly as seen in normally descended testes. Our experience paralleled Gilbert's finding that neither orchiopexy nor spontaneous descent have any lessening influence on the development of tumor in a cryptorchid. The large group of testis tumors which fall into the general category of teratoma testis, presents a difficult pathological picture for interpretation. Ewing's concept of a totipotent cell capable of producing undifferentiated tumors, tumors of one or more primitive germ layer, tumors of :immature or embryonic, mature or adult structure demands our serious consideration, for one cannot conceive of various teratomatous elements of the tumor metastasizing to distant parts as a tumor embolus. Such a migration would be expected to produce infarction and this has not been noted. In certain cases the most malignant cells of a mixed tumor may metastasize, leaving behind the less invasive structures. Classification of testis tumors according to their morphological pattern, undifferentiated carcinoma, adenocarcinoma, papillary carcinoma and teratocarcinoma may enable the pathologist to sort out his specimens but gives the clinician little aid in selection of a plan of therapy nor in prognosis. A division of this group of tumors into embryonal carcinoma and teratocarcinoma results in some benefit to the surgeon but there is no generally accepted concept as to what these terms imply. To one group of workers embryonal carcinoma implies any
TESTIS TUMORS
765
tumor with embryonic tissue; to another, the added term carcmoma signifies malignant change in the embryonic tissue. To one group, chorio-epithelioma is a clinical entity and to another, part of an embryonal carcinoma. Does teratocarcinoma imply the possibility of metastasis of mature teratoid structures of the tumor or malignant degeneration of parts of the tumor? Most distressing is the term "embryonal carcinoma-seminoma". Does that imply embryonal tUID.or with seminoma cells or a suspicion of undetected embryonic structure in addition to the obvious seminoma? The classification of testis tumors recently offered by the Army Institute of Pathology and presented by Drs. Friedman, Nathan, and Moore, Robert, meets most of our criteria. They regard seminoma as a clinical entity and have grouped under the heading "embryonal carcinoma", undifferentiated tumors and tumors of trophoblastic origin. Because of the variation in radiosensitivity and prognosis of undifferentiated carcinoma, tumors of cytotrophoblastic elements and tumors of syncytiotrophoblastic elements, we believe that the term "embryonal carcinoma" should be limited to the general classification and the type of most malignant cell recognized in the tissues be used in the diagnosis. These highly malignant elements may be seen with teratoid tumors of somatic cells. When such a complex picture is seen, the diagnosis of teratoma supplemented by a description of the most malignant cell should be made. In a limited number of cases (3.2 per cent in our series) the entire tumor is composed of somatic elements in immature or mature form. These tumors are relatively benign teratomas but the possibility of malignancy must be kept in mind. The classification which we suggest is based on embryonal form, pathological structure, radiosensitivity studies and results of combined surgical and radiation treatment carried out by Dr. Milton Friedman and myself at Walter Reed General Hospital. Classification: Tumors of Supporting Tissues of Testis 1. Cysts of tunica. albuginea 2. Fibromas 3. Fibrosarcomas 4. Fibroleiomosarcomas 5. Hemangimas 6. Endotheliomas Tumors of Interstitial Cells Tumors of Germ Cell Origin 1. Seminoma (dysgerminoma, spermatocytoma) 2. Carcinoma-(a) undifferentiated carcinoma (b) adenocarcinoma, Embryonal (c) papillary adenocarcinoma carcinoma 3. Trophocarcinoma (a) choriocarcinoma (from cytotrophoblast) _ (b) chorio-epithelioma (from syncytiotrophoblast) 4
1
l 1
Teratocarcinoma
(a) Teratoma w~th carci~oma,_ undifferentiated, adenopapillary. (b) Teratoma with chonocarcmoma (c) Teratoma with chorio-epithelioma 5. Teratoma (a) immature (b) mature (c) Rhabdomyosarcomas
766
LLOYD G. LEWIS
The fertilized ovum, after the initial stage of cell division and before the primitive germ layers are differentiated, is represented by an undifferentiated cell mass. The potentia of these cells is terrific, but lacking the normal stimulus to differentiate and to form germ layers, the improperly activated germ cell may form a tumor. The cells of undifferentiated carcinoma resemble closely the undifferentiated cells of the embryo. These primitive cells are seen in many cases of immature teratoma. They tend to form acinar patterns and the term adenocarcinoma is correctly applied by pathologists. Some embryonic cells may be arranged in definite papillary pattern. Clinically, undifferentiated carcinoma is more rapidly growing than seminoma; it is more irregular and invasion is the characteristic pattern differentiating it from the rounded or lobulated seminoma. The cell structure is unlike seminoma, and only at the periphery where seminoma cells undergo degenerative changes do they at all resemble each other. These embryonic cancer cells are irregular, tend to be spiculated, have irregular staining cytoplasm and comparatively large nuclei. Mitosis is common. This tumor varies in its radiosensitivity. Some of these tumors are destroyed with from 2000 to 3000 r. There is little tendency to spontaneous necrosis and after irradiation the diagnosis is most difficult. Tumors of embryonic tissue, for the most part in undifferentiated masses, but with a tendency to acinar formation, may differentiate into somatic and trophoblastic tissues resembling the blastocyst of the embryo as described by Peyron and by Melicow. We have observed four such tumors; one metastasized identically as described by Sabrazes and Peyron. Tumors of embryonic tissue present cystic areas lined by cells resembling embryonic entoderm or yolk sac entoderm. Certain adenoid developments of ectoderm and plates of cells in columnar form representing development of ectoderm are seen. There are evidences of embryonic connective tissue and suggestions of neural elements. Such tumors of embryonic structure we prefer to call immature teratoma with the appended term indicating its most malignant element. The undifferentiated embryonic cells having differentiated, a tumor made up of cells resembling the cytotrophoblast may develop. Chorionic tissue composed of large gray cells with large oval nuclei resembling Langhans cells are present in sheets or acinar pattern. The term choriocarcinoma is used, realizing that these cells of the cytotrophoblast are the parent cells of the syncytiotrophoblast. In many instances these chorionic cells form villus structures with a marked tendency to invade blood vessels and blood spaces. Theyresembleyoung chorionic villi and the term choriopapillary adenocarcinoma may be correctly applied. These chorionic cells over-grow the other elements of the tumor and metastasize early, making the prognosis but a little less grave than fpr chorioepithelioma. When definite syncytial cells are found with the chorionic elements described in the foregoing, the diagnosis of chorio-epithelioma is made. The transition from cytotrophoblast to syncytiotrophoblast may be obvious. These tumors tend to grow rapidly and to metastasize early. When chorioepithelioma occurs with teratoma, the teratoid elements are usually confined to the testis while the chorionic tissues metastasize to distant parts.
TESTIS TUMORS
767
These chorionic cancers and true chorio-epithelioma also appear with more mature or adult structures in teratoma. Then the term mature teratoma with the other features appended is used. Relatively benign tumors of mature structures grow very slowly, but when any tumor of this description has chorionic elements in it, rapid growth with hemorrhage into the tumor and into the hydrocele sac with or without recession in growth is common. The lethal x-ray tumor dose for chorionic cells is between 5000 and 6000 r. The lethal dose for mature teratoma cannot be reached with safety. SYMPTOMS
At the onset and for many weeks or months the testis tumor may present a painless swelling in the testis proper. Later, expansion of the capsule or trauma may produce pain. The history of acute painful swelling with redness and fever which characterizes inflammatory lesions is lacking. Hemorrhage may produce pain. Recession of the mass by absorption of blood may bring about actua1 decrease in size. Patients with chorio-epithelioma frequently present themselves with symptoms referable to metastatic involvement a:hd no testicular mass is felt. Seminoma very rarely metastasizes without a palpable testis tumor. Hormone bioassays by the modified Aschheim-Zondek technique are considered of little diagnostic value and positive findings are considered as confirmatory evidence when a testis tumor is present or metastasis obvious. The difficulty of interpretation of these tests lies in the fact that both chorionic gonadotropins and the follicle stimulating hormones are reported together. Laboratory tests using hypophysectomized animals may be used to isolate the gonadotropic hormone but that is not always practical. Thirty-five per cent of a series of control patients without testis tumor gave positive findings to the Friedman test. Thirty-four per cent of patients with seminoma who should have secreted no gonadotropins had high readings. All of the patients with chorio-epithelioma had strongly positive readings. A positive test cannot, therefore, be interpreted as evidence of testis tumor nor of metastasis. A repeatedly confirmed positive reaction from a patient with tumor indicates the likelihood of the presence of chorionic tissue in the tumor. DIAGNOSIS
The differential diagnosis of testis tumor should not be difficult. Bimanual palpation, which we must insist upon, will eliminate epididymitis, lesions of the spermatic cord, spermatoceles and lesions of the surrounding scrotum. The presence of a complicating hydrocele is the only difficult feature. Trans-illumination, tapping of the hydrocele to facilitate differentiation by palpation are indicated. Our only difficulty has been in the differentiation of thick-walled or calcified hydroceles, hematoceles and gumma. X-ray examination of the scrotum will help in the differentiation of calcified hydrocele from calcification of the testis tumor. Calcification occurs in the periphery in the hydrocle and more or less centrally in the tumor. When there is doubt, exploration of the scrotum is imperative and we are decidedly against the use of punch or needle biopsy.
768
LLOYD G. LEWIS
Seminoma can be differentiated by its radiosensitivity. We have, I believe, adequately studied this phase and upon the suspicion of testis tumor, early if not immediate orchiectomy is advised. THERAPY
Surgery. Orchiectomy, transscrotal or inguinal, should be done as early as possible. We prefer the inguinal approach so that the incision can be extended to perform the radical retroperitoneal dissection after examination of the tumor in gross. Personally, I would like to have a radical orchiectomy for any type of testis tumor. It may not be indicated for seminoma because of the radiosensitivity of that tumor, but I have in mind the possibility of inclusion of some more malignant elements unrecognized in the routine section. Radical orchiectomy may not be indicated for benign interstitial cell tumors nor for simple mature teratomata but here, too, the possibility of malignancy and lymphatic metastasis is not too remote. Chorionic tumors metastasize both by lymphatics and blood stream. The only rationale for radical surgery in chorio-epithelioma is to take the long internal spermatic vessels with the lymphatics. It is the most we can do. Radical orchiectomy consists of removal of the testis with its tunics, the epididymis, vas, entire spermatic cord and the retroperitoneal lymph chain from the inguinal ring to the renal pedicles as described by Chevassu, Young, Hinman and others. Orchiectomy with ligation of the cord at the internal inguinal ring is not radical orchiectomy. We have been fortunate in not having as high a percentage of inoperable metastases as did Young and Hinman. Crossed metastases below the renal pedicles have not been observed by us except when there is tremendous involvement of the precaval nodes from right testis tumor. Like other tumors, testicular tumors do not always involve nodes in continuity along the lymphatic chain. Metastases skip nodes, may even skip all retroperitoneal nodes and appear at the supraclavicular node on the left side. Chorio-epithelioma may invade the blood stream without lymphatic involvement. The external inguinal and femoral nodes are very rarely involved except when the tumor invades the scrotal wall. The internal iliac node at the internal inguinal ring over the external iliac artery is frequently involved. The lymphatic chain extends over the external iliac artery to a node medial to the artery distal to the bifurcation of the external iliac and hypogastric vessels. Then the lymphatic chain crosses the vessels to pass to a node lateral to the common iliac artery. On the left side the lymphatic chain and nodes lie lateral to the aorta to pass up to the nodes at the entrance of the internal spermatic vein into the left renal vein. Those nodes at the renal pedicle and medial to it are most frequently involved. On the right side the lymphatic pathways lead over the vena cava and between it and the aorta to the most frequently involved node at the entrance of the internal spermatic vein into the vena cava. Metastatic channels lead to midline inoperable nodes above the renal pedicles. I do not feel badly about removing uninvolved nodes nor does the surgeon who has the opportunity to do radical mastectomy upon a patient without lymphatic metastasis. My assistant at Walter Reed General Hospital, Dr. Carleton Smith, of Pontiac, Michigan, and
TESTIS TUMORS
769
I have performed 169 radical retroperitoneal resections without operative mortality. Sixty-six per cent of the patients had no metastatic involvement. Twentyfour per cent had operable metastatic nodes removed and we had to leave inoperable nodes in 10 per cent of our operative cases. X-ray. At Walter Reed General Hospital, Dr. Milton Friedman of New York did radiosensitivity studies on a large number of patients who presented themselves with the tumor intact. Many patients had had orchiectomy at other army installations. He found the seminoma most radiosensitive and, in fact, destroyed the tumor in 6 instances so that no tissue is available for microscopic identification. In others the tumor was diagnosed from its metastasis or from areas of spontaneous necrosis not affected by irradiation. Some embryonal tumors were markedly affected by dosage from 2000 to 3000 r. I cannot say that chorionic tumors were effectively changed by x-rays and our results in radiation of metastatic lesions of chorionic tumor -were most discouraging. X-ray therapy to be effective requires use of a full lethal tumor dose. Prophylactic irradiation of the retroperitoneal area or of other specific areas requires specific lethal tumor dosage. Using the million volt x-ray machine, there was no problem in administering the required dose, but the lethal tumor dose must be safe as far as normal tissue destruction and repair are concerned. Dr. Friedman was a pioneer in the field of million volt therapy. We soon learned that the skin is no protection to the therapist in restraining him from delivering lethal doses to the retroperitoneal tissues, nor to the gastro-intestinal tract. The patients have considerable variability in dosage resistance. However, we have found that whereas they can take large dosage and survive the immediate impact, they may develop radiation gastritis and late radionecrosis. Fourteen patients have perforated stomach and bowel 1½ to 2 years following therapy. The relatively small lethal dose for seminoma can be delivered to the retroperitoneal node area with safety. One thousand roentgens is considered adequate. It can be given in 2 weeks with the million volt machine, whereas it takes 6 weeks to deliver the same using the 200 KV machine. I do not feel it is safe to use prophylacbic irradiation for tumors which require more than 3000 r lethal tumor dose. In the presence of known metastasis, the higher dosage required is justified. Dr. Friedman agrees with me that all patients requiring more than 1000 r require radical surgery, and since the operative risk is so small, recommends it for seminoma also. PROGNOSIS
It is too early to present statistics on the value of radical surgery for testis tumor. Since only 1 patient has died from tumor after 1½ years following treatment, we may be able to estimate the trend. The cases illustrated in fig. 1 were operated upon between May 1942 and July 1946. The 2 patients with interstitial cell tumor are well. Seven patients with mature teratoma and one with immature teratoma are considered well after radical surgery without radiation therapy. Eight per cent of the patients with seminoma having radical surgery plus irradiation have died and only 9 per cent of the 109 patients with seminoma have died. We regret that 4 of these patients, who had excessive
770
LLOYD G. LEWIS
Fw. 1. (Upper left), embryonic body resembling a blastocyst composed of primitive ec toderm and entodermal cyst from a metastatic node removed from a patient whose pri mary testis tumor showed hundreds of such embryomas. (High power). (Upper ri ght), adenocarcinoma composed of large vacuolated cells wi th la rge prominent nuclei and ver y prominent nucleoli interpreted as cytotrophobl ast. This chorionic t issue was removed from a metastatic node from the same patient illustrated in the upper left photomicrograph. (High power) . (Left m iddle), papillary adenocarcinoma composed of primitive ectodermal t issue. Metastatic nodes from the same patient showed chorionic tissue. (Low power). (Right middle) , typical seminoma with sheets of seminoma cells inter spersed with lymphoid cells. There is a tendency to acinar formation. No teratoid elements were fo und in th is tumor. (Low power) . (Left lower), immature teratoma composed of embryonic ectodermal elements, entodermal cysts, embryonic connective tissue. (Low power). (Right lower). Chorio-ep ithelioma from a metastatic node illustrating hemorrhagic a reas bordered by syncytia l cells . Langhans cells a re not prominent .
771
TESTIS TUMORS
irradiation for a tumor diagnosed as embryonal carcinoma and later found to be seminoma when sections from overseas hospitals became available, died from radiation gastritis. It is to be noted that 23 per cent of seminomas had metastasis on admission; yet only 5 per cent died from cancer. Sixty per cent of the 28 patients with undifferentiated adeno- or papillary adenocarcinoma had metastasis on admission. Twenty of these patients had radical orchiectomy and 35 per cent have died. Fifty per cent of the total series of 28 have died. Seventy per cent of the 17 patients with choriocarcinoma (cytotrophoblast tumor) had metastasis on admission. Eleven were subjected to retroperitoneal gland resection and 45 per cent of these have died. Sixty-five per cent of the total series of 17 have died. All but one of our 12 patients with chorio-epithelioma had metastasis and TABLE
1.
Testis tumors
CONDITION ON ADMISSION
DIAGNOSIS
CASES
Inopeia-
ble metastases
-- --
Seminoma ... Undif. care ..... Choriocarc ... ....... Chorioepith .. .. Teratocarc. with undif. carcinoma. Teratocarc. & choriocare ...... Tera to care. & chorioepith .. .... Teratoma . .. . . . Inters tit. cell tumor . Total. ....
Operable roetastases - -
TREAT.MENT
Metasta£tasis ~-
Radical orchiec-
Simple orchiec-
tomy
tomy
-~
--
RESULTS RADICAL SERIES
Died
%
- -
- -
RESULTS TOTAL
Died
%
-- --
6 7 5 2
8 35 45 100
10 14
2
40 8 6 10
12
9 50 65 100
38%
29
5
5
17
8
24
10
75%
21
7
9
43
15
53
4 0 0
75% 0 0
7 8 2
5 0 0
6 0 0
86
11
83
109 28 17 12
15 8 8 10
10 9 4 1
23% 60% 70% 92%
69 20
34
9
4
28
11
12 8 2
5 0 0
250 - - - - 43 %
11
1----;;-1~-1~
11
0 0 - -- -- -
24
81
32
all have died from metastatic cancer. Thirty-eight per cent of 34 patients diagnosed teratoma with undifferentiated carcinoma had metastasis on admission. Twenty-nine were subjected to radical orchiectomy. Only 17 per cent of the radical series have died but 24 per cent of the total series of 34 have died. The teratoma apparently lessens the spread of the more malignant tumor cells. Seventy-five per cent of the 28 patients with teratoma and choriocarcinoma had metastasis on admission. Twenty-one of these patients were subjected to radical orchiectomy and 43 per cent of these have died. Fifty-three per cent of the total series of 28 died. Seventy-five per cent of the patients with teratoma and chorioepithelioma had metastasis on admission. Only 2 of these patients are living, 83 per cent having died. SUMi\IARY
In summary, 43 per cent of a series of 250 testis tumors had metastasis on admission. One hundred sixty-nine patients were subjected to radical orchi-
772
LLOYD G. LEWIS
ectomy. Twenty-four per cent of these have died. Eighty-one patients either had inoperable metastasis on admission or were subjected to simple orchiectomy and irradiation because of the diagnosis of seminoma. Thirty~two per cent of the total series have died, 8 of these patients having died from perforation of the stomach or bowel due to excessive irradiation. At autopsy no tumor was found. It is interesting to note that, except in the case of chorio-epithelioma, the metastasis rate was higher than the mortality rate, indicating that therapy by radiation and surgery was thorough. CONCLUSIONS
Treatment of testis tumor must be varied according to the pathology presented: For benign interstitial cell tumors, simple orchiectomy is probably sufficient. For teratomata, radical orchiectomy is indicated without radiation therapy. For seminoma, simple orchiectomy plus radiation therapy is probably sufficient. We recommend 1000 r prophylactic dose to the entire retroperitoneal lymph drainage area. Radical orchiectomy may not be indicated for seminoma but the information gained by retroperitoneal dissection aids the roentgen therapist in planning treatment. For undifferentiated carcinoma, adenocarcinoma and papillary adenocarcinoma, radical orchiectomy is indicated followed by prophylactic roentgen therapy in dosage not to exceed 3000 r. For trophoblastic tumors, choriocarcinoma and chorio-epithelioma radical orchiectomy is indicated and radiation therapy in dosage of 5000 r should not be used except when inoperable metastatic nodes remain. For teratoma with malignant embryonic elements, irradiation is only indicated when inoperable metastatic nodes are found.
1150 Connecticut Ave., Washington 6, D.C. REFERENCES CAMPBELL, H. E.: Arch. Surg., 44: 353, 1942. CHEVAssu, M.: Thesis of Paris, No. 193, 1906. FRIEDMAN, N. B. AND MooRE, R. A.: Mil. Surgeon, 99: 573, 1946. EWING, J.: Neoplastic Diseases. Philadelphia: W. B. Saunders Co., 1928, 3rd ed. GILBERT, J.B.: J. Urol., 46: 740, 1941. HINMAN, F.: Principles and Practice of Urology. Philadelphia: W. B. Saunders Co., 1935. MELICOW, M. M.: J. Urol., 44: 333, 1940. PEYRON, A.: Compt. rend. Soc. de biol., 135: 281,347,864, 1941. SABRAZES, J., AND PEYRON, A.: Compt. rend. Soc. de biol., 135: 350, 1941. YOUNG, H. H., AND DAVIS, D. M.: Young's Practice of Urology. Philadelphia: W. B. Saunders Co., 1926, vol. 2, p. 544.