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Lymphosarcoma of the Testis
THE JOURNAL OF UROLOGY
Vol. 73, No. 6, June 1955 Printed in U.S.A.
LYMPHOSARCOMA OF THE TESTIS DEAN C. VARNEY From the Cleveland Veterans Administration Hospital, Cleveland, Ohio
Although comn10nly accepted as a metastatic phenomenon, lymphosarcoma of the testis should be considered as a possible clinical entity. Since Malassez's original report in 1877, approximately 30 cases have been reported in the British and American literature. 1¥hile seldom evident as the only clinical manifestation of the disease, it constitutes the most common metastatic tumor of the testis. Several observers claim that it may originate primarily in that organ. In 1944 Helfert and Pinck were able to collect reports of less than 50 cases of metastatic testicular tumors. vVillis, in a review of over 500 cases of consecutive cancer necropsies, reported 2 cases, while 'Watson et al., in a rn.onumental study of 1073 cases of lymphoblastomas, of which 456 were lymphosarcomas, found 75 of the latter invading the genito-urinary tract and only 2 involving the testes. Dockerty and Priestley noted only 4 instances of lymphosarcoma in a survey of 400 cases of testicular malignancies. It is the purpose of this report to present 5 cases of proven lymphosarcorn.a of the testis, and to discuss certain diagnostic and therapeutic considerations in the management of the disease. CASE REPORTS
Case 1. G. W., a 57-year-old white man, entered the hospital April 13, 1950 complaining of swelling of the right cheek for 2½ months. Physical examination revealed moderate fullness and hypesthesia over the right cheek The initial laboratory studies and chest film were negative. Skull films revealed thickening of the right zygoma and anterior wall of the right antrum. X-rays of the pelvis revealed an osteoblastic reaction involving the right ischium and acetabulurn highly suggestive of Paget's disease. A Cald·well-Luc operation was performed April 18 and a large cystic mass overlying the entire right maxillary sinus removed. The microscopic diagnosis was lymphosarcoma, large cell type. Despite adequate irradiation to the right maxillary region and subsequent therapy directed at pulmonary metastases, the patient expired July 9. Autopsy revealed extension of the original tumor through the anterior medial wall of the middle cranial fossa and lateral wall of the right orbit into the retrobulbar fat. In addition to involvement of the lungs, liver, stomach, small bowel, adrenals, kidneys and lymph nodes, there was massive replacement by tumor of both testes and epididymides. Microscopic examination of the testes revealed a diffuse infiltration by neoplastic cells of the lymphocyte series between the seminiferous tubules (fig. 1). Case 2. J. H., a 62 year old white man, entered the hospital January 8, 1952 with a swollen left scrotum and testis of 4 to 5 weeks' duration. Past history Accepted for publication December 14, 1954. 1081
1082
DEAN C. VARNEY
FIG. 1. Case 1. Note dense replacement of normal testicular parenchyma by lymphoblasts. XlOO.
revealed a right orchiectomy in November 1950 followed by 32 deep x-ray treatments to the right scrotum and inguinal region. The admission laboratory studies, Friedman test and chest film were negative. Cystoscopy and retrograde pyelograms were nonrevealing. Because of the past history of a right testicular neoplasm, a biopsy of the left testis was performed January 10 and revealed lymphosarcoma, small cell type. In order to determine the radiosensitivity of the tumor a total dose of 2,400 r. (skin dose) was directed to the left testis over a 5-day period, and left orchiectomy was performed February 12. Microscopic examination revealed only fibrosis and atrophy with no evidence of tumor involving the testis; however there was neoplastic invasion of the spermatic cord by lymphosarcoma, small cell type (fig. 2). Irradiation therapy to the right and left inguinal regions, epigastrium, umbilical area and inferior and superior lumbar fields was then resumed, a total of 4,000 r. (skin dose) being given. Despite this cancerocidal bombardment cutaneous metastases developed and the patient expired May 24 in uremia. Autopsy revealed massive involvement of the heart, lungs, liver, pancreas, kidneys, adrenal glands, subcutaneous tissues and lymph nodes by lymphosarcoma, small cell type. Of incidental interest is the fact that slides of the previously removed right testicular tumor revealed embryonal cell carcinoma. The patient, although the
LYMPHOSARCOMA OF THE TESTIS
1083
Frn. 2. Case 2. Lymphosarcoma of spermatic cord missed by cancercidal irradiation directed at testis. XlOO.
unfortunate victim of two deadly tumors, apparently survived the first cancer as no traces of it were discovered at autopsy. Case 3. M. Z., a 58-year-old white man, entered the hospital on August 16, 1952 with a 3 months' history of a left scrotal mass. Examination revealed a markedly firm, nodular mass involving the left testis and epididymis. All laboratory studies, including a Friedman test, were negative. Chest film and skeletal survey showed no metastases. On August 22 a left orchiectomy through an inguinal approach was performed. The pathological diagnosis was lymphosarcoma, large cell type (fig. 3). The patient was started on irradiation therapy 1 week following operation and received approximately 2,500 r. (skin dose) to the left inguinal, umbilical and epigastric fields anteriorly and the lumbosacral, lumbodorsal fields posteriorly. He was discharged asymptomatic on October 10 with no evidence of metastases. He re-entered the hospital on June 11, 1953 because of radiographic evidence of several ill defined nodules in the right lower lung field, first evident on a chest film taken on April 23, 1953. Irradiation therapy was given to the anterior and posterior right lung fields, total dosage consisting of 2,400 r. (skin dose), with complete disappearance of the nodular densities. Readmission on September 21, 1953 was necessary because of metastatic nodules in the left lung field. These completely resolved following 1,800 r (skin dose) to the left hilum and anterior and posterior left lung fields.
1084
DEAN C. VARNEY
Fm. 3. Case 3. Note dense infiltration by anaplastic cells with compression of seminiferous tubules. X 100.
At the present date the patient is free of demonstrable metastases based upon excretory pyelography, skeletal survey and repeated chest films. Case 4. P. K., a 66-year-old white man, entered the hospital on August 12, 1953 complaining of bilateral scrotal enlargement of 2 years' duration. Physical examination revealed an enlarged, firm, right, anterior, cervical lymph node. The right scrotum was occupied by a firm, nontender mass, measuring 20 by 10 cm. The left scrotal cord was indurated and fixed. The admission chest film (fig. 4, A) revealed a confluent and linear increase in density throughout the right lower lung field. There were several large nodular densities in the posterior right lung and an osteolytic lesion was noted involving the posterior portion of the right eighth rib. An excretory urogram showed no excretion of contrast medium on the left side. Otherwise the laboratory studies were negative. In view of the cervical adenopathy and the bilaterality of the testicular masses, the clinical impression was lymphoma and bilateral orchiectomy was performed on August 14, 1953 in order to establish a working diagnosis (fig. 4, B). The microscopic examination revealed lymphosarcoma, small cell type (fig. 5). Despite intensive irradiation therapy this patient maintained a febrile course and expired on September 30, 1953. Autopsy revealed widespread lymphosarcoma of the small cell type involving the lungs, lymph nodes, liver, pancreas, adrenals, thyroid and left kidney with obstruction of the left ureter by enlarged retroperitoneal lymph nodes.
LYMPHOSARCOMA OF THE TESTIS
1085
Frn. 4. Case 4. A, note metastatic focus in right lung suggestive of abscess. B, gross specimen exhibiting unusual involvement of advential tissues by tumor.
Frn. 5. Photomicrograph demonstrates complete obliteration of normal testicular architecture. XlOO.
Case 5. C. G., a 38 year old white man, was admitted on July 29, 1953 with a 7 months' history of persistent nasal discharge. Physical exam.ination revealed a markedly swollen nose with the right naris obstructed by a necrotic tumor mass. There were several slightly enlarged, firm, nontender lymph nodes in the right
1086
DEAN C. VARNEY
anterior cervical chain. The admission hemogram, urinalysis and serology were within normal limits. The admission chest film and three subsequent films were negative. A biopsy of the right intranasal lesion shortly following admission was interpreted as lymphoepithelioma. The patient was given 7,100 r. through three portals to the nasal region with apparent good results. On August 22, 1935 an arciform, erythematous nodule appeared on the left thigh. Biopsy revealed only chronic inflammation, and the lesion disappeared following 1,000 r. of irradiation. Despite the uniform response of the initial lesions to irradiation, new skin lesions appeared and the original nasal tumor recurred. The patient expired on February 9, 1936. At autopsy, massive involvement by tumor of the lungs, lymph nodes and skin was observed. In addition, a well circumscribed, firm yellowish-gray nodule, 2.5 cm. in diameter was discovered in the left testis. The diagnosis was lymphosarcoma, large cell type. The microscopic picture revealed many lymphocyte-like cells infiltrating the interstitial tissues of the testis. The tubules exhibited varying degrees of degeneration. DISCUSSION
Lymphosarcoma is classified as one of the lymphoblastomas. In this group of neoplasms are also included reticulum cell sarcoma, lymphoid leukemia and Hodgkin's sarcoma. The disease occurs occasionally in the younger age group, but affects predominantly those in the fifth and sixth decades. Males are afflicted three times more frequently than females. The youngest reported case of testicular lymphosarcoma was a 4-year-old Negro boy. The average age in this series of 5 patients was 56.4 years. The lymphoblastomas are the most common cause of bilateral testicular tumor and accounted for 50 per cent of 21 cases reported by Hotchkiss and Laury. Case 4 of our series presented this picture, and cognizance of this fact aided in the clinical diagnosis of lymphoma. It should be stated that bilateral primary testicular carcinoma is extremely rare. Most authorities agree that the testicular involvement is only part of a diffuse metastatic infiltration of multiple organs. However, Mathe in 1946, Gandin and Konwaler in 1951, and Turley and Moore in 1952 reported cases in which the testicular tumor was the presenting abnormality and very possibly represented the primary site of the disease. The findings in two of our cases would appear to support this thesis. Case 2 exhibited a primary testicular mass that was the only evidence of disease until cutaneous metastases appeared 3 months later. Case 3 progressed 11 months following initial diagnosis and orchiectomy before pulmonary metastases were noted; the patient is now living and well 2 years after orchiectomy and irradiation therapy without evidence of generalized disease. Hutchinson's case, reported in 1889, died from widespread metastases 3 years following orchiectomy. The paradox of how a lymphoma may arise in an organ that does not contain lymphoid tissue has given rise to several interesting theories regarding etiology. Ficari cites the prostate (15 reported cases) and the urinary bladder (6 reported
LYMPHOSARCOMA OF THE TESTIS
1087
cases) as nonlymphoid organs presenting primary lymphosarcoma and postulates that the neoplasm may either originate from residual postinflammatory lymphoid tissue or may represent specific differentiation of a pre-existing teratocarcinoma. This interesting controversy of primary origin versus secondary invasion poses an academic desideratum. Should lymphosarcoma, originally manifest and only demonstrable as testicular tumor, be added to the classification of primary malignant testicular tumors; or should the occasional testicular involvement be considered as part of a wisely disseminated process? Prudence would seem to demand that final judgment be withheld until more statistics and studies have been compiled. It is interesting to note that the nasopharynx, richly endowed with lymphoid tissue, appears to be the most common primary site of lymphosarcoma, with eventual spread to the testis, having been demonstrated in over 20 per cent of the reported cases and being the original focus in two of our cases, an incidence of 40 per cent. The concomitant existence or subsequent appearance of cutaneous lesions is frequent and offers a definite aid in diagnosis. The only other such combination under similar circumstances occurs in chorioepithelioma of the testis. Cutaneous nodules were present in three, or 60 per cent, of our cases. The presence of lymphadenopathy, usually cervical or inguinal, has been noted in 40 per cent of the reported cases. Splenomegaly is often detectable, but it may be absent. None of our cases showed leukemic involvement. Grossly, these tumors are almost invariably confined within the tunica albuginea. However they may occasionally invade the epididymis and spermatic cord. Microscopically, the testicular parenchyma is massively infiltrated or replaced by a rather homogeneous sheet of cells of the lymphocyte or lymphoblast type, with only a few degenerating tubules discernible. The subclassification consists of small cell or large cell lymphosarcoma, utilizing the most predominant cellular pattern as a basis for diagnosis. Reticulum cell sarcoma may be confused with the above, but it can be differentiated by use of a reticulum cell stain. Hodgkin's sarcoma and lymphatic leukemia occasionally infiltrate the testis, but they seldom give rise to gross enlargement and there is invariably sufficient clinical and microscopic evidence present for establishment of their distinctive identity. The usual treatment of lymphosarcoma of the testis has been orchiectomy followed by irradiation therapy. However, 2 cases treated with nitrogen mustard have been reported. One patient so treated by Hotchkiss and Laury was unaffected, but Gandin and Konwaler's patient showed some initial improvement following 28 gm. of the agent. The prognosis is poor, with survival varying from 6 months to 3 years following onset of symptoms and/ or signs. CONCLUSIONS
Lymphosarcoma of the testis is a rare disease usually secondary to a primary origin elsewhere in the lymphoid tissues of the body. It may, however, present
1088
DEAN C. VARNEY
itself as a primary tumor of the testis and must therefore be considered in the differential diagnosis of testicular tumor. The diagnostic probability of its existence is enhanced by the presence of bilateral testicular tumor with the concomitant presence of skin lesions and lymphadenopathy. Although the lesion responds to irradiation therapy, the eventual prognosis 1s poor. The author expresses his appreciation to Dr. Thomas Kinney of Cleveland City Hospital for permission to use case 5.
626 E. Santa Clara St., San Jose 12, Calif. REFERENCES CoLBY, F. H.: Lymphosarcoma of both testicles, metastatic from the nasopharynx. New Eng. J. Med., 202: 657-658, 1930. DocKERTY, M. B. AND PRIESTLEY, J. T.: Lymphosarcoma of the testis. J. Urol., 48: 514-523, 1942. FrcARI, ANTELIO: A case of lymphosarcoma with metastases in unusual situations. J. Path. & Bact., 62: 103-110, 1950. GANDIN, M. M. AND KoNWALER, B. E.: Lymphosarcoma of the testicle. Ann. West. Med. & Surg., 5: 55-58, 1951. HERBUT, P.A.: Urological Pathology. Philadelphia: Lea and Febiger, 1952, vol. 2. HoTCHKISS, R. S. AND LAURY, R. B.: Concomitant bilateral malignant testicular tumors. J. Urol., 63: 1086-1092, 1950. HUTCHINSON, J.: Lymphosarcoma of both testes with considerable interval of time. Brit. Med. J., 1: 413, 1889. MATHE, C. P.: Lymphosarcoma of the testicle. J. Urol., 55: 530-541, 1946. MooRE, T. A.: A Textbook of Pathology. Philadelphia: M. B. Saunders Co., 1945. ORMOND, J. K. AND PRINCE, C. L.: Malignant tumors of the testicle. J. Urol., 45: 685-691, 1941. PEASE, G. L. AND McDONALD, J. R.: Lymphoblastomatous involvement of nonlymphoid organs. Am. J. Clin. Path., 17: 181-196, 1947. TURLEY, H.K. AND MooRE, T. D.: Malignant lymphoma primarily manifest as a testicular tumor. J. Urol., 68: 744-746, 1952. WATSON, E. M., SAUER, H. R. AND SADUGOR, M. G.: Manifestations of the lymphoblastomas in the genito-urinary tract. J. Urol., 61: 626--642, 1949.
Vol. 73, No. 6, June 1955 Printed in U.S.A.
LYMPHOSARCOMA OF THE TESTIS DEAN C. VARNEY From the Cleveland Veterans Administration Hospital, Cleveland, Ohio
Although comn10nly accepted as a metastatic phenomenon, lymphosarcoma of the testis should be considered as a possible clinical entity. Since Malassez's original report in 1877, approximately 30 cases have been reported in the British and American literature. 1¥hile seldom evident as the only clinical manifestation of the disease, it constitutes the most common metastatic tumor of the testis. Several observers claim that it may originate primarily in that organ. In 1944 Helfert and Pinck were able to collect reports of less than 50 cases of metastatic testicular tumors. vVillis, in a review of over 500 cases of consecutive cancer necropsies, reported 2 cases, while 'Watson et al., in a rn.onumental study of 1073 cases of lymphoblastomas, of which 456 were lymphosarcomas, found 75 of the latter invading the genito-urinary tract and only 2 involving the testes. Dockerty and Priestley noted only 4 instances of lymphosarcoma in a survey of 400 cases of testicular malignancies. It is the purpose of this report to present 5 cases of proven lymphosarcorn.a of the testis, and to discuss certain diagnostic and therapeutic considerations in the management of the disease. CASE REPORTS
Case 1. G. W., a 57-year-old white man, entered the hospital April 13, 1950 complaining of swelling of the right cheek for 2½ months. Physical examination revealed moderate fullness and hypesthesia over the right cheek The initial laboratory studies and chest film were negative. Skull films revealed thickening of the right zygoma and anterior wall of the right antrum. X-rays of the pelvis revealed an osteoblastic reaction involving the right ischium and acetabulurn highly suggestive of Paget's disease. A Cald·well-Luc operation was performed April 18 and a large cystic mass overlying the entire right maxillary sinus removed. The microscopic diagnosis was lymphosarcoma, large cell type. Despite adequate irradiation to the right maxillary region and subsequent therapy directed at pulmonary metastases, the patient expired July 9. Autopsy revealed extension of the original tumor through the anterior medial wall of the middle cranial fossa and lateral wall of the right orbit into the retrobulbar fat. In addition to involvement of the lungs, liver, stomach, small bowel, adrenals, kidneys and lymph nodes, there was massive replacement by tumor of both testes and epididymides. Microscopic examination of the testes revealed a diffuse infiltration by neoplastic cells of the lymphocyte series between the seminiferous tubules (fig. 1). Case 2. J. H., a 62 year old white man, entered the hospital January 8, 1952 with a swollen left scrotum and testis of 4 to 5 weeks' duration. Past history Accepted for publication December 14, 1954. 1081
1082
DEAN C. VARNEY
FIG. 1. Case 1. Note dense replacement of normal testicular parenchyma by lymphoblasts. XlOO.
revealed a right orchiectomy in November 1950 followed by 32 deep x-ray treatments to the right scrotum and inguinal region. The admission laboratory studies, Friedman test and chest film were negative. Cystoscopy and retrograde pyelograms were nonrevealing. Because of the past history of a right testicular neoplasm, a biopsy of the left testis was performed January 10 and revealed lymphosarcoma, small cell type. In order to determine the radiosensitivity of the tumor a total dose of 2,400 r. (skin dose) was directed to the left testis over a 5-day period, and left orchiectomy was performed February 12. Microscopic examination revealed only fibrosis and atrophy with no evidence of tumor involving the testis; however there was neoplastic invasion of the spermatic cord by lymphosarcoma, small cell type (fig. 2). Irradiation therapy to the right and left inguinal regions, epigastrium, umbilical area and inferior and superior lumbar fields was then resumed, a total of 4,000 r. (skin dose) being given. Despite this cancerocidal bombardment cutaneous metastases developed and the patient expired May 24 in uremia. Autopsy revealed massive involvement of the heart, lungs, liver, pancreas, kidneys, adrenal glands, subcutaneous tissues and lymph nodes by lymphosarcoma, small cell type. Of incidental interest is the fact that slides of the previously removed right testicular tumor revealed embryonal cell carcinoma. The patient, although the
LYMPHOSARCOMA OF THE TESTIS
1083
Frn. 2. Case 2. Lymphosarcoma of spermatic cord missed by cancercidal irradiation directed at testis. XlOO.
unfortunate victim of two deadly tumors, apparently survived the first cancer as no traces of it were discovered at autopsy. Case 3. M. Z., a 58-year-old white man, entered the hospital on August 16, 1952 with a 3 months' history of a left scrotal mass. Examination revealed a markedly firm, nodular mass involving the left testis and epididymis. All laboratory studies, including a Friedman test, were negative. Chest film and skeletal survey showed no metastases. On August 22 a left orchiectomy through an inguinal approach was performed. The pathological diagnosis was lymphosarcoma, large cell type (fig. 3). The patient was started on irradiation therapy 1 week following operation and received approximately 2,500 r. (skin dose) to the left inguinal, umbilical and epigastric fields anteriorly and the lumbosacral, lumbodorsal fields posteriorly. He was discharged asymptomatic on October 10 with no evidence of metastases. He re-entered the hospital on June 11, 1953 because of radiographic evidence of several ill defined nodules in the right lower lung field, first evident on a chest film taken on April 23, 1953. Irradiation therapy was given to the anterior and posterior right lung fields, total dosage consisting of 2,400 r. (skin dose), with complete disappearance of the nodular densities. Readmission on September 21, 1953 was necessary because of metastatic nodules in the left lung field. These completely resolved following 1,800 r (skin dose) to the left hilum and anterior and posterior left lung fields.
1084
DEAN C. VARNEY
Fm. 3. Case 3. Note dense infiltration by anaplastic cells with compression of seminiferous tubules. X 100.
At the present date the patient is free of demonstrable metastases based upon excretory pyelography, skeletal survey and repeated chest films. Case 4. P. K., a 66-year-old white man, entered the hospital on August 12, 1953 complaining of bilateral scrotal enlargement of 2 years' duration. Physical examination revealed an enlarged, firm, right, anterior, cervical lymph node. The right scrotum was occupied by a firm, nontender mass, measuring 20 by 10 cm. The left scrotal cord was indurated and fixed. The admission chest film (fig. 4, A) revealed a confluent and linear increase in density throughout the right lower lung field. There were several large nodular densities in the posterior right lung and an osteolytic lesion was noted involving the posterior portion of the right eighth rib. An excretory urogram showed no excretion of contrast medium on the left side. Otherwise the laboratory studies were negative. In view of the cervical adenopathy and the bilaterality of the testicular masses, the clinical impression was lymphoma and bilateral orchiectomy was performed on August 14, 1953 in order to establish a working diagnosis (fig. 4, B). The microscopic examination revealed lymphosarcoma, small cell type (fig. 5). Despite intensive irradiation therapy this patient maintained a febrile course and expired on September 30, 1953. Autopsy revealed widespread lymphosarcoma of the small cell type involving the lungs, lymph nodes, liver, pancreas, adrenals, thyroid and left kidney with obstruction of the left ureter by enlarged retroperitoneal lymph nodes.
LYMPHOSARCOMA OF THE TESTIS
1085
Frn. 4. Case 4. A, note metastatic focus in right lung suggestive of abscess. B, gross specimen exhibiting unusual involvement of advential tissues by tumor.
Frn. 5. Photomicrograph demonstrates complete obliteration of normal testicular architecture. XlOO.
Case 5. C. G., a 38 year old white man, was admitted on July 29, 1953 with a 7 months' history of persistent nasal discharge. Physical exam.ination revealed a markedly swollen nose with the right naris obstructed by a necrotic tumor mass. There were several slightly enlarged, firm, nontender lymph nodes in the right
1086
DEAN C. VARNEY
anterior cervical chain. The admission hemogram, urinalysis and serology were within normal limits. The admission chest film and three subsequent films were negative. A biopsy of the right intranasal lesion shortly following admission was interpreted as lymphoepithelioma. The patient was given 7,100 r. through three portals to the nasal region with apparent good results. On August 22, 1935 an arciform, erythematous nodule appeared on the left thigh. Biopsy revealed only chronic inflammation, and the lesion disappeared following 1,000 r. of irradiation. Despite the uniform response of the initial lesions to irradiation, new skin lesions appeared and the original nasal tumor recurred. The patient expired on February 9, 1936. At autopsy, massive involvement by tumor of the lungs, lymph nodes and skin was observed. In addition, a well circumscribed, firm yellowish-gray nodule, 2.5 cm. in diameter was discovered in the left testis. The diagnosis was lymphosarcoma, large cell type. The microscopic picture revealed many lymphocyte-like cells infiltrating the interstitial tissues of the testis. The tubules exhibited varying degrees of degeneration. DISCUSSION
Lymphosarcoma is classified as one of the lymphoblastomas. In this group of neoplasms are also included reticulum cell sarcoma, lymphoid leukemia and Hodgkin's sarcoma. The disease occurs occasionally in the younger age group, but affects predominantly those in the fifth and sixth decades. Males are afflicted three times more frequently than females. The youngest reported case of testicular lymphosarcoma was a 4-year-old Negro boy. The average age in this series of 5 patients was 56.4 years. The lymphoblastomas are the most common cause of bilateral testicular tumor and accounted for 50 per cent of 21 cases reported by Hotchkiss and Laury. Case 4 of our series presented this picture, and cognizance of this fact aided in the clinical diagnosis of lymphoma. It should be stated that bilateral primary testicular carcinoma is extremely rare. Most authorities agree that the testicular involvement is only part of a diffuse metastatic infiltration of multiple organs. However, Mathe in 1946, Gandin and Konwaler in 1951, and Turley and Moore in 1952 reported cases in which the testicular tumor was the presenting abnormality and very possibly represented the primary site of the disease. The findings in two of our cases would appear to support this thesis. Case 2 exhibited a primary testicular mass that was the only evidence of disease until cutaneous metastases appeared 3 months later. Case 3 progressed 11 months following initial diagnosis and orchiectomy before pulmonary metastases were noted; the patient is now living and well 2 years after orchiectomy and irradiation therapy without evidence of generalized disease. Hutchinson's case, reported in 1889, died from widespread metastases 3 years following orchiectomy. The paradox of how a lymphoma may arise in an organ that does not contain lymphoid tissue has given rise to several interesting theories regarding etiology. Ficari cites the prostate (15 reported cases) and the urinary bladder (6 reported
LYMPHOSARCOMA OF THE TESTIS
1087
cases) as nonlymphoid organs presenting primary lymphosarcoma and postulates that the neoplasm may either originate from residual postinflammatory lymphoid tissue or may represent specific differentiation of a pre-existing teratocarcinoma. This interesting controversy of primary origin versus secondary invasion poses an academic desideratum. Should lymphosarcoma, originally manifest and only demonstrable as testicular tumor, be added to the classification of primary malignant testicular tumors; or should the occasional testicular involvement be considered as part of a wisely disseminated process? Prudence would seem to demand that final judgment be withheld until more statistics and studies have been compiled. It is interesting to note that the nasopharynx, richly endowed with lymphoid tissue, appears to be the most common primary site of lymphosarcoma, with eventual spread to the testis, having been demonstrated in over 20 per cent of the reported cases and being the original focus in two of our cases, an incidence of 40 per cent. The concomitant existence or subsequent appearance of cutaneous lesions is frequent and offers a definite aid in diagnosis. The only other such combination under similar circumstances occurs in chorioepithelioma of the testis. Cutaneous nodules were present in three, or 60 per cent, of our cases. The presence of lymphadenopathy, usually cervical or inguinal, has been noted in 40 per cent of the reported cases. Splenomegaly is often detectable, but it may be absent. None of our cases showed leukemic involvement. Grossly, these tumors are almost invariably confined within the tunica albuginea. However they may occasionally invade the epididymis and spermatic cord. Microscopically, the testicular parenchyma is massively infiltrated or replaced by a rather homogeneous sheet of cells of the lymphocyte or lymphoblast type, with only a few degenerating tubules discernible. The subclassification consists of small cell or large cell lymphosarcoma, utilizing the most predominant cellular pattern as a basis for diagnosis. Reticulum cell sarcoma may be confused with the above, but it can be differentiated by use of a reticulum cell stain. Hodgkin's sarcoma and lymphatic leukemia occasionally infiltrate the testis, but they seldom give rise to gross enlargement and there is invariably sufficient clinical and microscopic evidence present for establishment of their distinctive identity. The usual treatment of lymphosarcoma of the testis has been orchiectomy followed by irradiation therapy. However, 2 cases treated with nitrogen mustard have been reported. One patient so treated by Hotchkiss and Laury was unaffected, but Gandin and Konwaler's patient showed some initial improvement following 28 gm. of the agent. The prognosis is poor, with survival varying from 6 months to 3 years following onset of symptoms and/ or signs. CONCLUSIONS
Lymphosarcoma of the testis is a rare disease usually secondary to a primary origin elsewhere in the lymphoid tissues of the body. It may, however, present
1088
DEAN C. VARNEY
itself as a primary tumor of the testis and must therefore be considered in the differential diagnosis of testicular tumor. The diagnostic probability of its existence is enhanced by the presence of bilateral testicular tumor with the concomitant presence of skin lesions and lymphadenopathy. Although the lesion responds to irradiation therapy, the eventual prognosis 1s poor. The author expresses his appreciation to Dr. Thomas Kinney of Cleveland City Hospital for permission to use case 5.
626 E. Santa Clara St., San Jose 12, Calif. REFERENCES CoLBY, F. H.: Lymphosarcoma of both testicles, metastatic from the nasopharynx. New Eng. J. Med., 202: 657-658, 1930. DocKERTY, M. B. AND PRIESTLEY, J. T.: Lymphosarcoma of the testis. J. Urol., 48: 514-523, 1942. FrcARI, ANTELIO: A case of lymphosarcoma with metastases in unusual situations. J. Path. & Bact., 62: 103-110, 1950. GANDIN, M. M. AND KoNWALER, B. E.: Lymphosarcoma of the testicle. Ann. West. Med. & Surg., 5: 55-58, 1951. HERBUT, P.A.: Urological Pathology. Philadelphia: Lea and Febiger, 1952, vol. 2. HoTCHKISS, R. S. AND LAURY, R. B.: Concomitant bilateral malignant testicular tumors. J. Urol., 63: 1086-1092, 1950. HUTCHINSON, J.: Lymphosarcoma of both testes with considerable interval of time. Brit. Med. J., 1: 413, 1889. MATHE, C. P.: Lymphosarcoma of the testicle. J. Urol., 55: 530-541, 1946. MooRE, T. A.: A Textbook of Pathology. Philadelphia: M. B. Saunders Co., 1945. ORMOND, J. K. AND PRINCE, C. L.: Malignant tumors of the testicle. J. Urol., 45: 685-691, 1941. PEASE, G. L. AND McDONALD, J. R.: Lymphoblastomatous involvement of nonlymphoid organs. Am. J. Clin. Path., 17: 181-196, 1947. TURLEY, H.K. AND MooRE, T. D.: Malignant lymphoma primarily manifest as a testicular tumor. J. Urol., 68: 744-746, 1952. WATSON, E. M., SAUER, H. R. AND SADUGOR, M. G.: Manifestations of the lymphoblastomas in the genito-urinary tract. J. Urol., 61: 626--642, 1949.