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Leydig cell tumor in patient on estrogen therapy
LEYDIG
CELL
ON ESTROGEN
A. S. DESHMUKH, W. H. HARTUNG,
TUMOR
IN PATIENT
THERAPY
M.D. M.D.
From the Departments of Urology and Pathology, St. Charles Hospital, Oregon, Ohio
ABSTRACT-The occurrence of a Leydig cell tumor in a sixty-nine-year-old man, who receizjed estrogen therapy for approximately two and one-haZf years, is reported. No similar situation has been reported in the medical literature, although there has been a search for the cause of these tumors in man. Experimentally, the administration of estrogen has caused these tumors in mice.
Aware of (1) the frequent use of estrogens in treating carcinoma of the prostate gland, (2) the small size of Leydig tumors (0.3 cm), (3) the limited manner in which testes are examined routinely when surgically removed in such cases, and (4) the continued interest in the cause of Leydig cell tumor, the authors wish to encourage a more elaborate gross examination of the testes so that the causation, incidence, and significance of this tumor in man may be evaluated properly. They report a case of Leydig cell tumor in a sixty-nine-year-old man who received estrogen therapy for approximately two and one-half years. Case Report A sixty-nine-year-old white man was seen in April, 1975, for urinary frequency with nocturia (4 x ), obstruction to the urinary flow, and dribbling. He had been receiving treatment for essential hypertension since 1974. Physical examination revealed a hard right lobe of the prostate without evidence of local extension. Acid and alkaline phosphatase in the serum were within normal limits. An excretory urogram was unremarkable except for prostatic filling defect in the bladder. A bone scan was negative for any significant changes. Cystourethroscopy revealed irregular hyperplasia
*5”j3x
of the lateral lobes of the prostate with evidence of obstruction. On April 21, 1975, a transurethral resection revealed adenocarcinoma of the prostate. The patient was given 1.0 mg stilbestrol daily until September 9, 1977, when a bilateral orchiectomy was performed. He received radiation therapy to his prostate from August to October, 1975, (a total of 7,000 rad). In July, 1976, he suffered a myocardial infarction. In November, 1976, he had an anal fissurectomy; at this time he had occasional urgency of urination. His serum alkaline phosphatase was within normal limits, but his acid phosphatase was 11.6 units (normal 0.0 to 0.8 units). A bone scan revealed multiple areas of increased radioactivity throughout his left ribs and dorsal spine, with a single area noted in the right ilium. In August, 1977, multiple osteoblastic and osteolytic metastases were noted throughout the left ribs and spine, and he complained of pain in his left shoulder and back. In September, 1977, the pain increased. An intravenous pyelogram revealed extensive osteoblastic changes in his pelvic bones. His acid phosphatase was 39.6 units and alkaline phosphatase 24.0 units (normal, 4.5 to 11.0 units). A bilateral orchiectomy was performed on September 19, 1977, after which he had dramatic relief of pain.
UROLOGY
:
ilAY 1983
:
\‘OLlNE
XXI. NUSlBER 5
FIGUHI; 1. (A) Leydig cell tumor of upper pole of left testis; (B) Leydig cell tumor shoukg uniformity of cells.
Histology Histologic examination revealed mild atrophy and aspermatogenesis of both testes. Within the upper pole of the left testis anteriorly there was a soft, dark brown, sharply demarcated nodule, measuring 0.3 cm in diameter. Microscopically this lesion was composed of a circumscribed mass of interstitial (Leydig) cells (Fig. 1A). They were closely packed, welldifferentiated, and uniform in size, shape, and staining reactions (Fig. 1B). No mitotic activity was noted. Comment Recently, Damjanov, Katy, and Jewett’ reviewed the characteristics of the Leydig cell tumor, emphasizing the limited experience with this neoplasm which comprises approximately 1 to 3 per cent of all testicular tumors. It occurs within various age groups, but is uncommon after the age of sixty years. It usually is benign, however, about 10 to 15 per cent may be malignant with metastases. The average age of patients with benign lesions is 26.4 years and malignant lesions 57.6 years.” In the prepubertal stage this lesion may produce all of the clinical features of precocious androgen excess, while in the postpubertal stage they may be associated with gynecomastia or have no apparent endocrine manifestations. The cause of Leydig cell tumors in man has not been identified. In th:is case the patient was sixty-nine years of age and had received estrogen and radiation therapy. Clinically. he showed no evident endo-
crine effects from the neoplasm. Did the estrogen and/or the radiation therapy cause the neoplasm? Did it develop spontaneously, regardless of therapy? Diamond and Impink reported 3 cases of Leydig cell tumor occurring in men above age sixty. Anderwont, Shimkin, and Canter4 implanted stilbestrol pellets within the subcutaneous tissue of strain BALBiC two-month-old male mice. This caused the formation of Leydig cell tumors, especially in the right testis. Administration of estrogens to A-strain mice has been reported to cause Leyrdig cell tumor in the testis. 5 The authors hope that this experience will stimulate careful gross examination of testes removed for cancer therapy and that positive findings be reported in medical literature. 723 Phillips Avenue Toledo, Ohio 43612 (DR. DESHMUKH) References
1. Damjamov I. Katz SM. and Jewett MAS: Leydig cell tumors of the testis. Ann Clin Lab Sci 9: 157 (19791. 2. Silverberg SG, Thompson JN< Higashi G, and Rasken AML: Malignant interstitial cell tumor of the testis. J Ural 96: 356 (1966). 3. Diamond JJ, and Impink RR: Interstitial cell tumor of testicle: report of a case and correlation xvith review of literature. Arch Surg 73: 274 (1956), 4. AnderLvont HB. Shimkin BM, and Canter HI’: The growth of estrogen-induced interstitial cell testicular tumors in BALRiC mice. J Nat1 Cancer Inst 24: 1219 (1960). 5. Hooker C1V and Pfeiffer CA: The morpholoq and development of testicular tumors in mice of the A-strain receiving estrogens. Can Hcs 2: 759 (1932).
5:39
CELL
ON ESTROGEN
A. S. DESHMUKH, W. H. HARTUNG,
TUMOR
IN PATIENT
THERAPY
M.D. M.D.
From the Departments of Urology and Pathology, St. Charles Hospital, Oregon, Ohio
ABSTRACT-The occurrence of a Leydig cell tumor in a sixty-nine-year-old man, who receizjed estrogen therapy for approximately two and one-haZf years, is reported. No similar situation has been reported in the medical literature, although there has been a search for the cause of these tumors in man. Experimentally, the administration of estrogen has caused these tumors in mice.
Aware of (1) the frequent use of estrogens in treating carcinoma of the prostate gland, (2) the small size of Leydig tumors (0.3 cm), (3) the limited manner in which testes are examined routinely when surgically removed in such cases, and (4) the continued interest in the cause of Leydig cell tumor, the authors wish to encourage a more elaborate gross examination of the testes so that the causation, incidence, and significance of this tumor in man may be evaluated properly. They report a case of Leydig cell tumor in a sixty-nine-year-old man who received estrogen therapy for approximately two and one-half years. Case Report A sixty-nine-year-old white man was seen in April, 1975, for urinary frequency with nocturia (4 x ), obstruction to the urinary flow, and dribbling. He had been receiving treatment for essential hypertension since 1974. Physical examination revealed a hard right lobe of the prostate without evidence of local extension. Acid and alkaline phosphatase in the serum were within normal limits. An excretory urogram was unremarkable except for prostatic filling defect in the bladder. A bone scan was negative for any significant changes. Cystourethroscopy revealed irregular hyperplasia
*5”j3x
of the lateral lobes of the prostate with evidence of obstruction. On April 21, 1975, a transurethral resection revealed adenocarcinoma of the prostate. The patient was given 1.0 mg stilbestrol daily until September 9, 1977, when a bilateral orchiectomy was performed. He received radiation therapy to his prostate from August to October, 1975, (a total of 7,000 rad). In July, 1976, he suffered a myocardial infarction. In November, 1976, he had an anal fissurectomy; at this time he had occasional urgency of urination. His serum alkaline phosphatase was within normal limits, but his acid phosphatase was 11.6 units (normal 0.0 to 0.8 units). A bone scan revealed multiple areas of increased radioactivity throughout his left ribs and dorsal spine, with a single area noted in the right ilium. In August, 1977, multiple osteoblastic and osteolytic metastases were noted throughout the left ribs and spine, and he complained of pain in his left shoulder and back. In September, 1977, the pain increased. An intravenous pyelogram revealed extensive osteoblastic changes in his pelvic bones. His acid phosphatase was 39.6 units and alkaline phosphatase 24.0 units (normal, 4.5 to 11.0 units). A bilateral orchiectomy was performed on September 19, 1977, after which he had dramatic relief of pain.
UROLOGY
:
ilAY 1983
:
\‘OLlNE
XXI. NUSlBER 5
FIGUHI; 1. (A) Leydig cell tumor of upper pole of left testis; (B) Leydig cell tumor shoukg uniformity of cells.
Histology Histologic examination revealed mild atrophy and aspermatogenesis of both testes. Within the upper pole of the left testis anteriorly there was a soft, dark brown, sharply demarcated nodule, measuring 0.3 cm in diameter. Microscopically this lesion was composed of a circumscribed mass of interstitial (Leydig) cells (Fig. 1A). They were closely packed, welldifferentiated, and uniform in size, shape, and staining reactions (Fig. 1B). No mitotic activity was noted. Comment Recently, Damjanov, Katy, and Jewett’ reviewed the characteristics of the Leydig cell tumor, emphasizing the limited experience with this neoplasm which comprises approximately 1 to 3 per cent of all testicular tumors. It occurs within various age groups, but is uncommon after the age of sixty years. It usually is benign, however, about 10 to 15 per cent may be malignant with metastases. The average age of patients with benign lesions is 26.4 years and malignant lesions 57.6 years.” In the prepubertal stage this lesion may produce all of the clinical features of precocious androgen excess, while in the postpubertal stage they may be associated with gynecomastia or have no apparent endocrine manifestations. The cause of Leydig cell tumors in man has not been identified. In th:is case the patient was sixty-nine years of age and had received estrogen and radiation therapy. Clinically. he showed no evident endo-
crine effects from the neoplasm. Did the estrogen and/or the radiation therapy cause the neoplasm? Did it develop spontaneously, regardless of therapy? Diamond and Impink reported 3 cases of Leydig cell tumor occurring in men above age sixty. Anderwont, Shimkin, and Canter4 implanted stilbestrol pellets within the subcutaneous tissue of strain BALBiC two-month-old male mice. This caused the formation of Leydig cell tumors, especially in the right testis. Administration of estrogens to A-strain mice has been reported to cause Leyrdig cell tumor in the testis. 5 The authors hope that this experience will stimulate careful gross examination of testes removed for cancer therapy and that positive findings be reported in medical literature. 723 Phillips Avenue Toledo, Ohio 43612 (DR. DESHMUKH) References
1. Damjamov I. Katz SM. and Jewett MAS: Leydig cell tumors of the testis. Ann Clin Lab Sci 9: 157 (19791. 2. Silverberg SG, Thompson JN< Higashi G, and Rasken AML: Malignant interstitial cell tumor of the testis. J Ural 96: 356 (1966). 3. Diamond JJ, and Impink RR: Interstitial cell tumor of testicle: report of a case and correlation xvith review of literature. Arch Surg 73: 274 (1956), 4. AnderLvont HB. Shimkin BM, and Canter HI’: The growth of estrogen-induced interstitial cell testicular tumors in BALRiC mice. J Nat1 Cancer Inst 24: 1219 (1960). 5. Hooker C1V and Pfeiffer CA: The morpholoq and development of testicular tumors in mice of the A-strain receiving estrogens. Can Hcs 2: 759 (1932).
5:39