0022-534 7/79/1216-0833$02 .00/0
Vol. 121, June Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
SQUAMOUS CELL CARCINOMA OF THE PROSTATE: REPORT OF 2 CASES AND REVIEW OF THE LITERATURE L. J. MICHAEL MOTI From the Department of Pathology, UCLA School of Medicine, Los Angeles, California
ABSTRACT
Two cases of squamous cell carcinoma of the prostate are reported and criteria for diagnosis are suggested. Squamous cancer, which accounts for 0.5 to 1 per cent ofprostatic malignancies, differs from the common adenocarcinoma of the prostate in certain clinical features. It also appears to have a worse prognosis and to be unresponsive to the usual therapies for prostatic cancer, perhaps because of a different cell of origin. Primary squamous cell carcinoma of the prostate gland is a relatively uncommon neoplasm that appears to differ in clinical features, therapeutic response and prognosis from the usual adenocarcinoma of the prostate gland. However, the literature contains only scattered reports of this malignancy and these often lack clinical or pathological detail. Two cases are reported of primary prostatic squamous cell carcinoma discovered in a review of 385 carcinomas of the prostate seen at the UCLA Hospital between 1945 and 1974. The literature is reviewed and the unique features of this neoplasm are discussed. CASE REPORTS
Case 1. A 65-year-old white man complained of increasing frequency and nocturia for 4 months accompanied by a 30 pound weight loss. On physical examination the prostate had discrete rocky nodules in both lobes superiorly. Cystoscopy showed a slightly elevated bladder neck but an unremarkable bladder mucosa with no bladder tumor. The prostatic urethra was markedly distorted by tumor of the prostate. A transurethral resection yielded 16 gm. of prostatic tissue, which was extensively infiltrated by keratinizing tumor cells with intercellular bridges and numerous squamous pearls (fig. 1). No glandular or acinar features were noted. The remaining urethral epithelium was unremarkable except for a small focus of squamous metaplasia. Additional examinations, including a chest x-ray, bronchoscopy, proctoscopy, barium enema and upper gastrointestinal series, were negative. A bone survey disclosed an osteolytic lesion of the right femur, which proved to be metastatic squamous carcinoma on biopsy. Serum acid phosphatase was 2.6 King-Armstrong units (normal Oto 4). The patient was treated with cobalt irradiation to the pelvis and femur (unknown total dose) but he deteriorated rapidly, developing urinary obstruction, metastases to the brain and heart failure. He died 8 months after initial symptoms and 2 months postoperatively. Case 2. A 59-year-old white man complained of sternal and left thigh pain 6 months in duration. A stony-hard non-tender mass occupied the left side of the prostate and involved the left seminal vesicle. Cystoscopy demonstrated an uninvolved bladder mucosa, with a mass on the left side distorting the prostatic urethra. Three perineal needle biopsy specimens showed a rather poorly differentiated malignant tumor without squamous pearls but with numerous intercellular bridges and individual keratinized cells (fig. 2). No adenocarcinoma features were present. An x-ray disclosed osteolytic sternal lesions and mottling of the right ischium. Serum acid phosphatase was 1. 7 King-Armstrong units (normal O to 4). Accepted for publication September 22, 1978.
Treatment consisted of bilateral orchiectomy, 5 mg. diethylstilbesterol orally 3 times a day and cobalt irradiation to the pelvis and sternum. Despite these measures the patient noticed increasing sternal pain, weakness and weight loss. He died 5 months after the initial diagnosis. INCIDENCE
Squamous cell carcinoma of the prostate is an uncommon but not truly rare lesion. Published incidence figures vary considerably from 3 per cent of prostatic cancers (6 of 195 cases') to zero squamous cancers in 12,000 prostate specimens (presumably not all cancers). 2 Most series have reported intermediate figures, including 4 of 176 prostate carcinomas (2 per cent), 3 2 of 193 (1 per cent), 4 1 of 310 (0.3 per cent) 5 and 1 of nearly 500 (0.2 per cent). 6 The present UCLA series included 2 squamous cancers of 385 prostate carcinomas (0.5 per cent). Therefore, a rough but probably acceptable mid range incidence figure would be 0.5 to 1 per cent of all prostatic cancer. In concrete terms this suggests that approximately 300 to 600 squamous cell carcinomas occur per year in the United States, based on the 1977 estimate of 57,000 new prostatic malignancies. 7 DIAGNOSIS
Recognition of this uncommon variety of prostatic cancer depends on the pathologist's microscopic examination. However, this lesion is not even mentioned in many pathology textbooks, including a recent book devoted exclusively to the prostate. 8 Likewise, authors of reported cases generally have failed to specify their criteria for the pathologic diagnosis. This is of some importance since squamous cell carcinoma of the prostate can be (and has been) confused with non-neoplastic squamous metaplasia that commonly occurs adjacent to infarctions, following chronic irritation or inflammation, or after estrogen therapy. Also, other neoplasms may be mistaken for squamous cancer, particularly transitional cell tumors and estrogen-treated adenocarcinomas that show extensive squamous change. Prostatic metastases from epidermoid cancer arising elsewhere are uncommon but direct invasion by bladder tumor is not. In recognition of these problems, the following criteria for the diagnosis of primary prostatic squamous cell carcinoma are suggested: 1) a clearly malignant neoplasm as judged by invasion, disordered growth and cellular anaplasia; 2) definite squamous features of keratinization, squamous pearls and/or numerous distinct intercellular bridges; 3) lack of any glandular or acinar pattern (such a finding should be interpreted as evidence of adenocarcinoma with squamous metaplasia); 4) no prior estrogen therapy and 5) the absence of primary squamous cancer elsewhere, particularly in the bladder. Note that some poorly differentiated 833
834
MOTT
Fm. 1. Transurethral prostatic resection from case 1 shows well differentiated squamous carcinoma with squamous pearls. No glandular differentiation was found. H & E, reduced from X250.
Fm. 2. Needle biopsy of prostate from case 2 with less differentiated squamous carcinoma. Individual cells are keratinized and there are numerous distinct intercellular bridges. H & E, reduced from x250. A, reduced from x 1,700. tumors lacking squamous features at the light microscopic level may show clear squamous characteristics at an ultrastructural level. LITERATURE REVIEW
Only 27 cases of claimed primary squamous cell carcinoma of the prostate were found in the English literature and many of these are devoid of useful clinical or pathological detail. An additional case was reported in detail by Spagnol in the Italian literature. 10 Of these 27 cases 5 are well detailed, 4• 11• 12 sketchy information is provided in 9 6• 13• 14 and squamous tumors are only mentioned in 13. 1• 3• 5• 15• 16 This scant information base provides the sum of our knowledge regarding the clinical features of these tumors. CLINICAL FEATURES
In many ways the squamous cell variety clinically resembles the usual adenocarcinoma of the prostate. Both occur in the same elderly population, with squamous cancer patients averaging 63 years of age (range 52 to 78). The presenting symptoms relate either to prostatism or to bone pain from metastatic deposits. Physical examination is variable. Thompson and associates thought that the prostate was usually abnormally soft and diffusely enlarged13 but other patients, including the present 2 cases, have had hard nodular glands
mimicking the classic description of adenocarcinomatous glands. Cystoscopy to exclude a primary bladder tumor usually demonstrates a distorted prostatic urethra, perhaps involved by tumor. However, there also are significant differences between the usual and the squamous variety of prostatic carcinoma. Metastatic adenocarcinoma typically causes an elevated serum acid phosphatase but this marker has been normal in all cases of metastatic squamous tumor so far reported. 13' 14 Bone metastases from adenocarcinoma are generally osteoblastic, 17 while all squamous cell metastases described, including the present 2 cases, have been osteolytic. 13 This cancer also appears to be more aggressive biologically. While adenocarcinoma victims have survival times measured in years and many are apparently cured, squamous cell tumor victims have a comparatively dismal prognosis. The 2 patients reported herein lived 2 and 5 months after diagnosis. Including these cases, the average post-diagnosis survival was only 14 months, with a range of 8 days to 9 years. Only 3 of 14 patients survived longer than 1 year. No cure has been claimed and only 1 patient was still alive at the time of the report (5 months after diagnosis). 14 Such poor survival indicates a lack of effective therapy for this cancer. Multiple treatments have been attempted but none with notable success. In general, estrogen therapy, so useful against prostatic adenocarcinoma, has been of little value against squamous cancer. 4• 12 This was the opinion of Thompson and associates13 and the experience of case 2 reported herein supports this position. Only Herbut was able to show a single case of histologic degenerative changes after 1 year of estrogen treatment but the clinical response of the patient was not mentioned. 15 Radiation therapy, given in both cases reported herein, has been of no demonstrable value, although 1 patient who survived 9 years did receive radiation. 4 An initially hopeful therapeutic response to adriamycin was reported in a patient with metastatic disease. 14 Only 3 cases reported had mention of a prostatectomy. 4• 11• 14 While no treatment has met with particular success, it must be realized that few cases have been reported adequately. More information is necessary before secure conclusions can be reached. HISTOGENESIS
The cell of origin of prostatic squamous cell carcinoma is unknown. Kahler, 1 and Thompson and associates, 13 as well as most other authors, have preferred origin from the transitional epithelium lining the urethra or major ducts. Sieracki nominated the basal or reserve cell of the prostatic acinus. 4 The common acinar columnar cell must also be a candidate, since it clearly retains the ability for squamous differentiation (metaplasia). However, lacking additional and more sophisticated studies, any opinion on histogenesis remains mere speculation. This unresolved question is of some practical significance, since tumors originating in the prostatic acinar cells would theoretically be estrogen responsive and, therefore, amenable to hormone therapy. Those derived from urethral transitional cells would not be hormone responsive. REFERENCES
1. Kahler, J. E.: Carcinoma of the prostate gland: a pathologic study. J. Urol., 41: 557, 1939.
2. Melicow, M. M.: Cancer of the prostate: concepts and guidelines in histologic diagnosis. J. Urol., 95: 791, 1966. 3. Arnheim, F. K.: Carcinoma of the prostate. A study of the postmortem findings in one hundred and seventy-six cases. J. Urol., 60: 599, 1948. 4. Sieracki, J. C.: Epidermoid carcinoma of the human prostate: report of three cases. Lab. Invest., 4: 232, 1955. 5. Ray, G. R., Cassady, J. R. and Bagshaw, M. A.: Definitive radiative therapy of carcinoma of the prostate. A report on 15 years of experience. Radiology, 106: 407, 1973.
SQUAMOUS CELL CARCINOMA OF PROSTATE
6. Dixon, F. J. and Moore, R. A.: Tumors of the male sex organs. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 1st series, p. 37, 1952. 7. National Cancer Institute: Third national cancer survey. Ca-A J. Clin., 27: 34, 1977. 8. Tannenbaum, M.: Urologic Pathology: The Prostate. Philadelphia: Lea & Febiger, 1977. 9. Mostofi, F. K. · and Morse, W. H.: Epithelial metaplasia in "prostatic infarction". Arch. Path., 51: 340, 1951. 10. Spagnol, G.: Epitelioma Pavimentoso Corneificante Primitivo Della Prostata. Pathologica, 18: 590, 1926. 11. Gray, G. F., Jr. and Marshall, V. F.: Squamous carcinoma of the prostate. J. Urol., 113: 736, 1975. 12. United States Naval Medical School: Color Atlas of Pathology: Endocrine System, Including Pituitary, Thyroid, Parathyroid,
/
13. 14. 15. 16. 17.
835
Adrenals and Pancreas; Gynecology and Obstetrics, Including Reproductive Organs; Breasts; Male Genital Tract; Skin. Philadelphia: J.B. Lippincott & Co., vol. II, p. 336, 1954. Thompson, G. J., Albers, D. D. and Broders, A. C.: Unusual carcinomas involving the prostate gland. J. Urol., 69: 416, 1953. Corder, M. P. and Cicmil, G. A.: Effective treatment of metastatic squamous cell carcinoma of the prostate with adriamycin. J. Urol., 115: 222, 1976. Herbut, P.A.: Urologic Pathology. Philadelphia: Lea & Febiger, vol. II, p. 945, 1952. Foot, N. C.: Identification of Tumors. Philadelphia: J.B. Lippincott & Co., p. 312, 1948. J orgens, J.: The radiographic characteristics of carcinoma of the prostate. Surg. Clin. N. Amer., 45: 1427, 1965.
Vol. 121, June Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
SQUAMOUS CELL CARCINOMA OF THE PROSTATE: REPORT OF 2 CASES AND REVIEW OF THE LITERATURE L. J. MICHAEL MOTI From the Department of Pathology, UCLA School of Medicine, Los Angeles, California
ABSTRACT
Two cases of squamous cell carcinoma of the prostate are reported and criteria for diagnosis are suggested. Squamous cancer, which accounts for 0.5 to 1 per cent ofprostatic malignancies, differs from the common adenocarcinoma of the prostate in certain clinical features. It also appears to have a worse prognosis and to be unresponsive to the usual therapies for prostatic cancer, perhaps because of a different cell of origin. Primary squamous cell carcinoma of the prostate gland is a relatively uncommon neoplasm that appears to differ in clinical features, therapeutic response and prognosis from the usual adenocarcinoma of the prostate gland. However, the literature contains only scattered reports of this malignancy and these often lack clinical or pathological detail. Two cases are reported of primary prostatic squamous cell carcinoma discovered in a review of 385 carcinomas of the prostate seen at the UCLA Hospital between 1945 and 1974. The literature is reviewed and the unique features of this neoplasm are discussed. CASE REPORTS
Case 1. A 65-year-old white man complained of increasing frequency and nocturia for 4 months accompanied by a 30 pound weight loss. On physical examination the prostate had discrete rocky nodules in both lobes superiorly. Cystoscopy showed a slightly elevated bladder neck but an unremarkable bladder mucosa with no bladder tumor. The prostatic urethra was markedly distorted by tumor of the prostate. A transurethral resection yielded 16 gm. of prostatic tissue, which was extensively infiltrated by keratinizing tumor cells with intercellular bridges and numerous squamous pearls (fig. 1). No glandular or acinar features were noted. The remaining urethral epithelium was unremarkable except for a small focus of squamous metaplasia. Additional examinations, including a chest x-ray, bronchoscopy, proctoscopy, barium enema and upper gastrointestinal series, were negative. A bone survey disclosed an osteolytic lesion of the right femur, which proved to be metastatic squamous carcinoma on biopsy. Serum acid phosphatase was 2.6 King-Armstrong units (normal Oto 4). The patient was treated with cobalt irradiation to the pelvis and femur (unknown total dose) but he deteriorated rapidly, developing urinary obstruction, metastases to the brain and heart failure. He died 8 months after initial symptoms and 2 months postoperatively. Case 2. A 59-year-old white man complained of sternal and left thigh pain 6 months in duration. A stony-hard non-tender mass occupied the left side of the prostate and involved the left seminal vesicle. Cystoscopy demonstrated an uninvolved bladder mucosa, with a mass on the left side distorting the prostatic urethra. Three perineal needle biopsy specimens showed a rather poorly differentiated malignant tumor without squamous pearls but with numerous intercellular bridges and individual keratinized cells (fig. 2). No adenocarcinoma features were present. An x-ray disclosed osteolytic sternal lesions and mottling of the right ischium. Serum acid phosphatase was 1. 7 King-Armstrong units (normal O to 4). Accepted for publication September 22, 1978.
Treatment consisted of bilateral orchiectomy, 5 mg. diethylstilbesterol orally 3 times a day and cobalt irradiation to the pelvis and sternum. Despite these measures the patient noticed increasing sternal pain, weakness and weight loss. He died 5 months after the initial diagnosis. INCIDENCE
Squamous cell carcinoma of the prostate is an uncommon but not truly rare lesion. Published incidence figures vary considerably from 3 per cent of prostatic cancers (6 of 195 cases') to zero squamous cancers in 12,000 prostate specimens (presumably not all cancers). 2 Most series have reported intermediate figures, including 4 of 176 prostate carcinomas (2 per cent), 3 2 of 193 (1 per cent), 4 1 of 310 (0.3 per cent) 5 and 1 of nearly 500 (0.2 per cent). 6 The present UCLA series included 2 squamous cancers of 385 prostate carcinomas (0.5 per cent). Therefore, a rough but probably acceptable mid range incidence figure would be 0.5 to 1 per cent of all prostatic cancer. In concrete terms this suggests that approximately 300 to 600 squamous cell carcinomas occur per year in the United States, based on the 1977 estimate of 57,000 new prostatic malignancies. 7 DIAGNOSIS
Recognition of this uncommon variety of prostatic cancer depends on the pathologist's microscopic examination. However, this lesion is not even mentioned in many pathology textbooks, including a recent book devoted exclusively to the prostate. 8 Likewise, authors of reported cases generally have failed to specify their criteria for the pathologic diagnosis. This is of some importance since squamous cell carcinoma of the prostate can be (and has been) confused with non-neoplastic squamous metaplasia that commonly occurs adjacent to infarctions, following chronic irritation or inflammation, or after estrogen therapy. Also, other neoplasms may be mistaken for squamous cancer, particularly transitional cell tumors and estrogen-treated adenocarcinomas that show extensive squamous change. Prostatic metastases from epidermoid cancer arising elsewhere are uncommon but direct invasion by bladder tumor is not. In recognition of these problems, the following criteria for the diagnosis of primary prostatic squamous cell carcinoma are suggested: 1) a clearly malignant neoplasm as judged by invasion, disordered growth and cellular anaplasia; 2) definite squamous features of keratinization, squamous pearls and/or numerous distinct intercellular bridges; 3) lack of any glandular or acinar pattern (such a finding should be interpreted as evidence of adenocarcinoma with squamous metaplasia); 4) no prior estrogen therapy and 5) the absence of primary squamous cancer elsewhere, particularly in the bladder. Note that some poorly differentiated 833
834
MOTT
Fm. 1. Transurethral prostatic resection from case 1 shows well differentiated squamous carcinoma with squamous pearls. No glandular differentiation was found. H & E, reduced from X250.
Fm. 2. Needle biopsy of prostate from case 2 with less differentiated squamous carcinoma. Individual cells are keratinized and there are numerous distinct intercellular bridges. H & E, reduced from x250. A, reduced from x 1,700. tumors lacking squamous features at the light microscopic level may show clear squamous characteristics at an ultrastructural level. LITERATURE REVIEW
Only 27 cases of claimed primary squamous cell carcinoma of the prostate were found in the English literature and many of these are devoid of useful clinical or pathological detail. An additional case was reported in detail by Spagnol in the Italian literature. 10 Of these 27 cases 5 are well detailed, 4• 11• 12 sketchy information is provided in 9 6• 13• 14 and squamous tumors are only mentioned in 13. 1• 3• 5• 15• 16 This scant information base provides the sum of our knowledge regarding the clinical features of these tumors. CLINICAL FEATURES
In many ways the squamous cell variety clinically resembles the usual adenocarcinoma of the prostate. Both occur in the same elderly population, with squamous cancer patients averaging 63 years of age (range 52 to 78). The presenting symptoms relate either to prostatism or to bone pain from metastatic deposits. Physical examination is variable. Thompson and associates thought that the prostate was usually abnormally soft and diffusely enlarged13 but other patients, including the present 2 cases, have had hard nodular glands
mimicking the classic description of adenocarcinomatous glands. Cystoscopy to exclude a primary bladder tumor usually demonstrates a distorted prostatic urethra, perhaps involved by tumor. However, there also are significant differences between the usual and the squamous variety of prostatic carcinoma. Metastatic adenocarcinoma typically causes an elevated serum acid phosphatase but this marker has been normal in all cases of metastatic squamous tumor so far reported. 13' 14 Bone metastases from adenocarcinoma are generally osteoblastic, 17 while all squamous cell metastases described, including the present 2 cases, have been osteolytic. 13 This cancer also appears to be more aggressive biologically. While adenocarcinoma victims have survival times measured in years and many are apparently cured, squamous cell tumor victims have a comparatively dismal prognosis. The 2 patients reported herein lived 2 and 5 months after diagnosis. Including these cases, the average post-diagnosis survival was only 14 months, with a range of 8 days to 9 years. Only 3 of 14 patients survived longer than 1 year. No cure has been claimed and only 1 patient was still alive at the time of the report (5 months after diagnosis). 14 Such poor survival indicates a lack of effective therapy for this cancer. Multiple treatments have been attempted but none with notable success. In general, estrogen therapy, so useful against prostatic adenocarcinoma, has been of little value against squamous cancer. 4• 12 This was the opinion of Thompson and associates13 and the experience of case 2 reported herein supports this position. Only Herbut was able to show a single case of histologic degenerative changes after 1 year of estrogen treatment but the clinical response of the patient was not mentioned. 15 Radiation therapy, given in both cases reported herein, has been of no demonstrable value, although 1 patient who survived 9 years did receive radiation. 4 An initially hopeful therapeutic response to adriamycin was reported in a patient with metastatic disease. 14 Only 3 cases reported had mention of a prostatectomy. 4• 11• 14 While no treatment has met with particular success, it must be realized that few cases have been reported adequately. More information is necessary before secure conclusions can be reached. HISTOGENESIS
The cell of origin of prostatic squamous cell carcinoma is unknown. Kahler, 1 and Thompson and associates, 13 as well as most other authors, have preferred origin from the transitional epithelium lining the urethra or major ducts. Sieracki nominated the basal or reserve cell of the prostatic acinus. 4 The common acinar columnar cell must also be a candidate, since it clearly retains the ability for squamous differentiation (metaplasia). However, lacking additional and more sophisticated studies, any opinion on histogenesis remains mere speculation. This unresolved question is of some practical significance, since tumors originating in the prostatic acinar cells would theoretically be estrogen responsive and, therefore, amenable to hormone therapy. Those derived from urethral transitional cells would not be hormone responsive. REFERENCES
1. Kahler, J. E.: Carcinoma of the prostate gland: a pathologic study. J. Urol., 41: 557, 1939.
2. Melicow, M. M.: Cancer of the prostate: concepts and guidelines in histologic diagnosis. J. Urol., 95: 791, 1966. 3. Arnheim, F. K.: Carcinoma of the prostate. A study of the postmortem findings in one hundred and seventy-six cases. J. Urol., 60: 599, 1948. 4. Sieracki, J. C.: Epidermoid carcinoma of the human prostate: report of three cases. Lab. Invest., 4: 232, 1955. 5. Ray, G. R., Cassady, J. R. and Bagshaw, M. A.: Definitive radiative therapy of carcinoma of the prostate. A report on 15 years of experience. Radiology, 106: 407, 1973.
SQUAMOUS CELL CARCINOMA OF PROSTATE
6. Dixon, F. J. and Moore, R. A.: Tumors of the male sex organs. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 1st series, p. 37, 1952. 7. National Cancer Institute: Third national cancer survey. Ca-A J. Clin., 27: 34, 1977. 8. Tannenbaum, M.: Urologic Pathology: The Prostate. Philadelphia: Lea & Febiger, 1977. 9. Mostofi, F. K. · and Morse, W. H.: Epithelial metaplasia in "prostatic infarction". Arch. Path., 51: 340, 1951. 10. Spagnol, G.: Epitelioma Pavimentoso Corneificante Primitivo Della Prostata. Pathologica, 18: 590, 1926. 11. Gray, G. F., Jr. and Marshall, V. F.: Squamous carcinoma of the prostate. J. Urol., 113: 736, 1975. 12. United States Naval Medical School: Color Atlas of Pathology: Endocrine System, Including Pituitary, Thyroid, Parathyroid,
/
13. 14. 15. 16. 17.
835
Adrenals and Pancreas; Gynecology and Obstetrics, Including Reproductive Organs; Breasts; Male Genital Tract; Skin. Philadelphia: J.B. Lippincott & Co., vol. II, p. 336, 1954. Thompson, G. J., Albers, D. D. and Broders, A. C.: Unusual carcinomas involving the prostate gland. J. Urol., 69: 416, 1953. Corder, M. P. and Cicmil, G. A.: Effective treatment of metastatic squamous cell carcinoma of the prostate with adriamycin. J. Urol., 115: 222, 1976. Herbut, P.A.: Urologic Pathology. Philadelphia: Lea & Febiger, vol. II, p. 945, 1952. Foot, N. C.: Identification of Tumors. Philadelphia: J.B. Lippincott & Co., p. 312, 1948. J orgens, J.: The radiographic characteristics of carcinoma of the prostate. Surg. Clin. N. Amer., 45: 1427, 1965.
