DIAGNOSTIC
PROBLEMS
OF EPITHELIAL
TUMORS OF PENIS* A. M. B. GOLDSTEIN, W. F. REYNOLDS, R. TERRY,
M.D. M.D.
M.D.
From the Departments of Urology and Pathology, Los Angeles County-University of Southern California Medical Center, Los Angeles, California
ABSTRACT - Malignant epithelial tumors of the penis often present aspects which make difficult an accurate clinical and pathologic diagnosis. Frequently, repeated biopsies yield a benign diagnosis while the tumor continues to progress and sections through it indicate malignant components. It is suggested that epithelial tumors of the penis may consist, in many instances from their start, of a mixture of benign and malignant elements in ratios varying from one extreme to the other. This may explain why biopsies are frequently misleading, yielding a benign result while, in fact, the tumor is malignant.
Malignant epithelial tumors of the penis can often present aspects which make an accurate clinical and pathologic diagnosis difficult. It has been stated that the “keystone of diagnosis is a biopsy.“’ This would appear obvious since such tumors are superficial and are easy to examine clinically; also it seems easy to take as many good biopsy specimens as necessary. Melicow and Ganen’ make a similar statement, namely, that “the diagnosis of cancer of the penis should be established by biopsy.” Obviously the diagnosis will be without doubt if the result of biopsy is unequivocal cancer. However, because of the unusual characteristics and histologic problems these tumors present, biopsy frequently can be equivocal and even misleading, resulting in a delay in the diagnosis of malignancy and in accurate treatment. The 2 cases presented herein emphasize the need for a better understanding of these tumors, as well as the need to perform excisional biopsies wherever possible, or at least multiple biopsies when the suspicion of cancer is high and the results of the first or even multiple biopsies are negative for malignancy. *Supported Medicine.
UROLOGY
in part
/
by
JANUARY 1977
a grant
/
of USC
VOLUME
School
IX, NUMBER
of
1
Case Reports Case 1 A sixty-nine-year-old Caucasian male was seen at this medical center in November, 1972. The patient became aware of penile swelling three months prior to seeking medical attention. He was noted to have an exophytic growth under the foreskin on the ventral aspect of the penis with an associated purulent drainage (Fig. 1A). Initial treatment consisted of a dorsal slit procedure and biopsy of the mass. The biopsy report indicated “acute and chronic inflammation with pseudoepitheliomatous hyperplasia.” The lesion persisted despite treatment with ampicillin after a culture identified Staphylococcus albus and streptococcus. Further evaluation revealed benign prostatic hypertrophy and bladder calculus but no other urologic lesion. By January, 1973, the draining lesion remained unchanged, but the exophytic lesion was more prominent. A second biopsy was taken during a second incision and drainage procedure, and that report indicated “welldifferentiated squamous cell carcinoma.” The previously identified inguinal nodes were also noted to be more prominent. Penectomy was performed with a perineal urethrostomy. Biopsy
79
FIGURE 1. (A) Squamous cell carcinoma of penis in sixty-nine-year-old man as seen when first examined. (B) Forty-six-year-old man on whom biopsy yielded diagnosis of condyloma while pathologic diagnosis of specimen was squamous cell carcinoma. (C) Fifty-three-year-old man on whom repeated punch biopsies indicated condyloma while pathologic report of whole tumor was squamous cell carcinoma. (D) Thirty-Jive-year-old man on whom repeated biopsies over a onediagnosis of year period yielded papilloma; pathologic diagnosis of specimen removed through penile amputation was squamous cell carcinoma. (E) Thirty-six-year-old man circumsized for squamous cell carcinoma of prepuce; pathologic diagnosis of recurring tumor was condyloma on amputated distal penis. (Figures 1B to E courtesy of Georg Thieme, Verlag, Leipzig, East Germany.)
This forty-nine-year-old Caucasian male was seen by his physician in 1966 with a fungating lesion on his prepuce and an associated phimosis. A circumcision was done as well as a left inguinal lymph node, biopsy of a firm, palpable node. Histologic report of the prepuce noted invasive characteristics with cellular atypia diagnosed as condyloma. The node showed inflammatory reaction without evidence of malignancy. In late 1970 the patient noted a small dark spot on the glans penis which was mildly pruri-
tic. This lesion slowly enlarged and finally ulcerated in July, 1971, a development which encouraged him to seek medical advice from the previous surgeon. A biopsy was done that September which indicated “atypia without invasion, suggestive of carcinoma.” The patient was then referred to this center for more definitive diagnosis and treatment. He was noted to have a large irregular lesion of the glans penis which cultured Proteus. The patient had a debridement, and the biopsy report indicated the lesion was “. . . consistent but not diagnostic of giant condylomata.” The patient was treated with podophyllum and ampicillin. His lesion persisted and was debrided. Two subsequent biopsies by December, 1971, showed metaplastic changes and persistent inflammation most consistent with condyloma. A fourth biopsy in mid-December revealed low-grade invasive carcinoma. Partial penectomy was accomplished, and workup of metastatic disease gave negative results except for lymphangiographic changes in the area of the previous lymph node biopsy of 1966. The patient did not return for further follow-up.
80
UROLOGY
of a right inguinal node showed inflammatory changes only. The surgical specimen revealed well-differentiated squamous cell carcinoma. Findings on metastatic workup were negative except for questionable replacement of right periaortic nodes on the lymphangiogram. The patient has been followed up to date without any other evidence of disease. A subsequent uneventful perineal transurethral resection of the prostate was accomplished. Case 2
/ JANUARY 1977 / VOLUME
IX, NUMBER
1
Comment “The pathologist knows that the process of establishing a diagnosis of tumor and deciding whether it is benign or malignant is not an exact science and that the most meaningful evaluations of tumors are usually those in which sufficient samples of the whole neoplasm have been studied histologically.“3 In Case 1 the biopsy of an exophytic subpreputial growth was negative for malignancy. Only three months later a repeated biopsy indicated squamous cell carcinoma. It appears obvious that if from the very beginning the prepuce was widely open or, even better, if a circumcision was performed, a correct diagnosis and possible cure would have been accomplished when the patient was first seen. In Case 2 the biopsy was excisional in the form of a circumcision, and the diagnosis was condyloma. Four years later biopsy of another growth on the glans penis was suggestive of carcinoma. However, this diagnosis was disregarded since three subsequent biopsies indicated a diagnosis consistent with giant condyloma. A later biopsy finally yielded the diagnosis of low-grade invasive carcinoma - this taken six months after the first biopsy. Lowenstein4 defined giant condyloma as being histologically identical to simple condyloma but with the clinical characteristics of destroying underlying tissues. This distinction was attributed to displacement rather than invasion. It has been mentioned that occasionally histologic evidence of malignancy on condylomatous lesions can be found.5 Even metastatic squamous cell carcinoma from giant condyloma has been reported, but by the time the diagnosis of squamous cell carcinoma metastasis to the inguinal nodes was made, the histology of the primary tumor indicated a squamous cell carcinoma as we11.6 Ackerman’ first called the giant condyloma verrucous carcinoma because of its deep penetration of adjacent tissues. Since the term condyloma has a meaning of absolute benignity, others8*g consider that the term giant condyloma should be replaced with verrucous carcinoma. Although verrucous carcinoma is extremely reluctant to metastasize, 2 rare cases have been reported of metastases of lymph nodes without findings in the original tumor of frank squamous cell carcinoma.5*‘0 Biopsies of verrucous carcinomas or Buschke-Lowenstein giant condyloma will almost invariably be underesti-
UROLOGY
/ JANUARY 1977 / VOLUME
IX, NUMBER
1
mated as benign when seen by the pathologist, and repeated biopsies will return the same resu1t.g Others consider giant condyloma benign and cite only 2 cases from the literature which have suffered malignant change.” On the other hand, the same author distinguishes a separate entity, the malignant condyloma, and considers the reported cases of giant condylomas with lymph node metastases as being malignant condylomas from the beginning. In another series of 6 cases of BuschkeLowenstein giant condyloma no malignant changes were found histologically.‘* It is speculated that the Buschke-Lowenstein tumor might represent an intermediate phase in viral carcinogenesis bridging the gap between the totally benign condyloma and anaplastic epidermoid carcinoma.8 Others consider that condyloma acuminatum can undergo malignant transformation and that the carcinoma supersedes an originally benign lesion. l3 In previous work one of us (A.G.) commented on the histologic difficulties in making an accurate diagnosis of malignant tumors of the penis. l4 In 2 patients, forty- six and fifty-three years old, respectively, who were seen with the penis destroyed down to its base, repeated biopsies yielded a diagnosis of condyloma (Fig. lB,C). Only on multiple sections through the whole tumor removed by emasculation was the diagnosis of squamous cell carcinoma established. A similar situation occurred in a thirtyfive-year-old in whom the tumor destroyed three quarters of the penis over a period of one year (Fig. 1D). In another case previously reported a circumcision was performed for squamous cell carcinoma located on the prepuce, .14 later a recurring tumor about 2 cm. in diameter developed on the ventral side of the penis over the scar of the previous circumcision which was clinically interpreted as recurring malignancy (Fig. 1E). On multiple sections through the whole tumor after partial penectomy only benign condyloma could be found histologically with no trace of squamous cell carcinoma. Such a case would suggest that the same stimulus which caused the development of squamous cell carcinoma at one time might have caused a recurrent tumor which histologically had the appearance of benign condyloma. Nine cases of penile carcinoma in which the first biopsy yielded a diagnosis of squamous cell carcinoma were carefully studied. l4 Multiple sections were taken through the whole speci-
81
ments in ratios varying from one extreme to the other (Fig. 2). Therefore, it should be concluded that the diagnosis of the epithelial tumors of the penis should not be based on histologic results only, but the clinical understanding of these tumors should also weigh heavily when making the diagnosis and indicating the treatment. P.O. Box 498 LACRJSC Medical Center Los Angeles, California 99933 (DR. GOLDSTEIN) References
men after penectomy. In 1 case at one level frank condyloma was found, while in another 2 cases at some levels condyloma with malignant changes was found. In another group of 12 patients, 4 of whom had an initial biopsy report of condyloma, squamous cell carcinoma was found on sections through the whole specimen. In cases such as those seen in Figure 1B and C in which multiple biopsy specimens were negative for malignancy and the diagnosis of squamous cell carcinoma was made only when multiple sections were taken from the whole specimen, a clear understanding of the condition is difficult. From the foregoing data it is understandable why a histologic diagnosis of malignancy of a tumor of the penis suspicious for malignancy can frequently not be made after one or even several biopsies. When first biopsied, even the squamous cell carcinomas proved histologically might have manifested different spee’ds of evolution from an extremely slow rate of many years to a rapid rate of a few months. l4 For the very slow growing ones, there is no way of knowing what their histology was at the start of their development. We suggest that epithelial tumors of the penis may be, in many circumstances from the beginning, a mixture of benign and malignant ele-
1. WHITMORE, W. F., JR.: Tumors of the penis, urethra, scrotum and testis, in Campbell, M. F., and Harrison, J. H., Eds.: Urology, Philadelphia, W. B. Saunders Company, 1970, vol. 2, p. 1190. 2. MELICOW, M. M., and GANEN, E. J.: Cancerous and precancerous lesions of the penis. A clinical and pathological study based on twenty-three cases, J. Urol. 55: 486 (1946). 3. TERRY, R.: Clinical Oncology for Medical Students and Physicians, 4th Ed., Rochester, University of Rochester, 1974, pp. 26-47. 4. LOWENSTEIN, L. W.: Carcinoma-like condylomata acuminata of penis, Med. Clin. North Am. 23: 789 (1939). 5. FITZGERALD, D. M., and HAMIT, H. F.: The variable significance of condylomata acuminata, Ann. Surg. 179: 328 (1974). 6. MADNACEK, G. F., and WEAKLEY, D. R.: Giant condyloma acuminata of Buschke and Lowenstein, Arch. Dermatol. 82: 41 (1960). 7. ACKERMAN, L. V.: Verrucous carcinoma of the oral cavity, Surgery 23: 670 (1948). 8. BRUNS, T. N. C., LAUVETZ, R. J., KERR, E. S., and ROSS, G., JR.: Buschke-Lowenstein giant condylomas, pitfalls in management, Urology 5: 6 (1975). 9. K~us, F. T., and PEREZ-MESA, C.: Verrucous carcinoma: clinical and pathologic study of 105 cases involving oral cavity, larynx and genitalia, Cancer, 19: 26 (1966). carcinoma presenting 10. DUCKWORTH, R. : Verrucous as mandibular osteomyelitis, Br. J. Surg. 49: 332 (1961). Giant condyloma acuminata: inci11. DAVIES, S. W.: dence among cases diagnosed as carcinoma of the penis, J. Clin. Pathol. 18: 142(1965). 12. GOLDSTEIN, A. M. B.: Besondere Verlaufsformen der rein papillomatosen Geschwulste des Penis, Hautarzt 13: 28 (1962). Mahg13. KOVI, J.. TILLMAN, R. L., and LEE, S. M.: nant transformation of condyloma acuminatum. A light microscopic and ultrastructural study, Am. J. Clin. Pathol. 61: 702 (1974). 14. GOLDSTEIN, A. M. B., BUNESCU, U., and DUTU, R.: Schwieriegkeiten und Fragen bei der Anatomisch - Klinischen Diagnose des Penis Karzinoms, Z. Urol. 53: 55 (1966). En15. GOLDSTEIN, A. M. B., and BUNESCU, U.: des Penis Karzinoms und twicklungsformen therapeutische Stellungnahme, ibid. 52: 127 (1959).
82
UROLOGY
FIGURE 2. Histologic view of squamous cell carcinoma adjacent to area of benignlooking condyloma. (Courtesy of Georg Thieme, Verlag, Leipzig, East Germany.)
/ JANUARY 1977 /
VOLUME IX, NUMBER 1
PROBLEMS
OF EPITHELIAL
TUMORS OF PENIS* A. M. B. GOLDSTEIN, W. F. REYNOLDS, R. TERRY,
M.D. M.D.
M.D.
From the Departments of Urology and Pathology, Los Angeles County-University of Southern California Medical Center, Los Angeles, California
ABSTRACT - Malignant epithelial tumors of the penis often present aspects which make difficult an accurate clinical and pathologic diagnosis. Frequently, repeated biopsies yield a benign diagnosis while the tumor continues to progress and sections through it indicate malignant components. It is suggested that epithelial tumors of the penis may consist, in many instances from their start, of a mixture of benign and malignant elements in ratios varying from one extreme to the other. This may explain why biopsies are frequently misleading, yielding a benign result while, in fact, the tumor is malignant.
Malignant epithelial tumors of the penis can often present aspects which make an accurate clinical and pathologic diagnosis difficult. It has been stated that the “keystone of diagnosis is a biopsy.“’ This would appear obvious since such tumors are superficial and are easy to examine clinically; also it seems easy to take as many good biopsy specimens as necessary. Melicow and Ganen’ make a similar statement, namely, that “the diagnosis of cancer of the penis should be established by biopsy.” Obviously the diagnosis will be without doubt if the result of biopsy is unequivocal cancer. However, because of the unusual characteristics and histologic problems these tumors present, biopsy frequently can be equivocal and even misleading, resulting in a delay in the diagnosis of malignancy and in accurate treatment. The 2 cases presented herein emphasize the need for a better understanding of these tumors, as well as the need to perform excisional biopsies wherever possible, or at least multiple biopsies when the suspicion of cancer is high and the results of the first or even multiple biopsies are negative for malignancy. *Supported Medicine.
UROLOGY
in part
/
by
JANUARY 1977
a grant
/
of USC
VOLUME
School
IX, NUMBER
of
1
Case Reports Case 1 A sixty-nine-year-old Caucasian male was seen at this medical center in November, 1972. The patient became aware of penile swelling three months prior to seeking medical attention. He was noted to have an exophytic growth under the foreskin on the ventral aspect of the penis with an associated purulent drainage (Fig. 1A). Initial treatment consisted of a dorsal slit procedure and biopsy of the mass. The biopsy report indicated “acute and chronic inflammation with pseudoepitheliomatous hyperplasia.” The lesion persisted despite treatment with ampicillin after a culture identified Staphylococcus albus and streptococcus. Further evaluation revealed benign prostatic hypertrophy and bladder calculus but no other urologic lesion. By January, 1973, the draining lesion remained unchanged, but the exophytic lesion was more prominent. A second biopsy was taken during a second incision and drainage procedure, and that report indicated “welldifferentiated squamous cell carcinoma.” The previously identified inguinal nodes were also noted to be more prominent. Penectomy was performed with a perineal urethrostomy. Biopsy
79
FIGURE 1. (A) Squamous cell carcinoma of penis in sixty-nine-year-old man as seen when first examined. (B) Forty-six-year-old man on whom biopsy yielded diagnosis of condyloma while pathologic diagnosis of specimen was squamous cell carcinoma. (C) Fifty-three-year-old man on whom repeated punch biopsies indicated condyloma while pathologic report of whole tumor was squamous cell carcinoma. (D) Thirty-Jive-year-old man on whom repeated biopsies over a onediagnosis of year period yielded papilloma; pathologic diagnosis of specimen removed through penile amputation was squamous cell carcinoma. (E) Thirty-six-year-old man circumsized for squamous cell carcinoma of prepuce; pathologic diagnosis of recurring tumor was condyloma on amputated distal penis. (Figures 1B to E courtesy of Georg Thieme, Verlag, Leipzig, East Germany.)
This forty-nine-year-old Caucasian male was seen by his physician in 1966 with a fungating lesion on his prepuce and an associated phimosis. A circumcision was done as well as a left inguinal lymph node, biopsy of a firm, palpable node. Histologic report of the prepuce noted invasive characteristics with cellular atypia diagnosed as condyloma. The node showed inflammatory reaction without evidence of malignancy. In late 1970 the patient noted a small dark spot on the glans penis which was mildly pruri-
tic. This lesion slowly enlarged and finally ulcerated in July, 1971, a development which encouraged him to seek medical advice from the previous surgeon. A biopsy was done that September which indicated “atypia without invasion, suggestive of carcinoma.” The patient was then referred to this center for more definitive diagnosis and treatment. He was noted to have a large irregular lesion of the glans penis which cultured Proteus. The patient had a debridement, and the biopsy report indicated the lesion was “. . . consistent but not diagnostic of giant condylomata.” The patient was treated with podophyllum and ampicillin. His lesion persisted and was debrided. Two subsequent biopsies by December, 1971, showed metaplastic changes and persistent inflammation most consistent with condyloma. A fourth biopsy in mid-December revealed low-grade invasive carcinoma. Partial penectomy was accomplished, and workup of metastatic disease gave negative results except for lymphangiographic changes in the area of the previous lymph node biopsy of 1966. The patient did not return for further follow-up.
80
UROLOGY
of a right inguinal node showed inflammatory changes only. The surgical specimen revealed well-differentiated squamous cell carcinoma. Findings on metastatic workup were negative except for questionable replacement of right periaortic nodes on the lymphangiogram. The patient has been followed up to date without any other evidence of disease. A subsequent uneventful perineal transurethral resection of the prostate was accomplished. Case 2
/ JANUARY 1977 / VOLUME
IX, NUMBER
1
Comment “The pathologist knows that the process of establishing a diagnosis of tumor and deciding whether it is benign or malignant is not an exact science and that the most meaningful evaluations of tumors are usually those in which sufficient samples of the whole neoplasm have been studied histologically.“3 In Case 1 the biopsy of an exophytic subpreputial growth was negative for malignancy. Only three months later a repeated biopsy indicated squamous cell carcinoma. It appears obvious that if from the very beginning the prepuce was widely open or, even better, if a circumcision was performed, a correct diagnosis and possible cure would have been accomplished when the patient was first seen. In Case 2 the biopsy was excisional in the form of a circumcision, and the diagnosis was condyloma. Four years later biopsy of another growth on the glans penis was suggestive of carcinoma. However, this diagnosis was disregarded since three subsequent biopsies indicated a diagnosis consistent with giant condyloma. A later biopsy finally yielded the diagnosis of low-grade invasive carcinoma - this taken six months after the first biopsy. Lowenstein4 defined giant condyloma as being histologically identical to simple condyloma but with the clinical characteristics of destroying underlying tissues. This distinction was attributed to displacement rather than invasion. It has been mentioned that occasionally histologic evidence of malignancy on condylomatous lesions can be found.5 Even metastatic squamous cell carcinoma from giant condyloma has been reported, but by the time the diagnosis of squamous cell carcinoma metastasis to the inguinal nodes was made, the histology of the primary tumor indicated a squamous cell carcinoma as we11.6 Ackerman’ first called the giant condyloma verrucous carcinoma because of its deep penetration of adjacent tissues. Since the term condyloma has a meaning of absolute benignity, others8*g consider that the term giant condyloma should be replaced with verrucous carcinoma. Although verrucous carcinoma is extremely reluctant to metastasize, 2 rare cases have been reported of metastases of lymph nodes without findings in the original tumor of frank squamous cell carcinoma.5*‘0 Biopsies of verrucous carcinomas or Buschke-Lowenstein giant condyloma will almost invariably be underesti-
UROLOGY
/ JANUARY 1977 / VOLUME
IX, NUMBER
1
mated as benign when seen by the pathologist, and repeated biopsies will return the same resu1t.g Others consider giant condyloma benign and cite only 2 cases from the literature which have suffered malignant change.” On the other hand, the same author distinguishes a separate entity, the malignant condyloma, and considers the reported cases of giant condylomas with lymph node metastases as being malignant condylomas from the beginning. In another series of 6 cases of BuschkeLowenstein giant condyloma no malignant changes were found histologically.‘* It is speculated that the Buschke-Lowenstein tumor might represent an intermediate phase in viral carcinogenesis bridging the gap between the totally benign condyloma and anaplastic epidermoid carcinoma.8 Others consider that condyloma acuminatum can undergo malignant transformation and that the carcinoma supersedes an originally benign lesion. l3 In previous work one of us (A.G.) commented on the histologic difficulties in making an accurate diagnosis of malignant tumors of the penis. l4 In 2 patients, forty- six and fifty-three years old, respectively, who were seen with the penis destroyed down to its base, repeated biopsies yielded a diagnosis of condyloma (Fig. lB,C). Only on multiple sections through the whole tumor removed by emasculation was the diagnosis of squamous cell carcinoma established. A similar situation occurred in a thirtyfive-year-old in whom the tumor destroyed three quarters of the penis over a period of one year (Fig. 1D). In another case previously reported a circumcision was performed for squamous cell carcinoma located on the prepuce, .14 later a recurring tumor about 2 cm. in diameter developed on the ventral side of the penis over the scar of the previous circumcision which was clinically interpreted as recurring malignancy (Fig. 1E). On multiple sections through the whole tumor after partial penectomy only benign condyloma could be found histologically with no trace of squamous cell carcinoma. Such a case would suggest that the same stimulus which caused the development of squamous cell carcinoma at one time might have caused a recurrent tumor which histologically had the appearance of benign condyloma. Nine cases of penile carcinoma in which the first biopsy yielded a diagnosis of squamous cell carcinoma were carefully studied. l4 Multiple sections were taken through the whole speci-
81
ments in ratios varying from one extreme to the other (Fig. 2). Therefore, it should be concluded that the diagnosis of the epithelial tumors of the penis should not be based on histologic results only, but the clinical understanding of these tumors should also weigh heavily when making the diagnosis and indicating the treatment. P.O. Box 498 LACRJSC Medical Center Los Angeles, California 99933 (DR. GOLDSTEIN) References
men after penectomy. In 1 case at one level frank condyloma was found, while in another 2 cases at some levels condyloma with malignant changes was found. In another group of 12 patients, 4 of whom had an initial biopsy report of condyloma, squamous cell carcinoma was found on sections through the whole specimen. In cases such as those seen in Figure 1B and C in which multiple biopsy specimens were negative for malignancy and the diagnosis of squamous cell carcinoma was made only when multiple sections were taken from the whole specimen, a clear understanding of the condition is difficult. From the foregoing data it is understandable why a histologic diagnosis of malignancy of a tumor of the penis suspicious for malignancy can frequently not be made after one or even several biopsies. When first biopsied, even the squamous cell carcinomas proved histologically might have manifested different spee’ds of evolution from an extremely slow rate of many years to a rapid rate of a few months. l4 For the very slow growing ones, there is no way of knowing what their histology was at the start of their development. We suggest that epithelial tumors of the penis may be, in many circumstances from the beginning, a mixture of benign and malignant ele-
1. WHITMORE, W. F., JR.: Tumors of the penis, urethra, scrotum and testis, in Campbell, M. F., and Harrison, J. H., Eds.: Urology, Philadelphia, W. B. Saunders Company, 1970, vol. 2, p. 1190. 2. MELICOW, M. M., and GANEN, E. J.: Cancerous and precancerous lesions of the penis. A clinical and pathological study based on twenty-three cases, J. Urol. 55: 486 (1946). 3. TERRY, R.: Clinical Oncology for Medical Students and Physicians, 4th Ed., Rochester, University of Rochester, 1974, pp. 26-47. 4. LOWENSTEIN, L. W.: Carcinoma-like condylomata acuminata of penis, Med. Clin. North Am. 23: 789 (1939). 5. FITZGERALD, D. M., and HAMIT, H. F.: The variable significance of condylomata acuminata, Ann. Surg. 179: 328 (1974). 6. MADNACEK, G. F., and WEAKLEY, D. R.: Giant condyloma acuminata of Buschke and Lowenstein, Arch. Dermatol. 82: 41 (1960). 7. ACKERMAN, L. V.: Verrucous carcinoma of the oral cavity, Surgery 23: 670 (1948). 8. BRUNS, T. N. C., LAUVETZ, R. J., KERR, E. S., and ROSS, G., JR.: Buschke-Lowenstein giant condylomas, pitfalls in management, Urology 5: 6 (1975). 9. K~us, F. T., and PEREZ-MESA, C.: Verrucous carcinoma: clinical and pathologic study of 105 cases involving oral cavity, larynx and genitalia, Cancer, 19: 26 (1966). carcinoma presenting 10. DUCKWORTH, R. : Verrucous as mandibular osteomyelitis, Br. J. Surg. 49: 332 (1961). Giant condyloma acuminata: inci11. DAVIES, S. W.: dence among cases diagnosed as carcinoma of the penis, J. Clin. Pathol. 18: 142(1965). 12. GOLDSTEIN, A. M. B.: Besondere Verlaufsformen der rein papillomatosen Geschwulste des Penis, Hautarzt 13: 28 (1962). Mahg13. KOVI, J.. TILLMAN, R. L., and LEE, S. M.: nant transformation of condyloma acuminatum. A light microscopic and ultrastructural study, Am. J. Clin. Pathol. 61: 702 (1974). 14. GOLDSTEIN, A. M. B., BUNESCU, U., and DUTU, R.: Schwieriegkeiten und Fragen bei der Anatomisch - Klinischen Diagnose des Penis Karzinoms, Z. Urol. 53: 55 (1966). En15. GOLDSTEIN, A. M. B., and BUNESCU, U.: des Penis Karzinoms und twicklungsformen therapeutische Stellungnahme, ibid. 52: 127 (1959).
82
UROLOGY
FIGURE 2. Histologic view of squamous cell carcinoma adjacent to area of benignlooking condyloma. (Courtesy of Georg Thieme, Verlag, Leipzig, East Germany.)
/ JANUARY 1977 /
VOLUME IX, NUMBER 1
