- Email: [email protected]
Unusual case of urethral carcinoma
UNUSUAL JAMES
R. ANGEL,
STEVEN TONY
M.D.
D. KRAUS, McCLUNG,
JEROME JEAN
CASE OF URETHRAL CARCINOMA
ROTH,
M.D. M.D.
M.D.
B. DEKERNION,
M.D.
From the Department of Urology, New Orleans, Louisiana
Tulane
University,
ABSTRACT - A case is presented of pigmented’epidermoid carcinoma of the urethra in a black man after a staged urethroplasty. Histology of the tumor suggests an origin from skin incorporated into the urethral repair. Response of the tumor to chemotherapeutic agents, proved effective in epidermoid carcinoma of the penis, is discussed.
Carcinoma of the urethra is an unusual tumor, occurring in males most frequently in the bulbomembranous and distal urethra in association with stricture disease. Less commonly, squamous carcinoma has arisen at the site of urethroplasty for strictures or trauma. The genesis of such tumors is usually thought to be the urethral mucosa. We present a case of a squamous cell carcinoma arising at the site of a two-stage urethroplasty, but apparently originating in the skin incorporated into the repair. The management of this locally advanced, nonresectable tumor is discussed. Case Report A fifty-year-old black man was referred to the Tulane urology service for treatment of extensive bulbar urethral stricture. On September 27, 1977, he underwent a first-stage modified Johanson urethroplasty, and in six months he returned for closure of the urethra. At the time of the second-stage urethroplasty a biopsy of irregular urethral mucosa near the proximal meatus showed stratified squamous epithelium consistent with urethral stricture disease. A urethral catheter was left in place for three weeks, and after its removal a urethrocutaneous fistula developed at the proximal end of the repair.
74
The patient voided well through his urethra, and the fistula closed spontaneously in six months. A urethrogram eight months after the repair revealed a small diverticulum at the distal end of the repair and no other unusual lesions. In April, 1979, the patient noticed pain in the perineum, slowing of his urinary stream, and a purulent urethral discharge. He presented in July, 1979, with recurrent urethrocutaneous fistula, a large perineal mass, and bilateral painful groin masses. Physical examination revealed a perineal urethrocutaneous fistula with an ulcerated mass extending into the base of the scrotum and both inguinal areas (Fig. 1). A suprapubic cystostomy tube was placed for urinary diversion, and biopsy of the perineal mass and inguinal nodes was done. Histologically, the tumor is a pigmented, poorly differentiated epidermoid carcinoma. Small squamous cells with no evidence of keratinization or intercellular bridges are arranged in nests. In focal areas, pigmented, dendritic melanocytes are interspersed between the tumor cells (Fig. 2). This is consistent with a primary skin origin of the tumor. A bone scan showed evidence of tumor invasion of the right side of the sacrum and ileum, and pelvic x-ray films revealed multiple lytic
UROLOGY
/ JULY1931 / VOLUMEXVIII,NUMBERl
FIGURE 1. (A) Appearance of patient at time of presentation shows ulcerated perineal tumor extending into inguinal nodes. (B) Progression of tumor growth after treatment with cis-diamminedichloroplatinum andbleomycin. (C) Partial tumor regression has occurred after three weeks of methotrerate therapy alone.
FIGURE 2. (A) Poorly differentiated epidermoid carcinoma infiltrates perineal skin from below (hematoxylin and eosin, original magni$cation x 59). (B) Pigmented melanocytes and their dendrites are present in this nest of poorly diffferentiated squamous cells (arrows) (hematoxylin and eosin, original magnijication x 360). (C) Melanocytes are most prominent at interface between stroma and tumor but are represented at all levels in this nest of tumor cells (Fontana-Masson, original magni$cation x 360).
lesions in the pubic rami (Fig. 3). Pelvic angiography demonstrated extensive intrapelvic, scrotal, and bilateral groin neovascularity. A chemotherapy regimen was instituted, consisting of bleomycin (20 units/m2 biweekly, a
UROLOGY
/ JULY1981 / VOLUMEXVIILNUMBERI
total dose 400 platinum (1.6 three doses). umented after therapy with
units), and cis-diamminedichloromg./Kg. every three weeks, total Tumor progression was doctherapy (Fig. l), and single agent methotrexate was substituted.
75
FIGURE 3. (A) Urethrogram showing urethral jistula and tumor Pelvic x-ray demonstrates lytic lesions in pubic rami (arrows).
After three weekly doses of 60 mg./m2 intravenously, partial tumor regression was achieved (Fig. 1). The tumor remains stable after three months of methotrexate therapy, and the patient’s functional status has improved markedly. Comment Urethral carcinoma is a rare disease with only approximately 400 cases reported. 1 Seventyseven per cent of cases in a large series reported by Kaplan, Bulkley, and Grayhock’ were squamous carcinoma, thought to arise from the urethral mucosa in areas of stricture disease subjected to chronic irritation or repeated trauma from dilatione3 Other less common types include transitional cell carcinomas, which arise from periurethral glands primarily in the bulbomembranous urethra.4 The prognosis of urethral carcinomas is generally poor. The best results have been obtained in patients with distal urethral carcinomas who have undergone partial or radical penile amputation. Tumors of the bulbomembranous urethra are associated with the worst prognosis and the highest local recurrence rate. Radical surgical extirpation is the recommended mode of treatment in operable cases. Inguinal and pelvic lymphadenectomy is reserved for patients with proved metastatic disease to these areas and may be effective in tumor control. Radiation therapy alone in the treatment of urethral carcinoma has led to higher local recurrence and death rate. 2*3
76
mass in site of previous
urethroplasty.
(B)
An occasional case of squamous cell carcinoma of the urethra in association with previous urethroplasty has been reported.57 The histology of these tumors is similar to other urethral carcinomas found in association with stricture disease in the absence of surgical intervention. No case has been reported of a pigmented epidermoid carcinoma developing in the site of a urethroplasty. Dendritic melanocytes are associated with keratinocytes in a variety of tumors and keratinocytic dysplasias including seborrheic keratosis, actinic keratosis, benign melanoacanthoma, Bowen disease, and basal cell carcinoma. They recapitulate the normal relationship between epidermal melanocytes and keratinocytes. They may transfer melanin to keratinocytes in a tumor. As in this case, epidermoid carcinomas occasionally contain melanocytes and are pigmented.8,g Poorlydifferentiated, pigmented epidermoid carcinomas may be confused with melanomas. The pigment may be microscopic or grossly apparent. Pigmented epidermoid carcinomas are relatively uncommon in the skin but have also been observed in other areas such as the conjunctiva in which melanocytes normally reside.‘O In the urethral mucosa, melanocytes are not normal residents. In general, pigmented epidermoid carcinomas arise in sites in which melanocytes normally reside in squamous epithelium. Melanocytes within epithelial tumors are not prognostically significant. This case is unusual since the appearance of melancocytes epidermoid suggested an
UROLOGY
/ JULY 1981 / VOLUME
XVIII, NUMBER
1
carcinoma arising from skin incorporated into the stricture repair, rather than from urethral mucosa. This suggests that careful follow-up may be indicated even after successful repair of strictures by use of various forms of skin grafts. The chemotherapy of urethral carcinoma has been largely unsuccessful, although several agents have been reported to produce responses. This epidermoid carcinoma of the urethra responded to chemotherapeutic agents proved to be effective against similar tumors of the penis and foreskin. Yagoda and coshown that cis-diamworkers 11-i3 have bleomycin, and minedichloroplatinum, methotrexate are all effective agents in this regard. Although there was a failure of bleomycin and cis-diamminedichloroplatinum to control tumor growth, a response was achieved with methotrexate. Tulane University 1430 Tulane Avenue New Orleans, Louisiana 70212 (DR. DE KERNION)
UROLOGY
/ JULY 1981
/ VOLUME
XVIIi,
NUMBER
1
References 1. Mostofi FK, and Price EB: Tumors of the urethra, in Firminger HI (Ed): Atlas of Tumor Pathology, Washington, D.C., Armed Forces Institute of Pathology, fast. 8. 1973, D. 263. 2. Kaplan GW, BuBdey CJ. and%rayhock JT: Ca&noma of the male urethra, J. Ural. 98: 356 (1967). 3. Roy B, Conto AR, and Whitmore WF: Experience with primary carcinoma of the male urethra ibid. 117: 591 (1977). 4. Grab&d H: Tumors of the urethra in men and women, Cancer 32: 1236 (1973). 5. Colapinto V, and Evans DH: Primary carcinoma of the male urethra developing after urethroplasty for stricture, J. Ural. 118: 581 (1977). 6. Kirkman NF: Urethral carcinoma following urethroplasty, Br. J. Surg. 48: 54% (1961). 7. @greid P: Development of carcinoma urethral after operation for stricture of the urethra, Scmd. J. Ural. Nephrol. 4: 176 (1970). 8. Lever WF, and Schaumberg-Lever G: Histopathology of the Skin, Philadelphia, 1. B. Lippincott. 1975, a. 240. 9. Khanolkar VR: Pigmented precancerous and cancerous changes in the skin, Cancer Res. 7: 692 (1947). 10. Jauregui HO, and Khnhvorth GK: Pigmented squamous, cell carcinoma of cornea and conjunctiva, Cancer 38: 778 (1976). 11. Yagoda A, et al: Bleomycin, an antitumor antibiotic, Ann. Intern. Med. 77: 861 (1972). 12. Skloroff RB, and Yagoda A: Cis-diamminedichloride platinum II (DDP) in the treatment of penile carcinoma, Cancer 44: 1563 (1979). 13. IDEM: Methotrexate in the treatment of penile carcinoma, ibid. 45: 214 (1980).
77
R. ANGEL,
STEVEN TONY
M.D.
D. KRAUS, McCLUNG,
JEROME JEAN
CASE OF URETHRAL CARCINOMA
ROTH,
M.D. M.D.
M.D.
B. DEKERNION,
M.D.
From the Department of Urology, New Orleans, Louisiana
Tulane
University,
ABSTRACT - A case is presented of pigmented’epidermoid carcinoma of the urethra in a black man after a staged urethroplasty. Histology of the tumor suggests an origin from skin incorporated into the urethral repair. Response of the tumor to chemotherapeutic agents, proved effective in epidermoid carcinoma of the penis, is discussed.
Carcinoma of the urethra is an unusual tumor, occurring in males most frequently in the bulbomembranous and distal urethra in association with stricture disease. Less commonly, squamous carcinoma has arisen at the site of urethroplasty for strictures or trauma. The genesis of such tumors is usually thought to be the urethral mucosa. We present a case of a squamous cell carcinoma arising at the site of a two-stage urethroplasty, but apparently originating in the skin incorporated into the repair. The management of this locally advanced, nonresectable tumor is discussed. Case Report A fifty-year-old black man was referred to the Tulane urology service for treatment of extensive bulbar urethral stricture. On September 27, 1977, he underwent a first-stage modified Johanson urethroplasty, and in six months he returned for closure of the urethra. At the time of the second-stage urethroplasty a biopsy of irregular urethral mucosa near the proximal meatus showed stratified squamous epithelium consistent with urethral stricture disease. A urethral catheter was left in place for three weeks, and after its removal a urethrocutaneous fistula developed at the proximal end of the repair.
74
The patient voided well through his urethra, and the fistula closed spontaneously in six months. A urethrogram eight months after the repair revealed a small diverticulum at the distal end of the repair and no other unusual lesions. In April, 1979, the patient noticed pain in the perineum, slowing of his urinary stream, and a purulent urethral discharge. He presented in July, 1979, with recurrent urethrocutaneous fistula, a large perineal mass, and bilateral painful groin masses. Physical examination revealed a perineal urethrocutaneous fistula with an ulcerated mass extending into the base of the scrotum and both inguinal areas (Fig. 1). A suprapubic cystostomy tube was placed for urinary diversion, and biopsy of the perineal mass and inguinal nodes was done. Histologically, the tumor is a pigmented, poorly differentiated epidermoid carcinoma. Small squamous cells with no evidence of keratinization or intercellular bridges are arranged in nests. In focal areas, pigmented, dendritic melanocytes are interspersed between the tumor cells (Fig. 2). This is consistent with a primary skin origin of the tumor. A bone scan showed evidence of tumor invasion of the right side of the sacrum and ileum, and pelvic x-ray films revealed multiple lytic
UROLOGY
/ JULY1931 / VOLUMEXVIII,NUMBERl
FIGURE 1. (A) Appearance of patient at time of presentation shows ulcerated perineal tumor extending into inguinal nodes. (B) Progression of tumor growth after treatment with cis-diamminedichloroplatinum andbleomycin. (C) Partial tumor regression has occurred after three weeks of methotrerate therapy alone.
FIGURE 2. (A) Poorly differentiated epidermoid carcinoma infiltrates perineal skin from below (hematoxylin and eosin, original magni$cation x 59). (B) Pigmented melanocytes and their dendrites are present in this nest of poorly diffferentiated squamous cells (arrows) (hematoxylin and eosin, original magnijication x 360). (C) Melanocytes are most prominent at interface between stroma and tumor but are represented at all levels in this nest of tumor cells (Fontana-Masson, original magni$cation x 360).
lesions in the pubic rami (Fig. 3). Pelvic angiography demonstrated extensive intrapelvic, scrotal, and bilateral groin neovascularity. A chemotherapy regimen was instituted, consisting of bleomycin (20 units/m2 biweekly, a
UROLOGY
/ JULY1981 / VOLUMEXVIILNUMBERI
total dose 400 platinum (1.6 three doses). umented after therapy with
units), and cis-diamminedichloromg./Kg. every three weeks, total Tumor progression was doctherapy (Fig. l), and single agent methotrexate was substituted.
75
FIGURE 3. (A) Urethrogram showing urethral jistula and tumor Pelvic x-ray demonstrates lytic lesions in pubic rami (arrows).
After three weekly doses of 60 mg./m2 intravenously, partial tumor regression was achieved (Fig. 1). The tumor remains stable after three months of methotrexate therapy, and the patient’s functional status has improved markedly. Comment Urethral carcinoma is a rare disease with only approximately 400 cases reported. 1 Seventyseven per cent of cases in a large series reported by Kaplan, Bulkley, and Grayhock’ were squamous carcinoma, thought to arise from the urethral mucosa in areas of stricture disease subjected to chronic irritation or repeated trauma from dilatione3 Other less common types include transitional cell carcinomas, which arise from periurethral glands primarily in the bulbomembranous urethra.4 The prognosis of urethral carcinomas is generally poor. The best results have been obtained in patients with distal urethral carcinomas who have undergone partial or radical penile amputation. Tumors of the bulbomembranous urethra are associated with the worst prognosis and the highest local recurrence rate. Radical surgical extirpation is the recommended mode of treatment in operable cases. Inguinal and pelvic lymphadenectomy is reserved for patients with proved metastatic disease to these areas and may be effective in tumor control. Radiation therapy alone in the treatment of urethral carcinoma has led to higher local recurrence and death rate. 2*3
76
mass in site of previous
urethroplasty.
(B)
An occasional case of squamous cell carcinoma of the urethra in association with previous urethroplasty has been reported.57 The histology of these tumors is similar to other urethral carcinomas found in association with stricture disease in the absence of surgical intervention. No case has been reported of a pigmented epidermoid carcinoma developing in the site of a urethroplasty. Dendritic melanocytes are associated with keratinocytes in a variety of tumors and keratinocytic dysplasias including seborrheic keratosis, actinic keratosis, benign melanoacanthoma, Bowen disease, and basal cell carcinoma. They recapitulate the normal relationship between epidermal melanocytes and keratinocytes. They may transfer melanin to keratinocytes in a tumor. As in this case, epidermoid carcinomas occasionally contain melanocytes and are pigmented.8,g Poorlydifferentiated, pigmented epidermoid carcinomas may be confused with melanomas. The pigment may be microscopic or grossly apparent. Pigmented epidermoid carcinomas are relatively uncommon in the skin but have also been observed in other areas such as the conjunctiva in which melanocytes normally reside.‘O In the urethral mucosa, melanocytes are not normal residents. In general, pigmented epidermoid carcinomas arise in sites in which melanocytes normally reside in squamous epithelium. Melanocytes within epithelial tumors are not prognostically significant. This case is unusual since the appearance of melancocytes epidermoid suggested an
UROLOGY
/ JULY 1981 / VOLUME
XVIII, NUMBER
1
carcinoma arising from skin incorporated into the stricture repair, rather than from urethral mucosa. This suggests that careful follow-up may be indicated even after successful repair of strictures by use of various forms of skin grafts. The chemotherapy of urethral carcinoma has been largely unsuccessful, although several agents have been reported to produce responses. This epidermoid carcinoma of the urethra responded to chemotherapeutic agents proved to be effective against similar tumors of the penis and foreskin. Yagoda and coshown that cis-diamworkers 11-i3 have bleomycin, and minedichloroplatinum, methotrexate are all effective agents in this regard. Although there was a failure of bleomycin and cis-diamminedichloroplatinum to control tumor growth, a response was achieved with methotrexate. Tulane University 1430 Tulane Avenue New Orleans, Louisiana 70212 (DR. DE KERNION)
UROLOGY
/ JULY 1981
/ VOLUME
XVIIi,
NUMBER
1
References 1. Mostofi FK, and Price EB: Tumors of the urethra, in Firminger HI (Ed): Atlas of Tumor Pathology, Washington, D.C., Armed Forces Institute of Pathology, fast. 8. 1973, D. 263. 2. Kaplan GW, BuBdey CJ. and%rayhock JT: Ca&noma of the male urethra, J. Ural. 98: 356 (1967). 3. Roy B, Conto AR, and Whitmore WF: Experience with primary carcinoma of the male urethra ibid. 117: 591 (1977). 4. Grab&d H: Tumors of the urethra in men and women, Cancer 32: 1236 (1973). 5. Colapinto V, and Evans DH: Primary carcinoma of the male urethra developing after urethroplasty for stricture, J. Ural. 118: 581 (1977). 6. Kirkman NF: Urethral carcinoma following urethroplasty, Br. J. Surg. 48: 54% (1961). 7. @greid P: Development of carcinoma urethral after operation for stricture of the urethra, Scmd. J. Ural. Nephrol. 4: 176 (1970). 8. Lever WF, and Schaumberg-Lever G: Histopathology of the Skin, Philadelphia, 1. B. Lippincott. 1975, a. 240. 9. Khanolkar VR: Pigmented precancerous and cancerous changes in the skin, Cancer Res. 7: 692 (1947). 10. Jauregui HO, and Khnhvorth GK: Pigmented squamous, cell carcinoma of cornea and conjunctiva, Cancer 38: 778 (1976). 11. Yagoda A, et al: Bleomycin, an antitumor antibiotic, Ann. Intern. Med. 77: 861 (1972). 12. Skloroff RB, and Yagoda A: Cis-diamminedichloride platinum II (DDP) in the treatment of penile carcinoma, Cancer 44: 1563 (1979). 13. IDEM: Methotrexate in the treatment of penile carcinoma, ibid. 45: 214 (1980).
77