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Primary Melanoma of the Female Urethra
THE JoUHNAL OF U.ROT,OG\
VoL 74, No, 3, September 1955 Pr1'.rded in U.S.A.
PRJ:;vIARY l\IELAN01\1A o:F THE FEMALE I,:-RETHRA MORRIS ABRAMS
Primary melanoma of the female urethra is extremely rare. The first case report ,ms published by Reed 1 in 1896. In 1946 Long, Counsellor and Dockerty 2 reviewed the literature and found a total of 11 cases. They added three additional 011es "·hich -were encountered at the Mayo Clinic among approximately 700,000 female patients who had been examined since 1907. Since that time no new additional cases have been reported. The fact that so fe,Y primary melanomas of tho female urethra have been recorded justifies this case report. CASE REPORT
M. a 60-year-old white ,rnman, ,ms operated upon Juno rn, 1952 by her private physician for a growth at the urethral opening. The preoperative diagnosis ,rns canrncle. The mass was excised 1Yithout difficulty and the base was fulguratcd. Microscopic exarnination of the removed tumor was thought to show a carcinoma (fig. 1, A). For that reason the patient was referred to me for evaluation and additional treatmen L Physical examination, an excretory urogram and chest roentgenogram were normal. Observation cystoscopy and urethros(:opy revealed no abnormal growths, The original slides were reviewed by another pathologist who also thought the tumor was a carcinoma. The patient was then referred to the radiologis1; for combined deep roentgen and radium therapy. At the conclusion of that treatment she was examined at frequent intervals and remained symptom-free and in apparent good health. In December 1953, eighteen months following the removal of the original tumor, examination for the first time, a 8mall, ,rnll defined, freely movable, painless, lymph node in the left inguinal region ,d1ich was not apparent to the patient. She was admitted to the hospital 2 later and the inguinal lymph node was excised. the removed specimen, rneasuring approximately 1.5 by 2 cm., was soft and purplish black in color. The microscopic report of this mass was definite mela1101m, (fig. 1, B). Additional microscopic sections of the original urethral tumor were then made, and it became clear that the original tumor was a melanoma. The cell of both the inguinal lymph node and the original tumor ,-rore similar for the presence of melanin pigment in the lymph node. The patient i;; still alive and asymptomatic. _'.\' o weight loss or weakne8s or change in the general appearance has developed since the primary tumor was removed. Examination of the urethra and bladder in September 1954 failed to unco\'er any new examination, hmYever, revealed another 1Yell defined, metastatic, lymph node on the left side. Becatrne of increasing pain thitl mass -was removed (fig. 2) _At no time was a lesion of a similar character found in the skin or eyes. Accepted for publication February 9, 1955. 1 Recd, C. A. L_: 2\Ie!anosarcoma of the female urethra. Am. J_ Obst_ & Dis. Women & Child , 34: 1896. 2 Long, G _ Counseller, \'. S, and Dockerty, l\I. B.: Primary melano-epithelioma of the female urethra" UroJ. 55: 520, 1946. 371
372
MORRIS ABRAMS
FIG. 1. A, primary tumor. :Mucosa! surface lies along left margin of section. Mucosa! epithelium is absent and replaced by completely necrotic tissue. Tumor cells are pleomorphic and have large, bizarre, hyperchromatic nuclei, some of which show atypical mitotic figures. A number of foci of infiltration with polymorphonuclear leukocytes appear in fibromuscular stroma of tumor. No melanin pigment is present in section. B, inguinal lymph node. Lymphoid architecture has been completely replaced by tumor. Latter consists of elongated spindle cells, compactly arranged, with regular vesicular nuclei. Note large amount of melanin pigment in contrast to its absence in section of primary lesion.
Fro. 2. Lymph node showing several large pigmented (black) masses, largest measuring approximately 4 cm. in greatest diameter. DISCUSSION
Melanoma has appeared in the literature under various synonyms. Those still in use are: melanocarcinoma, nevocarcinoma, melanoepithelioma, melanosarcoma and malignant melanoma. The apparent reason for this multiplicity of names is that the origin of the tumor has not been well understood. Three origins have been considered: 1) the tumor arises from epithelial tissue, 2) from mesodermal tissue, 3) from nervous tissue. The theory favored by most pathologists is that the tumor has its origin from nerve tissue. An excellent summary of these various theories can be found in Herbut's Urological Pathology 3 and in Long's review of the literature. The microscopic characteristics are variable; the primary lesion may simulate a squamous cell carcinoma, an adeno- or basal cell carcinoma, a neurofibrosarcoma, or other neoplasms. The usual melanoma is com3
Herbut, P.A.: Urological Pathology. Philadelphia: Lea and Febiger, 1952, vol. 1, p. 121.
J\;fELA~TO!\fA OF FEMALE URE'rHRA
373
posed of cells arranged in compact masses, cords, alveoli, or as irregularly scattered free cells, The cells may be uniform or exhibit considerable pleomorphism. ~ uclei generally do not shmv much anaplasia, although, as in the present case., there may be considerable variability in nuclear size, Mitoses are usually not numerous despite the aggressiveness of the tumor. JVIelanin pigment may be: present or absent ffithout prognostic significance, One of the most helpful histologic aids in diagnosis is the active junctional change overlying and continuous ,Yith the underlying tumor; this consists of a pagetoid loosening of the cells with vacuoli,mtion of cytoplasm around the nucleus forming a perinuclear halo, The present case was mistakenly diagnosed in the first instance as a squamous carcinoma because of the marked anaplasia and the numerous rnitotic figures. The absence of melanin. was also a contributing factor in arriving at an erroneous diagnosis, However, thr lack of melanin in the original material does not justify a diagnosis of amelanotic melanoma since the technique used in removing the neoplasm did not permit examination of the total tumor. A further misleading feature was the necrosis and ulceration of the overlying mucosa which elirmnated any possibility for studying junctional changes. The variability in histologic characteristics of melanoma is well illustrated tn the present case. While the primary lesion consisted of loosely arranged pleomorphic cells with anaplastic nuclei and probably little melanin (fig. l, A), the metastasis showed considerable pigment in con:1pactly arranged spindle cells with rather regular Yesicular nuclei (fig. 1, B). Primary melanoma of the female urethra has been found in the older age groups. Fourteen of the fifteen reported cases were in women more than 52 years of age. The youngest patient was thirty-two, the oldest was seventy-eight and the average age was sixty-five, Clinically, frequency and burning on urination were the only urinary symptoms recorded. The burning apparently occurs with mucosal ulceration. The frequency of urination is probably due to the associated inflammatory process produced by the tumor. In many of the patients the presence of a vaginal tumor or of a serosanguineous vaginal discharge with a foul odor were the first symptoms noted, The foul discharge is secondary to necrosis of the tumor. In the case reported here burning with frequency of urination and the presence of a vaginal tumor of 2 months' duration were the presenting complaints. Grossly, melanoma of the female urethra almost always occurs in the distal portion of the urethra. In ten of the 14 cases reviewed by Long, the tumor was in the meatal portion. ln the case reported here the tumor was attached to the mucous membrane on the posterior aspect of the urethral meatus. The typical melanoma has been described as being brown to black or purplish black in color. This apparently is not allrnys true and again gives mnphasis to the importanL principle stressed hy many urologists and gynecologists that all tumors of the urethra, regardless of their gross appearance, should be preserved for microscopic study. In the differential diagnosis, caruncle, carcinoma, sarcoma, fibroma, chancre and prolapsed mucosa should be considered. The typical appearance of the red, soft, tender mass of the caruncle is ·well known. In carcinoma of the urethra a
374
MORRIS ABRAMS
hard mass is usually palpable and the patient complains of pain in the region of the urethra plus frequency, urgency and difficulty in voiding because of obstruction of the urethra by the tumor. In no instance were urinary obstructive symptoms noted in the fourteen reported cases of melanoma of the urethra. In prolapse, an eversion of the mucous membrane of the entire circumference of the urethra through the meatus is easily differentiated from the above tumors. The treatment of melanoma of the female urethra has been unsatisfactory. The methods of treatment recorded have been roentgen and radium therapy in association with electrocautery excision and fulguration. The prognosis is extremely poor. No 5-year survivals are reported. Melanoma of the urethra spreads by direct extension into the vulva and vagina, by lymphatic vessels into the inguinal lymph nodes and by the blood stream throughout the body. Radical excision of the urethra and bladder with transplantation of the ureters to the skin, bowel or into a pouch has not been tried on any of the reported cases. Since most of the patients reported had metastatic lesions at the time of the first examination, the use of this method would not be logical. This patient received radiation to the site from which the lesion had been resected and fulgurated. The irradiation therapy included both x-rays generated at 220 k.v.p. and contact application of radium element. Between August 4, 1952 and August 22, 1952, she received 8 treatments, using a 2½ cm. metal cylinder which was coned down upon the urethral orifice. A total dose of 3200 r units at the lesion was given. This was delivered with 220 kV., ½ mm. copper and 1 mm. aluminum filtration. The radium therapy was given between August 6, 1952 and August 15, 1952. The treatments were alternated with the x-ray therapy for a total dose of 200 mg. hours. A 20 mg. tube of radium having a 17 mm. active length was placed within a capsule approximately 22 mm. in length with an outside diameter of 6.4 mm. and a brass wall thickness of 1.2 mm. This capsule was held in place in the anterior urethra by means of scotch tape and an attached wire. This capsule was placed within the anterior urethra for two hours at a time, every other day. A followup observation made on September 8, 1952 showed moderate erythema around the urethral orifice with a slight patch of mucositis. No evidence of induration or ulceration was present. The patient remained free of disease until August 25, 1953 at which time a small, indurated area about 4 mm. in diameter was observed in the suburethral area. This was excised and was reported as radiation reaction. There was no evidence of local recurrence of disease up to and including the present time. SUMMARY
Primary melanoma of the female urethra is a rare disease. A total of 15 cases have now been reported in the literature, the present report constituting the fifteenth case. The disease is always fatal. Metastasis to the inguinal nodes or in the skin occurs early. Melanoma is radioresistant. The importance of preserving all lesions of the urethra for microscopic study is exemplified in this report, and some of the problems in pathological diagnosis are presented.
4405 W. Pine St., St. Louis 8, Mo.
VoL 74, No, 3, September 1955 Pr1'.rded in U.S.A.
PRJ:;vIARY l\IELAN01\1A o:F THE FEMALE I,:-RETHRA MORRIS ABRAMS
Primary melanoma of the female urethra is extremely rare. The first case report ,ms published by Reed 1 in 1896. In 1946 Long, Counsellor and Dockerty 2 reviewed the literature and found a total of 11 cases. They added three additional 011es "·hich -were encountered at the Mayo Clinic among approximately 700,000 female patients who had been examined since 1907. Since that time no new additional cases have been reported. The fact that so fe,Y primary melanomas of tho female urethra have been recorded justifies this case report. CASE REPORT
M. a 60-year-old white ,rnman, ,ms operated upon Juno rn, 1952 by her private physician for a growth at the urethral opening. The preoperative diagnosis ,rns canrncle. The mass was excised 1Yithout difficulty and the base was fulguratcd. Microscopic exarnination of the removed tumor was thought to show a carcinoma (fig. 1, A). For that reason the patient was referred to me for evaluation and additional treatmen L Physical examination, an excretory urogram and chest roentgenogram were normal. Observation cystoscopy and urethros(:opy revealed no abnormal growths, The original slides were reviewed by another pathologist who also thought the tumor was a carcinoma. The patient was then referred to the radiologis1; for combined deep roentgen and radium therapy. At the conclusion of that treatment she was examined at frequent intervals and remained symptom-free and in apparent good health. In December 1953, eighteen months following the removal of the original tumor, examination for the first time, a 8mall, ,rnll defined, freely movable, painless, lymph node in the left inguinal region ,d1ich was not apparent to the patient. She was admitted to the hospital 2 later and the inguinal lymph node was excised. the removed specimen, rneasuring approximately 1.5 by 2 cm., was soft and purplish black in color. The microscopic report of this mass was definite mela1101m, (fig. 1, B). Additional microscopic sections of the original urethral tumor were then made, and it became clear that the original tumor was a melanoma. The cell of both the inguinal lymph node and the original tumor ,-rore similar for the presence of melanin pigment in the lymph node. The patient i;; still alive and asymptomatic. _'.\' o weight loss or weakne8s or change in the general appearance has developed since the primary tumor was removed. Examination of the urethra and bladder in September 1954 failed to unco\'er any new examination, hmYever, revealed another 1Yell defined, metastatic, lymph node on the left side. Becatrne of increasing pain thitl mass -was removed (fig. 2) _At no time was a lesion of a similar character found in the skin or eyes. Accepted for publication February 9, 1955. 1 Recd, C. A. L_: 2\Ie!anosarcoma of the female urethra. Am. J_ Obst_ & Dis. Women & Child , 34: 1896. 2 Long, G _ Counseller, \'. S, and Dockerty, l\I. B.: Primary melano-epithelioma of the female urethra" UroJ. 55: 520, 1946. 371
372
MORRIS ABRAMS
FIG. 1. A, primary tumor. :Mucosa! surface lies along left margin of section. Mucosa! epithelium is absent and replaced by completely necrotic tissue. Tumor cells are pleomorphic and have large, bizarre, hyperchromatic nuclei, some of which show atypical mitotic figures. A number of foci of infiltration with polymorphonuclear leukocytes appear in fibromuscular stroma of tumor. No melanin pigment is present in section. B, inguinal lymph node. Lymphoid architecture has been completely replaced by tumor. Latter consists of elongated spindle cells, compactly arranged, with regular vesicular nuclei. Note large amount of melanin pigment in contrast to its absence in section of primary lesion.
Fro. 2. Lymph node showing several large pigmented (black) masses, largest measuring approximately 4 cm. in greatest diameter. DISCUSSION
Melanoma has appeared in the literature under various synonyms. Those still in use are: melanocarcinoma, nevocarcinoma, melanoepithelioma, melanosarcoma and malignant melanoma. The apparent reason for this multiplicity of names is that the origin of the tumor has not been well understood. Three origins have been considered: 1) the tumor arises from epithelial tissue, 2) from mesodermal tissue, 3) from nervous tissue. The theory favored by most pathologists is that the tumor has its origin from nerve tissue. An excellent summary of these various theories can be found in Herbut's Urological Pathology 3 and in Long's review of the literature. The microscopic characteristics are variable; the primary lesion may simulate a squamous cell carcinoma, an adeno- or basal cell carcinoma, a neurofibrosarcoma, or other neoplasms. The usual melanoma is com3
Herbut, P.A.: Urological Pathology. Philadelphia: Lea and Febiger, 1952, vol. 1, p. 121.
J\;fELA~TO!\fA OF FEMALE URE'rHRA
373
posed of cells arranged in compact masses, cords, alveoli, or as irregularly scattered free cells, The cells may be uniform or exhibit considerable pleomorphism. ~ uclei generally do not shmv much anaplasia, although, as in the present case., there may be considerable variability in nuclear size, Mitoses are usually not numerous despite the aggressiveness of the tumor. JVIelanin pigment may be: present or absent ffithout prognostic significance, One of the most helpful histologic aids in diagnosis is the active junctional change overlying and continuous ,Yith the underlying tumor; this consists of a pagetoid loosening of the cells with vacuoli,mtion of cytoplasm around the nucleus forming a perinuclear halo, The present case was mistakenly diagnosed in the first instance as a squamous carcinoma because of the marked anaplasia and the numerous rnitotic figures. The absence of melanin. was also a contributing factor in arriving at an erroneous diagnosis, However, thr lack of melanin in the original material does not justify a diagnosis of amelanotic melanoma since the technique used in removing the neoplasm did not permit examination of the total tumor. A further misleading feature was the necrosis and ulceration of the overlying mucosa which elirmnated any possibility for studying junctional changes. The variability in histologic characteristics of melanoma is well illustrated tn the present case. While the primary lesion consisted of loosely arranged pleomorphic cells with anaplastic nuclei and probably little melanin (fig. l, A), the metastasis showed considerable pigment in con:1pactly arranged spindle cells with rather regular Yesicular nuclei (fig. 1, B). Primary melanoma of the female urethra has been found in the older age groups. Fourteen of the fifteen reported cases were in women more than 52 years of age. The youngest patient was thirty-two, the oldest was seventy-eight and the average age was sixty-five, Clinically, frequency and burning on urination were the only urinary symptoms recorded. The burning apparently occurs with mucosal ulceration. The frequency of urination is probably due to the associated inflammatory process produced by the tumor. In many of the patients the presence of a vaginal tumor or of a serosanguineous vaginal discharge with a foul odor were the first symptoms noted, The foul discharge is secondary to necrosis of the tumor. In the case reported here burning with frequency of urination and the presence of a vaginal tumor of 2 months' duration were the presenting complaints. Grossly, melanoma of the female urethra almost always occurs in the distal portion of the urethra. In ten of the 14 cases reviewed by Long, the tumor was in the meatal portion. ln the case reported here the tumor was attached to the mucous membrane on the posterior aspect of the urethral meatus. The typical melanoma has been described as being brown to black or purplish black in color. This apparently is not allrnys true and again gives mnphasis to the importanL principle stressed hy many urologists and gynecologists that all tumors of the urethra, regardless of their gross appearance, should be preserved for microscopic study. In the differential diagnosis, caruncle, carcinoma, sarcoma, fibroma, chancre and prolapsed mucosa should be considered. The typical appearance of the red, soft, tender mass of the caruncle is ·well known. In carcinoma of the urethra a
374
MORRIS ABRAMS
hard mass is usually palpable and the patient complains of pain in the region of the urethra plus frequency, urgency and difficulty in voiding because of obstruction of the urethra by the tumor. In no instance were urinary obstructive symptoms noted in the fourteen reported cases of melanoma of the urethra. In prolapse, an eversion of the mucous membrane of the entire circumference of the urethra through the meatus is easily differentiated from the above tumors. The treatment of melanoma of the female urethra has been unsatisfactory. The methods of treatment recorded have been roentgen and radium therapy in association with electrocautery excision and fulguration. The prognosis is extremely poor. No 5-year survivals are reported. Melanoma of the urethra spreads by direct extension into the vulva and vagina, by lymphatic vessels into the inguinal lymph nodes and by the blood stream throughout the body. Radical excision of the urethra and bladder with transplantation of the ureters to the skin, bowel or into a pouch has not been tried on any of the reported cases. Since most of the patients reported had metastatic lesions at the time of the first examination, the use of this method would not be logical. This patient received radiation to the site from which the lesion had been resected and fulgurated. The irradiation therapy included both x-rays generated at 220 k.v.p. and contact application of radium element. Between August 4, 1952 and August 22, 1952, she received 8 treatments, using a 2½ cm. metal cylinder which was coned down upon the urethral orifice. A total dose of 3200 r units at the lesion was given. This was delivered with 220 kV., ½ mm. copper and 1 mm. aluminum filtration. The radium therapy was given between August 6, 1952 and August 15, 1952. The treatments were alternated with the x-ray therapy for a total dose of 200 mg. hours. A 20 mg. tube of radium having a 17 mm. active length was placed within a capsule approximately 22 mm. in length with an outside diameter of 6.4 mm. and a brass wall thickness of 1.2 mm. This capsule was held in place in the anterior urethra by means of scotch tape and an attached wire. This capsule was placed within the anterior urethra for two hours at a time, every other day. A followup observation made on September 8, 1952 showed moderate erythema around the urethral orifice with a slight patch of mucositis. No evidence of induration or ulceration was present. The patient remained free of disease until August 25, 1953 at which time a small, indurated area about 4 mm. in diameter was observed in the suburethral area. This was excised and was reported as radiation reaction. There was no evidence of local recurrence of disease up to and including the present time. SUMMARY
Primary melanoma of the female urethra is a rare disease. A total of 15 cases have now been reported in the literature, the present report constituting the fifteenth case. The disease is always fatal. Metastasis to the inguinal nodes or in the skin occurs early. Melanoma is radioresistant. The importance of preserving all lesions of the urethra for microscopic study is exemplified in this report, and some of the problems in pathological diagnosis are presented.
4405 W. Pine St., St. Louis 8, Mo.