- Email: [email protected]
Transitional cell carcinoma of fossa navicularis in a man with three other synchronous malignancies
TRANSITIONAL CELL CARCINOMA OF FOSSA NAVICULARIS IN A MAN WITH THREE OTHER SYNCHRONOUS MALIGNANCIES ROBERT M. GENTA, M.D.” MARK A. ROSEN. M.D. From the Departments
of Pathology
of Urology,
Veterans
Baylor College
and Medicine
and the Scott Department
Affairs Medical
of Medicine,
Houston.
Center, Texas
ABSTRACT-Transitional cell carcinoma arising from the anterior portion of the male urethra is rare, with less than 10 cases reported in the literature. Our patient had a highgrade, highly invasive transitional cell carcinoma originating in the fossa navicularis and extending proximally along the corpus spongiosum, the corpora cavernosa, and blood and lymphatic vessels. In addition, the patient had a concurrent low-grade prostatic adenocarcinoma, a large basal cell carcinoma of the nose, and a squamous ceil carcinoma of the penile skin. The previously reported cases are reviewed, with particular reference to the possible association of these tumors with human papillomavirus infection.
In 1987 Leonard and Thomas’ reported what they reckoned to be the fourth case of primary transitional cell carcinoma of the male anterior urethra. The following year Maltby and Johnson’ added a fifth case. Irrespective of whether these authors were keeping an accurate count, the anterior urethra, normally lined with stratified columnar ciliated epithelium and, more distally, with squamous epithelium is -at least in North America and Europe-an exceedingly rare site of origin of primary transitional cell carcinomas. We report on a patient with an unusually aggressive transitional cell carcinoma originating from the fossa navicularis. In addition, this patient also had three other concurrent carcinomas, two of which were in the urogenital area. CASE REPORT A sixty-seven-year old white man was admitted to the VA Medical Center for the elective excision of a large basal cell carcinoma of the left nostril. During his hospital stay he complained of bloody discharge from the penis and was evaluated by the *Supported by u grant from the Medicul Reseun-h purtmmt oj Vcferuns Afkirs, Washington, D.C. Submirted: Svpombcr 2. 1993, accepted iwith tfmbo
Ii. IW.3
Office of the Dctc*visions)
Gp-
urology service. Physical examination revealed two warty lesions on the skin of t-he penis and a rock-hard, approximately 3 x s-cm mass in the glans penis. Except for palpable left inguinal lymph nodes and a nodular prostate, the remainder of the physical examination was normal. All routine hematologic and chemical laboratory tests were normal. The cutaneous lesions on the penis were excised. One was a verruca Lulgaris and the other was a squamous cell carcinoma with microinvasion. Cystoscopic examination revealed stenosis 01 the distal urethra with a whitish shaggy lesion extending for approximately 3 cm. The urethra proximal to the lesion was normal. The urinary bladder showed 3 (+> trabeculations and no lesions. At the time of the cystoscopy, a biopsy specimen was taken from the urethral tumor and a frozen section consultation was obtained. The lesion consisted of a poorly differentiated Infiltrating carcinoma with features that were interpreted as being reminiscent of glandular formation (Fig. 1). In the absence of other lesions in the urinar), tract, the pathologist suggested the possibility of a poorly differentiated prostatic adenocarcinoma. Needle biopsy specimens were obtained from the prostate, which showed a well-differentiated adenocarcinoma, Gleason grade 2 on the right side
251
FIGURE 1. Photomicrograph (medium-power view) of original frozen section tissue from urethral tumor shows infiltrative pattern into collagenous stroma suggested possibility of poorly differentiated adenocarcinoma.
FIGURE 3. Photomicrograph poorly differentiated transitional anterior urethra.
(high-power view) of cell carcinoma from
FIGURE 2. Photomicrograph (medium-power view) of section from prostate showing benign hyperplastic glands infiltrated by well-differentiated neoplastic glands [with only cell layer) in lower right corner.
FIGURE 4. Photomicrograph [low-power view) of section obtained from middle portion of resected penis shows cords of tumors infiltrating into corpora cavernosa and their vessels; note overlaying urethral epithelium is uninvolved.
(Fig. 2). This was thought to be an unlikely source for the urethral tumor, which when examined more extensively on permanent sections revealed a pattern suggestive of a poorly differentiated transitional cell carcinoma. A partial penectomy was then performed. The tumor consisted of a high-grade transitional cell carcinoma in continuity with the urethra only in the region of the fossa navicularis (Fig. 3). Proximal to this area, the tumor infiltrated the corpus spongiosum and the corpora cavernosa in large cords running parallel to the urethra, and was also present both in lymphatics and blood channels. However, the urethral epithelium proximal to the fossa navicularis was consistently free of neoplastic changes (Fig. 4). In an attempt to gain an understanding of the spatial distribution of the tumor, the formalin-fixed specimen was cut in se-
rial sections perpendicular to the penile axis. The sections were then examined microscopically, and the topography of the lesion at each level was recorded. An accurate, but not exact, three-dimensional reconstruction of the unusual arrangement of this tumor is depicted in Figure 5. In light of the extensive lymphatic and vascular invasion, the therapeutic options were discussed with the patient, who favored a total penectomy with pelvic and inguinal lymph node dissection. Pathologic examination of the resected specimen revealed metastatic transitional cell carcinoma in 4 of 15 left inguinal lymph nodes. No residual tumor was found in the proximal penis or the bulbar urethra. Recently, human papillomavirus type 6 messenger ribonucleic acid was demonstrated in grade I transitional cell carcinomas of the urethra.3 To
FIGURE 5. Drawing of three-dimensional representation of spatial distribution of tumor within penis. It was prepared by examining extension of tumor in serial sections of specimen sliced perpendicularly to its longitudinal axis. Sizes and proportions are approximate.
explore the possibility of such an association in our patient, we performed immunohistochemical staining of the urethral tumor and of the penile squamous cell carcinoma using peroxidasc-conjugated anti-human papillomavirus antibodies (Biogenies Laboratories, Dublin, California). Neither tumor exhibited positive staining for these viral antigen\. COMMENT Primary transitional cell carcinoma of the anterior urethra is considered to be rare. Although cases published in less accessible local journals may escape even a thorough search of the literature, it is probably safe to assume that. including the present patient, no more than a dozen cases have been reported in the Western literalure. In Japan, however, this tumor may be more common than is appreciated. In the recent report of a grade II papillary transitional cell carcinoma occurring in a young man with hypospadias, the authors note that 23 previous cases have been published in the Japanese literature.’ Of the cases reported from North America and Europe, 2 had grade 1 tumors successfully treated with excision and fulguration, and 2 were grade IV tumors cured with surgery and radiation.i~i One tumor was a grade l-11 well-differentiated carcinoma that was resected at cystourethroscop) and had no evidence of recurrence at follow-up twelve months later.’ Another case’ started as a lesion originally diagnosed as an intraurethral condyloma and treated with 5% 5-fluorouracil cream; when it failed to heal, a mcatotomy and laser vaporization of the lesion were performed. A deep excisional biopsy of a local tumor recurrence one year later revealed a grade II invasive transitional cell carcinoma that required partial penectomy. No follow-up was available. Since 1990, 3 more cases were added to the literature. One patient was a seventy-one-vcar-old
Italian man with a bean-sized tumor occupying the anterior urethra and exlensi\re metastatic involvement of the inguinal lymph nodes.H The patient was reportedly well and free of metastasis twenty-five months after partial penectomy and inguinal lymph node dissection. The second patient was a forty-seven-year-old Spanish man with a papillary transitional cell tumor of the urethral meatus, locally invasive but with neither lymphatic nor distant metastases.” The third case was a seventy-two-year-old man with a high-grade invasive transitional cell carcinoma of the anterior urethra that failed to respond to deep radiation therapy and required radical penec’tom):‘” One interesting aspect of the present case is the concurrent presence of a squan1ou.s cell carcinoma on the skin of the penis. An intraepithelial squamous cell carcinoma of the glans also was present in another case,’ and the possibility of a common relationship of these two entities with human papillomavirus is intriguing. Our failure to dcmonstrate human papillomaviru; annigcms in either the squamous cell carcinoma of the penile skin or the transitional cell carcinoma lends itself to several interpretations. One possibility is that human papillomavirus had played no etiologic role in the genesis of either of these tumors. Alternati\.ely, it is possible that the viral genome. which acts as a promoter in the initiation of I he oncogenic process, disappears as the tumor progresses and de-differentiates. Finally, the immunohistochemical method we used is less sensitive than the in situ hybridization technique with RNA probes employed by Mevorach and his colleagues,’ and it may have been inadequate to detec:t the
REFERENCES 1, Leonard SA, and Thomas R: Transitional cell carcinoma of fossa navicularis, fourth reported case. Urology 30: 393-394, 1987. 2. Maltby CC, and Johnston SR: Transitional cell carcinoma of the male anterior urethra. Br J Urol 62: 489, 1988. 3. Mevorach RA, Cos LR, Di Sant’Agnese PA, and Stoler M: Human papillomavirus type 6 in grade 1 transitional cell carcinoma of the urethra. J Urol 143: 126-128, 1990. 4. Hayashi Y, Komada S, Maruyama Y, Hirao Y, and Okajima E: Primary transitional cell carcinoma of the male urethra: report of a case. Hinyokika Kiyo 33: 428-432, 1987. 5. Bans LL, Eble JN, Lingeman JE, and Maynard BR: Transitional cell carcinoma of the fossa navicularis of the male urethra. J Urol 129: 1055-1056, 1983.
254
6. Mandler Jl, and Pool TL: Primary carcinoma of the male urethra. J Urol96: 67-72, 1966. 7. Robles JE, Luzuriaga J, Ponz M, Urementa JM, Selva A, Zudaire JJ, Joly M, and Berian JM: Transitional cell carcinoma of the anterior urethra. Em Ural 2: 139-140, 1985. 8. Verrini G, Ferrari E Brausi M, Gavioli M, Croce L, and Latini A: Carcinoma transizionale primitivo dell’uretra anteriore maschile. Minerva Urol Nefro142: 159-161, 1990. 9. Gonzalvo-Perez V, Eres-Saez FJ, Colomer-Gonzalez F, Unten-Kanashiro M, and Zaragoza-Orts J: Carcinoma transicional de la uretra an un varon. Actas Urol Esp 14: 78-79, 1990. 10. Fernando JJ, and Wanas TM: Primary transitional cell carcinoma of the anterior urethra: a rare presentation. Genitourin Med 67: 244-246,1991.
UROLOGY
/ F~BROARY 1994 / VOIUMF 43,
NLMUFR 2
of Pathology
of Urology,
Veterans
Baylor College
and Medicine
and the Scott Department
Affairs Medical
of Medicine,
Houston.
Center, Texas
ABSTRACT-Transitional cell carcinoma arising from the anterior portion of the male urethra is rare, with less than 10 cases reported in the literature. Our patient had a highgrade, highly invasive transitional cell carcinoma originating in the fossa navicularis and extending proximally along the corpus spongiosum, the corpora cavernosa, and blood and lymphatic vessels. In addition, the patient had a concurrent low-grade prostatic adenocarcinoma, a large basal cell carcinoma of the nose, and a squamous ceil carcinoma of the penile skin. The previously reported cases are reviewed, with particular reference to the possible association of these tumors with human papillomavirus infection.
In 1987 Leonard and Thomas’ reported what they reckoned to be the fourth case of primary transitional cell carcinoma of the male anterior urethra. The following year Maltby and Johnson’ added a fifth case. Irrespective of whether these authors were keeping an accurate count, the anterior urethra, normally lined with stratified columnar ciliated epithelium and, more distally, with squamous epithelium is -at least in North America and Europe-an exceedingly rare site of origin of primary transitional cell carcinomas. We report on a patient with an unusually aggressive transitional cell carcinoma originating from the fossa navicularis. In addition, this patient also had three other concurrent carcinomas, two of which were in the urogenital area. CASE REPORT A sixty-seven-year old white man was admitted to the VA Medical Center for the elective excision of a large basal cell carcinoma of the left nostril. During his hospital stay he complained of bloody discharge from the penis and was evaluated by the *Supported by u grant from the Medicul Reseun-h purtmmt oj Vcferuns Afkirs, Washington, D.C. Submirted: Svpombcr 2. 1993, accepted iwith tfmbo
Ii. IW.3
Office of the Dctc*visions)
Gp-
urology service. Physical examination revealed two warty lesions on the skin of t-he penis and a rock-hard, approximately 3 x s-cm mass in the glans penis. Except for palpable left inguinal lymph nodes and a nodular prostate, the remainder of the physical examination was normal. All routine hematologic and chemical laboratory tests were normal. The cutaneous lesions on the penis were excised. One was a verruca Lulgaris and the other was a squamous cell carcinoma with microinvasion. Cystoscopic examination revealed stenosis 01 the distal urethra with a whitish shaggy lesion extending for approximately 3 cm. The urethra proximal to the lesion was normal. The urinary bladder showed 3 (+> trabeculations and no lesions. At the time of the cystoscopy, a biopsy specimen was taken from the urethral tumor and a frozen section consultation was obtained. The lesion consisted of a poorly differentiated Infiltrating carcinoma with features that were interpreted as being reminiscent of glandular formation (Fig. 1). In the absence of other lesions in the urinar), tract, the pathologist suggested the possibility of a poorly differentiated prostatic adenocarcinoma. Needle biopsy specimens were obtained from the prostate, which showed a well-differentiated adenocarcinoma, Gleason grade 2 on the right side
251
FIGURE 1. Photomicrograph (medium-power view) of original frozen section tissue from urethral tumor shows infiltrative pattern into collagenous stroma suggested possibility of poorly differentiated adenocarcinoma.
FIGURE 3. Photomicrograph poorly differentiated transitional anterior urethra.
(high-power view) of cell carcinoma from
FIGURE 2. Photomicrograph (medium-power view) of section from prostate showing benign hyperplastic glands infiltrated by well-differentiated neoplastic glands [with only cell layer) in lower right corner.
FIGURE 4. Photomicrograph [low-power view) of section obtained from middle portion of resected penis shows cords of tumors infiltrating into corpora cavernosa and their vessels; note overlaying urethral epithelium is uninvolved.
(Fig. 2). This was thought to be an unlikely source for the urethral tumor, which when examined more extensively on permanent sections revealed a pattern suggestive of a poorly differentiated transitional cell carcinoma. A partial penectomy was then performed. The tumor consisted of a high-grade transitional cell carcinoma in continuity with the urethra only in the region of the fossa navicularis (Fig. 3). Proximal to this area, the tumor infiltrated the corpus spongiosum and the corpora cavernosa in large cords running parallel to the urethra, and was also present both in lymphatics and blood channels. However, the urethral epithelium proximal to the fossa navicularis was consistently free of neoplastic changes (Fig. 4). In an attempt to gain an understanding of the spatial distribution of the tumor, the formalin-fixed specimen was cut in se-
rial sections perpendicular to the penile axis. The sections were then examined microscopically, and the topography of the lesion at each level was recorded. An accurate, but not exact, three-dimensional reconstruction of the unusual arrangement of this tumor is depicted in Figure 5. In light of the extensive lymphatic and vascular invasion, the therapeutic options were discussed with the patient, who favored a total penectomy with pelvic and inguinal lymph node dissection. Pathologic examination of the resected specimen revealed metastatic transitional cell carcinoma in 4 of 15 left inguinal lymph nodes. No residual tumor was found in the proximal penis or the bulbar urethra. Recently, human papillomavirus type 6 messenger ribonucleic acid was demonstrated in grade I transitional cell carcinomas of the urethra.3 To
FIGURE 5. Drawing of three-dimensional representation of spatial distribution of tumor within penis. It was prepared by examining extension of tumor in serial sections of specimen sliced perpendicularly to its longitudinal axis. Sizes and proportions are approximate.
explore the possibility of such an association in our patient, we performed immunohistochemical staining of the urethral tumor and of the penile squamous cell carcinoma using peroxidasc-conjugated anti-human papillomavirus antibodies (Biogenies Laboratories, Dublin, California). Neither tumor exhibited positive staining for these viral antigen\. COMMENT Primary transitional cell carcinoma of the anterior urethra is considered to be rare. Although cases published in less accessible local journals may escape even a thorough search of the literature, it is probably safe to assume that. including the present patient, no more than a dozen cases have been reported in the Western literalure. In Japan, however, this tumor may be more common than is appreciated. In the recent report of a grade II papillary transitional cell carcinoma occurring in a young man with hypospadias, the authors note that 23 previous cases have been published in the Japanese literature.’ Of the cases reported from North America and Europe, 2 had grade 1 tumors successfully treated with excision and fulguration, and 2 were grade IV tumors cured with surgery and radiation.i~i One tumor was a grade l-11 well-differentiated carcinoma that was resected at cystourethroscop) and had no evidence of recurrence at follow-up twelve months later.’ Another case’ started as a lesion originally diagnosed as an intraurethral condyloma and treated with 5% 5-fluorouracil cream; when it failed to heal, a mcatotomy and laser vaporization of the lesion were performed. A deep excisional biopsy of a local tumor recurrence one year later revealed a grade II invasive transitional cell carcinoma that required partial penectomy. No follow-up was available. Since 1990, 3 more cases were added to the literature. One patient was a seventy-one-vcar-old
Italian man with a bean-sized tumor occupying the anterior urethra and exlensi\re metastatic involvement of the inguinal lymph nodes.H The patient was reportedly well and free of metastasis twenty-five months after partial penectomy and inguinal lymph node dissection. The second patient was a forty-seven-year-old Spanish man with a papillary transitional cell tumor of the urethral meatus, locally invasive but with neither lymphatic nor distant metastases.” The third case was a seventy-two-year-old man with a high-grade invasive transitional cell carcinoma of the anterior urethra that failed to respond to deep radiation therapy and required radical penec’tom):‘” One interesting aspect of the present case is the concurrent presence of a squan1ou.s cell carcinoma on the skin of the penis. An intraepithelial squamous cell carcinoma of the glans also was present in another case,’ and the possibility of a common relationship of these two entities with human papillomavirus is intriguing. Our failure to dcmonstrate human papillomaviru; annigcms in either the squamous cell carcinoma of the penile skin or the transitional cell carcinoma lends itself to several interpretations. One possibility is that human papillomavirus had played no etiologic role in the genesis of either of these tumors. Alternati\.ely, it is possible that the viral genome. which acts as a promoter in the initiation of I he oncogenic process, disappears as the tumor progresses and de-differentiates. Finally, the immunohistochemical method we used is less sensitive than the in situ hybridization technique with RNA probes employed by Mevorach and his colleagues,’ and it may have been inadequate to detec:t the
REFERENCES 1, Leonard SA, and Thomas R: Transitional cell carcinoma of fossa navicularis, fourth reported case. Urology 30: 393-394, 1987. 2. Maltby CC, and Johnston SR: Transitional cell carcinoma of the male anterior urethra. Br J Urol 62: 489, 1988. 3. Mevorach RA, Cos LR, Di Sant’Agnese PA, and Stoler M: Human papillomavirus type 6 in grade 1 transitional cell carcinoma of the urethra. J Urol 143: 126-128, 1990. 4. Hayashi Y, Komada S, Maruyama Y, Hirao Y, and Okajima E: Primary transitional cell carcinoma of the male urethra: report of a case. Hinyokika Kiyo 33: 428-432, 1987. 5. Bans LL, Eble JN, Lingeman JE, and Maynard BR: Transitional cell carcinoma of the fossa navicularis of the male urethra. J Urol 129: 1055-1056, 1983.
254
6. Mandler Jl, and Pool TL: Primary carcinoma of the male urethra. J Urol96: 67-72, 1966. 7. Robles JE, Luzuriaga J, Ponz M, Urementa JM, Selva A, Zudaire JJ, Joly M, and Berian JM: Transitional cell carcinoma of the anterior urethra. Em Ural 2: 139-140, 1985. 8. Verrini G, Ferrari E Brausi M, Gavioli M, Croce L, and Latini A: Carcinoma transizionale primitivo dell’uretra anteriore maschile. Minerva Urol Nefro142: 159-161, 1990. 9. Gonzalvo-Perez V, Eres-Saez FJ, Colomer-Gonzalez F, Unten-Kanashiro M, and Zaragoza-Orts J: Carcinoma transicional de la uretra an un varon. Actas Urol Esp 14: 78-79, 1990. 10. Fernando JJ, and Wanas TM: Primary transitional cell carcinoma of the anterior urethra: a rare presentation. Genitourin Med 67: 244-246,1991.
UROLOGY
/ F~BROARY 1994 / VOIUMF 43,
NLMUFR 2