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Transitional cell carcinoma presenting as clitoral priapism
Gynecologic Oncology 93 (2004) 540 – 542 www.elsevier.com/locate/ygyno
Case Report
Transitional cell carcinoma presenting as clitoral priapism Sarah DiGiorgi, a Peter F. Schnatz, a,b,* Srinivas Mandavilli, b John F. Greene, a,b and Stephen L. Curry a,b,c a
The University of Connecticut School of Medicine, Farmington, CT 06030, USA b Hartford Hospital, Hartford, CT 06102, USA c New Britain General Hospital, New Britain, CT 06050, USA Received 15 August 2003
Abstract Background. Clitoral priapism is an uncommon cause of clitoromegaly. It should be suspected in the absence of hirsuitism and the presence of clitoral engorgement, pain, and local irritation. Case. A 48-year-old female had a straight catheterization of her bladder for a history of frequent urinary tract infections. She was noted to have a clitoral size of 5 2.5 cm along with the classic findings of priapism. She had an 8 10 cm pelvic mass that was biopsied and revealed transitional cell carcinoma with papillary squamous component. Conclusion. Clitoral priapism presents with clitoral engorgement in the absence of sexual stimulation. The most common etiologies include medications, pelvic tumors, blood dyscrasias, or retroperitoneal fibrosis. A thorough investigation is warranted to identify potential pelvic venous or lymphatic obstruction. D 2004 Elsevier Inc. All rights reserved. Keywords: Clitoromegaly; Clitoral priapism; Pelvic mass; Bladder tumor; Transitional cell carcinoma
Introduction
Case
When a patient presents with clitoromegaly, the etiology is most often virilization. Within the differential diagnosis, however, is the less common entity of clitoral priapism. Distinguishing features of priapism include clitoral engorgement, pain, local irritation, and absence of other virilization features. Although priapism is more common in men, it has been well described in women. The potential etiologies include retroperitoneal fibrosis, medication side effects, blood dyscrasias, and tumor infiltration [1 – 3]. Clitoral priapism caused by cervical cancer [1], lymphoma, and a granular cell tumor [2] has been reported. We report a case of clitoral priapism caused by transition cell carcinoma of the bladder, which we believe is the first reported case.
A 48-year-old gravida 3 Hispanic female was referred for rapid onset of clitoromegaly. The patient reported clitoral swelling of 1 month duration, pain with wiping after micturition, but denied recent sexual activity or dysuria. Her medical history included a long history of tobacco abuse and multiple recurrent urinary tract infections. Her surgical history included a hysterectomy after her last vaginal delivery and a cholecystectomy. During the prior 3 years, with many outpatient problem visits, she had multiple abnormal urine analyses. The cultures were positive for Escherichia coli, Staphylococcus non-aureus, Corynebacterium, and Enterococcus; and she was treated with multiple courses of various antibiotics. The patient was scheduled for a cystoscopy and renal ultrasound but missed the appointment. During a follow-up visit, a straight catheterization of the bladder was performed, which revealed a post-void residual bladder capacity of 250 ml. At that time, the patient’s clitoromegaly was discovered and she was referred for gynecologic evaluation. On physical exam, her abdomen was soft and nondistended with moderate suprapubic tenderness. On pelvic
* Corresponding author. Women’s Ambulatory Health Services, Hartford Hospital, Conklin Building 203B, 80 Seymour Street, Hartford, CT 06102. Fax: +1-860-545-1377. E-mail address: [email protected] (P.F. Schnatz). 0090-8258/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2004.01.046
S. DiGiorgi et al. / Gynecologic Oncology 93 (2004) 540–542
Fig. 1. Photograph of clitoral priapism. Note the local irritation and vascular engorgement.
exam, her clitoris measured 5 cm in length and 2.5 cm in diameter (Fig. 1). The clitoris was significantly swollen with vascular engorgement consistent with priapism. The entire clitoris and labia majora were mildly erythematous and exquisitely tender to palpation. The patient had denuded skin on her inner thighs secondary to friction from the midline mass. When the clitoral hood was gently retracted, some denuded sloughed skin was evident, but no pus was present. Palpation of the external area revealed no induration or fluctuant areas. She had palpable inguinal adenopathy with lymph nodes that were 0.5– 1 cm, mobile, and nontender. Her urine was again positive for leukocytes and blood and a culture subsequently revealed Klebsiella and Proteus. Although vaginal and rectal exams were initially refused, a pelvic ultrasound revealed an 8 10 cm midline pelvic mass that was confirmed by CT scan. She underwent an exam under anesthesia, colonoscopy, and cystoscopy with bladder, urethral, and vaginal biopsies. The exam under anesthesia revealed a normal vaginal canal with a palpable anterior pelvic mass, which could also be appreciated on rectal exam. The cystoscopic exam revealed what appeared to be normal bladder mucosa with a posterior filling defect. Sections from both the urinary bladder and vaginal wall showed an invasive high-grade carcinoma with squamous and ‘‘transitional’’ features. There was no in situ component seen in the bladder mucosa or the vaginal wall. This morphology is consistent with primaries arising from both the vagina and the urinary bladder. Immunohistochemical stains were performed and showed tumor cells to be Cytokeratin 7 and Cytokeratin 20 negative, and positive for high molecular weight cytokeratin (clone 34BetaE12). This staining pattern favors this tumor to be of a squamous cell origin. The patient was subsequently referred for radiation therapy.
Discussion Virilization is the most common reason to present with clitoromegaly. Therefore, when evaluating a patient with
541
clitoral enlargement, it is important to determine the presence or absence of other virilizing characteristics. Virilization is defined as the concurrent presentation of clitoral hypertrophy and signs of androgen excess. Hirsutism, frontotemporal baldness, deepening of the voice, increased muscle mass, increased libido, and acne are all potential signs of hyperandrogenism [4]. The differential diagnosis of clitoral enlargement with virilizing signs includes diseases causing excess circulating androgens from either an exogenous or endogenous source. Clitoral priapism is defined as a prolonged clitoral erection in the absence of sexual stimulation. Although priapism is rare compared to clitoral hypertrophy, the presence of engorgement, pain, and local irritation without virilizing signs should raise suspicion for this condition. When suspected, a thorough history, physical exam, and appropriate radiological tests should proceed in search of the underlying cause. A complete review of the patient’s medications along with a search for a pelvic malignancy is important. The specific mechanism resulting in clitoral priapism is likely venous stasis of the corpora cavernosa. This stasis can be caused by a variety of factors leading to pelvic venous or lymphatic obstruction. The etiology of this obstruction can include a medication side effect, blood dyscrasias, retroperitoneal fibrosis, or mass effect from tumor infiltration. Alpha-adrenergic antagonists account for the most common pharmacological cause of episodic priapism, with trazodone hydrochloride being the most commonly reported. Other medications such as fluoxetine, bromocriptine, buproprion, citalopram, danazol, stanozolol, trazodone, and nefazodone have also been implicated. Drugs that cause clitoral hypertrophy by virilization are fluoxymesterone, methyltestosterone, nandrolone, oxymetholone, and oxandrolone [3]. Alpha-adrenergic antagonist medications, such as trazodone, cause sympathetic smooth muscle relaxation and dilation of the venous sinuses of the corpus cavernosa muscle. Serotonin reuptake inhibitors appear to have an independent effect that causes clitoral priapism. However, the mechanism for this is unknown. Fluoxetin, citalopram, and nefazodone, although primarily serotonin reuptake inhibitors, also have mild alpha-adrenegic antagonistic effect. Blood dyscrasias may also account for an additional cause of episodic venous congestion and stasis [5]. The constant compression of the venous or lymphatic outflow is the most likely cause of prolonged priapism. This compression can be secondary to mass effect from a tumor, venous or lymphatic congestion by direct tumor invasion, or embolism of the corpus cavernosa. Although a vaginal or cervical cancer cannot be totally excluded in the present case, the involvement of the bladder, the prior hysterectomy without a dysplasia history, and the transitional cell morphology makes bladder cancer the more likely diagnosis. This case helps to illustrate that constant priapism of unknown origin warrants consideration of a possible tumor of any pelvic origin.
542
S. DiGiorgi et al. / Gynecologic Oncology 93 (2004) 540–542
Effective treatment of clitoral priapism depends on eliminating the cause of venous or lymphatic stasis. Any potentially causative medications should be discontinued and the patient observed for symptom resolution. A thorough exam and imaging studies to rule out a pelvic mass should be performed. Instituting alpha-adrenegic agonist therapy such as phenylpropanolamine and phenylepherine has been reported [5]. If the cause is secondary to compression, then the mass should be removed or minimized. Our patient received radiation therapy in an attempt to arrest the growth of her cancer and to decrease its’ size. Unfortunately, treatment options were limited due to the advanced stage of the cancer. The patient was treated with pain medication and died 2 months later as a result of her chronic obstructive pulmonary disease. This case illustrates the importance of routine gynecologic examinations including a pelvic exam, despite a woman’s age or history of a prior hysterectomy. A thorough pelvic exam does not only include obtaining cervical cytology, but includes inspecting and palpating the entire pelvis. Physical findings, such as clitoromegaly, can be important clues to significant underlying pathology. An appropriate suspicion, evaluation, and treatment of this condition requires knowing the difference between clitoral
hypertrophy and priapism along with the subsequent workup and interventions.
Acknowledgment The authors would like to express their appreciation to J. David Schnatz, M.D. for his assistance in the preparation of this manuscript.
References [1] Lozano GB, Castaneda PF. Priapism of the clitoris. Br J Urol 1981; 53:390. [2] Slavin RE, Christie JD, Swedo J, Powell LC. Locally aggressive granular cell tumor causing priapism of the crus of the clitoris, a light and ultrastructural study, with observations concerning the pathogenesis of fibrosis of the corpus cavernosum in priapism. Am J Surg Pathol 1986; 10(7):497 – 507. [3] Micromedex R healthcare series: micromedex, greenwood village, Colorado, series, vol. 117. Addition expires September 2003. [4] Stricker T, Navratil F, Sennhauser FH. Visual diagnosis: an adolescent female who has increasing hair growth. Pediatr Rev 2001;22(7):240 – 4. [5] Medina C. Clitoral priapism: a rare condition presenting as a cause of vulvar pain. Obset Gynecol 2002;100(5):1089 – 91.
Case Report
Transitional cell carcinoma presenting as clitoral priapism Sarah DiGiorgi, a Peter F. Schnatz, a,b,* Srinivas Mandavilli, b John F. Greene, a,b and Stephen L. Curry a,b,c a
The University of Connecticut School of Medicine, Farmington, CT 06030, USA b Hartford Hospital, Hartford, CT 06102, USA c New Britain General Hospital, New Britain, CT 06050, USA Received 15 August 2003
Abstract Background. Clitoral priapism is an uncommon cause of clitoromegaly. It should be suspected in the absence of hirsuitism and the presence of clitoral engorgement, pain, and local irritation. Case. A 48-year-old female had a straight catheterization of her bladder for a history of frequent urinary tract infections. She was noted to have a clitoral size of 5 2.5 cm along with the classic findings of priapism. She had an 8 10 cm pelvic mass that was biopsied and revealed transitional cell carcinoma with papillary squamous component. Conclusion. Clitoral priapism presents with clitoral engorgement in the absence of sexual stimulation. The most common etiologies include medications, pelvic tumors, blood dyscrasias, or retroperitoneal fibrosis. A thorough investigation is warranted to identify potential pelvic venous or lymphatic obstruction. D 2004 Elsevier Inc. All rights reserved. Keywords: Clitoromegaly; Clitoral priapism; Pelvic mass; Bladder tumor; Transitional cell carcinoma
Introduction
Case
When a patient presents with clitoromegaly, the etiology is most often virilization. Within the differential diagnosis, however, is the less common entity of clitoral priapism. Distinguishing features of priapism include clitoral engorgement, pain, local irritation, and absence of other virilization features. Although priapism is more common in men, it has been well described in women. The potential etiologies include retroperitoneal fibrosis, medication side effects, blood dyscrasias, and tumor infiltration [1 – 3]. Clitoral priapism caused by cervical cancer [1], lymphoma, and a granular cell tumor [2] has been reported. We report a case of clitoral priapism caused by transition cell carcinoma of the bladder, which we believe is the first reported case.
A 48-year-old gravida 3 Hispanic female was referred for rapid onset of clitoromegaly. The patient reported clitoral swelling of 1 month duration, pain with wiping after micturition, but denied recent sexual activity or dysuria. Her medical history included a long history of tobacco abuse and multiple recurrent urinary tract infections. Her surgical history included a hysterectomy after her last vaginal delivery and a cholecystectomy. During the prior 3 years, with many outpatient problem visits, she had multiple abnormal urine analyses. The cultures were positive for Escherichia coli, Staphylococcus non-aureus, Corynebacterium, and Enterococcus; and she was treated with multiple courses of various antibiotics. The patient was scheduled for a cystoscopy and renal ultrasound but missed the appointment. During a follow-up visit, a straight catheterization of the bladder was performed, which revealed a post-void residual bladder capacity of 250 ml. At that time, the patient’s clitoromegaly was discovered and she was referred for gynecologic evaluation. On physical exam, her abdomen was soft and nondistended with moderate suprapubic tenderness. On pelvic
* Corresponding author. Women’s Ambulatory Health Services, Hartford Hospital, Conklin Building 203B, 80 Seymour Street, Hartford, CT 06102. Fax: +1-860-545-1377. E-mail address: [email protected] (P.F. Schnatz). 0090-8258/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2004.01.046
S. DiGiorgi et al. / Gynecologic Oncology 93 (2004) 540–542
Fig. 1. Photograph of clitoral priapism. Note the local irritation and vascular engorgement.
exam, her clitoris measured 5 cm in length and 2.5 cm in diameter (Fig. 1). The clitoris was significantly swollen with vascular engorgement consistent with priapism. The entire clitoris and labia majora were mildly erythematous and exquisitely tender to palpation. The patient had denuded skin on her inner thighs secondary to friction from the midline mass. When the clitoral hood was gently retracted, some denuded sloughed skin was evident, but no pus was present. Palpation of the external area revealed no induration or fluctuant areas. She had palpable inguinal adenopathy with lymph nodes that were 0.5– 1 cm, mobile, and nontender. Her urine was again positive for leukocytes and blood and a culture subsequently revealed Klebsiella and Proteus. Although vaginal and rectal exams were initially refused, a pelvic ultrasound revealed an 8 10 cm midline pelvic mass that was confirmed by CT scan. She underwent an exam under anesthesia, colonoscopy, and cystoscopy with bladder, urethral, and vaginal biopsies. The exam under anesthesia revealed a normal vaginal canal with a palpable anterior pelvic mass, which could also be appreciated on rectal exam. The cystoscopic exam revealed what appeared to be normal bladder mucosa with a posterior filling defect. Sections from both the urinary bladder and vaginal wall showed an invasive high-grade carcinoma with squamous and ‘‘transitional’’ features. There was no in situ component seen in the bladder mucosa or the vaginal wall. This morphology is consistent with primaries arising from both the vagina and the urinary bladder. Immunohistochemical stains were performed and showed tumor cells to be Cytokeratin 7 and Cytokeratin 20 negative, and positive for high molecular weight cytokeratin (clone 34BetaE12). This staining pattern favors this tumor to be of a squamous cell origin. The patient was subsequently referred for radiation therapy.
Discussion Virilization is the most common reason to present with clitoromegaly. Therefore, when evaluating a patient with
541
clitoral enlargement, it is important to determine the presence or absence of other virilizing characteristics. Virilization is defined as the concurrent presentation of clitoral hypertrophy and signs of androgen excess. Hirsutism, frontotemporal baldness, deepening of the voice, increased muscle mass, increased libido, and acne are all potential signs of hyperandrogenism [4]. The differential diagnosis of clitoral enlargement with virilizing signs includes diseases causing excess circulating androgens from either an exogenous or endogenous source. Clitoral priapism is defined as a prolonged clitoral erection in the absence of sexual stimulation. Although priapism is rare compared to clitoral hypertrophy, the presence of engorgement, pain, and local irritation without virilizing signs should raise suspicion for this condition. When suspected, a thorough history, physical exam, and appropriate radiological tests should proceed in search of the underlying cause. A complete review of the patient’s medications along with a search for a pelvic malignancy is important. The specific mechanism resulting in clitoral priapism is likely venous stasis of the corpora cavernosa. This stasis can be caused by a variety of factors leading to pelvic venous or lymphatic obstruction. The etiology of this obstruction can include a medication side effect, blood dyscrasias, retroperitoneal fibrosis, or mass effect from tumor infiltration. Alpha-adrenergic antagonists account for the most common pharmacological cause of episodic priapism, with trazodone hydrochloride being the most commonly reported. Other medications such as fluoxetine, bromocriptine, buproprion, citalopram, danazol, stanozolol, trazodone, and nefazodone have also been implicated. Drugs that cause clitoral hypertrophy by virilization are fluoxymesterone, methyltestosterone, nandrolone, oxymetholone, and oxandrolone [3]. Alpha-adrenergic antagonist medications, such as trazodone, cause sympathetic smooth muscle relaxation and dilation of the venous sinuses of the corpus cavernosa muscle. Serotonin reuptake inhibitors appear to have an independent effect that causes clitoral priapism. However, the mechanism for this is unknown. Fluoxetin, citalopram, and nefazodone, although primarily serotonin reuptake inhibitors, also have mild alpha-adrenegic antagonistic effect. Blood dyscrasias may also account for an additional cause of episodic venous congestion and stasis [5]. The constant compression of the venous or lymphatic outflow is the most likely cause of prolonged priapism. This compression can be secondary to mass effect from a tumor, venous or lymphatic congestion by direct tumor invasion, or embolism of the corpus cavernosa. Although a vaginal or cervical cancer cannot be totally excluded in the present case, the involvement of the bladder, the prior hysterectomy without a dysplasia history, and the transitional cell morphology makes bladder cancer the more likely diagnosis. This case helps to illustrate that constant priapism of unknown origin warrants consideration of a possible tumor of any pelvic origin.
542
S. DiGiorgi et al. / Gynecologic Oncology 93 (2004) 540–542
Effective treatment of clitoral priapism depends on eliminating the cause of venous or lymphatic stasis. Any potentially causative medications should be discontinued and the patient observed for symptom resolution. A thorough exam and imaging studies to rule out a pelvic mass should be performed. Instituting alpha-adrenegic agonist therapy such as phenylpropanolamine and phenylepherine has been reported [5]. If the cause is secondary to compression, then the mass should be removed or minimized. Our patient received radiation therapy in an attempt to arrest the growth of her cancer and to decrease its’ size. Unfortunately, treatment options were limited due to the advanced stage of the cancer. The patient was treated with pain medication and died 2 months later as a result of her chronic obstructive pulmonary disease. This case illustrates the importance of routine gynecologic examinations including a pelvic exam, despite a woman’s age or history of a prior hysterectomy. A thorough pelvic exam does not only include obtaining cervical cytology, but includes inspecting and palpating the entire pelvis. Physical findings, such as clitoromegaly, can be important clues to significant underlying pathology. An appropriate suspicion, evaluation, and treatment of this condition requires knowing the difference between clitoral
hypertrophy and priapism along with the subsequent workup and interventions.
Acknowledgment The authors would like to express their appreciation to J. David Schnatz, M.D. for his assistance in the preparation of this manuscript.
References [1] Lozano GB, Castaneda PF. Priapism of the clitoris. Br J Urol 1981; 53:390. [2] Slavin RE, Christie JD, Swedo J, Powell LC. Locally aggressive granular cell tumor causing priapism of the crus of the clitoris, a light and ultrastructural study, with observations concerning the pathogenesis of fibrosis of the corpus cavernosum in priapism. Am J Surg Pathol 1986; 10(7):497 – 507. [3] Micromedex R healthcare series: micromedex, greenwood village, Colorado, series, vol. 117. Addition expires September 2003. [4] Stricker T, Navratil F, Sennhauser FH. Visual diagnosis: an adolescent female who has increasing hair growth. Pediatr Rev 2001;22(7):240 – 4. [5] Medina C. Clitoral priapism: a rare condition presenting as a cause of vulvar pain. Obset Gynecol 2002;100(5):1089 – 91.