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Penile Plexiform Neurofibroma: Case Report and Review of the Literature
0022-5347 /88/1396-1310$02.00/0 Vol. 139, June
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1988 by The Williams & Wilkins Co.
PENILE PLEXIFORM NEUROFIBROMA: CASE REPORT AND REVIEW OF THE LITERATURE J. DAVID MAHER, GREGORY M. THOMPSON, STEFAN LOENING AND CHARLES E. PLATZ* From the Departments of Pathology and Urology, University of Iowa College of Medicine, Iowa City, Iowa
ABSTRACT
We report a rare case of a solitary plexiform neurofibroma of the penis. The patient had no other manifestations of von Recklinghausen' s disease. The literature pertaining to neurofibroma of the penis is reviewed. (J. Urol., 139: 1310-1312, 1988) More than 50 cases of genitourinary neurofibromas have been reported 1- 3 Pelvic involvement may be diffuse or localized. Occasionally, these masses have extended into and distorted the external genitalia. Only 7 cases of a solitary neurofibroma arising in the penis have been reported in the English literature. 4-a We report a rare case of a solitary penile plexiform neurofibroma and review the literature on penile neurofibromas.
Approximately 1 month postoperatively the patient was seen in the neurology clinic for evaluation of other manifestations of von Recklinghausen's disease. No cafe au lait spots or axillary freckles were noted. Cranial nerves were intact with normal motor strength. Cerebellar function was normal, as was sensory perception to light touch, pin prick, vibration and position sense. Visual acuity was 20/20 bilaterally. Penile examination revealed a well healed surgical incision with no masses.
CASE REPORT
A 29-year-old white man presented to our hospital with a penile mass that had been present since he was 10 years old. He denied a recent change in mass size, skin ulceration, enlargement on urination or erectile dysfunction. There was no history of urethral discharge, dysuria, hematuria or voiding difficulties. The patient denied visual or auditory problems, change in sense of smell or seizures and he had no signs of mental retardation. To his knowledge, no one in his family had neurofibromatosis. On physical examination the penis was of normal size and contour, except for a painless, mobile, rubbery hard, subcutaneous mass, approximately 4 cm. in diameter, on the left lateral aspect of the penile shaft just proximal to the glans. The mass contained no ulceration. No cafe au lait spots or other masses were noted. Cystoscopic examination revealed an intact urethra without lesions. The remainder of the examination was unremarkable. The mass was excised with the patient under local anesthesia. It was located in the subcutaneous tissue and surrounded by a delicate translucent connective tissue capsule. The mass was not adherent to the tunica albuginea and the corpus cavernosum was not involved. The mass was 3.5 cm. in greatest diameter, yellow-tan, ovoid, smooth and multilobulated, and covered on one aspect by a 4.5 X 3.5 cm. ellipse of brown-tan, wrinkled skin. The cut surface was an aggregate of loosely adherent, firm, homogeneous, yellow-tan cords and nodules, ranging from 0.3 to 1.2 cm. in diameter (fig. 1). A delicate translucent connective tissue membrane surrounded the entire mass. Histologically, the tumor was a plexiform neurofibroma, consisting of subcutaneous, well circumscribed masses and cords of disorganized, neural-appearing tissue composed of fascicles and bundles of spindle cells separated by collagen (fig. 2). Nuclei were uniform and oval to fusiform. Mitotic activity was not evident. The spindle cells were positive immunohistochemically for S-100 protein. Electron microscopy showed a predominance of spindle cells with extensive cell processes surrounding each other or collagen bundles. Basal lamina invested these cells, which occasionally exhibited micropinocytotic vesicles. Also present were fibroblasts with prominent endoplasmic reticulum, lacking basal lamina.
DISCUSSION
Neurofibromatosis is a relatively common, autosomal dominant, hereditary disorder with variable penetrance that occurs once in 3,000 live births. 7 The syndrome is distinguished by multiple skin pigmentations (cafe au lait spots) and the formation of multiple nerve sheath tumors. Manifestations of von Recklinghausen's disease may become apparent at any age and the diagnosis may not become apparent until adulthood. A patient with a solitary plexiform neurofibroma, as in our case, is considered to have neurofibromatosis. 1• 2 Those cases in which the complete syndrome is not evident, including those in which the only clinical manifestation is a single plexiform neurofibroma, are referred to as formes frustes. 1 Plexiform neurofibromas may be well circumscribed or poorly defined. Nonplexiform neurofibromas may or may not be associated with neurofibromatosis, depending on whether the patient has the characteristic skin pigmentation. 1 The identification of a plexiform neurofibroma is appropriately followed by a diagnostic clinical evaluation of the patient for neurofibromatosis. If no other manifestations are identified and the lesion is removed completely, further diagnostic evaluation should not be necessary unless other lesions develop subsequently. Neurofibromas originate from the Schwann cell and may occur in any location, although they are found predominantly in the skin and subcutaneous tissue. Neurofibromas also may involve any tissue or organ and they are associated with cranial, peripheral or visceral nerves. These tumors have been reported to arise in and around the genitourinary system. 1 -a Ogawa and Watanabe cited 20 cases of neurofibromas involving the genitalia, 8 yet neurofibromas of the penis are rarely seen. While the frequency of penile neurofibromas in von Recklinghausen's disease is not readily evident, we were able to find penile involvement in 13 patients with neurofibromas reported in the English literature (see table). 3-a.a-ia Of these cases 8 had other clinical manifestations of von Recklinghausen's disease. In addition, 6 of the 13 patients had secondary invasion of the penis by a pelvic or perinea! mass, while the remaining 7 had solitary penile tumors. Of these 7 tumors 2 arose on the glans, 4 on the shaft and 1 from an unspecified site. Three tumors arising on the shaft were plexiform neurofibromas, as in our case. The histological diagnosis ofplexiform neurofibroma is based on the recognition of a mass formed by expanded and distorted
Accepted for publication October 2, 1987. * Requests for reprints: Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242. 1310
1311
PENILE PLEXIFORM NEUROFIBROMA
nerves, and in most cases these are identified easily. The presence of S-100 protein on immunohistochemical study is additional evidence for the presence of cells of neural crest origin. Ultrastructural features also are found, as in our case, including cells with extensive cell processes with basal lamina interdigitated with each other or with collagen bundles and occasionally surrounding small axons intermixed with fibroblasts. The treatment for penile neurofibromas usually is local surgical intervention. However, even after rigorous excision, neurofibromas may recur in the proximal portion of the nerve of origin. Some have a tendency to involve that nerve progres-
Fm. 1. Cut surface of specimen (skin at lower left) shows nodular or cord-like character ofplexiform neurofibroma.
sively, ultimately extending to the spinal cord or brain. 1 Although they do not metastasize, malignant metastasizing neoplasms develop in 3 to 29 per cent of the cases of neurofibromatosis.13 No cases of sarcoma in a solitary neurofibroma of the penis have been reported, although sarcomas involving the penis in cases of neurofibromatosis have been noted. 5 Neurofibromas should be considered in the differential diagnosis of rare penile masses.
FIG. 2. Histologically tumor consists of cords of disorganized neural tissue with spindle cells and bland-appearing nuclei (inset, reduced from X260) separated by collagen. Reduced from X40.
Penile involvement by neurofihroma Reference McDonnell9
Pt. Age at Diagnosis (yrs.) 37
Daneman and Gratten-Smith10
2½
Borden and Shrader"
5
Rink and Mitchell3
3
Other Indications of von Recklinghausen's Disease Tumor Site Secondary involvement by pelvic mass Secondary involvement by pelvic
Histology
Other Neurofibromas
Cafe au Lait
Spots
Family History
Plexiform
Pos.
Pos.
Not given
Plexiform
Neg.
Pos.
Neg.
Diffuse
Neg.
Pos.
Neg.
Plexiform
Pos.
Pos.
Not given
Plexiform
Pos.
Neg.
Not given
Not given
Not given
Pos.
Neg.
Plexiform
Neg.
Pos.
Pos.
Plexiform Diffuse Diffuse Diffuse Plexiform Diffuse Plexiform
Not given Not given Neg. Neg. Neg. Neg. Neg.
Pos. Neg. Neg. Neg. Neg. Neg. Neg.
Neg. Not given Neg. Neg. Neg. Neg. Neg.
mass
Fethiere and associates 12
16
Peters and Samue[ 13
22
Ogawa and W atanabe8
Dwosh and associates• Elliott and associates• Dehner and Smith4
Present case
8
8 Not given 23 19 25 5 days 29
Secondary involvement by pelvic and perinea! mass Secondary involvement by pelvic mass Junction of shaft and glans Secondary involvement by scrotal and testicular mass Secondary involvement by pelvic and scrotal mass Shaft, base Glans Not given Shaft, base Shaft, dorsum Shaft, ventral Shaft, lateral
1312
MAHER AND ASSOCIATES REFERENCES
1. Harkin, J. C. and Reed, R. J.: Neurofibroma with neurofibromatosis, plexiform neurofibroma, and a description of neurofibromatosis. In: Tumors of the Peripheral Nervous System, Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 3, pp. 67-97, 1979. 2. Jepson, P. M.: Von Recklinghausen's disease presenting as a scrotal tumor. Urology, 5: 270, 1975. 3. Rink, R. C. and Mitchell, M. E.: Genitourinary neurofibromatosis in childhood. J. Urol., 130: 1176, 1983. 4. Dehner, L. P. and Smith, B. H.: Soft tissue tumors of the penis: a clinicopathologic study of 46 cases. Cancer, 25: 1431, 1970. 5. Elliott, F. G., Eid, T. C. and Lakey, W. H.: Genitourinary neurofibromas: clinical significance. J. Urol., 125: 725, 1981. 6. Dwosh, J., Mininberg, D. T., Schlossberg, S. and Peterson, P.: Neurofibroma involving the penis in a child. J. Urol., 132: 988, 1984.
7. Clark, S. S., Marlett, M. M., Prudencio, R. F. and DasGupta, T. K.: Neurofibromatosis of the bladder in children: case report and literature review. J. Urol., 118: 654, 1977. 8. Ogawa, A. and Watanabe, K.: Genitourinary neurofibromatosis in a child presenting with an enlarged penis and scrotum. J. Urol., 135: 755, 1986. 9. McDonnell, C. H.: Neurofibromatosis of bladder and prostate. Amer. J. Surg., 34: 90, 1936. 10. Daneman, A. and Gratten-Smith, P.: Neurofibromatosis involving the lower urinary tract in children. A report of three cases and a review of the literature. Ped. Rad., 4: 161, 1976. 11. Borden, T. A. and Shrader, D. A.: Neurofibromatosis of bladder in a child: unusual cause of enuresis. Urology, 15: 155, 1980. 12. Fethiere, W., Carter, H. W. and Sturim, H. S.: Elephantiasis neuromatosa of the penis: light and electron microscopical studies. Arch. Path., 97: 326, 1974. 13. Peters, W. J. and Samuel, E. S.: Extensive neurofibromatosis of the abdominal wall, penis and scrotum. Canad. J. Surg., 25: 576, 1982.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1988 by The Williams & Wilkins Co.
PENILE PLEXIFORM NEUROFIBROMA: CASE REPORT AND REVIEW OF THE LITERATURE J. DAVID MAHER, GREGORY M. THOMPSON, STEFAN LOENING AND CHARLES E. PLATZ* From the Departments of Pathology and Urology, University of Iowa College of Medicine, Iowa City, Iowa
ABSTRACT
We report a rare case of a solitary plexiform neurofibroma of the penis. The patient had no other manifestations of von Recklinghausen' s disease. The literature pertaining to neurofibroma of the penis is reviewed. (J. Urol., 139: 1310-1312, 1988) More than 50 cases of genitourinary neurofibromas have been reported 1- 3 Pelvic involvement may be diffuse or localized. Occasionally, these masses have extended into and distorted the external genitalia. Only 7 cases of a solitary neurofibroma arising in the penis have been reported in the English literature. 4-a We report a rare case of a solitary penile plexiform neurofibroma and review the literature on penile neurofibromas.
Approximately 1 month postoperatively the patient was seen in the neurology clinic for evaluation of other manifestations of von Recklinghausen's disease. No cafe au lait spots or axillary freckles were noted. Cranial nerves were intact with normal motor strength. Cerebellar function was normal, as was sensory perception to light touch, pin prick, vibration and position sense. Visual acuity was 20/20 bilaterally. Penile examination revealed a well healed surgical incision with no masses.
CASE REPORT
A 29-year-old white man presented to our hospital with a penile mass that had been present since he was 10 years old. He denied a recent change in mass size, skin ulceration, enlargement on urination or erectile dysfunction. There was no history of urethral discharge, dysuria, hematuria or voiding difficulties. The patient denied visual or auditory problems, change in sense of smell or seizures and he had no signs of mental retardation. To his knowledge, no one in his family had neurofibromatosis. On physical examination the penis was of normal size and contour, except for a painless, mobile, rubbery hard, subcutaneous mass, approximately 4 cm. in diameter, on the left lateral aspect of the penile shaft just proximal to the glans. The mass contained no ulceration. No cafe au lait spots or other masses were noted. Cystoscopic examination revealed an intact urethra without lesions. The remainder of the examination was unremarkable. The mass was excised with the patient under local anesthesia. It was located in the subcutaneous tissue and surrounded by a delicate translucent connective tissue capsule. The mass was not adherent to the tunica albuginea and the corpus cavernosum was not involved. The mass was 3.5 cm. in greatest diameter, yellow-tan, ovoid, smooth and multilobulated, and covered on one aspect by a 4.5 X 3.5 cm. ellipse of brown-tan, wrinkled skin. The cut surface was an aggregate of loosely adherent, firm, homogeneous, yellow-tan cords and nodules, ranging from 0.3 to 1.2 cm. in diameter (fig. 1). A delicate translucent connective tissue membrane surrounded the entire mass. Histologically, the tumor was a plexiform neurofibroma, consisting of subcutaneous, well circumscribed masses and cords of disorganized, neural-appearing tissue composed of fascicles and bundles of spindle cells separated by collagen (fig. 2). Nuclei were uniform and oval to fusiform. Mitotic activity was not evident. The spindle cells were positive immunohistochemically for S-100 protein. Electron microscopy showed a predominance of spindle cells with extensive cell processes surrounding each other or collagen bundles. Basal lamina invested these cells, which occasionally exhibited micropinocytotic vesicles. Also present were fibroblasts with prominent endoplasmic reticulum, lacking basal lamina.
DISCUSSION
Neurofibromatosis is a relatively common, autosomal dominant, hereditary disorder with variable penetrance that occurs once in 3,000 live births. 7 The syndrome is distinguished by multiple skin pigmentations (cafe au lait spots) and the formation of multiple nerve sheath tumors. Manifestations of von Recklinghausen's disease may become apparent at any age and the diagnosis may not become apparent until adulthood. A patient with a solitary plexiform neurofibroma, as in our case, is considered to have neurofibromatosis. 1• 2 Those cases in which the complete syndrome is not evident, including those in which the only clinical manifestation is a single plexiform neurofibroma, are referred to as formes frustes. 1 Plexiform neurofibromas may be well circumscribed or poorly defined. Nonplexiform neurofibromas may or may not be associated with neurofibromatosis, depending on whether the patient has the characteristic skin pigmentation. 1 The identification of a plexiform neurofibroma is appropriately followed by a diagnostic clinical evaluation of the patient for neurofibromatosis. If no other manifestations are identified and the lesion is removed completely, further diagnostic evaluation should not be necessary unless other lesions develop subsequently. Neurofibromas originate from the Schwann cell and may occur in any location, although they are found predominantly in the skin and subcutaneous tissue. Neurofibromas also may involve any tissue or organ and they are associated with cranial, peripheral or visceral nerves. These tumors have been reported to arise in and around the genitourinary system. 1 -a Ogawa and Watanabe cited 20 cases of neurofibromas involving the genitalia, 8 yet neurofibromas of the penis are rarely seen. While the frequency of penile neurofibromas in von Recklinghausen's disease is not readily evident, we were able to find penile involvement in 13 patients with neurofibromas reported in the English literature (see table). 3-a.a-ia Of these cases 8 had other clinical manifestations of von Recklinghausen's disease. In addition, 6 of the 13 patients had secondary invasion of the penis by a pelvic or perinea! mass, while the remaining 7 had solitary penile tumors. Of these 7 tumors 2 arose on the glans, 4 on the shaft and 1 from an unspecified site. Three tumors arising on the shaft were plexiform neurofibromas, as in our case. The histological diagnosis ofplexiform neurofibroma is based on the recognition of a mass formed by expanded and distorted
Accepted for publication October 2, 1987. * Requests for reprints: Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242. 1310
1311
PENILE PLEXIFORM NEUROFIBROMA
nerves, and in most cases these are identified easily. The presence of S-100 protein on immunohistochemical study is additional evidence for the presence of cells of neural crest origin. Ultrastructural features also are found, as in our case, including cells with extensive cell processes with basal lamina interdigitated with each other or with collagen bundles and occasionally surrounding small axons intermixed with fibroblasts. The treatment for penile neurofibromas usually is local surgical intervention. However, even after rigorous excision, neurofibromas may recur in the proximal portion of the nerve of origin. Some have a tendency to involve that nerve progres-
Fm. 1. Cut surface of specimen (skin at lower left) shows nodular or cord-like character ofplexiform neurofibroma.
sively, ultimately extending to the spinal cord or brain. 1 Although they do not metastasize, malignant metastasizing neoplasms develop in 3 to 29 per cent of the cases of neurofibromatosis.13 No cases of sarcoma in a solitary neurofibroma of the penis have been reported, although sarcomas involving the penis in cases of neurofibromatosis have been noted. 5 Neurofibromas should be considered in the differential diagnosis of rare penile masses.
FIG. 2. Histologically tumor consists of cords of disorganized neural tissue with spindle cells and bland-appearing nuclei (inset, reduced from X260) separated by collagen. Reduced from X40.
Penile involvement by neurofihroma Reference McDonnell9
Pt. Age at Diagnosis (yrs.) 37
Daneman and Gratten-Smith10
2½
Borden and Shrader"
5
Rink and Mitchell3
3
Other Indications of von Recklinghausen's Disease Tumor Site Secondary involvement by pelvic mass Secondary involvement by pelvic
Histology
Other Neurofibromas
Cafe au Lait
Spots
Family History
Plexiform
Pos.
Pos.
Not given
Plexiform
Neg.
Pos.
Neg.
Diffuse
Neg.
Pos.
Neg.
Plexiform
Pos.
Pos.
Not given
Plexiform
Pos.
Neg.
Not given
Not given
Not given
Pos.
Neg.
Plexiform
Neg.
Pos.
Pos.
Plexiform Diffuse Diffuse Diffuse Plexiform Diffuse Plexiform
Not given Not given Neg. Neg. Neg. Neg. Neg.
Pos. Neg. Neg. Neg. Neg. Neg. Neg.
Neg. Not given Neg. Neg. Neg. Neg. Neg.
mass
Fethiere and associates 12
16
Peters and Samue[ 13
22
Ogawa and W atanabe8
Dwosh and associates• Elliott and associates• Dehner and Smith4
Present case
8
8 Not given 23 19 25 5 days 29
Secondary involvement by pelvic and perinea! mass Secondary involvement by pelvic mass Junction of shaft and glans Secondary involvement by scrotal and testicular mass Secondary involvement by pelvic and scrotal mass Shaft, base Glans Not given Shaft, base Shaft, dorsum Shaft, ventral Shaft, lateral
1312
MAHER AND ASSOCIATES REFERENCES
1. Harkin, J. C. and Reed, R. J.: Neurofibroma with neurofibromatosis, plexiform neurofibroma, and a description of neurofibromatosis. In: Tumors of the Peripheral Nervous System, Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 3, pp. 67-97, 1979. 2. Jepson, P. M.: Von Recklinghausen's disease presenting as a scrotal tumor. Urology, 5: 270, 1975. 3. Rink, R. C. and Mitchell, M. E.: Genitourinary neurofibromatosis in childhood. J. Urol., 130: 1176, 1983. 4. Dehner, L. P. and Smith, B. H.: Soft tissue tumors of the penis: a clinicopathologic study of 46 cases. Cancer, 25: 1431, 1970. 5. Elliott, F. G., Eid, T. C. and Lakey, W. H.: Genitourinary neurofibromas: clinical significance. J. Urol., 125: 725, 1981. 6. Dwosh, J., Mininberg, D. T., Schlossberg, S. and Peterson, P.: Neurofibroma involving the penis in a child. J. Urol., 132: 988, 1984.
7. Clark, S. S., Marlett, M. M., Prudencio, R. F. and DasGupta, T. K.: Neurofibromatosis of the bladder in children: case report and literature review. J. Urol., 118: 654, 1977. 8. Ogawa, A. and Watanabe, K.: Genitourinary neurofibromatosis in a child presenting with an enlarged penis and scrotum. J. Urol., 135: 755, 1986. 9. McDonnell, C. H.: Neurofibromatosis of bladder and prostate. Amer. J. Surg., 34: 90, 1936. 10. Daneman, A. and Gratten-Smith, P.: Neurofibromatosis involving the lower urinary tract in children. A report of three cases and a review of the literature. Ped. Rad., 4: 161, 1976. 11. Borden, T. A. and Shrader, D. A.: Neurofibromatosis of bladder in a child: unusual cause of enuresis. Urology, 15: 155, 1980. 12. Fethiere, W., Carter, H. W. and Sturim, H. S.: Elephantiasis neuromatosa of the penis: light and electron microscopical studies. Arch. Path., 97: 326, 1974. 13. Peters, W. J. and Samuel, E. S.: Extensive neurofibromatosis of the abdominal wall, penis and scrotum. Canad. J. Surg., 25: 576, 1982.