CASE REPORT
Malignant peripheral nerve sheath tumour of penis J. Kaur1, R. Madan1, L. Singh2, D. N. Sharma1, P. K. Julka1, G. K. Rath1 & S. Roy1 1 Department of Radiation Oncology, Dr BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India; 2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Keywords malignant peripheral nerve sheath tumour— multimodality—penis—treatment Correspondence Dr Jaspreet Kaur, Department of Radiation Oncology, Dr BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India. Tel.: +91-9810966061; Fax: +91-124-4962222; E-mail: [email protected]
Summary Malignant peripheral nerve sheath tumour (MPNST) is a rare variety of soft tissue sarcoma that originates from Schwann cells or pluripotent cells of neural crest origin. They have historically been difficult tumours to diagnose and treat. Surgery is the mainstay of treatment with a goal to achieve negative margins. Despite aggressive surgery and adjuvant therapy, the prognosis of patients with MPNST remains poor. MPNST arising from penis is a very rare entity; thus, it presents a diagnostic and therapeutic challenge. We present a case of penile MPNST in a 38-year-old man in the absence of neurofibromatosis treated with surgery followed by post-operative radiotherapy to a dose of 60 Gray in 30 fractions and adjuvant chemotherapy with ifosfamide and adriamycin.
Accepted: December 14, 2013 doi: 10.1111/and.12267
Introduction
Case report
Malignant peripheral nerve sheath tumour (MPNST) is a rare variety of soft tissue sarcoma that usually arises from large peripheral nerves or nerve trunks and is derived from Schwann cells or pluripotent cells of neural crest origin. These tumours often create diagnostic difficulty because of their cellular origin and histopathological similarities with other spindle cell sarcomas (Ducatman et al., 1986). These tumours can either arise in a sporadic form (approximately 50% of cases) or in the setting of inherited syndrome of neurofibromatosis (NF-1). Patients with type 1 neurofibromatosis have almost a 10% lifetime risk of developing MPNST (Tucker et al., 2005). The term MPNST was coined by World Health Organization to replace a number of previously used terms such as malignant schwannoma, neurofibrosarcoma and neurogenic sarcoma, Weiss & Goldblum (2001). Malignant peripheral nerve sheath tumours have historically been difficult tumours to diagnose and treat. This is in large part due to their inherently aggressive nature. MPNST arising from penis is a very rare entity; it presents a diagnostic and therapeutic challenge. We present a case of penile MPNST in a 38year-old man in the absence of neurofibromatosis with emphasis on diagnosis and treatment.
A 38-year-old man presented with a swelling at the base of penis for the last month. The swelling was associated with intermittent pain in the whole penis, but the penile sensation was preserved. There was no history of trauma, ulceration or discharge. He was married and had completed his family. Actually, the presenting swelling was developed after partial excision of an original mass that was located in the same area. This original mass first appeared since 6 months, and its partial excision was carried out in another hospital since 2 months. Histopathology report turned out as malignant peripheral nerve sheath tumour. Recurrent swelling was noted 1 month after the surgery for which the patient presented to the cancer hospital. Local examination revealed 3 9 2 cm solid hard mass with an overlying scar in the skin near the dorsal surface of the base of penis at 5 o’clock position. The mass was not fixed to the nearby bones. There was no palpable inguinal lymphadenopathy. The scrotum and both testes appeared unremarkable. Ultrasonography with a linear high-frequency transducer (Machine – Philips Envisor) revealed a well-defined nodule (2.2 9 2.3 9 3.6 cm) on the left side of the dorsal surface of the base of penis. Contrast-enhanced magnetic resonance imaging (MRI) of pelvis revealed a soft tissue
© 2014 Blackwell Verlag GmbH Andrologia 2015, 47, 333–335
333
Penile MPNST
J. Kaur et al.
thickening with enhancement in the region of the left side of the base of the penis. There was loss of fat plane with left corpora spongiosa. There was no significant pelvic or inguinal lymph node enlargement (Fig. 1). Pathology review of the blocks from the earlier surgery showed features of a malignant peripheral nerve sheath tumour (Fig. 2a, b). Metastatic workup in the form of computed tomography of the chest and abdomen was done which was unremarkable. The patient underwent wide excision of the tumour along with scrotal transposition. The scrotal skin was advanced to cover the skin defect. The operative findings revealed a 3 9 3 cm solid mass at the dorsal surface of the base of the penile shaft with overlying previous incision scar at 5 o’clock position. The mass was adherent to the tunica albuginea of the left corpus spongiosum, but the left testis and left spermatic cord were not involved. The urethra was close to the mass, but it was free. Wide excision with 3 mm margin was done. Part of the corpora was excised along with the mass. Post-operative course was uneventful. The histopathological examination revealed a malignant spindle cell tumour with vague fascicular pattern and myxoid stoma. Individual tumour cells showed indistinct cell membrane and wavy nuclei. The nuclear pleomorphism, hyperchromasia, frequent
Fig. 1 T2W axial MR image at ischial tuberosity level showing the mass (arrow) to be heterogeneously hyperintense in the penile shaft.
(a)
334
(b)
mitotic activity and areas of necrosis were also noted. The tumour cells were immune-positive for S-100 protein and were negative for smooth muscle actin and desmin. All the resected margins were free of tumour. Thus, a diagnosis of MPNST was proffered. The patient was subjected to post-operative external beam radiotherapy to the penile shaft to a dose of 60 Gray in 30 fractions over a period of 6 weeks with 6 MV photons by 3-dimensional conformal radiotherapy. Radiotherapy was started 6 weeks after surgery. Four weeks after completion of radiotherapy, the patient received six cycles of ifosfamide and adriamycin-based chemotherapy (ifosfamide – 1800 mg m-2 for 5 days with MESNA (2-Mercapto Ethane Sulfonate Na) and adriamycin 25 mg m-2 day 1–3 every three weekly). Neither recurrent nor metastatic disease was found on follow-up MRI pelvis and abdomen and contrast-enhanced computed tomography (CECT) of chest after 3 months. Discussion Malignant peripheral nerve sheath tumour is a malignant tumour arising from or differentiating towards cells of the peripheral nerve sheath. It occurs in two principle forms: (i) sporadic and (ii) associated with NF-1. The cell of origin is the Schwann cell. The mature Schwann cells stain positive for S-100 protein, but they may be absent in about 50% of MPNST due to dedifferentiation (Bhattacharyya et al., 2004). It generally occurs in adulthood typically between 20 and 50 years of age and usually presents as a painless growing mass. The common sites of occurrence are limbs and retroperitoneum. Despite the rich innervations of genital area, penile MPNSTs are extremely rare. Till date, only two penile MPNSTs without evidence of neurofibromatosis have been reported in the literature. The index case will be the third in this category. Mortell et al. (2007) reported a case of penile MPNST in a 3 year old without evidence of NF-1, treated by excision. Follow-up for 5.5 years exhibited two episodes of recurrence. The second case was reported by Parekh et al. (2013) in a 14-month-old boy.
Fig. 2 (a) Malignant peripheral nerve sheath tumour (9200) showing alternate cellular and myxoid areas. Individual tumour cells have indistinct cytoplasm and wavy nuclei with tapering ends. Nuclear hyperchromasia, pleomorphism and frequent mitotic figures are noted. (b) Malignant peripheral nerve sheath tumour (9200) showing S-100 protein positivity in tumour cells.
© 2014 Blackwell Verlag GmbH Andrologia 2015, 47, 333–335
J. Kaur et al.
Surgery is the mainstay of treatment with a goal to achieve negative margins. Resectability depends largely on tumour location and ranges from 20% in paraspinal MPNSTs to 95% in tumours of the extremities (Gupta & Maniker, 2007). Adjuvant radiotherapy has been shown to provide local control and delay the onset of recurrence (Yang et al., 1998). Currently, post-operative radiotherapy is recommended by the Oncology Consensus Group as part of a uniform treatment policy for MPNSTs, much like other high-grade soft tissue sarcomas, even if clear surgical margins are obtained (Ferner & Gutmann, 2002). Chemotherapy is used in adjuvant as well as metastatic setting. Due to the rare incidence of MPNST, large trials exploring the optimum adjuvant treatment are not available. Most of the current data are based on case reports, small case series or treatments proven to be successful for other soft tissue sarcomas. Malignant peripheral nerve sheath tumours are associated with increased risk for local failure and tumourrelated morbidity (Pisters et al., 1996). Despite aggressive surgery and adjuvant therapy, the prognosis for patients with MPNST remains poor. The cumulative incidence of both local recurrence and distant metastases at 10 years is approximately 30%. Presentation with either recurrent disease, tumour size (>5 cm) and the site of origin are identified as the most important prognostic factors for cause-specific survival in patients with MPNST (Anghileri et al., 2006). Post-operative radiotherapy has been shown to reduce the risk of local recurrence and mortality by 50% irrespective of the margin status. Prognosis appears to be worse in patients with NF1 than in those without NF1. Patients without NF-1 tend to present at an early stage compared to those with NF-1. The reported 5-year survival rate for patients with MPNSTs without NF1 is as high as 50% and drops to as low as 10% in patients with MPNSTs and NF1 (Doorn et al., 1995). To conclude, MPNST of penis is an exceedingly rare entity. An extensive panel of immunohistochemistry to establish the diagnosis and to exclude other soft tissue sarcomas is mandatory to arrive at the correct diagnosis. Though no uniform treatment guidelines are available, the multimodality treatment approach is usually considered as the best treatment option.
© 2014 Blackwell Verlag GmbH Andrologia 2015, 47, 333–335
Penile MPNST
References Anghileri M, Miceli R, Fiore M, Mariani L, Ferrari A, Mussi C, Lozza L, Collini P, Olmi P, Casali PG, Pilotti S, Gronchi A (2006) Malignant peripheral nerve sheath tumors prognostic factors and survival in a series of patients treated at a single institution. Cancer 107:1065–1074. Bhattacharyya AK, Perrin R, Guha A (2004) Peripheral nerve tumors: management strategies and molecular insights. J Neurooncol 69:335–349. Doorn PF, Molenaar WM, Buter J, Hoekstra HJ (1995) Malignant peripheral nerve sheath tumors in patients with and without neurofibromatosis. Eur J Surg Oncol 21:78–82. Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM, Ilstrup DM (1986) Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer 57:2006–2021. Ferner RE, Gutmann DH (2002) International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis. Cancer Res 62:1573–1577. Gupta G, Maniker A (2007) Malignant peripheral nerve sheath tumors. Neurosurg Focus 22:E12. Mortell A, Amjad B, Breatnach F, Devaney D, Puri P (2007) Penile malignant peripheral nerve sheath tumour (schwannoma) in a three-year-old child without evidence of neurofibromatosis. Eur J Pediatr Surg 17:428–430. Parekh N, Cockrell E, McMahon D (2013) Malignant peripheral nerve sheath tumor of the penis: a case report and review of the literature. Urology 81:1067–1068. Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF (1996) Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 14:1679–1689. Tucker T, Wolkenstein P, Revuz J, Zeller J, Friedman JM (2005) Association between benign and malignant peripheral nerve sheath tumors in NF1. Neurology 65:205– 211. Weiss SW, Goldblum JR (2001) Enzinger and Weiss’s Soft Tissue Tumors. Mosby Inc., St. Louis, MO. Yang JC, Chang AE, Baker AR, Sindelar WF, Danforth DN, Topalian SL, DeLaney T, Glatstein E, Steinberg SM, Merino MJ, Rosenberg SA (1998) Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 16: 197–203.
335
Malignant peripheral nerve sheath tumour of penis J. Kaur1, R. Madan1, L. Singh2, D. N. Sharma1, P. K. Julka1, G. K. Rath1 & S. Roy1 1 Department of Radiation Oncology, Dr BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India; 2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Keywords malignant peripheral nerve sheath tumour— multimodality—penis—treatment Correspondence Dr Jaspreet Kaur, Department of Radiation Oncology, Dr BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India. Tel.: +91-9810966061; Fax: +91-124-4962222; E-mail: [email protected]
Summary Malignant peripheral nerve sheath tumour (MPNST) is a rare variety of soft tissue sarcoma that originates from Schwann cells or pluripotent cells of neural crest origin. They have historically been difficult tumours to diagnose and treat. Surgery is the mainstay of treatment with a goal to achieve negative margins. Despite aggressive surgery and adjuvant therapy, the prognosis of patients with MPNST remains poor. MPNST arising from penis is a very rare entity; thus, it presents a diagnostic and therapeutic challenge. We present a case of penile MPNST in a 38-year-old man in the absence of neurofibromatosis treated with surgery followed by post-operative radiotherapy to a dose of 60 Gray in 30 fractions and adjuvant chemotherapy with ifosfamide and adriamycin.
Accepted: December 14, 2013 doi: 10.1111/and.12267
Introduction
Case report
Malignant peripheral nerve sheath tumour (MPNST) is a rare variety of soft tissue sarcoma that usually arises from large peripheral nerves or nerve trunks and is derived from Schwann cells or pluripotent cells of neural crest origin. These tumours often create diagnostic difficulty because of their cellular origin and histopathological similarities with other spindle cell sarcomas (Ducatman et al., 1986). These tumours can either arise in a sporadic form (approximately 50% of cases) or in the setting of inherited syndrome of neurofibromatosis (NF-1). Patients with type 1 neurofibromatosis have almost a 10% lifetime risk of developing MPNST (Tucker et al., 2005). The term MPNST was coined by World Health Organization to replace a number of previously used terms such as malignant schwannoma, neurofibrosarcoma and neurogenic sarcoma, Weiss & Goldblum (2001). Malignant peripheral nerve sheath tumours have historically been difficult tumours to diagnose and treat. This is in large part due to their inherently aggressive nature. MPNST arising from penis is a very rare entity; it presents a diagnostic and therapeutic challenge. We present a case of penile MPNST in a 38year-old man in the absence of neurofibromatosis with emphasis on diagnosis and treatment.
A 38-year-old man presented with a swelling at the base of penis for the last month. The swelling was associated with intermittent pain in the whole penis, but the penile sensation was preserved. There was no history of trauma, ulceration or discharge. He was married and had completed his family. Actually, the presenting swelling was developed after partial excision of an original mass that was located in the same area. This original mass first appeared since 6 months, and its partial excision was carried out in another hospital since 2 months. Histopathology report turned out as malignant peripheral nerve sheath tumour. Recurrent swelling was noted 1 month after the surgery for which the patient presented to the cancer hospital. Local examination revealed 3 9 2 cm solid hard mass with an overlying scar in the skin near the dorsal surface of the base of penis at 5 o’clock position. The mass was not fixed to the nearby bones. There was no palpable inguinal lymphadenopathy. The scrotum and both testes appeared unremarkable. Ultrasonography with a linear high-frequency transducer (Machine – Philips Envisor) revealed a well-defined nodule (2.2 9 2.3 9 3.6 cm) on the left side of the dorsal surface of the base of penis. Contrast-enhanced magnetic resonance imaging (MRI) of pelvis revealed a soft tissue
© 2014 Blackwell Verlag GmbH Andrologia 2015, 47, 333–335
333
Penile MPNST
J. Kaur et al.
thickening with enhancement in the region of the left side of the base of the penis. There was loss of fat plane with left corpora spongiosa. There was no significant pelvic or inguinal lymph node enlargement (Fig. 1). Pathology review of the blocks from the earlier surgery showed features of a malignant peripheral nerve sheath tumour (Fig. 2a, b). Metastatic workup in the form of computed tomography of the chest and abdomen was done which was unremarkable. The patient underwent wide excision of the tumour along with scrotal transposition. The scrotal skin was advanced to cover the skin defect. The operative findings revealed a 3 9 3 cm solid mass at the dorsal surface of the base of the penile shaft with overlying previous incision scar at 5 o’clock position. The mass was adherent to the tunica albuginea of the left corpus spongiosum, but the left testis and left spermatic cord were not involved. The urethra was close to the mass, but it was free. Wide excision with 3 mm margin was done. Part of the corpora was excised along with the mass. Post-operative course was uneventful. The histopathological examination revealed a malignant spindle cell tumour with vague fascicular pattern and myxoid stoma. Individual tumour cells showed indistinct cell membrane and wavy nuclei. The nuclear pleomorphism, hyperchromasia, frequent
Fig. 1 T2W axial MR image at ischial tuberosity level showing the mass (arrow) to be heterogeneously hyperintense in the penile shaft.
(a)
334
(b)
mitotic activity and areas of necrosis were also noted. The tumour cells were immune-positive for S-100 protein and were negative for smooth muscle actin and desmin. All the resected margins were free of tumour. Thus, a diagnosis of MPNST was proffered. The patient was subjected to post-operative external beam radiotherapy to the penile shaft to a dose of 60 Gray in 30 fractions over a period of 6 weeks with 6 MV photons by 3-dimensional conformal radiotherapy. Radiotherapy was started 6 weeks after surgery. Four weeks after completion of radiotherapy, the patient received six cycles of ifosfamide and adriamycin-based chemotherapy (ifosfamide – 1800 mg m-2 for 5 days with MESNA (2-Mercapto Ethane Sulfonate Na) and adriamycin 25 mg m-2 day 1–3 every three weekly). Neither recurrent nor metastatic disease was found on follow-up MRI pelvis and abdomen and contrast-enhanced computed tomography (CECT) of chest after 3 months. Discussion Malignant peripheral nerve sheath tumour is a malignant tumour arising from or differentiating towards cells of the peripheral nerve sheath. It occurs in two principle forms: (i) sporadic and (ii) associated with NF-1. The cell of origin is the Schwann cell. The mature Schwann cells stain positive for S-100 protein, but they may be absent in about 50% of MPNST due to dedifferentiation (Bhattacharyya et al., 2004). It generally occurs in adulthood typically between 20 and 50 years of age and usually presents as a painless growing mass. The common sites of occurrence are limbs and retroperitoneum. Despite the rich innervations of genital area, penile MPNSTs are extremely rare. Till date, only two penile MPNSTs without evidence of neurofibromatosis have been reported in the literature. The index case will be the third in this category. Mortell et al. (2007) reported a case of penile MPNST in a 3 year old without evidence of NF-1, treated by excision. Follow-up for 5.5 years exhibited two episodes of recurrence. The second case was reported by Parekh et al. (2013) in a 14-month-old boy.
Fig. 2 (a) Malignant peripheral nerve sheath tumour (9200) showing alternate cellular and myxoid areas. Individual tumour cells have indistinct cytoplasm and wavy nuclei with tapering ends. Nuclear hyperchromasia, pleomorphism and frequent mitotic figures are noted. (b) Malignant peripheral nerve sheath tumour (9200) showing S-100 protein positivity in tumour cells.
© 2014 Blackwell Verlag GmbH Andrologia 2015, 47, 333–335
J. Kaur et al.
Surgery is the mainstay of treatment with a goal to achieve negative margins. Resectability depends largely on tumour location and ranges from 20% in paraspinal MPNSTs to 95% in tumours of the extremities (Gupta & Maniker, 2007). Adjuvant radiotherapy has been shown to provide local control and delay the onset of recurrence (Yang et al., 1998). Currently, post-operative radiotherapy is recommended by the Oncology Consensus Group as part of a uniform treatment policy for MPNSTs, much like other high-grade soft tissue sarcomas, even if clear surgical margins are obtained (Ferner & Gutmann, 2002). Chemotherapy is used in adjuvant as well as metastatic setting. Due to the rare incidence of MPNST, large trials exploring the optimum adjuvant treatment are not available. Most of the current data are based on case reports, small case series or treatments proven to be successful for other soft tissue sarcomas. Malignant peripheral nerve sheath tumours are associated with increased risk for local failure and tumourrelated morbidity (Pisters et al., 1996). Despite aggressive surgery and adjuvant therapy, the prognosis for patients with MPNST remains poor. The cumulative incidence of both local recurrence and distant metastases at 10 years is approximately 30%. Presentation with either recurrent disease, tumour size (>5 cm) and the site of origin are identified as the most important prognostic factors for cause-specific survival in patients with MPNST (Anghileri et al., 2006). Post-operative radiotherapy has been shown to reduce the risk of local recurrence and mortality by 50% irrespective of the margin status. Prognosis appears to be worse in patients with NF1 than in those without NF1. Patients without NF-1 tend to present at an early stage compared to those with NF-1. The reported 5-year survival rate for patients with MPNSTs without NF1 is as high as 50% and drops to as low as 10% in patients with MPNSTs and NF1 (Doorn et al., 1995). To conclude, MPNST of penis is an exceedingly rare entity. An extensive panel of immunohistochemistry to establish the diagnosis and to exclude other soft tissue sarcomas is mandatory to arrive at the correct diagnosis. Though no uniform treatment guidelines are available, the multimodality treatment approach is usually considered as the best treatment option.
© 2014 Blackwell Verlag GmbH Andrologia 2015, 47, 333–335
Penile MPNST
References Anghileri M, Miceli R, Fiore M, Mariani L, Ferrari A, Mussi C, Lozza L, Collini P, Olmi P, Casali PG, Pilotti S, Gronchi A (2006) Malignant peripheral nerve sheath tumors prognostic factors and survival in a series of patients treated at a single institution. Cancer 107:1065–1074. Bhattacharyya AK, Perrin R, Guha A (2004) Peripheral nerve tumors: management strategies and molecular insights. J Neurooncol 69:335–349. Doorn PF, Molenaar WM, Buter J, Hoekstra HJ (1995) Malignant peripheral nerve sheath tumors in patients with and without neurofibromatosis. Eur J Surg Oncol 21:78–82. Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM, Ilstrup DM (1986) Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer 57:2006–2021. Ferner RE, Gutmann DH (2002) International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis. Cancer Res 62:1573–1577. Gupta G, Maniker A (2007) Malignant peripheral nerve sheath tumors. Neurosurg Focus 22:E12. Mortell A, Amjad B, Breatnach F, Devaney D, Puri P (2007) Penile malignant peripheral nerve sheath tumour (schwannoma) in a three-year-old child without evidence of neurofibromatosis. Eur J Pediatr Surg 17:428–430. Parekh N, Cockrell E, McMahon D (2013) Malignant peripheral nerve sheath tumor of the penis: a case report and review of the literature. Urology 81:1067–1068. Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF (1996) Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 14:1679–1689. Tucker T, Wolkenstein P, Revuz J, Zeller J, Friedman JM (2005) Association between benign and malignant peripheral nerve sheath tumors in NF1. Neurology 65:205– 211. Weiss SW, Goldblum JR (2001) Enzinger and Weiss’s Soft Tissue Tumors. Mosby Inc., St. Louis, MO. Yang JC, Chang AE, Baker AR, Sindelar WF, Danforth DN, Topalian SL, DeLaney T, Glatstein E, Steinberg SM, Merino MJ, Rosenberg SA (1998) Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 16: 197–203.
335
