0022-534 7 /92/14 73-0673$03.00/0
VoL 147, 673-675, March 1992
THE JOURNAL OF UROLOGY Copyright© 1992 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Printed in US.A.
MELANOTIC NEUROECTODERMAL TUMOR OF INFANCY: AN IMPORTANT MIMICKER OF PARATESTICULAR RHABDOMYOSARCOMA DAVID A. DIAMOND, PHILIPP. BREITFELD, MARTIN BUR
AND
DAVID GANG
From the Division of Urology, University of Massachusetts Medical Center, Worcester, Massachusetts
ABSTRACT
We report a case of a paratesticular tumor in a 6-month-old infant. This tumor was originally believed to represent a poorly differentiated sarcoma of the cord but upon further pathological consultation it was recognized as a rare melanotic neuroectodermal tumor of infancy involving the epididymis. Since the former is a highly aggressive lesion and the latter an indolent tumor, treatment of these 2 entities differs markedly. Therefore, although the histological distinction between these lesions is often difficult, it is of critical importance. KEY WORDS: testicular neoplasms, testis, epididymis, rhabdomyosarcoma, pediatrics
Paratesticular tumors in infancy are extremely rare, with the most common being paratesticular rhabdomyosarcoma. 1 We describe a paratesticular tumor in a 6-month-old male infant, which was originally believed to represent a poorly differentiated sarcoma. On the basis of subsequent detailed pathological study a diagnosis of epididymal melanotic neuroectodermal tumor of infancy was made. Because of the reported benign natural history of this tumor, the patient was spared combination chemotherapy and possibly retroperitoneal lymph node dissection. We discuss the difficulty and clinical importance in making this histological distinction.
apparent lack of differentiation, it was initially classified as an undifferentiated sarcoma. Computerized tomography (CT) of the chest, abdomen and pelvis was normal, as were a bone scan and bone marrow aspirate. With the diagnosis of nonmetastatic undifferentiated sarcoma the patient was scheduled to receive adjuvant chemotherapy with vincristine, cyclophosphamide and doxombicin.
CASE HISTORY
A 6-month-old white male infant was noted on routine physical examination to have a right scrotal mass that was rock hard and twice the size of the immediately adjacent testis. Scrotal ultrasound demonstrated the solid spermatic cord mass to be independent of the testis and associated with a hydrocele. Serum a-fetoprotein and /1-human chorionic gonadotropin were normal. Right radical orchiectomy was performed, during which the hydrocele was drained, and the testis and cord were exposed. The testis appeared entirely normal with a normal caput epididymis. In continuity with the more distal epididymis was a flesh-colored, rock hard mass (figs. 1 and 2). On the basis of the clinical presentation a working diagnosis of paratesticular rhabdomyosarcoma was made. Microscopically the tumor was composed predominantly of small immature cells with scant cytoplasm and dark, round-oval nuclei with coarse chromatin. Numerous mitoses were present (fig. 3, A). The cells were arranged in loosely cohesive nests, sheets and cords with intervening septa. Focally larger epithelioid cells with more abundant cytoplasm and vesicular nuclei were present in small aggregates. These cells were scattered in the septa and were distinct from the aforementioned immature cells. Many of the larger cells contained yellow-brown, nonbirefringent pigment, and they were believed to represent residual atrophic epididymal tubules, containing lipofuchsin that appeared unrelated to the predominant tumor cell population. Although initial pathological review suggested that the tumor was a sarcoma, there were no rhabdomyoblasts identified on light or electron microscopy. In an attempt to establish the cellular origin of the tumor, histocytochemistry and immunoperoxidase staining were performed. Periodic acid, Schiff stains for glycogen, and immunoperoxidase stains for muscle specific actin, myoglobin, desmin, cytokeratin, chromogranin and S100 protein were negative. In view of the tumor location and Accepted for publication August 12, 1991. 673
FIG. L Surgical appearance of paratesticular tumor (white arrow) at time of radical orchiectomy. T, testis. M, tumor mass. E, epididymis.
674
DIAMOND AND ASSOCIATES
FIG. 2. Sagittal section of gross pathological specimen reveals 1 cm. well circumscribed white nodule involving tail of epididymis (white arrow). T, testis. M, tumor mass. E, epididymis.
munoperoxidase stains were positive for gliofibrillary acidic protein and synaptophysin, and focally positive for melanoma specific antigen, which is indicative of neuroectodermal origin and melanocytic differentiation. Thus, the tumor was recognized as a pigmented neuroectodermal tumor of infancy. Because melanotic neuroectodermal tumor of infancy has limited metastatic potential, plans for adjuvant chemotherapy were abandoned. The patient has been followed with serial CT scans of the abdomen and chest. In addition, because isolated previous reports had indicated an increased excretion of urinary vanillylmandelic acid in melanotic neuroectodermal tumors of infancy, urinary homovanillic acid and vanillylmandelic acid levels have been followed. 2 At I-year followup there is no evidence of recurrent or metastatic disease. DISCUSSION
FIG. 3. A, representative microscopic field of tumor shows small anaplastic cells and mitotic figures (black arrow). B, pigmented epithelioid cells surround cluster of immature tumor cells. H & E, reduced from X400.
Epididymal melanotic neuroectodermal tumor of infancy Reference Eaton and Ferguson• Frank and Koten 7 Zone8 Mostofi and Price (3 pts.) 9 Iwakiri et al'0 Johnson et al4 Ricketts and Majmudarr3 Murayama et al 5 Present case
Pt. Age
Tumor Biology
5 mos. 2 yrs. 3 mos. 4 to 5 mos. 1 yr. 5mos. 3 mos. 10 mos. 6 mos.
Benign Benign Benign Benign Benign Malignant Benign Benign Benign
Upon further pathological review and consultation, the aforementioned clusters of pigmented epithelial cells were found to be close to the nests of small tumor cells (fig. 3, B). FontanaMasson stain demonstrated the pigment to be melanin. Im-
Melanotic neuroectodermal tumor of infancy is a rare and generally benign lesion of neural crest origin, with only 3 to 4 % reported to be malignant. 3 A review of these tumors demonstrates that 95% occur in children less than 1 year old, and 93% occur in the head and neck, with the maxilla being the most common site. An epididymal origin is exceedingly rare, accounting for only 2% of all cases reported to date. 4 To our knowledge, our patient represents the eleventh reported case of melanotic neuroectodermal tumor of infancy arising from the epididymis (see table). 3· 10 Patients have ranged in age from 3 months to 2 years. Of the previous 10 cases 9 tumors were believed to be benign. The tenth patient was noted to have micrometastases on retroperitoneal lymph node dissection but he was without evidence of disease 4 years after diagnosis without further treatment. 4 A recent report of a melanotic neuroectodermal tumor of infancy arising from the epididymis belies the difficulty in making the diagnostic distinction from a poorly differentiated sarcoma histologically. 5 The tumor is recognizable on the basis of its pigment granule formation; however, several patterns have been described, which indicate a relative diversity of differentiation within the neoplasm. 11 Unlike the patient described by Murayama et al,5 with pigmented cells interspersed among the aplastic cells, our patient had a paucity of pigment granule formation located within only a few clusters of cells. In addition, the tumor described by Murayama et al was diagnosed in part by its positive staining for S-100 protein, which was negative in our patient. This finding emphasizes the importance of a meticulous pathological examination of the tumor and the use of all available stains for neural elements. Paratesticular tumors occurring in the first year of life are most commonly rhabodomyosarcomas and less commonly undifferentiated sarcomas of the spermatic cord. The treatment of these tumors entails radical orchiectomy followed by combination chemotherapy. Retroperitoneal lymph node dissection is performed primarily as a staging procedure to determine the need for external beam radiation therapy. 1 Thus, the ability to diagnose melanotic neuroectodermal tumor of infancy and rule out sarcoma of the spermatic cord potentially spares the patient the attendant risks of retroperitoneal lymph node dissection and adjuvant chemotherapy. Dr. Andrew Rosenberg, Department of Pathology, Massachusetts General Hospital, reviewed the pathological slides. REFERENCES
1.
Snyder, H. McC., III, D'Angio, G. J., Evans, A. E. and Raney, R. B.: Pediatric oncology. In: Campbell's Urology, 5th ed. Edited by P. C. Walsh, R. F. Gittes, A. D. Perlmutter and T. A. Stamey. Philadelphia: W. B. Saunders Co., chapt. 57, pp. 2244-2296,
1986. 2. Borello, E. D. and Gorlin, R. J.: Melanotic neuroectodermal tumor
of infancy-a neoplasm of neural crest origin. Report of a case associated with high urinary excretion of vanilmandelic acid. Cancer, 19: 196, 1966.
MELANOTIC NEUROECTODERMAL TUMOR OF INFANCY
3. Ricketts, R. R and Majmudarr, B.: Epididymal melanotic neuroectodermal tumor of infancy. Hum. Path., 16: 416, 1985. 4. Johnson, R. E., Scheithauer, B. W. and Dahlin, D. C.: Melanotic neuroectodermal tumor of infancy: a review of seven cases. Cancer, 52: 661, 1983. 5. Murayama, T., Fujita, K., Ohashi, T. and Matsushita, T.: Melanotic neuroectodermal tumor of the epididymis in infancy: a case report. J. Urol., 141: 105, 1989. 6. Eaton, W. L. and Ferguson, J. P.: A retinoblastic teratoma of the epididymis: case report. Cancer, 9: 718, 1956. 7. Frank, G. L. and Koten, J. W.: Melanotic hamartoma ("retinal anlage tumour") of the epididymis. J. Path. Bact., 93: 549, 1967. 8. Zone, R. M.: Retinal anlage tumor of the epididymis: a case report.
675
J. Urol., 103: 106, 1970. 9. Mostofi, F. K. and Price, E. B., Jr.: Miscellaneous tumors of epididymis, spermatic cord, and testicular tunics. In: Tumors of the Male Genital System. Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, series 2, fasc. 8, pp. 17 4-175, 1973. 10. Iwakiri, K., Hirai, Y., Hasegawa, Y., Suruga, K. and Kuwahara, N.: A case of melanotic hamartoma of epididymis. J. Ped. Pract., 44: 641, 1981. 11. Cutler, L. S., Chaudhry, A. P. and Topazian, P.: Melanotic neuroectodermal tumor of infancy: an ultrastructural study, literature review, and reevaluation. Cancer, 48: 257, 1981.
VoL 147, 673-675, March 1992
THE JOURNAL OF UROLOGY Copyright© 1992 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Printed in US.A.
MELANOTIC NEUROECTODERMAL TUMOR OF INFANCY: AN IMPORTANT MIMICKER OF PARATESTICULAR RHABDOMYOSARCOMA DAVID A. DIAMOND, PHILIPP. BREITFELD, MARTIN BUR
AND
DAVID GANG
From the Division of Urology, University of Massachusetts Medical Center, Worcester, Massachusetts
ABSTRACT
We report a case of a paratesticular tumor in a 6-month-old infant. This tumor was originally believed to represent a poorly differentiated sarcoma of the cord but upon further pathological consultation it was recognized as a rare melanotic neuroectodermal tumor of infancy involving the epididymis. Since the former is a highly aggressive lesion and the latter an indolent tumor, treatment of these 2 entities differs markedly. Therefore, although the histological distinction between these lesions is often difficult, it is of critical importance. KEY WORDS: testicular neoplasms, testis, epididymis, rhabdomyosarcoma, pediatrics
Paratesticular tumors in infancy are extremely rare, with the most common being paratesticular rhabdomyosarcoma. 1 We describe a paratesticular tumor in a 6-month-old male infant, which was originally believed to represent a poorly differentiated sarcoma. On the basis of subsequent detailed pathological study a diagnosis of epididymal melanotic neuroectodermal tumor of infancy was made. Because of the reported benign natural history of this tumor, the patient was spared combination chemotherapy and possibly retroperitoneal lymph node dissection. We discuss the difficulty and clinical importance in making this histological distinction.
apparent lack of differentiation, it was initially classified as an undifferentiated sarcoma. Computerized tomography (CT) of the chest, abdomen and pelvis was normal, as were a bone scan and bone marrow aspirate. With the diagnosis of nonmetastatic undifferentiated sarcoma the patient was scheduled to receive adjuvant chemotherapy with vincristine, cyclophosphamide and doxombicin.
CASE HISTORY
A 6-month-old white male infant was noted on routine physical examination to have a right scrotal mass that was rock hard and twice the size of the immediately adjacent testis. Scrotal ultrasound demonstrated the solid spermatic cord mass to be independent of the testis and associated with a hydrocele. Serum a-fetoprotein and /1-human chorionic gonadotropin were normal. Right radical orchiectomy was performed, during which the hydrocele was drained, and the testis and cord were exposed. The testis appeared entirely normal with a normal caput epididymis. In continuity with the more distal epididymis was a flesh-colored, rock hard mass (figs. 1 and 2). On the basis of the clinical presentation a working diagnosis of paratesticular rhabdomyosarcoma was made. Microscopically the tumor was composed predominantly of small immature cells with scant cytoplasm and dark, round-oval nuclei with coarse chromatin. Numerous mitoses were present (fig. 3, A). The cells were arranged in loosely cohesive nests, sheets and cords with intervening septa. Focally larger epithelioid cells with more abundant cytoplasm and vesicular nuclei were present in small aggregates. These cells were scattered in the septa and were distinct from the aforementioned immature cells. Many of the larger cells contained yellow-brown, nonbirefringent pigment, and they were believed to represent residual atrophic epididymal tubules, containing lipofuchsin that appeared unrelated to the predominant tumor cell population. Although initial pathological review suggested that the tumor was a sarcoma, there were no rhabdomyoblasts identified on light or electron microscopy. In an attempt to establish the cellular origin of the tumor, histocytochemistry and immunoperoxidase staining were performed. Periodic acid, Schiff stains for glycogen, and immunoperoxidase stains for muscle specific actin, myoglobin, desmin, cytokeratin, chromogranin and S100 protein were negative. In view of the tumor location and Accepted for publication August 12, 1991. 673
FIG. L Surgical appearance of paratesticular tumor (white arrow) at time of radical orchiectomy. T, testis. M, tumor mass. E, epididymis.
674
DIAMOND AND ASSOCIATES
FIG. 2. Sagittal section of gross pathological specimen reveals 1 cm. well circumscribed white nodule involving tail of epididymis (white arrow). T, testis. M, tumor mass. E, epididymis.
munoperoxidase stains were positive for gliofibrillary acidic protein and synaptophysin, and focally positive for melanoma specific antigen, which is indicative of neuroectodermal origin and melanocytic differentiation. Thus, the tumor was recognized as a pigmented neuroectodermal tumor of infancy. Because melanotic neuroectodermal tumor of infancy has limited metastatic potential, plans for adjuvant chemotherapy were abandoned. The patient has been followed with serial CT scans of the abdomen and chest. In addition, because isolated previous reports had indicated an increased excretion of urinary vanillylmandelic acid in melanotic neuroectodermal tumors of infancy, urinary homovanillic acid and vanillylmandelic acid levels have been followed. 2 At I-year followup there is no evidence of recurrent or metastatic disease. DISCUSSION
FIG. 3. A, representative microscopic field of tumor shows small anaplastic cells and mitotic figures (black arrow). B, pigmented epithelioid cells surround cluster of immature tumor cells. H & E, reduced from X400.
Epididymal melanotic neuroectodermal tumor of infancy Reference Eaton and Ferguson• Frank and Koten 7 Zone8 Mostofi and Price (3 pts.) 9 Iwakiri et al'0 Johnson et al4 Ricketts and Majmudarr3 Murayama et al 5 Present case
Pt. Age
Tumor Biology
5 mos. 2 yrs. 3 mos. 4 to 5 mos. 1 yr. 5mos. 3 mos. 10 mos. 6 mos.
Benign Benign Benign Benign Benign Malignant Benign Benign Benign
Upon further pathological review and consultation, the aforementioned clusters of pigmented epithelial cells were found to be close to the nests of small tumor cells (fig. 3, B). FontanaMasson stain demonstrated the pigment to be melanin. Im-
Melanotic neuroectodermal tumor of infancy is a rare and generally benign lesion of neural crest origin, with only 3 to 4 % reported to be malignant. 3 A review of these tumors demonstrates that 95% occur in children less than 1 year old, and 93% occur in the head and neck, with the maxilla being the most common site. An epididymal origin is exceedingly rare, accounting for only 2% of all cases reported to date. 4 To our knowledge, our patient represents the eleventh reported case of melanotic neuroectodermal tumor of infancy arising from the epididymis (see table). 3· 10 Patients have ranged in age from 3 months to 2 years. Of the previous 10 cases 9 tumors were believed to be benign. The tenth patient was noted to have micrometastases on retroperitoneal lymph node dissection but he was without evidence of disease 4 years after diagnosis without further treatment. 4 A recent report of a melanotic neuroectodermal tumor of infancy arising from the epididymis belies the difficulty in making the diagnostic distinction from a poorly differentiated sarcoma histologically. 5 The tumor is recognizable on the basis of its pigment granule formation; however, several patterns have been described, which indicate a relative diversity of differentiation within the neoplasm. 11 Unlike the patient described by Murayama et al,5 with pigmented cells interspersed among the aplastic cells, our patient had a paucity of pigment granule formation located within only a few clusters of cells. In addition, the tumor described by Murayama et al was diagnosed in part by its positive staining for S-100 protein, which was negative in our patient. This finding emphasizes the importance of a meticulous pathological examination of the tumor and the use of all available stains for neural elements. Paratesticular tumors occurring in the first year of life are most commonly rhabodomyosarcomas and less commonly undifferentiated sarcomas of the spermatic cord. The treatment of these tumors entails radical orchiectomy followed by combination chemotherapy. Retroperitoneal lymph node dissection is performed primarily as a staging procedure to determine the need for external beam radiation therapy. 1 Thus, the ability to diagnose melanotic neuroectodermal tumor of infancy and rule out sarcoma of the spermatic cord potentially spares the patient the attendant risks of retroperitoneal lymph node dissection and adjuvant chemotherapy. Dr. Andrew Rosenberg, Department of Pathology, Massachusetts General Hospital, reviewed the pathological slides. REFERENCES
1.
Snyder, H. McC., III, D'Angio, G. J., Evans, A. E. and Raney, R. B.: Pediatric oncology. In: Campbell's Urology, 5th ed. Edited by P. C. Walsh, R. F. Gittes, A. D. Perlmutter and T. A. Stamey. Philadelphia: W. B. Saunders Co., chapt. 57, pp. 2244-2296,
1986. 2. Borello, E. D. and Gorlin, R. J.: Melanotic neuroectodermal tumor
of infancy-a neoplasm of neural crest origin. Report of a case associated with high urinary excretion of vanilmandelic acid. Cancer, 19: 196, 1966.
MELANOTIC NEUROECTODERMAL TUMOR OF INFANCY
3. Ricketts, R. R and Majmudarr, B.: Epididymal melanotic neuroectodermal tumor of infancy. Hum. Path., 16: 416, 1985. 4. Johnson, R. E., Scheithauer, B. W. and Dahlin, D. C.: Melanotic neuroectodermal tumor of infancy: a review of seven cases. Cancer, 52: 661, 1983. 5. Murayama, T., Fujita, K., Ohashi, T. and Matsushita, T.: Melanotic neuroectodermal tumor of the epididymis in infancy: a case report. J. Urol., 141: 105, 1989. 6. Eaton, W. L. and Ferguson, J. P.: A retinoblastic teratoma of the epididymis: case report. Cancer, 9: 718, 1956. 7. Frank, G. L. and Koten, J. W.: Melanotic hamartoma ("retinal anlage tumour") of the epididymis. J. Path. Bact., 93: 549, 1967. 8. Zone, R. M.: Retinal anlage tumor of the epididymis: a case report.
675
J. Urol., 103: 106, 1970. 9. Mostofi, F. K. and Price, E. B., Jr.: Miscellaneous tumors of epididymis, spermatic cord, and testicular tunics. In: Tumors of the Male Genital System. Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, series 2, fasc. 8, pp. 17 4-175, 1973. 10. Iwakiri, K., Hirai, Y., Hasegawa, Y., Suruga, K. and Kuwahara, N.: A case of melanotic hamartoma of epididymis. J. Ped. Pract., 44: 641, 1981. 11. Cutler, L. S., Chaudhry, A. P. and Topazian, P.: Melanotic neuroectodermal tumor of infancy: an ultrastructural study, literature review, and reevaluation. Cancer, 48: 257, 1981.
