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Neurofibrosarcoma of spermatic cord
NEUROFIBROSARCOMA
DOUGLAS
E. JOHNSON,
M.D.
KELLY
E. KAESLER,
BRUCE
M. MACKAY, M.D.
ALBERT0
OF SPERMATIC CORD
M.D.
G. AYALA, M.D.
From the Departments of Surgery, Sections of Urology and Pathology, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas
ABSTRACT - The first report of a neurofibrosarcomu arising within the spermatic cord is presented. The light and electron microscopic features are discussed.
Malignant neoplasms arising within the spermatic cord are uncommon, with 161 cases reported in the literature by 1969.’ Sporadic cases have continued to appear, but the cumulative number remains relatively small.2-10 Although Banowsky and Schultz2 have described nineteen histologic types of sarcoma originating from the spermatic cord and tunics, none was classified as neurofibrosarcoma. We believe, therefore, that this report, detailing the light and electron microscopic features of neurofibrosarcoma of the spermatic cord, is the first to appear in the literature. Case Report A sixty-five-year-old white man was referred to the section of urology in 1973 for evaluation of symptoms of bladder outlet obstruction. He had been followed up in the Hematology Clinic at The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute for six years for chronic lymphocytic leukemia, which was currently in remission. Physical examination revealed a 5 by 3 cm. hard, nodular left scrotal mass located within the spermatic cord superiorly to the testis and epididymis. The lesion was not tender, did not transilluminate light, and by history had been present for several years without a noticeable change in size. After the preliminary investigation, which
680
included a chest x-ray examination and an excretory urogram, had failed to reveal evidence of metastatic disease, a left inguinal orchiectomy was performed, with excision of the spermatic cord at the internal inguinal ring (Fig. 1A). The patient’s postoperative recovery was uneventful, and he has remained free of recurrent or metastatic disease for fifteen months. Pathologic findings The surgical specimen consisted of a 15 cm. length of spermatic cord, the tumor nodule, and a normal-appearing epididymis and testis. Arising from the distal aspect of the spermatic cord, just cephalad to the epididymis, was a firm irregular multinodular tumor measuring 5 cm. in greatest diameter. Although there was no capsule, the margins appeared well demarcated from the surrounding cord structures. The cut section demonstrated a white fibrous-like Histosurface with rare areas of necrosis. logically, sections taken from the tumor revealed proliferation of spindle cells showing no particular pattern of growth. The vas deferens was surrounded by tumor, although not infiltrated. Sections taken from the peripheral portions of the tumor revealed well-differentiated malignant cells without significant pleomorphism (Fig. 1B). However, sections taken from the central portion of the tumor showed it to be quite cellular with closely apposed spindle cells and
UROLOGY
I
MAY 1975 / VOLUME
V, NUMBER 5
speciFIGURE 1. (A)Surgical men showing irregular multinodular mass arising in distal aspect of spermatic cord. (B) Neurojibrosarcoma: spindle cell neoplasm in$ltrating adipose tissue may be seen, with occasional large nuclei present; note cellular similarity between malignant cells and segment of (C) nerve trunk (X 400). Tumor is cellular with closely packed spindle cells; mitoses are prominent (X 600).
numerous mitotic figures (Fig. 1C). Focal necrosis and occasional giant cells were present. At the time of excision a small portion of the tumor was placed in 2 per cent glutaraldehyde solution and was subsequently processed for electron microscopy. Thin sections of tissue embedded with epoxy resin (Epon) were stained with uranyl acetate and lead citrate and subsequently examined using a Zeiss EM-QS electron microscope. Where the sections showed the tumor cells in longitudinal orientation, the striking feature
UROLOGY
/ MAY1975 / VOLUMEV,
NUMBER5
was their remarkable attenuated cytoplasm (Fig. 2). The long cytoplasmic processes formed parallel bundles, and the limiting cell membranes of adjacent processes were intimately apposed to one another. Frequent cell contact specializations united the cells and processes, and at high magnification these were identified as desmosomes with few or no associated tonofilament bundles. The cell nuclei were elongated and many had a wrinkled profile (Fig. 2A). The common cytoplasmic organelles were most numerous in the cytoplasm adjacent
681
FIGURE 2. (A)Electron micrograph shows portions of several adjacent tumor cells; parts of nuclei of two cells are included, and their elongated shape can be appreciated ( x 3,650). (B) Cytoplasm of tumor cells is attenuated to form long processes that run as parallel bundles, with close apposition of adjacent plasma membranes (x 3,350).
to the nucleus, but scattered mitochondria and short irregular profiles of rough-surfaced endoplasmic reticulum were present in most of the cell processes. A Golgi complex was identified in a number of the cells, lying close to one pole of the nucleus. Slender, longitudinally oriented filaments were present in many of the processes, but microtubules were not numerous. Comment The majority of tumors arising within the spermatic cord, exclusive of lipoma, are sarcomatous in nature and most frequently develop within the scrotum, just superior to the testis and epididymis.6 The primary treatment for all cases is inguinal exploration with cross clamping of the spermatic cord at the internal inguinal ring prior to delivery of the scrotal contents for examination. If malignant disease is believed to be present, a radical orchiectomy with high ligation of the spermatic cord is the treatment of choice. The integrity of the tunica vaginalis and cremasteric fascia should be carefully preserved.l The value of retroperitoneal lymphadenectomy in cases of sarcoma of the spermatic cord has not been proved2,6,8 and is best recommended only in selected cases, keeping in mind that the primary lymphatic drainage areas include both the external iliac and hypogastric nodes as well as the periaortic nodes.” In addition if the scrotum or infraumbilical abdominal wall is involved, spread may occur primarily to the superficial inguinal nodes. In these situations an ilioinguinal rather than a retroperitoneal dissection should be performed if a prophylactic
682
lymphadenectomy is planned. Distant metastases, however, are most frequently caused by hematogenous rather than lymphatic spread. We agree with other investigators that the treatment of choice remains wide local excision and close follow-up, with chemotherapy reserved for proved metastatic disease.3’5 Although we could find no mention in the literature of a primary neurofibrosarcoma arising within the spermatic cord, it is doubtful that this tumor is rare. Instead, we believe it is more likely that many of these tumors have been mistaken for fibrosarcoma or liposarcoma. It is frequently impossible to classify a sarcoma as neurogenic in origin in spite of the light microscopic findings of nuclear palisading and alternating cellular and loose myoid areas. Indeed, D’Agostino, Soule, and Milleri2,13 state that the only feature distinguishing a malignant neurilemoma and a fibrosarcoma is origin within a nerve trunk. In the present case the tumor was intimately related to a nerve bundle, and the histologic appearance of the tumor cells and their arrangement were considered strongly suggestive of neurofibrosarcoma. At M. D. Anderson Hospital we have been interested in studying a wide range of soft tissue sarcomas with electron microscopy in an attempt to delineate fine structural diagnostic criteria which would permit their classification when diagnostic features were absent on light microscopy. We have found that neurogenic sarcomas can be distinguished by the presence of certain specific fine structural features as well as the absence of ultrastructural characteristics diagnostic of other type-specific sarcomas.
UROLOGY
/ MAY1975 / VOLUMEV,
NUMBER5
In this case there were no myofilaments to suggest myosarcoma, nor was the rough-surfaced endoplasmic reticulum abundant as one would expect in fibrosarcoma or liposarcoma. The cells of neurogenic sarcomas, especially those that are relatively well differentiated, have long prolongations of their cytoplasm. These processes may be either closely packed to form wellorientated compact bundles, as seen in our case, or they may be separated by zones of structureless stroma. The presence of specialized membrane contact sites is a consistent finding in neurogenic soft tissue tumors and is not a feature of the other common types of sarcoma. Therefore, we believe that the diagnosis of a neurofibrosarcoma, which was suspected after light microscopic examination, was substantiated by the electron microscopic features.
3.
4. 5.
6.
7.
8.
9. 10.
Section of Urology 6723 Bertner Avenue Houston, Texas 77025 (DR. JOHNSON)
11.
1. ARLEN, M., GRABSTALD, H., and WHITMAN, W. F., JR. : Malignant tumors of the spermatic cord, Cancer 23: 525 (1969). 2. BANOWSKY, L. H., and SCHULTZ, G. N.: Sarcoma of
13.
12.
References
UROLOGY
/
MAY 1975 / VOLUME V, NUMBER 5
the spermatic cord and tunics: review of the literature, case report and discussion of the role of retroperitoneal lymph node dissection, J. Urol. 103: 628 (1970). KRAWITT, D. R., and SIEGEL, W.: Spermatic cord tumors: a case report, Mt. Sinai J. Med. N.Y. 37: 603 (1970). DUHART, J. E., et al.: Sarcoma de cordon espermatico, Rev. Argent. Ural. Nefral. 39: 160 (1970). DATTA, N. S., SINGH, S. M., and BAPNA, B. C.: Liposarcoma of the spermatic cord: report of a case and review of the literature, J. Urol 106: 888 (1971). MALEK, R. S., UTOZ, D. C., and FARROW, G. M.: Malignant tumors of the spermatic cord, Cancer 29: 1108 (1972). JENKINS, D. G., and SIJTTUSWAMY, S. G.: Leiomyosarcoma of the spermatic cord, Br. J. Surg. 59: 408 (1972). WERTZNER, S. : Leiomyosarcoma of the spermatic cord and retroperitoneal lymph node dissection, Am. Surg. 39: 352 (1973). BRENEZ, J. : La resection endoscopique, Acta Ural. Belg. 41: 61 (1973). BONZANNI, C.: Fibrosarcoma of the spermatic cord, Minerva Chir. 29: 156 (1974). ROUVIERE, H.: Anatomy of the Human Lymphatic System, Ann Arbor, Michigan, Edward Brackers, Inc., 1938. D’AGOSTINO, A. N., SOULE, E. H., and MILI.ER, R. H.: Sarcomas of the peripheral nerves and somatic soft tissues associated with multiple neurofibromatosis (von Recklinghausen’s disease), Cancer 16: 1015 (1963). IDEM: Primary malignant neoplasms of nerves (malignant neurilemomas) in patients without manifestations of multiple neurofibromatosis (von Recklinghausen’s disease), ibid. 16: 1003 (1963).
683
DOUGLAS
E. JOHNSON,
M.D.
KELLY
E. KAESLER,
BRUCE
M. MACKAY, M.D.
ALBERT0
OF SPERMATIC CORD
M.D.
G. AYALA, M.D.
From the Departments of Surgery, Sections of Urology and Pathology, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas
ABSTRACT - The first report of a neurofibrosarcomu arising within the spermatic cord is presented. The light and electron microscopic features are discussed.
Malignant neoplasms arising within the spermatic cord are uncommon, with 161 cases reported in the literature by 1969.’ Sporadic cases have continued to appear, but the cumulative number remains relatively small.2-10 Although Banowsky and Schultz2 have described nineteen histologic types of sarcoma originating from the spermatic cord and tunics, none was classified as neurofibrosarcoma. We believe, therefore, that this report, detailing the light and electron microscopic features of neurofibrosarcoma of the spermatic cord, is the first to appear in the literature. Case Report A sixty-five-year-old white man was referred to the section of urology in 1973 for evaluation of symptoms of bladder outlet obstruction. He had been followed up in the Hematology Clinic at The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute for six years for chronic lymphocytic leukemia, which was currently in remission. Physical examination revealed a 5 by 3 cm. hard, nodular left scrotal mass located within the spermatic cord superiorly to the testis and epididymis. The lesion was not tender, did not transilluminate light, and by history had been present for several years without a noticeable change in size. After the preliminary investigation, which
680
included a chest x-ray examination and an excretory urogram, had failed to reveal evidence of metastatic disease, a left inguinal orchiectomy was performed, with excision of the spermatic cord at the internal inguinal ring (Fig. 1A). The patient’s postoperative recovery was uneventful, and he has remained free of recurrent or metastatic disease for fifteen months. Pathologic findings The surgical specimen consisted of a 15 cm. length of spermatic cord, the tumor nodule, and a normal-appearing epididymis and testis. Arising from the distal aspect of the spermatic cord, just cephalad to the epididymis, was a firm irregular multinodular tumor measuring 5 cm. in greatest diameter. Although there was no capsule, the margins appeared well demarcated from the surrounding cord structures. The cut section demonstrated a white fibrous-like Histosurface with rare areas of necrosis. logically, sections taken from the tumor revealed proliferation of spindle cells showing no particular pattern of growth. The vas deferens was surrounded by tumor, although not infiltrated. Sections taken from the peripheral portions of the tumor revealed well-differentiated malignant cells without significant pleomorphism (Fig. 1B). However, sections taken from the central portion of the tumor showed it to be quite cellular with closely apposed spindle cells and
UROLOGY
I
MAY 1975 / VOLUME
V, NUMBER 5
speciFIGURE 1. (A)Surgical men showing irregular multinodular mass arising in distal aspect of spermatic cord. (B) Neurojibrosarcoma: spindle cell neoplasm in$ltrating adipose tissue may be seen, with occasional large nuclei present; note cellular similarity between malignant cells and segment of (C) nerve trunk (X 400). Tumor is cellular with closely packed spindle cells; mitoses are prominent (X 600).
numerous mitotic figures (Fig. 1C). Focal necrosis and occasional giant cells were present. At the time of excision a small portion of the tumor was placed in 2 per cent glutaraldehyde solution and was subsequently processed for electron microscopy. Thin sections of tissue embedded with epoxy resin (Epon) were stained with uranyl acetate and lead citrate and subsequently examined using a Zeiss EM-QS electron microscope. Where the sections showed the tumor cells in longitudinal orientation, the striking feature
UROLOGY
/ MAY1975 / VOLUMEV,
NUMBER5
was their remarkable attenuated cytoplasm (Fig. 2). The long cytoplasmic processes formed parallel bundles, and the limiting cell membranes of adjacent processes were intimately apposed to one another. Frequent cell contact specializations united the cells and processes, and at high magnification these were identified as desmosomes with few or no associated tonofilament bundles. The cell nuclei were elongated and many had a wrinkled profile (Fig. 2A). The common cytoplasmic organelles were most numerous in the cytoplasm adjacent
681
FIGURE 2. (A)Electron micrograph shows portions of several adjacent tumor cells; parts of nuclei of two cells are included, and their elongated shape can be appreciated ( x 3,650). (B) Cytoplasm of tumor cells is attenuated to form long processes that run as parallel bundles, with close apposition of adjacent plasma membranes (x 3,350).
to the nucleus, but scattered mitochondria and short irregular profiles of rough-surfaced endoplasmic reticulum were present in most of the cell processes. A Golgi complex was identified in a number of the cells, lying close to one pole of the nucleus. Slender, longitudinally oriented filaments were present in many of the processes, but microtubules were not numerous. Comment The majority of tumors arising within the spermatic cord, exclusive of lipoma, are sarcomatous in nature and most frequently develop within the scrotum, just superior to the testis and epididymis.6 The primary treatment for all cases is inguinal exploration with cross clamping of the spermatic cord at the internal inguinal ring prior to delivery of the scrotal contents for examination. If malignant disease is believed to be present, a radical orchiectomy with high ligation of the spermatic cord is the treatment of choice. The integrity of the tunica vaginalis and cremasteric fascia should be carefully preserved.l The value of retroperitoneal lymphadenectomy in cases of sarcoma of the spermatic cord has not been proved2,6,8 and is best recommended only in selected cases, keeping in mind that the primary lymphatic drainage areas include both the external iliac and hypogastric nodes as well as the periaortic nodes.” In addition if the scrotum or infraumbilical abdominal wall is involved, spread may occur primarily to the superficial inguinal nodes. In these situations an ilioinguinal rather than a retroperitoneal dissection should be performed if a prophylactic
682
lymphadenectomy is planned. Distant metastases, however, are most frequently caused by hematogenous rather than lymphatic spread. We agree with other investigators that the treatment of choice remains wide local excision and close follow-up, with chemotherapy reserved for proved metastatic disease.3’5 Although we could find no mention in the literature of a primary neurofibrosarcoma arising within the spermatic cord, it is doubtful that this tumor is rare. Instead, we believe it is more likely that many of these tumors have been mistaken for fibrosarcoma or liposarcoma. It is frequently impossible to classify a sarcoma as neurogenic in origin in spite of the light microscopic findings of nuclear palisading and alternating cellular and loose myoid areas. Indeed, D’Agostino, Soule, and Milleri2,13 state that the only feature distinguishing a malignant neurilemoma and a fibrosarcoma is origin within a nerve trunk. In the present case the tumor was intimately related to a nerve bundle, and the histologic appearance of the tumor cells and their arrangement were considered strongly suggestive of neurofibrosarcoma. At M. D. Anderson Hospital we have been interested in studying a wide range of soft tissue sarcomas with electron microscopy in an attempt to delineate fine structural diagnostic criteria which would permit their classification when diagnostic features were absent on light microscopy. We have found that neurogenic sarcomas can be distinguished by the presence of certain specific fine structural features as well as the absence of ultrastructural characteristics diagnostic of other type-specific sarcomas.
UROLOGY
/ MAY1975 / VOLUMEV,
NUMBER5
In this case there were no myofilaments to suggest myosarcoma, nor was the rough-surfaced endoplasmic reticulum abundant as one would expect in fibrosarcoma or liposarcoma. The cells of neurogenic sarcomas, especially those that are relatively well differentiated, have long prolongations of their cytoplasm. These processes may be either closely packed to form wellorientated compact bundles, as seen in our case, or they may be separated by zones of structureless stroma. The presence of specialized membrane contact sites is a consistent finding in neurogenic soft tissue tumors and is not a feature of the other common types of sarcoma. Therefore, we believe that the diagnosis of a neurofibrosarcoma, which was suspected after light microscopic examination, was substantiated by the electron microscopic features.
3.
4. 5.
6.
7.
8.
9. 10.
Section of Urology 6723 Bertner Avenue Houston, Texas 77025 (DR. JOHNSON)
11.
1. ARLEN, M., GRABSTALD, H., and WHITMAN, W. F., JR. : Malignant tumors of the spermatic cord, Cancer 23: 525 (1969). 2. BANOWSKY, L. H., and SCHULTZ, G. N.: Sarcoma of
13.
12.
References
UROLOGY
/
MAY 1975 / VOLUME V, NUMBER 5
the spermatic cord and tunics: review of the literature, case report and discussion of the role of retroperitoneal lymph node dissection, J. Urol. 103: 628 (1970). KRAWITT, D. R., and SIEGEL, W.: Spermatic cord tumors: a case report, Mt. Sinai J. Med. N.Y. 37: 603 (1970). DUHART, J. E., et al.: Sarcoma de cordon espermatico, Rev. Argent. Ural. Nefral. 39: 160 (1970). DATTA, N. S., SINGH, S. M., and BAPNA, B. C.: Liposarcoma of the spermatic cord: report of a case and review of the literature, J. Urol 106: 888 (1971). MALEK, R. S., UTOZ, D. C., and FARROW, G. M.: Malignant tumors of the spermatic cord, Cancer 29: 1108 (1972). JENKINS, D. G., and SIJTTUSWAMY, S. G.: Leiomyosarcoma of the spermatic cord, Br. J. Surg. 59: 408 (1972). WERTZNER, S. : Leiomyosarcoma of the spermatic cord and retroperitoneal lymph node dissection, Am. Surg. 39: 352 (1973). BRENEZ, J. : La resection endoscopique, Acta Ural. Belg. 41: 61 (1973). BONZANNI, C.: Fibrosarcoma of the spermatic cord, Minerva Chir. 29: 156 (1974). ROUVIERE, H.: Anatomy of the Human Lymphatic System, Ann Arbor, Michigan, Edward Brackers, Inc., 1938. D’AGOSTINO, A. N., SOULE, E. H., and MILI.ER, R. H.: Sarcomas of the peripheral nerves and somatic soft tissues associated with multiple neurofibromatosis (von Recklinghausen’s disease), Cancer 16: 1015 (1963). IDEM: Primary malignant neoplasms of nerves (malignant neurilemomas) in patients without manifestations of multiple neurofibromatosis (von Recklinghausen’s disease), ibid. 16: 1003 (1963).
683