THE JOURNAL OF UROLOGY
Vol. 115, March Printed in U.S.A.
Copyright© 1976 by The Williams & Wilkins Co.
Letter to the Editor RE: ADULT TERATOMA OF THE TESTIS METASTASIZING AS ADULT TERATOMA: CASE REPORT AND REVIEW OF LITERATURE
Kai/ash Kedia and Elwin E. Fraley J. Urol., 114: 636-639, 1975
To the Editor. In the article by Kedia and Fraley it is stated that "the benign-appearing components of these tumors have malignant potential". 1 However, if we look to the murine counterpart of the human testicular teratoma, which was first described in strain 129 mice by Stevens, 2 we have good biological evidence that this statement is probably incorrect. The mouse testis tumor begins as an intratubular proliferation of undifferentiated or embryonal carcinoma cells that arise from the germ cell line. 3 • ' As the tumor enlaFges and bursts out into the interstitium it begins to differentiate and it is wholly differentiated in time, a true teratoma (the term adult teratoma is unnecessary and confusing if the term teratocarcinoma is reserved for teratomas containing undifferentiated embryonal carcinoma cells). Transplantable tumors and a few tissue culture lines have been derived from these primary tumors and they exhibit the whole spectrum of histology in vivo, ranging from totally undifferentiated embryonal carcinomas to completely differentiated or benign teratomas. 5 The elegant experiments of Pierce demonstrate that the embryonal carcinoma cell is the progenitor of the differentiated tissues and the tumor will not grow and cannot be transplanted without the persistence of these cells.• Therefore, we have information that may be extrapolated to the human, suggesting that the so-called adult teratoma is the differentiated product of embryonal carcinoma and that without the presence of these undifferentiated cells at some time, growth and metastases cannot occur. Complete differentiation may occur spontaneously, during chemotherapy or with radiotherapy, at which time the tumor is truly benign. If we consider a histological section of a testis tumor as one frame from a moving picture, the case reported can be explained in 2 ways. First, a microscopic focus of embryonal carcinoma may have been present in the primary tumor and was not ruled out by step sections. Second, prior to therapy a focus of embryonal carcinoma was present which metastasized and then fully differentiated and stopped growing. The corollary to the second and more intellectually appealing explanation is that the predisposition to fully differentiate was also present in the metastatic tumor and by the time of retroperitoneal lymph node dissection, no malignant embryonal carcinoma cells remained. If that differentiation in this situation is irreversible the statement that adult teratoma components per se have malignant potential would be incorrect. Of course we can never be sure clinically that all cells in a tumor are fully differentiated to justify managing a case of teratoma as benign disease and these biological phenomena observed in the mouse are yet to be clearly demonstrated in the human. We certainly hope that Hartmann's statement at the end of the article, "Conceptually, there will probably never be an end to discussions of the teratoid nature of testicular germinal tumors," is not truly prophetic and we will accumulate the necessary information about human tumors to tailor therapy for
342
each individual tumor on the basis of its own unique capacity for differentiation. Respectfully, Michael A. S. Jewett and Willet F. Whitmore, Jr. Memorial Sloan-Kettering Cancer Center New York, New York 1. Kedia, K. and Fraley, E. E.: Adult teratoma of the testis metastasizing as adult teratoma: case report and review of literature. J. Urol., 114: 636, 1975. 2. Stevens, L. C.: The biology of teratomas. Adv. Morph., 6: 1, 1967. 3. Mount, B. M. and Stevens, L. C.: The early natural history of murine germinal testicular tumors. J. Urol., 105: 812, 1971. 4. Stevens, L. C.: Origin of testicular teratomas from primordial germ cells in mice. J. Nat. Cancer Inst., 38: 549, 1967. 5. Damjanov, I. and Solter, D.: Experimental teratoma. Curr. Top. Path., 59: 69, 1974. 6. Pierce, G. B.: Teratocarcinoma: model for a developmental concept of cancer. Curr. Top. Develop. Biol., 2: 223, 1967.
Reply by authors. The above letter begins by quoting our article out of context. The sentence cited partially actually read, "This case suggests that even the benign appearing components have malignant potential". The sentence did not imply a firm conclusion on our part but was merely intended to offer a possible explanation of the findings in our case. We agree that the histologically benign retroperitoneal metastases reported in our case may have represented a metastasis from a more malignant focus in the primary tumor, which then became more differentiated once it arrived in the retroperitoneal node. In support of this possibility is recent evidence to the effect that the mouse teratocarcinoma of the testis can differentiate to a more benign cell, depending upon the environment in which it is placed. 1• 2 However, it is also possible that the so-called benign appearing elements of human adult teratoma may themselves have malignant potential and may have the biological capacity to metastasize. The mouse teratocarcinoma model is found only in inbred mice and no similar tumor occurs in higher animals. We would agree with Stevens who, in one of the first reports describing this tumor, emphasized that it would be unwise to draw any conclusions from this model with respect to human teratocarcinoma of the testis. 3 In closing we would like to focus this discussion on what we believe is the most important clinical point related to adult teratoma of the testis-namely, that these tumors should never be considered benign and that the appellation 'benign teratoma' should not be used in describing these neoplasms. Based on our own experiences, the experiences related to us by other urologists who have treated similar cases and the literature adult teratomas have malignant potential and should be treated accordingly. 1. Papaioannou, V. E., McBurney, M. W., Gardner, R. L. and Evans,
M. J.: Fate of teratocarcinoma cells injected into early mouse embryos. Nature, 258: 70, 1975. 2. Brinster, R. L.: The effect of cells transferred into the mouse blastocyst on subsequent development. J. Exp. Med., 140: 1049, 1974. 3. Stevens, L. C.: The history of teratomas. Adv. Morph., 6: 1, 1967.
Vol. 115, March Printed in U.S.A.
Copyright© 1976 by The Williams & Wilkins Co.
Letter to the Editor RE: ADULT TERATOMA OF THE TESTIS METASTASIZING AS ADULT TERATOMA: CASE REPORT AND REVIEW OF LITERATURE
Kai/ash Kedia and Elwin E. Fraley J. Urol., 114: 636-639, 1975
To the Editor. In the article by Kedia and Fraley it is stated that "the benign-appearing components of these tumors have malignant potential". 1 However, if we look to the murine counterpart of the human testicular teratoma, which was first described in strain 129 mice by Stevens, 2 we have good biological evidence that this statement is probably incorrect. The mouse testis tumor begins as an intratubular proliferation of undifferentiated or embryonal carcinoma cells that arise from the germ cell line. 3 • ' As the tumor enlaFges and bursts out into the interstitium it begins to differentiate and it is wholly differentiated in time, a true teratoma (the term adult teratoma is unnecessary and confusing if the term teratocarcinoma is reserved for teratomas containing undifferentiated embryonal carcinoma cells). Transplantable tumors and a few tissue culture lines have been derived from these primary tumors and they exhibit the whole spectrum of histology in vivo, ranging from totally undifferentiated embryonal carcinomas to completely differentiated or benign teratomas. 5 The elegant experiments of Pierce demonstrate that the embryonal carcinoma cell is the progenitor of the differentiated tissues and the tumor will not grow and cannot be transplanted without the persistence of these cells.• Therefore, we have information that may be extrapolated to the human, suggesting that the so-called adult teratoma is the differentiated product of embryonal carcinoma and that without the presence of these undifferentiated cells at some time, growth and metastases cannot occur. Complete differentiation may occur spontaneously, during chemotherapy or with radiotherapy, at which time the tumor is truly benign. If we consider a histological section of a testis tumor as one frame from a moving picture, the case reported can be explained in 2 ways. First, a microscopic focus of embryonal carcinoma may have been present in the primary tumor and was not ruled out by step sections. Second, prior to therapy a focus of embryonal carcinoma was present which metastasized and then fully differentiated and stopped growing. The corollary to the second and more intellectually appealing explanation is that the predisposition to fully differentiate was also present in the metastatic tumor and by the time of retroperitoneal lymph node dissection, no malignant embryonal carcinoma cells remained. If that differentiation in this situation is irreversible the statement that adult teratoma components per se have malignant potential would be incorrect. Of course we can never be sure clinically that all cells in a tumor are fully differentiated to justify managing a case of teratoma as benign disease and these biological phenomena observed in the mouse are yet to be clearly demonstrated in the human. We certainly hope that Hartmann's statement at the end of the article, "Conceptually, there will probably never be an end to discussions of the teratoid nature of testicular germinal tumors," is not truly prophetic and we will accumulate the necessary information about human tumors to tailor therapy for
342
each individual tumor on the basis of its own unique capacity for differentiation. Respectfully, Michael A. S. Jewett and Willet F. Whitmore, Jr. Memorial Sloan-Kettering Cancer Center New York, New York 1. Kedia, K. and Fraley, E. E.: Adult teratoma of the testis metastasizing as adult teratoma: case report and review of literature. J. Urol., 114: 636, 1975. 2. Stevens, L. C.: The biology of teratomas. Adv. Morph., 6: 1, 1967. 3. Mount, B. M. and Stevens, L. C.: The early natural history of murine germinal testicular tumors. J. Urol., 105: 812, 1971. 4. Stevens, L. C.: Origin of testicular teratomas from primordial germ cells in mice. J. Nat. Cancer Inst., 38: 549, 1967. 5. Damjanov, I. and Solter, D.: Experimental teratoma. Curr. Top. Path., 59: 69, 1974. 6. Pierce, G. B.: Teratocarcinoma: model for a developmental concept of cancer. Curr. Top. Develop. Biol., 2: 223, 1967.
Reply by authors. The above letter begins by quoting our article out of context. The sentence cited partially actually read, "This case suggests that even the benign appearing components have malignant potential". The sentence did not imply a firm conclusion on our part but was merely intended to offer a possible explanation of the findings in our case. We agree that the histologically benign retroperitoneal metastases reported in our case may have represented a metastasis from a more malignant focus in the primary tumor, which then became more differentiated once it arrived in the retroperitoneal node. In support of this possibility is recent evidence to the effect that the mouse teratocarcinoma of the testis can differentiate to a more benign cell, depending upon the environment in which it is placed. 1• 2 However, it is also possible that the so-called benign appearing elements of human adult teratoma may themselves have malignant potential and may have the biological capacity to metastasize. The mouse teratocarcinoma model is found only in inbred mice and no similar tumor occurs in higher animals. We would agree with Stevens who, in one of the first reports describing this tumor, emphasized that it would be unwise to draw any conclusions from this model with respect to human teratocarcinoma of the testis. 3 In closing we would like to focus this discussion on what we believe is the most important clinical point related to adult teratoma of the testis-namely, that these tumors should never be considered benign and that the appellation 'benign teratoma' should not be used in describing these neoplasms. Based on our own experiences, the experiences related to us by other urologists who have treated similar cases and the literature adult teratomas have malignant potential and should be treated accordingly. 1. Papaioannou, V. E., McBurney, M. W., Gardner, R. L. and Evans,
M. J.: Fate of teratocarcinoma cells injected into early mouse embryos. Nature, 258: 70, 1975. 2. Brinster, R. L.: The effect of cells transferred into the mouse blastocyst on subsequent development. J. Exp. Med., 140: 1049, 1974. 3. Stevens, L. C.: The history of teratomas. Adv. Morph., 6: 1, 1967.
