Medical and Pediatric Oncology 6:235-242 (1979)
Teratomas in Children and Young Adults Dorothy J. Ganick, MD, Enid F. Gilbert, MD, and John M. Opitz, MD From the Departments of Pediatrics (D.J.G.), Pathology (E.F.G.) and Genetics (J.M.O.), University of Wisconsin Center for Health Sciences, Madison
A review of all teratomas seen at the University of Wisconsin Hospital between
1965 and 1977 revealed that sacrococcygeal and presacral teratomas were most common. In these cases survival was best in infants less than one year old, with the exception of two cases of malignant medulloepithelioma. Testicular teratomas were predominant in the young adult male, and survival was poor. Pathology and treatment of teratqmas are discussed, with an accompanying discussion of congenital anomalies associated with teratomas. Key words: saaococcygeal teratoma, medulloepitheliomata teratocarcinoma
INTRODUCTION
Teratomas are a group of congenital dysplasias composed of tissues from all three germ layers. They are true neoplasms in that they exhibit some degree of aggressive, uncoordinated growth. We report our experience with teratomas in children followed at the University of Wisconsin Hospital over a 12-year period. PATIENT MATERIAL
Twenty cases of teratoma were seen from 1965 to 1977; 14 cases (70%) males, six cases (30%)females. The clinical histories of these cases are reviewed and summarized. RESULTS Sacrococcygeal and Presacral Teratomas
Table I lists ten cases of sacrococcygeal and presacral teratomas. Of six patients less than six months of age, five had visible sacrococcygeal masses, and one had a presacral tumor protruding from the rectum. To date, two of these patients have died, one male and one female, both of whom at birth had multiple masses extending from the sacrococcygeal area down the thigh and lower leg. Initial biopsies showed benign teratoma with neuroectodermal components, and later biopsies revealed malignant medulloepithelioma.
Address reprint requests to Dorothy J. Ganick, MD,University of Wisconsin, Clinical Science Center, Room H4/432,600Highland Avenue, Madison, WI 53792.
0098-1532/79/6030-0235$1.70 0 1979 Alan
R. Liss, Inc.
5 days
3 months
6 months
12 months
3% years
16 nionths
1 year
JB
cw
ss
J LP
DD
RB
DS
NED = no evidence of disease.
Birth
EK
Sacrococcygeal, perineal, limb mass, malignant medulloepithelioma Presacral, predominantly cystic benign teratonia Presacral, yolk sac carcinoma Presacral, malignant embryonal carcinoma Presacral, malignant embryonal carcinoma
Uncle with imperforate anus
Comments
Died at 25 months Pulmonary metastases at diagnosis
Multiple anomaly syndrome with 46 G/G translocation NED (3+ years) Sib died of myelomeningocele; patient has large head Died at 21 months Incomplete surgical removal
NED (6+ years)
Multiple anomalies, ambiguous genitalia, partial absence of left leg, imperforate anus, myelocele, sacral dysplasia Died at 14 months Anal stenesis
Sacrococcygeal, predomi- NED (7+ years) nantly cystic benign teratoma Sacrococcygeal, perineal, Died at 9 months limb mass, malignant medulloepi thelioma
Presacral, predominantly cystic benign teratoma Sacrococcygeal, predomi- NED (last follownantly cystic benign up 1% years) tera toma
4.5 months
No evidence of disease (NED) (5+ years) NED (lo+ years)
I:ollow-up
MS
Type and pathology Sacrococcygeal, benign teratoma
Age a t diagnosis
2 days
Sex
JK
Patient
TABLE 1. Sacrococcyneal and Presacral Tumors
N
0
z.
E
V
OI
W
h)
Teratomas in Children and Adults
237
All patients older than one year had presacral tumors. Of these, one was found during repair of an imperforate anus and the other three were found in children with symptoms of urinary incontinence and constipation. Two children in this group died, and the other two are alive without evidence of tumor. Congenital anomalies particularly related to the long axis were common in the children less than one year of age, with three having multiple anomalies. Patient CW had ambiguous genitalia, imperforate anus, sacral dysplasia, myelocele, and partial absence of the left leg. Patient JLP also had multiple anomalies, which included imperforate anus, dislocation of the hips, and abnormal facies. Chromosome analysis revealed 46 C/C translocation Down syndrome. Patient SS had anal stenosis and multifocal sacral and limb masses. In addition, two patients had a family history of congenital anomalies of the long axis. Patient DD’s enlarged head suggested arrested hydrocephalus; he had a sib who died of myelomeningocele. Patient JK, appears to have the autosomal dominant trait of presacral teratoma and anal stenosis as described by Ashcraft and Holder [ 11 . He had an uncle with imperforate anus. No family history of twinning was found in our cases, and no patient was a twin. Pathology in the four surviving cases of sacrococcygeal teratomas in infants less than six months old showed elements from all three germ layers, with multiple cystic areas prominent in patients MS, EK, and JB. (Fig. 1). Patients CW and SS,who did not survive, had neuroectodermal elements in their original biopsies. Patient CW had prominent neuroepithelial elements in the original biopsy as well as other benign teratomatous structures, including ciliated epithelium of endodermal origin. The original biopsy from patient SS showed hematomas with neuroectodermal elements. Both patients showed malignant medullo-
Fig. 1. Microscopic appearance of focus of benign teratoma showing ductal structures lined by respirationtype epithelium in a mesenchymal stroma.
238
Ganick. Gilbert, and Opitz
Fig. 2. Microscopic appearance of medulloepitheliomatous elements resembling epithelium of ependymal type.
Fig. 3. Microscopic appearance of polyvitelline pattern seen in yolk sac tumor as component of a malignant teratoma.
Teratornas in Children and Adults
239
epithileomatous elements (Fig. 2) on repeat biopsy. CW and SS are reported in detail elsewhere [2]. Patient DD had a pure yolk sac tumor of extragonadal origin (Fig. 3). Patient RB also had elements of a yolk sac tumor as well as embryonal carcinoma. Several cases with malignant tumors were treated with chemotherapy and radiotherapy. Only one patient, DD, with a typical yolk sac tumor and without evidence of metastases at diagnosis responded to an aggressive regimen of radiotherapy and chemotherapy. In spite of the poor survival rate generally associated with these kinds of tumors [3], DD is doing well almost three years after diagnosis. Palliative radiotherapy did not affect the course of patient SS with multiple medulloepitheliomata. Combined radiotherapy and chemotherapy with actinomycin, methotrexate, and chlorambucil did not affect the course in patient DS, who had a presacral teratoma and evidence of lung metastases at diagnosis. Chemotherapy with vincristine, cyclophosphamide, and actinomycin was used in patient RB, who had no evidence of metastases at diagnosis at age 16 months. There was no effect on the course of her disease. Testicular Teratomas
Testicular teratomas were found in young adults (Table 11). Six patients died of the tumor; in these cases the tumors were metastatic at diagnosis. The patient who did not have metastases at diagnosis is alive and well more than six years after diagnosis. Chemotherapy with various agents, including actinomycin, cyclophosphamide, bleomycin, and Cis-platinum, was used in all cases, and radiotherapy was used in some. There was n o history of inguinal hernia or cryptorchidism in any of these patients. Ovarian Teratomas
Two young girls had ovarian teratoma with metastases at diagnosis (Table 11). One of the patients, who was treated with chemotherapy, which included actinomycin, cytoxan, bleomycin, and Cis-platinum, as well as radiotherapy, is alive with multiple metastases. Another patient was recently diagnosed and is being treated with vincristine, actinomycin, and cyclophosphamide and radiotherapy. Both patients had total abdominal hysterectomies as the primary surgical treatment. Other Teratoma
One case of chest wall teratoma with choriocarcinoma elements did not respond to surgical debulking; chemotherapy with methotrexate, actinomycin, and chlorambucil; and localized radiotherapy (Table 11). He died 37 months after diagnosis. DISCUSSION
Of twenty teratoma cases seen at our institution over the past 12 years, half were presacral and sacrococcygeal tumors. In adults, teratomas are more frequently located in the gonads; contrastingly, in children about two-thirds of all cases are sacrococcygeal teratomas and involve other sites less frequently [4] . Generally, the presacral location has the greatest potential for malignancy [ 5 , 6 ] .However, not all investigators have found presacral tumors to have an increased malignant potential [ 7 , 8 ] . In our series, three of five cases with presacral lesions are alive without evidence of disease many years after diagnosis. The origin of teratomas has been the subject of many theories. One theory holds that primordial germ cells originate in the yolk sac endoderm. During migration from the yolk
I:ollow-up
Teratocarcinoma (embryonal). well differentiated. of riaht testicle
19
20
18
19
18
17
14
10
DH
MK
RB TVL
LRK
ws
CL
JK
Died 2 years after diagnosis
Died 8 months after diagnosis Died 4 years after diagnosis
Chest teratoma with choriocarcinoma elements
Teratocarcinoma (embryonal) of right ovary
Teratocarcinoma (embryonal) of right ovary
Died 37 months after diagnosis
Other
Alive with inultiple metastases 3+ years after diagnosis On treatment, follow-up NED ( 2 years after diarnosis)
Advanced bone age, precocious puberty at diagnosis
Total abdominal hysterectomy
Total abdominal hysterectomy
Retroperitoneal nodes negative at diagnosis Local recurrence at 1 year pulmonary metastases 3 years after diagnosis Pulmonary metastases at diagnosis Retroperitoneal nodes positive at diagnosis Cervical and retroperitoneal nodes positive at diagnosis
NED (3+ years after diagnosis) Progression of disease -alive 5+ years after diagnosis
Ovarian Teratonias
Teratocarcinoma (embryonal) Teratocarcinoma (embryonal)
16
RM
Positive retroperitoneal nodes at diagnosis Pulmonary metastases at diagnosis
Comments
Died 26 months after diagnosis Died 5 months
Testicular Teratomas Teratocarcinoma (embryonal) and seminoma of right testicle Teratocarcinoma (embryonal) right testicle Tcratocarcinoma and seminoma of right testicle Teratocarcinoma (embryonal)
Pathology
20
Age at diagnosis
SM
Patient
TABLE 11. Testicular, Ovarian, and Other Teratomas
d
N
-
0
3. ..
sr
t. 0
a-
P 0
N
Teratomas in Children and Adults
24 1
sac on the way t o the gonads, these cells may become widely disseminated through the embryo and lodged in extragonadal sites. A recent study by Linder et a1 [9] showed that ovarian tumors are parthogenetic in origin; that is, they arise from a single germ cell which has undergone recombination in meiosis. On the other hand, extragonadal teratomas showed the same chromosome and enzyme patterns as normal host tissue, indicating origin from mitotic cell division [ 1 ] ). In our series defects related t o the long axis of the body, particularly the anorectal area, were associated with sacrococcygeal teratomas. This observation has been reported in other series [4,7, 1 I ] . In a review of 9 6 cases of teratoma, Berry et al found an increased incidence of major malformations, including anomalies of the cloaca1 area such as imperforate anus and rectovaginal fistula [7] .They hypothesized that these malformations were related t o local growth effect by the tumor. Contrastingly, in a comprehensive discussion of our patients SS and CW, who had malignant presacral tumors with associated limb malformations, DurkinStam et al concluded that neoplastic tissue interfered with morphogenesis in the region of the cloaca and limb bud [2]. Similarly, Fraumeni et al found an increased incidence of pelvic anomalies in female patients with sacrococcygeal teratomas; they attributed this to a primary embryopathic process affecting cells contributing to the structures along the long axis rather than to a tumor growth effect [ 121. The tumors in two of our patients with neural crest elements in their original biopsies were interpreted as benign teratomas. However, follow-up biopsies several months later in these two patients revealed the tumors to be malignant medulloepithelioma. Several reports emphasize that teratomas with neurologil elements do not undergo malignant transformation. Our two cases are unique since the usual malignant component in a teratoma is embryonal or yolk sac carcinoma, not medulloepithelioma. Controversy surrounds the hypothesis that earlier removal of teratoma will decrease the incidence of malignancy. Many reports emphasize that the earlier the removal of the teratoma, the less likely it will be that malignant transformation will occur; the incidence of malignancy increases if teratomas are operated on later than age two months [4, 131. However, Donnelan and Swenson reported that two-thirds of 27 teratomas operated on later than four months of age were benign [ 141 .They believe that if malignant potential is initially present in a teratoma, early operation does not prevent development of malignancy. A limited number of our patients with malignant teratoma received chemotherapy, radiotherapy, and surgery. Few patients with malignant sacrococcygeal teratomas have been successfully treated with multiple drug chemotherapy and radiotherapy [4, 141 . However, one patient in our series presented with a presacral teratoma with yolk sac components a t age three years. This patient was treated with pelvic irradiation and chemotherapy with vincristine, cyclophosphamide, and astinomycin as per a rhabdomyosarcoma protocol [ 151. This patient is alive and well more than three years after diagnosis. Two other patients with malignant sacrococcygeal teratomas received multiple drug chemotherapy, which did not affect their clinical course. Survival in the group with testicular teratomas was poor despite radiation and chemotherapy. Li and Fraumeni reported a 2 1% incidence of inguinal hernia, undescended testes, and other genitourinary defects in patients with testicular teratomas [ 161. There were no cryptochidism or hernias in our patients. Only two cases of ovarian teratoma were present in our series, whereas other investigators of childhood teratomas reported a 12% incidence [ 4 , 5 ] . Both of our patients had metastases at diagnosis. One girl received long-term palliation with chemotherapy, with many different agents, and the other patient is too recently diagnosed to predict outcome.
242
Ganick, Gilbert, and Opitz
The chest wall teratoma with choriocarcinomatous elements was fatal despite radiotherapy and chemotherapy. This child had a precocious puberty. probably related t o the chorioNc gonadotropin produced by the tumor. Grosfield et al studied two children with malignant mediastinal tumors who had not received adjunctive therapy; both died [4]. REFERENCES 1. Ashcraft KW, Holdes TM: Hereditary presacral teratoma. J Pediatr Surg 9:691-697, 1974. 2. Durkin-Stamm V , Gilbert EF, Ganick DJ, Opitz JM: An unusual dysplasia-malformation-cancer syndrome in two patients. Am J Med Genet (in press). 3. Huntington RW. Bullock WK: Yolk sac tumors of estragonadal origin. Cancer 25:1368-1376, 1970. 4. Grosfield JL, Ballantine TVN, Lowe D, e t al: Benign and malignant teratoma in children: Analysis of 85 patients. Surgery 80:297-304, 1976. 5. Bale PM, Painter DM, Cohen D: Teratomas in childhood. Pathology 7:209-218, 1975. 6. Gilbert EF: Clinical pathological delineations of teratomas in childhood. In Ghai OP (ed): “New Developments in Pediatric Research,” vol 3. XV International Congress of Pediatrics, New Delhi, lndia, 1977, pp 1201-1204. 7. Berry CL. Keeling J , Hilton C: Coincidence o f congenital malformation and embryonic tumors of childhood. Arch DisChild 45:229-231, 1970. 8. Malhour GH. Woolley MM, Trivedi SN, Landing BH: Teratomas in infancy and childhood: Experience with 81 cases. Surgery 76:309-318, 1974. 9. Linder D, McCaw BK, Hecht F: Pathogenetic origin of benign ovarian teratomas. N Engl J Med 292:63-66, 1975. 10. Hecht F, McCaw BK: Dissimilar origin o f ovarian vs estragonadal teratomas (abstract). Teratology 15:13A, 1977. 11. Hicky RC, Layton JM: Sacrococcygeal teratoma. Cancer 7:1031-1043, 1954. 12. Fraumeni JF, Li FP. Dalager N : Teratomas in children: Epidemiologic features. J Nat Cancer lnst 31:1425- 1430,1973. 13. Izant RJ. Filston HC: Sacrococcygeal teratomas: Analysis of forty-three cases. Am J Surg 130: 617-621, 1975. 14. Donnellan WA, Swenson P: Benign and malignant sacrococcygeal teratomas. Surgery 64:834-846.1%8 15. Maurer HM, Moon T. Donaldson M. Fernandez C, et al: The intergroup rhabdomyosarcoma study. Cancer 40:2015-2026, 1977. 16. Li FP, Fraumeni JF: Testicular cancers in children: Epidemiologic characteristics. J Natl Cancer lnst 48:1575-1581, 1972.
Teratomas in Children and Young Adults Dorothy J. Ganick, MD, Enid F. Gilbert, MD, and John M. Opitz, MD From the Departments of Pediatrics (D.J.G.), Pathology (E.F.G.) and Genetics (J.M.O.), University of Wisconsin Center for Health Sciences, Madison
A review of all teratomas seen at the University of Wisconsin Hospital between
1965 and 1977 revealed that sacrococcygeal and presacral teratomas were most common. In these cases survival was best in infants less than one year old, with the exception of two cases of malignant medulloepithelioma. Testicular teratomas were predominant in the young adult male, and survival was poor. Pathology and treatment of teratqmas are discussed, with an accompanying discussion of congenital anomalies associated with teratomas. Key words: saaococcygeal teratoma, medulloepitheliomata teratocarcinoma
INTRODUCTION
Teratomas are a group of congenital dysplasias composed of tissues from all three germ layers. They are true neoplasms in that they exhibit some degree of aggressive, uncoordinated growth. We report our experience with teratomas in children followed at the University of Wisconsin Hospital over a 12-year period. PATIENT MATERIAL
Twenty cases of teratoma were seen from 1965 to 1977; 14 cases (70%) males, six cases (30%)females. The clinical histories of these cases are reviewed and summarized. RESULTS Sacrococcygeal and Presacral Teratomas
Table I lists ten cases of sacrococcygeal and presacral teratomas. Of six patients less than six months of age, five had visible sacrococcygeal masses, and one had a presacral tumor protruding from the rectum. To date, two of these patients have died, one male and one female, both of whom at birth had multiple masses extending from the sacrococcygeal area down the thigh and lower leg. Initial biopsies showed benign teratoma with neuroectodermal components, and later biopsies revealed malignant medulloepithelioma.
Address reprint requests to Dorothy J. Ganick, MD,University of Wisconsin, Clinical Science Center, Room H4/432,600Highland Avenue, Madison, WI 53792.
0098-1532/79/6030-0235$1.70 0 1979 Alan
R. Liss, Inc.
5 days
3 months
6 months
12 months
3% years
16 nionths
1 year
JB
cw
ss
J LP
DD
RB
DS
NED = no evidence of disease.
Birth
EK
Sacrococcygeal, perineal, limb mass, malignant medulloepithelioma Presacral, predominantly cystic benign teratonia Presacral, yolk sac carcinoma Presacral, malignant embryonal carcinoma Presacral, malignant embryonal carcinoma
Uncle with imperforate anus
Comments
Died at 25 months Pulmonary metastases at diagnosis
Multiple anomaly syndrome with 46 G/G translocation NED (3+ years) Sib died of myelomeningocele; patient has large head Died at 21 months Incomplete surgical removal
NED (6+ years)
Multiple anomalies, ambiguous genitalia, partial absence of left leg, imperforate anus, myelocele, sacral dysplasia Died at 14 months Anal stenesis
Sacrococcygeal, predomi- NED (7+ years) nantly cystic benign teratoma Sacrococcygeal, perineal, Died at 9 months limb mass, malignant medulloepi thelioma
Presacral, predominantly cystic benign teratoma Sacrococcygeal, predomi- NED (last follownantly cystic benign up 1% years) tera toma
4.5 months
No evidence of disease (NED) (5+ years) NED (lo+ years)
I:ollow-up
MS
Type and pathology Sacrococcygeal, benign teratoma
Age a t diagnosis
2 days
Sex
JK
Patient
TABLE 1. Sacrococcyneal and Presacral Tumors
N
0
z.
E
V
OI
W
h)
Teratomas in Children and Adults
237
All patients older than one year had presacral tumors. Of these, one was found during repair of an imperforate anus and the other three were found in children with symptoms of urinary incontinence and constipation. Two children in this group died, and the other two are alive without evidence of tumor. Congenital anomalies particularly related to the long axis were common in the children less than one year of age, with three having multiple anomalies. Patient CW had ambiguous genitalia, imperforate anus, sacral dysplasia, myelocele, and partial absence of the left leg. Patient JLP also had multiple anomalies, which included imperforate anus, dislocation of the hips, and abnormal facies. Chromosome analysis revealed 46 C/C translocation Down syndrome. Patient SS had anal stenosis and multifocal sacral and limb masses. In addition, two patients had a family history of congenital anomalies of the long axis. Patient DD’s enlarged head suggested arrested hydrocephalus; he had a sib who died of myelomeningocele. Patient JK, appears to have the autosomal dominant trait of presacral teratoma and anal stenosis as described by Ashcraft and Holder [ 11 . He had an uncle with imperforate anus. No family history of twinning was found in our cases, and no patient was a twin. Pathology in the four surviving cases of sacrococcygeal teratomas in infants less than six months old showed elements from all three germ layers, with multiple cystic areas prominent in patients MS, EK, and JB. (Fig. 1). Patients CW and SS,who did not survive, had neuroectodermal elements in their original biopsies. Patient CW had prominent neuroepithelial elements in the original biopsy as well as other benign teratomatous structures, including ciliated epithelium of endodermal origin. The original biopsy from patient SS showed hematomas with neuroectodermal elements. Both patients showed malignant medullo-
Fig. 1. Microscopic appearance of focus of benign teratoma showing ductal structures lined by respirationtype epithelium in a mesenchymal stroma.
238
Ganick. Gilbert, and Opitz
Fig. 2. Microscopic appearance of medulloepitheliomatous elements resembling epithelium of ependymal type.
Fig. 3. Microscopic appearance of polyvitelline pattern seen in yolk sac tumor as component of a malignant teratoma.
Teratornas in Children and Adults
239
epithileomatous elements (Fig. 2) on repeat biopsy. CW and SS are reported in detail elsewhere [2]. Patient DD had a pure yolk sac tumor of extragonadal origin (Fig. 3). Patient RB also had elements of a yolk sac tumor as well as embryonal carcinoma. Several cases with malignant tumors were treated with chemotherapy and radiotherapy. Only one patient, DD, with a typical yolk sac tumor and without evidence of metastases at diagnosis responded to an aggressive regimen of radiotherapy and chemotherapy. In spite of the poor survival rate generally associated with these kinds of tumors [3], DD is doing well almost three years after diagnosis. Palliative radiotherapy did not affect the course of patient SS with multiple medulloepitheliomata. Combined radiotherapy and chemotherapy with actinomycin, methotrexate, and chlorambucil did not affect the course in patient DS, who had a presacral teratoma and evidence of lung metastases at diagnosis. Chemotherapy with vincristine, cyclophosphamide, and actinomycin was used in patient RB, who had no evidence of metastases at diagnosis at age 16 months. There was no effect on the course of her disease. Testicular Teratomas
Testicular teratomas were found in young adults (Table 11). Six patients died of the tumor; in these cases the tumors were metastatic at diagnosis. The patient who did not have metastases at diagnosis is alive and well more than six years after diagnosis. Chemotherapy with various agents, including actinomycin, cyclophosphamide, bleomycin, and Cis-platinum, was used in all cases, and radiotherapy was used in some. There was n o history of inguinal hernia or cryptorchidism in any of these patients. Ovarian Teratomas
Two young girls had ovarian teratoma with metastases at diagnosis (Table 11). One of the patients, who was treated with chemotherapy, which included actinomycin, cytoxan, bleomycin, and Cis-platinum, as well as radiotherapy, is alive with multiple metastases. Another patient was recently diagnosed and is being treated with vincristine, actinomycin, and cyclophosphamide and radiotherapy. Both patients had total abdominal hysterectomies as the primary surgical treatment. Other Teratoma
One case of chest wall teratoma with choriocarcinoma elements did not respond to surgical debulking; chemotherapy with methotrexate, actinomycin, and chlorambucil; and localized radiotherapy (Table 11). He died 37 months after diagnosis. DISCUSSION
Of twenty teratoma cases seen at our institution over the past 12 years, half were presacral and sacrococcygeal tumors. In adults, teratomas are more frequently located in the gonads; contrastingly, in children about two-thirds of all cases are sacrococcygeal teratomas and involve other sites less frequently [4] . Generally, the presacral location has the greatest potential for malignancy [ 5 , 6 ] .However, not all investigators have found presacral tumors to have an increased malignant potential [ 7 , 8 ] . In our series, three of five cases with presacral lesions are alive without evidence of disease many years after diagnosis. The origin of teratomas has been the subject of many theories. One theory holds that primordial germ cells originate in the yolk sac endoderm. During migration from the yolk
I:ollow-up
Teratocarcinoma (embryonal). well differentiated. of riaht testicle
19
20
18
19
18
17
14
10
DH
MK
RB TVL
LRK
ws
CL
JK
Died 2 years after diagnosis
Died 8 months after diagnosis Died 4 years after diagnosis
Chest teratoma with choriocarcinoma elements
Teratocarcinoma (embryonal) of right ovary
Teratocarcinoma (embryonal) of right ovary
Died 37 months after diagnosis
Other
Alive with inultiple metastases 3+ years after diagnosis On treatment, follow-up NED ( 2 years after diarnosis)
Advanced bone age, precocious puberty at diagnosis
Total abdominal hysterectomy
Total abdominal hysterectomy
Retroperitoneal nodes negative at diagnosis Local recurrence at 1 year pulmonary metastases 3 years after diagnosis Pulmonary metastases at diagnosis Retroperitoneal nodes positive at diagnosis Cervical and retroperitoneal nodes positive at diagnosis
NED (3+ years after diagnosis) Progression of disease -alive 5+ years after diagnosis
Ovarian Teratonias
Teratocarcinoma (embryonal) Teratocarcinoma (embryonal)
16
RM
Positive retroperitoneal nodes at diagnosis Pulmonary metastases at diagnosis
Comments
Died 26 months after diagnosis Died 5 months
Testicular Teratomas Teratocarcinoma (embryonal) and seminoma of right testicle Teratocarcinoma (embryonal) right testicle Tcratocarcinoma and seminoma of right testicle Teratocarcinoma (embryonal)
Pathology
20
Age at diagnosis
SM
Patient
TABLE 11. Testicular, Ovarian, and Other Teratomas
d
N
-
0
3. ..
sr
t. 0
a-
P 0
N
Teratomas in Children and Adults
24 1
sac on the way t o the gonads, these cells may become widely disseminated through the embryo and lodged in extragonadal sites. A recent study by Linder et a1 [9] showed that ovarian tumors are parthogenetic in origin; that is, they arise from a single germ cell which has undergone recombination in meiosis. On the other hand, extragonadal teratomas showed the same chromosome and enzyme patterns as normal host tissue, indicating origin from mitotic cell division [ 1 ] ). In our series defects related t o the long axis of the body, particularly the anorectal area, were associated with sacrococcygeal teratomas. This observation has been reported in other series [4,7, 1 I ] . In a review of 9 6 cases of teratoma, Berry et al found an increased incidence of major malformations, including anomalies of the cloaca1 area such as imperforate anus and rectovaginal fistula [7] .They hypothesized that these malformations were related t o local growth effect by the tumor. Contrastingly, in a comprehensive discussion of our patients SS and CW, who had malignant presacral tumors with associated limb malformations, DurkinStam et al concluded that neoplastic tissue interfered with morphogenesis in the region of the cloaca and limb bud [2]. Similarly, Fraumeni et al found an increased incidence of pelvic anomalies in female patients with sacrococcygeal teratomas; they attributed this to a primary embryopathic process affecting cells contributing to the structures along the long axis rather than to a tumor growth effect [ 121. The tumors in two of our patients with neural crest elements in their original biopsies were interpreted as benign teratomas. However, follow-up biopsies several months later in these two patients revealed the tumors to be malignant medulloepithelioma. Several reports emphasize that teratomas with neurologil elements do not undergo malignant transformation. Our two cases are unique since the usual malignant component in a teratoma is embryonal or yolk sac carcinoma, not medulloepithelioma. Controversy surrounds the hypothesis that earlier removal of teratoma will decrease the incidence of malignancy. Many reports emphasize that the earlier the removal of the teratoma, the less likely it will be that malignant transformation will occur; the incidence of malignancy increases if teratomas are operated on later than age two months [4, 131. However, Donnelan and Swenson reported that two-thirds of 27 teratomas operated on later than four months of age were benign [ 141 .They believe that if malignant potential is initially present in a teratoma, early operation does not prevent development of malignancy. A limited number of our patients with malignant teratoma received chemotherapy, radiotherapy, and surgery. Few patients with malignant sacrococcygeal teratomas have been successfully treated with multiple drug chemotherapy and radiotherapy [4, 141 . However, one patient in our series presented with a presacral teratoma with yolk sac components a t age three years. This patient was treated with pelvic irradiation and chemotherapy with vincristine, cyclophosphamide, and astinomycin as per a rhabdomyosarcoma protocol [ 151. This patient is alive and well more than three years after diagnosis. Two other patients with malignant sacrococcygeal teratomas received multiple drug chemotherapy, which did not affect their clinical course. Survival in the group with testicular teratomas was poor despite radiation and chemotherapy. Li and Fraumeni reported a 2 1% incidence of inguinal hernia, undescended testes, and other genitourinary defects in patients with testicular teratomas [ 161. There were no cryptochidism or hernias in our patients. Only two cases of ovarian teratoma were present in our series, whereas other investigators of childhood teratomas reported a 12% incidence [ 4 , 5 ] . Both of our patients had metastases at diagnosis. One girl received long-term palliation with chemotherapy, with many different agents, and the other patient is too recently diagnosed to predict outcome.
242
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