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“Mixed” gonadal dysgenesis with gonadoblastoma in situ
“Mixed” gonadal dysgenesis with gonadoblastoma J.
TETER,
J.
PHILIP,
GR.
M.D. M.D.
WECEWICZ,
Warsaw, Copenhagen,
in situ
M.D.
Poland Denmark
T H E T E R M “mixed’ gonadal dysgenesis refers, according to Sohval,14 to the coexistence of a rudimentary, fibrous “streak” gonad on one side and a testis on the other. Bergada and associates1 named this condition asymmetrical gonadal differentiation. Such gonads are situated abdominally in the normal position of ovaries. Uterus and Fallopian tubes are present, but usually they are underdeveloped or rudimentary. Several such cases have been reported in the literature,lm4 but were not classified as “mixed gonadal dysgenesis,” which seems to be most appropriate.
“Mixed” gonadal dysgenesis has characteristics classified between chromatin-negative pure gonadal dysgenesis with typical bilateral streak gonads and male pseudohennaphroditism with bilateral testes. The accumulation of results of chromosome analysis in patients with intersexuality will in the future elucidate what is the prevalent type of karyotypes in the syndrome of mixed gonadal dysgenesis. A review of the literature shows that sex chromosome mosaicism of XO/XYl* or 46/XY’, ‘I’ may occur. It has previously been shown that malformed testes in intersexual conditions have a special tendency to neoplastic chan,ges.“, IF. I7 In genetic males, as determined by the presence of a Y-chromosome, the neoplasm may show the pattern of gonadoblastoma (gonocytoma III ) .? It is possible that the risk of malignancy in mixed gonadal dysgenesis is extraordinarily high, as the gonad contains dysgenetic, malformed seminiferous tubules with groups of gonocytes. Such tubules may have a biz-
From the Department of Endocrinology, First Clinic of Obstetrics and Gynaecology,’ Medical Academy in Warsaw, and University Department of Obstetrics and Gynaecology, Rigshospitalet, Copenhagen. This work was supported in part by Leo Pharmaceutical Products, The Danish State Research Foundation, The Danish Cancer Society, and The Danish Foundation for the Advancement of Medical Science. 929
930
Teter,
Philip,
and
Wegewicz
Gynecological examination showed pubic hair of male type spreading toward the inguinal rcgions and internal part of the thighs. The external genitah were feminine except for a large phallus, which in the flaccid state measured 6 by 2 cm. (Fig. 2). The labia minora were rather rudimentary. The labia majora were swollen and covered by wrinkled skin of scrotal appearance (Fig. 2, A). The urethra opened at the base of the phallus in the normal female position. The vagina admitted easily one finger and measured 8 cm. in depth. A thickening could be felt at the vaginal vault and this was identified as a cervix. Findings
Fig. 1. Eunuchoidsl body proportions with line features. (Patient K. J., aged 19.)
mascu-
zare form, which suggests bisexual formation, containing both ovarian and testicular elements. Case report Patient K. J., aged 19, was admitted to the Endocrinological-Outpatient Department because of primary amenorrhea, retardation of sexual development, and virilization. Symptoms of androgenic influence began at the age of 13 (hirsutism, acne, seborrhea, and hypertrophy of the clitoris). Reared as a woman, the patient exhibited the female type of psychosexual orientation. Physical examination revealed eunuchoidal body proportion with masculine features. There was no breast development (Fig. 1) .
Radiologic investigation. A hysterosalpingography showed a small, narrow, smoothwalled uterine cavity and patent Fallopian tubes. Laboratory investigations. The sex-chromatin pattern was negative. Cytologic examination of vaginal smears revealed lack of estrogenic activity. Hormonal assays showed that the urinary 17-ketosteroid output was within normal limits for women, 7.2 and 9.4 mg. per 24 hours. The 17-hydroxycorticoids were 3.4 and 4.7 mg. per 24 hours on consecutive days. Urinary excretion of estrogens was 43 fig and 61 pg per 24 hours (average limits for normal healthy women). The gonadotropin level was 40 mu. (normal limits for healthy women, 20 to 30 mu.). (The method of Klinefelter, as modified by Dekanski and Loraine Brown). Laparotomy. Laparotomy disclosed a fetal uterus and Fallopian tubes. On the left a typical dysgenetic whitish streak in the place normally occupied by the ovary was found. On the right, also in the location normally occupied by the ovary, a gonad resembling a testis was found. It measured 4 by 3 by 1 cm. and its surface was smooth and glistening. The right gonad was totally removed and a biopsy of the left gonadal streak was taken. Microscopic examination. The right gonad showed a typical testicular structure with remnants of the cortical part of the gonad. Tubules were small and lined with undif-
Volume Numbrr
90 7, part
Mixed
1
gonadal
dysgenesis
931
Fig. 2. A and with labia
B. External genitals a la] w ,hallus and swollen ma rjor of I rota1 appeal *ante.
Fig.
3
Fig. 3. Seminiferous nucleoli.
Fig. 4.
tubules lined with Sertoli cells and germ Tubular wall is thickened. Two different tubules with malignant changes in the upper
ferentiated Sertoli-like and germinal cells in a single row. The tubular wall was thickened with hyalinosis (Fig. 3). In a few very small areas the tubules were fiIled with immature Sertoli-granulosa-like cells intermixed with germ cells (Fig. 4). In several layers the Sertoli-granulosa cells were arranged in coronal fashion around individual germ cells or in a folliculoid arrangement surrounding eosinophilic bodies and in a single file along the periphery of the tubular contents (Fig. 5). The histologic alterations of the tubular contents showed a mild, but
cells
containing
very
active
one.
definite, degree of cellular anaplasia with variations in size and shape of the nucleus and hyperchromatism. These malignant features were observed both in germ cells and Sertoli-granulosa-like cells (Fig. 6) . Calcified concretions in form of psammoma-like bodies or calcified flecks were also seen within malignant nests (Fig. 7). All of the histologic changes clearly illustrate a gonadal neoplasm, which should be classified as gonocytoma III (gonadoblastoma). There was no sharp dividing line between the ty-pica1 tissue and the gonadoblastic testicular
932
Teter,
Philip,
and
Wegewicz
nests. These lesions were limited to very small microscopic areas within the testicular tubes and were diagnosed as “gonadoblastoma in situ.” Only in one place was the tubular wall ruptured and neoplastic cells
tended somewhat to invade the interstitial spaces (Fig. 6). The Leydig cells were numerous and situated between seminiferous tubules and also at the periphery of neoplastic nests (Fig. 5).
Fig. 5. Typical nest of gonadoblastoma within tubule. Folliculoid arrangement of Sertoli-granulosa type of cells and single germ cells scattered among them (arrozu.) In the upper right corner a group of Leydig cells is visible.
Fig. 7
Fig.
Fig. 6. Rupture of tubular wall clearly visible in lower left vasion by neoplastie cells (~~rroze) . Fig. 7. Typical malignant changes seen in group of germ Psammoma-like calcifications are seen on the left.
corner cells
with and
incipient Sertoli-granulosa
stromal
incells.
Volume Number
90 7,
part
Mixed
1
Fig. 8. Karyotype
from cell from peripheral
Microscopic study of the left streak gonad showed that it was composed of a connective ovarian-like fibrous tissue without any germinal elements. Chromosomal investigations. Chromosomal analysis (W4/79) was carried out on dividing cells from the peripheral blood and from skin. A modification of the method of Moorhead and associates7 for chromosomal preparation of leukocytes cultured from human peripheral blood was used. Venous blood was withdrawn and injected into a universal container with heparin. The container was sent by air in crushed ice to Copenhagen and 6 hours after the blood was taken the red cells were allowed to sediment by gravitation in the container. The plasma containing the leukocytes was pipetted off and a leukocyte count was made. The suspension was diluted 1:2 with culture medium 199 (Glaxo) and phytohemagglutinin, 0.1 ml. per 5 ml., was added. The mixture was incubated at 36.5’ C. for three and a half days. After 3 hours of treatment with demecolcine (final concentration of 0.1 ;dg per milliliter) the cells were treated with
gonadal
dysgenesis
933
blood.
hypotonic saline solution, fixed, spread on slides by the air drying technique,” stained with aceto-orcein, and mounted with euparal. Skin preparations were made as described by Philip and Teter.8 Chromosome counts were carried out on 30 cells in blood and 30 cells in skin. < 43 Blood Skin
1
43 1
44 7
45 3 ‘I.
46 24 36 -
47
Total 30 30
By structural analysis of 6 cells with 46 chromosomes, 3 from each tissue, the complement was found to be that of a normal male (Figs. 8 and 9). Comment
A review of the literature*-‘jp lz. “’ and clinicopathological findings from our own cases of gonadoblastoma show that all such patients have the following common features: 1. Abnormal somatosexual development in a patient reared as a woman with primary amenorrhea and some signs of masculinization.
934
Teter,
Fig.
9. Cell
Philip,
and
WeGewicz
in metaphase.
2. Negative sex-chromatin pattern and a female type of genitals. 3. High urinary gonadotropin excretion despite clinical and, sometimes, biochemical signs of sex-hormone activity (analogous with some cases of the syndrome of testicular feminization). The tumor is histologically characterized by the presence of characteristic neoplastic nests composed of germ cells scattered among Sertoli-granulosa cells. Between these nests groups of Leydig-like cells are found, often in hyalinized stroma which contains calcified concretions. In some areas one may observe confusing admixtures of all these three cellular elements or only large nests composed solely of germ cells in an arrangement which is typical for “pure dysgerminOma
9212, 16, 17
In the present case typical gonadoblastomatic nests were found, containing a mixture of germ cells and Sertoli-granulosa cells with characteristic psammoma-like calcifications (Figs. 5, 6, and 7). These neoplastic changes occupy a very small area and present a malignant transformation. Such
incipient malignant changes may be classified as “gonadoblastoma in situ.” There were also groups of Leydig-like cells outside the neoplastic area. They did not however seem to be a neoplastic component of the gonadoblastoma. It is difficult to prove their origin. They may represent a stromal reaction (analogous with thecal reaction in other ovarian cancers) at the early stage of neoplastic development. These Leydig-like cells are present in all gonadoblastomas described thus far and are as characteristic a feature as calcified concretions. In many cases of gonadoblastoma, reported in the literature, it is difficult to define the type of malformed gonad in which the tumor arises18 4-6* I6 On the basis of the histological features it may be assumed that gonadoblastoma arises in and from dysgenetic or rudimentary testes.g* I51 I7 Chromosomal investigations give additional, very important evidence that the above mentioned hypothesis is correct. In all our investigated cases of gonadoblastoma the Y-chromosome was present. In 3 cases a male karyotype, 46/XY, and in one case
Vchme I’iumber
90 7, part 1
a sex-chromosome mosaic&m, XO/XY//XO, were found.“> I5 In the presented case the genetic sex is male. The sex-chromosome complement is XY and the neoplasm developed in welldefined testicular tissue. A similar situation was reported by Siebenmann13 in a case of male pseudohermaphroditism. The tumor was discovered at the periphery of definite testicular tissue. On the other side gradual transitions from seminiferous tubules to gonadoblastoma nests could be observed. This case may be the first to be diagnosed at such an early stage. The malignant changes were limited to the tubular content and presented a picture of gonadoblastoma in situ. Only at one spot neoplastic cells ruptured the tubular wall and invaded the stroma (Fig. 6).
Mixed
gonodai
dysgenesis
935
Conclusions 1. A case of intersexuality was diagnosed as “mixed” or asymmetrical gonadal dysgenesis because a rudimentary “streak“ gonad on the left side and a testis on the right side were found; both were situated abdominally in the normal position of the ovaries. 2. In the right gonad a typical testicular pattern was found with remnants of cortical parts and dysgenetic seminiferous tubules. In one small area microscopic foci of “gonadoblastoma in situ” were present. In the left gonad ovarian-like fibrous tissue without any germinal elements was found. 3. Chromosomal investigations in blood and skin showed a male karyotype. 4fi:XY. The Me&r
expert is gralefully
technical
assistance of XIirs
B.
acknowledgrd.
REFERENCES
Bergada, C., Cleveland, W. W. Jones, H. W., Jr., and Wilkins, L.: Acta endocrinol. 40: 493, 1962. 2. Conen, P. E., Baily, J. D., Allemang, W. H., Thompson, D. W., and Enin, C.: Lancet 2: 294, 1961. 3. Fe&son-Smith, M. A., and Johnston, A. W.: Ann. Tnt. Med. 53: 359. 1960. 4. Fine, G., Mellinger, R. C., aid Canton, J. N.: Am. J. Clin. Path. 38: 615, 1962. G., Borkhi, A., Bigozzi, U., Negri, L., 5. Giusti, and Toccafondl, R.: Obst. & Gynec. 20: 755, 1962. M. M., and Uson, A. C.: Cancer 6. Melicow, 12: 552, 1959. 7. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Batipps, D. M., and Hungerford, D. A.: Exper. Cell Res. 20: 613, 1960. 8. Philip, J., and Teter, J.: (To be published.) 9. Philip, J., and Teter, J.: Acta path. et microbial scandinav. 61: 543, 1964. 10. Polani, P. E.: Personal communication. 1.
11. 12. 13. 14. 15.
16. 17. 18.
Rothfels, K. H., and Siminovitch, L.: Stain Technol. 33: 73, 1958. Scully, R. E.: Cancer 6: 455, 1953. Siebenmann, R. B.: Path. et Microbial. 24: 233, 1961. Sohval, A.: Am. J. Human Genet. 15: 355, 1963. Teter, J., Philip, J., Wefewicz, Gr., and Potocki, J.: Acta endorrinol. 46: 1, 1964. Teter, J.: J. Obst. & Gynaec. Brit. Emp. 67: 238, 1960. Teter, J.: Acta path. et microbial. sc.andinav. 58: 306, 1963. Willemse, C. H., van Brink, J. M.. and Los, P. L.: Lancrt 1: 488, 1962. Starynkiewiecza 3 Warsaw, Poland Rigshospitalet Juliane Mariesuej 14 copenhapen, Denmark
TETER,
J.
PHILIP,
GR.
M.D. M.D.
WECEWICZ,
Warsaw, Copenhagen,
in situ
M.D.
Poland Denmark
T H E T E R M “mixed’ gonadal dysgenesis refers, according to Sohval,14 to the coexistence of a rudimentary, fibrous “streak” gonad on one side and a testis on the other. Bergada and associates1 named this condition asymmetrical gonadal differentiation. Such gonads are situated abdominally in the normal position of ovaries. Uterus and Fallopian tubes are present, but usually they are underdeveloped or rudimentary. Several such cases have been reported in the literature,lm4 but were not classified as “mixed gonadal dysgenesis,” which seems to be most appropriate.
“Mixed” gonadal dysgenesis has characteristics classified between chromatin-negative pure gonadal dysgenesis with typical bilateral streak gonads and male pseudohennaphroditism with bilateral testes. The accumulation of results of chromosome analysis in patients with intersexuality will in the future elucidate what is the prevalent type of karyotypes in the syndrome of mixed gonadal dysgenesis. A review of the literature shows that sex chromosome mosaicism of XO/XYl* or 46/XY’, ‘I’ may occur. It has previously been shown that malformed testes in intersexual conditions have a special tendency to neoplastic chan,ges.“, IF. I7 In genetic males, as determined by the presence of a Y-chromosome, the neoplasm may show the pattern of gonadoblastoma (gonocytoma III ) .? It is possible that the risk of malignancy in mixed gonadal dysgenesis is extraordinarily high, as the gonad contains dysgenetic, malformed seminiferous tubules with groups of gonocytes. Such tubules may have a biz-
From the Department of Endocrinology, First Clinic of Obstetrics and Gynaecology,’ Medical Academy in Warsaw, and University Department of Obstetrics and Gynaecology, Rigshospitalet, Copenhagen. This work was supported in part by Leo Pharmaceutical Products, The Danish State Research Foundation, The Danish Cancer Society, and The Danish Foundation for the Advancement of Medical Science. 929
930
Teter,
Philip,
and
Wegewicz
Gynecological examination showed pubic hair of male type spreading toward the inguinal rcgions and internal part of the thighs. The external genitah were feminine except for a large phallus, which in the flaccid state measured 6 by 2 cm. (Fig. 2). The labia minora were rather rudimentary. The labia majora were swollen and covered by wrinkled skin of scrotal appearance (Fig. 2, A). The urethra opened at the base of the phallus in the normal female position. The vagina admitted easily one finger and measured 8 cm. in depth. A thickening could be felt at the vaginal vault and this was identified as a cervix. Findings
Fig. 1. Eunuchoidsl body proportions with line features. (Patient K. J., aged 19.)
mascu-
zare form, which suggests bisexual formation, containing both ovarian and testicular elements. Case report Patient K. J., aged 19, was admitted to the Endocrinological-Outpatient Department because of primary amenorrhea, retardation of sexual development, and virilization. Symptoms of androgenic influence began at the age of 13 (hirsutism, acne, seborrhea, and hypertrophy of the clitoris). Reared as a woman, the patient exhibited the female type of psychosexual orientation. Physical examination revealed eunuchoidal body proportion with masculine features. There was no breast development (Fig. 1) .
Radiologic investigation. A hysterosalpingography showed a small, narrow, smoothwalled uterine cavity and patent Fallopian tubes. Laboratory investigations. The sex-chromatin pattern was negative. Cytologic examination of vaginal smears revealed lack of estrogenic activity. Hormonal assays showed that the urinary 17-ketosteroid output was within normal limits for women, 7.2 and 9.4 mg. per 24 hours. The 17-hydroxycorticoids were 3.4 and 4.7 mg. per 24 hours on consecutive days. Urinary excretion of estrogens was 43 fig and 61 pg per 24 hours (average limits for normal healthy women). The gonadotropin level was 40 mu. (normal limits for healthy women, 20 to 30 mu.). (The method of Klinefelter, as modified by Dekanski and Loraine Brown). Laparotomy. Laparotomy disclosed a fetal uterus and Fallopian tubes. On the left a typical dysgenetic whitish streak in the place normally occupied by the ovary was found. On the right, also in the location normally occupied by the ovary, a gonad resembling a testis was found. It measured 4 by 3 by 1 cm. and its surface was smooth and glistening. The right gonad was totally removed and a biopsy of the left gonadal streak was taken. Microscopic examination. The right gonad showed a typical testicular structure with remnants of the cortical part of the gonad. Tubules were small and lined with undif-
Volume Numbrr
90 7, part
Mixed
1
gonadal
dysgenesis
931
Fig. 2. A and with labia
B. External genitals a la] w ,hallus and swollen ma rjor of I rota1 appeal *ante.
Fig.
3
Fig. 3. Seminiferous nucleoli.
Fig. 4.
tubules lined with Sertoli cells and germ Tubular wall is thickened. Two different tubules with malignant changes in the upper
ferentiated Sertoli-like and germinal cells in a single row. The tubular wall was thickened with hyalinosis (Fig. 3). In a few very small areas the tubules were fiIled with immature Sertoli-granulosa-like cells intermixed with germ cells (Fig. 4). In several layers the Sertoli-granulosa cells were arranged in coronal fashion around individual germ cells or in a folliculoid arrangement surrounding eosinophilic bodies and in a single file along the periphery of the tubular contents (Fig. 5). The histologic alterations of the tubular contents showed a mild, but
cells
containing
very
active
one.
definite, degree of cellular anaplasia with variations in size and shape of the nucleus and hyperchromatism. These malignant features were observed both in germ cells and Sertoli-granulosa-like cells (Fig. 6) . Calcified concretions in form of psammoma-like bodies or calcified flecks were also seen within malignant nests (Fig. 7). All of the histologic changes clearly illustrate a gonadal neoplasm, which should be classified as gonocytoma III (gonadoblastoma). There was no sharp dividing line between the ty-pica1 tissue and the gonadoblastic testicular
932
Teter,
Philip,
and
Wegewicz
nests. These lesions were limited to very small microscopic areas within the testicular tubes and were diagnosed as “gonadoblastoma in situ.” Only in one place was the tubular wall ruptured and neoplastic cells
tended somewhat to invade the interstitial spaces (Fig. 6). The Leydig cells were numerous and situated between seminiferous tubules and also at the periphery of neoplastic nests (Fig. 5).
Fig. 5. Typical nest of gonadoblastoma within tubule. Folliculoid arrangement of Sertoli-granulosa type of cells and single germ cells scattered among them (arrozu.) In the upper right corner a group of Leydig cells is visible.
Fig. 7
Fig.
Fig. 6. Rupture of tubular wall clearly visible in lower left vasion by neoplastie cells (~~rroze) . Fig. 7. Typical malignant changes seen in group of germ Psammoma-like calcifications are seen on the left.
corner cells
with and
incipient Sertoli-granulosa
stromal
incells.
Volume Number
90 7,
part
Mixed
1
Fig. 8. Karyotype
from cell from peripheral
Microscopic study of the left streak gonad showed that it was composed of a connective ovarian-like fibrous tissue without any germinal elements. Chromosomal investigations. Chromosomal analysis (W4/79) was carried out on dividing cells from the peripheral blood and from skin. A modification of the method of Moorhead and associates7 for chromosomal preparation of leukocytes cultured from human peripheral blood was used. Venous blood was withdrawn and injected into a universal container with heparin. The container was sent by air in crushed ice to Copenhagen and 6 hours after the blood was taken the red cells were allowed to sediment by gravitation in the container. The plasma containing the leukocytes was pipetted off and a leukocyte count was made. The suspension was diluted 1:2 with culture medium 199 (Glaxo) and phytohemagglutinin, 0.1 ml. per 5 ml., was added. The mixture was incubated at 36.5’ C. for three and a half days. After 3 hours of treatment with demecolcine (final concentration of 0.1 ;dg per milliliter) the cells were treated with
gonadal
dysgenesis
933
blood.
hypotonic saline solution, fixed, spread on slides by the air drying technique,” stained with aceto-orcein, and mounted with euparal. Skin preparations were made as described by Philip and Teter.8 Chromosome counts were carried out on 30 cells in blood and 30 cells in skin. < 43 Blood Skin
1
43 1
44 7
45 3 ‘I.
46 24 36 -
47
Total 30 30
By structural analysis of 6 cells with 46 chromosomes, 3 from each tissue, the complement was found to be that of a normal male (Figs. 8 and 9). Comment
A review of the literature*-‘jp lz. “’ and clinicopathological findings from our own cases of gonadoblastoma show that all such patients have the following common features: 1. Abnormal somatosexual development in a patient reared as a woman with primary amenorrhea and some signs of masculinization.
934
Teter,
Fig.
9. Cell
Philip,
and
WeGewicz
in metaphase.
2. Negative sex-chromatin pattern and a female type of genitals. 3. High urinary gonadotropin excretion despite clinical and, sometimes, biochemical signs of sex-hormone activity (analogous with some cases of the syndrome of testicular feminization). The tumor is histologically characterized by the presence of characteristic neoplastic nests composed of germ cells scattered among Sertoli-granulosa cells. Between these nests groups of Leydig-like cells are found, often in hyalinized stroma which contains calcified concretions. In some areas one may observe confusing admixtures of all these three cellular elements or only large nests composed solely of germ cells in an arrangement which is typical for “pure dysgerminOma
9212, 16, 17
In the present case typical gonadoblastomatic nests were found, containing a mixture of germ cells and Sertoli-granulosa cells with characteristic psammoma-like calcifications (Figs. 5, 6, and 7). These neoplastic changes occupy a very small area and present a malignant transformation. Such
incipient malignant changes may be classified as “gonadoblastoma in situ.” There were also groups of Leydig-like cells outside the neoplastic area. They did not however seem to be a neoplastic component of the gonadoblastoma. It is difficult to prove their origin. They may represent a stromal reaction (analogous with thecal reaction in other ovarian cancers) at the early stage of neoplastic development. These Leydig-like cells are present in all gonadoblastomas described thus far and are as characteristic a feature as calcified concretions. In many cases of gonadoblastoma, reported in the literature, it is difficult to define the type of malformed gonad in which the tumor arises18 4-6* I6 On the basis of the histological features it may be assumed that gonadoblastoma arises in and from dysgenetic or rudimentary testes.g* I51 I7 Chromosomal investigations give additional, very important evidence that the above mentioned hypothesis is correct. In all our investigated cases of gonadoblastoma the Y-chromosome was present. In 3 cases a male karyotype, 46/XY, and in one case
Vchme I’iumber
90 7, part 1
a sex-chromosome mosaic&m, XO/XY//XO, were found.“> I5 In the presented case the genetic sex is male. The sex-chromosome complement is XY and the neoplasm developed in welldefined testicular tissue. A similar situation was reported by Siebenmann13 in a case of male pseudohermaphroditism. The tumor was discovered at the periphery of definite testicular tissue. On the other side gradual transitions from seminiferous tubules to gonadoblastoma nests could be observed. This case may be the first to be diagnosed at such an early stage. The malignant changes were limited to the tubular content and presented a picture of gonadoblastoma in situ. Only at one spot neoplastic cells ruptured the tubular wall and invaded the stroma (Fig. 6).
Mixed
gonodai
dysgenesis
935
Conclusions 1. A case of intersexuality was diagnosed as “mixed” or asymmetrical gonadal dysgenesis because a rudimentary “streak“ gonad on the left side and a testis on the right side were found; both were situated abdominally in the normal position of the ovaries. 2. In the right gonad a typical testicular pattern was found with remnants of cortical parts and dysgenetic seminiferous tubules. In one small area microscopic foci of “gonadoblastoma in situ” were present. In the left gonad ovarian-like fibrous tissue without any germinal elements was found. 3. Chromosomal investigations in blood and skin showed a male karyotype. 4fi:XY. The Me&r
expert is gralefully
technical
assistance of XIirs
B.
acknowledgrd.
REFERENCES
Bergada, C., Cleveland, W. W. Jones, H. W., Jr., and Wilkins, L.: Acta endocrinol. 40: 493, 1962. 2. Conen, P. E., Baily, J. D., Allemang, W. H., Thompson, D. W., and Enin, C.: Lancet 2: 294, 1961. 3. Fe&son-Smith, M. A., and Johnston, A. W.: Ann. Tnt. Med. 53: 359. 1960. 4. Fine, G., Mellinger, R. C., aid Canton, J. N.: Am. J. Clin. Path. 38: 615, 1962. G., Borkhi, A., Bigozzi, U., Negri, L., 5. Giusti, and Toccafondl, R.: Obst. & Gynec. 20: 755, 1962. M. M., and Uson, A. C.: Cancer 6. Melicow, 12: 552, 1959. 7. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Batipps, D. M., and Hungerford, D. A.: Exper. Cell Res. 20: 613, 1960. 8. Philip, J., and Teter, J.: (To be published.) 9. Philip, J., and Teter, J.: Acta path. et microbial scandinav. 61: 543, 1964. 10. Polani, P. E.: Personal communication. 1.
11. 12. 13. 14. 15.
16. 17. 18.
Rothfels, K. H., and Siminovitch, L.: Stain Technol. 33: 73, 1958. Scully, R. E.: Cancer 6: 455, 1953. Siebenmann, R. B.: Path. et Microbial. 24: 233, 1961. Sohval, A.: Am. J. Human Genet. 15: 355, 1963. Teter, J., Philip, J., Wefewicz, Gr., and Potocki, J.: Acta endorrinol. 46: 1, 1964. Teter, J.: J. Obst. & Gynaec. Brit. Emp. 67: 238, 1960. Teter, J.: Acta path. et microbial. sc.andinav. 58: 306, 1963. Willemse, C. H., van Brink, J. M.. and Los, P. L.: Lancrt 1: 488, 1962. Starynkiewiecza 3 Warsaw, Poland Rigshospitalet Juliane Mariesuej 14 copenhapen, Denmark