Call-Exner Bodies Research Articles

Sertoliform Endometrioid Carcinoma of the Endometrium With Dual Immunophenotypes for Epithelial Membrane Antigen and Inhibin ??

We report a rare case of sertoliform endometrioid carcinoma of the endometrium in a 71-year-old African American woman who presented with postmenopausal bleeding. Her medical condition was remarkable for hypertension, diabetes, and obesity. She underwent total hysterectomy, right salpingo-oophorectomy and lymph node sampling. The endometrium was occupied by a 4.5-cm solid polypoid tumor, which grossly invaded into the myometrium. Microscopically, the tumor consisted of small hollow tubules, anastomosing cords and trabeculae, and tightly packed nests. Microglandular areas mimicking adult granulosa cell tumors were also present. But true Call-Exner bodies were absent. Component of typical endometrioid carcinoma was noted only focally. The uninvolved endometrium demonstrated atypical complex hyperplasia. The tumor cells were diffusely immunoreactive for epithelial membrane antigen, estrogen receptor, and progesterone receptor (PR), and focally for vimentin. The tumor cells were also diffusely positive for inhibin alpha and CD99. Immunostains for other sex cord markers (calretinin, WT-1, and Melan-A) were also positive in approximately 30% to 40% of the tumor cells. Immunostains for CD10, smooth muscle actin, desmin, or HHF35 were negative. Two ovarian sertoliform endometrioid carcinomas from our archived tissue were, however, immunoreactive for epithelial membrane antigen but negative for inhibin alpha. Despite the prominent sertoliform features, both histologically and immunohistochemically, the tumor was of a high-grade endometrial carcinoma and will likely behave as such. As of today, dual differentiation of epithelium and sex cord by immunohistochemical staining has not been demonstrated in sertoliform endometrioid carcinomas of either endometrial or ovarian origin. Our case is the first documentation of such example and suggests that endometrial carcinoma can undergo true sex cord differentiation.

Diagnose und Differenzialdiagnose des Granulosazelltumors

Clinically and morphologically, two types of granulosa cell tumor can be distinguished, the more frequent adult type and the juvenile type. In the adult type, different growth patterns can be observed: microfollicular (most frequent, characterized by Call-Exner bodies), macrofollicular, trabecular, insular, solid-tubular, gyriform and diffuse (sarcomatoid). The juvenile type is characterized by solid and follicular structures. The neoplastic granulosa cells in the adult type have limited cytoplasm and haphazardly arranged angular, pale, mostly grooved nuclei. In the juvenile type, the cells have ample eosinophilic cytoplasm and polymorphic, sometimes bizarre nuclei, which are usually non-grooved. The number of mitoses in the adult type usually does not exceed 2/10 HPF, whereas it is considerably higher in the juvenile type, including atypical mitoses. A common feature in both types of tumor is the expression of inhibin-alpha, calretinin and CD 99. Epithelial membrane antigen is negative. Molecular genetics has demonstrated loss of heterozygosity at 19p13.3 in 52% of the cases. Besides chromosomal aberrations, there are a large number of cytogenetic anomalies. The most important prognostic factor in both types of tumor is tumor stage. Whereas recurrences in the adult type can develop even after decades, in the juvenile type they usually occur during the first 3 years after diagnosis.

The distribution of type IV collagen .ALPHA. chains in the mouse ovary and its correlation with follicular development

The present study aims to identify alpha chains of type IV collagen in the basement membrane of the mouse ovarian follicle and examine their changes during follicular development using immunofluorescence microscopy with specific monoclonal antibodies. The basement membrane of the serous mesothelium enveloping the ovary contained all alpha chains of type IV collagen, alpha1(IV) through alpha6(IV) chains. Primordial follicles showed a distinct immunoreactivity against all six alpha chains in their basement membranes. Immunolabeling for alpha3(IV) and alpha4(IV) chains was almost eliminated in the primary follicles. In basement membranes of secondary and Graafian follicles, the immunofluorescent reaction of alpha3(IV) and alpha4(IV) chains disappeared in Graafian follicles, a partial reduction in fluorescent immunostaining intensity to alpha5(IV) and alpha6(IV) chains was observed; only alpha1(IV) and alpha2(IV) chains were not degraded throughout follicular development. On atretic follicles, in addition to alpha1(IV) and alpha2(IV) chains, alpha3(IV), alpha4(IV), alpha5(IV) and alpha6(IV) chains frequently persisted. A basement membrane-like matrix within the follicular granulosa cell layer, such as the focimatrix (focal intraepithelial matrix) and/or Call-Exner body, was also recognized in mouse secondary and Graafian follicles and contained alpha1(IV), alpha2(IV), alpha5(IV) and alpha6(IV) chains but not alpha3(IV) and alpha4(IV) chains. We expect that the decrease in alpha(IV) chains prompts follicular development and is a prerequisite condition for follicular maturation.

Sex-Cord Tumors of the Testis

Abstract: Sex cord tumors of the testis come in three pure forms— Sertoli cell tumors, Leydig cell tumors, and granulosa cell tumors— and pose many problems in differential diagnosis. Sertoli cell tumors are divided into those that are not otherwise specified, those with abundant stromal sclerosis, and the large cell calcifying variant. Most of the not otherwise specified tumors are associated with exquisite hollow or solid tubular patterns, but diffuse patterns may be present either focally or, in occasional cases, extensively. When prominent and associated with septa and inflammatory cells a superficial resemblance to seminoma may result, but careful attention to differentiating cytologic features of these two neoplasms should result in the correct diagnosis being made. If indicated, immunohistochemical stains will help resolve the issue. The large cell calcifying Sertoli cell tumor is more frequently bilateral than other sex cord tumors and is sometimes associated with a variety of unusual clinical manifestations. Rare peculiar proliferations of Sertoli cells in young boys with Peutz-Jeghers syndrome have recently been described, but their full clinical and pathologic spectrum remains to be elucidated. Leydig cell tumors represent the commonest of the pure sex cord tumors of the testis and usually are a straightforward microscopic diagnosis being characterized by diffuse or nodular growths of bland cells with copious eosinophilic cytoplasm. However, a variety of unusual patterns may be encountered including a spindle cell pattern, microcystic change and, in some cases, striking adipose metaplasia. Careful search for typical foci of Leydig cell tumor is crucial in establishing the correct diagnosis when these unusual patterns predominate. Granulosa cell tumors are subdivided into the juvenile adult forms as in the ovary. The juvenile form has a remarkable tendency to occur in most instances in the first six months of life. Although a solid and follicular growth pattern is usually diagnostic, occasionally irregular arrangements of neoplastic granulosa cells in a loose matrix may impart a superficial resemblance to another important testicular tumor of children, the yolk sac tumor. If indicated, immunohistochemical studies will distinguish between these two neoplasms, but routine light microscopy should suffice. The rarest pure sex cord tumor of the testis is the adult granulosa cell tumor. Its morphologic features are as seen in the ovary, although based on personal experience, Call-Exner bodies may be less frequent in the male. When lutein cells are present within these neoplasms it may lead to confusion with an unclassified mixed germ cell sex cord-stromal tumor. A number of granulosa cell tumors of the testis have been clinically malignant in contrast to the benign behavior, to date, of the testicular juvenile granulosa cell tumor.

Cytologic Features of Granulosa Cell Tumors in Fluids and Fine Needle Aspiration Specimens

To describe the cytologic features of granulosa cell tumors in fluids and fine needle aspiration specimens, with histologic confirmation. Histologically confirmed granulosa cell tumors, 6 adult type and 1 juvenile type, were identified. All patients had local recurrences or metastases. Eleven specimens from 7 patients, including cytologic samples, cell blocks and histology, were reviewed. Inhibin immunostaining was performed on cell blocks to aid identification of this group of tumors in the cytologic and histologic samples. The patients were 22-72 years old. Sites included ovary and peritoneum; there were pelvic recurrences and metastatic lesions in the spleen, liver, perirectum and cervical lymph node. Cytologic features of adult granulosa cell tumors included 3-dimensional clusters, resettes loose monolayers and individual cells. Other features were Call-Exner bodies, vacuolated cytoplasm, exuberant capillaries associated with papillarylike fronds, a second population of elongated theca cells, and prominent or rare nuclear grooves. In juvenile granulosa cell tumor the features observed were monolayers, loosely cohesive sheets, single cells, occasional larger pleomorphic cells with nuclear clefting and nuclear protrusions, vacuolated cytoplasm, finely granular chromatin and frequent mitoses. The overall cytologic and histologic correlation was good. Inhibin was focally positive in one peritoneal fluid, correlating with the focal pattern of staining seen on histology. A definitive cytologic diagnosis of granulosa cell tumor can be made based on the above criteria. Aggressive tumors are discohesive and show pleomorphism and nuclear protrusions. Inhibin stain may be helpful in identifying granulosa cell tumors in cell block specimens.

Transitional cell carcinoma of the ovary: a morphologic study of 100 cases with emphasis on differential diagnosis.

Transitional cell carcinoma (TCC) of the ovary is a recently recognized subtype of ovarian surface epithelial-stromal cancer, and studies of its morphology are few. As a result, the criteria for its diagnosis and spectrum of its morphology are not clearly established. One hundred consecutive consultation cases of ovarian carcinoma with a pure or partial transitional cell pattern (excluding malignant Brenner tumor) diagnosed between 1989 and 2001 were evaluated for the frequency of various pathologic features and the relation of TCC to other surface epithelial-stromal carcinomas. The women were 33 to 94 years of age (mean, 56 years). A total of 47 tumors were stage I, 21 stage II, 31 stage III, and 1 stage IV; 13% of the stage I tumors and 41% of tumors of all stages were bilateral. The tumors ranged from 3.0 to 30 cm in greatest dimension (mean, 10 cm); 60% of them were solid and cystic, 24% solid, and 16% cystic. TCC was the exclusive or predominant component in 93% of the tumors and showed undulating (93%), diffuse (57%), insular (55%), and trabecular (43%) patterns. In four tumors with an insular growth, the pattern focally mimicked a Brenner tumor. Necrosis was present in 57% of the cases. Features that were seen in the tumors that in aggregate produced a relatively consistent appearance were "punched out" microspaces (87%), often the size of Call-Exner bodies, large cystic spaces (73%), and large blunt papillae (63%). Features that were sometimes seen, usually as a focal finding, included slit-like fenestrations (49%), bizarre giant cells (35%), small filiform papillae (18%), gland-like tubules (17%), squamous differentiation (13%), and psammoma bodies (4%). In 23 cases, TCC was a component of a mixed epithelial carcinoma, the additional components being serous adenocarcinoma in 16, endometrioid in 5, mucinous in 1, and clear cell carcinoma in 1. The tumor cells of the TCC component often were relatively monomorphic; 6% of the tumors were grade 1, 43% grade 2, and 51% grade 3. The nuclei were oblong or round and often had large single nucleoli (69%) or longitudinal grooves (48%). The cytoplasm was typically pale and granular but was rarely strikingly clear or oxyphilic. TCC of the ovary usually occurs in pure form but is also common as a component of a surface epithelial carcinoma of mixed cell type. In either situation, TCC has a constellation of architectural and cytologic features that readily distinguish it in most cases from other types of ovarian cancer. Recognition of these features will lead to a more consistent diagnosis of this tumor and aid in determining whether it has distinctive clinical features, particularly with regard to its behavior.

Extracellular matrix of the bovine ovarian membrana granulosa

Much is known about the control of the development of ovarian follicles by growth factors and hormones. The study of extracellular matrix in the ovary, though, is a relatively new area. To date much research has focused on identifying the matrix components present, and more recently, its production and the physiological roles. In this review we focus on the changes that occur in the follicular basal lamina from primordial follicles through to ovulation and formation of the corpus luteum, the changes that occur during follicular atresia, and we discuss our observations of a novel matrix which forms in the membrana granulosa. The follicular basal lamina changes considerably during follicular development in its expression pattern of type IV collagens. Of the laminin chains examined, there appears only to be an increase in amount, except for laminin α2. It is expressed only in a small proportion of healthy antral follicles and in the majority of atretic antral follicles. Call–Exner bodies have the same composition as the basal lamina, except they do not contain laminin α2, even when the follicular basal lamina does. The novel matrix that develops within the membrana granulosa is similar in composition to Call–Exner bodies which occur predominantly in preantral follicles, except that it is far more common in large antral follicles, does not induce polarization of the surrounding granulosa cells, and does not contain follicular fluid-like material as the Call–Exner bodies of some species do. The expression of this matrix occurs prior to and during the time when granulosa cells express steroidogenic enzymes. It does not exist in corpora lutea. In addition large luteal cells, derived from granulosa cells, do not appear to have a basal lamina. These findings suggest that the maturational changes in the membrana granulosa are accompanied by changes in the matrix.

Ultrastructure and composition of Call-Exner bodies in bovine follicles.

Call-Exner bodies are present in ovarian follicles of a range of species including human and rabbit, and in a range of human ovarian tumors. We have also found structures resembling Call-Exner bodies in bovine preantral and small antral follicles. Hematoxylin and eosin staining of single sections of bovine ovaries has shown that 30% of preantral follicles with more than one layer of granulosa cells and 45% of small (less than 650 microns) antral follicles have at least one Call-Exner body composed of a spherical eosinophilic region surrounded by a rosette of granulosa cells. Alcian blue stains the spherical eosinophilic region of the Call-Exner bodies. Electron microscopy has demonstrated that some Call-Exner bodies contain large aggregates of convoluted basal lamina, whereas others also contain regions of unassembled basal-lamina-like material. Individual chains of the basal lamina components type IV collagen (alpha 1 to alpha 5) and laminin (alpha 1, beta 2 and delta 1) have been immunolocalized to Call-Exner bodies in sections of fresh-frozen ovaries. Bovine Call-Exner bodies are presumably analogous to Call-Exner bodies in other species but are predominantly found in preantral and small antral follicles, rather than large antral follicles. With follicular development, the basal laminae of Call-Exner bodies change in their apparent ratio of type IV collagen to laminin, similar to changes observed in the follicular basal lamina, suggesting that these structures have a common cellular origin.

Malignant Sex-cord Stromal Tumor of the Testis: Report of a Case with Special Reference to its Unusual Intracytoplasmic Substructures

A case of malignant sex-cord stromal tumor (gonadal stromal tumor) in the left testis of a 42-year-old man with no sign of hormonal abnormality is reported. Histologically, a large portion of the tumor was composed of solid nests of round cells with a moderate amount of eosinophilic cytoplasm, but some areas contained small spaces somewhat resembling Call-Exner bodies and/or the follicular structures of granulosa cell tumors. In general, however, the tumor cells did not show a clear-cut differentiation into either Sertoli cells or granulosa cells. The tumor, because of its high mitotic rate, lymphatic, venous and capsular invasion, and metastasis to the para-aortic lymph nodes, was considered to be malignant. We simply designated this tumor, therefore, as a malignant sex-cord stromal tumor. An ultrastructural study revealed unique intracytoplasmic bodies composed of multiple stacks of tubular structures which superficially mimicked annulate lamellae. No lipid droplets, Reinke's crystalloids or Charcot-Böttcher filaments were seen. The rarity of the tumor and the presence of unusual substructures prompted us to report the case.

Immunoelectron microscopic localization of laminin in rat ovarian follicles.

We studied the immunohistochemical and ultrastructural distribution of laminin in ovaries of immature and mature rats. When sections from 1-8-week-old rat ovaries were labeled directly with conjugates of affinity purified anti-laminin IgG-horseradish peroxidase (HRP), the antibodies bound to all ovarian basement membranes including those surrounding follicles in different stages of maturation. In addition, intracellular labeling was seen in granulosa and theca cells of follicles undergoing rapid development (preantral and antral stages) and in basement membrane-like structures of the Call-Exner bodies. Intracellular laminin was generally not detected, however, in any cells of primordial or atretic follicles. Tissue processed for immunoelectron microscopy 1 hour after the intravenous injection of anti-laminin IgG-HRP showed binding of antibody in linear patterns along endothelial and follicular epithelial basement membranes. Discontinuous strands of laminin-positive, extracellular matrices were also seen between theca cells of all follicles. In addition, injected anti-laminin IgG labeled perisinusoidal basement membranes located within corpora luteae and patches of basement membrane material between granulosa lutein cells. When ovaries were examined 5 d after the intravenous injections of anti-laminin IgG-HRP, uneven or segmented labeling was found in subepithelial basement membranes surrounding developing follicles. Our results therefore indicate that granulosa and theca cells participate directly in basement membrane laminin biosynthesis and suggest that this new laminin is spliced into existing basement membranes during follicular growth.

Gynandroblastoma of the Ovary Having a Typical Morphological Appearance: A Case Study

A rare gynandroblastoma of the right ovary with a typical morphological appearance in a 65-year-old woman is reported. The tumor comprised both a granulosa cell element with a Call-Exner body and a Sertoli cell element. Pathologically, this case could be the most typical of all the world's established cases. Clinically, there were feminizing symptoms such as post-menopausal genital bleeding and endometrial cystic hyperplasia. Pre-operative serum hormonal assays indicated elevated levels of estrone, estradiol and testosterone, and low levels of gonadotropins. These returned to normal after surgery.

Ultrastructural and histochemical investigations of Call-Exner bodies in rabbit Graafian follicles.

In a histological survey of 19 mammalian species, Call-Exner bodies of conventional size and appearance were found in only 5, namely, human, rhesus monkey, rabbit, guinea-pig and sheep. Rabbit ovaries were used for characterizing these bodies using quantitative histochemistry, lectin binding and electron microscopy. Call-Exner bodies were topographically distinct lacunae of the extracellular space probably containing hyaluronic acid with proteoglycan complexes. The staining characteristics of the antrum and Call-Exner bodies were generally similar. However, in contrast to the antrum, the smaller lacunae contained suspended filaments with a distinctive peripheral membrane upon which a rosette of granulosa cells was resting. The membrane and narrow intercellular clefts probably prevent much exchange of large glycosaminoglycan complexes with the antrum. The origin and significance of Call-Exner bodies require further study, but it is clear that they are associated with secretion rather than with necrosis as sometimes suggested.

Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors.

In a retrospective study of 71 primary ovarian tumors in the dog, epithelial tumors (46%) were more common than sex cord stromal (34%) and germ cell tumors (20%). There were more adenocarcinomas (64%) than adenomas. Sex cord stromal tumors were equally divided into Sertoli-Leydig (12/24) and granulosa cell tumors (12/24). There were equal numbers (7/14) of dysgerminomas and teratomas among the germ cell tumors. Most teratomas (6/7) were malignant. Most granulosa cell tumors were solid; two were mostly cystic. Patterns included sheets of round and ovoid to spindle-shaped cells separated by thin, fibrovascular stroma; neoplastic cells formed rosettes or Call-Exner bodies. In some areas, neoplastic cells were in cords or columns and formed cyst-like structures. Four granulosa cell tumors were macrofollicular, having cysts lined with granulosa cells. Median ages of dogs with different ovarian neoplasms were similar; all were more than 10 years old, except the dogs with teratoma (mean age, 4 years). Most neoplasms were unilateral (84%), except the Sertoli-Leydig cell tumors, many of which were bilateral (36%). Size of ovarian neoplasms varied (2 cm3 to 15,000 cm3). Twenty-nine percent of neoplasms metastasized; adenocarcinomas (48%) and malignant teratomas (50%) had the highest rates, and distant metastasis was more common in malignant teratoma. Endometrial hyperplasia was in 67% of the dogs; it was most common in dogs with sex cord stromal tumors (95%). Uterine malignancy was not seen in dogs with granulosa cell tumors, although hyperplasia endometrium was in all dogs with this tumor. Cysts in the contralateral ovaries were most common in dogs with sex cord stromal tumors.

Ultrastructure of human preovulatory granulosa cells in follicular fluid aspirates.

The ultrastructure of preovulatory granulosa cells may be distinct in follicles containing competent as opposed to non-competent oocytes. To test this assumption, granulosa cells were looked for in 36 follicular fluid aspirates from 8 patients taking part in an in vitro fertilization and embryo transfer program. Granulosa cells were absent from 16 aspirates and present in 20. Both aspirate types contained oocytes able to develop in culture. Granulosa cells were subdivided into three developmental stages. Stage 1 (5% of aspirates) showed proliferating cells, while stage 2 (60% of aspirates) and 3 (35% of aspirates) cells were in the preluteinization stage. These cells were recognizable by their number of lipid droplets and differentiated according to possession of a rough (stage 2) or smooth (stage 3) endoplasmic reticulum. Luteinization did not occur in these cells. All stages displayed desmosomes, gap junctions, and annular junctions. The structure of Call-Exner bodies and of fibrin deposits were unexpected findings. Our study indicates that there is no correlation between the previously used morphological parameters of granulosa cells and oocyte maturity.

Effects of locally applied enzyme inhibitors of the arachidonic acid cascade on follicle growth and intra-ovarian oocyte release in hyperstimulated rabbits.

This study was conducted to examine follicle growth and intra-ovarian oocyte release in rabbit ovaries influenced by a local application of prostaglandin formation inhibitors. While five rabbits remained as unstimulated controls, twenty-seven mature rabbits were hyperstimulated by pure follicle stimulating hormone (FSH) followed by human chorionic gonadotropin (hCG) at time 0. At the same time, 1 mg lonazolac (lonazolac group), indomethacin (indomethacin group) or saline (so-called gonadotrophic stimulated controls) was applied into the vagina of each group. Both ovaries of each animal were evaluated morphometrically at 15, 20, 28 and 48 hr after hCG. The absolute numbers of smaller-sized preantral follicles were always higher in the gonadotrophic stimulated controls than in the unstimulated controls, the lonazolac, or the indomethacin group. The numbers of larger-sized preantral and antral follicles showed no differences. Unlike the gonadotrophic stimulated controls and the lonazolac group, the indomethacin group displayed an increase in its mature structures (large-sized antral and preovulatory follicles, follicle and luteinized cysts) from 20 to 28 hr after hCG. Call-Exner bodies underwent pseudomucification in preovulatory follicles. The absolute numbers of Call-Exner bodies were augmented by indomethacin. Maturation division of oocytes began to decrease in all three treated groups between 15 and 20 hr post hCG, but the height of intra-ovarian oocyte release (IOR) appeared at 28 hr. This coincided with a striking thrombus formation. It is assumed that: 1) lonazolac and indomethacin inhibit early development of proliferating follicles; 2) lonazolac and indomethacin have no effects on the maturation division of the oocyte and of IOR; 3) IOR extends over a longer period after ovulation induction in contrast to the maturation division of the oocyte; and 4) thrombus formation is related to IOR.

Studies on the morphology of the isolated perfused rabbit ovary. II. Ovulation in vitro after HCG-treatment in vivo.

Ovulation was induced in rabbits by intravenous administration of human chorionic gonadotrophin (HCG), and 4-5 h later the ovaries were isolated and introduced into an in-vitro perfusion system containing synthetic medium with albumin. Rupture of follicles occurred in vitro within the physiological time range (mean 11.3 h after injection of HCG), although with a reduced frequency. Preovulatory and ruptured follicles were studied in detail by light and electron microscopy. In the granulosa layer of ruptured or preovulatory follicles cytoplasmic blebbing activity, disappearance of Call-Exner bodies and differentiation toward luteinized cells were found. Perhaps the most important sign of normal preovulatory development in vitro was that the basement membrane surrounding the granulosa layer was penetrated by projections of granulosa cells. In the absence of this penetration phenomenon the granulosa layer prolapsed out of the follicle. Immediately before rupture, follicles showed marked degeneration, restricted to the outer layers of the apical wall, which is compatible with the hypothesis that degradative enzymes are released close to the surface of preovulatory follicles. Although the majority of follicles that ovulated under in-vitro conditions showed the same kind of morphological alterations as can be seen in vivo, occasional atypical ruptures occurred without any overt signs during perfusion. Also technical manipulations of the perfusion system, e.g., nonphysiological increase of perfusion pressure, could force follicles to rupture. This illustrates the importance of careful morphological study of all ovaries perfused in vitro before conclusions are drawn.

Granulosa theca cell tumors in premenarchal girls: a clinical and pathologic study of ten cases.

Granulosa theca cell tumor (GTCT) in the premenarche accounted for 7% of all ovarian tumors treated at the Children's Hospital Medical Center from 1928 through 1979. The average age of the ten girls at the time of diagnosis was 5 years (range 11 months-121/2 years) with precocious "pseudopuberty" and an abdominal mass being the most common presentation. GTCTs were solitary (five right, five left) with an average diameter of 12.1 cm. Histologic examination showed a predominantly diffuse or solid pattern with prominent luteinization; Call-Exner bodies and folded ("coffee-bean") nuclei were inconspicuous. Ultrastructural examination of one GTCT confirmed the presence of both granulosa and theca components with the latter showing extensive luteinization; estradiol, testosterone and prolactin were demonstrated in the same tumor using immunologic techniques. The average follow-up time was 21 years with nine of the ten patients being followed for more than ten years. Salpingo-oophorectomy resulted in cures despite the occurrence of tumor spillage in two patients. The prognosis for GTCTs in the premenarche appears more favorable than for those occurring in adulthood, but further study is needed to completely define their full biologic potential; the significance of subsequent breast cancer in two long-term survivors merits further investigation as well.

Microscopic gonadoblastoma in dysgenetic gonad of an infant: An ultrastructural study

A microscopic gonadoblastoma found in the dysgenetic gonad of a six-month-old phenotypic female with a 46,XY genotype was studied with the electron microscope and compared with the cells from the testicular portion of the contralateral gonad. The germ cells within the tumor resembled the testicular germ cells and were not different from previously described germ cells in other gonadoblastomas of postpubertal patients. The sex cord cells of the present tumor were inactive and immature, but differed from the Sertoli cells of the patient's testis. The presence of hyalin globules and Call-Exner bodies in the epithelial tumor nests, coupled with the ultrastructural appearance of the sex cord cells is more consistent with them being immature granulosa rather than Sertoli cells. The immaturity of the sex cord cells in gonadoblastoma of this infant suggest that they are responsive to normal regulatory hormonal influences.

Uterine tumors resembling ovarian sex-cord tumors. A clinicopathologic analysis of fourteen cases.

Uterine tumors with histologic resemblances to ovarian sex-cord tumors were encountered in 14 women in the fourth to sixth decades of life, most of whom had abnormal vaginal bleeding and enlarged uteri suggesting leiomyomas. The tumors in six cases (Group I) were identical to one or another form of well-recognized endometrial stromal tumor except for focal epithelial-like differentiation resembling that seen in sex-cord tumors. These tumors were mostly poorly circumscribed large mural masses. The focal sex-cord-like differentiation was manifested by cords, trabeculae, nests and tubules of epithelial-like cells; eosinophilic bodies resembling Call-Exner bodies were seen in one case. Five of the six patients with tumors of this type have been followed for postoperative intervals of 22 months to 15 years, and pelvic recurrences have developed in three. The tumors in eight cases (Group II) differed from those in Group I by having a predominant or exclusive pattern reminiscent of an ovarian sex-cord tumor. These tumors, most of which were single, well-circumscribed, yellow to tan, mural masses 4 to 10 cm in diameter, appeared benign, with no recurrence during postoperative periods of four months to seven years. The relations of the two groups of tumors to one another and to previously described similar tumors. including so-called granulosa-cell tumors and "plexiform tumors" of the uterus, are discussed, and an origin from endometrial stromal cells is postulated.

Gonadoblastoma: Histologic, ultrastructural, and histochemical observations in five cases

In this series of gonadoblastomas it appeared that the germ cells were the motivating force underlying either tumor proliferation or regression. The ultrastructural morphology confirmed the presence of undifferentiated gonadal cells with active steroid synthesis by the interstitial cells. The Call-Exner-like bodies which showed extensive calcification were composed of basement membrane material containing a sulfated mucosubstance. A histochemical comparison with the noncalficying Call-Exner bodies of a granulosa-cell tumor differed only in their glycoprotein content. The calcium deposits were identified as oriented hydroxyapatite crystals by electron diffraction, and it is proposed that the basement membrane material serves as a nucleation site for calcification. High serum testosterone levels were correlated with the presence solely of interstitial cells in one case. The finding of a gonadoblastoma without the presence of a Y chromosome contradicts earlier proposals concerning the requirement of a Y chromosome for germ cell proliferation.