Mixed Germ Cell-sex Cord-stromal Tumor Research Articles

Distribution of Y-chromosome-bearing cells in gonadoblastoma and dysgenetic testis in 45,X/46,XY infants

Gonadoblastoma is an unusual mixed germ cell–sex cord–stromal tumor that has the potential for malignant transformation and 30% of all patients with gonadoblastoma develop germ cell tumors mainly dysgerminoma/seminoma. An additional 10% gives rise to other malignant germ cell neoplasms. This tumor affects a subset of patients with intersex disorders. The age at diagnosis is variable ranging from birth to the fourth decade, but around 94% of cases are diagnosed during the first three decades of life and there are few cases with gonadoblastoma diagnosed in infants. In this paper, we present the histological and molecular findings of four patients with gonadal dysgenesis who developed gonadoblastoma in the first 2 years of life and one case with bilateral dysgerminoma diagnosed at 15 years of age. The sex chromosomes of mosaic patients do not distribute homogenously in dysgenetic gonads; however, statistical analysis of FISH results revealed significant differences between the XY cell line in the gonadoblastoma compared with the dysgenetic testis. Our cases demonstrate that tumors could be present at a very early age, so the prophylactic removal of the gonads is advised.

Neoplastic potential of germ cells in relation to disturbances of gonadal organogenesis and changes in karyotype.

The study consisted of 46 intersexual patients who underwent gonadectomy at the age of 3 months to 19 years because of gonadal dysgenesis (GD; 40 cases) or true hermaphroditism (bisexual gonads; 6 cases). In patients with GD, the incidence of the 46,XY karyotype was 67.5%, whereas the remaining patients exhibited numerical and structural aberrations of sex chromosomes (NSASs), and all patients with bisexual gonads revealed NSAS. Seminoma was diagnosed in 1 patient with the 46,XY karyotype and pure GD (streak gonads). Intratubular carcinoma in situ (CIS) appeared as an exclusive lesion in 61.5% of 13 patients with mixed GD, in 54% of 11 patients with partial GD (bilateral testes), in 16.7% of 6 patients with bisexual gonads, and in none of 13 patients with pure GD. CIS also appeared in tubules in the vicinity of sex cord-derived tumors (gonadoblastoma nests and unclassified mixed germ cell-sex cord-stromal tumor; MGCSCST) and within the tumors. In 3 patients, gonadoblastoma replaced the whole bilateral gonads and is referred to as gonadoblastoma-only GD. The incidence of neoplastic lesions (mostly bilateral) was 90.9% in patients with partial GD, 76.9% (mostly unilateral) in patients with mixed GD, 23.1% (unilateral) in patients with pure GD, and 16.7% (unilateral) in patients with bisexual gonads. Disregarding types of disturbances of gonadal organogenesis, the incidence of lesions was 71.4% in 28 patients with the 46,XY karyotype and 35.3% in 17 patients with NSAS. We conclude, first, that NSAS is not a prerequisite for the appearance of GD and GD is more frequently associated with the 46,XY karyotype. Second, the spectrum of germ cell neoplastic lesions in GD is wider than reported. Besides germ cell carcinoma, CIS, and gonadoblastoma nests, the spectrum also includes a tumor of gonadoblastoma-only in cases of GD and MGCSCST. Third, the incidence of neoplastic lesions is related more to the severity of the disturbances of gonadal organogenesis than it is to aberrations in sex chromosomes. Fourth, less disturbed testicular organogenesis predisposes these patients more toward germ cell neoplastic lesions, which suggests that the testicular environment of a dysgenetic gonad plays an important role in germ cell neoplasia initiation, maintenance, or both.

Sex cord-stromal tumors of the testis with entrapped germ cells: a lesion mimicking unclassified mixed germ cell sex cord-stromal tumors.

The authors describe 10 sex cord-stromal tumors of the testis that incorporated germ cells, thereby mimicking the unclassified type of mixed germ cell sex cord-stromal tumor (MGCSCST). These neoplasms occurred in patients from 3 to 48 years old (mean age, 26 years) who presented with testicular masses. On microscopic examination, nine tumors had a combination of tubular and cord-like arrangements of sex cord cells with transition to spindle-shaped tumor cells. They were diagnosed as either unclassified sex cord-stromal tumors (n = 5) or Sertoli-stromal cell tumors (n = 4). One tumor was a pure Sertoli cell tumor. The admixed germ cells were usually at the periphery and in clusters, but occasionally were in the center or more diffuse. In nine patients the germ cells resembled spermatogonia, having round nuclei with uniform, dusty chromatin and inconspicuous or small nucleoli. None of these cells stained with a variety of markers used for neoplastic germ cells, and in one case in which the non-neoplastic Sertoli cells were strongly reactive for inhibin but the neoplastic Sertoli cells were not, all the germ cells within the tumor occurred adjacent to inhibin-positive Sertoli cells. With static cytophotometry, a diploid deoxyribonucleic acid content was found in these germ cells in the two investigated cases. In one case the germ cells had the morphologic appearance of seminoma cells and they stained positively for the markers of neoplastic germ cells. This case was interpreted as a "collision" tumor between a Sertoli cell tumor and a seminoma. The authors conclude that sex cord-stromal tumors with entrapped germ cells of the testis are more common than unclassified MGCSCSTs--a bona fide testicular example of which has not been seen by any of the authors.

Monosomy 22 in a mixed germ cell-sex cord-stromal tumor of the ovary

Monosomy 22 in a mixed germ cell-sex cord-stromal tumor of the ovary

Monosomy 22 in a mixed germ cell-sex cord-stromal tumor of the ovary

We report the cytogenetic findings in a case of mixed germ cell-sex cord-stromal tumor of the ovary in a 5-month-old girl. Monosomy 22 was observed as the sole karyotypic abnormality. This result was confirmed by comparative genomic hybridization, which revealed no additional chromosomal imbalances. This is the first observation of a chromosomal aberration in a mixed germ cell-sex cord-stromal tumor of the ovary. Monosomy 22 has been previously observed in granulosa cell tumors of the ovary. This could suggest a common pathogenetic pathway for both types of tumors.

A Mixed Germ Cell-Sex Cord-Stromal Tumor of the Ovary with Retiform Tubular Structure

An unusual mixed tumor of the ovary in a 7-month-old girl with a normal 46,XX karyotype, is presented. The tumor was composed mainly of small epithelial cells of sex cord type, but also contained multiple foci in which the presence of large cells resembling germ cells warranted the diagnosis of mixed germ cell-sex cord-stromal tumor. An additional histologic feature was the presence in the fibrous stroma of the tumor of tubules of probable sex cord derivation arranged in a retiform pattern. These histologic features suggested that the tumor was a variant of the mixed germ cell-sex cord-stromal tumor of the ovary.