New insights into type II germ cell tumor pathogenesis based on studies of patients with various forms of disorders of sex development (DSD)

Hersmus, Remko; Leeuw, Bertie H.C.G.M. de; Wolffenbuttel, Katja P.; Drop, Stenvert L. S.; Oosterhuis, J. Wolter; Cools, Martine; Looijenga, Leendert H. J.

doi:10.1016/j.mce.2008.02.028

Cited by 68 publications

(54 citation statements)

References 81 publications

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“…It is a very malignant tumor that rapidly infiltrates adjacent organs, with distant metastasis and frequent recurrences. That is why bilateral gonadectomy is an essential element in the treatment of Swyer syndrome [11,12]. A study conducted by Radakovic et al [13] showed that 55% of patients suffering from Swyer syndrome were diagnosed with gonadoblastoma or dysgerminoma.…”

Section: Discussionmentioning

confidence: 99%

Dysgerminoma and gonadoblastoma in the course of Swyer syndrome

Milewicz¹,

Mrozińska²,

Szczepański³

et al. 2016

pjp

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We present a case of a woman with primary amenorrhea. Ultrasound imaging showed a uterus of normal size but bands of connective tissues at the site of ovaries. A genetic test was done which revealed the XY karyotype. Swyer syndrome was diagnosed. The patient did not report for the follow-up visits. Three years later, the woman reported back because of increasing abdominal circumference. The patient underwent an operation. Radical hysterectomy was performed. Histopathological examination showed dysgerminoma and gonadoblastoma on the left gonad and dysgerminoma on the right one. This case report presents the natural history of Swyer syndrome.

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Section: Discussionmentioning

confidence: 99%

Dysgerminoma and gonadoblastoma in the course of Swyer syndrome

Milewicz¹,

Mrozińska²,

Szczepański³

et al. 2016

pjp

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“…CIS cells originate from developmentally arrested foetal germ cells (gonocytes) [4,16,34]. A number of studies show that the arrest of germ cell differentiation is the key event, which may be followed by malignant transformation and invasive GCT development, usually occurring in young adults [16,32,35]. CIS cells have some morphological features of gonocytes, but also display a series of antigens present normally in the foetal period of life, some of them up to the first year after birth [35,36].…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies show that the arrest of germ cell differentiation is the key event, which may be followed by malignant transformation and invasive GCT development, usually occurring in young adults [16,32,35]. CIS cells have some morphological features of gonocytes, but also display a series of antigens present normally in the foetal period of life, some of them up to the first year after birth [35,36]. After this age, foetal antigen expression is used as an immunohistochemical marker of malignant germ cells.…”

Section: Discussionmentioning

confidence: 99%

The risk of neoplasm associated with dysgenetic testes in prepubertal and pubertal/adult patients

Słowikowska-Hilczer

Szarras‐Czapnik

Wolski

et al. 2015

Folia Histochem Cytobiol.

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Introduction. In patients with Y-chromosome in the karyotype, partial gonadal dysgenesis and disorders of male reproductive sex organs development are usually resected in childhood because of the high risk of germ cell tumours (GCT). In patients with Y-chromosome, complete gonadal dysgenesis and female genitalia gonadectomy is performed markedly later. However, due to the relatively low number of adult patients with preserved dysgenetic gonads, the true risk of neoplasm is unknown. The aim of the study was to evaluate the prevalence of neoplasia in dysgenetic gonads of children and adults with Y-chromosome in a retrospective study. Material and methods. A review of medical documentation of 94 patients with disorders of sex development (DSD), Y-chromosome and gonadal dysgenesis (GD), aged 1.2-32 years (47 prepubertal, 1.2-10 years; 47 pubertal/adult, 13-32 years), was conducted. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were determined. Bilateral gonadectomy was performed in 73.4% of patients, and unilateral gonadectomy with biopsy of the contralateral gonad in 26.4%. All gonadal tissues were subjected to immunohistochemical evaluation with antibodies against PLAP and OCT3/4 (markers of malignant germ cells, but also foetal multipotent germ cells), while gonads of prepubertal patients were examined by c-KIT, as well. Results. Streak gonads were identified on both sides (complete GD) in 30.8%, a streak gonad on one side and an underdeveloped testis on the other (asymmetric GD) in 38.3%, and underdeveloped testicular structure on both sides (partial GD) in 30.8% of cases. Germ cell neoplasia was found in 53.2% of patients (51.1% in children, 55.3% in pubertal/adults). Invasive GCT were identified in 11.7% of cases, of which 90.9% were in pubertal/adult patients. Other neoplastic lesions included gonadoblastoma (16% prevalence) and testicular carcinoma in situ www.fhc.viamedica.pl (25.5%). In younger patients FSH serum levels were increased in 81% of cases (mean 2.82 ± 2.18 IU/L), while LH in 58% (mean 1.82 ± 1.69 IU/L). Hypergonadotropic hypogonadism was diagnosed in most of the pubertal/ /adult patients (mean FSH 54.2 ± 23.3 IU/L, mean LH 21.7 ± 12.1 IU/L, mean testosterone 5.5 ± 4.5 nmol/L). Conclusions. Dysgenetic gonads in patients with Y chromosome have a high risk of germ cell neoplasia (ca. 50%). If they are preserved until puberty/early adulthood, they may develop overt, invasive GCT. The gonads also have poor hormonal activity (hypergonadotropic hypogonadism) in most of the pubertal/adult patients. Each of these cases must be considered individually and a decision to remove the gonad or not should be based on the comprehensive analysis of the phenotype by a multidisciplinary team of specialists in consultation with the patient and the parents. If dysgenetic gonads are not resected in childhood, these patients need careful ongoing follow-up examination, including biopsy and histopathological evaluation.

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“…25,26 In line with this origin of TGCTs, individuals with severe abnormalities of gonadal development associated with the intersex syndrome, currently referred to as Disorders of Sex Development (DSD) 27 show an increased risk for this kind of cancer, in which the Y chromosome genetic material is of crucial importance. 8,28 The Y Chromosome…”

Section: The Precursor Lesion Of Tgctsmentioning

confidence: 99%

“…1,[6][7][8] This is the most likely reason that markers for embryonic germ cells, like OCT3/4 (see below), are diagnostic for the precursor lesion of TGCTs. Epidemiological studies showing striking geographical and ethnic differences largely support the TDS hypothesis.…”

Section: Introductionmentioning

confidence: 99%

Genetic aspects of testicular germ cell tumors

Krausz

Looijenga²

2008

Cell Cycle

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Testicular Germ Cell Tumor (TGCT) is the most common malignant tumor in young Caucasian men with an annual increase of 3-6% in the past 50 years. Data in the literature indicate that both environmental and genetic factors acting on the primordial gonocyte/gonocyte are implicated in the etiopathogenesis of this tumour. Genetic linkage and genome-wide analyses did not reveal a major gene effect so far, implying that multiple loci must contribute to the development of TGCTs. Only one significant genetic risk factor has been reported, the so called "gr/gr" deletion of the Y chromosome which still request further confirmation by independent studies. On the other side, the analysis of somatic genetic changes through mutation and genome imbalance analyses and expression profiling has just began to unravel the complex interaction of multiple pathways involved in TGCTs. This review focuses on genetic factors (both genomic and somatic) involved in the etiology, progression and treatment sensitivity of TGCTs.

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New insights into type II germ cell tumor pathogenesis based on studies of patients with various forms of disorders of sex development (DSD)

Cited by 68 publications

References 81 publications

Dysgerminoma and gonadoblastoma in the course of Swyer syndrome

Dysgerminoma and gonadoblastoma in the course of Swyer syndrome

The risk of neoplasm associated with dysgenetic testes in prepubertal and pubertal/adult patients

Genetic aspects of testicular germ cell tumors

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