A novel splice mutation in the TP53 gene associated with Leydig cell tumor and primitive neuroectodermal tumor.

A 20-month-old boy presented with precocious puberty due to a Leydig cell tumor, and at the age of 6 years with a primitive neuroectodermal brain-tumor (PNET). A novel splice site mutation of the TP53-gene, likely to be associated with a nonfunctional protein, was found in the proband, his father and younger sister, but only the proband has so far developed malignancy. The clinical phenotype in the boy is suggestive of Li-Fraumeni syndrome, but the family does not strictly conform to the canonical definition.

Primordial germ cell proliferation in fetal testes in mouse strains with high and low incidences of congenital testicular teratomas.

The development of genital ridges in mouse strains were compared with high and low susceptibility to teratocarcinogenesis. The number of dividing primordial germ cells (PGC) was low at 12 days of gestation. The number increased sharply at 13 days and decreased precipitously by 15 days of gestation. The period of high mitotic activity closely paralleled the period of susceptibility to experimentally induced teratocarcinogenesis. Testes that had a long proliferative period had a higher incidence of teratomas than those that had a short proliferative period. A group of fetuses was identified that had markedly fewer than normal PGC. The incidence of teratomas in this group was very high, and nearly all growths were bilateral.

A recessive mutation (ter) causing germ cell deficiency and a high incidence of congenital testicular teratomas in 129/Sv-ter mice.

The genetic basis of a germ cell deficiency, accompanied by a high incidence of testicular teratomas, was studied in strain 129/Sv-ter mice (formerly designated "129/terSv"). Germ cell deficiency became more severe with advancing age in males, and they were sterile whether or not they had bilateral teratomas. Germ cell-deficient testes were smaller than normal except when the testes had teratomas. In females the ovaries were smaller than normal, but the germ cell deficiency did not progress and most were fertile. The germ cell deficiency resulted from the homozygous state of a recessive mutant gene designated "teratoma (ter)." Matings between females with small ovaries and homozygous normal males produced no germ cell-deficient offspring. When F1 offspring with normal gonads were mated together, germ cell-deficient F2 animals appeared at a frequency close to 1 in 4. When females with small ovaries (ter/ter) were mated with heterozygous males (ter/+), half of the offspring were germ cell deficient. It was concluded that the genetic factor is a single recessive gene. The incidence of teratomas in +/+ strain 129/Sv-ter males was 1.4% (3/216), and all teratomas were unilateral. Seventeen percent (20/117) of heterozygous males had teratomas, of which 18 were unilateral and 2 were bilateral. Ninety-four percent (167/178) of homozygous ter/ter males had teratomas, of which 75% were bilateral. Introduction of the mutant gene ter onto the C57BL/6 genetic background resulted in germ cell deficiency in homozygotes, but it reduced considerably the teratoma incidence in ter/ter males.

Sertoli cell tumour in a neonate calf: an unusual congenital tumour. A case report.

Congenital testicular tumours are seldom reported in bovine species. This case report describes the clinical, sonographical, haematological, pathomorphological and immunohistological features of a Sertoli cell tumour in a neonatal German Holstein calf. Microscopically, the enlarged testicle was composed of neoplastic cells, which were packed in well-formed tubules. The mostly polygonal shaped cells had round to elongated nuclei and a scanty eosinophilic cytoplasm. Some cells were arranged perpendicularly to the light PAS-positive basement membrane. These cells were packed in broad sheets separated by dense fibrous stroma. Mitotic figures were present. The features described above are indicative of a Sertoli cell tumour. The contralateral testicle showed a well formed rete testis, fusiform cells and a dense central capillary convolute and haemorrhagic foci. The features are indicative of an extensive fibrosis and older haemorrhage. The neoplasia was immunopositive for vimentin, α-oestrogen receptor, α-inhibin and S-100 protein, but immunonegative for cytokeratine, CD30, progesterone receptor, α-fetoprotein, SALL4, OCT4 and glypican-3. The mycotoxicological investigations revealed the presence of residues of zearalenone, deoxynivalenol, ochratoxin, HT2 toxin and their metabolites in feeds and urine of heavily pregnant cows of the herd. Furthermore, information is provided about oestrogen and testosterone levels of the affected and healthy neonatal calves. A possible influence of mycotoxins on the cancerogenesis is discussed.

Intrauterine torsion of a testicular teratoma: a case report.

Neonatal testicular tumors and intrauterine testicular torsions are very rare. The presented case is the first describing intrauterine torsion of a descended testis with a teratomatous tumor. Immediately after birth, right hemiscrotal swelling was seen in a preterm male newborn. Surgical intervention showed extravaginal testicular torsion and a highly differentiated testicular teratoma with haemorrhagic infarction. The testis was removed (orchiectomy). Over a period of twelve months no signs of tumor recurrence were found. While being extremely rare, testicular tumors should be included in the differential diagnosis of neonatal scrotal swelling.

Congenital juvenile granulosa cell tumor of the testis in a fetus showing full 69,XXY triploidy.

Testicular juvenile granulosa cell tumor (TJGCT) occurs predominantly in infancy and may be associated with sex chromosomal abnormalities. We report a fetus aborted because of cytogenetically confirmed complete XXY triploidy. External genitalia of the fetus were female, with a short and patent vagina. The tumor presented as an abdominal multicystic mass with typical histologic and immunohistological features of JGCT. It was connected with a tubular uterus-like structure. The other gonad was an inguinally localized testis that showed histologically a Sertoli cell adenoma. Malformations typical for triploidy were also present: agenesis of the corpus callosum, stenosis of the pulmonary ostium, and hypoplasia of the lungs and adrenals. To our knowledge this is the first case of TJGCT in a triploid fetus.

Congenital testicular juvenile granulosa cell tumor in a neonate with X/XY mosaicism.

A congenital sex cord-stromal tumor of the testis with morphologic features of juvenile granulosa cell tumor is reported. The tumor occurred in an abdominal testis of a newborn infant with an X/XY karyotype and ambiguous genitalia and presented as a partially cystic mass associated with ascites. Histologically the tumor was comprised of an admixture of solid, cellular, poorly differentiated lobules mimicking graafian follicles. Residual hypoplastic testicular tissue was present at the periphery. This is the 19th reported case of testicular juvenile granulosa cell tumor and the fourth with an underlying sex chromosome anomaly, further emphasizing the relationship of this uncommon neoplasm to abnormal sexual or gonadal development.

Prepubertal testicular tumor registry.

There are 327 patients in the Prepubertal Testicular Tumor Registry, and demographic data and a better understanding of the natural history and behavior of the tumors have evolved. Information on these rare tumors should be collected centrally and treatment using national protocols followed closely. Continuation of the Registry is important to help clarify the knowledge of these unusual tumors and to aid in the management of these patients through information from a large database.

Torsion of an undescended intraabdominal benign testicular teratoma.

A 4-year-old well boy was seen because of an asymptomatic left testicle undescended since birth; the testis was not palpable and the right side was normal. After an episode of left lower quadrant and left hip area pain, with some bladder symptoms and left leg limping, a work-up including a CAT scan showed a calcified retroperitoneal pelvic tumor on the left side. At laparotomy, an infarcted mass was found in the pelvis just above the internal ring. It was a torsion of an undescended intraabdominal testis with a benign testicular teratoma. The tumor was removed and his recovery was uneventful.

Paratesticular congenital malignant rhabdoid tumor diagnosed by fine-needle aspiration cytology. a case report.

We report the FNA features of a congenital malignant extrarenal rhabdoid tumor (MERT) located in the right paratesticular area of a newborn full-term boy (39 wk gestation), with disseminated metastases in the liver and right parietal region. The diagnosis was suggested two days after birth by fine-needle aspiration biopsy (FNAB) of the parietal mass, which demonstrated an atypical large cell proliferation with vesicular nuclei, prominent nucleoli, and abundant cytoplasm exhibiting paranuclear dense inclusions. The diagnosis was confirmed by histopathologic and immunohistochemical examination of the primary paratesticular tumor. To the best of our knowledge, this is the third MERT reported in the paratesticular region, one of the few congenital extrarenal non-central nervous system cases, and the third congenital case (renal or extrarenal) primarily diagnosed by FNAB. We emphasize the characteristic cytologic features of a congenital rhabdoid tumor, which must be known by pathologists because of the clinical and prognostic implications. Diagn. Cytopathol. 2004;30:46-50.

Ruptured cystic teratoma of the testis in a neonate.

Neonatal testicular tumors are extremely rare. We report the case of a full-term male newborn with right hemiscrotal swelling found immediately after birth. The right hemiscrotal skin gradually turned dusky dark and then adhered to the hard scrotal contents. Missed right testicular torsion was suspected and emergency exploration was not attempted. Right hemiscrotal swelling became aggravated, so right orchiectomy and left orchidopexy were performed. During surgery, severe inflammation of the right testis and the right hemiscrotum were observed and diffuse hemorrhage with focal hematomas was noted within the removed right testis. Histopathology of the specimen revealed a ruptured mature cystic teratoma of the testis. The alpha-fetoprotein concentration was 729 x 10(4) micrograms/L 10 days after the operation, and dropped to 185 x 10(4), 25 x 10(4), and less than 20 x 10(4) micrograms/L 2, 5, and 8 months later, respectively. Postoperative abdominal and pelvic computerized tomography scans revealed neither lymphadenopathy nor distant metastasis. During a follow-up of 8 months, no evidence of tumor recurrence was found. Although extremely rare, testicular tumors should be included in the differential diagnosis of an enlarged hard or firm scrotal mass in the male neonate.

WKY/Ztm-ter: a new rat inbred strain on the WKY/Ztm genetic background with congenital teratomas.

We describe a new rat model for teratomas (WKY/Ztm-ter) which arose through a spontaneous mutation in the inbred WKY/Ztm rat strain. When the tumours of the gonads became clinically apparent, affected males were 14 to 224 days of age, whereas the females only developed tumours between days 21 and 63. Tumour incidence is not gender-dependent. However, almost all females develop bilateral tumours, while 50% of the males show unilateral tumours. Histologically, all examined tumours (n = 65) represent partially undifferentiated teratocarcinomas.

Juvenile granulosal cell tumor of the testicle.

This is a case of a newborn with a rare testicular tumor-a juvenile granulosal cell tumor. This is a tumor of stromal origin, which is similar histologically to granulosal cell tumors of the ovaries. The authors present the imaging characteristics and differential diagnoses in this patient.

Testicular adrenal rest tumors in boys with congenital adrenal hyperplasia: 3D US and elastography--do we get more information for diagnosis and monitoring?

BACKGROUND: Testicular adrenal rest tumors (TART) are the nodular testicular lesions deriving from the adrenal remnant tissue reported in boys and men with congenital adrenal hyperplasia. Until now, the diagnostics of TART have been based on a combination of clinical features, imaging methods (primarily two dimensional ultrasound--2D US), response of the foci to glycocorticosteroid (GCS) therapy and exclusion of the neoplastic process. Application of 2D US supplies however a limited range of information about the volume, demarcation, structure and vascularization of the lesions. OBJECTIVE: To define whether the use of 3D US, power Doppler and elastography changes the algorithm of the diagnostics and monitoring or treatment of TART. MATERIAL AND METHODS: In this study, modern ultrasound techniques such as 3D US and elastography were introduced in two boys with TART. RESULTS: The 3D power Doppler option gives the opportunity for accurate assessment of the volume of testes and adrenal tissue foci and their vascularization. Sonographic elastography allows the assessment of stiffness of adrenal tissue areas compared to normal testis parenchyma. CONCLUSION: The use of these modern techniques enables more adequate and advanced diagnostics, and more precise monitoring of the effects of treatment in patients with TART.

Congenital intra-abdominal bilateral juvenile granulosa cell tumors of the testis associated with constitutional loss of material from chromosome 4.

Juvenile granulosa cell tumor (JGCT) is an uncommon gonadal stromal tumor that occurs rarely in the testis. We report a newborn boy with bilateral intra-abdominal JGCT presenting with abdominal distention and respiratory distress at birth. He was taken to the operating room emergently, and 2 large masses connected by gubernacula to the inguinal canals were resected. Associated abnormalities included a constitutional chromosome 4 abnormality, polymicrogyria, and renal cysts. This report describes a rare presentation of JGCT with abdominal compression and expands the literature to include bilateral testicular involvement. Additionally, it is the 1st report of JGCT associated with a chromosome 4 abnormality, highlighting a genetic region that may be important in JGCT development.

Congenital juvenile granulosa cell tumor of the testis in newborns.

BACKGROUND: Granulosa cell tumor of the testis is a rare intermediate stromal cell tumor that can be distinguished in the adult and juvenile type. The juvenile type is the most common reason for scrotal swelling in newborns under the age of six months. Less than fifty cases of this disease entity have been reported in the literature. PATIENTS AND METHODS: In the following article, two newborn patients with scrotal swelling and a histological confirmation of juvenile granulosa cell tumor of the testis will be presented. RESULTS: Case 1: A newborn patient presented with massive scrotal swelling. Sonography of the testicle exhibited a multiple septic and cystic enlargement of the testicle without distinction of the testicular parenchyma being possible. The laboratory findings demonstrated normal testosterone levels, beta-HCG and inhibin-B levels as well as an increased alpha-fetoprotein level of 35.350 ng/dl. Due to clinical and sonographic findings, an inguinal exploration and later, due to the impossibility of distinction of the testicular parenchyma, an inguinal orchiectomy of the right testicle was performed. Case 2: The clinical and sonographic examination of a newborn patient demonstrated a suspicious process of the left testicle. Sonography exhibited an enlarged testicle with cystic formations with the distinction of the testicular parenchyma not being possible. The laboratory findings demonstrated normal testosterone levels, beta-HCG and inhibin-B levels as well as an increased alpha-fetoprotein level of 9.038 ng/dl and LDH of 768 U/I. An inguinal orchiectomy of the left testicle was performed. In both cases, a histological diagnosis of juvenile granulosa cell tumor of the testis was made. CONCLUSION: These two aforementioned cases demonstrate that juvenile granulosa cell tumor of the testis is a benign disease encountered in newborns, which exhibits an excellent prognosis. Inguinal orchiectomy is the therapy of choice. After surgical removal of the involved testicle is performed no further management is required.