Mixed testicular germ cell tumor in an adult with cryptorchidism and Down's syndrome

We here present a case of mixed testicular germ cell tumor in an adult with cryptorchidism and Down's syndrome. A 20-year-old Japanese man with a mass in the left inguinal region underwent orchidectomy as a left testicular tumor was suspected. Histology showed a mixed germ-cell tumor with embryonal carcinoma and yolk sac tumor with syncytiotrophoblastic giant cells occurring in a cryptorchid testis. Chromosomal analysis of peripheral lymphocytes disclosed a karyotype of 47,XY,+21[20]. Our case provides further evidence that these three conditions-Down's syndrome, cryptorchidism and testicular germ cell tumor-may be closely associated. To our knowledge this is the first case of mixed germ cell tumor arising in a patient with Down's syndrome and cryptorchidism.     

Interphase cytogenetics on paraffin sections of paediatric extragonadal yolk sac tumours

Germ cell tumours in children are more often extragonadal than in adults and the most frequent type is the yolk sac tumour. Limited cytogenetic data exist on extragonadal yolk sac tumours in children. We applied in situ hybridization (ISH) to interphase cell nuclei of four paediatric extragonadal pure yolk sac tumours and one yolk sac tumour component of a mixed germ cell tumour using paraffin-embedded tissue sections. The panel of chromosome-specific DNA probes was selected on the basis of their relevance in adult germ cell tumours and consisted of five DNA probes specific for the (peri)centromeric regions of chromosomes 1, 8, 12, and/or 17, X and/or one DNA probe specific for the subtelomeric region of chromosome 1 (p36.3). Only one tumour failed to show numerical and structural chromosome aberrations with the DNA probes used. The other four had an increased incidence of numerical chromosome aberrations with an over-representation of at least one chromosome. The DNA indices determined in the paraffin-embedded tumour material correlated well with the in situ hybridization findings. In only a few cases were chromosomes over-represented, when compared with the corresponding DNA indices. Recently, we have shown that the short arm of chromosome 1 is a non-random site of deletion in paediatric gonadal pure yolk sac tumours. The occurrence of similar deletions in one extragonadal pure yolk sac tumour and in one yolk sac tumour component, in conjunction with two further ISH reports, suggests that the loss of gene(s) in this region is an important event in the pathogenesis of paediatric malignant germ cell tumours of nearly all sites.     

The Concept of Endodermal Sinus (Yolk Sac) Tumour

The concept of origin and natural history of endodermal sinus tumours (yolk sac tumours) is reviewed. These tumours were recognized and defined on a comparative histogenetic-embryologic basis as germ cell tumours with selective overgrowth of the extraembryonic endoderm and mesoblast of the yolk sac. The concept of endodermal sinus tumour has created solid and rational basis for the study of alpha-fetoprotein reappearance in a formerly heterogeneous and confusing group of tumours, whether they occur in the adult or in infantile gonads, or in such extragonadal sites as the mediastinum, the sacrococcygeal region, the pineal gland, the retroperitoneum or the infant vagina. Alpha-fetoprotein studies, in turn, have furnished new evidence in favour of the concept.     

Rhabdomyosarcomas developing in association with mediastinal germ cell tumours

Summary Two mediastinal rhabdomyosarcomas that arose in association with germ cell tumours are reported. One presented as a small component of a mixed germ cell tumour with yolk sac and immature teratomatous elements. The other appeared as a large mass 4 months after diagnosis of a yolk sac carcinoma that had been treated with chemotherapy. The first patient was alive and free of disease 7 years later, whereas the second died of tumour 3 months post-operatively. The proportion of rhabdomyosarcoma within the germ cell tumours appears to have influenced the prognosis of these patients. This observation emphasizes the necessity of performing a thorough search for sarcomatous elements and quantifying their relative proportion in germ cell tumours of the mediastinum.     

Intratubular germ cell neoplasia in an infantile testis with immature teratoma

A case of intratubular germ cell neoplasia adjacent to an immature teratoma is described in an 8-month-old boy with normally descended testes. The pattern of intratubular germ cell neoplasia in the infantile testis appeared different from that in the adult, but the abnormal germ cells were morphologically and immunohistochemically similar. In the few previous reports, which have investigated infantile testicular tissue for the presence of intratubular germ cell neoplasia adjacent to germ cell tumours, intratubular germ cell neoplasia in conjunction with a yolk sac tumour and mature teratoma have not been found, and cases with immature teratoma have not been reported. The presence of intratubular germ cell neoplasia in conjunction with immature teratoma and its apparent absence in conjunction with the mature form and with yolk sac tumour may indicate difference in tumour development. Whether there is a true difference in the occurrence of intratubular germ cell neoplasia in the infantile testis according to the various types of germ cell tumours remains, however, to be proven by investigations of more cases.     

Oral extragonadal yolk sac tumor in a patient with Aicardi syndrome: putative origin and differential diagnosis

We report, for the first time, a primary oral presentation of a germ cell yolk sac tumor in a 4-year-old girl with Aicardi syndrome. The diagnosis, differential diagnosis, and histogenesis are discussed.     

Features of prognostic significance in testicular germ cell tumours.

One hundred and one testicular tumours previously diagnosed as "teratoma" were examined and 93 of the patients were followed up. These neoplasm were assigned to one of three groups. Those compared exclusively of somatic tissues were the only tumours referred to as teratoma. The second group was exclusively extra embryonic and consisted of either yolk sac or choriocarcinoma. Neoplasms in the third group were called mixed germ cell tumours and incorporated somatic and extra embryonic tissue and occasionally seminoma. The patients with teratomas showed a very low mortality whereas pure yolk sac tumours proved highly malignant. In mixed germ cells tumours the malignant nature of the yolk sac components was maintained even when combined with somatic elements, but when seminoma was also present the survival rate was significantly improved. It would appear the yolk sac tumour tissue occurs more frequently in adult testicular neoplasms than was previously suspected and in mixed germ cell tumours it can be expected to dictate behaviour except when combined with seminoma.     

i(12p) in a malignant ovarian tumor

We have found one or more copies of i(12p) in an ovarian germ cell tumor, histologically a yolk sac tumor. This chromosome marker is characteristically associated with germ cell tumors in males. This report indicates that further investigation is necessary to establish the role of the i(12p) marker in the pathogenesis of germ cell tumors also in females.     

Ovarian hepatoid yolk sac tumours: morphological, immunohistochemical and ultrastructural features

AIM: The clinicopathological, immunohistochemical and ultrastructural features of two ovarian hepatoid yolk sac tumours (H-YST) from our files are reviewed. METHODS AND RESULTS: Using avidin-biotin-peroxidase complex technique, the immunoprofile of these tumours was compared to that of a classic yolk sac tumour and to that previously reported for hepatocellular carcinomas. The clinicopathological and morphological features of our cases are similar to the seven previously reported ovarian cases. This rare germ cell tumour occurs in young females (mean age = 17.6 years) and presents most commonly with abdominal pain and a large ovarian mass (average size = 140 mm). Histologically, the tumours display a striking resemblance to hepatocellular carcinoma. The absence of an associated typical pattern of yolk sac tumour or other germ cell neoplasm may make it difficult to recognize the germ cell origin of this lesion. Our cases demonstrated positive staining for alpha-fetoprotein and alpha-1-antitrypsin. In addition, there was immunoreactivity with polyclonal carcinoembryonic antigen (CEA) antiserum in a canalicular pattern, focal staining for inhibin, oestrogen and progesterone receptors and absence of immunoreactivity for CK7 that contrasts with the immunophenotype of a usual yolk sac tumour. CONCLUSIONS: Ovarian H-YST and hepatocellular carcinoma share a similar immunoprofile. Ovarian H-YST is a highly aggressive tumour, most patients exhibit recurrence or die of disease within 2 years of diagnosis.     

Primary mixed germ cell tumour of the liver--a case report

Germ cell tumours in liver are uncommon. Fewer than 20 cases have been reported in the literature. Primary mixed malignant germ cell tumours of liver are even rare. Here we describe a case of primary mixed malignant germ cell tumour of left lobe of liver in a two and half year old male boy. This is the first reported case of primary mixed malignant germ cell tumour with components of yolk sac tumour and mature teratoma in an infant. The patient complained of gradual increase in abdominal distension, upper abdominal pain and loss of weight. Ultrasonography and computed tomography of the abdomen revealed a large hepatic mass. Serum alpha-feto protein levels were raised. Left lobectomy of liver was done and chemotherapy was initiated. Histopathology of specimen disclosed yolk sac tumour and mature teratoma. Levels of serum alpha-feto protein declined rapidly. Widespread intrahepatic metastasis developed and patient died due to liver dysfunction after six months of left lobectomy.     

Germ cell tumours of the ovary: selected topics

We discuss germ cell tumours of the ovary, beginning with dysgerminoma as it is the most common malignant germ cell tumour in this location. Issues in differential diagnosis are highlighted as this tumour is associated with an excellent outcome nowadays and can be confused with small cell carcinoma, clear cell carcinoma, and rarely other neoplasms.The many patterns of yolk sac tumour are noted including the recently emphasized solid growth that may mimic dysgerminoma. Immunohistochemical stains are helpful in the diagnosis of both these primitive tumours, both being SALL4 positive and dysgerminoma expressing OCT4, D2-40 and c-KIT and yolk sac tumour having been recently reported to be GATA3 positive. Glypican-3 is also positive in yolk sac tumour but should be used with caution as it is often expressed in surface epithelial carcinomas, particularly clear cell carcinoma which can be in its differential. Where the fascinating polyembryoma should be placed in the classification of ovarian tumours is briefly considered.In the teratoma family emphasis is placed on the gross differences between the mature cystic and immature forms. The most important categories of monodermal teratoma are then considered emphasizing their varied problems in differential diagnosis.     

Laminin in testicular germ cell tumours. An immunohistochemical study

Thirty-five testicular germ cell tumours comprising 16 yolk sac tumours, 15 embryonal carcinomas and 13 seminomas were examined for the presence and distribution of laminin using an indirect immunoperoxidase technique. In addition, nine normal yolk sacs and 23 carcinomas of the lung were studied. All the yolk sac tumours were positively stained for laminin. Both extra- and intracellular staining were found. Hyaline, eosinophilic material present within the tumours was positively stained, although with varying intensity. In 12 out of 15 embryonal carcinomas, laminin was found as a membrane staining but cytoplasmic staining also occurred. In 10 out of 13 classical seminomas, a membrane staining of many tumour cells was found, while cytoplasmic staining occurred in only a few seminomas. In all but one of the yolk sacs, laminin was present in the membrane beneath both the mesoblastic outer cell layer and the visceral endoderm. Intracellular staining was seen in some of the cells in both cell layers. In nine out of 23 carcinomas of the lung, laminin occurred extra- as well as intracellularly. Thus, this study showed that in normal yolk sacs the presence of laminin was not found to be particularly associated with any of the cell layers. Likewise, demonstration of laminin within yolk sac tumours did not define different patterns or subtypes of the yolk sac tumour. In addition, demonstration of laminin was not found to be useful in differentiating either between yolk sac tumours and embryonal carcinomas or between seminomas and non-seminomatous germ cell tumours. The findings add, however, interesting knowledge to histogenesis and embryogenesis.     

Germ cell lineage differentiation in non-seminomatous germ cell tumours

Human germ cell tumours (GCTs) have long fascinated investigators for a number of reasons. Being pluripotential tumours, they can differentiate into both extra-embryonic and embryonic (somatic) tissues. However, it has never been shown convincingly that, in humans, these tumours are truly totipotent and can also give rise to the germ lineage, the third major differentiation lineage occurring early during embryonic life. Using a number of newly available, distinct, immunohistochemical markers, such as OCT3/4, VASA and TSPY, the occurrence of germ cells was investigated in a number of germ cell tumours. Development of germ cells was identified in three independent non-seminomas, including two pure yolk sac tumours and one mixed tumour composed of yolk sac tumour and immature teratoma. Our finding indicates a previously unknown totipotent potential of human GCTs and raises the question of whether, under certain culture conditions, primordial germ cells could be derived from human GCT cell lines.     

Primary Intracranial Germ Cell Tumors without an Isochromosome 12p

Primary intracranial germ cell tumors are the result of the transformation of primordial cells that are unable to migrate to their normal place. These tumors are rare, accounting for less than 5% of all intracranial tumors and less than 3% of childhood neoplasias. In this paper, we have studied cytogenetically two primary intracranial germ cell tumors, a pineal region germinoma, and a mature teratoma in the right lateral ventricle. Neither tumor presented polyploidy or isochromosome 12p, considered to be characteristic of gonadal germ cell tumors. In the five reports in the literature, only one intracranial germ cell tumor presented i(12p). Perhaps i(12p) negative cases characterize a subtype of germ cell tumors.     

Gastric cancer with choriocarcinoma and yolk sac tumor components: case report

Choriocarcinoma- and yolk sac tumor-like differentiation have rarely been reported in gastric cancers. We report a case of gastric adenocarcinoma, concurrently possessing choriocarcinoma and yolk sac tumor components, of a 74-year-old man. A hemorrhagic, 11 × 8 × 3 cm, tumor with ulceration was located in the body and pre-pylorus of the stomach. Histological examination of the resected specimens demonstrated intermingled proliferation of three different components, namely, adenocarcinoma, choriocarcinoma and yolk sac tumor, which were immunoreactive for carcinoembryonic antigen (CEA), beta-subunit of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP), respectively. Gastric cancers with germ cell tumor components are uncommon and this is the second reported case of gastric cancer with choriocarcinoma and yolk sac tumor components.     

Mediastinal germ cell tumors and histiocytosis

Two cases of mediastinal germ cell tumors associated with primary hemoproliferative disorders are reported. The first case was a 23-year-old man who presented simultaneously with a mediastinal immature teratoma with focal yolk sac differentiation and a cytologically benign histiocytic proliferation associated with refractory thrombocytopenia. In the second case, an unsuspected mediastinal immature teratoma with focal yolk sac and hepatic differentiation was found postmortem in a 33-year-old man who had died of fulminant malignant histiocytosis. Although the histiocytosis in the former case failed to fulfill all the usual diagnostic criteria of malignant histiocytosis, both cases probably represent different manifestations of the same pathologic process. Review of the 19 published cases of hematologic malignancies associated with mediastinal germ cell tumors and of related experimental studies suggests a role for yolk sac differentiation in the pathogenesis of this syndrome.     

Yolk sac tumor of vagina: a case report

Malignant germ-cell tumors (MGCT) are rare tumors of childhood accounting for less than 3% of pediatric malignancies. Yolk sac (endodermal sinus) tumor is one of the malignant germ cell tumor that usually involves the gonads (ovaries and testes). Its occurrence in the vagina is extremely rare. We report a 6-months old girl presented with a vaginal mass diagnosed as a yolk sac tumor. This diagnosis is confirmed by histopathologic examination, immunehistochemical studies as well as elevated serum alpha fetoprotein (AFP).     

Intrarenal pure yolk sac tumor: an extremely rare entity

Yolk sac tumor (endodermal sinus tumor) is a malignant germ cell tumor that usually arises in the gonads. Extragonadal germ cell tumors are rare and have been described in case reports. We report a pure intrarenal yolk sac tumor in a 1-year-old boy who presented with a huge abdominal mass and was operated for suspected Wilms tumor. The tumor exhibited histopathologic and immunohistochemical features identical to those of an endodermal sinus tumor of gonadal origin. The purpose of this report is to add a rare tumor to the differential diagnosis of pediatric renal neoplasms.     

Germ cell tumours of childhood: a review of 137 cases.

One hundred and thirty-seven germ cell tumours occurring in 134 children included in the Manchester University Children's Tumour Registry over a 25-year period have been studied. The incidence and sites of these tumours as seen in a comprehensive population-based registry are presented and the relation between the primary site and histological type is assessed. There were 48 deaths in this series of which 34 were directly due to the tumour. The cause of death in the other 14 cases is given. The behaviour of the germ cell tumours was closely related to the presence of yolk sac elements.     

Teratoma of the Sellar Region: a Case Report

The case report describes a teratoma of the sellar region with a gland forming and an immature, relatively clear undifferentiated component without signs of anaplasia. Both components express TTF-1 indicating their presumable origin in the neurohypophysis as part of the circumventricular organs. The differential diagnosis includes pituitary adenoma and spindle cell oncocytoma with inclusion of Rathke’s cleft cyst, pituitary blastoma, yolk sac tumor, and other germ cell tumors. The prognosis is the same as in the immature teratomas in the gonads, specifically unclear.