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Peptidylarginine deiminase type 4 (PADI4) converts arginine residues into citrulline. The current study focused on the expression of PADI4 in various subtypes of ovary cancers, and this study investigated the effects of estrogen on PADI4 expression in SKOV-3 cells that originated from ovary tumors. We utilized immunohistochemistry, real-time PCR and western blotting to analyze the expression of PADI4 in the tumor tissues and in the cell line that were cultured with estrodial-17β. PADI4 was detected in serious cystadenocarcinoma (n=39, positivity=100%), clear cell cancer (n=7, positivity= 100%), mucinous cystadenocarcinoma (n=6, positivity=100%), dysgerminoma (n=6, positivity=100%), squamous cell tumor (n=6, positivity=100%), sibnet-ring cell carcinoma (n=6, positivity=100%), endodermal sinus tumor (n=6, positivity=100%), germ cell tumors (n=6, positivity=100%) and immature teratoma (n=6, positivity=100%). However, PADI4 was either not detected or detected at low levels in granulosa cell tumor (n=6), malignant thecoma (n=6), ovarian cystadenoma (n=5) and normal ovarian tissue (n=11). For serious cystadenocarcinoma, all of the samples with high PADI4 expression belonged to the T1 and T2 stages of pTMN, whereas all of the samples that exhibited weak or moderate PADI4 expression belonged to the T3 and T4 stages. PADI4 was evenly distributed in the cytoplasm of tumor cells of serious cystadenocarcinoma that were classified as being grade II and III by histopathological scoring. However, PADI4 showed granular cellular distribution in the tumor tissues that were isolated from grade I cystadenocarcinoma. In addition, the PADI4 level was positively related with the ages of the patients that presented with serious adenocarcinoma (p=0.029). Real-time PCR and western blot analyses confirmed that PADI4 was expressed at higher levels in ovarian adenocarcinoma (n=8) compared to ovarian cystadenoma (n=5) (p< 0.05). The study also detected an increased level of PADI4 in SKOV-3 cells that were incubated with estrodial-17β in the range of 10(-12) to 10(-4)M. The results suggest an important role for PADI4 in the tumorigenesis of ovary cancers that are under the regulation of estrogen.

Lymphovenous shunts have been detected in patients by lymphography with Ultrafluid Lipiodol. No shunts were found in patients with normal lymphatic systems. They were found in patients with lymphoedema, with lymph nodes involved by malignant disease, and in patients who had had surgical interruption of lymphatic pathways, either vessels or nodes. The total incidence of lymphovenous shunts in 700 lymphographic studies was 2·3%. The incidence in the various pathological groups was highest in those with obvious lymph node involvement. In certain situations, particularly primary lymphoedema, the role of a lymphovenous shunt appears favourable to prognosis. In other situations a deleterious effect may be produced.

Our understanding of gonadal pathology has reached its current state as a result of the contributions of numerous outstanding investigators. Knowledge of testicular tumor pathology dates back to the great British workers Percival Pott and Sir Astley Cooper but the single greatest early stride was made with the description in 1906 by the French urologist Maurice Chevassu of the seminoma. The seminal 1946 paper of Nathan B Friedman and Robert A Moore, which segregated out as a distinct entity embryonal carcinoma, is, however, the foundation for the current classification of testicular tumors. In that year Pierre Masson described the distinctive neoplasm, the spermatocytic seminoma. The 1950s saw the publication of an important paper by Frank J Dixon and Dr Moore and they also wrote the first series fascicle on testicular tumors. In this same timeframe, and thereafter, Robert E Scully made significant contributions to testicular pathology, writing the first English language paper on spermatocytic seminoma, describing several subtypes of sex cord tumor, and also the distinctive lesion of intersex, the gonadoblastoma, as well as playing a major role in 1980 in formulating the current classification of premalignant lesions of the testis. The current classification of testicular tumors was arrived at in the early 1970s when the World Health Organization, under the leadership of Dr FK Mostofi, who himself made notable contributions to testicular pathology, devised what is fundamentally the current classification of neoplasms of the male gonad. Although comments on ovarian pathology were made by such legendary figures of earlier times as Giovanni Battista Morgagni and Matthew Baillie, it is only in the mid to later years of the 19th century that contributions, mostly in Europe, began to move knowledge of ovarian pathology to its current state. Thomas Hodgkin, Richard Bright, and Sir James Paget all wrote extensively on ovarian neoplasms. In 1870, Heinrich Waldeyer, and later in that century, another German, Hermann Johannes Pfannenstiel wrote important papers on the surface epithelial tumors. The latter was likely the first to refer to neoplasms now known as of 'borderline malignancy' and also wrote on pseudomyxoma peritonei and other topics. Their work was followed by that of Robert Meyer who made monumental contributions to gynecological pathology, including recognizing the Brenner tumor as a distinctive neoplasm and proposing the first classification of Sertoli-Leydig cell tumors (arrhenoblastomas). He also coined the term 'disgerminoma' (soon changed to dysgerminoma) for the ovarian tumor that had been described in detail by the French investigator Marcel Chenot 5 years after Chevassu had mentioned the tumor in his paper describing the seminoma. During the Meyer era other significant contributions were made by, among others, Howard C Taylor writing on the borderline tumors and John A Sampson writing on endometriosis and tumors, associated with it. In the second-half of the 20th century major contributions were made by Gunnar Teilum of Denmark and Lars Santesson of Sweden. Dr Teilum delineated the morphologic features of the yolk sac tumor and noted the resemblance of papillary formations within it to the endodermal sinuses of the rat placenta. He also wrote extensively on sex cord tumors in both gonads. At a FIGO meeting in 1961 Dr Santesson played a major role in formulating the first organized classification of the surface epithelial-stromal tumors of the ovary and also promoted the endometrioid carcinoma as a special variant of ovarian cancer. In a career spanning over 50 years, Dr Scully was the architect of the modern classification of ovarian tumors being the driving force behind the influential 1973 World Health Organization classification of them. His many original observations have touched upon virtually all categories of ovarian tumor pathology. His second series fascicle 'Tumors of the Ovaries and Maldeveloped Gonads' utilized the WHO classification and presented a lucid elaboration of his by then vast experience with ovarian tumors. All the above have left a rich legacy which those who follow in their path will be challenged to equal.

Dysgerminoma is one of the two most common types of ovarian germ cell tumors. Providing accurate pathologic diagnosis and treatment planning, the prognosis is good even in advanced stages. Pathologic diagnosis is generally straightforward. In microscopic examination, the usual known growth patterns in tumor cells are solid, trabecular, insular and rarely pseudoglandular. In this paper, we reported an advanced ovarian dysgerminoma with different microscopic patterns of growth, including pseudopapillary and macrofollicular structures, in an 18-year-old woman. The patient underwent staging laparotomy and is currently receiving chemotherapy.

AimsVery recent papers proposed a possible role for the expression of terminal deoxynucleotidyl transferase (TdT) in the tumourigenesis of gonadal and extragonadal germ cell-derived tumours (GCTs). Our multicentric study evaluated the magnitude of the immunoreactivity for TdT in GCTs, encompassing seminoma, dysgerminoma, mature teratoma and mixed GCTs.Methods and resultsThe histological series was stained with both monoclonal and polyclonal antibodies, yielding a positivity of 80% of cases with well-defined nuclear reactivity. A significant difference in staining intensity between monoclonal and polyclonal antibodies was observed (p=0.005). However, exploiting western blot and more innovative proteomic approaches, no clear-cut evidence of the TdT protein was observed in the neoplastic tissues of the series.ConclusionsAlternatively to the pathogenetic link between TdT expression and GCTs tumourigenesis, we hypothesised the occurrence of a spurious immunohistochemical nuclear cross-reaction, a well-known phenomenon with important implications and a possible source of diagnostic pitfalls in routine practice for pathologists.

In 1927 Wangensteen wrote, ‘No greater diversity of opinion probably exists concerning anything in medicine than the question of malignancy in the undescended testicle.’ Since this was written a great number of papers has been published on this subject, and now it is generally accepted that the maldescended testis is more liable to undergo malignant change than the normally descended organ. The main factors which swayed opinion to this view were Campbell's analytical papers of 1942 and 1959. His conclusions were that malignancy was eleven times more frequent in the inguinal testis and sixty times more frequent in the intra-abdominal testis. The maldescended testis is also known to be more liable to torsion and trauma than is the normal organ. The following case illustrates two of the dangers to which an intra-abdominal testis is exposed.

The birth of a child with a disorder of sex development (DSD) prompts a long-term management strategy that involves a myriad of professionals working with the family. There has been progress in diagnosis, surgical techniques and in understanding psychosocial issues related to this condition. However, since these kinds of disorders are rare and have many anatomical variations, individual care is necessary, especially regarding surgical management. Gonadectomy is indicated in a number of intersex disorders with a Y chromosome to reduce the associated risk of cancer. Recently, laparoscopy has gained wide acceptance in pediatric urology. Laparoscopy is also reported to be a useful tool for diagnosing and treating DSD because of its minimal invasiveness and favorable cosmetic outcome. However, reports of evaluation and management using laparoscopy for large numbers of DSD patients are limited and debate is still open about indications and timing of gonadectomy. In this study, we reviewed the literature of the last 10 years about the role of laparoscopic gonadectomy in patients with DSD. In the analyzed papers, all the procedures were accomplished successfully using laparoscopy. No conversions to open surgery neither intra-operative complications were reported in all series. Post-operative complications were reported only in one series and included 1 umbilical port infection [2% (1/50)] and 1 pelvic abscess [2% (1/50)], both treated with antibiotic therapy (grade I Clavien-Dindo). Of the analyzed series, 7/10 reported postoperative diagnosis of gonadal tumors. The histopathologic examinations revealed 15 cases of gonadoblastoma, 7 cases of dysgerminoma and 2 cases of seminoma. Analyzing the single series, the incidence of these tumors varied between 10% and 33%. The results of our review confirmed the safety and efficacy of laparoscopic gonadectomy in DSD patients. In our mind, laparoscopic gonadectomy should be accepted as the treatment of choice in children and adolescents with these rare conditions. It thereby eliminates the risk of malignancies of gonadal origin with the advantages of a minimally invasive procedure, with lower morbidity, quicker postoperative recovery and excellent cosmetic results.

Ovarian remnant syndrome (ORS) represents the presence of functional ovarian tissue after routine castration of the bitch, caused either by surgeon error or the presence of anomalous ovarian tissue. The piece of ovary that remains after the surgery, may continue to develop and become functional, secreting hormones as estrogen and progesterone which cause signs of pro-estrus or estrus, even pseudocyesis. All those signs cause consternation among owners, who thought that the reproductive activity in their dog will be completely abolished. One mixed-breed, 6 years old bitch, 27.3 kg, spayed 8 months before, was presented with purulent vaginal discharge and mammary lumps, after the animal has been treated by her veterinarian with Proligestone to suppress the persisting estrus signs. Our investigations included vaginal cytology, vaginoscopy, the examination of the mammary chain, ultrasound, radiography, serum chemistry, blood count and histopathological examinations. The ultrasound revealed a filled uterine stump and the presence of a mass caudal the right kidney, which was suspected as an ovarian neoplasm. The examination of the mammary chain revealed masses in right M 3, M4, M5 glands and in the left M2 gland. The bitch underwent surgery, and the results of the histopathological examination were: dysgerminoma, pyometra, and the mammary masses were classified as carcinomas. In this paper we wanted to underline the fact that the Ovarian Remnant Syndrome may imply serious clinical consequences which can even lead to the death of the animal. We recommend as a method of treatment for this condition the surgical removal of the remnant tissue.

Introduction While testicular germ cell tumors (TGCTs) are the most common malignancy in young men, germ cell tumors in women are uncommon. Familial clustering, epidemiologic evidence of increased risk with family or personal history of TGCT, and associations with genitourinary tract anomalies suggest an underlying genetic predisposition to TGCT, but traditional linkage studies have yet to identify a highly penetrant TGCT cancer susceptibility gene. In this paper, we investigate the familial occurrence of testicular and ovarian germ cell tumors. Methods We report a family in which a TGCT and an ovarian germ cell tumor (OGCT) occurred in two siblings, summarize the existing literature on familial occurrences of OGCT, either alone or in combination with extragonadal or TGCTs, and compare the incidence of familial and sporadic testicular and ovarian GCTs. Sporadic GCT data were obtained from the US Surveillance Epidemiology and End Results (SEER) registry. Results We identified 16 reports of OGCT occurring in conjunction with either ovarian, testicular or extragonadal GCT. In these familial cases, the mean age at onset of female dysgerminoma was younger than that noted in the general population (age 17 vs. age 24, p =0.01). In SEER, the incidence of TGCT was 15 times higher than that of OGCT. Histologic distributions in males and females showed distinctly different patterns. Discussion Although the incidence of OGCTs in the general population is quite low, its occurrence in multiple members of the same family and in families with TGCT suggests that a gene conferring susceptibility to GCTs may exist in some families.

Introduction. Malignant tumours of ovary germ epithelium are very rare and account for about 2-5% of all ovarian tumours of germ origin. In adolescent patients under 20 years of age diagnosed to have ovarian tumour, these tumours originate from germ cells in about 70% of cases. Depending on the stage of the disease, medical treatment and age, the death rate ranges from 25% to 84%. A special group of germ tumours are mixed germ cells tumours built of two or more different types of germ tumours. Case report. This paper gives a diagnostic-therapeutic procedure and the clinical picture with the course and outcome of the decease in a nineteen-year old patient with a mixed malignant germ tumour (dysgerminoma, choriocarcinoma, immature teratoma) found in one of the ovaries. It also deals with the appearance and development, some characteristics and histological build of the tumours diagnosed in this case. Conclusion. Malignant tumours of ovary germ epithelium are very rare and develop in female population under 30 years of age. They are characterized by a high degree of malignity. They are resistant to cytostatic treatment, they spread very quickly with the lethal outcome. The course of the disease is not characteristic and is usually masked under some other acute gynaecological disease. The definitive diagnosis is made after laparotomy and pathohistological analysis of the tumour tissue.

Here we present the case of a 30-year-old man diagnosed with a dysgerminoma with mediastinal involvement, who developed an isolated chylopericardium during treatment. The purpose of this paper is to review the etiology, diagnosis and new approaches to the treatment of chylopericardium.

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.

Gonadal distribution in 409 cases of human true hermaphroditism is reviewed. An ovary was found on the left side of the body in 62.8% of the cases and the testis on the right side in 59.5%. The ovotestis is the most common gonad of the true hermaphrodite; amongst 806 gonads in 406 cases it was found in 44.3%. In this paper we give a detailed description of the morphology of ovotestis, testis and ovary in the true hermaphrodite. In addition we discuss the effects of fetal androgens and Müllerian inhibiting factor on the Wolffian and Müllerian ducts. Correlations between chromosomal complement and gonadal distribution are presented. True hermaphrodites with a 46,XX karyotype most commonly have an ovary on one side and an ovotestis on the other side; those with a Y-chromosome have a testis in 61% of cases. An analysis of the ratio of ovarian and testicular tissue within ovotestes showed a continuum from very little ovarian tissue to a small portion of testicular tissue. Each type of tissue was clearly demarcated. Hypotheses for gonadal induction in the true hermaphrodite should take cognizance of these facts. True hermaphrodites with a 46,XX chromosomal complement were characterized by a male phenotype in 54% of cases. This group may suggest a greater testicular induction ability in the genome as compared to the 46% with a female phenotype.

Cure of patients with disseminated cancer using medical as opposed to surgical or radiotherapeutic treatments has been a reality, albeit for a tiny minority, since children with leukaemia were treated with aminopterin (Farber et al., 1948) and patients with Hodgkin's disease were treated with mustine (Dameshek et al., 1949). Although the cure rate with the single agent treatment was less than 20% it was this durable disease control which separated these two diseases from most of the other cancers when these and other cytotoxic drugs were subsequently tested. This criterion of having a durable cure rate with single agent chemotherapy is common to all the tumours in which combination chemotherapy was subsequently shown to produce more than 50% cure (Simone, 1979; Simone et al., 1982; Bagshawe, 1976; Devita, 1981). The most notable recent success in this respect has been the results of treatment of malignant germ cell tumours ofthe testicle. It is the purpose of this paper to review the results of this treatment and consider its significance in the broader context of the more general problem ofthe failure to produce such results from use of chemotherapy in the majority of adult solid tumours.

Our knowledge of the morphology and pathogenesis of malignant neoplasms of the female genital tract has traditionally depended heavily on their light microscopic characteristics. The introduction of transmission, and most recently, scanning electron microscopy, into the field of gynecologic pathology has resulted in a considerable improvement in the diagnosis of genital cancers that are difficult to classify and has provided valuable information for a better understanding of their subcellular dynamics and pathogenetic development. This paper describes and illustrates the ultrastructural alterations that are considered specific for the most common malignant and potentially malignant neoplasms of the genital system in this context. The value of electron microscopy in the morphologic study of genital cancers warrants its increased use in routine diagnostic pathology, as well as further evaluation of it in basic research in this challenging area of investigation.

A recent paper has suggested that there is a temporal cycle in birth rates of men with testis cancer with a peak in April/May. We have investigated the suggestion using data from the South Thames and Los Angeles cancer registries. There is some slight evidence of a peak in August, which is confined to teratomas. The effects demonstrated are, however, too small and inconsistent to provide any real clue to the aetiology of testis cancer.

The cytological features of testicular germ cell tumours were established in smears from 15 freshly resected tumours. These features were applied to the fine needle aspiration cytology diagnosis of metastases in 27 patients referred for chemotherapy. There were 16 positive reports in 32 aspirates of which 13 were taken before chemotherapy and three in patients with residual or new masses after chemotherapy. Teratomas and typical seminomas showed certain characteristic morphological features in cytological preparations which when present in fine needle aspiration cytology material enabled tumour types to be diagnosed. Spermatocytic and anaplastic seminoma were not represented in this series. It is unlikely that these could be distinguished from malignant teratoma undifferentiated (MTU) in the fine needle aspiration cytology material. Metastases from carcinomatous areas in MTU and malignant teratoma intermediate (MTI) may not be distinguishable in fine needle aspiration cytology material from metastatic adenocarcinoma or undifferentiated carcinoma from a different primary site. Positive cytological findings are of value to the oncologist in the management of patients with metastases from testicular germ cell tumours; negative cytology does not exclude the presence of viable tumour. The sampling of small foci of viable tumour in large necrotic masses persisting after chemotherapy is a problem for radiologists, cytologists, and histopathologists. This paper does not advocate the use of fine needle aspiration cytology for the diagnosis of primary testicular tumour.

This paper reports simultaneous occurrence of cryptorchidism and testicular tumor in three brothers within a single family. Two of the brothers had seminoma and the third brother had embryonal carcinoma. Tumor markers such as alpha fetoprotein, assay for beta subunit of human chorionic gonadotrophic hormone, and carcinoembryonic antigen were all negative. The simultaneous occurrence of familial cryptorchidism and testicular tumor has not been reported, although familial occurrence of both entities has been described separately. Because of the known risk of testicular malignancy in cryptorchidism, aggressive screening and examination are recommended in the form of either serial palpation or serial testicular biopsies. Hormonal replacement with testosterone cypionate is recommended for pubertal patients undergoing bilateral orchiectomy as a result of tumor removal. The overall prognosis of patients with cryptorchidism and abdominal testicular tumor seems to be good provided an early diagnosis is made.

Ovarian yolk sac carcinoma or endodermal sinus tumor is a rare neoplasm of germ cell origin. The rodent yolk sac is composed of visceral and parietal layers, contained by a thick basement membrane (Reichert’s membrane), which is secreted by the cells of the parietal la~er.~.~ The parietal yolk sac cells are small cuboidal cells with relatively large centrally placed nuclei6 External to Reichert’s membrane is a layer of trophoblastic giant cell^.^,^ Neither the parietal yolk sac cells nor the tumors derived from them secrete alphafetoproteh8 The human yolk sac does not have two distinct cell types and there is no counterpart of Reichert’s membrane; consequently, yolk sac tumors of humans differ in appearance.* In man, these neoplasms are found in ovaries, testis, and a variety of extragonadal sites, and they secrete alphafetoprotein.’ Yolk sac carcinoma may be induced in rats by transplantation of the extraembryonic portion of the 8-9-day-old egg or by fetectomy without removal of the fetal membranes.’ It has been produced experimentally in mice by serial passaging and conversion to ascitic form of testicular4 and ovarian5 teratocarcinomas, by transplantation of embryos without extraembryonic tissues under the kidney capsule of adult mice,2 and more recently by fetectomy and displacement of the visceral yolk sac to an extrauterine site.’ Spontaneous yolk sac carcinoma appears to be rare in mice,8 and the authors are aware of only one spontaneous case of pnmary ovarian yolk sac carcinoma.) The purpose of this paper is to document and describe the appearance of 16 ovarian yolk sac carcinomas found in one CD 1 and 15 B6C3F1 mice from chronic carcinogenesis studies. Seven of the 16 mice were control animals, the remainder were treated animals from different studies. The ages of the mice at necropsy ranged from 34 to 106 weeks, with a mean age of 66 weeks. The tumors were found during post-mortem examination of the abdominal cavity. They were unilateral, dark, gelatinous or cystic masses up to 25 millimeters in diameter, replacing the ovary and ovarian bursa, and attached to the uterine horn. The cystic spaces within the neoplasms contained serosanguinous fluid. The tumors were characterized histologically by a copious hyaline, periodic acid-Schiff (PAS) positive matrix in which the neoplastic cells were embedded. This intercellular matrix stained positively for laminin (Gibco Laboratories Inc., Grand Island, NY) using an immunogold method (Janssen Life Sciences Products, Piscataway, NJ) (Fig. 3). Areas of fine fibrovascular tissue, hemorrhage, and macrophages loaded with fine brown granules characteristic of hemosiderin were present in many sections.

SUMMARY The present paper has presented a clinicopathologic survey of ten benign teratomas, eight malignant teratomas, one seminoma and five choriocarcinomas, all primary in the mediastinum. These tumors appear to represent a spectrum of morphologic patterns that may be seen in teratoid tumors. The frequency with which pure or combination patterns will be seen appears to be a function of the number of sections evaluated. Regardless of the type of therapy undertaken, the malignant teratomas, seminomas and choriocarcinomas were universally and rapidly fatal, with the choriocarcinoma having the shortest clinical course. All the patients with benign teratomas ran a good course after surgical removal of the neoplasm. In the case of the mediastinal seminomas and choriocarcinomas, primary origin in the mediastinum can only be validated by the complete absence of testicular pathology, since the former are morphologically identical with their counterparts in a gonadal location.