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Extragonadal nonseminomatous germ cell tumour with hypercalcemia, masquerading as renal cell carcinoma: a case report.

Humoral hypercalcemia secondary to the production of parathyroid hormone-related peptide has been reported to occur in up to 17% of patients with renal cell carcinoma but has been reported only rarely in patients with other genitourinary cancers and never in patients with testicular or extragonadal nonseminomatous cancers. A 54-year-old man is reported who had an extragonadal nonseminomatous germ cell tumour with hypercalcemia that masqueraded as a renal cell carcinoma with metastases. The hypercalcemia was suspected to be humorally mediated.

Carcinoma, Renal Cell↗

Late recurrence of testicular cancer.

Late recurrence of nonseminomatous germ cell tumours of the testis is rare. The authors report on a 35-year-old man treated initially for embryonal cell carcinoma of the testis with metastases, who presented 12 years later with an increasing serum alpha-fetoprotein level and a biopsy-proven embryonal cell cancer in the hilus of the left lung. Because the tumour was highly resistant to two separate courses of cis-platinum-based chemotherapy and one course of radiotherapy, surgical resection for salvage was carried out. The patient was free of disease 3.5 years after the second operation. The possible reasons for the occurrence of this highly resistant metastatic testicular cancer are discussed. They include a second primary tumour and malignant degeneration of the original tumour. In this patient the latter cause was the most plausible.

Adult↗

Immunocytochemical and biochemical characterization of the Heymann nephritis antigenic complex in rat L2 yolk sac cells.

Heymann nephritis in the rat is the most widely used model of human membranous glomerulonephritis. Glycoprotein (gp)330, a large (M(r) > 550,000) membrane-associated glycoprotein, has been identified as the main antigen in this autoimmune disease. Studies of gp330 and receptor-associated protein (RAP), its 44-kd subunit, have been restricted largely to rat kidney, as no stable cultured cell line has been available that expresses gp330. We have recently identified a rat yolk sac carcinoma cell line (L2) that expresses both gp330 and RAP. In this report, we have carried out detailed morphological, immunocytochemical, and biochemical studies characterizing the biosynthesis and localization of gp330 and RAP in the L2 rat yolk sac cell line. At the electron microscope level, the L2 cells are seen to be attached by cell junctions, and their predominant morphological features include extensive networks of rough endoplasmic reticulum (ER) and numerous clathrin-coated pits found on the cell membrane. By immunocytochemistry, gp330 was localized primarily to clathrin-coated pits at the cell surface, whereas RAP was localized predominantly to the lumen of the rough ER. Pulse-chase experiments indicated that gp330 spends a prolonged time maturing in the ER of L2 cells, as transport of gp330 to the Golgi complex (based on acquisition of endoglycosidase H resistance) is slow (t1/2 = 90 to 120 minutes). Gp330 reached the L2 cell surface beginning at 2 hours after synthesis, where it could be detected by cell surface immunoprecipitation. RAP was found to be an N-linked glycoprotein, and it remained endoglycosidase H-sensitive up to 4 hours after synthesis. Co-precipitation and co-sedimentation experiments demonstrated that gp330 and RAP form a large heterodimer (M(r) approximately 669,000) immediately after biosynthesis and are further assembled into a large hetero-oligomer in the ER. These findings demonstrate that the localization and the kinetics of assembly of gp330 and RAP into the Heymann nephritis antigenic complex are similar in both L2 cells and rat kidney. They also provide new information on the intracellular processing of these two molecules and their delivery to the cell surface. Thus, the L2 cell system should facilitate further characterization of the functions and interactions of gp330 and RAP, which may shed light on the cellular and molecular mechanisms of Heymann nephritis.

Animals↗

Pregnancy following treatment of an adolescent with Yolk sac tumour.

The Authors present the case of a patient suffering from a highly malignant tumour, Yolk sac tumour, who received a combined treatment of operation and chemotherapy. The treatment was applied selectively, i.e. surgery was as radical and as conservative as deemed necessary. The patient was cured and after getting married, she gave birth to a baby girl with pes varus. Because of lack of experience with Yolk sac tumours, which up to the cytologic era had had bad prognoses, and of insufficient knowledge with the consequences of chemotherapy on the generative and reproductive functions of the patients cured, we consider our case to be worthy of attention.

Adult↗

Infantile mediastinal primary endodermal sinus tumour.

Primary extragonadal mediastinal endodermal sinus tumour is rare, and to date very few cases have been reported in the literature. We present here a case of rare extragonadal highly malignant commonest germ cell tumour in an infant who presented with a rapidly progressive mediastinal mass with dry non-productive cough, tachypnea without significant respiratory distress or toxicity.

Biopsy, Needle↗

A quantitative study of radiation-induced apoptosis in two rat yolk sac tumour cell lines with different radiosensitivities in vitro.

Two rat yolk sac tumour cell lines with different radiosensitivities were used to quantify the extent of apoptosis following irradiation by using a DNA fragmentation assay in vitro. Apoptosis was also confirmed by fluorescence analysis of nuclear morphological changes by using Hoechst 33258. A radiosensitive cell line, NMT-1 cells, showed morphological changes characteristic of apoptosis by fluorescence microscopic observation at 24 hours after irradiation with a single dose of 10 Gy. Development of apoptosis in NMT-1 cells was observed as a function of time within 24 hours after irradiation. There was a significant increase in the amount of apoptosis between 2 and 5 Gy only in NMT-1 cells but increasing the radiation dose from 5 Gy to 10 Gy did not result in increased apoptosis. A radioresistant NMT-1R cells, on the other hand, displayed a small apoptotic response to an irradiation dose of 10 Gy at 24 hours after irradiation.

Animals↗

Intracranial germ cell tumors in children: an immunohistochemical and electron microscopic study.

From a review of a series of 1,474 intracranial tumors occurring in children, we identified 49 patients (3.3%) with primary intracranial germ cell tumors: 65% germinomatous, 26% nongerminomatous (8 teratomas, 3 endodermal sinus, and 2 choriocarcinomas), and 8 degrees 10 mixed. Placental alkaline phosphatase was present in all germinomas tested. Human chorionic gonadotropin was identified in 7 patients, cytokeratin in 6, and alpha-fetoprotein in 4. The results of immunostaining with antisera against glial fibrillary acidic protein, desmin, and vimentin were essentially negative. Electron microscopy played an important role in confirming the diagnosis in patients with endodermal sinus and mixed tumors. The correct identification of mixed and non-germ-cell tumors requires adequate tumor sampling and proper preparation of tissue for immunohistochemical and electron microscopic examination.

Biomarkers, Tumor↗

Ovarian myxoma: ultrastructural and immunohistochemical findings.

The ultrastructural and immunohistochemical findings are reported in two ovarian myxomas, one of which was also associated with a sclerosing stromal tumor of the same ovary. Both neoplasms showed a myxoid, moderately cellular proliferation of spindle and stellate cells interspersed with areas of fibrosis and hemorrhage as well as delicate vascular spaces. Ultrastructurally, stellate neoplastic cells with irregular nuclei and occasional nucleoli were embedded in a mucinous and loose collagen matrix. Their cytoplasm showed abundant intracytoplasmic thin filaments that rarely condensed into poorly formed dense bodies. These thin filaments correlated with immunoreactivity for muscle-specific actin and vimentin. The neoplastic cells showed no immunoreactivity with antibodies to desmin, S-100 protein, cytokeratin AE1:AE3, factor VIII-related protein, or placental alkaline phosphatase. These ultrastructural and immunohistochemical findings are consistent with myofibroblastic differentiation. These ancillary studies exclude important, clinically more aggressive differential considerations such as myxoid rhabdomyosarcoma, myxoid liposarcoma, myxoid neural tumors, mucinous adenocarcinoma showing pseudomyxomatous change, and myxoid-appearing endodermal sinus (yolk sac) tumor.

Actin Cytoskeleton↗

The human yolk sac and yolk sac carcinoma. An ultrastructural study.

The ultrastructure of the yolk sac of a 39 day old human embryo was studied. The subcellular organization was suggestive of a highly specialized absorptive function proceeding in an exocelomic-viteline direction. These findings, compatible with intense metabolic activity, are at variance with the concept of rapid involution of the yolk sac following completion of its hemopoietic and angiogenetic functions. The speculation is advanced that a potential avenue exists in the yolk sac whereby maternally derived products encounter fetal endoderm. Ultrastructural features in the normal yolk sac were compared to those existing in a tumor showing the "endodermal sinus" pattern, and reviewed in the light of the pertinent literature. These findings support the concept that attributes an endomesoblastic derivation to such neoplasms.

Dysgerminoma↗

[Adjuvant chemotherapy of non-seminoma stage I germ cell tumors of the testis].

OBJECTIVE: To review the treatment of stage I nonseminomatous germ cell testicular tumor with adjuvant chemotherapy. METHODS: The literature on this subject was reviewed. RESULTS/CONCLUSIONS: Overall, 30% of stage I nonseminomatous germ cell testicular tumors that are followed recur within two subsequent years. Several factors associated with a higher risk have been described. The most important are the presence of venous or lymphatic infiltration, the presence of a carcinoembryonic component and the absence of tumor of the endodermal sinus. Patients with the foregoing characteristics have a recurrence rate of approximately 50%. Over the last few years, some experience using two cycles of BEP adjuvant chemotherapy in patients at a higher risk have shown that this recurrence rate can be reduced to less than 5% with minimal late toxicity.

Chemotherapy, Adjuvant↗

[An ultrastructural study of human ovarian yolk sac tumor--an investigation of its histogenesis compared to that of human yolk sacs (author's transl)].

For the purpose of investigating the histogenesis of the yolk sac tumor, 7 cases of the tumor and 9 cases of human yolk sac were used. Histological, ultrastructural investigations together with immunofluorescent antibody examinations revealed the following results. Ultrastructurally yolk sac endodermal cells prior to the 7th week of pregnancy were proved to have microvilli, abundant glycogen which formed rosette, parallel arranged rough endoplasmic reticulum (rER), mitochondria closely associated with rER and ovoid electron dense amorphous granules which showed positive diastase-resistant PAS-reaction. Morphologically endoderm after the 8th week of pregnancy showed degenerative changes. Light microscopically the tumors showed Schiller-Duval body, endodermal sinus structure and clear-cells endoblastic pattern, but ultrastructurally the tumor cells of these three types showed approximately similar appearances. Ultrastructural features of the tumor seem to resemble those of the yolk sac endoderm before the 7th week of pregnancy. The tumor cells which form the epithelial mantling of Schiller-Duval body closely resembled the endodermal cells facing the yolk sac cavity with respect to the presence of abundant glycogen granules, rER, mitochondria, short irregular microvilli on the cell surface and remarkable nucleolus with thread-like nucleolonema. Both the tumor cells facing the endothelial cell and those which form the endodermal sinus structure and clear-cells endoblastic pattern resembled the endodermal cells facing the mesenchyma in view of the features of intracellular organelles, the presence of extracellular basement membrane-like substances and tubular structure.

Adolescent↗

[Granulomatous nodule with Enterobius vermicularis in epiploon simulating metastasis of ovarian cancer].

The authors describe a case of peritoneal enterobiasis presenting as necrotizing granuloma, in a adolescent with tumor of the ovarian endodermic sinus. The diagnosis was established through biopsy of peritoneal nodule, during laparotomy for staging system of ovarian cancer. Granulomatous nodules due to parasites could simulate metastasis, and cause confusion in the staging system for cancer.

Adolescent↗

Endodermal sinus tumour of the omentum in a child.

Endodermal sinus tumour usually arises in a gonad; extragonadal endodermal sinus tumours are rare. We report a 3-year-old boy with an endodermal sinus tumour arising in the greater omentum, which may be the second reported case in the English literature. He presented with a solid mass in the upper abdomen and a markedly raised serum alpha-fetoprotein (AFP) level. Following percutaneous needle biopsy and omentectomy, histological examination revealed classic morphological features of an endodermal sinus tumour. This rare diagnosis is possible from the imaging features in association with a raised serum level of AFP.

Biomarkers, Tumor↗

A brief history of the pathology of the gonads.

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.

Europe↗

[Germinal cell tumors in young and adolescent girls].

OBJECTIVE: Germ cell tumours are the most common ovarian tumours in childhood and adolescence. This diverse group of tumours derives from germ cells. DESIGN: The aim of this work is presentation of germ cell tumours in the material from our clinic with characteristic clinical features, the scope of operation and effects of many years of observation. MATERIALS AND METHODS: We treated 109 girls with germ cell tumours of the ovary: 13 had malignant tumours: there were 7 patients with dysgerminomas, 2 with endodermal sinus tumour of the ovary, 3 with immature teratomas, 1 with carcinoma embryonale. Gonadoblastomas was diagnosed 4 patients and mature teratomas in 92 patients. RESULTS: 11 patient had gonadal dysgenesia with abnormal karyotype. These girls had no follicle apparatus in gonads and had elevated levels of gonadotropins. Gonadoblastoma is almost always found in patients with gonadal dysgenesis. Gonadoblastoma often produces estradiol or testosterone. There can be problems with diagnosis of the syndrome, because developmental features imitate the onset of normal puberty. Most patients with dysgerminoma have stage I of disease and surgery is sufficient. It must be suggested that patients of stage I who wish to preserve childbearing function may be treated with unilateral salpingoophorectomy and adjuvant chemotherapy. Monitoring of the treatment is connected with measurement of biochemical markers. Some of these markers are useful for monitoring of response to therapy. When levels of markers are low second look laparoscopic operation should be performed. Cytological smears and biopsy specimens from the remaining ovary, peritoneum and subdiaphragmatic area should be obtained laparoscopically. CONCLUSIONS: The sift ultrasonographic investigations can be helpful in the early diagnosis of germ cell tumours of the ovary in girls. Absence of follicle apparatus in the gonads requires determination of levels of gonadotropins and karyotype. Fertility sparing operative treatment is preferred when karyotype is normal.

Adolescent↗

Human yolk sac tumor serially transplanted in nude mice: its morphologic and functional properties.

Three human yolk sac tumors (TE, OE, and TT-1) were serially transplanted into nude mice. The histology of the transplanted tumors is moderately different from that of the original tumor; the transplants had mainly a tubular structure with an inconspicuous endodermal sinus structure due to a decreased mesenchymal element surrounding the vascular core. Ultrastructural features of the transplanted tumor cells, however, were identical to those of the original tumor. Immunochemical survey of the blood plasma of nude mice bearing these tumors demonstrated the production of adult type human plasma proteins including prealbumin, albumin (Alb), alpha 1-antitrypsin (alpha AT), transferrin (Tf), hemopexin, and alpha 1-fetoprotein (AFP). The types of adult plasma proteins that were produced varied, depending on the tumor line but were the same between serial passages within the same tumor line. The intracellular localization of AFP, alpha AT, Tf, and Alb was also investigated by immunoelectron microscopy. Plasma proteins of the adult type and AFP were localized mainly within the membrane systems of the endoplasmic reticulum and Golgi complex and occasionally on the microvilli. These results suggest that transplanted human yolk sac tumors have almost all of the protein-producing function possessed by their normal counterparts.

Animals↗