Mesonephric adenocarcinoma of the uterine cervix: a case report with immunohistochemical and ultrastructural studies.

A very rare case of mesonephric adenocarcinoma with lobular mesonephric hyperplasia in the uterine cervix of a 46-year-old female is presented. The lesion was a 4 cm, exophytic, almost circumferential, whitish yellow, friable mass in the uterine cervix. Microscopically, the tumor was composed predominantly of atypical round to polygonal cells arranged in a ductal, tubular, or papillary pattern. The tumor involved the entire cervix with varying depths of penetration. Lobular mesonephric hyperplasia was also observed in the lateral cervical wall and adjacent to the tumor. Immunohistochemically, the tumor was positive for CAM5.2, CK7, epithelial membrane antigen, calretinin, and chromogranin A, and was negative for vimentin, carcinoembryonic antigen, estrogen and progesterone receptors, and CD10. An ultrastructural analysis showed telolysomes, which were characteristic features of mesonephric epithelium. The patient was alive without disease at 4 months after surgery.

Poorly differentiated carcinoma of unknown primary site: correlation of light microscopic findings with response to cisplatin-based combination chemotherapy.

We have previously reported complete responses and long-term survival in patients with metastatic poorly differentiated carcinoma (PDC) of unknown primary site who received intensive cisplatin-containing chemotherapy regimens. We reviewed the light microscopic specimens from 113 patients with PDC in an attempt to identify common histopathologic features in the chemotherapy-responsive subgroup, and to rule out the presence of previously unrecognized germ cell tumors. Relatively few diagnoses more specific than PDC could be made. We could identify no histopathologic features by light microscopy that distinguished responsive from unresponsive neoplasms. Only one patient was found to have a previously unrecognized yolk sac carcinoma, and in five other patients the possibility of a germ cell neoplasm was considered in the differential diagnosis by at least one reviewer. The remaining tumors had no histologic features suggestive of germ cell neoplasms. Ninety-six patients had received combination chemotherapy (89 with cisplatin-containing regimens); 27 patients (28%) achieved complete remission, and 16 remain free of disease at a median of 65 months after completion of therapy. Patients with PDC of unknown primary site who are responsive to cisplatin-containing chemotherapy regimens cannot be reliably identified by light microscopy. At present, all such patients should be considered for an empiric trial of chemotherapy with cisplatin-based regimens, since cure is achievable in a minority.

Yolk sac tumor of the anterior mediastinum. Case report with light- and electron-microscopic examination and immunohistochemical study of alpha-fetoprotein.

A case of yolk sac tumor of the anterior mediastinum was studied by light and electron microscopy and found to have characteristic patterns which were similar to a neoplasm of gonadal origin. These findings, in addition to the immunohistochemical identification of alpha-fetoprotein in the tumor, indicated that the neoplasm was germ cell in origin. A brief review of previously reported cases is included. Prognosis of the patients with yolk sac tumor of the anterior mediastinum was generally dismal; however, those patients with tumors incidentally found but completely excised survived without evidence of reucrrence.

Endodermal sinus tumor of the ovary with virilization. Light- and electron-microscopic study.

A case of endodermal sinus tumor of the ovary associated with hirsutism and increased testosterone production is described. Electron-microscopic examination revealed accumulation of basement membrane-like material and other ultrastructural features consistent with endodermal sinus tumor. Groups of polyhedral cells associated with the tumor were found to contain abundant lipid material. These luteinized stromal cells were evidently responsible for the endocrine manifestations.

Yolk sac differentiation in germ cell tumors. A morphologic study of 50 cases with emphasis on hepatic, enteric, and parietal yolk sac features.

We assessed 50 germ cell tumors with areas of yolk sac tumor (YST) for a variety of features including histologic patterns; hyaline droplets; syncytiotrophoblastic elements; hepatic, enteric, and parietal yolk sac differentiation; and granulomatous reaction. Of prime interest was the fact that many YSTs formed hepatic-like foci (22%), enteric-like glands (34%), and parietal yolk sac structures (92%). Hepatoid areas were characterized by nests and cords of polygonal, acidophilic cells with prominent nucleoli and intense cytoplasmic staining for alpha-fetoprotein. Enteric differentiation occurred as well-defined glands with a sharp, striated border and relatively bland nuclear features. Ultrastructurally these glands had apical microvilli with associated glycocalyx and long anchoring rootlets. The apical cytoplasm and luminal contents stained for carcinoembryonic antigen. Parietal yolk sac differentiation was characterized by the intercellular accumulation of basement membrane substance as generally thick and longitudinally arranged bands of eosinophilic material. Such material, by electron microscopy, was both intra- and extracellular, and had irregular outlines and inhomogeneous electron density. It contrasted with the strictly intracellular, round, homogeneous, hyaline globules that, we believe, represent visceral yolk sac differentiation. This intercellular material stained positively for laminin, a basement membrane component. Assessment of 22 embryonal carcinomas and 24 germinomas failed to show hepatic, enteric, and parietal yolk sac features, with one possible exception. We believe these features, especially parietal yolk sac differentiation, are helpful in differentiating YSTs from embryonal carcinomas and germinomas.

Yolk sac tumors with pure and mixed polyvesicular vitelline patterns.

Four cases of polyvesicular vitelline tumor are presented; two were of a previously unreported pure type, and the other two were mixed with endodermal sinus tumor. The morphologic features of the vesicles favor an endodermal origin, as originally proposed by Teilum. Marked specialization of the vesicular lining cells, seen ultrastructurally, suggests a differentiation toward gut structures and mature yolk sac. One case of pure polyvesicular vitelline tumor showed massive erythropoiesis. We propose that the pure tumor reflects an intermediate degree of differentiation within the selectively endodermal yolk sac tumor group, that is, a further stage of organization than the endodermal sinus tumor. In our cases of pure polyvesicular vitelline tumor, the marked degree of differentiaiton was correlated with an improved prognosis, as in the case of the possible homologue of this tumor, the yolk sac tumor of the infant testis. In contrast, the two cases of the tumor admixed with endodermal sinus tumor illustrated the low survival rate expected in the pure endodermal sinus tumor; in these cases the metastases had no polyvesicular component. Because of the significance of such a difference in prognosis we emphasize the importance of an accurate diagnosis, suggesting that a large number of sections be taken in order to demonstrate any endodermal sinus tumor component that may be present, and that the possibility of pure polyvesicular vitelline tumor always be considered in the differential diagnosis of multicystic ovarian tumors.

Primary pulmonary alpha-fetoprotein-producing malignant germ cell tumor.

We are reporting the clinical and pathologic features of a primary, pulmonary, malignant germ cell tumor associated with a marked elevation of serum alpha-fetoprotein (38,427 ng/mL) and lactate dehydrogenase activity (756 U/L), in a 26-year-old female. This controversial, rare neoplasm has not been extensively discussed in the pathology literature. We emphasize the clinical importance of establishing this diagnosis in view of the favorable response to chemotherapy shown by malignant germ cell tumors.

Paravaginal wolffian duct (mesonephros) adenocarcinoma: a light and electron microscopic study.

This is a report of an adenocarcinoma of mesonephric origin studied by light microscopy, electron microscopy, and immunocytochemistry. Unlike previous reports, our lesion was located paravaginally and not in the leaves of the broad ligament or in the cervix. The light microscopic features are similar to those of previous cases in the literature. Although not specific, the ultrastructural features of the tumor are similar to those of mesonephric structures and different from those of müllerian structures. The diagnosis always should be considered when a tumor occurs at the site where mesonephric remnants may be found and after exclusion of a carcinoma of other pelvic organs or a metastasis from a primary neoplasm elsewhere.

Hypothesis: when is a seminoma not a seminoma?

A xenograft line, HX 53, has been established in immune-suppressed mice from a specimen of a lymph node metastasis in a patient with a histological diagnosis of seminoma but with markedly raised circulating levels of alpha-fetoprotein. Histological, immunocytochemical, and ultrastructural studies of this xenograft line have suggested that a solid variant of yolk sac carcinoma may exist, which morphologically resembles seminoma, or that a continuum of differentiation exists between seminoma and yolk sac carcinoma.

Mesonephroid carcinoma of the ovary. A clinicopathologic, histochemical, and electron microscopic study.

Eighteen patients with mesonephroid ovarian carcinoma were investigated. Typical findings for the mesonephroid tumors were abundant extracellular an some intracellular neutral mucin mixed with sulfate and carboxyl groups, and large amounts of glycogen, especially in clear cells. The latter observation is considered to be an important aid in distinguishing them from other epithelial ovarian carcinomas. Some cells contained intracellular cysts that were covered with stubby microvilli similar to those found on the lumenal surfaces of the larger cysts in the tumors. Simultaneous estrogenic endometrial activity in the post-menopausal patients was frequently observed. The significance of this observation is discussed.

Gonadal endodermal sinus (yolk sac) tumor with pure intestinal differentiation: a new histologic type.

We studied 3 cases of a variant of endodermal sinus tumor (EST) or yolk sac tumor (YST). Two tumors originated in the ovary and one in the testis. The patients had very high levels of serum alpha-fetoprotein (AFP). All three tumors had a characteristic histologic appearance and were composed of acinar structures lined by columnar epithelium with large, immature nuclei. Immunohistochemistry and electron microscopy, including freeze-fracture studies, confirmed that this unusual tumor is one with exclusive intestinal differentiation. We feel that this unique tumor is a pure EST (YST) with exclusive intestinal differentiation.

Germ cell tumors (germinoma and yolk sac tumor) in unusual sites in the brain.

This report presents three cases of primary intracranial germ cell tumor encountered in unusual sites, or essentially non-midline structures. The three provided the opportunity to examine surgically obtained tissues with the electron microscope. The histological diagnosis was initially made by light microscopic observations. The first case was a 10-year-old boy in whom the tumor occupied the right thalamic and basal ganglionic region and was diagnosed as a yolk sac tumor. The second an 11-year-old boy who presented with a mass lesion on the left thalamic and basal ganglionic region, diagnosed as germinoma. The third was a 39-year-old man who presented with multiple tumors in the ventricular system and posterior fossa, also diagnosed as germinoma. Among the three cases, neither diabetes insipidus nor ophthalmologic disorder was manifested. Extensive examination and autopsy findings indicated that these intracranial lesions had not metastasized from primary extracranial tumors, including those of the genital organs.

Recent developments in the pathology of germ cell tumors.

This article describes some of the recent developments in the pathology of germ cell tumors of the testis. Many germ cell tumors show different types of differentiation. Two different explanations for this phenomenon include the differentiation of other germ cell elements from totipotential embryonal carcinoma cells or the direct differentiation of neoplasms from a malignant intratubular germ cell. Although the concept that there is a subset of seminomas having a poorer prognosis still exists, the histologic identification of such "anaplastic seminoma" remains an unachieved goal, and we, therefore, do not recommend the use of the term anaplastic seminoma at present. A recent analysis of spermatocytic seminomas has failed to demonstrate that they are capable of meiotic division. They are composed of cells differentiating in the direction of spermatocytes, but they have not achieved that stage. The prognosis, in general, remains excellent, although recently sarcomas have been reported in association with spermatocytic seminomas with metastasis of the sarcomatous elements. The presence of human chorionic gonadotropin-producing syncytiotrophoblastic giant cells in otherwise pure seminomas does not appear to adversely affect the prognosis. Yolk sac tumors have a varied histology that many pathologists do not recognize. The presence of intercellular basement membrane (parietal differentiation) is useful in the recognition of yolk sac tumor. Sometimes solid foci of yolk sac tumor may be mistaken for seminoma, and alpha-fetoprotein and cytokeratin stains may be useful in this situation, although the presence of basement membrane, hyaline globules, and focal microcysts by light microscopy may obviate the need to use them. Hepatic and enteric (or endometrioid) differentiation may occur in yolk sac tumors and cause diagnostic confusion. The development most "non-germ" cell malignancies in patients with germ cell tumors appears to occur by transformation of aneuploid teratomatous elements at the primary or metastatic site. The identification of such malignancies depends on the recognition of invasion by the elements rather than on high-grade cytologic atypia. Unusual patterns of choriocarcinoma and yolk sac tumor may be encountered following chemotherapy, and there is circumstantial evidence that some sarcomas and carcinomas occurring in patients with testis cancer may develop directly from yolk sac tumor.

Fine-needle aspiration biopsy diagnosis of endodermal sinus tumor: histologic and ultrastructural correlations.

Fine-needle aspiration biopsies from five patients with endodermal sinus tumors (ESTs) were reviewed, and the findings were correlated with histologic and ultrastructural appearances. In the aspiration smears, two types of tumor cells were seen, forming clusters of variable sizes. Type A cells had distinct cell borders, and their cytoplasm contained only occasional vacuoles. Type B cells had ill-defined cell borders and formed syncytial clusters; their cytoplasm was characterized by large numbers of rounded vacuoles. The background contained patches of mucoid material and macrophages with foamy cytoplasm. Eosinophilic hyaline cytoplasmic bodies and irregular deposits of intercellular basement membrane-like material were recognized easily in aspiration smears. These features correlated well with histologic and ultrastructural appearances. The significance of these findings in the fine-needle aspiration biopsy diagnosis of EST and its distinction from other germ-cell and non-germ-cell tumors is discussed.

Fine needle aspiration biopsy findings in endodermal sinus tumors. A report of four cases with cytologic, immunocytochemical and ultrastructural findings.

We present four cases of endodermal sinus tumor affecting children (median age, 20 months). Three tumors were located in the sacrococcygeal region and one in the right testicle. All cases were diagnosed by fine needle aspiration biopsy. The most characteristic features were cells arranged in a papillary-like configuration, vacuolated cytoplasm and intracellular and extracellular deposits of pink, homogeneous material. Immunocytochemical study showed alpha-fetoprotein-positive cells. Ultrastructural study showed intracytoplasmic inclusions of electron-dense material and basement membrane-like material in the intercellular spaces.

An endodermal sinus tumor in the cerebellopontine angle.

Immunohistochemical and ultrastructural findings in a primary intracranial endodermal sinus tumor are reported in this paper. The tumor cells exhibited AFP, CEA and anti-alpha-1-trypsin positive immunoreactivity immunocytochemically. Aggregates of electron-dense material in the extra- and intracellular spaces and amorphous basement membrane-like substance were seen extracellularly by electron microscopy. The clinicopathological, immunocytochemical and ultrastructural features were consistent with the criteria for primary intracranial sinus tumor.

[Light and electron microscopic observations on endodermal sinus tumor of the ovary].

The results of light and electron microscopic studies of the endodermal sinus tumor of ovary are presented. Although histologic features of the tumors appeared to be much varied, ultrastructurally all tumor cell seemed to show changes essentially of the same nature. The histogenesis of endodermal sinus tumor production of AFP by the hyaline globule and the basement membrane-like substance present only in this type of tumor, are discussed. The results of the present study support the view that the tumor originate from the embryonal yolk sac cells.

[Histological and ultrastructural characteristics of yolk sac tumors of gonadal and extragonadal localization in children]. / Gistologicheskie i ul'trastrukturnye osobennosti opukholi zheltochnogo meshka gonadnoi i ekstragonadnoi lokalizatsii u detei.

30 yolk sac tumours of a gonadal and extragonadal localization in children (19 testis tumours, 5 ovarian tumours, 6 tumours of extragonadal sites: presacral, sacralcoccygens, gluteal, retroperitoneal regions, vagina, liver) are studied histologically, in 8 cases electron-microscopically as well. The description of main histological and ultrastructural features that either may be used for differential diagnosis or may indicate the degree of tumour cells differentiation is presented.

[Experimental yolk sac tumors in the rat (author's transl)].

A study on the experimentally induced yolk sac tumor in the rat was made in special regard to the characteristics and origin of tumor cells. Pregnant rats which fetuses were removed on the 12th day of gestation, developed tumors derived from the fetal membranes left outside the uterus, which were composed of differentiated teratomas and yolk sac tumors. Serial observation of the oncogenesis revealed that an early lesion of the yolk sac tumor appeared in a nodule found as early as 3 weeks after the fetectomy and production of alpha-phetoprotein (AFP) was observed histochemically in the tumor cells 5 weeks after the fetectomy. A cultured cell line established after cloning from the transplantable yolk sac tumor which had been induced similarly and converted into ascitic form was also investigated. Light and electron microscopic studies on both induced tumors and the cultured cells indicated a similarity of AFP producing tumor cells with parietal yolk sac cells and of PAS-positive hyaline-like substance with the Reichert membrane. It is reasonable to conclude that the yolk sac tumor observed is regarded as a parietal yolk sac carcinoma described by Pierce. Histogenesis of the tumor is also discussed.

[Yolk sac tumor by fetectomy in the rat: histopathological characteristics and histogenesis (author's transl)].

Experimentally induced yolk sac tumors in rats were investigated with special regard to morphological and histochemical characteristics. Pregnant rats whose fetuses were removed on the 12th day of gestation, developed tumors which were derived from fetal membranes left outside the uterus. Out of 119 operated rats which had been mated with syngenic males, 95 rats beared tumors, which were histologically yolk sac tumors (46 cases), adenocarcinomas (29 cases), choriocarcinomas (5 cases) and teratomas (69 cases). An early lesion of yolk sac tumor was observed as early as 3 weeks after the surgical procedure, and the sera from these tumor-bearing rats were positive for alpha-fetoprotein (AFP). Morphological features of both the induced tumors and the cultured tumor cell masses revealed a thick stroma consisting of a PAS-positive basement membrane-like material, which closely resembled Reichert's membrane of the parietal yolk sac in the normal placenta. The intracellular localization of AFP in cultured cells was investigated by immuno-electron microscopic method, and the reaction product for AFP was seen in the endoplasmic reticulum and Golgi complex. Histogenesis of the tumor is also discussed.