A Case of Urachal Yolk Sac Tumor With Spontaneous Rupture in a Child.

Tumors arising from urachus in children are exceedingly rare and sporadically reported in literature. Being a midline structure, the urachus may harbor neoplastic germ cell elements and can occasionally present as a case of acute abdomen. A 20-month-old toddler presented with spontaneous rupture of an urachal yolk sac tumor causing hemoperitoneum. He underwent resection, received platinum-based chemotherapy and presently remains well on follow-up. Despite its rarity, urachal germ cell tumors must be considered in a child with acute abdomen and tumor markers must be measured preemptively in such cases.

ZBTB16: a novel sensitive and specific biomarker for yolk sac tumor.

Although the function of zinc finger and BTB domain containing 16 (ZBTB16) in spermatogenesis is well documented, expression of ZBTB16 in germ cell tumors has not yet been studied. The aim of this study was to investigate the immunohistochemical expression and diagnostic utility of ZBTB16 in germ cell tumors. A total of 67 adult germ cell tumors were studied (62 testicular germ cell tumors, 2 ovarian yolk sac tumors, 1 mediastinal yolk sac tumor, and 2 retroperitoneal metastatic yolk sac tumors). The 62 testicular primary germ cell tumors are as follows: 34 pure germ cell tumors (20 seminomas, 8 embryonal carcinomas, 2 teratomas, 1 choriocarcinoma, 1 carcinoid, and 2 spermatocytic tumors) and 28 mixed germ cell tumors (composed of 13 embryonal carcinomas, 15 yolk sac tumors, 15 teratomas, 7 seminomas, and 3 choriocarcinomas in various combinations). Thirty-five cases contained germ cell neoplasia in situ. Yolk sac tumor was consistently reactive for ZBTB16. Among the 15 testicular yolk sac tumors in mixed germ cell tumors, all displayed moderate to diffuse ZBTB16 staining. ZBTB16 reactivity was present regardless of the histologic patterns of yolk sac tumor and ZBTB16 was able to pick up small foci of yolk sac tumor intermixed/embedded in other germ cell tumor subtype elements. Diffuse ZBTB16 immunoreactivity was also observed in 2/2 metastatic yolk sac tumors, 1/1 mediastinal yolk sac tumor, 2/2 ovarian yolk sac tumors, 2/2 spermatocytic tumors, 1/1 carcinoid, and the spermatogonial cells. All the other non-yolk sac germ cell tumors were nonreactive, including seminoma (n=27), embryonal carcinoma (n=21), teratoma (n=17), choriocarcinoma (n=4), and germ cell neoplasia in situ (n=35). The sensitivity and specificity of ZBTB16 in detecting yolk sac tumor among the germ cell tumors was 100% (20/20) and 96% (66/69), respectively. In conclusion, ZBTB16 is a highly sensitive and specific marker for yolk sac tumor.

Primary yolk sac tumor of endometrium: report of two cases and review of literature.

Primary YST of the endometrium is very rare, therefore there is no guideline for treatment. We report two cases of endometrial YSTs presenting different symptoms and showing different prognoses and discuss the clinical management of these tumors. The present report shows first time that bone and lung metastasis in primary YSTs of endometrium. As the number of reported cases with endometrial YSTs, more information about the prognosis of the disease may be obtained.

Primitive Embryonic-Type Neuroectodermal/Glandular Complexes in Testicular Germ Cell Tumors: A Mimic of Embryonic-Type Neuroectodermal Tumor.

Embryonic-type neuroectodermal elements are often intimately mixed with primitive endodermal-type glands, like those of yolk sac tumors, in germ cell neoplasia in situ (GCNIS)-derived germ cell tumors of the testis. Because the primitive glands mimic tubules or rosettes of embryonic-type neuroectodermal elements, these embryonic-type neuroectodermal/glandular complexes may be misinterpreted as pure lesions of embryonic-type neuroectodermal elements, which, if of sufficient size, may lead to a diagnosis of embryonic-type neuroectodermal tumor, despite that the criteria of the World Health Organization for a "somatic-type malignancy" are not met. A diagnosis of embryonic-type neuroectodermal tumor in the testis may lead to retroperitoneal lymphadenectomy even in clinical stage I patients, and in postchemotherapy resections indicates a poor prognosis. The distinction of the neuroectodermal and glandular elements is not always straightforward based on morphology alone. We, therefore, studied 34 testis-derived germ cell tumors with embryonic-type neuroectodermal/glandular complexes and 2 purely glandular yolk sac tumors to characterize the immunophenotypes and determine an efficient immunohistochemical panel to aid in this differential. We found that GFAP, synaptophysin, and paired-like homeobox 2B (PHOX2B) expression was specific to embryonic-type neuroectodermal elements, although PHOX2B had poor sensitivity. In contrast, positive reactions with antibodies directed against AFP, villin, and CDX2 were specific for the glandular elements, although CDX2 had poor sensitivity. Other markers, including AE1/AE3 cytokeratin, SALL4, glypican 3, SOX2, SOX11, CD56, INSM1, and neurofilament, proved less helpful because of their nonspecificity and/or poor sensitivity. We conclude that the optimal immunohistochemical panel for distinguishing the components of embryonic-type neuroectodermal/glandular complexes includes stains for synaptophysin, GFAP, villin, and AFP.

Vulvar Yolk Sac Tumors Are Somatically Derived SMARCB1 (INI-1)-Deficient Neoplasms.

So-called primary yolk sac tumors of the vulva are very rare and often have an aggressive disease course. Their molecular features have not been previously characterized. There is also a well-documented group of SMARCB1 (INI-1)-deficient vulvar neoplasms, which includes proximal-type epithelioid sarcoma and myoepithelial carcinoma. Until now, "vulvar yolk sac tumors" and SMARCB1-deficient neoplasms were considered unrelated diseases. After reviewing an index case of a vulvar yolk sac tumor with loss of SMARCB1 by immunohistochemistry, we retrospectively identified 2 additional cases diagnosed as vulvar yolk sac tumors. Patient ages were 34, 32, and 25 years old, and 2 tumors were associated with a pregnancy. All 3 cases showed morphology typical of a yolk sac tumor, and by immunohistochemistry all were positive for SALL4, glypican-3, keratins, and lacked CD34 positivity. All tumors also demonstrated loss of SMARCB1 in tumor cells. Targeted molecular profiling was performed in 2 cases and identified 2 copy deletion of SMARCB1, without genomic alterations typically seen in gonadal yolk sac tumors. In the third case, isochromosome 12p was not identified by fluorescence in situ hybridization. All 3 patients had either local recurrences or distant metastases, and 2 died of disease. One patient had progressive disease while receiving the enhancer of zeste homolog 2 inhibitor tazemetostat. Overall, these findings suggest that vulvar tumors with pure yolk sac-like morphology may represent morphologic variants of SMARCB1-deficient tumors and not veritable germ cell neoplasia. This potential reclassification may have both prognostic and treatment implications and warrants study of additional extragonadal yolk sac tumors.

Vasculogenic Mesenchymal Tumor: A Clinicopathologic and Molecular Study of 55 Cases of a Distinctive Neoplasm Originating From Mediastinal Yolk Sac Tumor and an Occasional Precursor to Angiosarcoma.

We report 55 postchemotherapy resections of primary nonseminomatous mediastinal germ cell tumors with prominent vasculogenic features showing the formation of rudimentary to well-developed neoplastic vessels within primitive mesenchyme. These cases represented 25% of a cohort of 221 such specimens. The patients were 19 to 49 years old (mean, 28 y) and 98% had serological evidence of yolk sac tumor. The vasculogenic lesions, felt to represent a neoplastic reiteration of embryonic vasculogenesis in the splanchnic mesoderm of the yolk sac, were further subdivided into teratoma with vasculogenic stroma (n=9), vasculogenic mesenchymal tumor (VMT) (n=42, further classified into low grade [n=24] and high grade [n=18]), and angiosarcoma (n=4). The distinction of teratoma with vasculogenic stroma from VMT was based solely on the greater extent of VMT (exceeding 1 low power [×4 objective] microscopic field), with both categories showing a spectrum of vessels lined by atypical endothelium in a nonendothelial neoplastic stroma that often also generated vascular walls comprised of atypical smooth muscle. The angiosarcomas showed stratification of highly atypical endothelial cells or anastomosing vessels lined by nonstratified but cytologically similar endothelium. Immunohistochemical studies supported the generation of neoplastic vessels from the tumor stroma, most commonly by the development of stromal clefts showing reactivity for podoplanin, CD34, and occasionally ERG, followed by the gradual development from the clefts of thin-walled vessels that later became encircled by stromal cells showing smooth muscle differentiation by immunohistochemistry. Occasionally, round collections of stromal erythrocytes became surrounded by stromal cells to generate blood vessels. Fluorescence in situ hybridization showed chromosome 12p copy number increase in both the endothelial component and stromal component in 8/9 VMT cases and in 1/1 angiosarcoma. On follow-up, no patient with teratoma with vasculogenic stroma had evidence of a subsequent vascular tumor or sarcoma, whereas 8 of the 35 (23%) patients with VMTs (2 low grade and 6 high grade) and meaningful follow-up developed sarcoma (1 angiosarcoma, 2 rhabdomyosarcomas, and 5 not further characterized). The difference between low-grade and high-grade tumors was of borderline significance (P=0.058). Two of the 4 patients with angiosarcoma died of metastatic angiosarcoma, with the other 2 disease-free at 6.8 and 7 years. Compared with the 165 patients with follow-up and no vasculogenic lesions, there was a highly significant (P=4.3×10-5) association of any vasculogenic lesion with sarcomatoid tumors during the clinical course of VMT patients. In addition, 5/46 patients with follow-up and vasculogenic lesions (11%) died of either leukemia or myelodysplastic syndrome compared with 2 of 166 (1%) lacking them (P=0.0012). Three of the 5 patients had identifiable immature hematopoietic cells within their vasculogenic lesions, but 4 other VMT patients with these did not develop leukemia or myelodysplasia. We conclude: (1) vasculogenic lesions are frequent in postchemotherapy resections of primary mediastinal germ cell tumors with yolk sac tumor components; (2) they mostly consist of neoplastic vessels in a stroma that also generates neoplastic vascular walls of smooth muscle; (3) VMTs are associated with an increased incidence of sarcomas, even though most vasculogenic lesions in this context do not meet criteria for angiosarcoma; (4) the presence of vasculogenic lesions in postchemotherapy resections of primary mediastinal germ cell tumors place patients at increased risk for leukemia or myelodysplasia.

Oncofetal protein glypican-3 distinguishes yolk sac tumor from clear cell carcinoma of the ovary.

Clear cell carcinoma (CCC) of the ovary is the surface epithelial neoplasm most often confused with primitive germ cell tumors, particularly yolk sac tumor (YST) and dysgerminoma. OCT3/4 has proven to be a sensitive and relatively specific marker for the latter entity, but existing markers for YST are limited. Recent studies suggest that glypican-3 (GPC3), an oncofetal protein expressed in fetal liver and malignant tumors of hepatocytic lineage, is also expressed in germ cell tumors, particularly YST. To investigate whether GPC3 is useful in distinguishing YST from ovarian CCC, we studied the expression of GPC3 in a large series of ovarian neoplasms and compared it to the expression profiles of CK7 and alpha-fetoprotein. Tissue microarrays containing over 400 benign and malignant ovarian neoplasms, including 34 CCCs were stained with monoclonal GPC3 (clone 1G12, Biomosaics, Burlington, VT). These arrays contained a wide assortment of ovarian surface epithelial neoplasms and sex cord stromal neoplasms, as well as germ cell tumors. Full paraffin tissue sections from 32 YSTs and 10 CCCs were also assessed. All but one YST (97%), including those associated with mixed germ cell tumor were positive for GPC3, whereas all teratomas and embryonal carcinomas were negative. Both cytoplasmic and membrane staining were present in the positive cases, with no background staining. The syncytiotrophoblastic cells in the germ cell tumors and placental villi included in the arrays were also positive for GPC3. Most CCCs (83%) were completely negative for GPC3, as were 99% serous, 94% endometrioid, and 100% mucinous tumors. Five CCCs exhibited focal, moderate to strong GPC3 expression and in 2 the expression was focal and weak. All other tissues, including normal ovary were negative for GPC3. GPC3 seems to be a promising diagnostic marker for differentiating YST from ovarian CCC (P < 0.0001). Because GPC3 may be associated with alpha-fetoprotein expression, further studies are required to determine the utility of GPC3 in differentiating YST from CCC with hepatoid differentiation.

Role of HNF1ß in the differential diagnosis of yolk sac tumor from other germ cell tumors.

Identification of the yolk sac tumor (YST) component in germ cell tumors (GCT) may prove challenging, and highly sensitive and specific immunohistochemical markers are still lacking. Preliminary data from the literature suggest that HNF1ß may represent a sensitive marker of YST. The specificity of HNF1ß has not been addressed in GCT. A cohort of 49 YST specimens from 45 patients was designed, occurring either as pure tumors, or as a component of a mixed GCT. Immunohistochemistry was conducted on whole tumor sections using HNF1ß. SALL4, OCT4, CD30, CDX2, Cytokeratin 19, Glypican 3, and GATA3 were used for classification of the GCT components. Patients were mostly male (39/45), aged 14 months to 49 years, with primary testicular tumors (37/39), or primary mediastinal pure YSTs (2/39). All 6 primary tumors occurring in females (6/45) were pure ovarian YSTs; age range was 4 to 72 years. HNF1ß nuclear reactivity was seen in the YST component in all 49 tumors, with a moderate to strong nuclear pattern of staining. Embryonal carcinoma (EC, 0/32) and seminoma (0/6) were negative. Choriocarcinoma (6/6) showed faint focal cytoplasmic reactivity to HNF1ß but no nuclear staining. In teratomas, only enteric-type glands showed nuclear reactivity to HNF1ß (11/16). Therefore, HNF1ß sensitivity in YST component identification was 100% and specificity was 80%. Thus, in our experience, HNF1ß is a sensitive and reliable marker of the YST component in GCT, and allows distinction of YST from intricately admixed EC, especially in the diffuse embryoma pattern.

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.

An unusual primary malignant tumor of the stomach: fetal gutlike gastric adenocarcinoma with "blastoma"-like component.

An unusual case of a polypoid, malignant gastric tumor in a 62-year-old man is presented. Endoscopy and subsequent polypectomy revealed an 8.5 × 6.5 × 4.5-cm lesion in the body of the stomach. Microscopy showed surface dysplasia with an invasive adenocarcinoma displaying prominent tubulopapillary areas composed of large vacuolated cells, pleomorphic nuclei, and occasional cytoplasmic hyaline globules. This component then blended with tubular structures lined by more primitive-appearing vacuolated cells embedded within a stroma made up of cellular primitive, high-grade blastemalike areas and less cellular, more pleomorphic foci with spindle and several bizarre, large cells. Immunohistochemistry showed the adenocarcinoma and primitive tubules to be strongly SALL4 and epithelial marker positive but with only focal expression of α-fetoprotein and glypican-3. The stromal component made up of blastemalike areas displayed strong immunoreactivity for glypican-3. The pleomorphic stromal areas were negative for all markers, including epithelial and muscle markers. The overall morphology and expression of primitive oncofetal proteins, especially SALL4 and glypican-3, are in keeping with this being a primitive adenocarcinoma showing fetal gutlike differentiation with an accompanying blastomalike component, a combination not previously described in a primary gastric cancer.

A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma.

Lectin-affinity electrophoretic separation of serum alpha-fetoprotein (AFP) was carried out using AFP Differentiation Kits, which used Lens culinaris agglutinin-A (Kit L) and erythroagglutinating phytohemagglutinin (Kit P). Separated AFP bands were detected with a sensitive antibody-affinity blotting technique and determined quantitatively by densitometry, and the results were expressed as percentages of the intensity of total AFP bands. Sera from 424 patients with acute hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, and extrahepatic tumors were assayed for proportion of AFP present as Lens culinaris agglutinin-A-reactive AFP (AFP-L3) and erythroagglutinating phytohemagglutinin-reactive AFPs (AFP-P4+P5). From the maximum Youden indices determined, cutoff levels were set at 15% for both AFP-L3 and AFP-P4+P5 to discriminate between patients with chronic hepatitis and liver cirrhosis and patients with hepatocellular carcinoma. AFP-L3 and AFP-P4+P5 showed sensitivities of 55.3 and 61.0% at specificities of 93.9% and 82.3%, respectively. Thirty-eight % of tumors that measured less than 20 mm in diameter were positive for AFP-L3 and AFP-P4+P5. AFP-L3 exceeded the cutoff level of 15% 4.0 +/- 4.9 months before detection of hepatocellular carcinomas by imaging techniques with a sensitivity of 48% and a specificity of 81%. Thus, these tests are useful for the early detection of hepatocellular carcinomas in patients with hepatitis or liver cirrhosis.

Endodermal sinus tumor of the omentum: case report.

We report a case of primary endodermal sinus tumor of the omentum in a 46-year-old woman. The patient had been referred to our hospital for pain in the right abdomen. CT scan revealed a right-sided abdominal mass. At laparotomy, a large omental tumor extending to the bowel, uterus, ovaries and peritoneum was found, and it was totally resected. The tumor displayed the typical histological patterns observed in endodermal sinus tumor, and the immunohistochemical findings confirmed the diagnosis. Serum AFP level was 21.550 ng/ml prior to laparotomy, and decreased to 13.845 ng/mL after surgery, whereas the level of serum beta human chorionic gonadotropin was normal. Post-surgery, the patient received combination chemotherapy consisting of cisplatin, etoposide and bleomycin every 3 weeks for a total of 6 cycles. At the end of the treatment, all the findings, including AFP level, were normal.

CK19 is a sensitive marker for yolk sac tumours of the testis.

BACKGROUND: Malignant germ cell tumours are the most common malignant tumours in young men. They are histologically divided into seminomas and non-seminomas. Non-seminomas are further subdivided into embryonic carcinomas, yolk sac tumours, chorionic carcinomas, and teratomas. For the therapeutic management it is essential to differentiate between these histological subtypes. METHODS: Investigated cases included normal testis (n = 50), intratubular germ cell neoplasia (n = 25), seminomas (n = 67), embryonic carcinomas (n = 56), yolk sac tumours (n = 29), chorionic carcinomas (n = 2), teratomas (n = 7) and four metastases of YST's for their CK19 expression. In addition Leydig cell- (n = 10) and Sertoli cell- tumours (n = 4) were included in this study. RESULTS: All investigated seminomas, embryonic carcinomas as well as normal testis and intratubular germ cell neoplasias did not express CK19. In contrast, all investigated yolk sac tumours strongly expressed CK19 protein. These findings became also evident in mixed germ cell tumours consisting of embryonic carcinomas and yolk sac tumours, although CK19-expression could also be observed in analysed chorionic carcinomas and epithelial components of teratomas. CONCLUSION: CK19 proved to be a sensitive marker to identify yolk sac tumours of the testis and to distinguish them from other germ cell tumours, especially seminomas and embryonic carcinomas. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4075546891400979.

Mediastinal Yolk Sac Tumor Producing Protein Induced by Vitamin K Absence or Antagonist-II.

Extragonadal yolk sac tumors (YSTs) are rare. We herein report the case of a 66-year-old man with mediastinal, lung and liver tumors. The largest mass was located in the liver and contained a high concentration of protein induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha-fetoprotein. Therefore, the lesion was difficult to distinguish from hepatocellular carcinoma. Finally, YST was diagnosed based on the results of a liver biopsy. Although chemotherapy was effective, the patient died of respiratory failure. The autopsy revealed primary mediastinal YST. In the current report, we describe this case of PIVKA-II-producing YST and review previous cases of PIVKA-II-producing tumors other than hepatoma.

Pediatric germ cell tumors presenting beyond childhood?

Four cases are reported meeting the criteria of a pediatric (i.e., Type I) testicular germ cell tumor (TGCT), apart from the age of presentation, which is beyond childhood. The tumors encompass the full spectrum of histologies of pediatric TGCT: teratoma, yolk sac tumor, and various combinations of the two, and lack intratubular germ cell neoplasia/carcinoma in situ in the adjacent parenchyma. The neoplasms are (near)diploid, and lack gain of 12p, typical for seminomas and non-seminomas of the testis of adolescents and adults (i.e., Type II). It is proposed that these neoplasms are therefore late appearing pediatric (Type I) TGCT. The present report broadens the concept of earlier reported benign teratomas of the post-pubertal testis to the full spectrum of pediatric TGCT. The possible wide age range of pediatric TGCT, demonstrated in this study, lends credence to the concept that TGCT should according to their pathogenesis be classified into the previously proposed types. This classification is clinically relevant, because Type I mature teratomas are benign tumors, which are candidates for testis conserving surgery, as opposed to Type II mature teratomas, which have to be treated as Type II (malignant) non-seminomas.

Yolk sac tumors of the mediastinum with prominent spindle cell features: a clinicopathologic study of three cases.

Three cases of primary mediastinal yolk sac tumors with prominent spindle cell features are presented. The patients were three men 24-34 years of age (mean 29). Clinically, two patients presented with symptoms of chest pain and cough; no clinical information was provided for the third patient. Grossly, the tumors were described as large mediastinal masses, with a hemorrhagic and necrotic cut surface. Histologically, the tumors were characterized by a predominantly atypical spindle cell proliferation admixed with areas that showed focally the characteristic reticular growth pattern of yolk sac tumors, with the presence of Schiller-Duval bodies and intra- and extracellular hyaline globules. Immunohistochemical studies performed in one case showed positive staining for keratin and alpha-fetoprotein in both the spindle cell and reticular components of the tumor. Follow-up information was obtained in two patients; they both died of tumor with metastases to the lungs 1 year after initial diagnosis. The present cases expand the spectrum of histopathologic growth patterns that may be observed in yolk sac tumors of the mediastinum and stress the issue of careful sampling and evaluation of mediastinal neoplasms for arriving at the correct diagnosis.

Hepatoid yolk sac tumors of the mediastinum: a clinicopathologic and immunohistochemical study of four cases.

Four cases of primary hepatoid yolk sac tumors of the anterior mediastinum are described. The patients were all men between the ages of 26 and 40 years (median 33). Clinically, they all presented with a history of shortness of breath and chest pain of several weeks' duration. None of the patients had a history of germ cell tumor elsewhere or evidence of any hepatic abnormality. Grossly, all the tumors were described as large mediastinal masses that impinged on adjacent structures. Histologically, they were characterized by sheets of medium-sized, round to polygonal neoplastic cells with moderate amounts of eosinophilic cytoplasm and round to oval nuclei with prominent nucleoli. The cellular proliferation was homogeneous and displayed moderate cellular atypia and scattered mitotic activity. All the tumors showed focally the presence of more conventional areas of yolk sac tumor, with islands of tumor cells showing a reticular pattern of growth admixed with scattered intra- and extracellular hyaline globules and occasional Schiller-Duval bodies. Immunohistochemical studies showed strong positivity of the tumor cells for alpha-fetoprotein in both components of the lesions. Follow-up information was available in three patients, all of whom developed lung metastases within a year after initial diagnosis. Two of these patients died of tumor within the same period, whereas a third patient has been lost to follow-up. The present cases illustrate an unusual histologic pattern of yolk sac tumor in the mediastinum and highlight the importance of considering this tumor in the differential diagnosis of lesions showing a hepatoid pattern of growth in the mediastinal area.

New and unusual aspects of ovarian germ cell tumors.

Ovarian germ cell tumors are reviewed with emphasis on recent developments. In the primitive germ cell tumor group the recently recognized subtypes of yolk sac tumor, the hepatoid and glandular variants are described. Hepatoid tumors, which resemble hepatocellular carcinomas, are usually admixed with other patterns of yolk sac neoplasia but when the hepatoid component predominates, distinction from metastatic hepatocellular carcinoma may be difficult. Glandular yolk sac tumors include those with a cribriform pattern as well as tumors that may be confused with endometrioid carcinoma. Within the teratoma category, a recent paper exploring the occasional relation between immature teratomas and dermoid cysts is reviewed. Problems caused by some of the monodermal teratomas are also highlighted. Struma ovarii may be the source of many diagnostic problems. It may be cystic and microscopic examination may reveal inconspicuous numbers of clearly recognizable thyroid follicles, resulting in confusion with other cystic ovarian tumors. In noncystic strumas many patterns, such as solid or pseudotubular, may be seen and the presence of cells with abundant clear or eosinophilic cytoplasm may add to the diagnostic difficulty, particularly if other teratomatous elements are lacking. Immunohistochemical staining for thyroglobulin may be crucial in establishing the diagnosis of a struma in these situations. The problem of identifying reliable criteria for malignancy of struma ovarii is explored on the basis of recent information. The two most recently recognized subtypes of carcinoid tumor, strumal and mucinous, are reviewed as are primary neuroectodermal and sebaceous tumors of the ovary. Unusual clinical features of germ cell tumors are discussed under three main categories: endocrine syndromes, paraendocrine and paraneoplastic syndromes, and miscellaneous. Included in these categories are disorders such as sexual precocity in association with germ cell tumors containing syncytiotrophoblast cells, endocrine abnormalities associated with the recently described functioning ovarian tumors with peripheral steroid cell proliferation, hyperthyroidism with struma ovarii, the carcinoid syndrome, autoimmune hemolytic anemia associated with dermoid cysts, complications of dermoid cyst rupture, which may simulate disseminated carcinomatosis, and ascites and Meigs' syndrome associated with struma ovarii.

OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma.

OCT4 (POU5F1) is a transcription factor expressed in embryonic stem and germ cells and is involved in the regulation and maintenance of pluripotency. It has been detected in primary testicular germ cell tumors with pluripotent potential, seminoma, and embryonal carcinoma. We undertook immunohistochemical staining of OCT4 in a wide variety of primary testicular neoplasms (germ cell tumors and other tumors) to assess the specificity and usefulness of this marker as a diagnostic tool. We examined histologic sections from 91 primary testicular neoplasms, including 64 cases of mixed germ cell tumors containing embryonal carcinoma (54), seminoma (51), yolk sac tumor (38), mature teratoma (31), immature teratoma (20), and choriocarcinoma (15). In addition, we examined sections from spermatocytic seminomas (5), Leydig cell tumors (8), Sertoli cell tumors (6), unclassified sex-cord stromal tumors (4), adenomatoid tumors (2), testicular tumor of adrenogenital syndrome (1), and granulosa cell tumor (1). Each tumor was examined with hematoxylin and eosin staining and with antibodies to OCT4. In all cases of mixed germ cell tumor with components of embryonal carcinoma (54) and seminoma (51), there was greater than 90% nuclear staining of the embryonal carcinoma and seminoma tumor cells with little to no background staining. In all but 1 of these cases (embryonal carcinoma), there was strong (3+) staining intensity. The other germ cell tumor components (yolk sac tumor, mature teratoma, immature teratoma, and choriocarcinoma) showed no staining. Syncytiotrophoblast cells, which were present in 15 of the cases, were also completely negative, as were all 5 of the spermatocytic seminomas. The 22 cases of non-germ cell tumors were all immunohistochemically negative for OCT4. Fifteen of the 54 germ cell tumors containing embryonal carcinoma were also examined with antibodies to CD30. These embryonal carcinoma components were all positive for CD30 with staining of greater than 90% of the tumor cells but with variable staining intensity. We conclude that immunostaining with antibodies to OCT4 is a useful diagnostic tool in the identification of primary testicular embryonal carcinomas and "usual," but not spermatocytic, seminomas. OCT4 immunostaining has comparable sensitivity but greater consistency compared with CD30 in the diagnosis of embryonal carcinoma.

Gonadal malignant germ cell tumors express immunoreactive inhibin/activin subunits.

OBJECTIVE: Inhibin and activin are proteins produced by ovarian granulosa cells and testicular Sertoli cells and are members of the transforming growth factor-beta superfamily. Since increased circulating levels of immunoreactive inhibin were detected in women with malignant ovarian tumors, they were proposed as tumor markers for ovarian carcinoma. Immunohistochemical studies later confirmed the presence of inhibin and activin subunits in granulosa cell tumors and epithelial ovarian cancer, as well as in Sertoli and Leydig cell testicular cancer. However, there is discrepant information on the detection of inhibin and activin in malignant germ cell tumors (MGCT). The aim of the present study was to evaluate the immunohistochemical expression of the inhibin/activin alpha, betaA and betaB subunits in ovarian and testicular MGCT specimens using polyclonal antisera. METHODS: The ovarian tissue samples were composed of 19 MGCT, including dysgerminoma (n=18) and yolk sac tumor (n=1). The testis specimens included classic seminomas (n=20), embryonal carcinomas (n=7), choriocarcinomas (n=2), and yolk sac tumor (n=1). RESULTS: Ovarian and testicular malignant germ cell tumors expressed positive staining for inhibin/activin alpha, betaA and betaB subunits, with some variations between and within individual tumors: while ovarian dysgerminomas were diffusely positive for alpha, betaA and betaB, testicular tumors expressed alpha and betaB subunits, whereas betaA staining was weak. CONCLUSIONS: The present results show positive staining for inhibin/activin subunits in ovarian and testicular MGCT, suggesting a possible role in tumorigenesis with the resultant clinical implication.