Immature Neuroepithelium Research Articles

Immature teratoma with microscopic yolk sac tumor: A case of diagnostic challenge on histology

An adolescent girl with raised alpha-fetoprotein (AFP) levels presented with a left-sided large solid ovarian mass. Microscopically, the tumor was composed of a variety of immature and mature tissues derived from the three germ layers having very sparse (single focus of) immature neuroepithelium. Few areas also showed the presence of a reticular pattern of yolk sac tumor (YST). Hence, the tumor was diagnosed as immature teratoma with microscopic foci of yolk sac elements. After 6 months of cisplatin-based chemotherapy, she developed a recurrence which was composed of mature teratoma on histology. In this case, the single focus of immature neuroepithelium caused a difficulty in labeling this tumor as an immature teratoma which otherwise resembled a mature teratoma. The raised AFP levels suggested the presence of yolk sac element, the classical form of which was seen at microscopy in only a few areas. As compared to the markedly elevated serum AFP levels, the classical yolk sac tumorous area was very limited thus advocating the view that differentiated glands with subnuclear vacuoles similar to immature endoderm represent well-differentiated forms of YST. [1]

腹水細胞診で腹膜神経膠症と未熟神経上皮成分が示唆された卵巣未熟奇形腫の 1 例

腹水細胞診で腹膜神経膠症と未熟神経上皮成分が示唆された卵巣未熟奇形腫の 1 例

Immature ovarian teratoma. A case report and review of literature

Immature ovarian teratomas are rare tumours occurring most commonly in the first two decades of life. These tumours differ from their mature counterparts both histologically by the presence of immature tissue, and clinically by their more malignant behaviour. Microscopic examination reveals tissue from all three germ layers with at least one of the components having an immature appearance. The grade is based on the proportion of immature neuroepithelium and highly correlates with the tumour grade and hence prognosis. These tumours usually are confined to the ovary and are typically chemo- and radiosensitive. They may metastasise to peritoneum, liver or lung. We present a case of bilateral teratomas in a 25-year-old nulliparous woman who was found to have immature elements including neuroectodermal tissue, mesenchymal nodules, immature fat and cartilage within the left sided tumour. She is currently undergoing chemotherapy.

Lefty1 and Lefty2 Control the Balance Between Self-Renewal and Pluripotent Differentiation of Mouse Embryonic Stem Cells

Lefty expression has been recognized as a stemness marker because Lefty is enriched both in undifferentiated embryonic stem cells (ESCs) and in blastocysts. Here, we examined the function of Lefty1 and Lefty2 in the maintenance of self-renewal and pluripotency of mouse ESCs (mESCs). Suppression of Lefty1 or Lefty2 expression in mESCs did not alter the self-renewal properties of mESCs under nondifferentiating conditions, but suppression of these genes did affect Smad2 phosphorylation and differentiation. Lefty1 knockdown mESCs showed enhanced phosphorylation of Smad2 and increased differentiation potential, whereas Lefty2 knockdown mESCs exhibited reduced phosphorylation of Smad2 and enhanced self-renewal in the presence of a differentiation signal. In vivo, teratomas developed from Lefty2 knockdown mESCs contained massive expansions of immature neuroepithelium, a marker of malignant teratomas. Taken together, these results suggest that optimal expression of Lefty1 and Lefty2 is critical for the balanced differentiation of mESCs into three germ layers.

Infratentorial medulloepithelioma with divergent differentiation: Possibly a predictor of poor outcome

Medulloepitheliomas (WHO grade IV) are rare, malignant embryonal tumors of pediatric population, classified under the central nervous system (CNS) primitive neuroectodermal tumors (PNET). Histologically, these tumors are characterized by neoplastic neuroepithelium recapitulating the embryonic neural tube. We describe a rare case of infratentorial medulloepithelioma with divergent differentiation in a 1-year-old male child who presented with headache, vomiting, and seizures. Histopathologic examination of the excised tumor revealed the characteristic neuroepithelium, along with other areas showing primitive neuroectodermal (blastemal) cells in sheets, ependymoblastic rosettes, and nodular areas of neuronal differentiation. Possibly, this proliferating immature neuroepithelium is the cause of poor outcome in medulloepitheliomas. Due to the rarity of these tumors, it remains to be established whether infratentorial location or tumors with divergent differentiation are also predictors of adverse prognosis.

RNA-binding protein LIN28 is a sensitive marker of ovarian primitive germ cell tumours

LIN28 is an RNA-binding protein that has been detected in testicular germ cell tumours (GCTs), but its status in ovarian GCTs is unknown. The aim was to determine the immunohistochemical profile of LIN28 in ovarian GCTs. Immunohistochemistry of LIN28 was performed in 110 primary and 11 metastatic ovarian GCTs. The percentage of tumour cells stained was scored as 0, 1+ (1-30% cells), 2+ (31-60%), 3+ (61-90%), and 4+ (>90%). To determine its specificity, we stained LIN28 in 119 non-GCTs, including 37 clear cell carcinomas. Strong 4+ LIN28 staining was seen in 4/4 (100%) gonadoblastomas, 7/7 (100%) embryonal carcinomas (ECs), and 41/41 (100%) yolk sac tumours (YSTs). Among 39 dysgerminomas, 4+ staining was seen in 37 and 3+ staining in two (strong in 37; mixed weak and strong in two). Twelve of 14 immature teratomas showed variable LIN28 staining (1+ to 4+) in the immature neuroepithelium (weak to strong staining), whereas mature teratomas, carcinoids, struma ovarii and strumal carcinoids were negative. Only 5/117 non-GCTs (1/37 clear cell carcinomas) showed weak to moderate 1-2+ staining. LIN28 is a sensitive marker for gonadoblastomas, dysgerminomas, ECs, and YSTs. LIN28 can be used to distinguish them from non-GCTs.

Protocol for the Examination of Specimens From Pediatric and Adult Patients With Extragonadal Germ Cell Tumors

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the ‘‘Surgical Pathology Cancer Case Summary (Checklist)’’ portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of these documents.

Immature teratoma of the ovary: A clinicopathological study of 28 cases

Immature teratoma (IT) of the ovary represents 1% of all ovarian cancers and 20% of malignant ovarian germ cell tumors. This retrospective study of 28 such cases aims to look at its morphological spectrum and to study the correlation of the grade and stage of the tumor with prognosis. A retrospective study of 28 cases of IT of the ovary was done. Neuroepithelium was graded as grade I, II and III according to the standard criteria. The presence of immature mesenchyme was also looked for and similarly graded. The median age for the cases was 19 years and abdominal pain was the commonest symptom. Neuroepithelium was seen in 26 cases (6 were grade I, 13 were grade II, and 7 were grade III); and two showed immature mesenchymal tissue (IM) only. IM was seen in all 28 cases, but no correlation with the grade of the IT of the ovary is found. The follow up is available in 23 cases ranging from 6 months to 78 months (median 33 months). Of these, 13 were stage I, 3 were stage II and 7 were stage III ITs. Out of 23 patients, 17 patients were alive without evidence of disease recurrence during the last follow up. Adverse events in the form of death and local recurrence occurred in 6 patients. One patient died of the disease at 7 months duration from the disease onset (stage III, grade II IT). Morphological spectrum of IT of ovary is varied. Immature mesenchyme was seen in all the cases of IT of ovary and its presence should prompt a careful search for immature neuroepithelium. Stage I IT of ovary has better prognosis. Combination of surgery and chemotherapy can give longer survival even in recurrent disease.

Oct4 Expression in Immature Teratoma of the Ovary

Immature teratoma of the ovary is an uncommon tumor comprising 1% of ovarian malignancies. The amount of immature neuroepithelium in the teratoma is an important prognostic factor. Although the current grading system based on this criterion is widely accepted, the biological significance of immature neuroepithelium is poorly understood. In this study, we used immunohistochemistry to evaluate the expression of Oct4 (also known as Oct3 or POU5F1), a transcription factor expressed in primordial germ cells and embryonic stem cells, along with that of PAX6, a transcription factor contributing to neurogenesis, and CD56, a known marker for tumors of neural origin, in 18 cases of pure immature teratoma of the ovary. Oct4 was expressed in the immature neuroepithelium of all 7 grade-3 cases and 2 grade-2 cases. It was not expressed in 4 grade-2 cases and all 5 grade-1 cases. These tumor cells lacked CD30 or α-fetoprotein expression, which supported the diagnosis of pure immature teratoma. PAX6 was expressed in the immature neuroepithelium of all immature teratomas, but not in Oct4-positive cells. CD56 was expressed in neural components of various maturities including PAX6-positive immature neuroepithelium, but not in Oct4-positive cells. These data suggest that the expression of these markers probably reflects the differentiation status of neural tissue in immature teratomas. The finding that Oct4 expression was exclusively detected in immature neuroepithelium of high-grade immature teratomas indicates that Oct4 might serve as a promising biomarker for the diagnosis of highly malignant cases of immature teratoma.

Expression of Glial Cell Line–Derived Neurotropic Factor Receptor α-1 in Immature Teratomas

The immaturity of teratomas is usually manifested as immature neuroepithelium. The amount of immature neuroepithelium has been correlated with the survival of adult patients with ovarian immature teratoma. To date, no immunohistochemical marker has been found to facilitate the identification of immature teratoma. In this study, we evaluated the expression of glial cell line-derived neurotropic factor receptor alpha-1 (GFRalpha-1) for this purpose. We retrieved 38 cases of germ cell tumors: 26 cases contained immature teratoma, of which 24 had immature neuroepithelium and showed strong membrane staining for GFRalpha-1. No significant staining was seen in other components including embryonal carcinoma, seminoma, yolk sac tumor, choriocarcinoma, immature mesenchyme, and intratubular germ cell neoplasia. Immunohistochemical staining for GFRalpha-1 in immature neuroepithelium may facilitate its identification.

Sinonasal teratocarcinosarcoma: report of a case with review of literature and treatment outcome

Sinonasal teratocarcinosarcoma is a highly malignant, polymorphous neoplasm that combines features of carcinosarcoma and teratoma. We describe the clinicopathologic features and management of a well-documented example of this unique entity that involved a 41-year-old Hispanic man. The patient presented with a history of multiple episodes of epistaxis, nasal obstruction and frontal headaches. Computerized tomography scans and magnetic resonance imaging revealed a large mass filling the left nasal cavity and extending to the cribriform plate with involvement of the ethmoid sinuses, lamina papyracea, and orbit. The patient underwent a complex procedure for a T3N0 tumor. Histologic examination revealed a heterogeneous admixture of epithelial, mesenchymal, and neuroepithelial elements. The mesenchymal components consist of fibrous stroma and myxomatous areas, labeled with calponin and smooth muscle actin. The epithelial components vary from clear cells, nonkeratinizing epithelium to glandular pattern, and keratin containing cysts. Immature neuroepithelium and olfactory neuroblastomalike tissue are highlighted with neuroendocrine markers. Postoperatively, the patient had a rapid local recurrence of the tumor and underwent reexcision, and was treated with radiotherapy and chemotherapy. Twelve months after his primary resection, computerized tomography scans revealed an intrathoracic tumor with dominant mass in the left hilum and metastases to the mediastinum, left pleural space, and both lungs. The histologic nature of his chest mass remains undetermined. Among 54 cases of reported sinonasal teratocarcinosarcoma, 67% of patients with initial single surgical resection and 80% of patients primarily treated with radiotherapy had recurrence, or metastatsis, or unresponsiveness to treatment. The high rate of local recurrence and metastasis is indicative of its highly aggressive biologic behavior. Almost half of the patients died of tumor within 3 years of diagnosis, despite aggressive therapy. Seventy percent of the patients who survived more than 1 year had the initial therapeutic regiments of combined surgery and adjuvant therapies, suggesting that aggressive therapeutic approaches may improve the treatment outcome.

Tératome immature de l'ovaire avec gliomatose péritonéale. À propos d'un cas et revue de la littérature

We return a case of ovarian immature teratoma with peritoneal gliomatose at a woman aged of 20 years. The diagnosis discovered following pelvic mass increasing volume and treaty by a one-sided annexectomy, with chemotherapy. Eighty-seven cases have been published in the literature. Although potential for recurrence is high, the risk of malignancy is very low. Ovarian immature teratoma is a malignant germ cell tumor and represents less than 1% of ovarian malignant tumors. Tissues are derived from the three germ layers (endo-, meso- and ectoderm). Tumor grading is based on the amount of immature neuroepithelium present. The prognosis is directly correlated to histological grade. Rapid (fast) growth leads to large tumors with an early diagnosis. Gliomatosis peritonei is a rare situation, characterized by the recurrence of peritoneal implants after the surgical treatment of ovarian teratoma. This entity does not modify the good prognosis of mature teratomas, but we recommend regular follow-up.

Sinonasal teratocarcinosarcoma: a clinical, radiologic and pathologic study of 5 cases

To study the clinical, radiologic and pathologic features, as well as differential diagnosis of teratocarcinosarcoma in nasal cavity and paranasal sinuses. Light microscopic examination and immunohistochemical study was performed in 5 cases of sinonasal teratocarcinosarcoma. The clinical, radiologic and pathologic features were analyzed and the literature was reviewed. All 5 patients were males and their age ranged from 34 to 43 years (mean age = 39 years). The clinical presentation was nasal obstruction, epistaxis and headache. Physical examination often revealed a polypoid mass with contact bleeding. Computed tomography showed a homogeneous nasal mass with obturation of sinuses. Cystic changes, calcification or ossification was not observed. Histologically, the tumor showed a heterogeneous admixture of components from the 3 germ cell layers, exhibiting various degrees of maturation. Squamous epithelium, smooth muscle cells, chondro-osseous tissue, intestinal or respiratory type epithelium, "fetal-type" clear cells and immature neuroepithelium were commonly seen. Immunohistochemical study demonstrated that the epithelial component expressed cytokeratin and epithelial membrane antigen, while the mesenchymal component variably expressed vimentin, smooth muscle actin and S-100 protein. On the other hand, the neuroepithelial component expressed neuron-specific enolase, synaptophysin and chromogranin, and the primitive component expressed CD99. The initial biopsy diagnosis included capillary hemangioma, olfactory neuroblastoma, craniopharyngioma and malignant mixed tumor. Follow-up information was available in all patients. Two of which had local recurrence and 1 had cervical lymph node metastasis. Sinonasal teratocarcinosarcoma is a rare and highly malignant tumor occurring in sinonasal tract. It manifests mainly in adult males and is characterized by a complex admixture of teratomatous and carcinosarcomatous components. "Fetal-type" clear cells, squamous epithelium and immature neuroepithelium represent important histologic characteristics useful in diagnosis.

Uterine cervical teratoma with divergent neuroepithelial differentiation and development of an oligodendroglioma: report of a case and review of the literature

Teratomas of the uterine cervix are rare. Immature and malignant uterine cervical teratomas are extremely rare. A uterine cervical teratoma with divergent neuroepithelial differentiation and/or development of a neurological tumor has never been reported. We describe a case of uterine cervical teratoma exhibiting ectodermal, endodermal, mesodermal, and various types of neuroepithelial differentiation and development of a small oligodendroglioma in a 38-year-old female. The presence of immature neuroepithelium defines this teratoma as immature, and the development of a low-grade malignant neoplasm from one of its components makes it malignant. The pertinent literature is reviewed.

Evaluation de la prise en charge des teratomes immatures de l'ovaire. A propos de trois cas et revue de la littérature

Ovarian immature teratoma is a malignant germ cell tumor and represents less than 1% of ovarian malignant tumors. Tissues are derived from the three germ layers (endo-, meso- and ectoderm). Tumor grading is based on the amount of immature neuroepithelium present. The prognosis is directly correlated to histologic grade. Rapid growth leads to large tumors with an early diagnosis. Therapeutic management is balanced between adjuvant chemotherapy and surgery alone. Nevertheless, as immature teratoma mostly occurs in young women, the main objective is to preserve fertility.

Developmental distribution of coxsackie virus and adenovirus receptor localized in the nervous system

Mouse coxsackie virus and adenovirus receptor (mCAR), which was isolated from the nerve growth cone-enriched fraction of newborn mouse brains, is a member of immunoglobulin-super family, and functions as a homophilic adhesion molecule. We observed the expression of mCAR in embryos to adult tissues by means of immunohistochemical analysis with a peptide antibody. mCAR expression was first detected in the embryonic ectoderm in the uterus on embryonic day 6.5 (E6.5). Then it was strongly expressed in the neuroepithelium of the neural tube, the developing brain and the spinal cord from E8.5 to postnatal day 7 (P7), in the cranial motor nerves from E9.5 to E11.5, and in the optic nerve from E13.5 to P7, which agrees with periods of their respective morphogenetic peaks. This expression of mCAR decreased postnatally and was absent in adult tissues. We found that mCAR occurred in a few proliferating cells of the hippocampal dentate gyrus, the subventricular zone (SVZ) of the lateral ventricles, and the rostral migratory stream (RMS) over P21. These observations demonstrate that mCAR was expressed characteristically in the immature neuroepithelium including progenitor cells or radial cells derived from the neural tube and in immature cells in a selected germinal zone of the mature brain. Based on our findings, we propose that mCAR is involved in migration and fasciculation during a restricted period as an adhesion molecule.

Characterization of the biological functions of a transcription factor, c-myc intron binding protein 1 (MIBP1).

The c-myc intron binding protein 1 (MIBP1) is a gigantic zinc finger protein comprising 2,437 amino acids and belonging to the MHC binding protein (MBP) family. MIBP1 is suggested to be a transcription factor involved in various biological functions. We show here that MIBP1 represses c-myc transcription from the major promoter, P2. Screening by the yeast two-hybrid system revealed that the MIBP1 protein interacts with the Ski-interacting protein (SKIP). In vitro pull-down assays and in vivo co-immunoprecipitation experiments confirmed this interaction. The acidic region of MIBP1 was found to be the site of interaction with the N-terminal half of SKIP. In situ hybridization analysis using developing rat embryos revealed that the MIBP1 mRNA is highly expressed in post-mitotic neurons, but the expression in immature neuroepithelium is low. The expression of MIBP1 in adult rat brain is also predominantly in neuronal cells, indicating that MIBP1 is involved in the physiology of mature neuronal cells.

The influence of grade on the outcome of stage I ovarian immature (malignant) teratomas and the reproducibility of grading.

An analysis of 244 immature teratomas (IT) was undertaken to evaluate the clinical usefulness and reproducibility of the grading system. Clinical follow-up was available for 143 stage I tumors and ranged from 7 to 204 months (mean 85 months, median 84). Sixteen of 91 (18%) patients with high-grade teratomas were dead with metastases. These results are much improved over the years before the use of modern (1970 or later) combination chemotherapy. In contrast, only 3 of 52 (6%) patients with grade 1 tumors died, 1 of whom was living with tumor 6 years after surgery. None of the three neoplasms was adequately sampled. Of the three grade 1 tumors that progressed, the smallest one weighed > 1,500 g and the other two were huge; yet, only one to five slides per tumor were available for review. The study confirmed that small foci (2 mm or less) of other germ cell elements do not adversely affect the prognosis of IT. The reproducibility between pathologists of the traditional grading system for IT, based on the amount of immature neuroepithelium, is only moderate if a three-tiered scale is used and limited by the results of the least skilled observer (kappa = 0.54). Although never approaching complete agreement, interobserver variability is reduced if a two-tiered system is used (kappa = 0.66). Microscopic patterns that were the source of disagreement were identified. Agreement could be improved with training sessions.

Immature Teratoma of the Uterine Fundus.

An exceedingly rare case of extragonadal immature teratoma, which occurred primarily in the uterus, is described. The tumor developed into the pelvic cavity from the uterine fundus and consisted of ectodermal, mesodermal and endodermal derivatives. There were also significant amounts of immature elements; immature neuroepithelium with brisk mitotic activity, immature mesenchymal tissue, immature cartilage, immature striated muscle and immature hepatic tissue. Histologically, it was classified as a grade 3 immature teratoma. Treatment consisted of total simple hysterectomy followed by 2 courses of combination chemotherapy with vincristine, actinomycin D and cyclophosphamide (VAC). The patient was well and without evidence of recurrence at 5 years post-operatively.

Intrapericardial teratoma in the newborn

Two cases of intrapericardial teratomas occurring in the newborn are reported. The first was a cystic, well differentiated tumour which was totally excised. The child was alive and well with no evidence of the disease 10 months later. The second was a predominantly solid teratoma which consisted of both mature and immature tissues. It was removed but recurred 2 months later with pleural and pericardial invasion. The patient underwent reoperation but death occurred 9 days after surgical treatment. The recurrence was histologically similar to the primary tumour. The second case is probably the first malignant intrapericardial teratoma described in a neonate. Its morphology and clinical behaviour suggest that, as in ovarian and sacrococcygeal teratomas, the presence of immature neuroepithelium carries a poor prognosis. In such cases radio- or chemotherapy should be performed.