Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics.

Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors manifesting in infancy. They split into four molecular types. The major three (AT/RT-SHH, AT/RT-TYR, and AT/RT-MYC) all carry mutations in SMARCB1, the fourth quantitatively smaller type is characterized by SMARCA4 mutations (AT/RT-SMARCA4). Molecular characteristics of disease recurrence or metastatic spread, which go along with a particularly dismal outcome, are currently unclear. Here, we investigated tumor tissue from 26 patients affected by AT/RT to identify signatures of recurrences in comparison with matched primary tumor samples. Microscopically, AT/RT recurrences demonstrated a loss of architecture and significantly enhanced mitotic activity as compared to their related primary tumors. Based on DNA methylation profiling, primary tumor and related recurrence were grossly similar, but three out of 26 tumors belonged to a different molecular type or subtype after second surgery compared to related primary lesions. Copy number variations (CNVs) differed in six cases, showing novel gains on chromosome 1q or losses of chromosome 10 in recurrences as the most frequent alterations. To consolidate these observations, our cohort was combined with a data set of unmatched primary and recurrent AT/RT, which demonstrated chromosome 1q gain and 10 loss in 18% (n = 7) and 11% (n = 4) of the recurrences (n = 38) as compared to 7% (n = 3) and 0% (n = 0) in the primary tumors (n = 44), respectively. Similar to the observations made by DNA methylation profiling, RNA sequencing of our cohort revealed AT/RT primary tumors and matched recurrences clustering closely together. However, a number of genes showed significantly altered expression in AT/RT-SHH recurrences. Many of them are known tumor driving growth factors, involved in embryonal development and tumorigenesis, or are cell-cycle-associated. Overall, our work identifies subtle molecular changes that occur in the course of the disease and that may help define novel therapeutic targets for AT/RT recurrences.

Seminoma metastásico de primario gonadal / Metastatic seminoma of primary gonadal

El seminoma es la neoplasia testicular más frecuente alcanzando hasta el 50% de todos los casos de cancer del testículo. Dependiendo de su naturaleza, seminomatoso o no seminomatoso, las conductas de manejo y tratamiento médico quirúrgicas varían según los centros, los protocolos de manejo y la experiencia de los equipos de atención. Objetivos. Promover la discusión de adyuvancia o neoadyuvancia en caso de seminoma clásico. Paciente y Método. Presentar un caso de seminoma clásico tratado quirúrgicamente con orquidectomía y una década después se presenta con extensión metastásica mediastinal y retroperitoneal. Conclusiones. Para la etiología no seminomatosa, se establece la orquidectomía seguida de vigilancia; mientras que en caso de origen seminomatoso la discusión se basa en el momento del rol de la cirugía, radiación y quimioterapia, por lo tanto, se debe individualizar cada paciente según las características clínicas manifestadas. (AU)

Seminoma is the most common testicular neoplasm, reaching up to 50% of all cases of testicular cancer. Depending on its nature, seminomatous or non-seminomatous, the management behaviors and surgical medical treatment vary according to the centers, the management protocols and the experience of the care teams. Objective. Promote the discussion of adjuvant or neoadjuvant in case of classic seminoma. Patient and Method. To present a case of classic seminoma treated surgically with orchidectomy and a decade later it presents with mediastinal and retroperitoneal metastatic extension. Conclusions. For non-seminomatous etiology, orchidectomy followed by surveillance is established; while in the case of seminomatous origin, the discussion is based on the time of the role of surgery, radiation and chemotherapy, therefore, each patient must be individualized according to the clinical characteristics manifested. (AU)

Advances in the molecular classification of pediatric brain tumors: a guide to the galaxy.

Central nervous system (CNS) tumors are the most common solid tumor in pediatrics, accounting for approximately 25% of all childhood cancers, and the second most common pediatric malignancy after leukemia. CNS tumors can be associated with significant morbidity, even those classified as low grade. Mortality from CNS tumors is disproportionately high compared to other childhood malignancies, although surgery, radiation, and chemotherapy have improved outcomes in these patients over the last few decades. Current therapeutic strategies lead to a high risk of side effects, especially in young children. Pediatric brain tumor survivors have unique sequelae compared to age-matched patients who survived other malignancies. They are at greater risk of significant impairment in cognitive, neurological, endocrine, social, and emotional domains, depending on the location and type of the CNS tumor. Next-generation genomics have shed light on the broad molecular heterogeneity of pediatric brain tumors and have identified important genes and signaling pathways that serve to drive tumor proliferation. This insight has impacted the research field by providing potential therapeutic targets for these diseases. In this review, we highlight recent progress in understanding the molecular basis of common pediatric brain tumors, specifically low-grade glioma, high-grade glioma, ependymoma, embryonal tumors, and atypical teratoid/rhabdoid tumor (ATRT). © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Recurrent DICER1 Hotspot Mutations in Malignant Thyroid Gland Teratomas: Molecular Characterization and Proposal for a Separate Classification.

Thyroid gland teratomas are rare tumors that span a wide clinicopathologic spectrum. Although benign and immature teratomas arise in infants and young children and generally have good outcomes, malignant teratomas affect adults and follow an aggressive course. This divergent behavior raises the possibility that benign/immature and malignant teratomas are separate entities rather than different grades of a single tumor. However, the histogenesis and molecular underpinnings of thyroid gland teratomas are poorly understood regardless of grade. In this study, we performed next-generation sequencing on 8 thyroid gland teratomas, including 4 malignant, 3 benign, and 1 immature. We identified DICER1 hotspot mutations in all 4 malignant cases (100%) but not in any benign/immature cases (0%). No clinically significant mutations in other genes were found in either group. We also performed immunohistochemistry to characterize the primitive components of malignant teratomas. Not only did all cases consistently contain immature neural elements (synaptophysin and INSM1 positive), but also spindled cells with rhabdomyoblastic differentiation (desmin and myogenin positive) and bland epithelial proliferations of thyroid follicular origin (TTF-1 and PAX8 positive). Although DICER1 mutations have previously been implicated in multinodular hyperplasia and well-differentiated thyroid carcinomas, these findings demonstrate the first recurrent role for DICER1 in primitive thyroid tumors. The combined neural, rhabdomyoblastic, and homologous epithelial elements highlighted in this series of malignant thyroid gland teratomas parallel the components of DICER1-mutated tumors in other organs. Overall, these molecular findings further expand the differences between benign/immature teratomas and malignant teratomas, supporting the classification of these tumors as separate entities.

[Testicular germ cell tumors: Histopathological and molecular features]. / Tumeurs germinales du testicule : caractéristiques histopathologiques et moléculaires.

In 2016, the WHO classification of testicular germ cell tumors was revised considering advances in the understanding of their tumorigenesis and molecular features. This restructuring led to a division into two major groups with, on one hand, prepubertal-type tumors, not derived from germ cell neoplasia in situ (GCNIS), and on the other hand, postpubertal-type tumors, GCNIS-derived, which occur in youg men (seminoma and non seminomatous germ cell tumors - embryonal carcinoma, yolk sac tumor, teratoma and choriocarcinoma essentially). The term germ cell neoplasia in situ is consensually accepted as a new terminology for the precursor lesion. In this new classification, the term "spermatocytic seminoma" is replaced by "spermatocytic tumor", reclassified among non-GCNIS-derived tumors. The purpose of this change of nomenclature is to reflect the usually non-aggressive behaviour of this tumor and to avoid any confusion with usual seminoma. The spectrum of trophoblastic tumors continues to expand with the description of new rare entities such as the cystic trophoblastic tumor, the placental site trophoblastic tumor and the epithelioid trophoblastic tumor. This review aims to provide a focus on testicular germ cell tumors highlighting the new immunohistochemical and molecular features responsible for the restructuring of classification. The TNM staging is presented according to the AJCC 8th edition 2017 update.

Review of molecular classification and treatment implications of pediatric brain tumors.

PURPOSE OF REVIEW: Brain tumors are the most common solid tumors and leading cause of cancer-related death in children. The advent of large-scale genomics has resulted in a plethora of profiling studies that have mapped the genetic and epigenetic landscapes of pediatric brain tumors, ringing in a new era of precision diagnostics and targeted therapies. In this review, we highlight the most recent findings, focusing on studies published after 2015, and discuss how new evidence is changing the care of children with brain tumors. RECENT FINDINGS: Genome-wide and epigenome-wide profiling data have revealed distinct tumor entities within, virtually, all pediatric brain tumor groups including medulloblastoma; ependymoma; high-grade and low-grade gliomas; atypical teratoid/rhabdoid tumors; and other embryonal tumors, previously called CNS primitive neuroectodermal tumors. Whenever integrated with clinical information, many molecular alterations emerge as powerful prognostic markers and should thus be used to stratify patients and tailor therapies. SUMMARY: Optimal integration of this newly emerging knowledge in a timely and meaningful way into clinical care is a remarkable task and a matter of active debate. The historical morphology-based classification of tumors is being replaced by a genetic-based classification, and the first generation of molecularly informed clinical trials is underway.

Sacrococcygeal teratomas in newborns: a comprehensive review for the radiologists.

Sacrococcygeal teratomas are the most common solid tumor in newborn infants. The diagnosis is not difficult in many cases; however, there should be additional information on imaging studies in order to manage those infants properly. Details include histology, morphologic classification, complications such as rupture, bleeding, and mass effects on the adjacent structures. Although imaging features cannot accurately predict the histologic subtypes of the tumors, thorough evaluation of the imaging features can help distinguish malignant tumors from benign tumors. In this article, pathogenesis, histological characteristics, clinical considerations, and morphologic characteristics will be discussed.

[Laparoscopic-assisted mobilisation and resection of a sacrococcygeal teratoma Altman type III]. / Die laparoskopisch assistierte Mobilisation und Resektion eines Steißbeinteratoms Altman Typ III.

Objective This video is a step-by-step illustration of the laparoscopic-assisted mobilisation and resection of a sacrococcygeal teratoma Altman type III. Indication Laparoscopic supralevatory tumour mobilisation is an established method in selected centres and can be the initial step in approaching sacrococcygeal teratomas with an intrapelvic portion, facilitating a complete (R0) resection. Method Laparoscopic surgery is performed in supine position with a 5 mm umbilical trocar, a 5 mm trocar in the right upper abdomen, and two 3 mm trocars in the left middle and lower abdomen. We use a 5 mm 45° optic and 3 mm laparoscopic grasping forceps as well as Overholt clamps. For coagulation, a laparoscopic 5 mm diathermy Sealer (LigaSure™, Covidien, Neustadt) is used. Conclusion In selected tumours, laparoscopic assisted tumour mobilisation enables surgeons to clearly identify and ligate the primary tumour-supplying vascular structures at the beginning of the operation, thereby avoiding the risk of major bleeding throughout the subsequent tumour mobilisation. The laparoscopic approach also allows an accurate dissection and mobilisation of the supralevatory tumour parts under direct vision. After repositioning the patient into the prone position, infralevatory preparation can be carried out safely and fast in the conventional sacral approach without any major risk of bleeding.

Lipomatous tumours in adrenal gland: WHO updates and clinical implications.

Adrenal lipomatous tumour is a group of adrenal tumours with a significant component of adipose tissue. According to the current World Health Organization (WHO) classification of tumours of endocrine organs, adrenal myelolipoma is the only entity amongst the group of tumours being described. In the literature, other more recently documented adrenal lipomatous tumours included 24 lipomas, 32 teratomas and 16 angiomyolipomas. Rare fatty tumours of the adrenal gland comprised liposarcoma, hibernoma, adrenocortical tumours with fat component and rare adrenal tumours with fat component. Myelolipoma comprises approximately 3% of primary adrenal tumour. It is noted more commonly in females and in the right adrenal gland. Approximately 40 bilateral myelolipomas were reported. The tumour is most frequently recorded in patients between fifth and seventh decades of life. Adrenal lipomas are often seen in males and in the right adrenal gland. They were commonly noted in patients in the sixth decade of life. The diagnosis could only be possible on examination of the surgically removed specimen. Adrenal teratomas were more common in females and with a bimodal age distribution. Slightly over 60% of the patients with adrenal teratoma are symptomatic. Adrenal angiomyolipomas were often symptomatic, more common in females and in the fifth decades of life. To conclude, adrenal lipomatous tumour is uncommon. They are often benign and non-functional. It is important to recognize the features of this group of lipomatous tumours in the adrenal gland as they are being detected on increasing incidence as a result of the wide-spread use of modern imaging modalities.

Estruma ovárico / Struma ovarii

Introducción: 20 por ciento de los tumores ováricos son de células germinales; y, aunque muchos no pueden ser clasificados por citología, los teratomas sí, y entre estos, el estruma formado por tejido tiroideo. Reconocerlo, ayuda al patólogo en el manejo de la biopsia intraoperatoria y define el proceder clínico quirúrgico. Presentación del caso: mujer de 29 años atendida en urgencias por dolor en región inguinal derecha. Al examinarla se constató tumoración de alrededor de 8 cm en región pélvica derecha, dolorosa al palparla. En el tacto vaginal se percibió masa tumoral gonadal de consistencia firme. El ultrasonido arrojó en el ovario derecho una imagen ecolúcida de paredes gruesas con imágenes hipoecogénicas en su interior, con bordes irregulares de 67 x 97 mm, e imagen ecogénica que ocupa el 20 por ciento de la lesión, con pobre patrón vascular. Conclusiones: los datos clínicos, y los exámenes imagenológicos y citológicos, permiten diagnosticar un estruma ovárico benigno(AU)

Introduction: twenty percent of ovarian tumors are of germinal cells and although many cannot be classified through cytology, teratomes can, and among them, the struma formed by the thyroid tissue. Recognizing this fact helps the pathologist to manage intraoperative biopsy and to define the surgical clinical procedure. Case presentation: a 29 years-old woman seen in the emergency service to relieve pain in her right inguinal region. On the physical exam, an 8 cm tumor was found in the right pelvic region, causing pain when palpating it. The vaginal exam revealed solid gonadal tumor mass. The ultrasound test showed in the right overy an echolucent image of thick walls with hypoechogenic images inside with 67 x 97 mm irregular contours and echogenic image covering 20 percent of lesion, with poor vascular pattern. Conclusions: clinical data and imaging and cytological exams allow diagnosing benign struma ovarii(AU)

Estruma ovárico / Struma ovarii

Introducción: 20 por ciento de los tumores ováricos son de células germinales; y, aunque muchos no pueden ser clasificados por citología, los teratomas sí, y entre estos, el estruma formado por tejido tiroideo. Reconocerlo, ayuda al patólogo en el manejo de la biopsia intraoperatoria y define el proceder clínico quirúrgico. Presentación del caso: mujer de 29 años atendida en urgencias por dolor en región inguinal derecha. Al examinarla se constató tumoración de alrededor de 8 cm en región pélvica derecha, dolorosa al palparla. En el tacto vaginal se percibió masa tumoral gonadal de consistencia firme. El ultrasonido arrojó en el ovario derecho una imagen ecolúcida de paredes gruesas con imágenes hipoecogénicas en su interior, con bordes irregulares de 67 x 97 mm, e imagen ecogénica que ocupa el 20 % de la lesión, con pobre patrón vascular. Conclusiones: los datos clínicos, y los exámenes imagenológicos y citológicos, permiten diagnosticar un estruma ovárico benigno(AU)

Introduction: twenty percent of ovarian tumors are of germinal cells and although many cannot be classified through cytology, teratomes can, and among them, the struma formed by the thyroid tissue. Recognizing this fact helps the pathologist to manage intraoperative biopsy and to define the surgical clinical procedure. Case presentation: a 29 years-old woman seen in the emergency service to relieve pain in her right inguinal region. On the physical exam, an 8 cm tumor was found in the right pelvic region, causing pain when palpating it. The vaginal exam revealed solid gonadal tumor mass. The ultrasound test showed in the right overy an echolucent image of thick walls with hypoechogenic images inside with 67 x 97 mm irregular contours and echogenic image covering 20 percent of lesion, with poor vascular pattern. Conclusions: clinical data and imaging and cytological exams allow diagnosing benign struma ovarii(AU)

MRI findings in intraspinal mature teratoma.

AIM: To characterise and evaluate magnetic resonance imaging (MRI) images for their clinical value in diagnosing and assessing intraspinal mature teratoma. MATERIALS AND METHODS: MRI images obtained from eight patients with a histopathologically verified intraspinal mature teratoma were analysed retrospectively regarding tumour location, size, and margins. Additionally, the signal intensity and enhancement pattern on MRI and other associated malformations were also assessed. RESULTS: Three cases that contained fatty tissue showed markedly heterogeneous hyperintense signalling on T1-weighted images, and mixed hyperintense and hypointense signalling on T2-weighted images and fat-suppression sequences. All three of those cases showed an irregular peripheral fatty tissue signal, and one case showed additional patches of an interspersed calcification signal. The remaining five cases without fatty tissue displayed heterogeneous hyperintense signalling on T1-weighted images and T2-weighted images, and also on fat-suppression sequences. Four of the five cases showed additional patches of interspersed nodular calcification signals. Contrast-enhanced MRI images showed only slight enhancement (n=3). CONCLUSIONS: MRI is regarded as the reference standard diagnostic technique to reveal the location of teratomas and the degree of spinal cord involvement. In most cases, MRI provides accurate anatomical and histological information, which is necessary for patients with suspected intraspinal mature teratoma.

Practical molecular pathology and histopathology of embryonal tumors.

There have been significant improvements in understanding of embryonal tumors of the central nervous system (CNS) in recent years. These advances are most likely to influence the diagnostic algorithms and methodology currently proposed by the World Health Organization (WHO) classification scheme. Molecular evidence suggests that the tumors presumed to be specific entities within the CNS/primitive neuroectodermal tumors spectrum are likely to be reclassified. All these developments compel reassessing current status and expectations from the upcoming WHO classification efforts. This review provides a synopsis of current developments and a practical algorithm for the work-up of these tumors in practice.

Analysis of recurrence risks for sacrococcygeal teratoma in children.

BACKGROUND/PURPOSE: The purpose of this study was to investigate effects of risk factors on recurrence of sacrococcygeal teratoma (SCT). METHODS: A retrospective review was conducted of 107 SCTs treated between January 2003 and December 2012 in our center. Risk factors were identified by univariate and multivariate analysis. RESULTS: Sixteen children had recurrence of SCT a median interval of 16.25months after primary surgery. 15.6% tumors recurrence were Altman type I, 10.5% type II, 10.0% type III, and 31.3% type IV. The recurrence of mature teratoma was observed in 8 patients, immature in 2, malignant in 5. More than half of the recurrences showed a shift towards histological immaturity or malignancy, compared with the primary tumor pathology. Risk factors for recurrence were spillage of tumor parenchyma during operation (P=0.028), incomplete resection (p=0.000), and primary immature (P=0.029) and malignant histology (P=0.026). Size, Altman classification, and age were not risk factors for recurrence. There was a statistically significant difference in OS between patients who developed relapse (64.8%) and those who did not (95.0%) (P=0.0002). CONCLUSIONS: Tumor recurrence affected the outcome of children with SCT. Risk factors were tumor spillage, immature and malignant histology, or incomplete resection. Regular follow-up after surgery is mandatory to find tumor relapse earlier and to improve the outcome.

Rhabdoid tumor: the Irish experience 1986-2013.

Nomenclature for the three recognized forms of rhabdoid tumor reflect their anatomic localization and include malignant rhabdoid tumor of the kidney (MRTK), extrarenal extracranial rhabdoid tumor (EERT), and atypical teratoid rhabdoid tumor (ATRT) involving the central nervous system. A strikingly simple karyotype belies the fact that rhabdoid tumors are among the most lethal human cancers, and now early strides are beginning to elucidate their molecular pathogenesis. Rhabdoid tumors are largely confined to the pediatric population, where they occur preferentially during infancy. Given the rarity of this tumor, international consensus on best treatment has only recently been achieved in conjunction with the establishment of the European Rhabdoid Tumor Registry. Between 1986 and 2013, 25 pediatric patients were diagnosed with rhabdoid tumor in the Republic of Ireland. Of these patients, 13 presented with ATRT, eight had MRTK, and four had EERT. The mean age at diagnosis was 38.8 months, with an equal sex incidence. Because of the lack of a standardized treatment strategy for rhabdoid tumors, these patients have been treated largely according to anatomic site, based on sarcoma, renal, or brain tumor protocols contemporary to their diagnoses. Of the patients, 84% received chemotherapy, 80% underwent surgery, and 44% had radiation therapy. The outcome overall was poor, independent of anatomic location. The overall survival rate was 24%, and mean time to death was just under 9 months.

Extragonadal teratomas of the adult abdomen and pelvis: a pictorial review.

Teratomas comprise a spectrum of tumours that have striking imaging appearances and are commonly considered when evaluating a mass in the female pelvis. A subgroup of these tumours located in an extragonadal abdominopelvic location, in contrast, are extremely rare and can affect both sexes. Extragonadal teratomas can occur at all ages, are particularly unusual in adults and can cause confusion in the differential diagnosis, especially in children. Familiarity with the imaging features of the spectrum of teratomas within the abdominal cavity is therefore of great importance, as radiological diagnosis can guide treatment, prevent delays in diagnosis and avoid sequelae. This article summarizes the radiological appearances of these rare extragonadal tumours in adults in relation to their pathology, malignant potential, location and behaviour. Although uncommon, teratomas should be considered in the differential diagnosis of extragonadal abdominal masses, particularly in young adults.

Well-differentiated pediatric glial neoplasms with features of oligodendroglioma, angiocentric glioma and dysembryoplastic neuroepithelial tumors: a morphological diagnostic challenge.

OBJECTIVE: Oligodendrogliomas are rare in the pediatric population, and most oligodendroglioma-like tumors in this age group may belong to other entities. In addition, accurate diagnosis and grading of such lesions using criteria developed for adult oligodendrogliomas prove difficult, and often controversial. MATERIAL AND METHOD: During a study of tumors previously diagnosed as pediatric oligodendroglioma, we identified four tumors displayed features of that resembled oligodendroglioma, angiocentric glioma and dysembryoplastic neuroepithelial tumor but could not be classified as either one of these entities. Ther clinical, histological and immunohistochemical features of these cases were investigated in this study. RESULTS: Two male (both 9 years old) and two female (ages 4 years and 20 months) patients presented with new onset of seizures. All patients were treated surgically, and two required reoperation. Histologically, the tumors were well-differentiated glial neoplasms with focal angiocentric pattern, delicate vascularity, diffuse growth, infiltrative margins, cortical nodules, focal myxoid areas, and leptomeningeal extension. Immunohistochemical studies showed diffuse nuclear positivity with Olig-2 and GFAP antibodies, whereas staining with neuronal markers, EMA, p53, and IDH1 were negative. Fluorescent in-situ hybridization analysis demonstrated intact 1p/19q in all tumors, and there was no ultrastructural evidence of ependymal differentiation. All patients were alive with disease with a mean follow-up of 112 months. CONCLUSION: These four cases illustrate the morphological diversity of well-differentiated, oligodendroglioma-like glial neoplasms and the uncertainty in their classification among pediatric tumors.

Clinicopathological analysis of small-sized anterior mediastinal tumors.

PURPOSE: The purpose of this study was to determine the clinicopathological findings and prognosis of small-sized anterior mediastinal tumors (SSAMTs). METHODS: A retrospective study was conducted on 43 patients who underwent surgery between January 1989 and December 2011 for SSAMTs. RESULTS: From the preoperative radiological findings, the tumors were classified into solid (n = 28) and cystic lesions (n = 15). The pathological diagnoses of the solid lesions included thymoma (n = 24), thymic carcinoma (n = 1), mucosa-associated lymphoid tissue lymphoma (n = 1), teratoma (n = 1) and neurofibroma (n = 1), and those of the cystic lesions included thymic cysts (n = 8), thymoma (n = 3), bronchogenic cysts (n = 2), teratoma, (n = 1) and a pericardial cyst (n = 1). The 27 thymomas were composed of stages I (n = 22), II (n = 3), III (n = 1) and IVb (n = 1). The overall survival in the 43 patients was 97.1 % at 5 years. In the 28 patients with solid lesions, the overall survival was 95.8 % at 5 years. All patients with cystic lesions were still alive at the last follow-up. CONCLUSION: Cystic lesions of SSAMTs were benign lesions or stage I thymoma, and most of the solid lesions of SSAMTs were stage I or II thymomas. SSAMTs are good candidates for video-assisted thoracic surgery procedures, as conversion to sternotomy can be selected based on the intraoperative findings of pericardial invasion and a rapid pathological diagnosis of thymic carcinoma.